leuprolide and Hirsutism

Hirsutism is the excessive growth of terminal hair in a typical male pattern in a female. It is often a sign of excessive androgen levels. Although many conditions can lead to hirsutism, polycystic ovary syndrome and idiopathic hyperandrogenism account for more than 85% of cases. Less common causes include idiopathic hirsutism, nonclassic congenital adrenal hyperplasia, androgen-secreting tumors, medications, hyperprolactinemia, thyroid disorders, and Cushing syndrome. Women with an abnormal hirsutism score based on the Ferriman-Gallwey scoring system should be evaluated for elevated androgen levels. Women with rapid onset of hirsutism over a few months or signs of virilization are at high risk of having an androgen-secreting tumor. Hirsutism may be treated with pharmacologic agents and/or hair removal. Recommended pharmacologic therapies include combined oral contraceptives, finasteride, spironolactone, and topical eflornithine. Because of the length of the hair growth cycle, therapies should be tried for at least six months before switching treatments. Hair removal methods such as shaving, waxing, and plucking may be effective, but their effects are temporary. Photoepilation and electrolysis are somewhat effective for long-term hair removal but are expensive.

Topics: Adrenal Hyperplasia, Congenital; Androgen Antagonists; Antineoplastic Agents, Hormonal; Contraceptives, Oral, Hormonal; Cushing Syndrome; Drug-Related Side Effects and Adverse Reactions; Eflornithine; Female; Glucocorticoids; Gonadotropin-Releasing Hormone; Hair Removal; Hirsutism; Humans; Hyperandrogenism; Hyperprolactinemia; Leuprolide; Mineralocorticoid Receptor Antagonists; Neoplasms; Ornithine Decarboxylase Inhibitors; Polycystic Ovary Syndrome; Spironolactone; Thyroid Diseases

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

Hirsutism is the presence of terminal (coarse) hairs in females in a male-like pattern, affecting between 5% and 15% of women, depending on definition. Hirsutism has a significant negative impact on psychosocial development and is usually a sign of an underlying endocrine abnormality-namely, androgen excess. The most common cause of androgen excess is the polycystic ovary syndrome (PCOS), with 21-hydroxylase-deficient nonclassic adrenal hyperplasia, the hyperandrogenic insulin-resistant acanthosis nigricans syndrome, androgen-secreting tumors, and androgenic drug intake occurring less frequently. However, although 70-80% of patients with androgen excess demonstrate hirsutism, this sign may be less prevalent among women of Asian extraction. Conversely, not all hirsute patients have evidence of detectable androgen excess, as 5-15% of these women have "idiopathic hirsutism," with normal ovulatory function and androgen levels. There is a strong familial predilection for hirsutism, primarily because the underlying endocrine disorders (eg, PCOS) and the factors regulating the development of hair growth (eg, androgen receptor activity, 5alpha-reductase activity) have a strong genetic component. The diagnostic evaluation of the potentially hirsute patient first involves confirming the presence of hirsutism and then excluding associated or etiological abnormalities and disorders (eg, ovulatory dysfunction, adrenal hyperplasia, diabetes, thyroid hormone abnormalities). Treatment should be undertaken using combination therapy, to possibly include 1) hormonal suppression (oral contraceptives, long-acting gonadotropin-releasing hormone analogues, and insulin sensitizers), 2) peripheral androgen blockade (spironolactone, flutamide, cyproterone acetate, or finasteride), and 3) mechanical/cosmetic amelioration and destruction of the unwanted hairs (electrology and, potentially, laser hair removal). The application of eflornithine hydrochloride 13.9% topical cream may also be useful to ameliorate unwanted facial hair growth. Overall, although hirsutism is a frequent and distressing abnormality often signaling an underlying endocrine disorder, a systematic approach to evaluation will uncover the etiology, and combination therapy will provide satisfactory treatment for most patients.

Topics: Androgen Antagonists; Contraceptives, Oral; Diagnosis, Differential; Eflornithine; Female; Hair Removal; Hirsutism; Humans; Leuprolide; Prevalence

In the May 1993 issue of the Journal we reviewed the basic science of androgen biology in women. We now discuss the evaluation of suspected hyperandrogenism and the therapeutic modalities available.

