Combined OCPs and anti-androgens: menstrual regulation and androgen control
Combined oral contraceptive pills (COCPs) are first-line for menstrual regulation and androgen-related symptoms in PCOS women not currently seeking pregnancy. They work through multiple mechanisms: suppressing LH (reducing ovarian androgen production), increasing sex hormone binding globulin (reducing free testosterone by 40-60%), and providing regular endometrial shedding (preventing hyperplasia from unopposed estrogen).
Choice of pill
The progestin component matters more than the estrogen dose for PCOS. Anti-androgenic progestins are preferred:
- Drospirenone (Yasmin, Yaz, Krimson): most anti-androgenic, with slight aldosterone antagonism (mild diuretic effect). Good for acne, hirsutism and PMS symptoms. Slightly higher VTE risk than levonorgestrel-containing pills.
- Cyproterone acetate (Diane-35, Ginette-35): strong anti-androgen effect, excellent for severe hirsutism and acne. Higher VTE risk profile; guidelines recommend limited duration (3-6 months) once benefit is achieved, then switching.
- Desogestrel or Gestodene: mild anti-androgen. Alternatives if drospirenone is contraindicated.
- Levonorgestrel: cheapest and safest VTE profile, but slightly androgenic, so not first choice for hirsutism-predominant PCOS.
Effects: Regular monthly withdrawal bleeds within 1-2 cycles. Reduced acne visible by 3-6 months. Hirsutism improvement is slower, 6-12 months for meaningful effect, and often needs an anti-androgen add-on. Reduced menstrual pain and volume. Contraceptive benefit. Reduced ovarian cyst formation. Long-term data suggests reduced endometrial cancer risk (about 50% reduction with sustained use).
Side effects: Nausea, breast tenderness, mood changes and spotting (usually resolve in 3 months). Weight gain reports are mostly anecdotal; RCTs show minimal effect. VTE risk is 3-9 per 10,000 women-years (baseline 2, pregnancy 30). Blood pressure elevation. Rare: hepatic adenoma. Contraindications: smoker over 35, migraine with aura, history of VTE/stroke/CAD, uncontrolled hypertension, active liver disease, breast cancer.
Alternatives to combined OCPs (for those who cannot take estrogen): cyclical progesterone (medroxyprogesterone 10 mg for 10-14 days every 1-3 months) for endometrial protection; levonorgestrel-releasing IUD (Mirena) for endometrial protection with lighter periods; progestin-only pills (less effective for androgen control).
Anti-androgens
Anti-androgens add substantial benefit for hirsutism, acne and androgenic alopecia beyond what COCPs alone achieve. They should never be used without effective contraception (teratogenic, can feminize a male fetus).
Spironolactone is the workhorse anti-androgen. Originally a potassium-sparing diuretic, it blocks androgen receptors and inhibits 5-alpha-reductase. Dose 50-200 mg/day (typically 100 mg). Visible effects take 3-6 months for acne and 6-12 months for hirsutism. Monitor potassium (baseline and at 4 weeks, then annually). Common side effects: menstrual irregularity, breast tenderness, dizziness, increased urination. Well studied and well tolerated for long-term use.
Cyproterone acetate (25-100 mg for 10 days per cycle when used separately from Diane-35) is a potent anti-androgen. Now less commonly used due to VTE and hepatic concerns, but effective for severe hirsutism resistant to spironolactone.
Finasteride and dutasteride are 5-alpha-reductase inhibitors used off-label for PCOS-related hair loss and hirsutism. Not first-line, but sometimes added for refractory androgenic alopecia. Absolutely contraindicated in pregnancy.
Topical eflornithine (Vaniqa) for facial hirsutism slows hair growth over 4-8 weeks. It is an adjunct to systemic therapy and mechanical hair removal.
Adjuncts: Laser hair removal (5-8 sessions typical for durable reduction) and electrolysis (permanent removal, slower and area-limited) work synergistically with anti-androgen therapy. Without addressing the hormonal driver, hair regrows; with a combined approach, hair-free intervals extend dramatically.
