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Effects of hormone therapy on quality of life in postmenopausal women with CAD differed according to menopausal symptoms


ACP J Club. 2002 Nov-Dec;137:105. doi:10.7326/ACPJC-2002-137-3-105

Source Citation

Hlatky MA, Boothroyd D, Vittinghoff E, et al. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA. 2002 Feb 6;287:591-7. [PubMed ID: 11829697] (All 2002 articles were reviewed for relevancy, and abstracts were last revised in 2008.)



Does hormone therapy (HT) improve health-related quality of life (HRQL) in postmenopausal women with coronary artery disease (CAD)?


Randomized {allocation concealed*}†, blinded {patients, clinicians, data collectors, and outcome assessors}‡*, placebo-controlled trial with follow-up to 3 years.


Outpatient and community settings at 20 U.S. clinical centers.


2763 postmenopausal women < 80 years of age (mean age 67 y) with documented CAD (previous myocardial infarction [MI], > 50% luminal narrowing of a major vessel on angiography, or previous coronary revascularization). Exclusion criteria were MI or revascularization in the past 6 months, previous hysterectomy, contraindications to HT, HT in the previous 3 months, or life-threatening illness. 2762 patients were included in the analysis; 2246 had HRQL data for all time points (baseline, 4 mo, 1 y, and 3 y).


1380 women were allocated to HT (0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate [Prempro, Wyeth Ayerst, Radnor, PA, USA]), and 1383 were allocated to placebo.

Main outcome measures

HRQL questionnaires assessing physical function (Duke Activity Status Index), energy/fatigue (E/F) (4-item RAND scale), mental health (RAND Mental Health Inventory), and depressive symptoms (8-item scale).

Main results

Analysis was by intention to treat. At 3 years, scores for physical function and E/F declined progressively in both groups. Women who received HT had faster reductions in physical function and a trend toward faster declines in E/F scores but had greater improvements in depressive symptoms than did women who received placebo (Table). The groups did not differ for mental health (Table).

Subgroup analysis based on presence of flushing at baseline showed that women with flushing (n = 434) who received HT had improved mental health and depressive symptoms over 3 years but did not differ from those who received placebo for physical function or E/F scores (Table). Women with no flushing (n = 2325) who received HT had greater declines in physical function and E/F scores but did not differ for mental health or depressive symptoms from those who received placebo.


In postmenopausal women with CAD, hormone therapy reduced physical function and energy/fatigue scores but improved depressive symptoms overall. Hormone therapy improved emotional quality of life in women with flushing, but reduced physical quality of life in women with no flushing.

*See Glossary.

†Hulley S, Grady D, Bush T, et al. JAMA. 1998;280:605-13.

‡Information provided by author.

Source of funding: Wyeth-Ayerst Research.

For correspondence: Dr. M.A. Hlatky, Stanford University, School of Medicine, Stanford, CA, USA. E-mail

Table. Hormone therapy vs placebo for postmenopausal women with coronary artery disease

Outcomes at 3 y Mean change in scores (hormone therapy vs placebo, P value)
All patients Patients with flushing Patients with no flushing
Physical function −4.4 vs −3.1§ −3.1 vs −2.2, P = 0.42 −4.2 vs −3.3, P = 0.04
Energy/fatigue −4.6 vs −3.0§ −2.3 vs −2.4, P = 0.99 −4.6 vs −3.1, P = 0.03
Mental health −0.2 vs −0.9§ 2.6 vs −0.5, P = 0.04 −0.06 vs −1.1, P = 0.40
Depressive symptoms No data available§ −0.5 vs 0.007, P = 0.1 −0.08 vs 0.06, P = 0.08

§P values not reported. Scales for physical function ranged from 0 (worst) to 58.2; energy/fatigue and mental health scores ranged from 0 (worst) to 100; and depression ranged from 4 (worst) to −8.2.


The study by Hlatky and colleagues is important because of its large sample size and the paucity of existing research on HRQL in postmenopausal women, especially as it pertains to HT. The results suggest that HT improves HRQL only for women with menopausal symptoms and does not generally benefit postmenopausal women with CAD. Presence or absence of hot flushing seemed to be the defining factor in improvement of depressive symptoms. Women with flushing who received HT also had lower HRQL scores at baseline. Physical illness, chest pain, and education level had an even greater negative effect on HRQL than did HT.

What factors need to be considered before applying these results to other patients? Participants apparently were not screened for smoking, which is known to interact with HT. Participants had a mean age of 67 years, whereas the detrimental effects of menopause are known to occur within the first few years after cessation of menses. Hlatky and colleagues noted that women with flushing who improved on HT tended to be much younger. Progesterone is sometimes said to be an “anti-estrogen,” so would similar results be obtained in a study of unopposed estrogen or of HT in women having surgical menopause? Some clinicians also claim that oral and transdermal therapies have different effects, in that transdermal estrogen does not give the full benefit of lowering cholesterol and may compromise the benefits of HT.

The findings of Hlatky and colleagues suggest that HT does not reverse preexisting CAD in postmenopausal women. The effects of HT in preventing CAD in younger, perimenopausal women are unknown. The findings also suggest that estrogen improves depressive symptoms in postmenopausal women, especially those with flushing. However, given recent findings showing an increased risk for cancer and heart disease for women on HT (1), the role of estrogen needs to be reassessed.

Joan Haynes, MD
Manatee Glenns
Bradenton, Florida, USA


1. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2002;288:321-33. [PubMed ID: 12117397]