What is the recommended progesterone (medroxyprogesterone acetate or micronized progesterone) dosing regimen to induce a withdrawal bleed in a patient with Polycystic Ovary Syndrome (PCOS) experiencing amenorrhea?

Progesterone Dosing to Induce Withdrawal Bleed in PCOS

For PCOS patients with amenorrhea, use medroxyprogesterone acetate 10 mg daily for 12-14 days per month to induce withdrawal bleeding and provide endometrial protection. 1, 2

Primary Recommended Regimen

Medroxyprogesterone acetate (MPA) 10 mg orally daily for 12-14 days per month is the first-line progesterone regimen for inducing withdrawal bleeding in PCOS patients with amenorrhea. 1, 2 This dosing provides critical endometrial protection against hyperplasia and cancer risk in anovulatory PCOS patients, while reliably inducing secretory transformation of the endometrium. 2

• MPA is the only progestin with robust evidence demonstrating full effectiveness in inducing secretory endometrium when used cyclically. 2
• Regular monthly cycling (every 28 days) is essential to maintain adequate endometrial protection. 2
• MPA suppresses circulating androgen levels and pituitary gonadotropin levels in women with PCOS, providing additional therapeutic benefit beyond endometrial protection. 1

Alternative Progesterone Options

Oral micronized progesterone (OMP) 300 mg daily for 10 days is an effective alternative with a superior safety profile compared to synthetic progestins. 3, 4

• OMP 300 mg induced withdrawal bleeding in 90% of women with oligomenorrhea/amenorrhea, compared to only 29% with placebo. 3
• The 200 mg dose is less effective, inducing bleeding in only 58% of women. 3
• OMP does not significantly alter circulating androgen levels in PCOS patients, making it safe for timing blood sampling. 4
• OMP has demonstrated lower cardiovascular risk and better thrombotic safety profile compared to synthetic progestogens. 2

Dydrogesterone 10 mg daily for 12-14 days per month is another synthetic progesterone option with enhanced oral bioavailability. 2

Critical Dosing Principles

The 12-14 day duration is critical—shorter durations provide inadequate endometrial protection. 2 This extended exposure ensures complete secretory transformation of the endometrium, which is essential for preventing endometrial hyperplasia and cancer in chronically anovulatory PCOS patients. 2

• Monthly cycling should be maintained consistently to prevent unopposed estrogen exposure. 2
• The optimal frequency to prevent endometrial cancer in PCOS is not definitively established, but monthly cycling is standard practice. 2

Alternative Routes of Administration

Vaginal micronized progesterone 200 mg daily for 12-14 days can be used if oral administration causes intolerable side effects or is contraindicated. 2 This route provides equivalent endometrial protection with potentially fewer systemic side effects. 2

When Combined Oral Contraceptives Are Preferred

Combined oral contraceptives (COCs) are the preferred first-line treatment for long-term management of PCOS in women not attempting to conceive, as they provide contraception, suppress ovarian androgen production, increase sex hormone-binding globulin, and reduce endometrial cancer risk. 1, 2 However, progesterone-only regimens are appropriate when COCs are contraindicated or not tolerated. 2

Common Pitfalls to Avoid

• Never use progesterone for fewer than 12 days per cycle—this provides inadequate endometrial protection and fails to induce complete secretory transformation. 2
• Do not rely on lower doses of oral micronized progesterone (200 mg or less) for withdrawal bleeding induction—the 300 mg dose is significantly more effective. 3
• Avoid irregular or infrequent cycling—monthly administration is necessary to prevent endometrial hyperplasia in chronically anovulatory patients. 2
• Do not assume bleeding response predicts adequate endometrial protection—up to 29% of women may bleed with placebo, so consistent dosing is essential regardless of bleeding pattern. 3

Monitoring and Follow-Up

Annual clinical review focusing on compliance, bleeding patterns, and symptom control is recommended, with no routine laboratory monitoring required unless specific symptoms arise. 2 The progestin challenge test has limited utility since up to 60% of women with functional hypothalamic amenorrhea (who may be misdiagnosed as PCOS) can have withdrawal bleeding after progesterone. 1