menotropins and Hypogonadism

Subfertility is defined as the condition of being less than normally fertile though still capable of effecting fertilization. When these subfertile couples seek assistance for conception, a thorough evaluation of male endocrine function is often overlooked. Spermatogenesis is a complex process where even subtle alterations in this process can lead to subfertility or infertility. Male endocrine abnormalities may suggest a specific diagnosis contributing to subfertility; however, in many patients, the underlying etiology is still unknown. Optimizing underlying endocrine abnormalities may improve spermatogenesis and fertility. This manuscript reviews reproductive endocrine abnormalities and hormone-based treatments.

Topics: Adrenal Hyperplasia, Congenital; Androgen-Insensitivity Syndrome; Aromatase Inhibitors; Chorionic Gonadotropin; Clomiphene; Follicle Stimulating Hormone, Human; Humans; Hyperprolactinemia; Hypogonadism; Infertility, Male; Male; Menotropins; Obesity; Reproductive Control Agents; Selective Estrogen Receptor Modulators; Tamoxifen; Thyroid Diseases

Infertility is generally defined as a couple's inability to conceive after 1 year of unprotected intercourse. When infertile couples seek assistance, a male factor will be identified half of the time. Once the male has been evaluated, there are four main categories to describe his infertility: (1) idiopathic, (2) post-testicular/obstructive, (3) primary-where the Sertoli and/or Leydig cells of the testis fail, and (4) secondary-where there is a problem with the hypothalamus and/or pituitary. The last, hypogonadotropic hypogonadism (HH), accounts for up to 2% of infertile men. HH is either congenital or acquired and usually can be successfully treated by medical intervention. This review will focus on the hypothalamus-pituitary-gonadal axis, specific defects of this coordination center, and potential interventions for improving male-factor fertility.

Topics: Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropins; Hormone Replacement Therapy; Humans; Hypogonadism; Hypothalamus; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Pituitary Gland; Recombinant Proteins; Testis

Several clinical studies have recently been published documenting the possible role of adjuvant growth hormone treatment in in vitro fertilization. These studies have been performed on different groups of patients including poor ovarian responders, patients with polycystic ovary syndrome and with hypogonadotrophic-hypogonadism. The aim of this review is to examine relevant studies in the last 25 years, on the use of growth hormone in assisted conception and trace the train of events that has lead to the resurgence of interest in this subject.

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Human Growth Hormone; Humans; Hypogonadism; Menotropins; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Reproductive Techniques, Assisted

Topics: Chorionic Gonadotropin; Fluoxymesterone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Infertility, Male; Leydig Cells; Luteinizing Hormone; Male; Menotropins; Prognosis; Reproductive Techniques, Assisted; Testosterone

Topics: Adult; Bromocriptine; Chorionic Gonadotropin; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infertility, Male; Infusion Pumps; Male; Menotropins; Testosterone

In order to evaluate the possibilities for induction of ovulation, the functional competence of the pituitary gland of a woman with Kallmann syndrome was examined by two consecutive dynamic GnRH tests. The second test was conducted after 1 week's treatment by a GnRH pump. The results, which showed some rise of LH but no response of FSH, favored induction by hMG/hCG therapy. Three treatment cycles resulted in a twin pregnancy which was normal and was carried to term. Review of the literature shows only six previously reported pregnancies in women with Kallmann syndrome. Five of them were treated by hMG/hCG, and one by pulsatile GnRH. The two methods of induction are discussed in relation to the heterogeneity of the pituitary and ovarian function in Kallmann syndrome. We show that this heterogeneity dictates that the treatment for induction of ovulation should be individually adjusted according to the pituitary and ovarian competence.

Topics: Adult; Chorionic Gonadotropin; Female; Humans; Hypogonadism; Infertility, Female; Menotropins; Olfaction Disorders; Ovulation Induction; Pituitary Hormone-Releasing Hormones; Twins

There are many methods that can be used to induce ovulation when there is a fault in ovulation in patients who have normal prolactin levels. These are: Bringing the weight to a normal level. Giving Clomiphene. Giving Tamoxifen. Giving cyclofenil and bromocriptine, which really have no more effect than giving a placebo. Giving gonadotrophins in a classical way. This is very useful where there is hypogonadic amenorrhoea but much less useful when the failure of ovulation occurs with normal gonadic function. It is accompanied by a risk of multiple pregnancies and of hyperstimulation, which should be monitored by ultrasound very strictly so that it cannot become too serious. The use of purified FSH which theoretically should be more adequate, at least in cases where the gonadic function is normal in spite of failure of ovulation. Pulsatile administration of LHRH, which in cases of hypothalamic amenorrhoea carries less total risk than giving gonadotrophins. Finally, wedge resection of the ovaries which is reversed for polycystic ovaries that are larger than normal in size, and allied methods. The first choice for hypogonadic hypothalamic amenorrhoea would seem to be the LHRH pump; and for failure of ovulation with normal gonadic function Clomiphene or Tamoxifen. When anti-oestrogens fail to correct these latter cases one can choose according to the case between gonadotrophins, choosing if possible pure FSH, and/or wedge resection. In the last resort in these cases the LHRH pump can be used. The frequent failure of these methods show that perhaps it is possible to create a hypogonadotrophic hypogonadism by giving agonists for a long time or antagonists to LHRH in such a way that a second attempt can be made to induce ovulation using gonadotrophins in better conditions of efficacy and safety.

Topics: Amenorrhea; Anovulation; Clomiphene; Cyclofenil; Epimestrol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypopituitarism; Hypothalamic Diseases; Menotropins; Obesity; Ovary; Ovulation Induction; Tamoxifen; Thinness

Despite the efforts of a large number of investigators, the role of GnRH in clinical gynecology is uncertain. At present, its greatest utility is in research directed toward the understanding of hypothalamic-pituitary interrelationships. However, a clear understanding of the hypothalamic control of gonadotropin secretion awaits the actual measurement of the secretion of GnRH by the hypothalamus. In addition, a better understanding of the ability of the pituitary to secrete gonadotropins in various disorders of menstruation and maturation will probably be achieved through the determination of the capacity of the pituitary to synthesize as well as release gonadotropins in response to GnRH. Such determinations will probably utilize repeated or continuous infusions of GnRH rather than the currently more popular single injection technique. Finally, GnRH may be useful in the induction of ovulation. A definition of its role in ovulation induction awaits the results of additional clinical studies. Understanding of the nature of hypothalamic control of the pituitary is as yet incomplete. The availability of hypothalamic releasing factors will make it possible to study in greater detail the mechanisms by which the fine regulation of the endocrine system is achieved.

Topics: Adenoma; Amenorrhea; Clomiphene; Cushing Syndrome; Diabetes Mellitus; Disorders of Sex Development; Female; Galactorrhea; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Menotropins; Menstruation; Myotonic Dystrophy; Ovulation; Pituitary Diseases; Pituitary Neoplasms; Polycystic Ovary Syndrome; Postpartum Period; Pregnancy

To compare the efficacies of gonadotropin-releasing hormone (GnRH) pulse subcutaneous infusion with combined human chorionic gonadotropin and human menopausal gonadotropin (HCG/HMG) intramuscular injection have been performed to treat male hypogonadotropic hypogonadism (HH) spermatogenesis.. In total, 220 idiopathic/isolated HH patients were divided into the GnRH pulse therapy and HCG/HMG combined treatment groups (n = 103 and n = 117, respectively). The luteinizing hormone and follicle-stimulating hormone levels were monitored in the groups for the 1st week and monthly, as were the serum total testosterone level, testicular volume and spermatogenesis rate in monthly follow-up sessions.. In the GnRH group and HCG/HMG group, the testosterone level and testicular volume at the 6-month follow-up session were significantly higher than were those before treatment. There were 62 patients (62/117, 52.99%) in the GnRH group and 26 patients in the HCG/HMG (26/103, 25.24%) group who produced sperm following treatment. The GnRH group (6.2 ± 3.8 months) had a shorter sperm initial time than did the HCG/HMG group (10.9 ± 3.5 months). The testosterone levels in the GnRH and HCG/HMG groups were 9.8 ± 3.3 nmol/L and 14.8 ± 8.8 nmol/L, respectively.. The GnRH pulse subcutaneous infusion successfully treated male patients with HH, leading to earlier sperm production than that in the HCG/HMG-treated patients. GnRH pulse subcutaneous infusion is a preferred method.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Drug Administration Routes; Drug Administration Schedule; Drug Combinations; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infusion Pumps; Luteinizing Hormone; Male; Menotropins; Reproductive Control Agents; Spermatogenesis; Testosterone; Young Adult

The objective of this study was to determine the efficacy of gonadotropin therapy in men with hypogonadotropic hypogonadism. Gonadotropin therapy is a safe and effective therapy for hypogonadotropic hypogonadism.

Topics: Adolescent; Adult; Child; Chorionic Gonadotropin; Drug Therapy, Combination; Follow-Up Studies; Genitalia, Male; Humans; Hypogonadism; Male; Menotropins; Middle Aged; Organ Size; Sperm Count; Testis; Treatment Outcome

Testosterone substitution, needed for normal physical development in male hypogonadal adolescents, does not induce testicular growth. We treated 37 hypogonadal adolescents with gonadotropins (hCG/hMG), to obtain complete virilization during the first two years of treatment, to avoid psychological sequellae and to allow normal sexual development. Testicular volume increased significantly during therapy (from 1.98 +/- 1.2 to 9 +/- 3.3 ml), while testosterone rose from 0.26 +/- 0.04 to 5.3 +/- 0.8 ng/ml, with worse results in adolescents with cryptorchidism. hCG/hMG treatment had a better outcome than testosterone during the induction of puberty, avoiding psychological problems induced by atrophic testes. Further long term studies are necessary to evaluate whether early hCG/hMG treatment facilitates later spermatogenesis even in patients with cryptorchidism.

Topics: Adolescent; Adult; Body Height; Chorionic Gonadotropin; Cryptorchidism; Drug Therapy, Combination; Hormone Replacement Therapy; Humans; Hypogonadism; Libido; Male; Menotropins; Puberty; Sexual Maturation; Sperm Count; Testis; Testosterone

Stimulatory therapy with either GnRH or gonadotropins is an effective treatment to induce spermatogenesis and achieve paternity in men with secondary hypogonadism. However, there is still uncertainty about the optimal treatment modality and schedule, the duration of treatment necessary and the influence of interfering factors such as maldescended testes. We have extended our previous series of men treated for secondary hypogonadism and now present our therapeutic experience with 42 cases. Twenty-one patients with hypothalamic disorders (11 with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with hypopituitarism (group II) were treated with hCG/hMG. A total of 5 7 treatment courses were initiated for induction of spermatogenesis, 36 of these for the purpose of induction of pregnancy in the female partner. Bilateral testicular volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by the appearance of sperm in the ejaculate was induced in 54/57 courses. Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not preclude patients with IHH or KalS from gaining fertility under therapy and spermatogenesis could be successfully initiated even in some individuals with bilateral maldescended testes. In general there was a tendency for a longer duration of therapy until induction of spermatogenesis in patients with a history of bilateral cryptorchidism. However, this did not reach statistical significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH there were no statistically significant differences in terms of duration to appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years spermatogenesis could be induced. In repeatedly treated patients stimulation of spermatogenesis tended to be faster while time until induction of pregnancy was significantly shorter in the second treatment course. In conclusion, GnRH or hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It remains to be determined whether highly purified urinary gonadotropin preparations or recombinant LH and FSH will provide therapeutic advantages.

Topics: Adult; Chorionic Gonadotropin; Female; Fertility; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Male; Menotropins; Pregnancy; Retrospective Studies; Spermatogenesis; Testis; Time Factors

Three women with hypogonadotrophic hypogonadism, all desiring pregnancy, participated in a prospective open study attempting to assess the ability of the human corpus luteum to recover after 7 days of deprivation from gonadotrophin stimulation. Follicular growth was induced by gonadotrophins. An endogenous luteinizing hormone (LH) surge was induced by the s.c. injection of a gonadotrophin-releasing hormone agonist. For luteal support, 10 mg/day oral medroxyprogesterone acetate were given for 7 days, after which a single i.m. injection of human chorionic gonadotrophin (HCG) was administered. Monitoring during the follicular phase consisted of daily measurements of serum oestradiol, LH and follicle stimulating hormone (FSH) concentrations, and of follicular growth by transvaginal ultrasonography. During the luteal phase, monitoring consisted of measurements of serum concentrations of LH, FSH, oestradiol, progesterone, 17-hydroxyprogesterone and beta-HCG. Ovulation and luteinization occurred in two patients, demonstrated by transient marked increases in serum progesterone and 17-hydroxyprogesterone concentrations which decreased to basal preovulatory values and increased again following the administration of HCG 7 days later. In the third patient, ovulation and luteinization did not occur, and the subsequent administration of HCG did not result in an increase in progesterone concentration. Of the two patients who ovulated, one conceived and the second had a luteal phase of 15 days duration. Our preliminary results suggest that the human corpus luteum can be 'rescued' and can function normally after 7 days of deprivation from gonadotrophin stimulation in patients with hypogonadotrophic hypogonadism.

Topics: 17-alpha-Hydroxyprogesterone; Adult; Buserelin; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Corpus Luteum; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hydroxyprogesterones; Hypogonadism; Infertility, Female; Luteinizing Hormone; Menotropins; Ovulation Induction; Pregnancy; Progesterone

The purpose of this study is to clarify the pathological and endocrinological variations of male idiopathic hypogonadotropic hypogonadism (IHH) from the viewpoint of testicular maturation. Twenty-five patients with IHH were classified into 3 groups according to the degree of germ cell maturation. The most mature germ cells in patients with severe IHH, moderate IHH and mild IHH were spermatogonia, primary spermatocytes and postmeiotic germ cells, respectively. All patients were treated with hCG alone or a combination of hMG-hCG for 1 year or more. The therapeutic efficacy of gonadotropin therapy was evaluated by findings of semen analysis, spermatogenesis and sexual maturation. The total GCI, which was expressed as the number of germ cells per Sertoli cell, diameter of the seminiferous tubules and testicular volume in mild IHH were the largest among the 3 IHH groups, and those in severe IHH were the smallest. Even in mild IHH, spermatogonial proliferation and meiotic activity were quantitatively smaller than those of normal pubertal boys. All patients showed extremely low basal testosterone levels. Response of serum testosterone to hCG administration correlated to the maturity of germ cells. Basal serum gonadotropin levels and responses to GnRH administration varied widely among the 3 groups. In particular, the response of serum gonadotropin to GnRH correlated to the maturity of the germ cells. Spermatogenesis could be initiated by hCG alone in IHH patients without cryptorchidism. Normal sperm density was obtained by hCG alone in the case of mild IHH; however, in moderate and severe IHH groups, hMG-hCG therapy was required for sufficient spermiogenesis. Sexual maturation was completely obtained by gonadotropin therapy within 1 year in moderate and mild IHH. However, in severe IHH, satisfactory sexual maturation could not be obtained within 1 year. The therapeutic prognosis for sexual maturation could be made based on the response to the hCG test at 6 months of gonadotropin therapy. In conclusion, the maturity of germ cells before treatment, which varies widely among patients with IHH, is a sensitive parameter for hypothalamo-pituitary-testicular function and the efficacy of gonadotropin therapy for testicular function. In severe IHH groups, to obtain satisfactory sexual maturation, the administration of testosterone should be considered in addition to gonadotropin replacement.