Topics: Adrenal Hyperplasia, Congenital; Androgen Antagonists; Androgens; Contraceptives, Oral; Cushing Syndrome; Female; Hirsutism; Humans; Leuprolide; Polycystic Ovary Syndrome; Reference Values; Virilism

To compare the efficacy of finasteride and GnRH agonist in the treatment of idiopathic hirsutism.. Sixty women with hirsutism were randomly assigned to receive either 5 mg of finasteride or long-acting GnRH agonist (depot leuprolide 3.75 mg) intramuscularly monthly for six months.. Hirsutism scores were measured according to the Ferriman-Gallway scoring system, and side-effects were monitored for six months of treatment. Blood samples were taken at each visit for assessment of endocrine (FSH, LH, estradiol, progesterone, total and free testosterone, androstenedione, DHEAS-S, 17-OH-P. SHBG), biochemical, and hematologic para- meters.. All of the patients treated with finasteride or GnRH agonist showed neither menstrual abnormalities nor side-effects. The mean percent change (+/- SD) in hirsutism scores in the GnRH and finasteride groups was 36% +/- 14% and 14% +/- 11% at six months, respectively. Serum total testosterone, free testosterone, androstenedion and DHEA-S showed a meaningful decrease in patients treated with GnRH agonist. On the other hand, only serum total testosterone and free testosterone levels decreased with finasteride treatment (p < 0.05 and p < 0.0001, respectively).

Topics: 5-alpha Reductase Inhibitors; Adolescent; Adult; Androstenedione; Animals; Dehydroepiandrosterone Sulfate; Delayed-Action Preparations; Enzyme Inhibitors; Estrogens, Conjugated (USP); Female; Finasteride; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hirsutism; Horses; Humans; Leuprolide; Luteinizing Hormone; Medroxyprogesterone Acetate; Testosterone

To determine if combination GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy was more effective than GnRH-a or OC alone in the treatment of hirsute women with ovarian hyperandrogenism.. Thirty-three hirsute women (ages 15 to 39 years) were randomized into three groups: 3.75 mg IM leuprolide acetate (LA) depot every 28 days for 6 months, combination monophasic oral contraceptive for 6 months (OC), or GnRH-a plus OC for 6 months (LA + OC).. Comparative studies of changes in hormonal and hair parameters were performed at baseline, 3, and 6 months after starting therapy.. After 6 months, serum T and LH levels were decreased significantly in all groups although reduction was greater in GnRH-a groups than OC alone. The reduction of free T was significantly greater with LA + OC compared with LA or OC alone. This could be a consequence of the significant rise in sex hormone-binding globulin (SHBG) in LA + OC and OC groups compared with LA in which there was no change in SHBG. Reduced facila hair density and decrease in hirsutism score was observed in both GnRH-a groups after 6 months.. "Add-back" OC therapy used in combination with a GnRH-a increases SHBG and more effectively lowers free T levels in women with ovarian hyperandrogenism. Enhanced suppression of "bioavailable" androgens with combined GnRH-a and OC therapy failed to improve significantly the therapeutic effect of GnRH-a treatment alone on hirsutism.

Topics: Adolescent; Adult; Contraceptives, Oral; Drug Therapy, Combination; Endometrium; Ethinyl Estradiol; Female; Hirsutism; Humans; Hyperandrogenism; Leuprolide; Luteinizing Hormone; Norethindrone; Ovarian Diseases; Testosterone

