trelstar and Hirsutism

Topics: 11-beta-Hydroxysteroid Dehydrogenases; Adrenal Hyperplasia, Congenital; Body Height; Bone Development; Child; Dwarfism; Female; Hirsutism; Hormones; Humans; Hydrocortisone; Leuprolide; Physical Examination; Prognosis; Puberty, Precocious; Triptorelin Pamoate; Ultrasonography

Polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (COH) are heterogeneous disorders, in which excess of androgens may be caused by improper function of ovaries and/or adrenals. In many cases an overlap between ovarian and adrenal type of functional hyperandrogenism has been observed. The relationship between adrenal and ovarian metabolism in hyperandrogenic women is not totally known and etiologic diagnosis of female hyperandrogenism is often difficult. The aim of the present study was to evaluate the usefulness of combined Dexamethasone-Triptoreline testing in distinguishing ovarian and adrenal type of functional hyperandrogenism, and checking if the test could be shortened in order to economise it.. We have examined 57 women with androgen excess divided into two groups: ovarian (n = 42) and adrenal (n = 15) and 20 women with idiopathic hirsutism. There was also one patient suffering from Morris syndrome taken under examination just for curiosity. The blood for hormonal assay was taken in baseline conditions at 8.00 a.m. for LH, FSH, PRL, cortisol, T, DHEAS, 17OHP, E2. Dx was given for 4 days 0.5 mg p.o. every 6 hours. 8 hours after the last Dx administration, the blood was taken for 17OHP and T. Immediately after that Triptorelin 100 mg was given s.c. Then the blood was collected every 4 hours during 24 hours for 17OHP estimation.. Decrease in T levels (from 1.65 +/- 0.52 to 0.73 +/- 0.25 ng/ml) after Dexamethasone administration was observed in adrenal group, which indicates adrenal glands as a source of excessive androgen production. No significant differences were seen in ovarian group. But in women from ovarian group supranormal 17OHP response after Triptoreline administration was seen: (ng/ml): at 8.00 am-0.68 +/- 0.44, 12.00--1.21 +/- 0.7*, 16.00--1.71 +/- 1.19*, 20.00--2.39 +/- 1.81*, 24.00--3.41 +/- 2.64*, 4.00--3.91 +/- 2.82*, 8.00--6.06 +/- 2.43* (*p < 0.01, **p < 0.001). Such a response is typical for women with well defined PCOS and other forms of functional ovarian hyperandrogenism and indicates ovary as a source of androgens. Significant differences were also noticed in idiopathic group: 8.00--0.31 +/- 0.09, 12.00--0.38 +/- 0.17, 16.00--1.41 +/- 0.62*, 20.00--1.52 +/- 0.97*, 24.00--1.89 +/- 0.83*, 4.00--2.17 +/- 0.83*, 8.00--1.83 +/- 0.71** (*p < 0.01). 17OHP levels did not change significantly during the whole test in adrenal group: 8.00--1.83 +/- 1.24, 12.00--1.91 +/- 1.37, 16.00--1.95 +/- 0.86, 20.00--2.19 +/- 0.93, 24.00--2.63 +/- 1.58, 4.00--2.56 +/- 1.78, 8.00--237 +/- 0.94. But patients from this group had exaggerated 17OHP response to ACTH (from 4.32 +/- 1.31 to 15.34 +/- 4.1 ng/ml). In patient suffering from Morris syndrome, after Triptoreline, serum 17OHP levels reminded on the same level as they were before drug administration.. Combined Dx-Triptorelin test can be very useful to distinguish ovarian and adrenal type of functional hyperandrogenism. The number of times of blood collection for 17OHP can be reduced to 4 times a day (during 24 hours): at 8.00, 20.00, 24.00, 8.00.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Dexamethasone; Drug Administration Schedule; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Luteinizing Hormone; Luteolytic Agents; Ovary; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Testosterone; Triptorelin Pamoate; Ultrasonography

