Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause

Harvard University, Cambridge, Massachusetts, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 05/2007; 297(13):1465-77. DOI: 10.1001/jama.297.13.1465
Source: PubMed


The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.
To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.
Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998.
Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials.
In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [corrected] cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years; for women 10 to 19 years since menopause began, 4 per 10,000 person-years; and for women 20 or more years from menopause onset, 17 per 10,000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was -2 per 10,000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and -1 per 10,000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10,000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06).
Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms. Identifier: NCT00000611.

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    • "This variation in the reported prevalence can be attributed to different factors. Hot flushes resolve within few years of menopause in most of women, but some women report symptoms for many years after they cease to menstruate [32] [33]. Menopausal status and symptoms vary across racial/ethnic groups [34] [35]. "

    Clin. Exp. Obstet. Gynecol. - Zakia Mahdy Abolill - Stats. Available from: [accessed Mar 21, 2015].; 02/2015
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    • "This variation in the reported prevalence can be attributed to different factors. Hot flushes resolve within few years of menopause in most of women, but some women report symptoms for many years after they cease to menstruate [32] [33]. Menopausal status and symptoms vary across racial/ethnic groups [34] [35]. "
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    ABSTRACT: Summary Objective: To assess the prevalence of menopausal-related symptoms and to evaluate their impact on quality of life (QoL) among a sample of menopausal women from Egypt. Materials and Methods: A cross-sectional hospital-based study conducted at the Gynecology department, Suez Canal University, Ismailia – Egypt. A total 1,214 women aged 40 – 70 years were recruited and studied using an interview questionnaire. The questionnaire contains four main items: socio-demographic data, menstruation status assessment, modified Menopausal Rating Scale (MRS), and World Health Organization Quality of Life (WHOQOL-BREF) questionnaire. Results: Mean age was 48.1 ± 10.3 years, with 26.6% of the studied participants were illiterates. According to menstruation status, 40.9% of the studied women were postmenopausal, 41.4% were premenopausal, while 17.7% were perimenopausal. Most of the studied participants have mild/moderate somatic symptoms. Mild/moderate depressive mode, irritability, and anxiety have been reported in 63%, 58.4%, and 58.2% of women, respectively. Postmenopausal women have significantly higher scores on MRS except for urogenital score that was higher in perimenopausal women. They also had significantly lower QoL score in all subscales of WHOQOL-BREF except for psychological domain that was lowest among perimenopausal women. MRS total score has significant negative correlation to all domains of WHOQOL questionnaire. Conclusion: Postmenopausal women have higher prevalence of menopausal symptoms that significantly affect their quality of life more than pre- and perimenopausal women. Those in the transition period (perimenopausal) have higher prevalence of psychological symptoms with higher impact on their psychological welfare. Key words: Menopause; Menopause Rating Scale; WHOQOL-BREF; Quality of life.
    Clin. Exp. Obstet. Gynecol. - ISSN: 0390-6663 XLII, n. 2, 2015 doi: 10.12891/ceog1828.2015; 02/2015
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    • "Hormonal replacement therapy is not a recommended method for coronary heart disease (CHD) prevention. Nevertheless, hormonal replacement therapy prescription at early perimenopause and at intact coronary arteries is believed to decelerate formation of atherosclerotic lesions and to result in decreased mortality from cardiovascular diseases [1, 2]. Thus, the experts of International Menopause Society remark that hormonal replacement therapy prescription to patients aged fewer than 60 and being at their early postmenopause is safe and promotes decrease of mortality due to CHD [3]. "
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    ABSTRACT: Background The goal of the study was to assess the state of coronary arteries in perimenopausal women undergoing examination before prescription of hormonal replacement therapy. Methods One hundred ninety-three patients were screened, and 43 of them were selected for inclusion to the study. Pretest probability of coronary heart disease (CHD) was 47% for patients with typical angina pain and 20.5% with atypical pain. Patients with typical and atypical pain syndromes had no essential differences in terms of age, but had different hormonal status assessed by follicle stimulating hormone level and different menopause durations. Results Atherosclerotic lesion causing luminal occlusion by more than 50% was detected in 13 (61.9%) patients with typical pain syndrome and in eight (36.4%) patients with atypical pain syndrome manifestations. Numbers of patients with intact coronary arteries were six (28.6%) and 10 (45.5%) in groups with typical and atypical pain syndrome, respectively. Myocardial bridges were found in five (23.8%) patients with typical pain syndrome and seven (31.8%) patients with atypical manifestations. Conclusion In spite of modest pretest CHD probability in the group with typical pain syndrome and low pretest CHD probability in the group with atypical manifestations, patients with major atherosclerotic lesions were detected in both groups. Use of this approach to assessment of the state of coronary arteries allows detecting patients at high risk of cardiovascular complications and avoiding the use of hormonal replacement therapy in them.
    Journal of Clinical Medicine Research 12/2014; 6(6):451-5. DOI:10.14740/jocmr1915w
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