Topics: Adolescent; Adult; Cell Division; Child; Chorionic Gonadotropin; Germ Cells; Humans; Hypogonadism; Male; Menotropins; Sexual Maturation; Spermatogenesis; Testis

This study was designed to examine ovarian performance, i.e. follicular growth, normal steroidogenesis and luteal phase function, following the administration of multiple increasing doses of human follicle stimulating hormone (FSH) with a constant low dose of luteinizing hormone (LH) in women with isolated hypogonadotrophic hypogonadism. Human menopausal gonadotrophin (HMG) was used in the first treatment cycle, starting with 150 IU of LH and 150 IU of FSH per day, for 7 days. The dose was increased daily with 75 IU of LH and 75 IU of FSH for another 7 days if no response was detected by serial ultrasound measurements and serum oestradiol determinations. In the second treatment cycle, a constant dose of 75 IU of LH (using HMG) was administered per day and up to 150 IU of FSH (using urofollitrophin) was supplemented. If no response was detected after 7 days of treatment, the dose of FSH was increased. For the final stage of ovulation induction, human chorionic gonadotrophin (HCG) was administered in the presence of at least one follicle > 17 mm in diameter but with no more than three follicles > 16 mm in diameter. To verify the adequacy of the luteal phase, a pharmacokinetic/pharmacodynamic study of beta-HCG, oestradiol and progesterone was performed following the second treatment cycle only. Ovarian stimulation using a constant dose of 75 IU of LH and increasing doses of FSH up to 225 IU, resulted in normal follicular growth and hormonal milieu. Both women showed normal luteal phase oestradiol and progesterone production and both women conceived following the second treatment cycle.

Topics: Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteal Phase; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovulation Induction; Peptide Fragments; Progesterone; Prospective Studies; Steroids

To compare ovarian performance and hormonal levels, after ovulation induction, in patients with isolated hypogonadotropic hypogonadism, using two different gonadotropin drugs.. Patients were treated during consecutive cycles, using the same stimulation protocol, with human menopausal gonadotropin (hMG) in the first treatment cycle and purified follicle-stimulating hormone (FSH) in the second one.. Specialist Reproductive Endocrine Unit.. Nine patients with isolated hypogonadotropic hypogonadism.. Duration of stimulation, number of leading follicles, serum estradiol (E2) concentration and endometrial thickness at the time of human chorionic gonadotropin administration, and the occurrence of ovulation.. Compared with hMG, treatment with purified FSH required significantly more ampules of drug (P less than 0.04) but resulted in a significant reduction in the number of leading follicles (P less than 0.05), serum E2 concentrations (P less than 0.002), endometrial thickness (P less than 0.02) and the occurrence of ovulation (P less than 0.05).. This study in isolated hypogonadotropic hypogonadism patients is consistent with the two-cell two-gonadotropin hypothesis, that both gonadotropins are required to accommodate their synergistic action for appropriate steroidogenesis. In treating this group of patients, the superior efficacy of hMG compared with purified FSH preparation is beyond question.

Topics: Adult; Drug Therapy, Combination; Endometrium; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Ovulation Induction; Prospective Studies; Ultrasonography

Topics: Adult; Chorionic Gonadotropin; Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Hypogonadism; Infertility, Female; Infertility, Male; Male; Menotropins; Ovulation Induction; Prospective Studies; Spermatogenesis

A randomized, double-blind, placebo-controlled trial of cotreatment with biosynthetic, human sequence, growth hormone (GH), and human menopausal gonadotropins (hMG) for induction of ovulation was performed in 16 women with amenorrhea and anovulatory infertility. Patients were randomly allocated to treatment with hMG + GH (24 IU on alternate days, total dose 144 IU) or hMG + placebo. Those who received placebo were given GH in a subsequent course of treatment. On cotreatment with GH compared with placebo, there was a significant reduction in the required dose of hMG, duration of treatment, and the daily effective dose of gonadotropins. Serum insulin-like growth factor-I (IGF-I) rose during treatment with GH but not with placebo. We conclude that growth hormone augments the response of the human ovary to stimulation by gonadotropins. These results suggest a role for the use of GH in induction of ovulation.

Topics: Adult; Amenorrhea; Anovulation; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Growth Hormone; Humans; Hypogonadism; Hypophysectomy; Infertility, Female; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Menotropins; Ovulation Induction; Pituitary Neoplasms; Random Allocation

In a long-term hypophysectomized male HCG treatment was unable to initiate spermatogenesis. However, a spermatogenesis induced by HMG/HCG treatment could be maintained by HCG alone for 7 years with clinical fertility. In another hypogonadotrophic male HCG was also unable to initiate spermatogenesis. But a spermatogenesis once induced by HMG/HCG treatment could be maintained for more than one year with HCG alone. It is suggested that gonadotrophin treatment of the hypogonadotrophic male should consist of HMG + HCG until complete spermatogenesis is induced followed by maintenance treatment with HCG.

Topics: Adult; Chorionic Gonadotropin; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Humans; Hypogonadism; Hypophysectomy; Male; Menotropins; Spermatogenesis

Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH.. Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance).. Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ± 0.5 cm and 2.0 ± 0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference.. The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research.. ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Topics: Adolescent; Adult; Child; Chorionic Gonadotropin; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Male; Menotropins; Spermatogenesis; Testosterone

Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5-16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis.

Topics: Chorionic Gonadotropin; Drug Therapy, Combination; Humans; Hypogonadism; Male; Menotropins; Retrospective Studies; Spermatogenesis; Treatment Outcome; Young Adult

Do patients with congenital combined pituitary hormone deficiency (CCPHD) have different responses to gonadotrophin-induced spermatogenesis compared with those with idiopathic hypogonadotropic hypogonadism (IHH)?. CCPHD patients have a better response to gonadotrophin therapy than IHH patients.. Gonadotrophins are effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism.. This retrospective cohort study included 75 patients, 53 of whom had IHH and 22 CCPHD. They were diagnosed, treated and followed up between January 2008 and December 2013.. Combined gonadotrophin therapy, consisting of human chorionic gonadotrophin and human menopausal gonadotrophin, was administered for 24 months. The success rate of spermatogenesis (≥1 sperm in ejaculate), serum total testosterone level, testicle size and sperm concentration during the treatment, as well as the first time sperm were detected in the ejaculate, were compared between the two diagnostic groups. All patients were treated in Peking Union Medical College Hospital.. Spermatogenesis was successfully induced in 85% of IHH patients and 100% of CCPHD patients after 24-month combined gonadotrophin treatment (P = 0.03). In comparison with IHH, CCPHD patients had larger mean testicle sizes during the gonadotrophin treatment at 6, 12, 18 and 24 months (all P < 0.05). The initial time for sperm appearance in IHH group (n = 45) and CCPHD group (n = 22) was 13.2 ± 5.9 versus 10.4 ± 3.8 months (P = 0.045). Generally, CCPHD patients had higher sperm counts [median (quartiles)] than IHH patients during the treatment, but the difference was only statistically significant at 12 months of treatment, 3.3 (1.8, 12.0) versus 1.0 (0.0, 4.6) million/ml, P = 0.001. There was a higher level of serum total testosterone [mean (SD)] in the CCPHD group than the IHH group (676 ± 245 versus 555 ± 209 ng/dl, P = 0.035).. First, the inherent nature of a retrospective designed study was a main shortcoming. Secondly, pathological gene mutations in IHH and CCPHD patients should be further investigated. Clarification of the underlying mechanisms between cryptorchidism and mutated genes may provide more information for the divergent therapeutic responses between two groups. Only a minority of patients were actively seeking to have children so information about fertility is limited.. CCPHD patients had a lower incidence of cryptorchidism and a better response to gonadotrophin therapy than IHH patients, reflecting multiple defects on the different levels of reproduction axis in IHH. Furthermore, growth hormone is not indispensable for spermatogenesis in CCPHD patients.. The study was supported by Natural Science Foundation of China (No: 81100416). None of the authors has any conflicts of interest to declare.

Topics: Adolescent; Adult; Cell Count; Chorionic Gonadotropin; Cryptorchidism; Follow-Up Studies; Humans; Hypogonadism; Hypopituitarism; Male; Menotropins; Outcome Assessment, Health Care; Reproductive Control Agents; Retrospective Studies; Sperm Count; Spermatogenesis; Testis; Testosterone; Young Adult

Classical congenital adrenal hyperplasia (CAH), a genetic disorder characterized by 21-hydroxylase deficiency, impairs male fertility, if insufficiently treated.. A 30-year-old male was referred to our clinic for endocrine and fertility assessment after undergoing unilateral orchiectomy for a suspected testicular tumor. Histopathological evaluation of the removed testis revealed atrophy and testicular adrenal rest tumors (TARTs) and raised the suspicion of underlying CAH. The remaining testis was also atrophic (5 ml) with minor TARTs. Serum 17-hydroxyprogesterone levels were elevated, cortisol levels were at the lower limit of normal range, and gonadotropins at prepubertal levels, but serum testosterone levels were within the normal adult range. Semen analysis revealed azoospermia. CAH was confirmed by a homozygous mutation g.655A/C>G (IVS2-13A/C>G) in CYP21A2. Hydrocortisone (24 mg/m(2)) administered to suppress ACTH and adrenal androgen overproduction unmasked deficient testicular testosterone production. As azoospermia persisted due to sustained hypogonadotropic hypogonadism, a combined s.c. gonadotropin replacement with human chorionic gonadotropin (hCG) (1500 IU twice weekly) and FSH (human menopausal gondadotropin (hMG) 150 IU three times weekly) was initiated.. Normalization of testosterone levels and a stable low sperm concentration (0.5 mill/ml) with good sperm motility (85% A+B progressive) were achieved within 21 months of treatment. Despite persisting TARTs, while receiving treatment, the patient successfully impregnated his wife twice, the latter impregnation leading to the birth of a healthy girl.. TARTs in unrecognized (simple virilizing) CAH may lead to unnecessary orchiectomy. In hypogonadotropic, azoospermic CAH, a combined treatment with oral corticosteroids and subcutaneously administered hCG and FSH can successfully restore testicular testosterone production and fertility, even if only one hypoplastic and atrophic testis with adrenal rest tumors is present.

Topics: Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Adult; Azoospermia; Chorionic Gonadotropin; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Menotropins; Orchiectomy; Reproductive Control Agents; Testicular Neoplasms

To study the sperm deoxyribonucleic acid (DNA) fragmentation index (DFI), testicular volume, semen parameters, and hormone profile in human chorionic gonadotropin (hCG)- and human menopausal gonadotrophin (hMG)-treated patients with hypogonadotropic hypogonadism (HH) with and without a successful pregnancy.. This is a cross sectional study. The study initially included 81 patients with HH and azoospermia at the Infertility Unit of Royan Institute between 2010 and 2012. Fifty-eight of 81 patients achieved >1 × 10(6) sperm/mL during hCG and hMG therapy. These 58 patients were divided into the following 2 groups: 20 patients with HH who achieved pregnancy in response to hCG/hMG (responders, 16 naturally and 4 by intrauterine insemination) and 38 gonadotropin-treated patients with HH with failed pregnancy (nonresponders, 29 naturally, 5 by intrauterine insemination, 1 by in vitro fertilization, and 3 by intracytoplasmic sperm injection). Sperm DNA fragmentation was visualized by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.. Average of DFI (responders: 13.45 ± 0.64; nonresponders: 21.92 ± 0.86), age, body mass index, testis volume semen parameters, and follicle-stimulating hormone, luteinizing hormone, and testosterone levels in the 2 groups were calculated. Cut-off point for DFI was determined by receiver operating curve analysis (17.5%).. It was shown that DFI in responders is significantly lower than DFI in nonresponders (P <.001), and duration of hCG and hMG therapy in responders is significantly higher than those of nonresponders (P <.05). DFI could be predictive of conception (P <.001; odds ratio 0.57; 95% confidence interval 0.417-0.778). It can be concluded that despite low sperm quality, especially sperm concentration in these patients, decreasing sperm DNA damage may result in successful fertilization.

Topics: Cross-Sectional Studies; DNA Damage; DNA Fragmentation; Female; Fertility Agents, Female; Humans; Hypogonadism; In Situ Nick-End Labeling; Male; Menotropins; Organ Size; Spermatogenesis; Spermatozoa; Testis

Topics: Anovulation; Body Mass Index; Exercise; Feeding and Eating Disorders; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hypogonadism; Hypopituitarism; Hypothalamic Diseases; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; World Health Organization

Data on the management of male infertility secondary to hypogonadotrophic hypogonadism (HH) are limited. We report our extensive experience with intramuscular injections of gonadotropins, one of the two methods used for this purpose. Eighty-seven married men (median age, 28 years) with either congenital (47 men) or acquired (40 men) HH were treated for a median of 26 months (range, 6-57) with intramuscular injections of gonadotropins (HCG/HMG) three times weekly for the purpose of achieving fertility. The outcome was assessed by achievement of one or more pregnancies. Of the 151 courses of HCG/HMG treatment administered to 87 patients, 85 courses (56.3%) were successful, resulting in 85 pregnancies (median pregnancy rate 2, range 1-10) in 35 patients (40%) while 52 cases did not achieve pregnancy. Responders had larger pretherapy testicular volume (9 +/- 3.6 cc) compared to non-responders [(5.7 +/- 2.0 cc), P < 0.0001], but there was no difference in age, LH, FSH or testosterone levels or doses of HCG/HMG used. The pregnancy rate was similar in those with congenital (51.4%) and acquired causes (48.6%) of HH (P = 0.83). Only testicular size was predictive of conception (P < 0.001, odds ratio 1.5, 95% CI 1.21-1.92) while age, pretherapy levels of testosterone, LH, FSH and doses of HCG/HMG did not predict the success of pregnancy. Gonadotropins are moderately effective in achieving one to several pregnancies in HH. Only testicular size is predictive of success in achieving pregnancy. There is no difference in success between those with congenital and acquired causes of HH.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropins; Humans; Hypogonadism; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Retrospective Studies; Testosterone; Treatment Outcome; Young Adult

A 19-year-old male, who had undergone bilateral orchiopexy at 5 years of age in the Department of Pediatric Surgery, was referred to our clinic presenting with bilateral small testes. Bilateral testis volume was 4 ml involving a small penis and scant pubic hair per Tanner Stage 2. Serum luteinizing hormone, follicle stimulating hormone and testosterone levels were low. Results of hormonal loading tests, including luteinizing hormone-releasing hormone (LH-RH) and human chorionic gonadotropin (HCG), were positive. Brain computed tomographic scan revealed no abnormal findings. The diagnosis of male hypogonadotropic hypogonadism was rendered based on these data. Administration of LH-RH for 1 year was ineffective. Subsequently, HCG and human menopausal gonadotropin (HMG) treatments were initiated. The symptoms of male insufficiency improved; moreover, sperm formation was apparent following HCG and HMG treatments. The patient has received HCG and HMG injections for eight years; furthermore, his wife delivered a boy consequent to the first intracytoplasmic sperm injection.