The aim of the study was to evaluate the hormonal (focusing on the urinary steroid profile) and clinical effects of chronic gonadotropin-releasing hormone (GnRH) agonist treatment in patients with polycystic ovary syndrome (PCOS) suffering from hirsutism. A long-acting GnRH agonist was administered for 6 months in eight PCOS patients. Hormonal effects were measured by determining serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and estradiol concentrations, and by profiling urinary steroids using capillary gas chromatography of 24-hour urine samples. To evaluate 5 alpha-reductase enzyme activity, the ratios of androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol were calculated in urine samples. The ratio of androgen to cortisol metabolites was also determined before, and 3 and 6 months after therapy. LH and estradiol levels were suppressed significantly after the first injection and testosterone after the second injection of the GnRH agonist. Thus, serum testosterone was normalized. Ratios of urinary steroids reflecting 5 alpha-reductase enzyme activity (androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol) and the ratio of androgen to cortisol metabolites decreased significantly after 3 months of treatment. Degree of hirsutism, assessed by Ferriman-Gallwey score, diminished after 6 months, but not significantly. In conclusion, our data show that long-acting GnRH agonist treatment of PCOS patients is effective in reducing serum and urinary androgen levels, but it is not accompanied by an effective reduction in hirsutism during a 6-month treatment period. A longer or a combined treatment would be needed to achieve significant improvement in hirsutism. Gas chromatographic profiling of urinary steroids and the use of specific ratios of the excreted metabolites seems to be a sensitive tool both in the diagnosis of PCOS and in monitoring ovarian suppression.

Topics: Adult; Androsterone; Drug Implants; Estradiol; Etiocholanolone; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Luteinizing Hormone; Luteolytic Agents; Polycystic Ovary Syndrome; Prolactin; Testosterone; Time Factors; Triptorelin Pamoate

The objective of this prospective randomized study was to evaluate and compare the hormonal and clinical effects of long-acting gonadotropin-releasing hormone (GnRH) agonist and a combination of GnRH agonist with combined oral contraceptive (COC) or flutamide in women with polycystic ovary syndrome (PCOS). Thirty-five hirsute women with PCOS, ranging in age from 19-27 years, were randomly divided into three groups: group A treated with GnRH agonist (n = 12), group B (n = 12) treated with GnRH agonist plus COC and group C (n = 11) treated with GnRH agonist plus flutamide for 6 months. Before, at the end and 6 months after the end of treatment, blood samples were drawn from all women (in early follicular phase in those with menstrual cycles) to measure ovarian and adrenal androgens, gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estradiol and estrone plasma levels. The results showed that all three protocols had good therapeutic efficacy. A significant reduction in hirsutism was observed in all patients after 6 months of therapy, the Ferriman-Gallwey scores dropping to 9 +/- 3 in group A, 10 +/- 4 in group B and 11 +/- 5 in group C. Six months after the end of therapy, the hirsutism score continued to be significantly reduced in all groups. After 6 months of therapy, a reduction in plasma levels of LH, FSH, estrone, estradiol, testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) was observed in all groups although this was more pronounced in group B and group C. These therapies may be the basis of future treatments that quickly reduce hirsutism and remove its causes by reducing the secretion of ovarian and adrenal androgens and by blocking androgen receptors.

Topics: Adult; Amenorrhea; Androgen Antagonists; Contraceptives, Oral, Combined; Cyproterone Acetate; Estradiol; Estradiol Congeners; Estrone; Ethinyl Estradiol; Female; Flutamide; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Luteinizing Hormone; Luteolytic Agents; Polycystic Ovary Syndrome; Progesterone Congeners; Prospective Studies; Triptorelin Pamoate

To compare triptorelin, cyproterone acetate (CPA), and flutamide, in combination with an oral contraceptive, in the treatment of hirsutism.. Prospective randomized study.. Tertiary care hospital.. Thirty-nine hirsute women with idiopathic or functional ovarian hyperandrogenism.. Patients were randomly assigned to receive triptorelin (3.75 mg IM every 28 days), CPA (100 mg/d orally on days 1-10 of the menstrual cycle), or flutamide (250 mg orally twice daily). All the patients also received a triphasic oral contraceptive.. Before and after 3 and 9 months of treatment, the Ferriman-Gallwey score, hepatic function, and gonadal and adrenal steroid profiles were evaluated.. Thirty-three patients completed the 9-month study period. The Ferriman-Gallwey score decreased in all the groups. In the patients treated with CPA or flutamide, a decrease in the hirsutism score was noted as soon as after 3 months of treatment. This decrease was more pronounced after 9 months of treatment, especially in the patients who received flutamide, who had lower hirsutism scores compared with the other treatment groups. None of the patients had abnormal liver function test results. There was a mild increase in serum lipid concentrations, mostly in the group treated with triptorelin.. Triptorelin, CPA, and flutamide are effective drugs for the treatment of hirsutism. Flutamide results in a greater reduction in the hirsutism score, but CPA also offers satisfactory results at a much lower cost. Triptorelin has no advantages over flutamide and CPA, and is the most expensive of the three drugs tested.

