Yılmaz Şahin

Comparison of Diane 35 and Diane 35 plus finasteride in the treatment of hirsutism

OBJECTIVE To compare the clinical efficacy and safety of the combination of Diane 35 (2 mg of cyproterone acetate, and 35 microg of ethinyl estradiol) plus finasteride (5 mg), and Diane 35 alone in the treatment of hirsutism. DESIGN Prospective randomized clinical study. SETTING Outpatients in Erciyes University Medical School. PATIENT(S) Forty women with hirsutism were selected. INTERVENTION(S) For 1 year, group 1 patients (n = 20) were treated with Diane 35 alone (2 mg of cyproterone acetate and 35 microg of ethinyl estradiol) daily on days 5 to 25 of the menstrual cycle and group 2 patients (n = 20) with Diane 35 plus finasteride (5 mg daily). MAIN OUTCOME MEASURE(S) Hirsutism was graded at 6-month intervals using the Ferriman-Gallwey method. The basal hormone levels of total and free testosterone (T), androstenedione, DHEAS, and sex-hormone-binding globulin (SHBG) were measured by radioimmunoassay before the study. Total T, free T, SHBG, and DHEAS were also measured at 6-month intervals for 1 year. Multiscreen blood chemistry and side effects were evaluated during the treatment. RESULT(S) Thirty-four patients completed the 12-month study period. A significant decrease in the hirsutism score as compared to baseline was observed after 12 months with both Diane 35 treatment (mean +/- SD, 15.62 +/- 4.89 vs. 9.75 +/- 3.97) and Diane 35 plus finasteride treatment (16.27 +/- 6.90 vs. 8.38 +/- 4.44). The percentage decreases in the hirsutism score (mean percent +/- SD) were 30.26 +/- 14.56 vs. 34.70 +/- 11.60 at 6 months, 38.09 +/- 11.46 vs. 48.14 +/- 14.27 at 12 months in the Diane 35 and the Diane 35 plus finasteride groups, respectively. The percentage reduction in the hirsutism score in the Diane 35 plus finasteride group at 12 months was greater than in the Diane 35 group (P <.05). CONCLUSION(S) The percentage decrease in the hirsutism score at 12 months was higher in the Diane 35 plus finasteride group than in the Diane 35 group. We believe that Diane 35 plus finasteride is an effective and safe combination for the treatment of hirsutism.

A comparison between two doses of flutamide (250 mg/d and 500 mg/d) in the treatment of hirsutism

OBJECTIVE To compare the effects of flutamide at 250 mg/d and 500 mg/d in the treatment of hirsutism. DESIGN Randomized, prospective clinical study. PATIENT(S) Sixty-five patients with moderate to severe hirsutism. INTERVENTION(S) Group I (n = 35) patients were treated with flutamide, 250 mg/d, and group II (n = 30) patients were treated with flutamide, 500 mg/d, for 12 months. Baseline hormone levels, body mass index, and hirsutism scores were similar between the groups. Hirsutism score, hormone levels, and multiscreen blood chemistry were measured at 3-month intervals for 12 months. RESULT(S) The modified Ferriman-Gallwey scores for hirsutism decreased significantly at months 6 and 12 from a mean +/- SEM of 17.8 +/- 0.9 to 6.0 +/- 0.6 (P < 0.001) and 17.8 +/- 0.9 to 4.8 +/- 0.7 (P < 0.001) in group I and from 17.0 +/- 0.9 to 6.6 +/- 0.7 and 17.0 +/- 0.9 to 5.2 +/- 0.7 (P < 0.001) in group II, respectively. The reductions in hirsutism scores (mean +/- SEM) were similar in group I at 6 months (64.6% +/- 2.5%) and at 12 months (71.2% +/- 2.2%) and in group II at 6 months (62.1% +/- 3.0%) and at 12 months (70.3% +/- 3.0%). The percent reductions in hirsutiam scores at 6 and at 12 months were similar within group I (64.6% +/- 2.5% and 71.2% +/- 2.2%) and group II (62.1% +/- 3.0% and 70.3% +/- 3.0%), respectively. The decreases in hirsutism scores in the first 6 months were more significant than in the last 6 months of treatment in both groups. There were no significant differences in any of the hormone levels during therapy in either group. One patient in group II was excluded from the study because of liver dysfunction. CONCLUSION(S) This study shows that two different doses of flutamide (250 mg/d and 500 mg/d) are similarly effective in reducing hair growth. Flutamide at a dose of either 250 mg/d or 500 mg/d has no further effect after 6 months. We conclude that if flutamide is administered at a dose of 250 mg/d it may represent an effective and well tolerated treatment with reduced cost for the patient.