Topics: Adult; Chorionic Gonadotropin; Female; Humans; Hypogonadism; Male; Menotropins; Pregnancy; Sperm Injections, Intracytoplasmic; Spermatogenesis

To observe the efficacy of human chorionic gonadotrophin (hCG) and hCG plus human menopausal gonadotropin (HMG) for central hypogonadism in male patients.. 64 men with central hypogonadism were recruited in this study, including 19 patients with Kallmann syndrome, 41 patients with idiopathic hypogonadotrophic hypogonadism (IHH) and 4 patients with hypogonadism after brain surgery. 33 patients were treated with hCG 1500 IU intramuscularly twice a week, whereas 31 patients were treated with intramuscular hCG 1500 IU plus HMG 75 IU twice a week, for at least 6 months.. After treatment, all patients felt stronger physically and 42/64 patients developed beard, pubes or armpit hair. The testis volume enlarged significantly [(3.08 +/- 2.44) ml vs (8.92 +/- 5.37) ml, P < 0.001], and serum follicle-stimulating hormone, luteinizing hormone and testosterone concentrations were higher significantly than those before treatment (P < 0.05). 6/64 patients underwent spermatorrhea and 2 patient were found to have spermatogenesis. If judged by the testis volume, 52 patients (81.2%) were effective and 12 patients were ineffective.. For male patients with the central hypogonadism, hCG and hCG plus HMG can promote the pubertal development and maturation of second sex characteristics, as well as enhance the physical strength; in some patients both androgen production and spermatogenesis can be achieved.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Humans; Hypogonadism; Injections, Intramuscular; Male; Menotropins

A 23-year-old man visited our hospital, complaining of a lack of secondary sexual characteristics. Based on both clinical and endocrinological examinations, he was diagnosed as suffering from idiopathic hypogonadotropic hypogonadism (IHH). With human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) replacement therapy, clinical symptoms and serum testosterone levels improved to normal ranges. Interestingly, prostate volume as measured by transrectal ultrasonography increased considerably from 3.6 ml before treatment to 20.2 ml after treatment. The monitoring of prostate volume might be a parameter useful for evaluating the treatment effect of hCG/hMG replacement therapy in IHH.

Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Gonadotropins; Humans; Hypogonadism; Male; Menotropins; Prostate; Testosterone; Ultrasonography

Topics: Adult; beta-Thalassemia; Chorionic Gonadotropin; Drug Combinations; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Menotropins; Ovulation Induction; Treatment Outcome

In the present study, we aimed to investigate the effects of testosterone deficiency and gonadotropin therapy on the in vitro production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) by peripheral blood mononuclear cells (PBMCs) from patients with idiopathic hypogonadotropic hypogonadism (IHH) in order to elucidate the modulatory role of androgen in cytokine production. Fifteen male patients with untreated IHH and 15 age-matched healthy male subjects were enrolled in the study. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (FT), sex hormone binding globulin (SHBG), prolactin, and IL-2 and IL-4 levels were also measured. In unstimulated cultures, IL-1beta and TNF-alpha secretion were not significantly different between patient and control groups. However, after stimulation with lipopolysaccharide (LPS), secretion of IL-1beta and TNF-alpha was significantly higher in cultures from untreated patients with IHH than in control subjects. Mean FSH, LH and FT levels were significantly lower, whereas SHBG, IL-2 and IL-4 levels were significantly higher in patients with IHH compared than in controls. In patients with IHH, FT negatively affected the serum levels of IL-4 and in vitro secretion of IL-1beta and TNF-alpha. In addition, IL-2 and IL-4 affected the in vitro secretion of IL-1beta in a positive manner. Gonadotropin therapy decreased both TNF-alpha and IL-1beta in PBMCs from patients with IHH. The levels of serum IL-2 and IL-4 were also decreased by therapy. In conclusion, in the present study, gonadotropin treatment restored the in vitro production of IL-1beta and TNF-alpha by PBMCs from patients with IHH, suggesting that androgen modulates proinflammatory cytokine production, at least directly through its effects on PBMCs. It seems probable that this effect plays an important role in the immunosuppressive action of androgens.

Topics: Adult; Case-Control Studies; Chorionic Gonadotropin; Gonadotropins, Pituitary; Humans; Hypogonadism; Interleukin-1; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Menotropins; Regression Analysis; Statistics, Nonparametric; Testosterone; Tumor Necrosis Factor-alpha

Circulating leptin shows a pulsatile secretory pattern along with a nocturnal rise. We have previously shown that circulating leptin concentrations are high in males with untreated idiopathic hypogonadotropic hypogonadism (IHH). However, circadian leptin secretion in IHH before and after gonadotropin treatment is not known. Thus, we studied 14 adult males with IHH who had no history of previous hormonal therapy, and 12 age- and body mass index-matched healthy men. Plasma leptin concentrations were measured with 1-h intervals for 24 h before and 6 months after gonadotropin treatment. The 24-h mean leptin concentration showed a significant decrease, from 11.78 +/- 1.908 microg/liter at baseline to 10.85 +/- 1.939 microg/liter after 6 months of therapy (z = 3.107; P = 0.002). Before and after treatment, 24-h mean leptin concentrations were also significantly higher in the patient group when compared with controls (4.275 +/- 0.711 microg/liter) (z = 5.938; P = 0.0001). Hourly leptin levels demonstrated a diurnal pattern in hypogonadal patients, a surge in the midday, and a peak just after midnight, and this pattern did not differ before and after treatment. We observed a similar diurnal pattern in the control subjects too. Leptin levels were negatively and significantly correlated with free testosterone and total testosterone levels both before (r = -0.656, P = 0.011; and r = -0.639, P = 0.014, respectively) and after (r = -0.537, P = 0.048; and r = -0.563, P = 0.036, respectively) gonadotropin administration. Our observations suggest that the diurnal rhythm of leptin is intact in males with IHH, and short-term gonadotropin treatment does not effect its diurnal rhythm. Moreover, testosterone produced under the influence of the gonadotropin treatment led to decreases in the leptin levels.

Topics: Adult; Chorionic Gonadotropin; Circadian Rhythm; Gonadotropins; Hormone Replacement Therapy; Humans; Hypogonadism; Leptin; Male; Menotropins; Testosterone

The authors report a rare case of a patient with panhypopituitarism who became pregnant by gonadotropin therapy and gave birth to a healthy baby. A brain tumour and/or the surgical resection of a brain tumour occasionally results in pituitary dysfunction. An 18-year-old Japanese patient developed hypogonadotropic secondary amenorrhoea because of a craniopharyngioma, which was surgically removed. The patient came to us, and peripheral blood was collected every 15 minutes for four hours. The levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH) were measured. Results showed that LH and FSH levels were very low and did not fluctuate. Several years later, the patient complained of infertility, and treatment with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) was started. The therapy was repeated for several cycles, but she did not conceive, so hMG-hCG therapy combined with conjugated oestrogen administration was started. The patient became pregnant at the seventh cycle of this combined therapy. She was not treated with supplementary growth hormone.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Craniopharyngioma; Estrogens; Female; Fertility Agents, Female; Humans; Hypogonadism; Menotropins; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome

Serial measurements of body mass index (BMI), serum concentrations of testosterone (T), estradiol (E) and leptin (L) were performed before and after gonadotropin (Gn) therapy in an 18-year-old male subject (BMI 25.4 kg/m2) with idiopathic hypothalamic hypogonadism (IHH). We also measured the BMI and serum concentrations of L in 99 age-matched healthy subjects. Serum L correlated significantly with BMI in control subjects (r=0.84, p<0.0001). Baseline serum concentrations of L in our case were markedly high and both T and E were very low, but Gn therapy resulted in a gradual decrease in L and improvement in T and E, finally reaching the control levels of BMI-matched subjects. Our results demonstrate that T is a powerful negative modulator of serum L independent of BMI in conditions associated with low T levels, such as IHH.

Topics: Adolescent; Body Composition; Body Mass Index; Chorionic Gonadotropin; Estradiol; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamic Diseases; Leptin; Male; Menotropins; Testosterone

Topics: Adult; Female; Fertilization in Vitro; Humans; Hypogonadism; Infertility, Female; Menotropins; Ovulation Induction; Pregnancy; Twins

Topics: Adult; Estradiol; Estrogens, Conjugated (USP); Female; Fertility Agents, Female; Humans; Hypogonadism; Menotropins; Ovulation Induction; Prospective Studies

We have studied a 20-yr-old male patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism (HH) due to a C to A transversion at nucleotide 825 in the DAX-1 gene, resulting in a stop codon at position 197. The same mutation was detected in his affected first cousin (adrenal hypoplasia congenita and HH) and in a heterozygous state in their carrier mothers. The patient had had acute adrenal insufficiency at the age of 2 yr and 6 months, bilateral cryptorchidism corrected surgically at the age of 12 yr, and failure of spontaneous puberty. Plasma testostereone (T) was undetectable (<0.30 nmol/L), gonadotropin levels were low (LH, <0.4 IU/L; FSH, 1.5 IU/L) and not stimulated after i.v. injection of 100 microg GnRH. The endogenous LH secretory pattern was apulsatile, whereas free alpha-subunit (FAS) levels depicted erratic pulses, suggesting an incomplete deficiency of hypothalamic GnRH secretion. During i.v. pulsatile GnRH administration (10 microg/pulse every 90 min for 40 h), each GnRH pulse induced a LH response of low amplitude (0.54 +/- 0.05 UI/L), whereas mean LH (0.45 +/- 0.01 IU/L) and FAS (63 +/- 8 mU/L) levels remained low. Amplitude of LH peaks (0.83 +/- 0.09 IU/L), mean LH (0.53 +/- 0.02 IU/L), and FAS (161 +/- 18 mU/L) levels increased (P < 0.01), whereas the T concentration remained low (0.75 nmol/L) when the pulsatile GnRH regimen was raised to 20 microg/pulse for a 40-h period, suggesting a partial pituitary resistance to GnRH. Thereafter, plasma T levels remained in prepubertal value after three daily im injections of 5000 IU hCG (3.6 nmol/L) and after 1-yr treatment with weekly i.m. injections of 1500 IU hCG (1.2 nmol/L), implying Leydig cell resistance to hCG. The patient had a growth spurt, bone maturation, progression of genital and pubic hair stages, and normalization of plasma T level (15.8 nmol/L) after a 12-month treatment with twice weekly injections of hCG and human menopausal gonadotropin (75 IU International Reference Preparation 2) preparations, suggesting that, in presence of FSH, a Sertoli cell-secreted factor stimulated Leydig cell production of T. In conclusion, we report a novel mutation in the DAX-1 gene in patients with AHC and HH. Our results suggest that the hypogonadism is due to a combined hypothalamic-pituitary-gonadal defect and imply that the DAX-1 gene may play a critical role in human testicular function.

Topics: Base Sequence; Child, Preschool; Chorionic Gonadotropin; DAX-1 Orphan Nuclear Receptor; DNA-Binding Proteins; Drug Therapy, Combination; Genitalia, Male; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Male; Menotropins; Mutation; Pedigree; Receptors, Retinoic Acid; Repressor Proteins; Transcription Factors

The Gordon Holmes spinocerebellar ataxia syndrome (GHS) is associated with idiopathic hypogonadotrophic hypogonadism (IHH). There are conflicting reports in the literature as to whether the primary neuroendocrine defect is of hypothalamic GnRH secretion, as with most causes of IHH, or of pituitary resistance to GnRH action. Because of the anatomical inaccessibility of the hypophyseal portal circulation, direct measurement of GnRH levels in human subjects is not possible. Previous investigators have attempted to unravel this problem through the use of GnRH stimulation tests and the limitations of this approach may explain the differing results obtained. We used the more physiological approach of treating a male GHS patient for four weeks with GnRH, 7-10 microg/pulse, delivered subcutaneously at 90 minute frequency via a portable minipump. This therapy failed to induce any rise in plasma gonadotrophin and testosterone concentrations. By contrast, eight weeks treatment with exogenous gonadotrophins maintained physiological plasma testosterone concentrations and induced testicular enlargement with induction of spermatogenesis. The data indicate that the primary endocrinopathy in GHS is of pituitary gonadotrophin secretion and not of hypothalamic GnRH. Moreover, the patient did not harbour any mutation of the GnRH receptor gene. Two clinical observations are consistent with progressive involution of gonadotrophic function, rather than a congenital gonadotrophin deficiency. First, the patient's development was arrested at early mid-puberty at the time of original presentation and, second, effective spermatogenesis was induced extremely rapidly during gonadotrophin treatment, suggesting prior exposure of the testes to FSH. Both spinocerebellar ataxia and pituitary dysfunction might thus have been in evolution since late childhood.

Topics: Adult; Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Replacement Therapy; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Pulse Therapy, Drug; Spinocerebellar Ataxias; Syndrome; Testosterone

We demonstrate that antitestosterone autoantibody is produced in a 24-yr-old woman with hypergonadotropic hypogonadism. The serum testosterone level measured by RIA was extremely elevated (5.80 ng/mL); after elution, serum testosterone had returned to a normal female value (0.21 ng/mL). The clinical features were suggestive of no androgen activity. Primary follicles were present in the patent's ovary. After gonadotropin treatment, conception was achieved, and a normal female infant was delivered. A gel filtration study showed that the testosterone-binding activity was eluted at the position of 15,000-kDa Ig. Scatchard analysis revealed a low affinity antibody; the association constant was 0.034 x 10(3) mol-1, and the maximal binding capacity was 162 mumol/mL. An immunoprecipitation study the chain-specific antibodies showed that the antitestosterone autoantibody belonged to kappa-type IgG. This subject is the first reported case with an endocrine disorder who possessed autoantibodies against testosterone.

Topics: Adult; Autoantibodies; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Infant, Newborn; Infertility, Female; Karyotyping; Luteinizing Hormone; Male; Menotropins; Ovarian Follicle; Ovulation; Pregnancy; Pregnancy Outcome; Radioimmunoassay; Testosterone

A 17-year-old male diagnosed as having Cat Eye Syndrome (CES) with hypogonadotropic hypogonadism showed short stature and no development of secondary sex characteristics. Exogeneous gonadotropin replacement therapy combining human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) was started. As a result, the short stature and androgen deficiency were relieved. The critical region of CES was tetrasomy of 22 pter-->q11. Abnormalities of other chromosomes which cause hypogonadotropic hypogonadism may exist, thus further investigation is needed.

Topics: Abnormalities, Multiple; Adolescent; Anus, Imperforate; Chorionic Gonadotropin; Chromosomes, Human, Pair 22; Dwarfism, Pituitary; Humans; Hypogonadism; Hypopituitarism; Male; Menotropins; Pituitary Hormones; Puberty, Delayed; Syndrome; Testosterone; Trisomy

Idiopathic hypogonadotrophic hypogonadism (IHH) is a potentially correctable cause of male infertility. However hormonal treatment is usually a slow process and artificial reproductive techniques such as intracytoplasmic sperm injection (ICSI) might be resorted to before full testicular response has been achieved. We report here an unusual variant of IHH of post-pubertal onset in which early intervention with ICSI was attempted. Our patient was 37 years old and presented with male infertility due to azoospermia and undetectable serum gonadotrophin concentrations. He had an apparently normal pubertal development, a testicular volume of 8 ml, normal pituitary-thyroid and pituitary-adrenal function, as well as normal computerized tomographic appearance of the sella region. A combination of human chorionic gonadotrophin (HCG) and menopausal gonadotrophins (HMG) was administered. Spermatozoa were first detected in the semen after 3 months and reached a concentration of approximately 2x10(6)/ml after 9 months. ICSI was attempted at this point; the spermatozoa had good fertilizing ability and three embryos were obtained and replaced. Unfortunately no pregnancy resulted. Treatment with 5000 IU HCG and 150 IU HMG three times per week was continued and sperm counts rose rapidly thereafter to reach 28.3x10(6)/ml after 16 months of injections. His wife conceived naturally during this period and the pregnancy is now in the second trimester. This case illustrates the good prognosis of the rare patient with IHH of post-pubertal onset when treated with gonadotrophins, and suggests that ICSI procedures should be delayed until final testicular maturation is attained.