Topics: Adult; Androgen Antagonists; Body Mass Index; Contraceptives, Oral, Hormonal; Cyproterone Acetate; Drug Therapy, Combination; Female; Flutamide; Hirsutism; Humans; Hyperandrogenism; Liver Function Tests; Luteolytic Agents; Prospective Studies; Triptorelin Pamoate

GnRH agonists (GnRHa) have recently been proposed for the treatment of hirsutism in women with the polycystic ovary syndrome (PCOS). As most of these subjects have increased androgen secretion from both ovaries and adrenal glands, the association of GnRHa with antiandrogen drugs might enhance the clinical response to treatment. On the other hand, this association might also potentiate the adverse effects of GnRHa on bone metabolism, generating a potentially harmful situation at the skeletal level. In this study we investigated in 41 PCOS patients the skeletal effects of a 6-month course of GnRHa (tryptorelin, 3.75 mg, i.m., monthly), either alone (n = 12) or associated with the antiandrogen drugs spironolactone (100 mg, orally, once daily; n = 14) or flutamide (250 mg, once daily; n = 15). In all subjects bone mineral density was measured before and after treatment by dual energy x-ray absorptiometry at the lumbar spine (L2-L4) and at the femoral neck and Ward's triangle. In addition, at baseline and after 6 months of therapy, bone metabolism markers (serum and urinary calcium, serum phosphorus and alkaline phosphatase, plasma osteocalcin, and urinary hydroxyproline) and endocrine parameters (serum gonadotropins, estradiol, and free testosterone) were assayed. Women given either GnRHa alone or associated with spironolactone or flutamide were similar for age and body mass index. At baseline, the 3 groups of PCOS women were also similar for endocrine and bone parameters. After 6 months, all treatments determined similar striking suppressions of serum gonadotropins and sex steroids. Concurrently, bone mineral density was significantly reduced at all examined sites in subjects receiving either GnRHa alone or GnRHa plus flutamide. Conversely, women given GnRHa plus spironolactone did not show any change in skeletal mass from baseline values (P < 0.05-0.01 among groups). Biochemical parameters of bone metabolism were consistent with densitometric assessments. In conclusion, after a 6-month course of therapy, bone mineral density is reduced in PCOS women given either GnRHa alone or GnRHa plus flutamide, but not in those receiving GnRHa plus spironolactone. The mechanisms of the bone-sparing effect of spironolactone remain to be determined. Nevertheless, this drug could represent a useful tool to prevent skeletal loss in women given GnRHa as well as in other hypoestrogenic conditions, in particular when estrogens are not recommended.

Topics: Adult; Bone and Bones; Bone Density; Bone Resorption; Female; Flutamide; Hirsutism; Humans; Polycystic Ovary Syndrome; Spironolactone; Triptorelin Pamoate

To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism.. Controlled clinical study.. Tertiary care institutional hospital.. Forty hirsute women and 13 healthy control women.. The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin.. CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels.. Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression.. The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Dehydroepiandrosterone Sulfate; Female; Genotype; Heterozygote; Hirsutism; Humans; Hyperandrogenism; Mutation; Phenotype; Reference Values; Sex Hormone-Binding Globulin; Steroid 21-Hydroxylase; Testosterone; Triptorelin Pamoate

To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.. Controlled clinical study.. Tertiary care institutional hospital.. Forty hirsute women and 17 women with normal menstrual cycles.. Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.. Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E2, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.. Patients with idiopathic hirsutism were identified by normal serum androgen levels (n=17). Those with functional ovarian hyperandrogenism (n=15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n=8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal TGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.. The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Analysis of Variance; Blood Glucose; Female; Hirsutism; Human Growth Hormone; Humans; Hyperandrogenism; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Isoenzymes; Ovary; Steroid 17-alpha-Hydroxylase; Triptorelin Pamoate

