Spironolactone in the treatment of hirsutism

Spironolactone (100 mg) for 25 days in each menstrual cycle was assessed over 6 months for treatment of hirsutism in 35 patients. Five patients withdrew due to either nausea or polymenorrhea. the latter problem was encountered in 16 patients. Of the 30 remaining patients, 17 had a significant reduction in hair growth as assessed by Ferriman and Gallwey hair scores (p less than 0.05). The only significant change in endocrine parameters was a reduction in serum testosterone (p less than 0.05). Treatment with spironolactone alone was inferior to our previous experience with the cyproterone acetate--estrogen combination.     

Spironolactone in combination drug therapy for unresponsive hirsutism

Clinical and laboratory evaluations of nine hirsute women were performed for determination the efficacy of combination drug therapy. Each patient had previously failed to respond to single drug therapy with oral contraceptives (OC), dexamethasone (DEX), or spironolactone (S) and received S (100 to 150 mg) and either an OC (mestranol, 0.05 to 0.08 mg, and norethindrone, 1 mg) or DEX (0.5 mg) daily. Total testosterone, dehydroepiandrosterone sulfate, free testosterone, and sex-hormone-binding globulin were measured before therapy and 4 to 6 weeks after initiation of therapy and were compared with the responses to OC (n = 7), DEX (n = 8), and S (n = 6). A satisfactory clinical response in the rate of hair growth was defined as at least a doubling of the time interval between adjunctive therapies (electrolysis, shaving, or bleaching) and patient satisfaction with treatment. The responses of the androgenic parameters were not statistically different between combination and single drug therapy. Although all patients noted a subjective improvement in hair growth, eight of nine fulfilled the criteria for a clinical response (P less than 0.001). Transient diuresis was the only side effect noted. The study suggests that combination drug therapy is an efficacious and well-tolerated approach to the management of unresponsive hirsutism.     

Spironolactone in combination with an oral contraceptive: an alternative treatment for hirsutism

The clinical efficacy of a combination of spironolactone and an oral contraceptive pill (Conova 30) was assessed in 23 patients presenting with hirsutism of whom 20 completed 6 months of treatment. Of the 20 patients, 16 showed improvement on objective (Ferriman & Gallwey hair score) and subjective assessment. Serum levels of androgens (testosterone, androstenedione and 17-hydroxy progesterone) were suppressed and sex hormone binding globulins were elevated. Nausea was the only significant side effect.     

Spironolactone in combination with an oral contraceptive: an alternative treatment for hirsutism

Summary. The clinical efficacy of a combination of spironolactone and an oral contraceptive pill (Conova 30) was assessed in 23 patients presenting with hirsutism of whom 20 completed 6 months of treatment. Of the 20 patients, 16 showed improvement on objective (Ferriman & Gallwey hair score) and subjective assessment. Serum levels of androgens (testosterone, androstenedione and 17-hydroxy progesterone) were suppressed and sex hormone binding globulins were elevated. Nausea was the only significant side effect.     

Flutamide in the treatment of hirsutism.

Ten hirsute women were treated with flutamide (250 mg/day) for 6 months to evaluate its effect. Hair growth as assessed by the Ferriman and Gallwey hair score was significantly reduced in all patients (P less than 0.01). The only significant change in endocrine levels was an increase in serum androstenedione (P less than 0.01). Acne and seborrhea improved markedly. No side effects were noted during the treatment. Our data suggest that the antiandrogenic properties of flutamide render it a suitable single agent in the treatment of hirsutism.     

Low-dose spironolactone in the treatment of female hirsutism

Twelve women, 11 with hirsutism and one with alopecia areata, were treated with low-dose spironolactone (50 mg daily) from the 4th until the 22nd cycle day over 12 consecutive menstrual cycles. Eight hirsute women observed a favorable effect on hirsutism in 3 to 8 months, and hair loss ceased in the one patient with alopecia areata. No significant side effects occurred. Low-dose spironolactone decreased the concentration of total and free testosterone and elevated the concentration of prolactin on the 10th cycle day, while LH, FSH, estradiol, progesterone, DHEAS, SHBG, and cortisol levels remained unchanged. The plasma aldosterone concentration increased significantly during the treatment, although serum potassium and sodium concentrations remained unchanged. Low-dose spironolactone is, thus, safe and effective in the treatment of hirsutism. It seems to be useful as an initial or alternative treatment.     