Topics: Adult; Chorionic Gonadotropin; Cytoplasm; Female; Fertilization in Vitro; Humans; Hypogonadism; Infertility, Male; Male; Menotropins; Microinjections; Pregnancy; Sperm Count; Spermatogenesis; Spermatozoa; Testis

Using a retrospective analysis, we compared cumulative pregnancy rates, early pregnancy failure rates and multiple pregnancy rates in couples with polycystic ovarian syndrome (PCOS) (n = 148), hypogonadotrophic or eugonadotrophic hypogonadism (n = 91) and unexplained infertility (n = 117), who were treated in an ovulation induction clinic between January 1991 and December 1995. The women were treated with either human menopausal gonadotrophin (HMG) or purified follicle stimulating hormone (FSH). The cumulative pregnancy rate (derived from life-table analysis) after four ovulatory treatment cycles was 70% in the PCOS group, 74% in the hypogonadism group and 38% in the unexplained infertility group. The cumulative pregnancy rate in the unexplained infertility group was significantly lower than the other groups (P < 0.001) but there was no significant difference between PCOS and hypogonadism using the log rank test. The early pregnancy failure rate was 25% in the PCOS group, 27% in the hypogonadism group and 26% in the unexplained infertility group (chi(2) = 0.132, not significant). The multiple pregnancy rate was 20% in the PCOS group, 30% in the hypogonadism group and 17% in the unexplained infertility group (chi(2) = 2.105, not significant). Treatment of anovulatory infertility using HMG or FSH is effective irrespective of the cause. Couples with unexplained infertility are less successfully treated using HMG: correction of unexplained infertility may involve more than simple correction of possible subtle ovulatory defects.

Topics: Adult; Body Mass Index; Female; Fetal Death; Follicle Stimulating Hormone; Humans; Hypogonadism; Infertility, Female; Male; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Retrospective Studies

It is known that prostate specific antigen (PSA) is strongly androgen dependent, but little is known about the effects of gonadotropin and testosterone treatments on the prostate and serum PSA levels in male hypogonadism. We have therefore determined serum PSA levels before and 3 months after treatment in 13 patients with idiopathic hypogonadotropic hypogonadism (IHH) and 14 patients with Klinefelter's syndrome. Plasma FSH, LH, testosterone, PRL, testis and prostate volumes were also determined before and 3 months after treatments. Patients with IHH were treated with hCG/hMG and patients with Klinefelter's syndrome received testosterone treatment. PSA levels were determined by a kinetic enzyme immunoassay method. In patients with Klinefelter's syndrome FSH and LH levels were significantly decreased but total and free testosterone and PSA levels were significantly increased after 3 months of treatment. Right and left testicular volumes were not significantly changed whereas prostate volumes were significantly increased after treatment. In this group PSA levels were significantly and positively correlated with the prostate volume both before (r=0.54, P=0.048) and after treatment (r=0.61, P=0.012). In the IHH group total and free testosterone and PSA levels were significantly increased after gonadotropin treatment but FSH and LH levels did not change significantly. Right and left testicular volumes and the prostate volumes were also significantly increased after 3 months of gonadotropin treatment. In this group PSA levels were correlated with prostate volume before (r=0.74, P=0.004) treatment but not after therapy (r=0.35, P=NS). Our results show that serum PSA levels increase after gonadotropin and testosterone treatment in male hypogonadism, but this could not be used as an index for the evaluation of the androgen action in the treatment of male hypogonadism, since PSA levels following treatments were correlated with the prostate volume or T levels only in patients with Klinefelter's syndrome but not in the IHH group.

Topics: Adult; Biomarkers; Biomarkers, Tumor; Chorionic Gonadotropin; Drug Therapy, Combination; Humans; Hypogonadism; Klinefelter Syndrome; Male; Menotropins; Prostate; Prostate-Specific Antigen; Testosterone

It has previously been shown that increased nocturnal melatonin (MT) secretion exists in male patients with hypogonadotropic hypogonadism. However, little is known about the effects of gonadotropin and testosterone (T) treatment on early morning plasma MT levels in male hypogonadism. Also, the impact of gonadal steroids on plasma MT levels is an open question. We, therefore, determined early morning plasma MT levels at the same hour before and 3 months after treatment in 21 patients with idiopathic hypogonadotropic hypogonadism (IHH), 10 patients with primary hypogonadism, and 11 male controls. Plasma FSH, LH, PRL, T, and estradiol levels were also determined before and 3 months after treatment. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with primary hypogonadism received T treatment. Short term treatments did not achieve normal T levels, although significant increases in T were observed in both groups. Plasma MT levels were measured by a RIA with a sensitivity of 10.7 pmol/L. Mean plasma MT levels before treatment were significantly higher in IHH (41.8 +/- 24.4 pmol/L) compared with those in the controls (21.7 +/- 10.8 pmol/L; P < 0.05). However, a slight, but not significant, increase in MT (34.2 +/- 21.1 pmol/L) was found in primary hypogonadism. Mean MT levels did not change significantly 3 months after the initiation of gonadotropin (41.7 +/- 22.8 pmol/L) or T (28.4 +/- 12.6 pmol/L) treatment in either IHH or primary hypogonadism, although a tendency for MT to decrease was observed in both groups. No correlation was found between MT and circulating FSH, LH, PRL, and gonadal steroids either before or after therapy. We conclude that male patients with IHH have increased early morning MT levels, although the pathophysiological mechanism is not clear. Furthermore, our study demonstrated that mean plasma MT levels are not influenced by short term gonadotropin or T treatment in male hypogonadism, although a longer time effect of gonadotropins or T treatment may not be excluded. The lack of correlation between plasma MT and circulating gonadal steroids before and after treatment suggests that there is no classic feedback regulation between the pineal gland and the testes.

Topics: Adult; Chorionic Gonadotropin; Circadian Rhythm; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Melatonin; Menotropins; Prolactin; Sex Hormone-Binding Globulin; Testis

Ovarian hyperstimulation syndrome (OHSS) is the most serious, life-threatening, iatrogenic complication of ovulation induction. The importance of excessive oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration as a predictor and factor in the pathophysiology of OHSS has been extensively studied and discussed. We present the case report of a woman with hypogonadotrophic hypogonadism who developed severe OHSS during ovulation induction with urinary human follicle stimulating hormone (FSH) and HCG in the presence of low circulating oestradiol concentrations. The implication of FSH treatment and complications in hypogonadotrophic hypogonadal patients, and the role of preovulatory oestradiol concentrations in the prediction of OHSS, are discussed.

Topics: Adult; Chorionic Gonadotropin; Craniopharyngioma; Estrogens; Female; Humans; Hypogonadism; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pituitary Neoplasms

Topics: Adult; Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropins; Growth Hormone; Humans; Hypogonadism; Insulin-Like Growth Factor I; Luteinizing Hormone; Male; Menotropins; Spermatogenesis; Testosterone

It is known that lipoprotein(a) [Lp(a) is an independent risk factor for developing atherosclerosis, whereas the LpA-I particle of high density lipoprotein (HDL) is an antiatherogenic factor. The effects of androgen replacement therapy on lipid and lipoproteins have previously been reported in male hypogonadism. However, no study reported the effect of gonadotropin or testosterone treatment on Lp(a), LpA-I, or LpA-I;A-II levels in make hypogonadism. We, therefore, determined Lp(a), LpA-I, LpA-I:A-II, and other lipoprotein levels before and 3 months after treatment in 22 patients with idiopathic hypogonadotropic hypogonadism (IHH) and in 9 patients with Klinefelter's syndrome. All patients had been previously untreated for androgen deficiency. Plasma FSH, LH, PRL, testosterone (T), estradiol, and dehydroepiandrosterone sulfate levels were also determined before and 3 months after treatment. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with Klinefelter's syndrome received T treatment. Three months after treatment, mean T levels role to low normal levels in both groups. Triglyceride, LpA-I:A-II, Lp(a), HDL cholesterol, HDL3 cholesterol, and apolipoprotein (apo) A-I concentrations did not change significantly after treatment, whereas total cholesterol, low density lipoprotein cholesterol, LpA-I, and HDL2 concentrations were significantly increased 3 months after treatment in both groups. The apo B concentration significantly increased in patients with klinefelter's syndrome, whereas no change was observed in the IHH group. Lp(a) concentrations were not related to all hormonal and clinical parameters in both groups. LpA-I concentrations were significantly and negatively correlated with free T (r = -0.80; P = 0.010) in patients with Klinefelter's syndrome and were not correlated with all hormonal and clinical parameters in the IHH group. The LpA-I:A-II concentration was only correlated with body mass index (r = -0.83; P = 0.005) in patients with Klinefelter's syndrome, whereas it was correlated negatively with dehydroepiandrosterone sulfate (r = -0.57; P = 0.005) in the IHH group.2 Overall, our study demonstrates that gonadotropin or T treatment has a complex effect on lipids and lipoproteins. This complexity will be resolved when sufficient large scale androgen treatment data are available for assessment of the long term outcome of androgen treatment. The increases in total cholesterol and low density lipoprotein chol

Topics: Adult; Apolipoprotein A-I; Apolipoprotein A-II; Chorionic Gonadotropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Follicle Stimulating Hormone; Humans; Hypogonadism; Klinefelter Syndrome; Lipoprotein(a); Lipoproteins; Lipoproteins, HDL; Luteinizing Hormone; Male; Menotropins; Testosterone

Delayed puberty and hypogonadism are frequently observed in patients with homozygous beta-thalassaemia. We evaluated the pituitary-testicular axis in 30 thalassaemic men, aged from 17 to 35 years who were regularly transfused and underwent chelation therapy, while emphasis was given to pituitary reserves of gonadotrophins and the correlation of hormones with serum ferritin (SF). The investigation included endocrinological examination, evaluation of serum basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and gonadotrophin-releasing hormone (GnRH) test and also spermiograms. According to the results, patients were divided into three groups: group A, which included 18 eugonadal patients with moderately elevated SF, group B which included six patients who had hypogonadotrophic hypogonadism and excessive elevation of SF, and group C, which included six patients characterized as intermediate, with regard to sexual maturation and SF levels. In conclusion, beta-thalassaemia major leads to variable pituitary iron overload and thus hypophyseal damage. This endocrine disturbance is becoming less frequent nowadays with early and intensive chelation therapy.

Topics: Adolescent; Adult; beta-Thalassemia; Chorionic Gonadotropin; Drug Combinations; Ferritins; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hypogonadism; Male; Menotropins; Pituitary Gland; Puberty, Delayed; Spermatozoa; Testis; Treatment Outcome

To investigate the role of FSH in the depletion of follicular reserve in a human being.. Prospective evaluation of a very rare case.. Academic research environment.. A 43-year-old woman with primary hypogonadotropic hypoestrogenic amenorrhea, with very low levels of plasma FSH throughout her life.. Pulsatile GnRH was administered IV at the dose of 4 micrograms every 90 minutes for 20 days. Blood samples were collected every 3 to 4 days.. Plasma levels of E2, FSH, and LH.. During the 20 days of treatment there was no increase in E2 plasma levels. On the contrary, FSH and LH levels began to rise after 3 days and reached postmenopausal levels within 20 days.. Depletion of follicular reserve may occur also when the levels of FSH are very low throughout a woman's life. Thus FSH seems only able to rescue follicles from atresia without interfering with the onset of menopause.

Topics: Adult; Amenorrhea; Estradiol; Estrogen Replacement Therapy; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovulation Induction

To evaluate the relative importance of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in follicular development and oocyte fertility in the human species, the use of recombinant human FSH, human menopausal gonadotrophin (HMG), and very highly purified urinary human FSH (FSH-HP) plus oestradiol valerate for ovarian stimulation and in-vitro fertilization (IVF) were compared in three cycles in a woman with isolated congenital gonadotrophin deficiency who had never been treated with ovarian stimulating agents. The total number of ampoules of gonadotrophins used was lower in the HMG treatment cycle. Ovarian response and IVF outcome in the three treatment cycles were as follows: (i) HMG cycle: normal follicular growth, normal pattern of oestradiol and inhibin through the menstrual cycle, high fertilization rate (93%); (ii) recombinant FSH cycle: normal follicular growth, low oestradiol and abnormal inhibin, finally poor rate of fertilization (28%); (iii) FSH-HP plus oestradiol valerate cycle: normal follicular growth, normal pattern of inhibin and poor fertilization rate (27%). Luteal plasma progesterone concentrations were much higher in the HMG treatment cycle. This case shows that FSH is the only factor required in order to induce follicular growth in the human, although LH or a product derived from its action may assist in order to achieve full follicular maturity and oocytes capable of fertilization. Though oestradiol might have a mediatory role in the process of follicular maturation, our results favour a direct primary role of LH in complete maturation of the follicle.

Topics: Adult; Chronic Disease; Drug Therapy, Combination; Estradiol; Female; Fertility; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Oocytes; Ovarian Follicle; Recombinant Proteins

The effects of gonadotrophin administration to 17 Chinese patients with hypogonadotrophic hypogonadism (HH) on testicular volume and induction of spermatogenesis were studied. Ten subjects had isolated HH and seven had hypopituitarism. Twelve of the subjects had prepubertal onset of HH and five of them had been treated previously with hCG for induction of puberty. None had a history of cryptorchidism. During hCG treatment for induction of spermatogenesis, all subjects had an increase in serum levels of testosterone into the normal adult male range and their testes increased in size from 3 (1-20) ml to 11.6 (5-20) ml [median(range), p < 0.02]. Six subjects required treatment with hCG alone. However, the remaining 11 subjects, after at least 6 months treatment with hCG, required the addition of human menopausal gonadotrophin (hMG) to induce spermatogenesis. Two subjects remained azoospermic. One had a history of mumps orchitis and the other had isolated elevation of blood FSH levels, suggestive of primary testicular failure in addition to HH. Excluding one subject with fertile eunuch syndrome, the mean duration for first appearance of spermatozoa was 13 (4-52) months. Twelve subjects became fertile and pregnancy was achieved in their partners after 20 (4-78) months. The weekly doses for hCG and hMG were 4000 (3000-10,000) IU and 225 (225-450) IU, respectively. Patients who responded to hCG alone had a significantly larger pretreatment testicular volume, suggesting that they had only partial gonadotrophin deficiency. Prepubertal onset of hypogonadism was not a determining factor for requirement of hMG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; China; Chorionic Gonadotropin; Drug Therapy, Combination; Humans; Hypogonadism; Male; Menotropins; Middle Aged; Spermatogenesis; Treatment Outcome

Topics: Adult; Aged; Chorionic Gonadotropin; Fertility; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Puberty; Sperm Count; Spermatogenesis; Testosterone

The objective of this paper was to assess the ability of gonadotropin administration to induce ovarian steroidogenesis, follicle maturation and ovulation in hypogonadal women affected by beta-thalassemia. Thirteen hypogonadal thalassemic women underwent a test with gonadotropin-releasing hormone (GnRH), with estimation of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. They were then administered human menopausal gonadotropin (hMG) for a period ranging from 11 to 15 days with a total dose variable from 3,300 to 4,200 IU. In each patient, the initial dosage of 300 IU daily, adopted for the first 9 days, was modified subsequently according to the ovarian morphology, as shown by serial echographic examinations and by serum estradiol levels. In those patients in whom a dominant follicle was evidenced and the occurrence of pregnancy could be excluded, induction of ovulation was attempted by administration of 10,000 IU of human chorionic gonadotropin (hCG). All patients displayed a reduced LH and FSH rise in response to GnRH. Upon hMG administration, they exhibited echographic evidence of follicular growth with a clear-cut increase of serum estradiol, which peaked between the 9th and the 16th day from the start of treatment. In two out of three patients in whom a dominant follicle developed, ovulation was induced successfully by hCG injection, as shown by the increase of serum progesterone and by the ultrasonographic demonstration of a corpus luteum. This study has shown that, by proper pharmacological stimulation, the steroidogenic function of the gonads and even ovulation can be reinstated in hypogonadal thalassemic women.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; beta-Thalassemia; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovary; Ovulation Induction; Ultrasonography

