FINDINGS:

Using a single-center, randomized, double-blind, placebo-controlled trial (RCT), the authors randomized one group of women to receive oral 17ß-estradiol (1 mg/day) while the other group received placebo. Women in the estrogen group who had a uterus also received progesterone (45 mg).  The primary outcome measure was rate of change of intima-media wall thickness of the common carotid artery (CIMT)  to assess atherosclerosis progress.  Women were stratified into 2 groups – those who were < 6 years since menopause (early postmenopause) and those > 10 years since menopause (late postmenopause).

After a median of 5 years, in women receiving estrogen the following outcomes were observed:

• In the early postmenopause group, rate of carotid artery atherosclerosis progression was significantly lower (P=0.007)
• In the late postmenopause group, there was no difference in atherosclerosis progression
• Progesterone did not alter this effect
• No difference was found in coronary artery atherosclerosis with estrogen use using CT angiography
• There was no difference in adverse events such as breast cancer or myocardial infarction – although these were not primary outcome measures

SYNOPSIS:

There have been conflicting studies regarding cardiovascular benefits  with the use of estrogen and progesterone following menopause.  One hypothesis suggested that this is a reflection of timing – if greater than 10 years after menopause, the vasculature and hormone receptors may no longer be sufficiently functional to result in any benefit.  The authors in this study (NEJM, 2016), used a well designed trial to show that hormone replacement therapy may be beneficial in protecting against cardiovascular disease

KEY POINTS:

• Oral estradiol therapy is associated with decreased progression to atherosclerosis (using carotid artery measurements) but only if therapy is started within 6 years of menopause
• The differing response based on time from menopause may explain the conflicting results in multiple studies
• The study was not designed to assess the effects of estrogen on new coronary artery lesions
• ACOG recommends against using hormone therapy to prevent coronary heart disease but can be considered for use in women in early menopause who are in good cardiovascular health and at low risk for adverse events to relieve menopausal symptoms.

Learn More – Primary Sources:

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

ACOG Committee Opinion 565: Hormone Therapy and Heart Disease

Related ObG Topics:

Levels of Evidence – How to Rate the Quality of a Study