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We aimed to determine whether ovarian suppression affects the production rate of prostate-specific antigen (PSA) in hirsute women. A total of 34 hirsute women who had a modified Ferriman-Gallwey (FG) score of > or = 7 and 14, non-hirsute women as the control group were recruited for this prospective controlled study. Serum samples for evaluation of basal hormones and PSA concentration were collected and were analyzed by commercial kits and chemiluminescent enzyme immunoassay. The hirsute women were given 400 microg/day nafarelin acetate for 3 months. Basal hormones, PSA levels and FG scores were then assessed. ANOVA and Tukey test were used to compare differences in means between the hirsute and the non-hirsute group at the beginning of the study. Student's t test, Tukey test and repeated measures variance analysis were used to evaluate differences in the study group and between the women with polycystic ovary syndrome (PCOS) and idiopathic hirsutism after gonadotropin releasing hormone (GnRH)-agonist administration. Statistical significance was assumed with a value of p < 0.05. PCOS and idiopathic hirsutism were diagnosed in 58.8% and 41.2% of 34 hirsute women, respectively. Age and body mass index (BMI) were similar in the hirsute and the control group (p > 0.05). FG scores in the PCOS group (20.3 +/- 1.7) were statistically similar to those of the group with idiopathic hirsutism (17.6 +/- 1.7) (p > 0.05). The non-hirsute women had significantly lower serum PSA concentrations than the hirsute group (p < 0.001). The basal mean level of PSA was 0.095 +/- 0.001 in the PCOS, 0.0061 +/- 0.009 in the idiopathic hirsute and 0.0040 +/- 0.004 ng/ml in the control group. No significant difference in the mean PSA levels was noted between the PCOS and the idiopathic hirsute subgroups before and after GnRH agonist treatment (0.0096 +/- 0.01 and 0.0051 +/- 0.032 ng/ml, respectively) (p > 0.05). FG scores, testosterone, 17alpha-hydroxyprogesterone and dehydroepiandrosterone sulfate levels were significantly decreased in the hirsute group following treatment (p < 0.001). PSA levels in hirsute women were higher than in non-hirsute women and independent of BMI, age and androgen deprivation. PSA concentration may be mediated through extragonadal sites and possibly through a long-standing hyperandrogenemic environment such as in PCOS and idiopathic hirsutism. Further investigation as to the significance of PSA in women with hirsutism and whether antiandrogens directly act to inhibit biosynthesis of PSA is warranted.
OBJECTIVE: To assess the prevalence of hirsutism and study its etiology in the Kashmir Valley of the Indian subcontinent. DESIGN: Prospective random sample of the general population attending outpatient medical clinics and prospective evaluation of hirsute patients referred to our endocrinology clinic. SETTING: A tertiary care hospital and district-level primary care hospitals. PATIENT(S): Five thousand women attending various hospitals for reasons unrelated to hirsutism and 150 consecutive women referred for hirsutism. INTERVENTION(S): Assessment of body hair as per the Ferriman and Gallwey scoring system and an investigative protocol including detailed clinical assessment with endocrinologic workup including estimations of gonadotropins, PRL, T, and 17-hydroxyprogesterone and abdominopelvic ultrasound. MAIN OUTCOME MEASURE(S): Presence and cause of hirsutism. RESULT(S): Of 4,780 adult women for whom adequate data were available, 504 (10.5%) had hirsutism, among whom 484 (10.1%) had mild (score of 6-9) and 20 (0.4%) had moderate hirsutism (score of 10-14). The etiology of hirsutism revealed idiopathic hirsutism in 38.7%, polycystic ovary syndrome (PCOS) in 37.3%, postmenopausal state in 9.2%, adrenal tumors in 2.1%, congenital adrenal hyperplasia in 1.4%, and drug-induced hirsutism in 0.7%. The cause remained undetermined in 10.6% of patients for whom the available information was not adequate. CONCLUSION(S): Hirsutism is as common a problem in the Kashmir Valley (India) as elsewhere in the world. Idiopathic hirsutism (38.7%), PCOS (37.3%), and postmenopausal state (9.2%) are common causes of hirsutism. Late-onset congenital adrenal hyperplasia is a relatively uncommon cause of hirsutism in the Kashmir Valley.