The aim of this study was to compare the clinical and hormonal effects of the combination of a long-acting gonadotrophin-releasing hormone analogue (GnRH-a) plus an oral contraceptive (OC) pill containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone in patients with polycystic ovarian disease (PCOD) and related hyperandrogenisms, in order to evaluate whether the addition of GnRH-a has any advantage. A total of 12 PCOD patients were treated with the EE-CPA pill alone for 10 consecutive cycles according to an OC standard regimen. A further 12 patients were treated with GnRH-a, one i.m. injection every 28 days for a total of eight injections, combined with the EE-CPA pill for 10 consecutive cycles. The latter was thus prolonged for two cycles more than GnRH-a. Clinical evaluations (symptoms, weight, Ferriman-Gallwey score) and hormonal and biochemical analyses were assessed before, during (at 3 or 6 months) and after treatment, either when spontaneous cycles had resumed or after 3 months of amenorrhoea. There was a significant improvement in hirsutism, and a strong reduction in gonadotrophin, oestradiol, testosterone, androstenedione and 17-OH-progesterone concentrations in both treatment groups but with no significant differences between them, except in the gonadotrophin concentrations. Cortisol and triglyceride concentrations increased during treatment in both groups. The Ferriman-Gallwey score remained significantly decreased in both groups after treatment, as did androstenedione in the GnRH-a plus EE-CPA pill group, but there were no significant differences between the two groups. No changes were observed in prolactin, dehydroepiandrosterone sulphate (DHEA-S), insulin, glycaemia and cholesterol concentrations. However, when only the obese and more hirsute patients were considered, significant differences between the two groups were found during treatment in the Ferriman-Gallwey score and the gonadotrophin and DHEA-S concentrations (which increased during treatment in obese patients with the pill alone), and after treatment in the Ferriman-Gallwey score and the concentration of 17-OH-progesterone in the more hirsute patients, with the GnRH-a plus pill group having better results. In conclusion, a cyclic prolonged treatment with OC EE-CPA pills is not improved in most PCOD patients by the addition of GnRH-a, and is complicated and expensive. However, the addition of a long-acting GnRH-a may be recommended in obese and

Topics: Adolescent; Adult; Contraceptives, Oral, Hormonal; Cyproterone Acetate; Drug Therapy, Combination; Ethinyl Estradiol; Female; Hirsutism; Hormones; Humans; Polycystic Ovary Syndrome; Treatment Outcome; Triptorelin Pamoate

Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone agonist (GnRHa) have been shown to be effective for the treatment of hirsutism. We wished to compare the effectiveness of CPA in two standard doses with GnRHa and add-back therapy and to compare the length of remission after these treatments. A total of 60 hirsute hyperandrogenic women was assigned to the following treatment groups: CPA 2 mg with 35 microg of ethinylestradiol for 21 days each month (Diane group), CPA 50 mg, days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of conjugated oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate 10 mg, days 12-21 (GnRHa group). Hirsutism was graded by the Ferriman-Gallwey-Lorenzo (FGL) index and anagen hair shaft diameters and serum luteinizing hormone (LH) and testosterone were assessed before and every 3 months during and after treatment. All women were treated for 1 year with 1 year follow-up. At baseline hirsutism and endocrine patterns were similar in all groups. After one year of treatment, hirsutism decreased in all groups but the changes were greater (P <0.05) in the CPA and GnRHa groups than in the Diane group. Serum LH and testosterone were lowest in the GnRHa group. After withdrawal, hirsutism increased rapidly in the Diane and CPA groups and after 6 months, FGL scores and hair shaft diameters were similar to pretreatment values. In the GnRHa group, hirsutism increased more gradually and after 1 year of withdrawal, FGL scores and hair diameters were significantly (P <0.05) less than pretreatment values. Serum LH and testosterone increased rapidly in all three groups reaching pretreatment values by 6 months. These data suggest equal efficacy of the GnRHa and the high dose CPA regimen for the treatment of hirsutism in hyperandrogenic women. GnRHa with add-back treatment appears to result in a longer remission of hirsutism in comparison with CPA.

