What oral progestin dosing should be used to induce a withdrawal bleed in a woman on a progestin‑only contraceptive?

Progestin Dosing to Induce Withdrawal Bleeding in Women on Progestin-Only Contraceptives

For a woman on progestin-only contraception who needs a withdrawal bleed, administer oral micronized progesterone 300 mg daily for 10 days, which induces withdrawal bleeding in 90% of cases. 1

Evidence-Based Dosing Regimen

Primary Recommendation: Oral Micronized Progesterone

• Oral micronized progesterone 300 mg daily for 10 days is the most effective regimen, producing withdrawal bleeding in 90% of women with amenorrhea or oligomenorrhea 1
• The 200 mg daily dose is less effective, inducing bleeding in only 58% of women compared to 29% with placebo 1
• Side effects occur at similar rates across all dosing groups, making the higher 300 mg dose preferable for efficacy without additional adverse effects 1

Alternative Progestin Options

If oral micronized progesterone is unavailable, use these sequential regimens:

• Medroxyprogesterone acetate 10 mg daily for 12-14 days provides proven endometrial stimulation and withdrawal bleeding 2, 3
• Dydrogesterone 10 mg daily for 12-14 days is an alternative endorsed by ESHRE for inducing withdrawal bleeding 2
• Norethindrone acetate 5 mg daily for 12-14 days offers superior cardiovascular safety compared to medroxyprogesterone acetate while maintaining efficacy 3

Clinical Context and Mechanism

Why This Works

• Progestin-only contraceptives (pills, DMPA, implants, IUDs) commonly cause amenorrhea or irregular bleeding through endometrial suppression 4
• A 10-14 day course of progestin at withdrawal-inducing doses stimulates endometrial organization, followed by coordinated shedding when stopped 2
• The 12-14 day duration mimics the luteal phase and is critical for adequate endometrial preparation 2

Predictive Factors

• Baseline endogenous estradiol levels and achieved progesterone concentrations have limited predictive value for bleeding response—the 300 mg dose works regardless of these factors 1
• Women with higher endogenous estrogen are more likely to bleed, but the 300 mg dose overcomes most variability 1

Important Clinical Caveats

Common Pitfalls to Avoid

• Do not use shorter durations than 10 days—inadequate endometrial preparation reduces bleeding likelihood 2
• Do not expect bleeding timing to predict endometrial health—withdrawal bleeding onset does not correlate with endometrial histology or hyperplasia risk 5
• Avoid continuous progestin regimens if withdrawal bleeding is the goal—these induce amenorrhea rather than predictable bleeding 2

Managing Expectations

• Withdrawal bleeding typically begins around day 13 after starting progestin (approximately 3 days after completing the 10-day course) 5
• Approximately 10% of women will not bleed even with the 300 mg dose—this does not necessarily indicate pathology 1
• Bleeding irregularities are the most common reason for dissatisfaction and discontinuation of progestin-only contraceptives 4, 6

Practical Implementation

Administration Protocol

1. Prescribe oral micronized progesterone 300 mg once daily at bedtime for 10 consecutive days (bedtime dosing minimizes sedation side effects) 1
2. Expect withdrawal bleeding 2-5 days after completing the 10-day course 5
3. If no bleeding occurs within 7 days of completing treatment, consider repeating the course or investigating other causes of amenorrhea 1

When to Use Alternative Progestins

• If oral micronized progesterone causes intolerable sedation or is unavailable, switch to medroxyprogesterone acetate 10 mg daily for 12-14 days 2, 3
• For patients with cardiovascular risk factors, prefer norethindrone acetate 5 mg daily for 12-14 days over medroxyprogesterone acetate 3

Contraindications

• Active liver disease contraindicates all oral progestins 2
• History of breast cancer or hormone-sensitive malignancies requires careful risk-benefit assessment 2
• Antiphospholipid syndrome is an absolute contraindication to oral micronized progesterone 2