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Hirsutism and virilism in women.

Hirsutism in women may be defined as excessive thick (terminal) hair growth in facial and body regions. It is one of the early manifestations of virilization that correlate closely with elevated testosterone production. Testosterone production rates in normal women average 0.2 mg/day, with 25% secreted by the ovaries, 25% by the adrenals, and 50% arising from the peripheral metabolism of prehormones, notably androstenedione. Increased testosterone from adrenal and/or ovarian sources induces 5 alpha-reductase activity within the susceptible hair follicle. This results in the local production of dihydrotestosterone, the potent androgen that is likely responsible for the growth and stimulation of the hair follicle that leads to hirsutism. Activation of the hair follicle by androgens provides a secondary pathway for testosterone metabolism, unfortunately at the expense of undesirable hair growth. Although virilization in women may be caused by exogenous androgens, it occurs primarily from diseases of the adrenals or ovaries. Androgen-producing tumors of the adrenals cause virilization in association with excessive production of a wide variety of C19 androgens. In contrast, ovarian tumors tend to secrete a narrower range of androgens and their presence may be more occult. The most common causes of hirsutism in women arise from nontumorous states, chiefly ovarian in origin. The androgenized ovary syndrome represents a spectrum of abnormalities ranging from idiopathic hirsutism to the polycystic ovary syndrome to ovarian hyperthecosis. These states are associated with mild to severe abnormalities of androgen production and concomitant mild to severe abnormalities of ovarian histology. The pathogenesis of these abnormalities is still speculative, but appears to be related to increased pulsatile and tonic secretion of LH with ovarian hyperstimulation. Of the various laboratory tests to evaluate hirsutism, simple measurements of plasma testosterone, free testosterone, and most recently androstanediol glucuronide seem to provide the best chemical evidence of androgen abnormalities. Treatment of hirsutism/virilism in women is difficult and frequently unsatisfactory. At present, treatment schemes include local methods, suppression of androgens via glucocorticoids or oral contraceptives, and antiandrogens.

Adrenal Cortex Neoplasms↗

Comparison between buserelin and dexamethasone testing in the assessment of hirsutism.

Many hirsute women may present a form of functional ovarian hyperandrogenism (FOH), since they show an exaggerated 17-hydroxyprogesterone (17-OHP) response to GnRH agonists administration. As the failure of dexamethasone to reduce testosterone levels may be indicative of an ovarian source of androgen secretion, we evaluated the usefulness of dexamethasone suppression test, in comparison with buserelin challenge, in the assessment of hirsutism. Twenty-seven hirsute women (aged 15-42 yr) underwent ACTH and buserelin tests: 4 patients were heterozygotes for 21-OH deficiency and 8 patients were affected with FOH: 2 of the patients with hyperresponse to buserelin also had 21-hydroxylase deficiency. The results of the dexamethasone suppression test (2 mg/day for 7 days) were compared to those obtained after buserelin test. Basal T and delta4 levels (mean+/-SE) were higher than in controls (4.2+/-0.5 vs 2.2+/-0.2 nmol/l and 10.9+/-0.9 vs 5.9+/-0.6 nmol/l, p<0.02), while no differences were found in 17-OHP and DHEAS levels. A significant reduction (p<0.001) in T (1.8+/-0.4 nmol/l), delta4 (3.2+/-0.5 nmol/l) and DHEAS levels (2.4+/-0.3 micromol/l) was observed at the 3rd day of dexamethasone administration and no differences between sampling at 3rd, 5th and 7th day were found. Serum T was not suppressed in 6 cases, delta4 and DHEAS levels in 3 and 1 of them, respectively. Buserelin injection caused an excessive 17-OHP response in 8 patients, only 4 of them did not reduce T levels during dexamethasone. The sensitivity and specificity of the dexamethasone suppression test, with respect to the buserelin test, were 50% and 89%, respectively. In conclusion, 37% of hirsute patients had an abnormal responsiveness to buserelin and/or ACTH tests, indicating that hormonal investigations are mandatory. An ovarian origin of hirsutism was identified by buserelin test in 30% of patients and by dexamethasone in 22% of cases; only 4 of 8 patients showed concordant results to both tests. Therefore, buserelin challenge seems a more useful, cost-effective and less time consuming tool than dexamethasone administration in order to recognize the possible ovarian origin of hyperandrogenism.