Topics: Adult; Androgen Antagonists; Cyproterone Acetate; Dose-Response Relationship, Drug; Drug Administration Schedule; Estradiol Congeners; Ethinyl Estradiol; Female; Hirsutism; Humans; Medroxyprogesterone Acetate; Receptors, LHRH; Remission Induction; Triptorelin Pamoate

Treatment with gonadotropin-releasing hormone (GnRH) agonist leads to enhanced bone turnover and accelerated bone loss in premenopausal women with endometriosis, uterine leiomyomatomas and hirsutism. Sodium etidronate is a powerful inhibitor of bone resorption which had been proven efficacious in the prevention and treatment of postmenopausal osteoporosis. The objective of this study was to evaluate the skeletal effects of 6 months of therapy with the depot preparation of the GnRH agonist triptorelin (decapeptil 3.75 mg intramuscularly every 4 weeks) in 24 hirsute patients, aged 24-33 years, with hyperandrogenic chronic anovulation. Ten patients also received cyclical etidronate in an oral dose of 400 mg/day for 2 weeks, followed by an 11-week period of 500 mg/day elemental oral calcium (one cycle). The remaining 14 patients received 500 mg/day of elemental calcium continuously. After 6 months all treatments were discontinued for at least a further 6 months. Bone mineral density (BMD) at lumbar spine and hip (dual-energy X-ray absorptiometry, Sophos LXRA, France) and biochemical markers (serum alkaline phosphatase, osteocalcin, urinary N-telopeptide and hydroxyproline/creatinine ratio) were evaluated at baseline, 6 months and 12 months. In the group given GnRH agonist alone BMD fell significantly at all measured skeletal sites during the first 6 months. In the patients treated with etidronate a significant decrease in BMD was observed at lumbar spine but not in the femoral neck and trochanter, and the changes at lumbar spine and trochanter were significantly smaller than those in the control group. At 6 months bone turnover was also increased in patients treated with GnRH and calcium. Cyclical etidronate prevented the increase in biochemical markers of bone formation and resorption, with the exception of calcium/creatinine excretion, which was significantly increased in both groups. Six months after treatment withdrawal BMD did not recover in either group. Biochemical markers (N-telopeptide, serum alkaline phosphatase) remained increased in those patients previously treated with calcium alone while they remained close to baseline values in the patients treated with cyclical etidronate. Our study indicates that: (1) GnRH agonist therapy causes remarkable bone loss in young individuals with androgen excess who are expected to have increased bone mass; (2) this bone loss can be partially prevented by intermittent cyclical etidronate therapy.

Topics: Adult; Anthropometry; Bone Density; Calcium; Drug Therapy, Combination; Etidronic Acid; Female; Hirsutism; Humans; Luteolytic Agents; Osteoporosis; Polycystic Ovary Syndrome; Triptorelin Pamoate

We evaluated modifications in the pituitary-ovarian-adrenal axis in severely hirsute women after administration of the gonadotropin-releasing hormone analog (GnRHa), D-Trp-6-luteinizing hormone-releasing hormone (LHRH) (Triptorelin) in a prospective study at a tertiary hospital. A total of 20 hirsute women aged 19 to 38 years were included. Hyperandrogenism of adrenal origin was excluded in all subjects. Patients received 3.75 mg D-Trp-6-LHRH intramuscularly (Decapeptyl 3.75; Lasa-Ipsen, Barcelona, Spain). Serum levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (delta 4 An), dehydroepiandrosterone sulfate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone-binding globulin (SHBG) were determined before GnRHa administration, 24 and 48 hours after, and on days 7, 15, 30, and 45. GnRHa suppresses FSH, LH, and E2 in all women. Unexpectedly, adrenal steroids showed a flare-up phenomenon in the first days and subsequent decrease to lower values than before GnRHa administration. SHBG showed slight changes. After GnRHa, patients showed a significant decrease in T and delta 4 An: these hormones were reduced to half the basal levels. We conclude that GnRHa can potentially be used in the treatment of hyperandrogenism to reduce androgen levels in hirsute women.

