Medroxyprogesterone Acetate for Inducing Withdrawal Bleeding in PCOS and Oligomenorrhea
Medroxyprogesterone acetate (MPA) is the first-line medication for inducing withdrawal bleeding in patients with PCOS and oligomenorrhea, with a recommended dosage of 5-10 mg daily for 12-14 days every 1-3 months. 1
Mechanism of Action and Efficacy
Medroxyprogesterone acetate works by transforming proliferative endometrium into secretory endometrium when administered to women with adequate endogenous estrogen. It also inhibits pituitary gonadotropin secretion, which prevents follicular maturation and ovulation 2. Key benefits include:
- Induces withdrawal bleeding in 93% of women with oligomenorrhea or amenorrhea 3
- Provides endometrial protection by inducing secretory transformation of the endometrium 1
- Reduces the risk of endometrial hyperplasia 1, 4
Dosing Recommendations
- Standard dosing: 5-10 mg daily for 12-14 days every 1-3 months 1
- For endometrial hyperplasia: Depo-Provera (injectable form) can be administered once every 3 months 4
- Frequency considerations:
- Every 3 months for patients with very infrequent periods
- Monthly administration for patients desiring more regular cycles 1
Clinical Considerations
Endometrial Assessment
- Endometrial thickness measured by transvaginal ultrasound correlates significantly with bleeding response 3
- Withdrawal bleeding typically occurs within 3-7 days after discontinuing progestin therapy 1
Hormonal Effects
- MPA suppresses serum testosterone, androstenedione, and luteinizing hormone (LH) levels in women with PCOS 5, 6
- These hormone levels return to pre-treatment levels within a few weeks after discontinuation 5
- Progestogen treatment can mask the biochemical findings of PCOS, so diagnostic hormonal analyses should be obtained without prior progestogen treatment 6
Alternative Options
If MPA is not suitable, consider:
Micronized progesterone: 200 mg daily for 12-14 days every 1-3 months 1
- Associated with lower risk of cardiovascular disease and venous thromboembolism
- Preferred for patients with high cardiovascular risk factors
Dydrogesterone: 10 mg twice daily for 5 days 3
- Similar efficacy to MPA in inducing withdrawal bleeding (93%)
- May have different side effect profile
Combined oral contraceptives (COCs): First-line if contraception is also needed 1
- Provides multiple therapeutic benefits beyond contraception
- Regulates menstrual cycles and improves hyperandrogenism symptoms
Monitoring and Follow-up
- Assess endometrial thickness periodically by transvaginal ultrasound 1
- Persistent abnormal bleeding despite therapy warrants endometrial sampling 1
- Cyclic progestin therapy should be continued until menopause or desire for pregnancy 1
Cautions and Contraindications
- Not recommended for secondary amenorrhea or dysfunctional uterine bleeding due to its prolonged action and difficulty in predicting withdrawal bleeding time 2
- For these conditions, oral therapy is recommended instead of injectable forms 2
- When planning ovulation induction with clomiphene citrate, be aware that MPA-induced withdrawal bleeding may delay time to ovulation by approximately 15 days 7
MPA remains a cornerstone therapy for managing menstrual irregularities in PCOS and oligomenorrhea, with strong evidence supporting its efficacy for endometrial protection and inducing withdrawal bleeding.