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Anti-androgens may be beneficial for managing certain hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS) in cases where combined oral contraceptive pills are contraindicated, poorly tolerated, or ineffective, according to the first systematic review and meta-analysis on the subject.

Using data from 13 studies including a total of 961 patients, combination treatment with antiandrogens, metformin, and lifestyle intervention helped to lower testosterone levels in patients with PCOS compared with metformin and lifestyle intervention alone (weighted mean difference [WMD] -0.29 nmol/L, 95% CI -0.52 to -0.06, P=0.01), reported Aya Mousa, PhD, of Monash University in Clayton, Australia, and colleagues.

According to their study published in , adding anti-androgens to lifestyle intervention was also superior to lifestyle intervention with metformin in managing:

• Hirsutism: WMD -1.59 (95% CI -3.06 to -0.12, P=0.03)
• Sex-hormone binding globulin (SHBG): WMD 7.70 nmol/L (95% CI 0.75-14.66, P=0.03)
• Fasting insulin: WMD -2.11 μU/mL (95% CI -3.97 to -0.26, P=0.03)
• Fasting insulin to glucose ratio: WMD -1.12 (95% CI -1.44 to -0.79, P<0.0001)

However, looking just at hirsutism and SHBG, the combination of anti-androgens and lifestyle intervention was not superior to lifestyle intervention alone.

"Based on findings from this review, the guideline recommends that anti-androgen pharmacological agents could be considered to treat clinical hyperandrogenism (hirsutism), in situations where the [combined oral contraceptive pills] and/or cosmetic therapies (including mechanical laser and light therapies for hair reduction) are contraindicated, poorly tolerated, or present a suboptimal response after a minimum period of six months," Mousa's group concluded.

That being said, they noted that when it's appropriate, patients should still be "strongly recommended" to use combined oral contraceptive pills for managing PCOS symptoms, "and women should be advised that anti-androgens may cause under-virilization of a male fetus."

"The recommendation remains general, and should not override clinical judgment with consideration of individual circumstances and perspectives," they added.

Compared with dosing every 3 days, daily use of anti-androgens was more effective in managing hirsutism (WMD -3.48, 95% CI -4.58 to -2.39, P<0.0001), and in lowering androstenedione levels (WMD -0.30 ng/mL, 95% CI -0.50 to -0.10, P=0.004).

Regarding safety, in a limited meta-analysis of two trials that looked at combining anti-androgens with combined oral contraceptive pills, lipid profiles were worse compared with taking oral contraceptive pills alone.

Because of the heterogeneity of the studies included in the analysis, Mousa and team said they couldn't make any specific recommendations on optimal doses or formulations of therapies. However, they pointed out that general population recommendations suggest that spironolactone at doses of 25-100 mg daily are likely to have lower risks of adverse effects, but higher doses of cyproterone acetate (10+ mg) could potentially lead to meningioma or venous thromboembolism. They also noted that flutamide and bicalutamide are associated with increased risks of liver toxicity.

The anti-androgens included in the 13 trials were finasteride, flutamide, spironolactone, or bicalutamide. Most of the trials were conducted among adults, while two were done in adolescents. Most study participants were women with a BMI of 25 or higher.

Mousa's group said that this analysis has "directly informed" the recommendations of the , which will be released in mid-August.

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