OBJECTIVE: To compare the effectiveness of finasteride and flutamide in the treatment of hirsutism in patients with polycystic ovary syndrome (PCOS) and with idiopathic hirsutism. DESIGN: Randomized study. PATIENTS: One hundred and ten hirsute patients were selected: 64 women with PCOS and 46 with idiopathic hirsutism. METHODS: Patients were assigned randomly to receive 5mg finasteride once daily or 250mg of flutamide twice daily, for 12 consecutive months. Hirsutism was evaluated at 12 months of therapy, with the Ferriman-Gallwey score and with measurement of the terminal hair diameters (microm) taken from four different body areas. Blood samples were taken for assessment of endocrine and hematochemical parameters. Side effects were monitored during the treatment. RESULTS: Both finasteride and flutamide induced a significant decrease in the hirsutism scores and hair diameters at the end of 12 months. Finasteride reduced the Ferriman-Gallwey score by 31.4% in the PCOS cases and by 34.2% in the idiopathic hirsutism cases, and hair diameter by 27.0-34.1% in PCOS and by 29.6-37.9% in idiopathic hirsutism. Flutamide reduced the Ferriman-Gallwey score by 56.7% in PCOS and by 50.9% in idiopathic hirsutism, and hair diameter by 50. 3-60.0% in PCOS and by 47.7-56.5% in idiopathic hirsutism. Flutamide did not induce hormone variations, while finasteride increased testosterone levels by 40% in PCOS and by 60% in idiopathic hirsutism and decreased 3alpha-androstanediol glucuronide (3alpha-diolG) by 66.7% in PCOS and by 69.5% in idiopathic hirsutism. No important side effects or changes in the hematochemical parameters were observed with finasteride, while two patients (3.6%) in the flutamide group expressed abnormal transaminase levels after 6 months of treatment. Dry skin also appeared significantly more with flutamide (67.3%) than with finasteride (23.6%). CONCLUSIONS: Both drugs are effective in the treatment of hirsutism but flutamide is more effective than finasteride.
OBJECTIVE: The study objective was to assess the role of 3alpha-androstanediol glucuronide (3alpha-diolG) as the marker of peripheral androgen action in the young women with hirsutism diagnosed as polycystic ovary syndrome (PCOS), in patients with idiopathic hirsutism (IH) and in normal non-hirsute women. STUDY DESIGN: Fifty-nine young women with mean age 21.90+/-3.52 years suffered from hirsutism were included in the study. Among these 59 hirsute women 31 women with mean age 21.60+/-3.56 years were diagnosed as PCOS and 28 women with mean age 22.20+/-3.59 years were classified as idiopathic hirsutism patients. Twenty-seven normal women, age-matched (mean age 22.60+/-2.90 years), without signs of hirsutism and with normal menstrual cycle served as control for this study. Serum was collected from women with hirsutism (due to PCOS or idiopathic hirsutism) and from non-hirsute women. Serum levels of 3alpha-androstanediol glucuronide (3alpha-diolG), main androgens such as: testosterone, free testosterone, dehydroepiandrosterone (DHEAS) and also others hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and sex hormone-binding globuline (SHBG) were measured using radioimmunoassay (RIA) method in the study and control group. Hirutism was assessed using modified Ferriman-Gallwey method. Serum 3alpha-diolG levels in PCOS women were significantly higher than in controls. RESULTS: There were no significant differences between serum 3alpha-diolG levels in PCOS group and IH group. Similarly, there were significant differences between serum 3alpha-diolG levels in IH group and control subjects. CONCLUSION: We conclude that 3alpha-diolG is not useful as the marker for peripheral androgen metabolism and for differentiation between idiopathic hirsutism and PCO-related hirsutism.
