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

Learn More – Primary Sources:

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

Related ObG Topics:

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