Topics: Adolescent; Adult; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dose-Response Relationship, Drug; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Injections, Intramuscular; Luteinizing Hormone; Ovary; Pituitary-Adrenal System; Progesterone; Prolactin; Prospective Studies; Radioimmunoassay; Sex Hormone-Binding Globulin; Testosterone; Triptorelin Pamoate

To determine the effectiveness of GnRH-agonist (GnRH-a) treatment in women with late onset congenital adrenal hyperplasia.. Prospective assessment of GnRH-a treatment in six women with documented late-on-set congenital adrenal hyperplasia who were not preselected. Comparisons were made to previous responses in the same patients receiving dexamethasone. Eight age- and weight-matched ovulatory women served as controls.. Academic medical center.. Baseline blood determinations before and after i.v. ACTH, before and after 6 months of GnRH-a treatment. Estrogen and progestin replacement was begun in all women after the 3rd month of treatment.. Serum 17-hydroxyprogesterone (17-OHP), gonadotropin, and androgen levels before and after GnRH-a treatment. Responses of 17-OHP and androgens to ACTH assessment of hirsutism using a modified Ferriman-Gallwey score.. Gonadotropins, estrogen, androgen, and 17-OHP were suppressed with GnRH-a treatment. Levels were similar before and after estrogen and progestin replacement. Responses of 17-OHP after ACTH were blunted but still were elevated compared with responses in controls. Ferriman-Gallwey scores decreased significantly (-8 +/- 1; mean +/- SE). This response was greater than that observed previously with 6 months of dexamethasone (-2 +/- 0.3).. Suppression of the ovary with GnRH-a treatment was beneficial in these patients with late-onset congenital adrenal hyperplasia. An ovarian influence on the clinical and biochemical findings of the disorder is suggested.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Age of Onset; Androgens; Dexamethasone; Endocrine Glands; Female; Gonadotropins; Hirsutism; Humans; Hydroxyprogesterones; Ovary; Prospective Studies; Triptorelin Pamoate

The study evaluates the efficacy of tryptorelin treatment in cases of acne and hirsutism associated with polycystic ovarian (PCO) disease. This non-comparative open study in a sample population of 20 young patients who wished to have children demonstrates the reduction of the hirsutism and acne score after six months' treatment. Tryptorelin was even capable of normalizing the hematic hormonal levels examined and ovarian function following six months of treatment, as well as at an initial follow-up after three months. The authors state their intention of performing a larger trial in order to observe the real efficacy of tryptorelin in a study which includes a 12-month follow-up to assess the pregnancy rate.

Topics: Acne Vulgaris; Adult; Female; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Italy; Longitudinal Studies; Polycystic Ovary Syndrome; Time Factors; Triptorelin Pamoate

GnRH agonists (GnRH-A) have been used for the treatment of hirsutism in women with ovarian hyperandrogenism. However, significant side-effects, including vasomotor symptoms and bone loss, have prevented the long term use of this therapy. In this study, we evaluated the effects of low dose (physiological) estrogen replacement on the side-effects and clinical and hormonal parameters of 22 hirsute women with ovarian hyperandrogenism when treated with a long-acting GnRH-A, Decapeptyl. Ten patients with Ferriman-Gallwey (FG) scores averaging 13.4 +/- 1.5 were randomly assigned to be treated with Decapeptyl alone (3.75 mg, im, every 28 days for 6 months), and 12 other patients with FG scores averaging 13.3 +/- 1 received Decapeptyl with estrogen (conjugated equine estrogens, 0.625 mg) for 21 days and medroxyprogesterone acetate (10 mg) for 10 days (days 12-21). After 6 months, LH was suppressed in both groups, whereas FSH was significantly reduced only in the group receiving GnRH-A with estrogen (2.5 +/- 4 vs. 4.8 +/- 0.6 IU/L; P < 0.01). Serum androgen levels were reduced in both groups, although the reduction of testosterone and unbound testosterone was greater in the group receiving hormonal replacement [1.73 +/- 0.3 vs. 2.57 +/- 0.4 nmol/L for testosterone (P < 0.05); 8.3 +/- 1 vs. 14.6 +/- 2.8 pmol/L for unbound testosterone (P < 0.05)]. The reduction in hirsutism scores was greater with hormonal replacement (FG scores, -4.1 +/- 0.3 vs. -2.5 +/- 0.3; P < 0.05), whereas the polycystic appearance of ovaries by ultrasound was decreased in both groups. Amenorrhea and vasomotor symptoms were observed only with GnRH-A alone. Serum osteocalcin rose significantly with GnRH-A alone, reflecting a change in bone turnover (0.49 +/- 0.05 to 0.64 +/- 0.09 nmol/L; P < 0.05), but was unchanged with hormonal replacement. Patients receiving hormonal replacement had treatment extended to 1 yr. A further improvement of hirsutism, with scores dropping into the normal range (4.9 +/- 0.7), as well as a normalization of ovarian morphology were evident at this time. In conclusion, low dose (physiological) estrogen replacement may enhance the effects of GnRH-A treatment, while preventing most of the side-effects encountered with GnRH-A alone. This may allow more prolonged treatment, which is necessary for hirsutism.