Comparison of Diane 35 and Diane 35 plus spironolactone in the treatment of hirsutism

OBJECTIVE To compare the clinical efficacy and safety of Diane 35 (cyproterone acetate [2] mg and ethinyl estradiol [35 microg]) plus spironolactone [100 mg] combination and Diane 35 alone in the treatment of hirsutism. DESIGN Prospective clinical study. SETTING Outpatients in Erciyes University Medical School. PATIENT(S) Fifty women with hirsutism. INTERVENTION(S) Group I patients (n = 22) were treated with Diane 35 alone and group II patients (n = 28) with Diane 35 plus spironolactone [100 mg]. MAIN OUTCOME MEASURE(S) The basal hormone levels total and free T, androstenedione, DHEAS, sex hormone-binding globulin (SHBG), and prolactin (PRL) were measured by RIA before the study. Free T, SHBG, and DHEAS were also measured at 6-month intervals for 12 months. Hirsutism was graded at 6-month intervals. RESULT(S) The basal hormone levels were similar between the groups. Hirsutism score significantly decreased at the end of the therapy in both groups. The reduction in hirsutism score in group II at 12 months was greater than in group I. But the scores before the treatment, at 6 and 12 months were similar between the groups. CONCLUSION(S) Although the actual hirsutism score and free T concentration are not significantly different between the two groups at 12 months, percentage change in the hirsutism score at 12 months was higher in the Diane 35 plus spironolactone group. Therefore, the addition of spironolactone to Diane 35 may have a synergistic effect on hirsutism score.

Comparison of cyproterone acetate plus ethinyl estradiol and finasteride in the treatment of hirsutism

The aim of this study was to compare the clinical efficacy and safety of low dose cyproterone acetate-estrogen combination (Diane®) and the 5α-reductase inhibitor finasteride in the treatment of hirsutism. Fourty-two women with hirsutism were included in the study. Twenty-one patients treated with cyproterone acetate (CPA) 2 mg and ethinyl estradiol (E) 35 µg daily on days 5–25 of the menstrual cycle, 21 with finasteride 5 mg daily. Hirsutism score, hormone levels, multiscreen blood chemistry and side effects were evaluated at three-monthly intervals for 9 months. A significant decrease in hirsutism score as compared to baseline was observed after 9 months with either CPA+E (Diane®) (mean ± SE, 15.81±1.19 i 8.38±1.21) or finasteride treatment (17.81±1.05 vs 10.86±0.91) (p<0.0005). The reductions in hirsutism scores (mean% ± SE) were 14.23 ± 2.29 vs 19.77±2.22 (p<0.05) at 3, 40.23±4.58 vs 29.49±2.69 (p<0.02) at 6 and 50.99±4.13 vs 39.87±3.30 (p<0.02) at 9 months in CPA+E and finasteride groups, respectively. No significant changes were observed in hormone levels during finasteride treatment. Serum free testosterone significantly decreased at the third month of treatment, and remained suppressed for the duration of treatment in CPA+E group. DHEAS levels also decreased significantly after 6 and 9 months of therapy with CPA+E. SHBG significantly increased during CPA+E treatment. We conclude that both drugs are effective and well tolerated, but CPA+E appears to be more effective than 5α-reductase inhibitor finasteride in long-term treatment of hirsute women. Diane® is also a cost-effective drug.