Adolescent↗

Lack of correlation between sex hormone binding globulin and free testosterone in some cases of "idiopathic" hirsutism.

Plasma 3 alpha-androstanediol levels are increased in a high percentage of hirsute women, including those with normal plasma levels of its precursors, repeatedly evaluated during the menstrual cycle. To better ascertain the origin of this form of hirsutism, so called "idiopathic", 17 hirsute women (aged 19.5 +/- 4.8 SD yr), with normal bw, showing an isolated increase in plasma 3 alpha-androstanediol (0.65 +/- 0.18 SD nmol/l) were studied in basal conditions (on day 6, 7, 17, 18 of the menstrual cycle). A hirsute female (aged 14 yr) with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was also included in the protocol. Sex hormone binding globulin was evaluated using a saturation method (dihydrotestosterone- 3H 0.5-25 nM) with and without 200x cold dihydrotestosterone. Maximum number of binding sites and Ka were calculated in all cases with Scatchard analysis. Free testosterone was evaluated by the equilibrium dialysis technique. The results obtained showed a significant increase in Ka values in 10 out of the 17 cases; low plasma levels of sex hormone binding globulin in 13 cases and normal levels in 4 cases; high levels of free testosterone fraction in 5 cases and in the upper limits of the normal range or normal in the remaining 12. These findings demonstrate that some cases of "idiopathic" hirsutism may present an alteration in the binding affinity of the sex hormone binding globulin which may be genetically transmitted, being found to be increased in two sisters and in their brother.

Adolescent↗

Effect of finasteride in idiopathic hirsutism.

Increased 5 alpha-reductase activity has been found in hair follicles of hirsute women, suggesting a pathogenetic role. The aim of the present study was to evaluate the effect of finasteride in the treatment of idiopathic hirsutism. Twenty-seven women with idiopathic hirsutism, aged 16-35 years, were treated for 6 months with finasteride, 5 mg once daily. Fourteen patients were on finasteride alone (group A), while the remaining received in addition an oral contraceptive (group B). Clinical, hormonal and biochemical evaluation were performed before, and after 3 and 6 months of treatment. Clinical evaluation was repeated 6 months after drug discontinuation in seven patients. Treatment was well tolerated by all patients; no side effects or adverse reactions were reported. A significant improvement of hirsutism was obtained by finasteride; clinical score observed at the 6th month of therapy was reduced from 11.71 +/- 2.23 to 7.92 +/- 1.81 (p < 0.05) and from 14.92 +/- 6.13 to 9.3 +/- 2.75 (p < 0.05) in group A and B, respectively. Clinical score in seven patients was still 8.61 +/- 2.28 (p < 0.05) 6 months after the end of therapy. Finasteride treatment alone (group A) induced a slight increase, though not significant, in serum androgens; DHT and SHBG did not change. In group B (finasteride plus oral contraceptive) total testosterone and free testosterone showed no significant decrease; after 6 months of therapy DHT was reduced significantly, while SHBG levels were increased. These data demonstrate that 5 alpha-reductase inhibition may be an effective treatment in women suffering from idiopathic hirsutism. This approach may be attractive due to the absence of adverse reactions, although the necessity of an adequate contraception should be kept in mind.

Adolescent↗

Free testosterone concentration in serum: elevation is the hallmark of hirsutism.

A simple, reliable procedure for quantitating the concentration of free (not protein bound and thus biologically active) testosterone in serum has been applied to normal and hirsute patients. Each of 32 hirsute women studied had a significantly elevated level of free testosterone (that is, more than two standard deviations above the mean of that found in normal women), although half of them had a total serum testosterone level within normal limits. Suppression of free testosterone to within normal limits could be accomplished by dexamethasone alone in 47 per cent of the hirsute group. In the remainder of the hirsute group, suppression of free testosterone to within normal limits could be accomplished by addition of Enovid-E. Use of free serum testosterone concentration is clearly superior to the use of total serum testosterone concentration for the identification and rational therapy of simple hirsutism.