The administration of long-acting GnRH analogs (GnRH-a) results in gonadotropin and androgen suppression in hyperandrogenic women. Nonetheless, no randomized studies are available comparing GnRH-a with currently used treatments for hirsutism. We have hypothesized that the greater degrees of androgen suppression achieved with GnRH-a therapy could result in a more rapid improvement in hirsutism compared to oral contraceptive (OCP) administration. To test this hypothesis, we studied 17 hirsute women before and during 6 months of randomized treatment with 1) leuprolide depot (3.75 mg/month) plus conjugated estrogen (0.625 mg/day) and medroxyprogesterone acetate (10 mg; days 1-12; n = 9; leuprolide+ERT), or 2) an OCP containing ethynodiol diacetate (1 mg) and ethinyl estradiol (35 micrograms; n = 8). LH, FSH, estradiol, dehydroepiandrosterone sulfate, androstenedione (A4), sex steroid-binding globulin, and total and free testosterone (T) were measured at weeks 0, 2, 4, 8, 12, and 28. At 0 and 28 weeks of treatment, hirsutism was evaluated subjectively by patient self-evaluation and by the Ferriman-Gallwey score, and objectively by determination of facial hair density, outer hair shaft diameter, and growth rate, determined both photographically and in plucked hairs. In the leuprolide+ERT, but not OCP, groups, there was a significant decrease in the circulating LH and FSH levels. In both groups, T and A4 decreased with treatment, although the decrease in A4 levels did not reach significance in OCP-treated women. The circulating sex steroid-binding globulin level increased in both treatment groups, but the changes in the OCP-treated women was greater. Consequently, although the calculated percent free T decreased significantly in both treatment groups, the decrease was greater in the OCP-treated women. The dehydroepiandrosterone sulfate level did not change with either therapy. A significant percent decrease in the Ferriman-Gallwey score was noted in the leuprolide+ERT, but not OCP, patients, and by self-evaluation, seven (78%) and five (55%) of leuprolide+ERT patients, compared to two (25%) and two (25%) OCP-treated women, noted an improvement in hair growth and texture, respectively. No significant difference in mean facial hair density or outer hair diameter was noted with either therapy. Patients treated with leuprolide+ERT demonstrated a decrease in the actual hair growth rate, using the photographic method, or percent decrease in growth rate, using plucked

Topics: Adolescent; Adult; Contraceptives, Oral; Estrogen Replacement Therapy; Face; Female; Hair; Hirsutism; Hormones; Humans; Leuprolide; Prospective Studies; Treatment Outcome

To determine the efficacy of treatment of significant hirsutism with a GnRH agonist (GnRH-a) and estrogen and progestin replacement therapy.. Clinical series.. Ambulatory gynecology clinic in a community hospital.. Ten women with significant hirsutism caused by polycystic ovarian disease.. The patients were treated with leuprolide acetate 20 micrograms/kg per day in combination with E2 (2 mg) and medroxyprogesterone acetate (5 mg) for 6 months.. Hirsutism scores and hair growth rates determined before and upon completion of treatment protocol.. Hirsutism scores and hair growth rates significantly decreased by 23% and 26%, respectively. The duration of hirsutism was the only significant covariate for hirsutism scores and hair growth rates. Only two patients had minimal, irregular bleeding that was corrected by increasing the estrogen dose.. The combination of a GnRH-a and estrogen replacement therapy was an effective and well-tolerated treatment in a small group of women with significant hirsutism caused by PCOD.

Topics: Adolescent; Adult; Estrogen Replacement Therapy; Female; Hair; Hirsutism; Humans; Leuprolide; Medroxyprogesterone Acetate; Polycystic Ovary Syndrome; Testosterone

To compare the therapeutic effects of a GnRH-agonist (GnRH-a), leuprolide acetate (LA) depot, versus LA plus and oral contraceptive (OC) containing cyproterone acetate in the treatment of hirsutism.. Randomized study.. Women addressed to the Department of Gynecological Endocrinology, University of Brescia, Brescia, Italy.. Thirty-two patients suffering from moderate and severe hirsutism secondary to polycystic ovary syndrome (PCOS) or idiopathic causes were selected.. Leuprolide acetate was injected IM every 28 days in all patients; 16 women, randomly allocated, received LA plus OC. At the beginning and at the end of treatment hirsutism score and hair diameters were evaluated.. Both treatment arms resulted in a decrease of hirsutism score and hair diameter, both in idiopathic hirsutism (16% to 31% versus 24% to 32%) and in hirsutism secondary to PCOS (23% to 33% versus 24% to 36%).. Gonadotropin-releasing hormone agonist can improve moderate and severe hirsutism effectively. It is necessary to add an OC.