The efficacy of 250 mg/day flutamide in the treatment of patients with hirsutism

OBJECTIVE To investigate the effects of low dose flutamide (250 mg/d) on hirsutism score and hormone levels in women with hirsutism. DESIGN Nonrandomized, prospective clinical trial. PATIENTS Forty-one patients with moderate-severe hirsutism were included in the study. INTERVENTION Hirsute patients received 250 mg/d flutamide for a period of 6 months. MAIN OUTCOME MEASURES Hirsutism score, FSH, LH, E2, total T, free T, androstenedione, DHEAS, PRL, 17-hydroxyprogesterone, and sex hormone-binding globulin levels were detected in all the patients before treatment and every 3 months during treatment. RESULTS Treatment with the antiandrogen flutamide resulted in a particularly rapid and marked decrease in the hirsutism score, which decreased from 17.48 +/- 5.35 to 5.07 +/- 2.89 after 6 months. No significant changes in the levels of hormone and no serious side effects were observed in the study. CONCLUSION The low-dose flutamide, 250 mg/d, is a cost-effective drug in the treatment of hirsutism. Low-dose flutamide may be used in place of high-dose flutamide, 500 to 750 mg/d.

Assessment of paraoxonase 1, xanthine oxidase and glutathione peroxidase activities, nitric oxide and thiol levels in women with polycystic ovary syndrome

Objective. To investigate whether there is any relation between oxidative stress and the antioxidant system in the development of polycystic ovary syndrome (PCOS) by measuring serum nitric oxide (NO) levels and xanthine oxidase (XO) activity (a generator of reactive oxygen species) and antioxidant status by measuring serum thiol levels and glutathione peroxidase (GSHPx) and paraoxonase 1 (PON1) activities. Design. Prospective case–control study. Setting. University hospital in Turkey. Sample. Thirty women with polycystic ovary syndrome and 20 age‐ and sex‐matched healthy control subjects were included. Methods. Serum XO, PON1 and GSHPx activity and NO and thiol levels were determined by spectrophotometric methods. Main outcome measures. Activity of serum XO, PON1 and GSH, as well as NO and thiol levels. Results. Serum XO activities were higher in women with PCOS than in the control women (p<0.001). The PON1 activity was lower in women with PCOS than in the control women (p<0.001). No significant difference was found between NO and thiol levels and GSHPx activities of women with PCOS and the control women (p>0.05). Serum PON1 activities were negatively correlated with serum XO activities and NO levels. Conclusion. Increased oxidant XO activity and decreased lipid antioxidant PON1 activity, along with the observed negative correlation between these parameters, suggests that women with PCOS are under oxidative stress and that there is XO‐mediated lipid peroxidation, which may be related to increased atherosclerosis seen in later life in such women.

Alternate pathway 17,20-lyase enzyme activity in the adrenals is enhanced in patients with polycystic ovary syndrome

OBJECTIVE To assess the activity of the enzyme cytochrome P450c17alpha in patients with polycystic ovary syndrome (PCOS). DESIGN Prospective clinical study. SETTING Outpatients at Erciyes University Medical School, Kayseri, Turkey. PATIENT(S) Twenty-eight women with PCOS aged 25.44 +/- 4.37 years (mean +/- SD) and 18 normal women aged 26.94 +/- 3.17 years. MAIN OUTCOME MEASURE(S) Serum levels of 11-deoxycortisol, androstenedione (A), and 17alpha-hydroxy progesterone were measured before and 30 and 60 minutes after ACTH (0.25 mg i.v.) injection. RESULT(S) There was a statistically significant correlation between basal levels of 11-deoxycortisol (4.05 +/-1.16 ng/mL) and A (3.36 +/- 0.97 ng/mL) (r = 0.539). The peak level of 11-deoxycortisol (7.82 +/- 2.36 ng/mL) was also significantly correlated with the peak level of A (6.66 +/- 1.32 ng/mL) (r = 0.570) in women with PCOS. There was no statistically significant correlation between basal A (2.33 +/- 0.50 ng/mL) and basal 11-deoxycortisol (2.71 +/- 0.59 ng/mL) or between peak A (3.38 +/- 0.50 ng/mL) and peak 11 -deoxycortisol (3.68 +/- 0.48 ng/mL) levels in control subjects. CONCLUSION(S) We believe that PCOS is characterized by enhanced activity of 17,20-lyase enzyme in an alternate pathway between 11-deoxycortisol and A in the adrenal glands.