This study was designed to determine the response to therapy using human chorionic gonadotrophin (hCG) and human menopausal gonadotrophin (hMG) in males with idiopathic isolated hypogonadotrophic hypogonadism (IHH), and to compare the responses in patients presenting with and without cryptorchidism.. Analysis of male patients with IHH treated with hCG or combined hCG/hMG for a minimum of 6 months at St Bartholomew's Hospital. Clinical and endocrine assessment was performed in all patients prior to commencing therapy.. A total of 26 males with IHH have been treated with exogenous gonadotrophins. Thirteen patients (Group 1) had cryptorchidism (unilateral in 7, bilateral in 6) at presentation, and 13 (Group 2) did not.. All patients had basal serum testosterone, LH and FSH determinations. An i.v. GnRH test was performed in 25 patients and an i.m. hCG stimulation test in 19. Testicular volume and serum testosterone were measured during both hCG and combined hCG/hMG therapy. Seminal analysis was performed at the start and monthly during hCG/hMG therapy.. Eighty-five per cent of the 13 patients in Group 1 had an olfactory defect (Kallmann's syndrome), compared with 23% of Group 2. Both groups of patients showed a subnormal response to initial i.v. GnRH and i.m. hCG testing. During hCG therapy only three patients in Group 1 and six in Group 2 achieved normal adult testosterone levels. The non-cryptorchid group achieved a higher mean testicular volume on hCG therapy than the cryptorchid group (mean (SD); 4.7 (1.8) ml vs 3.0 (1.6) ml (P < 0.02)), and for all patients there was a correlation between initial and maximal testicular volume (R = 0.69, P = 0.001). Four patients in Group 1 and five patients in Group 2 were treated with combined hCG/hMG for 6-15 months to induce fertility; only one patient in Group 1 achieved spermatogenesis, compared to all patients in Group 2 (leading to three pregnancies).. These data indicate that patients with idiopathic hypogonadotrophic hypogonadism (IHH) have a poor response to hCG therapy in terms of testicular growth and normalization of serum testosterone. Final testicular volume is dependent on initial testicular size. In addition, patients with IHH associated with cryptorchidism have a poor fertility potential to combined hCG/hMG therapy.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Cryptorchidism; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Male; Menotropins; Middle Aged; Testis; Testosterone

An analysis was performed on the cumulative conception rates, cumulative live birth rates and adverse effects of ovulation induction in patients with anovulatory infertility attending a single unit over an 11-year period. A total of 200 patients were included, 103 with clomiphene-resistant polycystic ovary syndrome (PCOS), 77 with hypogonadotrophic hypogonadism (HH) and 20 with weight-related amenorrhoea (WRA). Ovulation induction was performed using a number of protocols in which pulsatile luteinizing hormone-releasing hormone was administered s.c. or i.v. and gonadotrophins (human menopausal gonadotrophins or follicle-stimulating hormone) were administered i.m. The cumulative conception and live birth rates in the first course of therapy and after 12 cycles of treatment were, respectively, 73.2 and 62.4% in PCOS patients, 82.1 and 65.4% in the HH group and 95.0 and 85.3% in the WRA group. The miscarriage rates for all courses of treatment were 15.5% in PCOS patients, 22.9% in HH patients and 32.3% in WRA patients which resulted in cumulative live birth rates that were not significantly different. The median number of cycles and ovulations to achieve a pregnancy was 2 in all groups. The multiple pregnancy rate was significantly greater in women with PCOS (17.9%) than in women with HH (3.6%, P = 0.0052, 95% CI 5.12-23.36%) but not WRA (3.2%, P = 0.07, 95% CI 4.35-24.92%). The rate of multiple pregnancy fell after the introduction of monitoring by transvaginal ultrasound. Correction of anovulatory infertility by appropriately selected ovulation induction regimens results in cumulative conception and live birth rates indistinguishable from normal.

Topics: Amenorrhea; Anovulation; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple

Epidermal growth factor (EGF) content in seminal plasma of 17 patients with androgen deficiency (12 Klinefelter's syndrome and 5 hypogonadotropic hypogonadism) was determined before and after hormone replacement. No significant increase of plasma testosterone level was demonstrated after testosterone administration in Klinefelter's syndrome, although the level in 4 of 5 patients with hypogonadotropic hypogonadism reached the normal range. In 16 patients, except 1 with hypogonadotropic hypogonadism with no increase of blood testosterone level, prostate volume increased after hormone therapy, and volumes after treatment were significantly larger than those before treatment. On the other hand, EGF concentration in seminal plasma remained at the pretreatment level in most patients. It is therefore concluded that although the prostate volume increases to almost normal after treatment, prostate function does not improve in most patients, indicating that in patients with hypogonadotropic hypogonadism fertility potential may remain low, even if they obtain normal seminal parameters after treatment.

Topics: Adult; Chorionic Gonadotropin; Epidermal Growth Factor; Humans; Hypogonadism; Klinefelter Syndrome; Male; Menotropins; Prostate; Semen; Testosterone

Exogenous gonadotropins or pulsatile gonadotropin-releasing hormone is now most commonly used to treat male infertility due to hypogonadotropic hypogonadism. We report three cases of hypogonadotropic hypogonadism with variable etiologies and presentations who were successfully treated with exogenous gonadotropins and/or testosterone for their infertility. The diagnosis and clinical presentations of these three patients are summarized as follows. The first patient was a case of Kallmann's syndrome presented with short stature, infantile genitalia and anosmia. The second patient was a case of idiopathic hypogonadotropic hypogonadism presented with small genitalia and impotence. The third patient was a case of acquired hypogonadotropic hypogonadism due to pituitary adenoma presented with impotence, cold intolerance and visual field defect. After adequate therapy with human chorionic gonadotropin, human menopausal gonadotropin and/or testosterone, the secondary male characteristics of these three patients improved and the fertility were all restored.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Humans; Hypogonadism; Infertility, Male; Male; Menotropins; Testosterone

We report a very rare case of a girl with hypogonadism probably due to inactive FSH. She had been diagnosed as carbohydrate-deficient glycoprotein syndrome. The 14-year-old patient had no secondary sexual characteristics with the 46,XX karyotype and estradiol (E2) levels were undetectable. Follicle stimulating hormone (FSH) levels were extremely high and responded exaggeratedly to luteinizing hormone-releasing hormone (LH-RH). The E2 levels, on the other hand, were elevated after stimulation with human menopausal gonadotropin (75 units/day) for 5 days, suggesting biologically inactive FSH in the circulation. Abnormal structure in the glycoprotein may be possibly related with hypogonadism.

Topics: Adolescent; Carbohydrate Metabolism, Inborn Errors; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Intellectual Disability; Menotropins; Sexual Maturation; Syndrome

In men with hypogonadotropic hypogonadism, prolonged treatment with LH and FSH induces spermatogenesis. To compare the respective role of exogenous testosterone and intratesticular testosterone on the induction and maintenance of spermatogenesis, 10 men with hypogonadotropic hypogonadism and without history of cryptorchidism were studied. They were treated with human gonadotropins (hMG; 150 IU FSH and LH and 1500 IU hCG, im, three times weekly) or pure FSH (150 IU, im, three times a week) and testosterone (T: 250 mg, im, once a week). Five men were treated first with hMG-hCG and then with pure FSH plus T. The other five men started with pure FSH plus T. Each treatment period lasted 24 months. In all men, hMG-hCG induced spermatogenesis after 24 months, with normal motility and quality. The combination of pure FSH and T was not able to induce spermatogenesis after 24 months. In addition, sperm count dropped dramatically to 0.3 +/- 0.1 x 10(6)/mL within 3 months and to 0 after 6 months when pure FSH and T followed [corrected] hMG-hCG. Plasma T levels were increased by both treatments, but significantly more after pure FSH and T (35.3 +/- 5.2 nmol/L) than after hMG-hCG (20.4 +/- 5.2 nmol/L; P < 0.05). Plasma estradiol levels after treatment with pure FSH and T were also increased, but the difference from those obtained during hMG-hCG treatment was not significant. In conclusion, in men with complete gonadotropin deficiency, FSH and exogenous T are not able to induce spermatogenesis. Furthermore, spermatogenesis induced by LH plus FSH (hMG-hCG) cannot be maintained when exogenous T replaced LH in the regimen. Thus, exogenous T is unable to replace LH (and intratesticular T) to induce spermatogenesis. These data are noteworthy in the prospect of male contraception after a complete blockade of gonadotropin activity.

Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Follicle Stimulating Hormone; Humans; Hypogonadism; Male; Menotropins; Spermatogenesis; Testosterone

We report on two males with prolactinoma in whom hyperprolactinaemia and hypogonadism persisted for several years postoperatively despite the administration of a dopamine agonist or bromocriptine. In these patients, a GnRH test revealed no response in the levels of serum LH or FSH. An hCG stimulation test provoked no response in the serum levels of testosterone. Case 1, who was 28 years old at the first visit, received parenteral testosterone and appreciable virilization of the genitalia was noted within a few months. When he married and desired to father a child, the treatment was switched to hCG/hMG combined therapy and spermatozoa appeared subsequently in the ejaculate, although their numbers were low. His wife conceived and delivered a healthy baby girl. Case 2 was a single young man who presented with hypogonadotrophic hypogonadism and hyperprolactinaemia. He was started on hCG injections three times per week and the maturation of his genitalia was advanced rapidly. Semen analyses showed sperm concentration and motility to be within the normal range. Post-treatment GnRH test revealed no improvement in gonadotrophin responses for LH or FSH. In both cases, the hCG test repeated after the gonadotrophin treatment showed normal basal and stimulated testosterone levels. During the course of gonadotrophin treatment in these cases, serum prolactin levels remained elevated, and it is suggested that, in the two cases, the hypothalamo-pituitary function was disturbed by the tumour or its manipulation and the capacity of the pituitary gland to secrete gonadotrophin was impaired. Under such circumstances with persisting hyperprolactinaemia, hCG and/or hCG/hMG combination treatment can induce normal virilization and advance spermatogenesis sufficiently to achieve fertility.

Topics: Adult; Chorionic Gonadotropin; Gonadotropins; Humans; Hyperprolactinemia; Hypogonadism; Male; Menotropins; Pituitary Neoplasms; Postoperative Complications; Prolactinoma

In this study, pulsatile gonadotrophin releasing hormone (GnRH) therapy and gonadotrophin therapy were compared for male patients with idiopathic hypothalamic hypogonadism. Thirty-six patients, 19 with this condition, and 17 with Kallmann's syndrome, were included in the study. Their mean age was 21.1 +/- 3.0 years (+/- SD). They were divided into two groups of similar age, number and testicular volume. Pulsatile GnRH therapy was started with 4 micrograms GnRH s.c. every 2 h using a portable pump and gonadotrophin therapy with weekly i.m. injections of 3 x 2500 IU human chorionic gonadotrophin (HCG). After 8-12 weeks of HCG treatment, 150 IU human menopausal gonadotrophin (HMG) 2-4 times weekly were added and the dose of HCG reduced if necessary. Testosterone concentrations increased significantly more (P < 0.03) in the gonadotrophin group than in the GnRH group (22.5 +/- 8.1 versus 16.8 +/- 5.5 nmol/l). The rise in oestradiol levels was also significantly higher (P < 0.001) in the gonadotrophin group than in the GnRH group (150 +/- 70 versus 88 +/- 59 pmol/l). Five patients developed gynaecomastia during gonadotrophin therapy. An increased testicular volume (TV) occurred more rapidly (P < 0.001) and was significantly more pronounced (P < 0.001) after GnRH therapy (delta TV = 8.1 +/- 2.0 ml) than with gonadotrophins (delta TV = 4.8 +/- 1.8 ml). Sperm counts were performed in 14 patients given GnRH and in 17 patients given gonadotrophins. Ten patients given GnRH had positive sperm counts, ranging from 1.5 to 14 x 10(6) spermatozoa/ml; eight of those given gonadotrophins also developed spermatogenesis (2-26 x 10(6)/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chorionic Gonadotropin; Estradiol; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamic Diseases; Male; Menotropins; Sperm Count; Spermatogenesis; Testis; Testosterone

We determined whether or not self-administered subcutaneous human menopausal gonadotrophin (hMG) therapy is safe and effective in the stimulation of testicular growth and initiation of spermatogenesis in men with hypogonadotrophic hypogonadism where human chorionic gonadotrophin alone had failed.. Human menopausal gonadotrophin was self-administered subcutaneously in two dosage regimens to patients requiring (a) fertility (Group I), 37.5 IU twice daily (total weekly dose 525 IU) (n = 7) and (b) increased testicular size (Group II) 37.5 IU once daily (total weekly dose 265.5 IU) (n = 2). Patients were assessed on a monthly basis.. Nine patients with hypogonadotrophic hypogonadism were studied. Six patients had idiopathic isolated hypogonadotrophic hypogonadism, one Kallman's syndrome, one idiopathic isolated hypogonadotrophic hypogonadism secondary to trauma and one with panhypopituitarism secondary to radiotherapy for a hypothalamic pituitary tumour. Five of these patients had a history of unilateral or bilateral cryptorchidism.. Semen analysis and serum testosterone. Testicular size was assessed by use of a Prader orchidometer.. Six of seven patients (four with a history of cryptorchidism) requesting fertility attained sperm counts of > 10 million/ml. Three pregnancies have been achieved so far. One failure occurred in a patient with a previous history of cryptorchidism. In Group I patients (a) with an initial testicular volume of 4 ml or less (n = 4), mean size increased from 3.25 +/- 0.9 (SD) ml to 12.2 +/- 3.8 ml, (b) an initial testicular volume of > 4 ml mean size (n = 3) increased from 9.2 +/- 3.9 ml to 10.3 +/- 4 ml. In Group II (n = 2) testis size increased from a mean of 3.0 +/- 1.4 ml to 9.0 +/- 1.4 ml over a 6-months treatment period.. Self-administered subcutaneous human menopausal gonadotrophin is a safe and effective mode of therapy in increasing testicular size and inducing spermatogenesis in males with hypogonadotrophic hypogonadism.

Topics: Adolescent; Adult; Drug Administration Schedule; Humans; Hypogonadism; Male; Menotropins; Self Administration; Spermatogenesis; Testis

A case of latent Addison's disease accompanied by hypogonadotropic hypogonadism and dwarfism is described. A 20-year-old man was admitted to our department complaining of short stature and immature development of the external genitalia. Pigmentation was most evident on the fingers and face. Endocrinologically, serum ACTH level was very high, and serum cortisol level was in the lower limit of the normal range. Serum aldosterone and adrenal androgen levels were below their normal ranges. Based on these clinical and laboratory findings, the patient was diagnosed as having latent Addison's disease. Serum LH did not respond to a bolus injection of LH-RH. However, after 3 days administration of LH-RH, the response of serum LH to a bolus injection of LH-RH was enhanced. Serum testosterone level was not increased after the administration of hCG. These findings suggested a hypothalamic cause for the hypogonadism. It was indicated that short stature was apparently caused by GH neurosecretory dysfunction, since nocturnal GH secretion was below that in normal males and the response of GH to the administration of arginine was normal. In regard to the thyroid function, the peak of serum TSH after a bolus injection of TRH was delayed compared with normal subjects, and although serum T4 level was high, the basal metabolic rate was very low. This suggests that there is tissue resistance to the elevated thyroid hormone.

