leuprolide and Anovulation

The use of exogenous gonadotropins for treatment of clomiphene-resistant chronic anovulation in women with the polycystic ovary syndrome (PCO) is hazardous and often ineffective, possibly because of the abnormal endogenous gonadotropin secretion characteristic of PCO. We evaluated the effect of leuprolide acetate, a long-acting GnRH agonist, on serum gonadotropin and sex steroid concentrations before and during human menopausal gonadotropin (hMG) induction of ovulation in women with PCO. In this controlled prospective randomized study, leuprolide was administered daily for 4 weeks, followed by concomitant hMG administration. Gonadotropin and steroid hormone concentrations were compared with those during ovulation induction cycles in women with PCO receiving hMG only. Daily administration of leuprolide for 4 weeks resulted in significantly decreased serum LH, estradiol, and testosterone concentrations, but no change in serum progesterone, FSH, and dehydroepiandrosterone sulfate. Compared to ovulation induction using hMG alone, leuprolide administration before and during hMG treatment prevented preovulatory rises in serum LH and P concentrations, while having no effect on serum FSH, testosterone, estradiol, and dehydroepiandrosterone sulfate. We conclude that leuprolide administered to women with PCO decreases gonadal steroid production and is capable of preventing premature luteinization during hMG induction of ovulation.

Topics: Adult; Anovulation; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Testosterone

In this study, a GnRH agonist, leuprolide acetate (LA), was given as a single depot injection before 48 h of life to Wistar female rats allotted to prenatal (E16-18) and postnatal androgenization (day 5 of life) by the use of testosterone propionate, looking for reproductive endpoints. Remarkably, a single injection of LA increased the estrus cycles in the postnatal group (PostN) from 0% to 25% of the estrus cycles in the postnatal LA treated group (PostN L). LA also reduced the serum testosterone levels and cysts and atretic follicles in PostN L in contrast with rats (>100 days) from the PostN group (p = 0.04). Prenatally androgenized rats (PreN) exhibited significant modifications in the hypothalamic genes, such as Gnrh. To the best of our knowledge, this is the first study to show that blockage of the GnRH axis with leuprolide acetate depot prevented the development of typical features (anovulation, cysts, atretic follicles) in a postnatal testosterone propionate rat model of PCOS.

Topics: Animals; Anovulation; Estrous Cycle; Female; Gonadotropin-Releasing Hormone; Leuprolide; Male; Ovarian Follicle; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Reproduction; Testosterone; Virilism

To evaluate the protective effect of GnRH agonist for the prevention of ovarian reserve during treatment with paclitaxel and cisplatin.. Experimental study.. University-based research laboratory.. Seventy female Wistar-Albino rats.. Each group consisted of 10 rats. Group 1 served as controls. Groups without GnRH agonist (groups 2, 3, and 4) were administered paclitaxel and cisplatin, respectively; the remaining groups (groups 5, 6, and 7) were given the same regimens with GnRH agonist. The GnRH agonist (leuprolide acetate; 2.5 microg/d subcutaneously for 5 weeks) was started four weeks before chemotherapy to achieve anovulation. Paclitaxel (7.5 mg/kg) and cisplatin (5 mg/kg) were administered intraperitoneally on the 28th day as a single dose.. One week after the chemotherapy, the animals were euthanized and primordial, primary, secondary, and tertiary follicle counts were evaluated.. Primordial, primary, and tertiary follicle counts in group 5 (paclitaxel plus GnRH agonist) and tertiary follicles in groups 2 and 3 had not decreased, but there was a significant decrease in other treatment groups compared with controls (P < 0.05). Binary comparison between all groups demonstrated that the primordial follicle count in group 5 was comparable to those of the controls.. Paclitaxel plus GnRH agonist treatment may be an appropriate option for patients deserving further fertility in the preservation of primordial follicles.

