What is the recommended dosing of medroxyprogestone (Provera) to induce a withdrawal bleed in a female patient of reproductive age with Polycystic Ovary Syndrome (PCOS)?

Medroxyprogesterone Dosing to Induce Withdrawal Bleed in PCOS

For women with PCOS requiring withdrawal bleeding, administer medroxyprogesterone acetate (MPA) 10 mg orally daily for 12-14 days per month. 1, 2

Recommended Dosing Regimen

The standard dose is MPA 10 mg daily for 12-14 consecutive days every 28 days (monthly cycling). 1, 2 This regimen:

• Induces withdrawal bleeding within 3-7 days after completing the course 2
• Provides endometrial protection against hyperplasia and cancer risk in anovulatory PCOS patients 1
• Suppresses circulating androgen levels and pituitary gonadotropin levels, offering additional therapeutic benefit beyond endometrial protection 1, 3

Alternative Dosing Options

While 10 mg for 12-14 days is the evidence-based standard, the FDA label indicates flexibility:

• Lower dose option: MPA 5 mg daily for 5-10 days can induce withdrawal bleeding 2
• Optimal endometrial transformation: 10 mg daily for 10 days is specifically recommended for achieving adequate secretory transformation 2

However, for PCOS patients specifically, the 12-14 day duration at 10 mg is strongly preferred because it provides more reliable endometrial protection in the context of chronic anovulation. 1

Alternative Progestogen Options

If MPA is not tolerated or contraindicated, consider:

• Oral micronized progesterone (OMP) 200 mg daily for 12-14 days per month 1 - This has a superior cardiovascular and thrombotic safety profile compared to synthetic progestins 1
• Dydrogesterone 10 mg daily for 12-14 days per month 1 - This has enhanced oral bioavailability 4

Research demonstrates that OMP 100 mg in the morning and 200 mg before bedtime for 7 days does not significantly alter circulating androgen levels in PCOS patients, making it safe for timing blood sampling. 5 However, the 12-14 day duration is preferred for endometrial protection. 1

When to Start Treatment

MPA can be started at any time in women with secondary amenorrhea or oligomenorrhea - there is no need to wait for spontaneous bleeding. 2 This is particularly relevant for PCOS patients who may have prolonged intervals between periods.

First-Line Treatment Context

Combined oral contraceptives (COCs) are actually the preferred first-line medication treatment for long-term PCOS management in women not attempting to conceive. 1, 6 COCs provide:

• Suppression of ovarian androgen production 1
• Increased sex hormone-binding globulin 1
• Reduced endometrial cancer risk 1
• Contraception 1

Cyclic progestogen therapy (like MPA) is reserved for patients who:

• Have contraindications to estrogen-containing COCs 1
• Cannot tolerate COCs 1
• Refuse COCs 1
• Only need periodic withdrawal bleeding without contraception 1

Critical Clinical Considerations

Monthly cycling is essential - do not allow intervals longer than 3 months without inducing a withdrawal bleed, as this increases endometrial cancer risk in anovulatory PCOS patients. 1 The regular monthly cycling (every 28 days) maintains endometrial protection. 1

Baseline cardiometabolic assessment is mandatory before initiating any hormonal therapy in PCOS patients. 6 Document:

• Age and smoking status 6
• Obesity and body mass index 6
• Glucose tolerance or diabetes 6
• Blood pressure 6
• Lipid profile 6
• Personal or family history of venous thromboembolism 6

Re-evaluate patients every 3-6 months to determine if treatment is still necessary and assess for side effects. 2

Common Pitfalls to Avoid

• Do not use shorter durations (5-7 days) for routine PCOS management - while this may induce bleeding, the 12-14 day duration provides superior endometrial protection in chronic anovulation 1, 2
• Do not use MPA as a pregnancy test - the FDA label explicitly warns against this practice 2
• Do not prescribe without first ruling out pregnancy in women with amenorrhea, as MPA exposure in early pregnancy may increase risk of minor birth defects 2
• Do not forget that withdrawal bleeding does not confirm ovulation - PCOS patients remain anovulatory despite induced bleeding and require contraception if sexually active 1

Monitoring for Adverse Effects

Common side effects of MPA include breast tenderness, breakthrough bleeding, irregular periods, headaches, nervousness, dizziness, depression, weight gain, and bloating. 2 Serious but rare complications include thrombophlebitis and blood clots. 2

Instruct patients to seek immediate care for: 2

• New breast lumps
• Unusual vaginal bleeding patterns
• Severe headaches
• Chest pain or leg pain with shortness of breath
• Vision changes
• Signs of allergic reaction (hives, difficulty breathing, facial swelling)