Adolescent↗

Evidence for adrenal and/or ovarian dysfunction as a possible etiology of idiopathic hirsutism.

Thirty-one cases of idiopathic hirsutism, characterized biochemically in the basal state by increased levels of urinary 3 alpha-androstane-5 alpha, 17 beta-diol and normal levels of the main androgens, were studied. In order to determine a possible etiologic heterogeneity of idiopathic hirsutism, pituitary gonadotropin responses to synthetic luteinizing-releasing hormone (LRH) and adrenal steroid responses to adrenocorticotropic hormone (ACTH) stimulation were evaluated and the results were compared to those in six normal women. On the basis of the results obtained in each hirsute patient after LRH and ACTH tests, two groups were identified. The majority, 23 of 31 hirsute patients (group I), had results similar to those in the control group. In the other eight patients (group II), biologic abnormalities were disclosed and suggested a partial adrenal 11 beta-hydroxylase defect in two patients, an incomplete form of adrenal 3 beta-ol deficiency in one patient, an adrenal hyperreactivity without evident cause in two patients, and polycystic ovary syndrome in association with an adrenal hyperreactivity in three patients. As a group, the eight patients showed ACTH-stimulated increments in testosterone, delta 4-androstenedione, dehydroepiandrosterone, and 17-ketosteroids that were significantly greater (p less than 0.01) than the mean responses in the control group. The conclusion is that some women who previously were designated as having "idiopathic" hirsutism had an adrenal and/or ovarian component to their hyperandrogenism which could be shown only by appropriate dynamic tests.

17-Ketosteroids↗

Urinary 5 alpha-androstane-3 alpha,17 beta-diol levels in normal and hirsute women: discriminating power and relation to other urinary steroids.

The urinary levels of seven steroids, 5 alpha-androstane-3 alpha,17 beta-diol, 5 beta-androstane-3 alpha,17 beta-diol, androsterone, etiocholanolone, tetrahydrocortisone, tetrahydrocortisol and allotetrahydrocortisol were measured in both normal (n = 18) and hirsute (n = 24) women. The results confirmed 5 alpha-androstane-3 alpha,17 beta-diol as the most significant steroid with respect to discrimination between hirsute and normal subjects. Investigation of the inter-steroid relationships, using multivariate techniques established that the mode of steroid metabolism was different between the two groups. Whereas in normal women the strong correlation amongst all the androgen metabolites inferred a predominant hepatic route to 5 alpha-androstane-3 alpha,17 beta-diol formation, the same analogy was not applicable to the hirsute subjects. Excellent agreement was found for the predicted vs actual excretion of 5 alpha-androstane-3 alpha,17 beta-diol in normal women, based on a regression model involving the six other steroids as independent variables. When the same model was used for estimation of 5 alpha-androstane-3 alpha,17 beta-diol levels in thirteen hirsute subjects, misclassified as "normal", 50% gave values which were considerably less than actually measured. It is suggested that this discrepancy, with respect to these hirsute subjects is a reflection of extrahepatic production of 5 alpha-androstane-3 alpha,17 beta-diol due to increased 5 alpha-reductase activity.

Adult↗

Fat distribution, endocrine and metabolic profile in obese women with and without hirsutism.

The relationship between adipose tissue distribution, androgen levels, and metabolic complications of obesity was studied in 20 hirsute and 20 nonhirsute obese premenopausal women. The group of hirsute women showed preferentially an upper body type of obesity as assessed by the waist-to-hip ratio (0.902 + 0.017 v 0.778 +/- 0.015, P less than .01). They had higher serum concentrations of total testosterone (100.4 + 11.7 v 48.8 +/- 4.5 ng/dL, P less than .01) and lower levels of serum sex-hormone-binding globulin (28.1 +/- 3.6 v 44.0 + 4.2 nmol/L, P less than .05) exhibiting an increased androgenic activity as compared to the nonhirsute women. Serum glucose and insulin levels after an oral glucose load were significantly higher in the hirsute women. In addition, the group of hirsute females has significantly higher fasting concentrations of total cholesterol (5.82 +/- 0.28 v 4.75 +/- 0.14 mmol/L, P less than .05) and triglycerides (2.51 +/- 0.38 v 1.14 +/- 0.10 mmol/L, P less than .01). The hirsute group also showed higher systolic (166.7 +/- 5.1 v 142.1 +/- 4.5 mm Hg, P less than .01) and diastolic (100.9 +/- 3.6 v 85.2 +/- 2.5 mm Hg, P less than .01) blood pressure values than the nonhirsute women. Analysis of correlation revealed that an increasing waist-to-hip ratio was accompanied by increasing testosterone levels (r = .39, P less than .05) and by decreasing sex-hormone-binding globulin levels (r = .37, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Menstrual dysfunction in hirsute women.

