It's About Time: Hormone Therapy and Subclinical Atherosclerosis

March 30, 2016

It's About Time: Hormone Therapy and Subclinical Atherosclerosis

  1. Andrew M. Kaunitz, MD and
  2. JoAnn Manson, MD, DrPH

ELITE trial results provide support for the estrogen timing hypothesis.

  1. Andrew M. Kaunitz, MD and
  2. JoAnn Manson, MD, DrPH

Abundant data support the timing hypothesis, which proposes that hormone therapy (HT) slows atherosclerosis progression in recently menopausal women but has neutral or adverse effects in women who are at least a decade past menopause onset. To directly test this hypothesis, investigators for the ELITE trial randomized healthy women (<6 years or ≥10 years past menopause) without cardiovascular disease (CVD) to oral estradiol (1 mg daily) or placebo. Women with a uterus also received vaginal progesterone or placebo gel. Carotid-artery intima-media thickness (CIMT) was assessed at baseline and every 6 months. Coronary artery atherosclerosis was evaluated at study completion using computed tomography (CT). An earlier report (NEJM JW Womens Health Jul 2015 and Menopause 2015; 22:391) showed that baseline CIMT correlated well with CVD risk factors.

Among 643 participants, median age at enrollment and years since menopause were 55.4 and 3.5, respectively (early-postmenopause group), and 63.0 and 14.1 (late-postmenopause group). After a median 5 years of study medications, among the younger women, the estradiol group had less progression of CIMT than the placebo group (P=0.008). In contrast, in the older women, CIMT progression rates were similar in the HT and placebo groups (P=0.29). The strength of this relation between HT and CIMT progression differed significantly in the younger versus older groups (P=0.007). Coronary artery CT parameters did not differ significantly between the placebo and HT groups regardless of age.


Editorialists conclude that, although estrogen had a favorable effect on atherosclerosis in early menopause, recommending HT for preventing cardiovascular events would be premature. We agree, while noting that use of HT for management of menopausal symptoms has plummeted since the initial Women's Health Initiative findings in 2002, even among symptomatic women in early menopause (N Engl J Med 2016; 374:803). Our take-away message is that this important new clinical trial provides additional reassurance about the cardiovascular safety of HT when initiated by recently menopausal women for bothersome vasomotor symptoms.

Dr. Manson is Chief, Division of Preventive Medicine, Brigham and Women's Hospital, and Professor of Medicine and the Michael and Lee Bell Professor of Women's Health, Harvard Medical School.

Editor Disclosures at Time of Publication

  • Disclosures for Andrew M. Kaunitz, MD at time of publication Consultant / Advisory board Actavis plc; Bayer AG; Merck Royalties UpToDate Grant / Research support Therapeutics MD; Bayer; Agile; NIH Editorial boards Contraception; Menopause; Contraceptive Technology Update; OBG Management; Medscape OB/GYN & Women’s Health Leadership positions in professional societies North American Menopause Society (Treasurer)


Reader Comments (1)

SANDEEP BANSAL , MD Physician, Cardiology, Safdarjung Hospital , New Delhi

This study is in an area which has been 'see sawing' over last few decades. First it was said that HRT was good for postmenopausal women, then it was deemed as increasing mortality to the extent that it was proscribed by most international bodies . Then came a period when it was felt that it was harmful in first few years ( ~ 3years) and then was harmless . The present study provides another ' time frame' (<6 years or ≥10 years past menopause) . The major drawback appears to be using CIMT as a marker . Ii is known that CIMT has its own short comings as a marker for CV events . So it seems that rather than jumping to conclusions , one needs to take this study with a pinch of salt .

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