BACKGROUND: Studies on the psychopathologic aspects of hirsutism are sparse. Attempts to correlate these aspects with either the extent of the facial hirsutism and/or circulating serum androgens are virtually nonexistent. This study evaluates the psychopathologic aspects of hirsutism and correlates these findings with the extent of the facial hirsutism as well as with the circulating serum androgens. OBJECTIVE: Our purpose was to assess the psychopathologic aspects of facial hirsutism and to determine whether any correlation exists between these findings and either the extent of the facial hirsutism or the circulating serum androgens. METHODS: Twenty consecutive women with facial hirsutism were studied by administration of psychologic tests (DeRogatis Symptom Inventory and the Affects Balance Scale). The results of these tests were correlated with the grade of facial hirsutism as well as serum levels of total testosterone (T), biologically active testosterone (BT), free testosterone (FT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione (A-dione). RESULTS: Significant levels of depression were found. No correlation was found between the psychopathologic measurements and the extent of facial hirsutism or serum levels of T, DHEA, DHEA-S, and A-dione. Significant correlations were found between depression and serum levels of FT and BT. CONCLUSION: There is an increased incidence of depression in facially hirsute women and this correlates with their circulating active testosterone levels and not with the extent of their facial hirsutism.
OBJECTIVE: To test the hypothesis that scoring terminal hair growth on only the chin or abdomen can serve as a reliable predictor for hirsutism. DESIGN: A prospective observational study. PATIENT(S): Six hundred and ninety-five consecutive hyperandrogenic women seen between June 1987 and December 1997. MAIN OUTCOME MEASURE(S): All hirsutism exams were performed by one examiner. Hirsutism was scored using a modification of the Ferriman-Gallwey (F-G) method. An F-G score of > or = 8 defined hirsutism. RESULT(S): Of the 695 women examined 352 (50.1%) had hirsutism scores of 8. Thirty percent (79 of 344) of women who had an F-G score of <8 had previously underwent electrology. If either the chin or lower abdomen hair growth score was > or = 2, the sensitivity was 100% for the prediction of hirsutism, although the specificity was 27%. The positive predictive value (PPV) for hirsutism using a hair score of > or = 2 at either of these sites was 58%. CONCLUSION(S): A hair growth score of > or = 2 on the chin or lower abdomen only was found to be a highly sensitive predictor for hirsutism. However, because of its very low PPV, this screening method is virtually useless in populations where the hirsutism frequency is expected to be low, about 5%. However, this screening method for the detection of hirsutism would be useful for the study of high-risk populations with an expected hirsutism prevalence of >20% (e.g., family studies).
OBJECTIVE: To evaluate the prevalence of idiopathic hirsutism in a large population of hirsute women. DESIGN: 588 hirsute women (mean age 24+/-1, range 15-36 years) were evaluated as outpatients at the Department of Endocrinology of the University of Palermo, Italy. The diagnosis of idiopathic hirsutism was established in hirsute patients presenting regular ovulatory menstrual cycles and normal serum androgen levels (total testosterone, unbound testosterone and dehydroepiandrosterone sulfate). METHODS: Hirsutism was calculated by the Ferriman-Gallwey-Lorenzo index. Serum androgens were evaluated in the follicular phase (days 5 or 6) and normal androgen ranges were calculated as the mean+/-2S.D. of serum levels of 30 ovulatory non-hirsute women. The presence of ovulation was determined by serum progesterone levels during the presumed luteal phase (days 21 or 22). All steroids were determined by specific RIAs. RESULTS: 36 hirsute women (6%) had regular ovulatory cycles and normal androgen levels and were diagnosed as being affected by idiopathic hirsutism. CONCLUSIONS: Idiopathic hirsutism is a relatively uncommon cause of hirsutism, affecting approximately 6%, of our population.