Medical treatment regimens of hirsutism

Hirsutism, which is a common clinical problem in women of reproductive age, is characterized by excessive growth of terminal hair in the androgen-sensitive skin regions. It is the result of either androgen excess or increased sensitivity of the hair follicles to normal levels of androgens. The management, which includes cosmetic measures and medical treatment, is far from satisfactory. Anti-androgen drugs play a key role in the treatment of hirsutism, but they have some side-effects which may result in cessation of the drug. On the other hand, anti-androgen treatment often needs to be continued for a long time. So, safe, inexpensive, and effective anti-androgen drugs are needed. Recently low-dose anti-androgen drugs have been shown to be effective in the maintenance of treatment. On the other hand, cyproterone acetate plus ethyniloestradiol and spironolactone, cyproterone acetate plus ethyniloestradiol and finasteride, and spironolactone and finasteride combinations have been used successfully in decreasing the hirsutism score. There are also some promising data regarding the effects of insulin sensitizers in the treatment of hirsutism, particularly in patients with polycystic ovarian syndrome. In the present review, the main features of anti-androgen drugs, new combined treatments, and insulin sensitizers in the treatment of hirsutism are discussed.     

Comparison of finasteride versus spironolactone in the treatment of idiopathic hirsutism

Objective: To compare the efficacy of finasteride and spironolactone in the treatment of idiopathic hirsutism.

Design: Prospective, randomized, single-blind study.

Setting: A tertiary hirsutism clinic.

Patient(s): Forty women with idiopathic hirsutism were selected.

Intervention(s): Patients were assigned randomly to receive either 5 mg of finasteride or 100 mg of spironolactone for 9 months.

Main Outcome Measure(s): Hirsutism scores were measured according to the Ferriman-Gallwey scoring system, and side effects were monitored for 9 months of treatment. Blood samples were taken at each visit for assessment of endocrine, biochemical, and hematologic parameters.

Result(s): Hirsutism scores were decreased significantly in both groups at the end of 9 months. The mean percent change (±SD) in hirsutism scores in the finasteride and spironolactone groups was as follows: 5.91% ± 7.18% and 20.60% ± 12.59% at 3 months, 10.61% ± 12.18% and 32.57% ± 15.68% at 6 months, and 15.15% ± 15.38% and 42.36% ± 12.31% at 9 months, respectively. There was a significantly better response with spironolactone treatment at the end of 9 months. Eleven (55%) of 20 patients in the spironolactone group experienced side effects. However, none of them stopped treatment because of side effects.

Conclusion(s): The present data suggest that both finasteride and spironolactone are effective in the treatment of idiopathic hirsutism. However, it appears that the spironolactone group responded significantly better.     

Finasteride versus cyproterone acetate-estrogen regimens in the treatment of hirsutism.

OBJECTIVES: To compare the clinical and hormonal effects of finasteride and a combination regimen of cyproterone acetate (CPA) plus ethinyl estradiol (EE2) in the treatment of hirsutism. METHODS: Forty hirsute women were enrolled in a prospective randomized trial. Twenty-nine had polycystic ovary syndrome (PCOS) and 11 had idiopathic hirsutism. Patients were randomly treated with finasteride (5 mg/day; n=20) or CPA plus EE2 [CPA (25 mg/day on days 5-14) plus EE2 (20 microg/day on days 5-25) n=20] for 9 months. Main outcome measurement was a reduction in hair growth. Hirsutism score and hormone levels were measured at the beginning and at the end of the study. The student t-test and Mann-Whitney U tests were used for analysis of the data. RESULTS: The modified Ferriman-Gallwey scores for hirsutism decreased significantly at the end of the study from a mean+/-SD of 23.7+/-4.4 to 11.3+/-1.5; P=<0.001 in finasteride group and from 22.3+/-4.2 to 11.4+/-1.2; P=<0.001 in CPA plus EE2 group. Improvement of hirsutism induced by the two treatment methods was similar (47.6 % vs. 51.1%; P=0.2). Treatment with CPA plus EE2 significantly decreased serum total and free T, A, DHEAS, and DHT and increased SHBG levels. Finasteride significantly increased total T but reduced DHT levels. CONCLUSION: Finasteride and CPA plus EE2 are equally effective in decreasing hirsutism, despite significantly different effects on serum hormone levels.     