Topics: Adult; Contraceptives, Oral; Cyproterone Acetate; Delayed-Action Preparations; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Injections, Intramuscular; Leuprolide; Luteinizing Hormone; Polycystic Ovary Syndrome; Severity of Illness Index; Sex Hormone-Binding Globulin

Ten hirsute women with polycystic ovarian syndrome (PCO) and nine with idiopathic hirsutism (IH) underwent selective ovarian suppression with leuprolide for 5-6 months and then were randomized to receive, in addition, dexamethasone or placebo for 4 more months. Serum hormone levels and hair growth rates were determined before and after each treatment period. During the initial treatment period with leuprolide alone, testosterone decreased by 54 +/- 6% (mean +/- SEM) in PCO and by 36 +/- 3% in IH (P = 0.02). Androstenedione decreased by 53 +/- 6% in PCO and by 31 +/- 7% in IH (P = 0.02). Androstanediol glucuronide (Adiol-G) decreased by 14 +/- 6% in PCO and by 7 +/- 3% in IH. There was no change in dehydroepiandrosterone sulfate (DHEAS). While initial serum androgen levels were higher in PCO than in IH, they were similar after ovarian suppression in the two groups. After ovarian suppression, Adiol-G was more consistently correlated with testosterone and androstenedione than was DHEAS, suggesting that Adiol-G may be a better marker than DHEAS of adrenal androgen secretion. Hair growth rates decreased by 37 +/- 6% in PCO and by 14 +/- 10% in IH (P = 0.07). The change in hair growth correlated with the change in androstenedione (r = 0.66; P = 0.002), but not significantly with the change in testosterone (r = 0.29; P = 0.2). After the addition of dexamethasone therapy (0.5 mg daily), testosterone, androstenedione, and DHEAS levels fell to near or below assay detection limits, while Adiol-G decreased by 80 +/- 3%. Hair growth rates decreased slightly more in women during dexamethasone (46 +/- 6%) than during placebo (26 +/- 9%; P = 0.18). In summary, the ovary was the major source of circulating testosterone and androstenedione in PCO. The adrenal contributed a substantial minority of these hormones in PCO and was the major source of androgen secretion in IH. Adrenal hyperandrogenism was common in both IH and PCO. Hair growth rates correlated best with changes in serum androstenedione levels. Adiol-G, which was derived primarily from adrenal precursors, was a better marker of adrenal androgen secretion than was DHEAS in these subjects.

Topics: Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Androgens; Androstenedione; Bone Density; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hair; Hirsutism; Humans; Leuprolide; Luteinizing Hormone; Ovary; Polycystic Ovary Syndrome; Random Allocation; Testosterone

The most frequent cause of virilization in postmenopausal women is excessive androgen production of ovarian origin. Bilateral oophorectomy is usually performed, even in cases of benign tumors or hyperthecosis. This is the first report of a case series of long-term GnRH-agonist treatment of hyperandrogenism in postmenopausal women.. We present three women with postmenopausal hyperandrogenism of ovarian origin who were treated with GnRH agonists.. We describe three cases of postmenopausal women with virilization and hyperandrogenism of presumed ovarian origin, all with slight enlargement of the ovaries but without visualization of a tumor, who had long-term treatment with GnRH agonists. No histological diagnosis was available, and therefore all patients received careful follow-up, including periodic testing of androgen levels and ovarian imaging by computed tomography scans. The three patients responded in different ways to treatment with GnRH agonists.. Long-term GnRH agonist treatment is an acceptable choice for treatment of postmenopausal hyperandrogenism in patients where ovarian origin of androgen excess is ascertained, and especially in those patients who have an increased risk for surgery due to comorbidities or who are unwilling to undergo bilateral oophorectomy.

Topics: Aged; Alopecia; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Hyperandrogenism; Hypertension; Leuprolide; Liver Cirrhosis, Alcoholic; Magnetic Resonance Imaging; Middle Aged; Obesity; Ovary; Postmenopause; Tomography, X-Ray Computed