Topics: Adolescent; Adult; Androgens; Drug Synergism; Drug Therapy, Combination; Estrogen Replacement Therapy; Female; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Hirsutism; Humans; Medroxyprogesterone Acetate; Menstruation; Triptorelin Pamoate

To assess the long-term effects of GnRH agonist (GnRH-a) therapy in a patient with benign ovarian hyperandrogenism.. Case report.. University Hospital endocrine outpatient's clinic.. A 55-year-old postmenopausal woman with hirsutism and virilization of ovarian origin.. Treatment with a course of GnRH-a (triptorelin 3.75 mg IM every 28 days for 4 months). Follow-up for 3 years.. Serum gonadotropin and androgen levels, clinical assessment using the Ferriman-Gallwey score, and assessment of ovarian morphology by ultrasonography.. Administration of triptorelin resulted in suppression of serum testosterone and gonadotropin values and relief of the hyperandrogenic symptoms. Upon discontinuation of treatment, the patient's serum gonadotropin levels returned to the postmenopausal range, but the testosterone levels remained normal and the patient was asymptomatic for an observation period of 3 years.. This case is the first example of long-term remission of ovarian hyperandrogenism in a postmenopausal woman, after short-term treatment with GnRH-a. This supports the view that GnRH-a therapy could be used, even in short courses, for the long-term suppression of benign ovarian hyperandrogenism.

Topics: Adrenocorticotropic Hormone; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hirsutism; Hormones; Humans; Hyperandrogenism; Middle Aged; Ovarian Diseases; Testosterone; Time Factors; Triptorelin Pamoate

The aim of this study was to prove the utility of GnRH analogues for the suppression of androgen secretion in a postmenopausal woman with a suspected virilizing ovarian tumour.. We present a case of a 72-year-old woman with virilization of recent onset. Hormonal studies revealed a fourfold increase in serum testosterone levels, normal dehydroepiandrosterone sulphate concentrations and high levels of serum 17-hydroxyprogesterone levels. Computed axial tomography scan of the ovaries was normal and the adrenal glands showed a discrete enlargement. The long-acting GnRH analogue, triptorelin, was injected initially (3.75mg i.m.) and serum hormone levels were measured weekly throughout one month.. GnRH produced a decrease in serum testosterone levels to normal values, in parallel with the suppression of serum LH and FSH concentrations. The patient was treated for three months with triptorelin and she experienced an amelioration of the hyperandrogenic symptoms. In order to achieve a diagnosis, the patient was submitted to a laparotomy that revealed a small hilus cell tumour in the left ovary.. GnRH analogues may offer a good therapeutic option in some states of gonadotrophin-dependent hyperandrogenism of ovarian origin.

Topics: Aged; Female; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Hyperandrogenism; Neoplasms, Gonadal Tissue; Ovarian Neoplasms; Postmenopause; Testosterone; Triptorelin Pamoate