Hepatotoxicity during low-dose flutamide treatment for hirsutism

Background. The nonsteroidal antiandrogenic drug flutamide is a safe and generally well-tolerated drug used for the treatment of prostate cancer and female hyperandrogenism.

Case. We describe the case of a 26-year-old girl with amenorrhea and severe hirsutism who was treated with flutamide 250 mg/day and developed liver toxicity during therapy.

Results. Other causes of liver toxicity were appropriately ruled out. The use of the standard Council for International Organization of Medical Sciences (CIOMS) scale and the Maria & Vitorino (M&V) scale indicated a highly probable relationship between the development of liver toxicity and flutamide therapy. Severe liver dysfunction has been rarely documented in women with hirsutism treated with flutamide, even though cases of fulminant liver failure have been described. The mechanisms responsible for the occurrence of hepatotoxicity during treatment with flutamide are unknown, but mitochondrial dysfunction seems to be implicated.

Conclusion. The potential of flutamide to act as a potent hepatotoxin should be kept in mind when treatment with this drug is being planned. This case reminds us that patients who are receiving flutamide should be regularly monitored for liver function. If drug-induced liver injury is suspected, flutamide must be discontinued promptly to avoid progression of liver injury.     

Comparison of finasteride and flutamide in the treatment of idiopathic hirsutism.

OBJECTIVE: To compare the effectiveness of finasteride and flutamide in the treatment of idiopathic hirsutism. DESIGN: Randomized study. SETTING: Department of Gynecological Endocrinology, University of Brescia, Italy. PATIENT(S): Forty-six women with idiopathic hirsutism were selected. INTERVENTION(S): Patients were assigned randomly to receive 5 mg of finasteride once daily or 250 mg of flutamide twice daily for 12 consecutive months. MAIN OUTCOME MEASURE(S): Hirsutism was evaluated at 6 and 12 months of therapy by measuring the Ferriman-Gallwey score and the terminal-hair diameters (microm) taken from different body areas. Blood samples were taken and side effects were monitored during the treatment. RESULT(S): Both finasteride and flutamide induced a statistically significant decrease in hirsutism scores and hair diameters at the end of 12 months. Finasteride reduced the Ferriman-Gallwey score by 20.5% at 6 months and by 34.2% at 12 months, and hair diameter by 18.9%-23.6% at 6 months and by 29.6%-37.9% at 12 months. Flutamide reduced the Ferriman-Gallwey score by 26.6% at 6 months and by 50.9% at 12 months, and hair diameter by 22.3%-28.2% at 6 months and by 47.7%-56.5% at 12 months. Flutamide did not induce hormonal variations, whereas finasteride increased T levels by 60% and decreased 3alpha-androstanediol glucuronide by 69.5% at 12 months. CONCLUSION(S): Both drugs were effective in the treatment of idiopathic hirsutism, but flutamide was more effective than finasteride.     

Parenteral and oral cyproterone acetate treatment in severe hirsutism

In the present study a parenteral treatment regimen with cyproterone acetate was compared with the high dose peroral administration in patients with severe hirsutism. Two groups consisting of 10 patients each performed treatment with either 100 mg cyproterone acetate perorally for the first 10 days of the menstrual cycle or received a monthly implant of 300 mg cyproterone acetate intramuscularly applied on the first day of each cycle. In addition, contraception was performed with Diane in both patient groups. 9 treatment cycles were followed by a posttreatment period of 3 months. Hair parameters and serum androgens were monitored regularly. No significant differences of testosterone, androstenedione, dehydroepiandrosterone-sulfate and prolactin serum levels became evident between both cyproterone acetate regimens. Measurements of facial hair diameters revealed a better reduction for the parenteral application. Also the improvement of dermatological parameters was more prominent in the parenteral treatment group. The good effects of a medium dose parenteral application against higher dose peroral treatment thus was documented. The lack of significant differences of androgenic suppression in both regimens turns up the question if different metabolism at the cellular level may be responsible for that phenomenon.     

Further clinical experience in the treatment of hirsutism with cyproterone acetate.

Further experience in the treatment of female hirsutism with the anti-androgen cyproterone acetate is reported. Two-thirds of treated patients have shown improvement but relapse occurred within two or three months of stopping treatment. Acne also healed in two patients.