To evaluate the role of TNF-alpha in the pathogenesis of hyperandrogenism, we have evaluated the serum TNF-alpha levels, as well as several polymorphisms in the promoter region of the TNF-alpha gene, in a group of 60 hyperandrogenic patients and 27 healthy controls matched for body mass index. Hyperandrogenic patients presented with mildly increased serum TNF-alpha levels as compared with controls (mean[median] +/- SD: 7.2[7.0] +/- 3.3 pg/ml vs. 5.6[4.4] +/- 4.0 pg/ml, P < 0.02). Although no differences in body mass index and insulin resistance indexes were observed between patients and controls, when subjects were classified by body weight, serum TNF-alpha was increased only in lean patients as compared with lean controls, but this difference was not statistically significant when comparing obese patients with obese controls. The TNF-alpha gene polymorphisms studied here (-1196C/T, -1125G/C, -1031T/C, -863C/A, -857C/T, -316G/A, -308G/A, -238G/A, and -163G/A) were equally distributed in hyperandrogenic patients and controls. However, carriers of the -308A variant presented with increased basal and leuprolide-stimulated serum androgens and 17-hydroxyprogesterone levels when considering patients and controls as a group. No differences were observed in serum TNF-alpha levels, body mass index, and insulin resistance indexes, depending on the presence or absence of these variants. In conclusion, our present results suggest that the TNF-alpha system might contribute to the pathogenesis of hyperandrogenism, independent of obesity and insulin resistance. However, elucidation of the precise mechanisms underlying the relationship between the TNF-alpha system and androgen excess is needed before considering TNF-alpha as a significant contributing factor to the development of hyperandrogenism.

Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Adult; Androgens; Blood Glucose; Body Mass Index; DNA; Estradiol; Female; Follicle Stimulating Hormone; Genotype; Hirsutism; Humans; Hydrocortisone; Hyperandrogenism; Insulin; Leuprolide; Luteinizing Hormone; Menstrual Cycle; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Reference Values; Sex Hormone-Binding Globulin; Tumor Necrosis Factor-alpha

Hirsute women with normal ovulatory menstrual function are often diagnosed as having idiopathic hirsutism. We prospectively evaluated 62 hirsute ovulatory women to determine if they had a subtle form of polycystic ovary syndrome, and if they exhibited any of the metabolic abnormalities commonly associated with classic polycystic ovary syndrome.. Baseline hormonal profiles, ovarian responses to gonadotropin-releasing hormone agonist, and ovarian morphology by ultrasound were compared in the hirsute women and two groups of ovulatory controls.. Among 62 women, only 8 (13%) had normal androgen levels and were considered to have idiopathic hirsutism. Twenty-four (39%) had characteristic polycystic ovaries on ultrasound, an exaggerated response of 17-hydroxyprogesterone to leuprolide, or both, suggesting ovarian hyperandrogenism and the diagnosis of mild polycystic ovary syndrome. The remaining 30 women (48%) were considered to have unspecified hyperandrogenism. Age, body weight, and androgen level were similar among the hyperandrogenic subgroups. However, when compared with both normal and overweight controls and with patients with idiopathic hirsutism, the women who had mild polycystic ovary syndrome had higher fasting insulin levels [P < 0.01, mean (+/- SD) increase of 7 +/- 3 microU/mL], lower glucose-insulin ratios (P < 0.01, mean reduction of 3 +/- 1.5), higher low-density lipoprotein cholesterol levels (P < 0.05, mean increase of 26 +/- 10 mg/dL), and lower high-density lipoprotein (HDL) cholesterol levels (P < 0.01, mean reduction of 10 +/- 4 mg/dL). Compared with patients who had unspecified hyperandrogenism, these women also had higher fasting insulin levels (P < 0.05), lower glucose-insulin ratios (P < 0.05), and lower HDL cholesterol levels (P < 0.05).. These data suggest that mild polycystic ovary syndrome is more common than idiopathic hirsutism, and it is also associated with subtle metabolic abnormalities.

Topics: Adult; Analysis of Variance; Androgens; Blood Glucose; Body Mass Index; Cholesterol; Female; Fertility Agents, Female; Gonadal Steroid Hormones; Hirsutism; Humans; Insulin; Leuprolide; Menstrual Cycle; Polycystic Ovary Syndrome; Prospective Studies; Triglycerides; Ultrasonography