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; Aldosterone; Chorionic Gonadotropin; Cortisone; Dwarfism; Follicle Stimulating Hormone; Growth Hormone; Humans; Hydrocortisone; Hypogonadism; Luteinizing Hormone; Male; Menotropins

To determine whether delay of puberty alters adult height, we retrospectively evaluated the adult height of 41 patients who met rigorous criteria for the diagnosis of isolated hypogonadotropic hypogonadism. The adult height of these patients was compared with the mean height of normal American men at age 18 in the 1979 National Center for Health Statistics survey and with the mean adult height of 50 male normal volunteers who had been studied on the same wards as the patients with hypogonadotropic hypogonadism. The mean adult height of the men with isolated hypogonadotropic hypogonadism was 179.7 cm, which exceeded the height of the 50 control subjects and the normal American men (both 176.8 cm) by 2.9 cm (P less than 0.05 and P less than 0.006, respectively). The mean age at treatment to induce puberty was 20.0 yr, which corresponded to a mean delay in the onset of puberty of more than 8 yr relative to normal males. The final height of the men with hypogonadotropic hypogonadism correlated significantly with the duration of pubertal delay (r = 0.32, P = 0.04). Most of the enhanced mean adult height of the patients with isolated hypogonadotropic hypogonadism was attributable to those patients in whom treatment to induce puberty had been delayed to age 18 or greater. The mean adult height of these patients was 182.4 cm, or 5.6 cm greater than the mean height of the 50 controls or of normal American men (P less than 0.001). The mean adult height of patients whose treatment began between 10 and 17 yr of age was 175.0 cm, which did not differ significantly from that of normal men. We conclude that prolonged delay of puberty (6 or more yr) in men with isolated hypogonadotropic hypogonadism is associated with a modest increase (approximately 5 cm) of adult height.

Topics: Adolescent; Adult; Body Height; Chorionic Gonadotropin; Drug Therapy, Combination; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Prolactin; Puberty, Delayed; Reference Values; Retrospective Studies; Testosterone

To induce spermatogenesis by cotreatment with growth hormone (GH) and gonadotropin therapy in patients with hypogonadotropic hypogonadism who had failed to respond adequately to conventional treatment.. Cotreatment with GH (4 IU) and human menopausal gonadotropin, 150 IU of follicle-stimulating hormone and 150 IU of luteinizing hormone (LH), three times a week, and human chorionic gonadotropin, 2,500 IU, two times a week for 24 weeks after unsuccessful treatment for 12 weeks with either pulsatile LH-releasing hormone or gonadotropins.. Specialist Reproductive Endocrine Unit.. Seven patients, four of whom had failed to respond adequately to the conventional treatment.. Serum testosterone (T), estradiol, and sperm production, testicular and semen volume, and serum insulin-like growth factor-I and inhibin concentrations.. Of the four patients who received cotreatment with GH, three increased T secretion (greater than 11 nmol/L) within a relatively short period of time, two produced adequate amount of sperm (13 and 12 x 10(6)/mL), and one of them impregnated his wife. One patient did not respond.. The results offer a new approach to the problem of induction of spermatogenesis in patients who respond poorly to conventional treatment because cotreatment with GH enhanced T secretion and sperm production in a relatively short period of time.

Topics: Adult; Chorionic Gonadotropin; Gonadotropin-Releasing Hormone; Gonadotropins; Growth Hormone; Humans; Hypogonadism; Male; Menotropins; Osmolar Concentration; Sperm Count; Spermatogenesis; Testosterone

Nine female and 20 male hypogonadotropic GH-deficient patients were studied for sexual development by hCG/hMG. In the female patients, gonadotropin therapy was started at the mean age of 22.7 +/- 2.1 years. The administration of progesterone induced withdrawal bleeding at an average of 2.77 +/- 1.94 years after the initiation of hMG/hCG therapy in 8 of the 9 patients studied. Of 6 patients who had been confirmed as positive in a gestagen test, induction of ovulation by hMG/hCG was observed in 5 patients at an average of 5.58 +/- 1.23 years after the onset of therapy, but not in the remaining patient who had been given estrogen and progesterone 4 years 9 months prior to the initiation of the gonadotropin therapy. In male patients, gonadotropin therapy was started at the mean age of 23.6 +/- 5.7 years. Seminal fluid was obtained by masturbation and brought to our clinic in the morning. Of the 20 patients, 19 patients could be observed once a month regularly. Of the 19 patients, spermatozoa could be detected at a mean period of 2.19 +/- 0.87 years after initiation of hCG/hMG therapy in 18, but not in the remaining patient, after 5 years of therapy, who did not receive hCG/hMG regularly. The sperm count exceeded 20 x 10(6)/ml and more in 12 and was lower than that in 8 patients after 3 years of the therapy. No side effects were observed in female patients, but gynecomastia developed in 2 of the 20 male patients. These data suggest that gonadotropin therapy for hypogonadotropic GH-deficient patients is effective in promoting ovulation and spermatogenesis despite the initial replacement therapy with sex hormones.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Female; Gonadal Steroid Hormones; Growth Hormone; Humans; Hypogonadism; Male; Menotropins; Ovulation Induction; Progesterone; Sperm Count; Spermatogenesis

A 37 year-old female with Kallmann syndrome and NIDDM who had two successful deliveries is reported. She had experienced no menstruation until she had treatment with gestagen in her early twenties. She had withdrawal bleeding only once. At the age of 25, she consulted her family doctor, complaining of amenorrhea. Estrogen progesterone cyclic therapy caused withdrawal bleeding, and clomiphene citrate failed to induce apparent ovulation. In January 1978, 150 IU of hMG was administered daily for 9 days, and then 3000 IU of hCG daily for the following 2 days. This therapy induced pregnancy, which failed spontaneously on June 4th. A year later, in January 1979, 150 IU of hMG was again administered daily for 7 days followed by 6000 IU of hCG for 3 days. This therapy again induced pregnancy. On September 27th, 1979, she delivered a girl vaginally, weighing 3830 g. After this delivery, she experienced no menstruation. In June 1985, she consulted her family doctor again, and she was diagnosed as being pregnant. Since her fasting blood glucose was 145 mg/dl, she was admitted to Kosei Hospital to control her blood glucose. On October 15th, she delivered a girl weighing 2600 g. On June 13th, 1989, she was referred to Kosei Hospital by her family doctor to achieve an accurate control of her blood glucose. During this admission, she was diagnosed as having Kallmann syndrome because of congenital anosmia and hypogonadotropic hypogonadism without any abnormal morphological changes. Vitamin B1 infusion test was negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chorionic Gonadotropin; Diabetes Mellitus, Type 2; Female; Humans; Hypogonadism; Labor, Obstetric; Menotropins; Nervous System Diseases; Pregnancy; Pregnancy in Diabetics; Smell; Syndrome

The response to subcutaneous (SC) gonadotropin replacement therapy, using human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or hCG alone, was evaluated in male hypothalamic hypogonadism.. Sixteen patients with hypothalamic hypogonadism were treated with gonadotropins for induction of puberty and normalization of spermatogenesis. The results were analyzed retrospectively.. The study was carried out in a clinical endocrinology department providing tertiary care and in private practices of endocrinology.. Eight patients with idiopathic hypogonadotropic hypogonadism and eight patients with Kallmann's syndrome in prepubertal or early pubertal stages.. Human chorionic gonadotropin and hMG were administered SC in individual dosages.. Increase of serum testosterone (T), testicular volume, semen volume, and sperm count were evaluated.. Normalization of serum T and complete sexual maturation was achieved in all patients. Spermatogenesis was induced in all but two patients. Seven patients showed normal findings in semen volume and sperm count, and two patients had semen quality close to normal. In five patients sperm count remained less than 10 x 10(6)/mL.. The results obtained by SC gonadotropin replacement prove this mode of administration to be effective in stimulating steroidogenesis and spermatogenesis in hypogonadotropic males.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Eunuchism; Humans; Hypogonadism; Injections, Intramuscular; Male; Menotropins; Retrospective Studies; Sexual Maturation; Spermatogenesis; Testis; Testosterone

Four anovulatory patients who did not respond to large doses of hMG over 18-33 days were co-treated in subsequent cycles with human growth hormone. Treatment with growth hormone markedly raised serum insulin-like growth factor concentrations. Two patients had a dramatic ovarian response within 7 days of co-treatment; two menopausal patients did not respond. This combined therapy may be of practical value for ovulation induction in non-menopausal patients with non-responsive ovaries.

Topics: Addison Disease; Adult; Drug Therapy, Combination; Female; Growth Hormone; Humans; Hypogonadism; Infertility, Female; Insulin-Like Growth Factor I; Menopause; Menotropins; Ovarian Follicle; Ovulation Induction; Uterus

The aim of human menopausal gonadotropin treatment (hMG), to simulate normal follicular development by injecting FSH and LH and induce follicular rupture with hCG, is rarely met. Multiple follicular development occurs because hypothalamic-pituitary feedback is bypassed. This, exacerbated by the long half-life of hCG, causes the principal complications of hMG therapy--multiple pregnancy and hyperstimulation. The initial use of hMG in pituitary deficiency has been widened to include failure to respond to clomiphene, polycystic ovaries, 'unexplained infertility' and in vitro fertilization. Reported pregnancy rates, incidence of hyperstimulation and of multiple pregnancy vary widely. We reviewed the results of hMG therapy from 1977 to 1989 in 260 consecutive women with clomiphene-resistant infertility. Conception and live birth rates after six treatment cycles were 45.7% and 43.3%, respectively and were influenced by the cause of infertility, age, weight and sperm parameters. The miscarriage rate was 18.6% and multiple pregnancy rate 19.3%. The conception rate fell during the 12-year period in all groups except those with regular anovulatory cycles. Over this period, age, weight and male subfertility increased in patients referred to us. hMG is an effective and safe treatment for women with clomiphene-resistant infertility and patent tubes.

Topics: Adult; Age Factors; Estradiol; Female; Fertilization; Humans; Hypogonadism; Infertility, Female; Menotropins; Obesity; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Progesterone

To document the persistence of a sensitizing effect of human growth hormone on the ovarian responsiveness to human menopausal gonadotrophin in anovulatory patients resistant to standard gonadotrophin doses.. We performed an open study of three patients given 4, 12 or 24 IU recombinant growth hormone on alternate days for 5-7 doses, concomitantly with gonadotrophin, and assessed gonadotrophin dose requirements before, during and after the cycle of growth hormone therapy.. We studied two with isolated gonadotrophin deficiency and primary amenorrhoea and one with a pituitary tumour and hyperprolactinaemia which normalized with bromocriptine but in whom there was persisting secondary amenorrhoea.. We measured body mass index, FSH, LH, prolactin, growth hormone, insulin-like growth factor I (IGF-I), oestradiol and inhibin at baseline and growth hormone, IGF-I, oestradiol and inhibin during treatment. In addition we noted the numbers of ampoules (75 IU) and the last pre-hCG dose of gonadotrophin used before, during and after growth hormone therapy.. Baseline growth hormone levels were low but IGF-I levels were normal. IGF-I increased by 20% in the subject given 4 IU growth hormone, and by 50-100% in the other two. Pretreatment daily gonadotrophin dosage of 8-11 ampoules pre-hCG was reduced to 3-6 ampoules during growth hormone and 3-4 post growth hormone. This effect persisted for 4 cycles over 7 months in one subject.. Growth hormone causes persisting ovarian sensitization to gonadotrophin and may produce a substantial lowering of gonadotrophin requirement for ovulation induction in patients with large dosage needs.

Topics: Adult; Anovulation; Female; Growth Hormone; Humans; Hypogonadism; Insulin-Like Growth Factor I; Menotropins; Menstruation; Ovary; Ovulation Induction; Time Factors

To attempt the monitoring of ovulation induction solely with ultrasound (US).. Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle.. Specialist Reproductive Endocrine Unit.. Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients.. Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations.. Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008).. Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.

Topics: Adult; Anovulation; Endometrium; Estradiol; Female; Humans; Hypogonadism; Luteal Phase; Menotropins; Monitoring, Physiologic; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Ultrasonography; Uterus

We measured by RIA the inhibin concentrations in the sera of 20 men with hypogonadotropic hypogonadism before and during treatment with gonadotropins in order to determine the role of gonadotropins in the control of inhibin secretion and the utility of the serum inhibin concentration in assessing the spermatogenic response to gonadotropin treatment in these patients. Before treatment the mean serum inhibin concentration in the 20 hypogonadotropic men as a group (391 +/- 49 U/L) was significantly lower (P less than 0.001) than that in 27 normal men (741 +/- 52 U/L). In the 7 men whose hypogonadism was of postpubertal onset, the mean serum inhibin concentration (559 +/- 69 U/L) was not significantly lower than that in normal men. In the 13 men whose hypogonadism was of prepubertal onset, the serum inhibin level was significantly lower [381 +/- 74 U/L (P less than 0.01) in the 7 without a history of cryptorchidism and 207 +/- 46 U/L (P less than 0.01) in the 6 with a history of cryptorchidism]. All 20 patients were azoospermic or severely oligospermic and had distinctly subnormal serum testosterone concentrations, even those whose serum inhibin values were normal. In the 7 patients with postpubertal hypogonadism, treatment with hCG alone for 6 months increased the serum testosterone concentration and maximum sperm count to normal, even though the previously normal inhibin concentration was not increased further. In the 13 patients with prepubertal hypogonadism, treatment with hCG alone increased the serum inhibin concentration, and combined treatment with hCG and human menopausal gonadotropin (hMG) increased inhibin further, to well within the normal range (742 +/- 143 U/L) in the patients without a history of cryptorchidism and to just within the normal range (487 +/- 96 U/L) in those with such a history. In the 7 patients with prepubertal hypogonadism but no history of cryptorchidism, treatment with hCG and hMG increased the maximum sperm count to normal in 5. In the 6 patients with prepubertal hypogonadism who did have a history of cryptorchidism, hCG and hMG treatment produced a normal sperm count in only 1. Of 12 patients whose serum inhibin level was more than 300 U/L before treatment, 11 developed a normal maximum sperm count in response to treatment, but of 8 patients whose inhibin concentration was less than 300 U/L before treatment, only 2 developed a normal sperm count in response to treatment (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Chorionic Gonadotropin; Eunuchism; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Hypogonadism; Inhibins; Luteinizing Hormone; Male; Menotropins; Middle Aged; Oligospermia

A 30-year-old woman with primary amenorrhea, hypothalamic hypogonadism, decreased sense of smell, and primary infertility failed to respond to pulsatile exogenous gonadotropin-releasing hormone. In addition, failure to respond to stimulation with human menopausal gonadotropins was consistent with concomitant ovarian failure. Perturbation of normal cellular migration during embryogenesis in the regions of the olfactory placode, yolk sac, hindgut, and gonadal ridge may explain both the hypothalamic defect and ovarian failure experienced by this woman. She demonstrates that gonadal failure need not be accompanied by elevated gonadotropin levels; nor do low gonadotropin levels necessarily indicate potentially responsive ovaries. These findings are consistent with the coexistence of isolated gonadotropin deficiency and ovarian failure in the same individual.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Hypogonadism; Infertility, Female; Menotropins; Ovulation Induction

In order to study the function of the hypothalamic-pituitary-testicular axis in men referring for severe oligospermia, the hormonal pattern of 57 oligospermic men was compared to those of 19 healthy volunteers. Fourteen patients had plasma gonadotrophin levels in the normal range contrasting with low plasma testosterone (T) levels. An hyperprolactinemia was found in 2 of these men who were treated with bromocriptine. A dramatic increase in sperm count was obtained on month 9 to 12 of the therapy and 5 pregnancies were obtained. Two men with hypogonadotrophic hypogonadism and azoospermia were treated with gonadotrophins. Such a treatment induced a desquamation of immature germinal cells in the sperm on month 6 and the maturation et spermatozoa on month 18. By contrast to the latter patients, 8 men had a decrease in plasma T levels without clinical signs of hypoandrogenism. The spermocytogram showed numerous immature germinal cells. On month 7 of a treatment using gonadotrophins, the sperm count rose and 4 pregnancies were obtained after 3 to 12 months of therapy. In 2 patients an isolated FSH deficiency was suspected on the basis of undetectable FSH levels unresponsive to the infusion of GnRH. These patients were treated with hMG. This treatment induced a sharp increase in sperm count on month 6. Forty-three patients had an increase in either LH and/or FSH: 24 men had plasma testosterone and LH levels in the normal ranges, contrasting with an increase in plasma FSH level. In such men, the mean of testosterone level was significantly (p less than 0.001) lower than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Bromocriptine; Chorionic Gonadotropin; Estradiol; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hyperprolactinemia; Hypogonadism; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Prolactin; Sperm Count; Tamoxifen; Testosterone

The pituitary-gonadal function was studied in 18 beta-thalassemic female adolescents, 8 with delayed puberty and 10 with primary amenorrhea,treated with repeated transfusions and long-term iron chelation therapy by subcutaneous infusion. A 100 micrograms gonadotropin-releasing hormone (GnRH) test, a double-bolus GnRH test after estradiol administration in non-responders, a 400 micrograms thyrotropin-releasing hormone (TRH) test and a 'high dose' human menopausal gonadotropin (hMG) test were performed. LH and FSH peak levels were significantly lower in thalassemic patients than in controls, both in the 100 micrograms GnRH test (LH was 4.3 +/- 0.7 mIU/ml vs 40.8 +/- 6.0 mIU/ml and FSH 3.3 +/- 0.5 mIU/ml vs 9.6 +/- 1.1 mIU/ml, respectively) and in the double-bolus GnRH test (LH was 2.3 +/- 0.2 mIU/ml vs 59.0 +/- 4.9 mIU/ml and FSH 1.8 +/- 0.3 mIU/ml vs 14.0 +/- 1.0 mIU/ml). The mean prolactin response to the TRH test was 27.8 +/- 3.2 ng/ml. After the 'high dose' hMG test 12 out of 14 admitted patients showed a poor response, lower than 250 pg/ml. Our data suggest that the hypogonadotropic condition of the thalassemic adolescents is due to pituitary hyporesponsiveness to GnRH and that most of these patients also have an impairment of ovarian function. Both conditions are a consequence of iron deposits in glands. Moreover, there is evidence that pituitary-gonadal function cannot be preserved by long-term iron chelation therapy.

