Does Prometrium (progesterone) induce withdrawal bleeding in amenorrhea?

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Prometrium (Progesterone) for Inducing Withdrawal Bleeding in Amenorrhea

Yes, Prometrium (micronized progesterone) can effectively induce withdrawal bleeding in women with amenorrhea who have adequate estrogen levels, with clinical studies showing 73.8-80% of women experiencing withdrawal bleeding within 7 days after a 10-day course of treatment. 1

Mechanism and Efficacy

Prometrium works by causing endometrial secretory transformation and subsequent shedding when withdrawn. According to FDA-approved clinical data:

  • In premenopausal women with secondary amenorrhea for at least 90 days, 80% experienced withdrawal bleeding within 7 days after completing a 10-day course of Prometrium 300 mg daily 1
  • In another multicenter study, 73.8% and 76.8% of women with secondary amenorrhea experienced withdrawal bleeding after 10 days of Prometrium at 300 mg or 400 mg daily, respectively 1

Dosing Recommendations

For inducing withdrawal bleeding in amenorrhea:

  • Prometrium 300-400 mg daily for 10 days 1
  • After completing the progesterone course, withdrawal bleeding typically occurs within 7 days

Clinical Context and Considerations

When to Use Prometrium for Amenorrhea

  • In women with normal estrogen levels but absent menses
  • When endometrial protection is needed due to unopposed estrogen
  • For diagnostic purposes to assess estrogen status (bleeding response indicates adequate estrogen levels)

Contraindications and Cautions

  • Pregnancy should be ruled out before initiating therapy 2
  • Not effective in women with hypoestrogenic states (will not induce bleeding if estrogen is inadequate)
  • Common side effects include fatigue (8%), headache (16%), dizziness (24%), and abdominal pain/cramping (20%) 1

Alternative Options

For comparison, other progestins can also induce withdrawal bleeding:

  • Dydrogesterone has shown efficacy with 65.4% of women experiencing withdrawal bleeding versus 30.8% with placebo 3
  • Medroxyprogesterone acetate (MPA) 10 mg daily for 12-14 days can be used as an alternative 4

Long-Term Management Considerations

For women requiring ongoing management of amenorrhea:

  • Cyclic regimen: Prometrium 200 mg daily for 12-14 days every 28 days (with estrogen if needed) 4
  • For those preferring amenorrhea: Continuous low-dose progesterone regimens can be used 5, 6

Monitoring

  • Assess for withdrawal bleeding within 7 days after completing progesterone course
  • If no bleeding occurs, consider evaluation for hypoestrogenism or structural abnormalities
  • Regular follow-up to assess response and adjust treatment as needed

Prometrium offers the advantage of being bioidentical to endogenous progesterone with potentially fewer metabolic side effects compared to synthetic progestins, making it a suitable option for inducing withdrawal bleeding in women with amenorrhea who have adequate estrogen levels.

References

Guideline

Evaluation and Management of Irregular Menstruation

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Cyclical dydrogesterone in secondary amenorrhea: results of a double-blind, placebo-controlled, randomized study.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2007

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[A "no-bleeding" substitute hormone treatment with an oral microdose progesterone. A prospective multicenter study].

Journal de gynecologie, obstetrique et biologie de la reproduction, 1994

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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