To test the hypothesis that ovarian hormones in women with hyperandrogenism alter adrenocortical steroidogenesis.. Combination of two prospective studies.. Academic medical centers.. Eighteen hyperandrogenic patients demonstrating hirsutism with either hyperandrogenemia, oligomenorrhea, or both. Eighteen healthy nonhirsute eumenorrheic untreated women served as controls.. Blood sampling basally and after acute adrenal stimulation with ACTH, before and after 20-24 weeks of leuprolide administration. Nine patients also received 0.625 mg/d of oral conjugated esterified estrogens and 10 mg of medroxyprogesterone acetate days 1-12 of the month (i.e., estrogen replacement therapy [ERT]), whereas the remaining nine did not.. Before and after the administration of the GnRH agonist (GnRH-a), the basal concentrations of DHEAS; and the levels of androstenedione (A4), DHEA, androstenediol, 11 beta-hydroxyandrostenedione (11-OHA4), and cortisol before and 60 minutes after acute adrenal stimulation, were measured.. Levels of DHEAS, androstenediol, and 11-OHA4 decreased by 15%-30%, regardless of whether patients initially had or did not have DHEAS excess. However, only hyperandrogenic patients with elevated levels of DHEAS showed a significant decrease in basal DHEA levels. No statistically significant difference in the response of either androgen to ACTH (1-24) stimulation was noted with ovarian suppression, regardless of initial DHEAS level or use of ERT.. We found no evidence that ovarian hormone secretion affected adrenal steroidogenesis, and those women with the highest adrenal androgen levels had the least response to GnRH-a suppression. These findings further support the concept of an intrinsic, and possibly primary, abnormality of adrenocortical steroidogenesis in a subset of hyperandrogenic women that is independent of ovarian abnormalities.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Androgens; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estrogen Replacement Therapy; Female; Hirsutism; Humans; Leuprolide; Ovary; Prospective Studies

Topics: Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Leuprolide; Middle Aged; Ovarian Neoplasms; Testosterone; Time Factors

To evaluate the therapeutic effects of a GnRH agonist (GnRH-a), leuprolide acetate (LA) plus a pill containing ethinyl E2 plus cyproterone acetate (CPA) in a group of women with severe hirsutism who were unresponsive to oral contraceptive (OC) therapy.. Twenty-four patients suffering from severe hirsutism secondary to polycystic ovary disease (PCOD) were treated for 12 months with 3.75 mg IM LA every 28 days in association with 0.035 mg/d ethinyl E2 plus 2 mg/d CPA (Diane; Schering, Berlin, Germany) for 21 d/mo.. Patients were recruited in the Institute of Obstetrics and Gynecology, St. Bambino Hospital, University of Catania, Catania, Italy. Hormonal assays were performed in the Hormone Laboratories of St. Bambino Hospital, University of Catania, Catania, Italy.. Every 3 months the hirsutism score was evaluated. Mean serum concentrations of LH, FSH, E2, total and free T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS were determined. Every 6 months a vaginal ultrasound examination was performed.. In all patients after 6 and 12 months of treatment with LA plus OC, the hirsutism score improved significantly. Serum levels of LH, FSH, E2, total and free T, A, and DHEAS decreased significantly, whereas SHBG showed a marked increase. A significant reduction in the ovarian size was observed.. Gonadotropin-releasing hormone agonist, associated with a pill containing CPA, reduced the hirsutism in severely affected women with PCOD who are unresponsive to OC treatment alone.

Topics: Adult; Contraceptives, Oral; Cyproterone Acetate; Drug Therapy, Combination; Ethinyl Estradiol; Female; Hirsutism; Humans; Leuprolide; Polycystic Ovary Syndrome

To determine the dose of leuprolide acetate (LA) needed to maximally suppress serum androgens in hirsute women.. Prospective, dose-escalation study.. Outpatient endocrinology clinic.. Eight hyperandrogenic women with moderate to severe hirsutism.. A LA dose-response study was done in women receiving depot LA plus estrogen-progestin replacement.. Serum concentrations of T, androstenedione (A), and basal and GnRH-stimulated LH.. The lowest LA dose (3.75 mg/mo) suppressed serum T by 62% +/- 6% and A by 56% +/- 7%. No further decrease in serum androgens was seen with doses up to 15 mg/mo. Maximal suppression of basal and stimulated LH was also seen with the lowest dose of LA.. As opposed to results previously published in children with precocious puberty, the 3.75 mg dose of depot LA is sufficient to maximally suppress serum androgens in hyperandrogenic women.