Hirsutism in women is frequently associated with increased levels of androgens. Studies of biochemical changes, however, have yielded conflicting results. This study compares the findings in 30 hirsute women with normal menses and those of 30 hirsute women with abnormal cycles. Of the women with abnormal menstruation, 73% had oligoamenorrhea only and the others had dysfunctional uterine bleeding. The abnormally menstruating group had a similar mean age but tended to have heavier body weights than those with normal cycles. Free and total testosterone levels were significantly higher in the abnormal group (total testosterone, 54 +/- 35 ng/dl vs 35 +/- 12 ng/dl, p = 0.004; free testosterone, 7.8 +/- 4.9 pg/ml vs 4.2 +/- 1.4 pg/ml, p = 0.002). The abnormal group tended to have higher levels of androstenedione than the normal group (227 +/- 116 ng/dl vs 139 +/- 59 ng/dl) but dehydroepiandrosterone sulfate (DHEAS) levels were similar (320 +/- 142 mg/dl vs 298 +/- 169 pg/dl). Levels of thyroxin, thyrotropin, and prolactin were comparable in the two groups. Among hirsute women those with abnormal menses tended to be heavier and to have higher levels of total testosterone, free testosterone, and androstenedione. This is consistent with the clinical impression, not previously documented, that of hirsute women, those with abnormal menses have more severe endocrine abnormalities than those with normal cycles.

Adult↗

Serum androstanediol glucuronide in women with facial hirsutism.

BACKGROUND: Measurement of serum 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) has been proposed as a useful biochemical marker of peripheral androgen metabolism. Is 3 alpha-diol G a useful biochemical marker of peripheral androgen metabolism and does it correlate with degree of facial hirsutism? OBJECTIVE: Our purpose was to assess possible correlation between serum 3 alpha-diol G and degree of facial hirsutism and to compare serum 3 alpha-diol G levels with levels of other commonly measured serum androgens. METHODS: Twenty-three consecutive women with facial hirsutism were studied, and serum concentrations of 3 alpha-diol G, testosterone (total, free, and biologically active portions), dehydroepiandrosterone sulfate, and androstenedione were measured. RESULTS: There was no correlation between serum 3 alpha-diol G levels and degree of facial hirsutism. There was a correlation between levels of 3 alpha-diol G and dehydroepiandrosterone sulfate (p less than 0.01), biologically active testosterone (p = 0.01), free free testosterone (p less than 0.02), and androstenedione (p less than 0.05). CONCLUSION: Serum 3 alpha-diol G concentrations have no correlation with degree of facial hirsutism and do not provide additional information over the commonly measured androgens.

Adolescent↗

Plasma androgens, 17 beta-estradiol, and sex hormone-binding globulin in patients with hirsutism and/or clitoromegaly.

Plasma androgen, 17 beta-estradiol, and sex hormone-binding globulin (SHBG) levels were measured in 11 normal subjects (group 1), 18 hirsute patients with no clitoromegaly (group 2), 13 hirsute patients with clitoromegaly (group 3), and 8 patients with clitoromegaly but no hirsutism (group 4). Significantly elevated levels of testosterone (T) and dihydrotestosterone (DHT) were found in groups 2 and 3 but not in group 4 when compared with group 1. In contrast, levels of dehydroepiandrosterone (DHEA) in groups 1 and 2 were comparable but significantly lower than those in group 3 and 4; the levels in the latter two groups were not significantly different from each other. In groups 2, 3, and 4, levels of androstenedione (delta 4A) and the factor T/SHBG were significantly elevated whereas SHBG levels were significantly suppressed when compared with those of group 1. The clitoral index correlated (P less than 0.01) with DHEA levels in group 3. It is concluded that clitoromegaly without hirsutism is associated with increased plasma levels of DHEA and delta 4A. In contrast, hirsutism without clitoromegaly is associated with elevated levels of T, DHT, and delta 4A but normal DHEA levels.