BACKGROUND: Hirsutism is a distressing and relatively common endocrine problem in women which may prove difficult to manage. Cyproterone acetate, an anti-androgen, is frequently used to treat hirsutism, usually in combination with ethinyl estradiol. OBJECTIVES: The objective of this review was to investigate the effectiveness of cyproterone acetate alone, or in combination with ethinyl estradiol, in reducing hair growth in women with hirsutism secondary to ovarian hyperandrogenism. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group trials register was searched (last search - 4 June 2002). The Cochrane Menstrual Disorders and Subfertility Group register is based on regular searches of MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CINAHL (1982 to 2002), PsycINFO (1987 to 2002) and CENTRAL (Issue 2, 2002 of the Cochrane Library) the handsearching of several journals and conference proceedings, and searches of several key grey literature sources. All publications of randomised controlled trials of cyproterone acetate with or without estrogen versus placebo or other drug therapies for hirsutism were identified. SELECTION CRITERIA: All randomised controlled studies comparing:- cyproterone acetate to placebo- cyproterone acetate with ethinyl estradiol to placebo- cyproterone acetate with ethinyl estradiol to cyproterone acetate alone- cyproterone acetate (with or without estradiol) to other medical therapies for treatment of hirsutism. DATA COLLECTION AND ANALYSIS: Eleven studies were identified which fulfilled the inclusion criteria. Nine randomised studies were included in the review, and two were excluded because of insufficient information. Only one study had more than 100 women included in the analysis. The major outcomes included: subjective improvement in hirsutism, changes in Ferriman Gallwey scores, changes in linear hair growth and hair shaft diameter, alterations in endocrine parameters, side effects to treatment, withdrawals during therapy MAIN RESULTS: There were no clinical trials comparing cyproterone acetate alone with placebo. There was one small study comparing cyproterone acetate in combination with ethinyl estradiol to placebo. In this study there was a significant subjective reduction in hair growth with cyproterone acetate therapy, although the confidence limits were large. There were no studies comparing cyproterone acetate alone with cyproterone acetate in combination with ethinyl estradiol to treat hirsutism. In studies where cyproterone acetate was compared to other drug modalities (ketoconazole, spironolactone, flutamide, finasteride, GnRH analogues) no difference in clinical outcome was noted. There were, however, endocrinological differences in androgen and estrogen levels between different drug therapies. There were insufficient data to assess differences in side effects between women treated with cyproterone acetate and other medical therapy. REVIEWER'S CONCLUSIONS: Cyproterone acetate combined with estradiol results in a subjective improvement in hirsutism compared to placebo. Clinical differences in outcome between cyproterone acetate and other medical therapies were not demonstrated in the studies included in this review. This may be because of the small size of the studies, lack of standardized assessment and lack of objective determinants of improvement in hirsutism. The endocrinological effects of the different drug therapies reflect the mode of action. Larger carefully designed studies are needed to compare efficacy and safety profiles between drug therapies for hirsutism.
