Postmenopausal Hormone Use and Secondary Prevention of Coronary Events in the Nurses’ Health Study. A Prospective, Observational Study - Nurses Health Study HRT Substudy


Postmenopausal Hormone Use and Secondary Prevention of Coronary Events in the Nurses’ Health Study. A Prospective, Observational Study.


This study examined the relationship between HRT and major coronary events in nurses with established CHD participating in the Nurses’ Health Study (NHS).

Study Design

Study Design:

Patients Enrolled: 2489

Drug/Procedures Used:

A total of 2489 postmenopausal women with self-reported CHD defined as previous MI or documented coronary disease entered into the NHS observational cohort from 1976 to 1996 and were followed for a total of 17,239 person years. Second coronary events (CVE), death and MI were documented by review of medical records in the majority.

Principal Findings:

There were 138 nonfatal MIs and 75 coronary deaths. In women younger than 60 years without HRT, the recurrent event rate was 139/10,000 person years and 60 to 75 years 169/10,000. 38.6% of women were never users, 32.4% post users and 32.4% current users of HRT. Of HRT users, 53% used oral conjugated estrogen, 19% in combination with a progestin and 28% other. The age- and other risk-factor–adjusted relative risk for recurrent CVE was 0.65 among current vs. never users of HRT. There was a 25% increase in risk for recurrent CVEs among women using HRT for less than 1 year compared to never; however, longer term HRT was associated with 72% reduction in CVE compared to never users. There was a trend to decreasing risk for CVE with increasing duration (p for trend = 0.002). There was no significant difference in CVE in women who began HRT during the year after the first event compared to previous users. The risk for recurrent major coronary events seems to increase among short-term hormone users with previous coronary disease but to decrease with longer term use.


The increased risk for major events associated with HRT during the initial year after a coronary event, including death, MI and pulmonary emboli, has been documented in both a randomized placebo-controlled trial (HERS) and this large cohort study. Hypercoagulability and a pro-inflammatory destabilization of vulnerable plaque are two proposed mechanisms for the early increased event rate attributable to estrogens. While HRT should be discontinued following the initial coronary event and not be started after, there is reasonable support for continuing HRT in women with CHD who have taken it safely for at least 1 year.


1. Grodstein F, Manson JE, Stampher MJ. Ann Intern Med 2001;1351:1-8.

Keywords: Progestins, Secondary Prevention, Thrombophilia, Estrogens, Conjugated (USP), Coronary Disease, Risk Factors, Hormone Replacement Therapy, Medical Records

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