Does Estrace (estradiol) cream contain estrogen and progesterone?

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Last updated: December 10, 2025View editorial policy

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Estrace Cream Composition

No, Estrace cream contains only estrogen (estradiol), not progesterone. This is a common point of confusion that requires clarification for safe prescribing.

What Estrace Cream Contains

  • Estrace cream is a vaginal estrogen preparation containing only estradiol (17β-estradiol), with no progesterone component 1
  • The cream delivers estrogen that is rapidly and efficiently absorbed into the systemic circulation through the vaginal mucosa 1
  • Vaginal estrogen preparations like Estrace result in sustained high estrogen levels systemically, not just local effects 1

Clinical Implications of Estrogen-Only Formulation

When Progesterone Must Be Added

  • Women with an intact uterus who use systemic estrogen (including vaginally absorbed estrogen) require progestogen therapy to prevent endometrial hyperplasia and cancer 2
  • Estrogen-only therapy should only be prescribed to hysterectomized women, as there is no therapeutic advantage in prescribing progestins to women without a uterus 2
  • Sequential regimens typically require 200 mg of oral or vaginal micronized progesterone for 12-14 days every 28 days when using estradiol 2

Systemic Absorption Concerns

  • Vaginal estrogen creams produce significant systemic absorption, making them dangerous when estrogen is contraindicated 1
  • Women with cardiovascular risk factors, high thromboembolism risk, or conditions like cyanotic heart disease should avoid estrogen-containing preparations entirely 3
  • Two cases of endometrial proliferation have been documented with vaginal estrogen use, highlighting the need for progestogen protection in non-hysterectomized women 4

Common Prescribing Pitfall

  • The most critical error is prescribing Estrace cream alone to women with an intact uterus without adding systemic progestogen protection 2
  • While vaginal estrogens were historically considered "local only," evidence clearly demonstrates sustained systemic estrogen levels that require endometrial protection 1
  • If using vaginal estradiol in women taking aromatase inhibitors (such as breast cancer patients), estriol-containing preparations may be preferable as they cannot convert to estradiol 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Contraindications and Precautions for Estrogen-Containing Contraceptives

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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