Topics: Animals; Anovulation; Antineoplastic Agents; Cisplatin; Disease Models, Animal; Drug Administration Schedule; Female; Fertility; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Infertility, Female; Injections, Subcutaneous; Leuprolide; Ovarian Follicle; Paclitaxel; Rats; Rats, Wistar

Insulin-like growth factors (IGFs) in the intraovarian autocrine control mechanism may serve as a central signal, and the granulosa cell is their site of production, reception, and action. In addition, various IGF-binding proteins (IGFBPs) are thought to modulate and regulate the actions of IGFs and in turn influence the growth and maturation of ovarian follicles.. To further investigate the follicular growth and maturation regulated by IGFs and IGFBPs in the ovary of low responders, 14 cases of low responders cotreated with growth hormone (GH) were studied. Another 14 normal responders without GH treatment were also recruited as controls.. Serum levels of estradiol on day 6 and day 9 of the cycle and on the day of HCG administration, and the numbers of oocytes retrieved and follicles on the day of oocyte retrieval were significantly lower in low responders before growth hormone (GH) treatment than those in low responders after GH treatment as well as those in normal responders. Expression of both IGF-II and IGFBP-1 mRNA was elevated (by 23% and 35%, respectively) in granulosa cells from low responders after GH treatment as compared to that in low responders before GH treatment. In contrast, there was a substantial decrease (16%) in expression of IGFBP-3 mRNA in granulosa cells from low responders after GH treatment. Clinically, the pregnancy rate was lower in low responders after GH treatment as compared to controls (7% vs. 29%).. Cotreatment with growth hormone in low responders might not increase the pregnancy rate.

Topics: Anovulation; Drug Therapy, Combination; Female; Fertility Agents, Female; Granulosa Cells; Growth Hormone; Humans; Infertility, Female; Insulin-Like Growth Factor Binding Proteins; Leuprolide; Menotropins; Ovarian Follicle; Ovulation Induction; Pregnancy; RNA, Messenger; Somatomedins; Treatment Outcome

To examine the interaction between circulating beta-endorphin levels and sex steroids during sustained submaximal exercise in runners who are either anovulatory and oligomenorrheic (AO) or ovulatory and eumenorrheic (EO).. Controlled clinical study.. General clinical research center at an academic medical center.. Three AO and four EO runners.. The athletes underwent 60 minutes of submaximal treadmill exercise on three separate occasions. Anovulatory and oligomenorrheic runners underwent exercise at baseline and after physiologic estrogen and combined estrogen and progesterone replacement. Ovulatory and eumenorrheic runners underwent exercise in the follicular and luteal phases and after GnRH agonist desensitization.. Serum cortisol, beta-endorphin, progesterone, estrogen, and gonadotropin levels at rest and during exercise.. Serum levels of E2 increased in response to exercise in both EO and AO runners during sex steroid replacement. Baseline peripheral beta-endorphin and cortisol levels were not different between the EO and AO groups. A significant increase in beta-endorphin levels in response to exercise occurred only in the EO group after GnRH agonist desensitization.. Alterations in menstrual cyclicity and ovulation in conditioned runners probably are not due to an increase in opioid tone. The hypothalamic-gonadotropic axis appears to be intact in AO runners, as measured by the gonadotropic response to exogenous exposure to estrogen and progesterone. Sex steroid administration had no effect on basal beta-endorphin levels, but this probably was not due to preexisting increased opioid tone.

Topics: Adult; Amenorrhea; Anovulation; beta-Endorphin; Estradiol; Estrogens; Exercise; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Hydrocortisone; Kinetics; Leuprolide; Menstrual Cycle; Progesterone; Rest; Running