Androgens are the main hormonal regulators of human hair growth and they are related to clinical conditions such as hirsutism. The aim of this study was to analyze the gene expression of androgen receptor (AR) and type 2 17 beta hydroxysteroid dehydrogenase (17 beta-HSD) in keratinocytes of plucked scalp hairs from hirsute patients and normal subjects. We studied 58 women with hirsutism (31 with polycystic ovary syndrome (PCOS), 27 with idiopathic hirsutism (IH)); 15 control women; and 10 control men. Hirsutism was assessed by a modified Ferriman-Gallwey method. Hormonal status was assessed between days 2 and 10 of the menstrual cycle or on any day when the patients were amenorrheic. AR and type 2 17 beta-HSD mRNA levels were estimated by reverse transcription-polymerase chain reaction (RT-PCR). AR expression was similar in all groups. Type 2 17 beta-HSD gene expression in untreated hirsute patients was lower (2.1+/-0.10) than in normal women (3.1+/-0.17), and similar to men (1.8+/-0.22). Comparing hirsute patients, type 2 17 beta-HSD expression was higher in treated PCOS (3.0+/-0.34 versus 2.2+/-0.13) and IH patients (2.5+/-0.19 versus 2.0+/-0.15); hirsutism score was lower (P=0.003, PCOS; P=0.003, IH); and SHBG levels were higher (P=0.001, PCOS; P=0.024, IH) in treated patients. The free androgen index was lower in treated women (P=0.024 for the IH group). In conclusion, the lower expression of type 2 17 beta-HSD mRNA in scalp hairs of untreated hirsute patients suggests androgen metabolism disturbances with predominance of more potent androgens, as occurs in men. The enzyme's higher gene expression in treated hirsute patients could be an indirect evidence of restored enzyme activity and intracellular androgen metabolism.
This review reports our own experience with, and literature studies of, the pharmacological management of hirsutism in women with hyperandrogenism (polycystic ovary syndrome) or with normal serum androgen levels and regular ovulatory menstrual cycles (idiopathic hirsutism). Treatment consists of suppressing ovarian or adrenal androgen secretion, or blocking androgen actions in the skin. The major drugs used are gonadotropin-releasing hormone (GnRH) agonists, combined oral contraceptives (COCs), and steroidal (cyproterone acetate and spironolactone) or nonsteroidal (flutamide and finasteride) antiandrogens. GnRH agonists, suppressing the pituitary, decrease androgen and estradiol secretion and improve severe hirsutism. To avoid estrogen deficiency problems, 'add back' therapy with estrogen-progestogen or COCs is advisable. This method of treatment is complicated and expensive, limiting its use to severe forms of ovarian hyperandrogenism with hyperinsulinemia. The third-generation COCs, containing new progestogens or cyproterone, have very restricted effectiveness in the short term (6 cycles), but their long term use (> 12 cycles) cures mild-to-moderate hirsutism and improves severe hirsutism. As well as suppressing gonadotropins and ovarian androgen steroidogenesis, these formulations decrease free testosterone levels and may also decrease adrenal androgen production. In women being treated with antiandrogens, COCs are important to provide control of the menstrual cycle and contraception. Cyproterone, a progestational agent, inhibits gonadotropin secretion and blocks androgen action. It is used in COCs or in a reverse sequential regimen. In the latter, it is very effective in the short term treatment of hirsutism. Spironolactone blocks androgen receptors. Its effectiveness in hirsutism is dosage-dependent: low dosages are less active than other antiandrogens, whereas high dosages (200 mg/day) are very effective at the cost of several adverse effects (particularly dysfunctional uterine bleeding), but the concomitant use of a COC may prevent these. Flutamide is a pure antiandrogen that blocks androgen receptors and inhibits hair growth. It is very effective in treating hirsutism within 6 to 12 months. Dry skin is very frequent during treatment with flutamide, and hepatotoxicity is possible at high dosages. Finasteride, a 5 alpha-reductase type 2 inhibitor, is the least effective antiandrogen, but a dosage of 5 mg/day decreases hirsutism without adverse effects. Pregnancy must be avoided during therapy with antiandrogens because of the possible risk of abnormal development of a male fetus. Antiandrogens, especially flutamide (250 to 500 mg/day) and cyproterone (12.5 to 50 mg/day in a reverse sequential regimen), alone or in association with COCs, seem to be the most effective agents for the treatment of hirsutism.
