What is the purpose and findings of the Stop-Hormone Replacement Therapy (HRT) trial in postmenopausal women?

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Last updated: January 29, 2026View editorial policy

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The Stop-HER Trial: A Clarification

There is no trial called "Stop-HER" in the medical literature. You may be confusing this with the HERS (Heart and Estrogen/progestin Replacement Study) trial, which was a landmark study examining hormone replacement therapy in postmenopausal women with established coronary heart disease 1.

The HERS Trial: What You're Likely Asking About

HERS was designed to test whether combined estrogen-progestin therapy (conjugated equine estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day) would reduce cardiovascular events in postmenopausal women with pre-existing coronary heart disease 1.

Key Findings from HERS

Primary Outcome: No Cardiovascular Benefit

  • After 4.1 years of follow-up, there was no difference in the combined primary outcome of nonfatal myocardial infarction and coronary death between hormone therapy and placebo groups 1.
  • The overall null effect contradicted earlier observational studies that suggested cardiovascular protection from HRT 1.

Temporal Pattern of Risk

  • A post-hoc analysis revealed a 52% increase in cardiovascular events in the first year of HRT compared to placebo (42.5 vs 28.0 per 1000 person-years) 1.
  • In later years, there was a nonsignificant trend toward fewer events in the treatment arm (23.0 vs 34.4 per 1000 person-years), suggesting possible early harm followed by late benefit 1.

Secondary Outcomes

  • No reduction in fractures: Total fracture relative hazard was 1.04 (95% CI, 0.87 to 1.25) 1.
  • Breast cancer increase: Comparable increases in breast cancer incidence were observed (RH 1.27,95% CI 0.84 to 1.94) over 6.8 years 1.
  • Colorectal cancer reduction: Reduced incidence of colon cancer (RH 0.8,95% CI 0.46 to 1.45) 1.

Clinical Implications from HERS

HRT should NOT be used for secondary prevention of cardiovascular disease in women with established coronary heart disease 1. The data suggest no overall cardiovascular benefit and a possible early increased risk when HRT is initiated in women with documented atherosclerosis 1.

Limitations and Context

Several factors limit interpretation of HERS results 1:

  • Relatively short duration of treatment (4.1 years average)
  • Nonadherence issues (more women discontinued HRT than placebo, but analysis was by intention-to-treat)
  • Results may not generalize to different HRT formulations
  • Average participant age was 66.7 years—potentially too old to benefit from therapy
  • The specific preparation (CEE/MPA) may not represent all HRT regimens

The HERS II Follow-Up

HERS II was an unblinded follow-up study that continued to show no reduction in hip, wrist, vertebral, or total fractures with hormone therapy (relative hazard for total fractures 1.04,95% CI 0.87 to 1.25) 1.

Common Pitfall

Do not confuse secondary prevention (HERS population with existing heart disease) with primary prevention or symptom management in healthy postmenopausal women 1. The risk-benefit profile differs substantially based on baseline cardiovascular status and timing of HRT initiation relative to menopause 2, 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Hormone Replacement Therapy Initiation and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Estrogen Replacement Therapy in Postmenopausal Women

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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