Topics: Adolescent; Adult; Androstenedione; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Leuprolide; Luteinizing Hormone; Prospective Studies; Testosterone

Topics: Androgen Antagonists; Bromocriptine; Contraceptives, Oral, Combined; Dexamethasone; Female; Finasteride; Goserelin; Hirsutism; Humans; Ketoconazole; Leuprolide; Medroxyprogesterone Acetate; Nafarelin

Androsterone sulfate (Andros-S) is the most abundant 5 alpha-reduced androgen metabolite in serum. To determine whether this steroid could serve as a marker of 5 alpha-reductase activity, we developed a specific RIA, using tritiated Andros-S to assess procedural losses. Baseline serum Andros-S levels (mumol/L; mean +/- SEM) in 14 hirsute women (3.0 +/- 0.4) were not reduced by ovarian suppression with leuprolide (3.0 +/- 0.3), but were decreased by 79% with combined ovarian and adrenal suppression with leuprolide and dexamethasone. The mean Andros-S level in polycystic ovarian syndrome (3.2 +/- 0.4) and in idiopathic hirsutism (3.5 +/- 0.5) was not significantly different from levels in normal women (3.0 +/- 0.5), but were significantly greater than levels in obese women (1.7 +/- 0.3; P < 0.05). The serum concentrations of Andros-S were about 10-fold greater than those of androsterone glucuronide and 100-fold greater than those of androstanediol glucuronide. Serum Andros-S concentrations correlated strongly with dehydroepiandrosterone sulfate (R = 0.59; P < 0.001) and to a lesser degree with androstanediol glucuronide and androsterone glucuronide (R = 0.28 and 0.49, respectively). There was a weak correlation with androstenedione levels and the androstenedione response to ACTH (R = 0.38 and 0.34, respectively), and no significant correlation with serum testosterone (R = 0.19). The ratio of any of the 5 alpha-reduced products (Andros-S, androstanediol glucuronide, and androsterone glucuronide) to precursors (androstenedione and testosterone) was not increased in hirsute women, suggesting that these women did not have a generalized increase in 5 alpha-reductase activity. In conclusion, these results confirm that Andros-S is the most abundant 5 alpha-reduced androgen metabolite in serum. It is primarily, if not exclusively, of adrenal origin in hirsute women. The fact that its levels were not elevated in hirsutism, although those of other adrenal androgens and androgen metabolites (androstanediol glucuronide and androsterone glucuronide) were, suggests that variations in sulfotransferase activity or metabolic clearance of Andros-S may be important determinants of serum Andros-S levels. Although Andros-S may be a marker of systemic 5 alpha-reductase activity, there was no evidence of a generalized increase in 5 alpha-reductase activity in hirsute women. Andros-S is therefore not recommended as a marker of either adrenal androgen production or of hirsutism.

Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Adult; Androstenedione; Androsterone; Biomarkers; Body Mass Index; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Female; Follicle Stimulating Hormone; Glucuronates; Hirsutism; Humans; Hydrocortisone; Hydroxyprogesterones; Leuprolide; Luteinizing Hormone; Obesity; Reference Values; Testosterone

Topics: Female; Hirsutism; Humans; Leuprolide; Polycystic Ovary Syndrome

In the syndrome of familial virilization, insulin resistance, and acanthosis nigricans, the interrelationships are not understood. Twin sisters were studied, along with a lesser affected sister and mother. They manifested amenorrhea, hirsutism, masculinization, hypertension, hyperinsulinemia, hypertriglyceridemia, and hyperprolactinemia. Medical therapy with a gonadotropin-releasing hormone agonist plus an antiandrogen resulted in reversal of the hirsutism, yet with preservation of potential fertility. In response to luteinizing hormone (LH) and follicle-stimulating hormone suppression, there was normalization of the serum androgens, but not of the hyperinsulinemia, hypertriglyceridemia, hyperprolactinemia, hypertension, or acanthosis nigricans.. (1) This syndrome may be familial. (2) Medical therapy for the virilization is successful. (3) The hyperandrogenemia is primarily LH dependent and not primarily insulin dependent, although insulin may have an amplification effect. (4) Hyperinsulinemia, hypertriglyceridemia, hyperprolactinemia, and the hypertension are not androgen dependent.