Adolescent↗

Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior.

OBJECTIVE: To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women. DESIGN: Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment. RESULTS: Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug. CONCLUSIONS: Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.

Acne Vulgaris↗

Clinical and hormonal effects of gonadotropin-releasing hormone agonist plus an oral contraceptive in severely hirsute patients with polycystic ovary disease.

OBJECTIVE: 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. DESIGN: 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. SETTING: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗

Outcome of long-term treatment with the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism: clinical and hormonal effects during a 1-year course of therapy and 1-year follow-up.

OBJECTIVE: To evaluate the long-term efficacy of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism. DESIGN: Prospective clinical study. SETTING: Outpatients in a university hospital. PATIENT(S): Fourteen young women with idiopathic hirsutism. INTERVENTION(S): Finasteride, 5 mg once daily, was given for 12 months. MAIN OUTCOME MEASURE(S): Degree of hirsutism, graded by a modified Ferriman and Gallwey score, serum sex hormones, and serum and urinary markers of 5 alpha-reductase activity. Clinical outcome was evaluated up to and including the 1-year post-treatment period. RESULT(S): The Ferriman and Gallwey score showed a remarkable reduction after 12 months of finasteride treatment (4.4 +/- 0.7 versus 11.8 +/- 1.0; mean +/- SEM). Serum levels of the two 5 alpha-reductase activity markers, dihydrotestosterone and 3 alpha-androstanediol glucuronide, decreased, and urinary C19 and C21 5 beta:5 alpha steroid metabolite ratios consistently increased during finasteride administration. These changes were reversed readily after cessation of treatment. No significant adverse effect was reported. Nine of 14 women completed the 1-year post-treatment follow-up. Their hirsutism scores were increased substantially as compared with values recorded at the end of therapy, but still were lower than baseline values. CONCLUSION(S): The 5 alpha-reductase inhibitor finasteride is effective and well tolerated in longterm treatment of women with idiopathic hirsutism. Post-treatment follow-up suggests that drug effects on hair growth are sustained in the majority of subjects with this disorder.

5-alpha Reductase Inhibitors↗

Influence of body mass index and age on the grade of hair growth in hirsute women of reproductive ages.

The relationships between the hair growth in different body regions, body mass index (BMI) and age were studied in 225 women of reproductive ages referred for hirsutism. The regularity of the cycles was registered, and 109 of the patients were interviewed for their maximum weight, teenage obesity, and age of menarche. The serum androgens were measured in the follicular phase. The results indicate that facial hirsutism is associated with BMI (rho = 0.41, P less than 0.001) independently of age and the testosterone (T) to sex hormone-binding globulin (SHBG) ratio. Facial hirsutism is also correlated with age (rho = 0.37, P less than 0.001) irrespective of BMI (rho = 0.26, P less than 0.001) or the T/SHBG ratio (rho = 0.43, P less than 0.001). In contrast, the hair growth on trunk area is related to the T/SHBG ratio (rho = 0.35, P less than 0.001) but not to BMI or age when the correlations are adjusted for the grade of hyperandrogenemia. The women with severe facial hirsutism had a higher maximum weight (P less than 0.001) and more teenage obesity (P less than 0.01) than other hirsute patients. They also had a slightly earlier menarche compared with their agemates than the women with mild or absent facial hair (P less than 0.05). The data suggest differences in the regulation of hair growth between the face and trunk areas.

Adolescent↗

The addition of dexamethasone to antiandrogen therapy for hirsutism prolongs the duration of remission.

