Withdrawal Bleeding Dosing for Menstrual Regulation in PCOS
Recommended Regimen
For anovulatory women with PCOS requiring menstrual regulation, prescribe oral micronized progesterone 200 mg at bedtime for 12–14 consecutive days each month to induce withdrawal bleeding and protect the endometrium. 1
This sequential progestogen regimen replicates the natural luteal phase and provides complete endometrial protection while inducing predictable withdrawal bleeding 2–3 days after the final dose. 2, 1
Evidence-Based Dosing Protocol
Micronized Progesterone (First-Line)
- Dose: 200 mg orally at bedtime 1
- Duration: 12–14 consecutive days per 28-day cycle 2, 1
- Timing: Typically days 15–28 of each cycle 2
- Withdrawal bleed: Occurs 2–3 days after completing the progesterone course 2
Clinical trial data demonstrate that 73.8–76.8% of women with secondary amenorrhea experience withdrawal bleeding after 10 days of progesterone 300–400 mg daily. 1 The 200 mg dose for 12–14 days provides equivalent efficacy with better tolerability. 2
Alternative Progestogen Options
If micronized progesterone is unavailable or not tolerated:
- Medroxyprogesterone acetate (MPA): 10 mg orally daily for 12–14 days per month 2, 1
- Dydrogesterone: 10 mg orally daily for 12–14 days per month 2
Micronized progesterone is preferred over synthetic progestins because it offers superior breast safety and cardiovascular profiles while maintaining adequate endometrial protection. 2
Critical Duration Requirement
Progestogen must be administered for at least 12 days per cycle—shorter durations fail to prevent endometrial proliferation and increase endometrial cancer risk by approximately 1.8-fold. 2
Sequential regimens shorter than 10–12 days are considered unsafe for endometrial protection. 2 The 12–14 day window ensures complete secretory transformation of the endometrium, mimicking the natural luteal phase. 2, 1
Endometrial Protection Evidence
Unopposed estrogen (from peripheral conversion of androgens in PCOS) increases endometrial cancer risk 10- to 30-fold after 5+ years, with relative risk of 2.3–9.5. 2, 3
Adding progestogen for 12–14 days per month reduces this endometrial cancer risk by approximately 90% compared to no treatment. 2, 3, 1
In the pivotal FDA trial, women receiving conjugated estrogens plus cyclic progesterone 200 mg for 12 days had only 6% incidence of hyperplasia versus 64% with estrogen alone over 36 months. 1
Alternative: Combined Oral Contraceptives
For women with PCOS who also desire contraception or reject progestogen-only therapy:
Combined oral contraceptives (COCs) are first-line medical therapy for long-term PCOS management, restoring regular menses, improving androgen excess, and providing endometrial protection. 4, 5, 6
COC Selection for PCOS
- Standard dose: 30–35 μg ethinyl estradiol with levonorgestrel or norgestimate 2
- Regimen: Monophasic formulations are preferred initially 2
- Extended cycles: Can be used for women with severe dysmenorrhea or those preferring fewer withdrawal bleeds 2, 7
Extended-cycle COC regimens (84–168 days of active pills) reduce withdrawal bleeding frequency while maintaining endometrial protection and may improve quality of life in PCOS. 2, 7
Cardiometabolic Risk Assessment Required
Before prescribing any hormonal therapy for PCOS, document the following risk factors: 4, 5
- Age and smoking status
- Body mass index (obesity amplifies VTE risk 2–3 fold)
- Blood pressure (hypertension)
- Fasting glucose and HbA1c (prediabetes/diabetes)
- Lipid profile (dyslipidemia)
- Personal or family history of venous thromboembolism
- Known thrombophilia
COCs increase venous thromboembolism risk 2–4 fold, with risk varying by estrogen dose and progestin type. 4, 5 Arterial thrombosis risk is not significantly increased in young nonsmoking women. 4
Morbidly obese women with PCOS and severe insulin resistance may have increased diabetes risk with COC use and should be monitored closely. 4
Monitoring and Follow-Up
- Reassess cardiometabolic risk factors at each visit (more frequently if baseline risk factors present) 5
- If withdrawal bleeding does not occur within 3 weeks of completing progestogen, perform pregnancy testing 3
- Annual blood pressure measurement is required during hormonal therapy 3
- No routine pelvic examination is required before initiating therapy unless clinically indicated 3
Common Pitfalls to Avoid
Never prescribe progestogen for fewer than 12 days per cycle—this provides inadequate endometrial protection and increases cancer risk. 2
Do not assume all women with PCOS are anovulatory—spontaneous ovulation can occur, so pregnancy testing is essential if withdrawal bleeding fails to occur. 2, 3
Avoid prescribing oral estrogen-containing COCs to obese women with PCOS due to amplified VTE risk; if hormonal contraception is needed in this population, consider progestin-only methods or carefully weigh risks. 4, 5
Do not initiate COCs in women over 35 who smoke—this dramatically increases cardiovascular and thrombotic risk. 2