To study ovarian and adrenal steroid profiles of women with idiopathic hirsutism, we compared sex steroid and basal and corticotropin (ACTH)-stimulated adrenal steroid levels before and after ovarian suppression induced by a long-acting gonadotropin-releasing hormone agonist analog (GnRH-a) in 24 hirsute women without hyperandrogenemia. Twelve healthy women served as controls for basal and ACTH-stimulated adrenal steroid levels. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), estradiol (E2), basal and ACTH-stimulated 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), delta 4-androstenedione (delta 4-A), 11-deoxycortisol (S) and cortisol (F), and basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin levels were measured before and 21 days after 3.75 mg intramuscular triptorelin in hirsute women. Basal T levels and basal and ACTH-stimulated delta 4-A, DHEA, and DHEAS levels were not different in hirsute women with respect to controls. Basal and ACTH-stimulated 17OHP was elevated, and decreased to normal after ovarian suppression with triptorelin. Although basal and ACTH-stimulated delta 4-A levels were normal, the delta delta 4-A/delta F and delta delta 4-A/delta 17OHP ratios were elevated and remained elevated after ovarian suppression, suggesting enhanced adrenal delta 4-17,20-lyase activity. T, F, S, and DHEAS levels were not affected by ovarian suppression. Basal and ACTH-stimulated 17OHP and delta 4-A, and stimulated DHEA concentrations were reduced with ovarian suppression, but their net increment and ratio to the increase of F in response to ACTH remained unchanged, reflecting the ovarian contribution to the secretion of these steroids. We conclude that idiopathic hirsute women with normoandrogenemia show an increase in ovarian secretion of 17OHP and a minimally increased adrenal delta 4-17, 20-lyase activity, suggesting that mild forms of ovarian and adrenal functional hyperandrogenism may be present in these patients with otherwise unexplained hirsutism.

Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Adult; Androgens; Androstenedione; Case-Control Studies; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Gonadotropins; Hirsutism; Humans; Hydrocortisone; Luteinizing Hormone; Luteolytic Agents; Ovary; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Triptorelin Pamoate

To evaluate serum leptin concentrations in hirsute women.. Controlled clinical study.. Tertiary institutional hospital.. Thirty-three hirsute women and 11 healthy female controls.. Serum samples were obtained at baseline and on day 1 (gonadal stimulation) and day 21 (gonadal suppression) after the IM injection of a single 3.75-mg dose of triptorelin.. Leptin, T, sex hormone-binding globulin (SHBG), insulin, and glucose levels and free androgen index.. Leptin levels were increased in hirsute women in comparison with control subjects at baseline and on day 1. Leptin levels increased on day 1 compared with baseline and then decreased to baseline by day 21. Leptin levels correlated with body mass index (r = 0.76), SHBG levels (r = -0.52), free androgen index (r = 0.38), insulin levels (r = 0.46), and the glucose/insulin ratio (r = -0.38). When the effect of obesity on these results was removed by analysis of covariance and partial correlation analysis, leptin levels remained elevated only on day 1 and the only correlations that remained significant were those of leptin with insulin (r = 0.24) and the glucose/insulin ratio (r = -0.24).. The increased leptin levels found in hirsute women are related mainly to obesity and also to insulin resistance. Leptin levels increased during gonadal stimulation and returned to baseline during gonadal suppression, suggesting that leptin also is influenced by the gonadal axis.

Topics: Adrenocorticotropic Hormone; Adult; Body Mass Index; Estradiol; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Leptin; Luteinizing Hormone; Obesity; Proteins; Reference Values; Sex Hormone-Binding Globulin; Testosterone; Triptorelin Pamoate

The clinical utility of serum 3 alpha-androstanediol glucuronide level has been controversial. Among the concerns regarding its lack of utility has been the finding that suppression of serum 3 alpha-androstanediol glucuronide does not occur readily with treatment. We hypothesized that because the treatment of hirsutism requires a prolonged duration, a longer observation period is required for changes in serum 3 alpha-androstanediol glucuronide to be measured. Therefore, we studied the clinical and hormonal changes in 11 women treated for hirsutism with a gonadotropin-releasing hormone agonist (GnRH-a) for 1 year. A progressive reduction in Ferriman-Gallwey scores occurred, which was significant at 6 weeks and was maximal at 12 months. Serum 3 alpha-androstanediol glucuronide and another peripheral marker, androsterone glucuronide, also fell commensurately. While there was no correlation at 3 months, by 6 weeks a significant correlation had occurred between the suppression in Ferriman-Gallwey scores and the suppression of serum 3 alpha-androstanediol glucuronide and androsterone glucuronide. The suppression of these steroids also correlated with the suppression of non-sex hormone-binding globulin-bound testosterone. These data confirm that markers of peripheral androgen action, particularly serum 3 alpha-androstanediol glucuronide, reflect the clinical manifestation of hirsutism. However, it appears that modifications in peripheral androgen activity (presumably through 5 alpha-reductase activity) are time-dependent, and that serum markers reflect changes after 6 months of treatment.

Topics: Adult; Androstane-3,17-diol; Androsterone; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Testosterone; Triptorelin Pamoate