OBJECTIVE: To determine whether the addition of dexamethasone to antiandrogen therapy prolongs the duration of remission in women with hirsutism. DESIGN: Follow-up study of patients treated with one of four regimens: spironolactone (100 mg/d) for 1 year, dexamethasone (0.37 mg/d) for 1 year, dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 1 year, or dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 2 years. SETTING: Academic medical practice in reproductive endocrinology. PATIENT(S): Fifty-four women with hirsutism and hyperandrogenism. INTERVENTION(S): Ferriman-Gallwey-Lorenzo scores were obtained and serum levels of testosterone, unbound testosterone, and dehydroepiandrosterone sulfate were measured before therapy, every 6 months during therapy, and for 1 year after the withdrawal of therapy. MAIN OUTCOME MEASURE(S): Hirsutism scores and serum indices of hormonal changes were monitored. RESULT(S): Ferriman-Gallwey-Lorenzo scores and androgen levels remained low 1 year after the withdrawal of therapy in patients who were treated with dexamethasone, either alone or in combination with spironolactone. In patients who were treated with spironolactone alone, hirsutism scores had returned to baseline values after 1 year. CONCLUSION(S): The addition of an agent that suppresses androgen levels may be useful to prolong the duration of remission of hirsutism in women with hyperandrogenism who are treated with antiandrogens.

Adult↗

Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects.

OBJECTIVE: To compare the clinical and endocrinologic effects of cyproterone acetate (CPA), an antiandrogen with progestational activity; flutamide, a nonsteroidal antiandrogen, and finasteride, an inhibitor of 5alpha-reductase. DESIGN: Randomized, open, controlled clinical study. SETTING: Department of Obstetrics and Gynecology, University of Pisa, Pisa, Italy. PATIENT(S): Forty-five hirsute women were enrolled in the study: 29 were hyperandrogenic and 16 had idiopathic hirsutism. Three women dropped out of the study. INTERVENTION(S): Women were randomly treated with finasteride (5 mg/d; n = 14), CPA (25 mg plus ethinyl E2 (EE); n = 13), or flutamide (500 mg/d; n = 15) for 1 year. MAIN OUTCOME MEASURE(S): Hirsutism was assessed using the Ferriman-Gallwey method. Levels of total and free T, androstenedione (A), DHEAS, sex hormone-binding globulin, dihydrotestosterone, and 3alpha-androstanediol glucuronide were evaluated at the beginning of the study and every 3 months. RESULT(S): Treatment with finasteride, flutamide, and CPA significantly decreased the Ferriman-Gallwey score. The percent decreases in the hirsutism score induced by the different treatments were similar. Treatment with CPA plus EE significantly decreased levels of total and free T, A, dihydrotestosterone, and 3alpha-androstanediol glucuronide. These parameters were unchanged with flutamide therapy. Finasteride significantly increased total T levels but reduced dihydrotestosterone and 3alpha-androstanediol glucuronide concentrations. CONCLUSION(S): Finasteride, CPA, and flutamide are equally effective in decreasing hirsutism, despite different mechanisms of action.

Adolescent↗

Analysis of gonadotropin pulsatility in hirsute women with normal menstrual cycles and in women with polycystic ovary syndrome.

OBJECTIVE: To study the relation between plasma gonadotropin pulsatility, androgen levels, and estrogen levels in patients with polycystic ovary syndrome (PCOS), in hirsute women with normal menstrual cycles, and in healthy women. DESIGN: Prospective study. SETTING: University medical center-based cellular and molecular endocrinology laboratory. PATIENT(S): Eight healthy women (group 1), 9 hirsute women with normal menstrual cycles (group 2), and 19 women with PCOS (group 3). INTERVENTION(S): Plasma concentrations of LH and FSH were measured by RIA every 15 minutes for 12 hours. MAIN OUTCOME MEASURE(S): Rhythmic parameters of 12-hour LH and FSH secretion. RESULT(S): Rhythmic parameters of 12-hour LH secretion were significantly higher in patients with PCOS (group 3) than in controls (group 1) or in hirsute women with normal menstrual cycles (group 2). The frequency of LH pulses was statistically higher in patients with PCOS (group 3) than in controls (group 1). Statistically significant correlations were found when the frequency of LH pulses was plotted against basal LH concentrations and rhythmic parameters of 12-hour LH secretion. CONCLUSION(S): Luteinizing hormone pulse amplitude was higher in patients with PCOS than in hirsute women with normal menstrual cycles or in healthy women. The LH pulse frequency was increased only in patients with PCOS compared with healthy women and not in hirsute women with normal menstrual cycles.

Adolescent↗