Topics: Adolescent; Chelation Therapy; Child; Deferoxamine; Dose-Response Relationship, Drug; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Iron; Luteinizing Hormone; Menotropins; Ovary; Pituitary Gland; Prolactin; Thalassemia; Thyrotropin-Releasing Hormone

To study the effectiveness of hCG and hMG administration on spermatogenesis of patients with hypogonadotropic hypogonadism (HH), the DNA synthesis of spermatogonia was investigated by the method of 3H-thymidine uptake by cultured tissue fragments of human testis with or without treatment with hCG and/or hMG. Although in two groups treated with different concentrations of hCG the value of 3H-thymidine incorporation into testicular tissue showed no significant difference compared with the untreated control group, treatment with both hCG and hMG induced significant changes in the value of 3H-thymidine incorporation compared with the untreated control group. Combined hCG and hMG therapy was effective for induction of spermatogenesis in patients with HH.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Culture Techniques; DNA; Drug Combinations; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Spermatogenesis; Testis; Testosterone; Thymidine

Topics: Buserelin; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infertility, Female; Menotropins; Ovulation Induction; Pregnancy; Triptorelin Pamoate

Eight men with isolated hypogonadotropic hypogonadism were treated with pulsatile gonadotropin-releasing hormone (GnRH) after maximal testicular growth and function had already been achieved with human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG). Only four subjects could normalize plasma testosterone (T) levels (group A). After 18 months of GnRH therapy, testicular size of group A increased by 53% (P less than 0.01) over that previously attained with exogenous gonadotropins. However, despite further testicular growth, two men who were previously azoospermic on hCG/hMG remained so on GnRH. In the other two patients, total sperm count increased minimally. Thus, pulsatile gonadotropin levels achieved with GnRH are more effective in stimulating testicular growth, but not necessarily sperm output, than are stable gonadotropin concentrations obtained with hCG/hMG.

Topics: Adult; Chorionic Gonadotropin; Humans; Hypogonadism; Infusion Pumps; Male; Menotropins; Pituitary Hormone-Releasing Hormones; Spermatogenesis; Stimulation, Chemical; Testis; Testosterone; Time Factors

A 43-year-old woman with a history of 5 years of amenorrhea sought help in achieving a pregnancy. Her gonadotropins were found to be elevated and thus she was diagnosed as having ovarian failure. She was made to ovulate on many occasions by suppressing her gonadotropins first with estrogen, then stimulating her ovaries with hMG. However, she became refractory to this therapy and she was switched from estrogen to LA to suppress gonadotropins. The woman ovulated three times just with leuprolide therapy before any hMG was added. A possible hypothesis is that, on the way down to subnormal levels of LH and FSH, a critical level of gonadotropins was attained where they were still high enough to stimulate the follicles, but low enough to allow restoration of gonadotropin receptors, which previously had been down-regulated by the elevated gonadotropin levels.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Leuprolide; Menotropins; Ovulation

Topics: Adolescent; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Hormones; Humans; Hypogonadism; Male; Menotropins; Spermatogenesis; Stimulation, Chemical

In order to define the minimal number of sperm needed for conception, we studied semen characteristics of men with isolated hypogonadotropic hypogonadism (IHH) who became sperm-positive during gonadotropin therapy. Twenty-two of 24 men (92%) proved fertile, initiating a total of 40 pregnancies. The mean (+/- standard error of the mean) sperm concentration at the time of conception was 16.7 +/- 4.0 X 10(6)/ml. However, 71% of pregnancies were conceived when the mean sperm concentration was less than 20 X 10(6)/ml; in 16%, the mean sperm concentration was less than 1 X 10(6)/ml. Mean total sperm count correlated highly with sperm concentration (r = 0.67, P less than 0.001). We conclude that men with IHH can initiate conception even when their sperm concentration is well below the conventional lower limit of 20 X 10(6)/ml.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Fertility; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Pregnancy; Sperm Count; Testis; Testosterone

A case of Rothmund-Thomson syndrome of a 24-year old woman with primary amenorrhoea is presented. This autosomal recessive disorder is characterised by atrophy, hyperpigmentation and teleangiectasiae of the skin, furthermore by juvenile cataracts and congenital bone defects as saddle nose. Endocrinologic and morphologic parameters suggest a resistant ovary syndrome as cause of this hypergonadotropic hypogonadism.

Topics: Adult; Amenorrhea; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Syndrome

Men with the complete form of isolated hypogonadotropic hypogonadism (initial mean testes volume less than 4 mL) require 2 or more yr of exogenous gonadotropin therapy combining hCG and human menopausal gonadotropin (hMG) to achieve maximal, but subnormal, testis size and sperm output. To test whether pulsatile GnRH therapy, which more closely mimics normal hormonal stimulation, would accelerate or further augment testicular growth, hasten the onset of sperm production, and/or increase sperm output more than occurs during conventional exogenous gonadotropin therapy, we administered either hCG/hMG or GnRH from the inception of therapy to 2 comparable groups of men with complete IHH (initial testicular volume, less than 4 mL) and compared their testicular responses during the first 2 hr of therapy. Five men were treated with pulsatile GnRH in doses of 143-714 ng/kg every 2 h, sc, while 11 other men received hCG (2000 IU) and hMG (75 IU FSH and 75 IU LH) im 3 times/week. In the GnRH-treated men, the mean plasma total and free testosterone levels during therapy rose to within the normal range, but were significantly lower (P less than 0.01 and P less than 0.02, respectively) than those in the hCG/hMG-treated men. The mean plasma estradiol concentrations during therapy were within the high normal range and were similar in the two groups. The mean plasma FSH levels achieved in the GnRH-treated men were significantly (P less than 0.01) and 1.3- to 3.2-fold higher than those in the hCG/hMG-treated men. The mean testicular size achieved in the GnRH-treated men was not significantly different from that in the hCG/hMG-treated men (P = 0.08); the mean testicular volumes after 2 yr were 4.8- and 4.3-fold the pretreatment values in the GnRH and hCG/hMG groups, respectively. After 12 months of therapy, sperm production had occurred in one man in the GnRH group and in no subject in the hCG/hMG group. After 24 months, two men in the GnRH group and eight men in the hCG/hMG group produced sperm. Thus, 40% of the GnRH-treated men and 80% of the hCG/hMG-treated men (P = NS) produced sperm after 2 yr of therapy. The sperm concentrations in all men were below 5 million/mL and were comparable in the two groups (P = NS). These results suggest that pulsatile sc GnRH therapy for the first 2 yr does not accelerate or enhance testicular growth, hasten the onset of sperm production, or increase sperm output significantly compared to hCG/hMG.

Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Organ Size; Spermatogenesis; Testis; Testosterone

This study evaluated the activity of central opiate receptors modulating luteinizing hormone (LH) secretion before and during treatment with human menopausal gonadotropin (n = 8) or purified human urinary follicle-stimulating hormone (n = 6) in 14 patients with hypogonadotropic hypogonadism (n = 6) or secondary amenorrhea (n = 8). LH response to saline infusion and naloxone administration (4 mg intravenously) was assessed. As control, 6 normal ovulating women were studied. Before therapy, all amenorrheic patients showed no LH increase after naloxone injection. Gonadotropin treatment restored the naloxone-induced LH response at preovulatory and midluteal phases in ovulating patients with secondary amenorrhea. The same response was present in spontaneously ovulating women but was absent in the hypogonadotropic hypogonad patients, despite the gonadotropin therapy's efficiency. In conclusion, when the alteration of gonadotropin-releasing hormone synthesis and/or release is reversible, the opioid system actively participates in the regulation of the hypothalamus-pituitary-gonadal axis.

Topics: Adult; Amenorrhea; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Naloxone; Ovulation Induction; Pituitary Hormone-Releasing Hormones; Receptors, Opioid; Sodium Chloride; Stimulation, Chemical

Steroidogenic responsiveness and amelioration of sperm number and motility following long-term intramuscular hCG and hMG administration were evaluated in 18 males with hypogonadotrophic hypogonadism (HH). The patients consisted of 13 patients with isolated gonadotrophin deficiency (IGD) and 5 patients hypophysectomized at an early or middle pubertal period. Basal serum levels of testosterone and 17 beta-estradiol were within prepubertal range in all patients before the treatment. Serum testosterone levels reached the normal adult male levels within 12-24 months of the treatment in only 2 of 7 younger patients and 1 of 6 older patients with IGD, whereas in all hypophysectomized patients serum levels of both testosterone and 17 beta-estradiol increased to the levels found in normal adult males within 6 months of the treatment. The mean peak levels of serum testosterone and 17 beta-estradiol, respectively, during the treatment were 2.1 +/- 0.8 (SD) ng/ml and 10.8 +/- 4.9 (SD) pg/ml in younger patients with IGD, 1.4 +/- 0.9 ng/ml and 9.7 +/- 5.1 pg/ml in older patients with IGD and 6.0 +/- 1.2 ng/ml and 34.2 +/- 14.8 pg/ml in hypophysectomized patients. Quantitative improvement in both sperm density and sperm motility were found in 4 of 7 younger patients, 1 of 6 older patients with IGD and all hypophysectomized patients, but only 3 of hypophysectomized patients (3 of 18 patients) could become fertile.

Topics: Adolescent; Adult; Aging; Chorionic Gonadotropin; Estradiol; Gonadotropins; Humans; Hypogonadism; Hypophysectomy; Male; Menotropins; Puberty; Sperm Count; Sperm Motility; Spermatogenesis; Testis; Testosterone; Time Factors

Patients with normal menstrual rhythm and normal luteinizing hormone were treated with exogenous gonadotropins to induce multiple follicular development. This was effected in the absence (34 cycles in 12 patients) or with concurrent suppression of endogenous gonadotropin levels with a gonadotropin-releasing hormone analog (84 cycles in 18 patients). In the absence of the analog, "premature" luteinization occurred in 51% of cycles before the ultrasonic visualization of a follicle with a diameter of 20 mm. In the analog-treated cycles, premature luteinization was almost totally eliminated and progesterone elevations were delayed until after administration of human chorionic gonadotropin. Follicular estrogen production was unaffected by the analog treatment, compared with hypogonadal patients treated with exogenous gonadotropins. The characteristics of follicular development showed that two to three follicles of mature size were induced with this technique, and the capacity for the induction of a larger number of follicles was evident.

Topics: Buserelin; Chorionic Gonadotropin; Corpus Luteum; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Menstrual Cycle; Ovarian Follicle; Progesterone; Ultrasonography

A woman with secondary amenorrhea following head trauma showing isolated gonadotropin deficiency of hypothalamic origin did not respond to massive doses of hMG therapy (11 250 IU daily dose). Ovarian biopsy showed the absence of follicles, despite persistently low FSH levels. In this case the occurrence of premature ovarian failure was only suspected from the lack of response to hMG and diagnosed by ovarian histology.

Topics: Adult; Amenorrhea; Craniocerebral Trauma; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovary

Pituitary function studies were performed on a 31-year-old man who had oligospermia and a very low seminal volume (0.1 ml). The low testosterone and gonadotropin levels, the remarkable testosterone response to human chorionic gonadotropin (hCG) stimulation, and the sluggish luteinizing hormone (LH) response to luteinizing hormone stimulating hormone (LH-RH) stimulation suggested the presence of hypogonadotropic hypogonadism. Treatment with a combination of human menopausal gonadotropin (hMG)-hCG resulted in the increase in the volume of seminal fluid and the sperm density. His wife achieved two pregnancies during the treatment. This report indicates that the findings of oligospermia and very low seminal volume should be followed by an investigation of the hypothalamo-pituitary testicular axis. Fertility in men with hypogonadotropic hypogonadism can be effectively induced with a combination of hMG-hCG treatment.

Topics: Adult; Chorionic Gonadotropin; Humans; Hypogonadism; Infertility, Male; Male; Menotropins; Semen; Sperm Count

We evaluated the efficacy of gonadotropin treatment in stimulating spermatogenesis in men with hypogonadotropic hypogonadism. When 21 men with hypogonadotropic hypogonadism were treated with human chorionic gonadotropin, the sperm count increased to within the normal range in the 6 in whom hypogonadism had begun after puberty, but in only 1 of the 15 in whom it had begun before puberty (P less than 0.002). When the remaining 14 men with prepubertal hypogonadism were treated with human menopausal gonadotropin in addition to human chorionic gonadotropin, the sperm count increased to normal in 5 of the 7 who had not had cryptorchidism, but in only 1 of the 7 who had (P less than 0.05). The need for human menopausal gonadotropin as a replacement for follicle-stimulating hormone could not be predicted by pretreatment serum and urinary levels of follicle-stimulating hormone. We conclude that gonadotropin treatment will usually increase the sperm count to normal in men with hypogonadotropic hypogonadism, unless cryptorchidism has occurred. The need for human menopausal gonadotropin treatment appears to depend on the time of onset of hypogonadism.