To determine whether 3-month GnRH analogue (GnRH-a) administration to hyperandrogenic anovulatory patients and healthy women affects glucose utilization or endogenous glucose production (EGP) in the postabsorptive state and during variable hyperglycemic-hyperinsulinemic infusions.. Prospective, nonrandomized study.. Academic research environment.. Twelve hyperandrogenic anovulatory patients and 11 healthy women matched by body mass index and waist to hip circumference ratio.. Variable hyperglycemic-hyperinsulinemic infusions replicated physiological increases in circulating glucose and insulin levels before and after 3-month GnRH-a administration.. Glucose utilization and EGP.. In the postabsorptive state, plasma glucose and insulin levels, glucose utilization, and EGP were similar in hyperandrogenic patients and healthy women. During variable hyperglycemic-hyperinsulinemic infusions, glucose use increased and EGP decreased to similar degrees in both groups of women. Three-month GnRH-a administration to hyperandrogenic patients and healthy women did not affect plasma glucose and insulin levels, glucose utilization and EGP in the postabsorptive state, or glucose utilization and EGP during variable hyperglycemic-hyperinsulinemic infusions.. Glucose use and EGP in the postabsorptive state and during variable hyperglycemic-hyperinsulinemic infusions are similar in hyperandrogenic anovulatory patients and healthy women of similar body fat distribution and are unaffected by 3-month GnRH-a administration.

Topics: Adolescent; Adrenal Glands; Adult; Anovulation; Blood Glucose; Body Composition; C-Peptide; Female; Glucagon; Human Growth Hormone; Humans; Hyperandrogenism; Insulin; Insulin Resistance; Leuprolide; Middle Aged; Ovary; Prospective Studies; Steroids

We have reported a 36% pregnancy rate (eight of 22 transfers) with the transfer of cryopreserved-thawed embryos in patients with anovulatory or irregular cycles following a protocol using pituitary suppression with leuprolide acetate after preparation of the endometrium with transdermal E2 and i.m. P. This protocol is simple, easy to follow, and safe and could be used in future for all patients with cryopreserved pre-embryos.

Topics: Adult; Anovulation; Cryopreservation; Embryo Transfer; Endometrium; Estradiol; Female; Hot Temperature; Humans; Leuprolide; Menstruation Disturbances; Progesterone

Continuous exposure to GnRH eliminates the pituitary as a source of gonadotropins and may have direct suppressive effects on the ovary. A woman with PCO syndrome received leuprolide acetate (1 mg/d SC) for 4 weeks before and simultaneously with hMG stimulation. Human chorionic gonadotropin (5,000 IU) was administered IM on the 8th day of hMG therapy. There were 10 follicles greater than 15 mm and a polycystic appearance to the ovaries with 25 follicles measuring less than 10 mm. The serum E2 concentration was 2,280 pg/mL. She developed severe ovarian hyperstimulation and required hospitalization for 12 days for fluid management. A viable intrauterine pregnancy was present. Four weeks of pretreatment with leuprolide did not prevent hyperstimulation in the presence of an intrauterine pregnancy.

Topics: Adult; Anovulation; Chorionic Gonadotropin; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Menotropins; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Stimulation, Chemical

Four women with unexplained infertility and two anovulatory oligomenorrheic women who experienced repeated premature luteinization when treated with human menopausal gonadotropin (hMG) or gonadotropin-releasing hormone (GnRH) were given the gonadotropin-releasing hormone agonist (GnRHa), luprolide acetate, in order to effect medical hypophysectomy. This was followed by hMG for induction of ovulation. Four of the six patients had hMG-only cycles, which were compared with the luprolide acetate/hMG cycles. The luprolide acetate/hMG cycles resulted in normal folliculogenesis with presumptive ovulation. In luprolide/hMG cycles, significantly more hMG was needed for induction of ovulation than in hMG-only cycles. Premature luteinization was abolished with luprolide acetate treatment.

Topics: Adult; Anovulation; Drug Administration Schedule; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Luteal Phase; Luteinizing Hormone; Menotropins; Oligomenorrhea; Ovulation Induction; Prospective Studies

Ovulatory dysfunction is a leading cause of female infertility in the United States. Fortunately, ovulatory dysfunction is often amenable to treatment. Thorough testing is necessary to identify the exact cause of anovulation before conventional ovulation-inducing therapy is started. Careful patient monitoring is essential to avoid risks such as the ovarian hyperstimulation syndrome. Several newer ovulation-inducing agents are available for use in special situations.

Topics: Anovulation; Bromocriptine; Clomiphene; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Menotropins; Ovulation Induction; Pituitary Hormone-Releasing Hormones