Aim of this prospective diagnostic study was to determine the serum 3 alpha-androstanediol-glucuronide (AdiolG) level in hirsute women in order to assess the androgenic activity in peripheral tissue and to differentiate between hirsutism of peripheral origin and that of adrenal or ovarian origin. Diagnostic advantages might have been expected in patients with idiopathic hirsutism, in whom increased 5 alpha-reductase activity may be reflected by this parameter. Apart from serum AdiolG, we determined the established parameters testosterone, androstendione and dehydroepiandosterone sulfate in 63 hirsute premenopausal women and in 51 non-hirsute controls. AdiolG (P < 0.05), as well as the 3 established parameters (P < 0.001) were elevated in the hirsute women as compared with the controls; however, the subgroup of women with idiopathic hirsutism (n = 32) showed no elevation of serum AdiolG. Analysis of the combined hirsute and control groups showed that the correlation of AdiolG to the hirsutism score (r = 0.42) was markedly weaker than that of testosterone to the latter (r = 0.62). Moreover, no correlation was found between the body-mass index and AdiolG. Our data show that serum AdiolG is obviously not a specific marker for peripheral 5 alpha-reductase activity, but appears to reflect the adrenal and ovarian androgen precursors. Thus, determination of serum AdiolG is of no diagnostic benefit in the clinical assessment of hirsute women.
Hirsutism usually results from a subtle excess of androgens. As such, it is a clue to possible endocrine disturbance in addition to presenting cosmetic problems. We use the term hirsutism to mean male-pattern hirsutism--excessive growth of hair in areas where female subjects normally have considerably less than male subjects. An elevation of the plasma free (unbound) testosterone level is the single most consistent endocrinologic finding in hirsutism. The plasma free testosterone level is sometimes elevated when the total level of plasma testosterone is normal because testosterone-estradiol--binding globulin (TEBG) levels are often depressed in hirsute women. Frequent blood sampling is sometimes necessary to demonstrate subtle hyperandrogenic states since androgen levels in the blood are pulsatile and seemingly reflect episodic ovarian and adrenal secretion. The source of hyperandrogenemia can usually be determined from dexamethasone suppression testing. Those patients whose plasma free androgen levels do not suppress normally usually have functional ovarian hyperandrogenism (polycystic ovary syndrome variants). Very high plasma androgen levels or evidence of hypercortisolism, which is not normally suppressible by dexamethasone, should lead to the search for a tumor or Cushing's syndrome. Those patients in whom hyperandrogenemia is suppressed normally by dexamethasone have a form of the adrenogenital syndrome, a prolactinoma, obesity, or idiopathic hyperandrogenemia. In such patients, glucocorticoid therapy may reduce hirsutism and acne and normalize menses. The treatment of hirsutism resulting from functional ovarian hyperandrogenism is not as satisfactory; estrogen-progestin treatment is the most useful adjunct to cosmetic approaches to hirsutism in this country. However, other manifestations of polycystic ovary syndrome, such as infertility, may take precedence over hirsutism when an optimal therapeutic program is designed for many patients.
We investigated whether plasma androstanediol glucuronide (ADG) levels reflect the increased androgenicity in women with idiopathic hirsutism (n = 24) or hirsutism associated with polycystic ovary syndrome (n = 10). We also evaluated whether ADG levels parallel the clinical evolution of the hirsutism during a combined treatment, with cyproteroneacetate (2 mg) and ethinylestradiol (35 micrograms), of women with moderate idiopathic hirsutism. Finally, we investigated if there is evidence for increased conversion of precursors to ADG in hirsutism, by comparing the ADG levels, measured by RIA, to ADG levels obtained by applying the conversion rates of precursors obtained in non-hirsute women. ADG levels were increased in less than half of the patients with mild hirsutism. The clinical cure of hirsutism, which was obtained by the treatment in majority of patients, was accompanied by a significant decrease of plasma ADG levels, but a similar decrease was also observed in the 5 patients who did not respond to treatment. The data show that, although there is evidence for increased conversion of precursors to plasma ADG in mildly hirsute women, the latter is not a reliable parameter of androgenicity. Our data suggest, moreover, that treatment with cyproterone acetate and ethinylestradiol decreases 5 alpha-reductase activity, as indicated by the more important decrease in ADG levels than in the precursors.