Topics: Adult; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Gonadotropins; Gonadotropins, Pituitary; Humans; Hypogonadism; Hypothalamic Diseases; Infertility, Male; Male; Menotropins; Middle Aged; Pituitary Diseases; Pregnancy; Sperm Count; Spermatogenesis; Stimulation, Chemical

Although testosterone (T) therapy is sufficient for maturation and maintenance of secondary sex characteristics in hypogonadal men, gonadotropins are required for stimulation of spermatogenesis. Thirteen men with hypogonadotropic hypogonadism received treatment with hCG, followed in 12 by the addition of human menopausal gonadotropin (hMG). All initially had undetectable serum LH and FSH and low T levels and were azoospermic with small testes. During therapy, all achieved normal male levels of T. Twelve of 13 had marked and continuous increase in testicular volume. Three men had sperm in the ejaculate with hCG treatment alone. All but 1 patient developed sperm in their seminal fluid during combined hCG and hMG therapy. Two men achieved three pregnancies, and 2 more had semen that produced hamster oocyte penetration assays in the fertile range during the protocol period. Four of 5 who achieved sperm densities greater than 1 million/ml while receiving combined therapy maintained or increased sperm production while receiving continued hCG therapy after hMG was withdrawn. We examined the response to gonadotropin therapy of men who had received previous T therapy and those who had not. There were no differences in rapidity or degree of response, as assessed by rise in serum T, increase in testis volume, or maximal sperm density achieved. Multiple pituitary deficits and cryptorchidism were negative prognostic factors. In summary, the prognosis for successful stimulation of spermatogenesis in men with hypogonadotropic hypogonadism treated with hCG/hMG is good and not adversely affected by prior androgen treatment. Despite undetectable serum FSH levels, hCG treatment was sufficient to both initiate and maintain spermatogenesis in some patients.

Topics: Adult; Androgens; Chorionic Gonadotropin; Fertility; Follicle Stimulating Hormone; Gonadotropins; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Prognosis; Testis; Testosterone

A patient with the resistant ovary syndrome is reported. To evaluate the hypothesis that the hypogonadism might be the result of circulating antibodies to gonadotropin receptors or to an abnormal gonadotropin molecule, a series of clinical and laboratory studies was carried out. Administration of human menopausal gonadotropin had no effect on the serum estradiol level. The patient's serum did not affect follicle-stimulating hormone binding to a membrane preparation of monkey testes, suggesting the absence of antibodies to follicle-stimulating hormone receptors, nor did the patient's serum affect in vitro responsiveness of human granulosa cells to human menopausal gonadotropin. Unresponsiveness to exogenous gonadotropins, combined with anatomically normal follicular apparatus and the absence of serum antibodies to gonadotropin receptors, supports the concept of a gonadotropin receptor or a postreceptor defect.

Topics: Adult; Autoantibodies; Cytotoxicity Tests, Immunologic; Estradiol; Female; Follicle Stimulating Hormone; Granulosa Cells; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Ovarian Diseases; Ovary; Receptors, Cell Surface; Receptors, FSH; Receptors, LH; Syndrome

Free L-carnitine was assayed in semen from patients with various andrologic diseases by an enzymatic-spectrophotometric method. Extremely low concentrations were found in semen from patients with agenesis of the vas deferens (31.8 +/- 18.8 nm/ml). Semen from men with vasectomies contains a higher concentration of free carnitine (105.0 +/- 8.1 nm/ml). When comparing these data with those of ten fertile control subjects (817.0 +/- 200 nm/ml), we assume that seminal free L-carnitine mainly originates from the epididymis. Semen from patients with azoospermia caused by testicular failure also contains a low carnitine concentration. In hypogonadotropic eunuchoids the gonadotropin treatment increased the low basal concentration. A correlation between semen carnitine content and sperm motility and number was also tested in 124 infertile patients. The results show a positive correlation between free L-carnitine and sperm count (r = 0.617; P less than 0.01), between free L-carnitine and sperm motility (r = 0.614; P less than 0.01), and between free L-carnitine and the number of motile spermatozoa per milliliter (r = 0.646; P less than 0.01).

Topics: Adult; Carnitine; Chorionic Gonadotropin; Humans; Hypogonadism; Klinefelter Syndrome; Male; Menotropins; Semen; Sperm Count; Sperm Motility; Vas Deferens; Vasectomy

Topics: Adolescent; Adrenal Cortex Hormones; Androgens; Bromocriptine; Chorionic Gonadotropin; Humans; Hypogonadism; Lisuride; Male; Menotropins; Puberty, Delayed; Testicular Diseases

Out of 49 patients who received gonadotropic therapy, 29 presented with FSH less than 1.5 mIU/ml and 20 had more than 1.5 mIU/ml. The success rate (as determined by semen analysis) in the former group was 86% (25 patients - 22 of those patients fathered one or more children) and in the latter - 5% (only 1 patient). The mean FSH level in the 20 patients who showed improvement following HMG/hCG therapy was 0.9 mIU/ml and in the 25 patients in whom gonadotropic therapy was ineffective - 2 mIU/ml.

Topics: Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropins; Humans; Hypogonadism; Infertility, Male; Luteinizing Hormone; Male; Menotropins

Etiologic factors in hypergonadotropic hypogonadism are discussed. On the basis of these data a classification system is proposed for women with hypergonadotropic hypogonadism to be used in future investigations of the natural history of this disorder. The classification system can also be used in attempts at therapeutic intervention in these women. Recommendations for clinical management and future studies of women with hypergonadotropic hypogonadism are provided.

Topics: Adult; Antineoplastic Agents; Estradiol; Estrogens; Female; Humans; Hypogonadism; Infertility, Female; Karyotyping; Menopause, Premature; Menotropins; Ovarian Diseases; Radiation Dosage

Topics: Adolescent; Adult; Chorionic Gonadotropin; Gonadotropins, Pituitary; Humans; Hypogonadism; Injections, Intramuscular; Male; Menotropins; Testis; Testosterone

Topics: Chorionic Gonadotropin; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypogonadism; Male; Menotropins; Oligospermia; Spermatogenesis; Time Factors

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infertility, Female; Menotropins; Olfaction Disorders; Ovulation Induction; Pregnancy; Syndrome

We evaluated gonadal function in 18 female and eight male patients with galactosemia due to transferase deficiency; it was normal in the males, but 12 females had signs of hypergonadotropic hypogonadism. All female patients had a 46,XX karyotype, normal levels of thyroid hormone and prolactin, and no anti-ovarian antibodies. The biologic activity of urinary gonadotropins was normal. Ultrasonography of the pelvis revealed that ovarian tissue was diminished or absent. Total estrogens increased in one of two patients after administration of human menopausal gonadotropin. The frequency of hypergonadotropic hypogonadism was higher in females in whom dietary treatment for galactosemia was delayed. Clinical course and mean erythrocyte galactose-1-phosphate and urinary galactitol levels did not correlate with ovarian function. We conclude that female patients with galactosemia have a high incidence of ovarian failure due to acquired ovarian atrophy. Galactose or its metabolites may be toxic to the ovarian parenchyma, particularly during the immediate neonatal period.

Topics: Adolescent; Adult; Amenorrhea; Atrophy; Child; Estradiol; Female; Follicle Stimulating Hormone; Galactosemias; Gonadotropins, Pituitary; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Ovarian Diseases; Puberty; Sex Factors

Topics: Adult; Anovulation; Drug Evaluation; Female; Humans; Hypogonadism; Infertility, Female; Menotropins; Ovulation Induction

Topics: Adult; Chorionic Gonadotropin; Gonadotropins, Pituitary; Humans; Hypogonadism; Leydig Cells; Male; Menotropins; Olfaction Disorders; Spermatogenesis; Syndrome

Amoung 95 cases of infertility due to oligo-asthenospermia with normal or low FHS, treated by the association HMG/HCG, 13 cases could be considered a success. From this particularly favourable slries, the author attempts to codify the indications of gonadotrophines in male sterilities. He suggests that such an indication, obvious in case of hypogonadotrophic hypogonadism could be expanded to some normoor hypogonadotrophic hypofertilities.

Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Humans; Hypogonadism; Infertility, Male; Male; Menotropins; Oligospermia

A new case of familial idiopathic hypogonadotrophic hypogonadism is presented: 3 males and 2 females among 9 siblings are affected. Very low to non-detectable levels of plasma LH and FSH levels were found in each patient. LH-RH stimulation test gave in one male a slight increase in plasma LH levels while no change was observed in the others. Prolonged treatment with gonadotrophins or testosterone gave poor results in the males while evidence of ovulation was obtained in the two females during a unique induced artificial cycle with combined HMG and HCG treatment; rapid feminization was also obtained in the females with oestrogen therapy. The striking difference in the results of the substitution treatments between males and females suggest that some degree of acquired insensitivity of the testes to gonadotrophins and of peripheral tissues to male sex hormones are present in male hypogonadotrophic hypogonadism. This may be the consequence of a lack of hormonal stimulation or impregnation during infancy and childhood

Topics: Adult; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Testosterone

Two brothers, 16 and 14 years of age, with hypogonadotrophic hypogonadism and anosmia were treated with subcutaneous injections of 200 microng gonadotropin-releasing hormone at 8-hour intervals for 4 weeks. Serum FSH increased to the range of normal adult men, but serum LH and serum testosterone showed little change and no clinical signs of pubertal development occurred. Thereafter the 2 patients were given HCG for 11 months and a combination of HCG and HMG for a further 3 months. In response to this treatment, the serum testosterone levels increased to the range of normal adult men and marked development of the secondary sex characteristics was seen.

Topics: Adolescent; Chorionic Gonadotropin; Drug Therapy, Combination; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Injections, Intramuscular; Injections, Subcutaneous; Luteinizing Hormone; Male; Menotropins; Testosterone

Six patients with all of the clinical and laboratory characteristics of isolated hypogonadotropic hypogonadism (bihormonal gonadotropin deficiency) were treated with human menopausal gonadotropins (hMG, Pergonal) and human chorionic gonadotropin (hCG). Of a total of 37 courses of treatment administered, there was evidence of ovulation in 32 (29%). The first four subjects had a total of six pregnancies in 13 treatment cycles. In the remaining two subjects, there were abnormalities in the seminal fluid of both husbands and, as a consequence, only one patient conceived. The average dose and duration of hMG therapy was 3310 IU (44 ampules), administered for 13 days. A wide range of hCG dosage was used to induce ovulation, but three subjects conceived following 5000 IU of hCG on 2 successive days. None of our subjects developed any evidence of the hyperstimulation syndrome, and there was only one instance of twin birth. Serial determinations of hLH performed during hMG therapy were lower than those noted during the normal follicular phase. In contrast, hFSH levels were in the normal follicular phase range. the high success rate in these subjects indicates that the prognosis for inducing ovulation in patients with hypogonadotropic hypogonadism is good.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Hypogonadism; Luteinizing Hormone; Menotropins; Ovulation; Progesterone

Topics: Adolescent; Adult; Chorionic Gonadotropin; Humans; Hypogonadism; Male; Menotropins

In mammals, pituitary control of spermatogenesis varies with age. In the rat, before puberty FSH is highly active whereas LH is not; after puberty it seems that LH alone is able to support spermatogenesis. The mode of action of hormones is discussed. In the human, in case of infertility due to hypogonadotrophic hypogonadism, spermatogenesis can be restored by HCG or HMG. The best results are obtained after simultaneous treatment with both hormones, LH activity being predominant.. A review of the hormonal regulation of spermatogenesis in experimental animals and in man is presented. In the rat, the roles of follicle stimulating hormone (FSH) and luteinizing hormone (LH) vary with the age of the animal. FSH is effective in the prepubertal rat in the support of spermatogonial multiplication. LH is active in the hypophysectomized adult. FSH acts by binding specifically to receptor sites on cellular membranes of the seminiferous epithelium inducing biochemical changes. The development of a system which limits the response to FSH according to age is suggested. Information on the action of LH is less understood. In the human, information on spermatogenesis comes from treating disorders. In treating infertility, gonadotropins are used from human origin: 1) human pituitary extracts (HPG); 2) human chorionic gonadotropin (HCG); and 3) human menopausal gonadotropin (HMG). In the prepubertal testis, spermatogenic activity can be initiated with HCG or HMG. Spermatogenesis proceeds only to primary spermatocytes. Morphological maturation of Sertoli cells occurs as long as LH-like activity exceeded FSH-like activity. In hypogonadotropic hypogonadism, FSH has been shown to be inactive on germ cells while LH allows resumption of meiosis after hypophysectomy. HMG or HCG given simultaneously often provoke a noticeable stimulation of spermatogenesis which progresses to the release of some sperm. Further research is needed to elucidate the relationship between different testicular compartments in the production of sperm.

Topics: Age Factors; Animals; Chorionic Gonadotropin; Follicle Stimulating Hormone; Humans; Hypogonadism; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Rats; Spermatogenesis

Six theoretically possible syndromes of IGD are shown in Table 1. 1) IBGD is well-substantiated both in males and in females, and appears to be either of pituitary or more frequently of nonpituitary origin. 2) An example of isolated FSH deficiency has been described. The defect appears to reside at the pituitary level and may be localized to the FSH beta subunit. Recently a male patient has been studied with isolated FSH deficiency and a concordant testicular picture viz germinal cell aplasia. However, the syndrome is complicated by an associated chromosomal abnormality (XO/XXY/XY) whose significance is unclear. 3) Several examples of isolated hLH deficiency have been described. Several questions remain about the exact nature of the defect in some of the published reports of this syndrome.

Topics: Amenorrhea; Clomiphene; Estradiol; Eunuchism; Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Sex Characteristics; Syndrome; Testosterone

Eight hMG-hCG therapy cycles in 6 anovulatory infertile patients are presented. Daily plasma estrogen monitoring during the therapy contributed to success in inducing ovulation in all 6, 3 of whom established pregnancies and delivered healthy babies. The duration of hMG therapy required varies among individuals. Duration and dosage can be determined on the basis of daily plasma estrogen levels. Administration hCG is recommended to trigger ovulation when these levels reach 300 to 600 pg/ml. Although success in ovulation induction and pregnancy is achievable, multiple ovulation and multiple pregnancy cannot be predicted or prevented.

Topics: Adult; Amenorrhea; Chorionic Gonadotropin; Clomiphene; Estrogens; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Infertility, Female; Luteinizing Hormone; Menotropins; Ovulation; Ovulation Detection; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Progesterone

Topics: Adult; Androgens; Chorionic Gonadotropin; Clomiphene; Estrogens; Female; Gonadotropins; Humans; Hydroxysteroids; Hypoglycemia; Hypogonadism; Male; Menotropins; Prolactin; Sulpiride; Thyrotropin-Releasing Hormone

Topics: Adult; Biopsy; Cell Count; Chorionic Gonadotropin; Ejaculation; Erectile Dysfunction; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Menotropins; Metabolic Clearance Rate; Microscopy, Electron; Progesterone; Semen; Spermatogenesis; Spermatozoa; Stimulation, Chemical; Testis; Testosterone; Tritium

Topics: Adolescent; Adult; Chorionic Gonadotropin; Eunuchism; Gonadotropins; Humans; Hypogonadism; Long-Term Care; Male; Menotropins; Mental Disorders; Pituitary Function Tests; Prognosis; Spermatogenesis; Testosterone

Topics: Adult; Chorionic Gonadotropin; Gonadotropins, Pituitary; Humans; Hypogonadism; Infertility, Male; Male; Menotropins; Semen; Sperm Capacitation; Spermatogenesis; Spermatozoa; Testosterone; Thyroid Hormones

Topics: Adult; Amenorrhea; Cervix Mucus; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Gonads; Humans; Hypogonadism; Hypophysectomy; Menotropins; Ovary; Ovulation; Pituitary Function Tests; Pituitary Gland; Pregnanediol; Stimulation, Chemical

Topics: Adult; Brain Diseases; Chorionic Gonadotropin; Female; Frontal Lobe; Gonadotropins; Humans; Hypogonadism; Limbic System; Menotropins; Olfaction Disorders; Ovary; Ovulation; Pregnancy; Stimulation, Chemical; Syndrome; Thalamus