Topics: Acanthosis Nigricans; Adult; Androgen Antagonists; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Dexamethasone; Diseases in Twins; Family Health; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Hyperinsulinism; Hyperlipidemias; Hyperprolactinemia; Hypertension; Insulin Resistance; Leuprolide; Luteinizing Hormone; Male; Pituitary Hormone-Releasing Hormones; Syndrome; Virilism

Androsterone glucuronide (Andros-G), a dihydrotestosterone metabolite, is present in serum at concentrations at least tenfold greater than those of androstanediol glucuronide. To investigate the significance of serum androsterone glucuronide, we developed a direct radioimmunoassay for this compound and measured its levels in normal women, women with mild or severe idiopathic hirsutism (IH), hirsute women with polycystic ovarian syndrome (PCO), and non-hirsute obese women. To determine the source of Andros-G precursors, serum levels were measured before and after selective ovarian suppression with leuprolide, combined ovarian and adrenal suppression with leuprolide and dexamethasone, and adrenal stimulation with ACTH. Androsterone glucuronide levels (nmol/l; mean +/- SD) were significantly higher (P less than 0.025) in women with mild idiopathic hirsutism (IH) (185 +/- 91), severe IH (173 +/- 97), and hirsute women with polycystic ovarian syndrome (PCO) (178 +/- 102) than in normal women (110 +/- 26). Levels in non-hirsute obese women (64 +/- 19) were lower than in normal women (P less than 0.01). Baseline levels (mean +/- SEM) in hirsute women given 20 micrograms/kg/day leuprolide for 5-9 months (171 +/- 15) were not significantly changed after leuprolide alone (153 +/- 18), and were decreased after adding dexamethasone (19 +/- 6; P less than 0.001). Andros-G levels did not increase significantly in normal women 60 min after i.v. ACTH (112 +/- 14 to 126 +/- 19), but rose in IH (170 +/- 24 to 216 +/- 26; P less than 0.001) and in PCO (179 +/- 26 to 238 +/- 31; P = 0.002). We conclude that Andros-G in women arises primarily from adrenal gland precursors and is elevated in hirsute women as a group. Its levels do not correlate with the severity of hirsutism, or the presence or absence of PCO, but reflect an increased production of adrenal androgens in both IH and PCO.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Adult; Androgens; Androsterone; Biomarkers; Dexamethasone; Female; Gonadotropin-Releasing Hormone; Hirsutism; Hormones; Humans; Leuprolide; Middle Aged; Ovary; Polycystic Ovary Syndrome; Radioimmunoassay

To determine the dose of the GnRH agonist leuprolide necessary to maximally suppress ovarian testosterone secretion, 10 moderately to severely hirsute women (5 with idiopathic hirsutism and 5 with polycystic ovarian syndrome) were given gradually increasing leuprolide doses, starting with either 5 or 10 micrograms/kg.day. Serum testosterone and estradiol, basal LH, and the LH response to GnRH were measured before and at the end of each treatment period, until maximal suppression of estradiol and testosterone occurred. Leuprolide was then continued for a total of 6 months to assess its clinical efficacy. Hirsutism scores and hair growth rates were determined before and after therapy. Serum estradiol and the LH response to GnRH were maximally or near-maximally suppressed in all women by the lowest doses of leuprolide used. Basal serum LH was not maximally suppressed in all women until a dose of 15 micrograms/kg.day was reached, and maximal testosterone suppression required 15 micrograms/kg.day or more in 7 of the 10 women. The addition of 0.5 mg dexamethasone daily for 4 weeks at the end of the study in 5 of the women reduced serum testosterone to undetectable levels. Symptomatic improvement in hirsutism occurred in 9 women, hirsutism scores decreased by at least 3 points in 5 women, and hair growth rates decreased in 8 women. These data indicate that low doses of leuprolide were sufficient to maximally suppress serum estradiol and the LH response to exogenous GnRH. Higher leuprolide doses were needed to maximally suppress serum testosterone and the basal LH levels. Leuprolide (20 micrograms/kg.day) effectively reduced hair growth in the majority of these women.

Topics: Adult; Dose-Response Relationship, Drug; Estradiol; Female; Gonadotropin-Releasing Hormone; Hair; Hirsutism; Humans; Leuprolide; Luteinizing Hormone; Radioimmunoassay; Testosterone