The association of age at menopause and all-cause and cause-specific mortality by race, postmenopausal hormone use, and smoking status

Angela M Malek; Catherine J Vladutiu; Michelle L Meyer; Mary Cushman; Roger Newman; Lynda D Lisabeth; Dawn Kleindorfer; Sindhu Lakkur; Virginia J Howard

doi:10.1016/j.pmedr.2019.100955

The association of age at menopause and all-cause and cause-specific mortality by race, postmenopausal hormone use, and smoking status

Prev Med Rep. 2019 Jul 14:15:100955. doi: 10.1016/j.pmedr.2019.100955. eCollection 2019 Sep.

Authors

Angela M Malek¹, Catherine J Vladutiu², Michelle L Meyer³, Mary Cushman^{4

5}, Roger Newman⁶, Lynda D Lisabeth^{7

8}, Dawn Kleindorfer⁹, Sindhu Lakkur¹⁰, Virginia J Howard¹¹

Affiliations

¹ Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
² Department of Obstetrics & Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Med-Hematology Oncology, University of Vermont, Burlington, VT, USA.
⁵ Department of Pathology & Laboratory Medicine, University of Vermont, Burlington, VT, USA.
⁶ Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA.
⁷ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
⁸ Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
⁹ Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
¹⁰ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
¹¹ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.

Abstract

While a mean age at menopause of 51 years has been reported in the United States (U.S.), some U.S. women experience menopause before age 45, possibly increasing risk of cardiovascular mortality; however, the role in all-cause and cerebrovascular-related mortality is unclear. The purpose of this study was to investigate the association between age at menopause and all-cause and cause-specific mortality by race, hormone replacement therapy (HRT) use, and smoking status. REasons for Geographic and Racial Differences in Stroke (REGARDS) is a population-based study of 30,239 participants aged ≥45 years enrolled between 2003 and 2007 of whom 14,361 were postmenopausal women. Age at menopause was defined as <45 (early) or ≥45. All-cause and cause-specific mortality were ascertained through 2013. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between age at menopause and mortality, adjusting for baseline measures. Of 11,287 eligible women (6403 white; 4884 black), mean menopause age was 45.2 (SD 7.9) with 1524 deaths over 7.1 years. Significant interactions were detected between early age at menopause (39%) and HRT use in association with all-cause mortality (p < 0.01), mortality from coronary heart disease (p = 0.06), and mortality from all other causes (p = 0.04). An association between early age at menopause and all-cause mortality was observed among ever-HRT users (HR = 1.31, 95% CI: 1.10-1.56), but not never-HRT users (HR = 1.01, 95% CI: 0.85-1.20). There were no differences in associations examined by race or smoking status. Increased all-cause mortality risk was observed for ever-HRT users with menopause before age 45.

Keywords: Age; BMI, body mass index; BWHS, Black Women's Health Study; CHD, coronary heart disease; CI, confidence interval; CVD, cardiovascular disease; Coronary heart disease; ECG, electrocardiogram; FDA, Food and Drug Administration; HR, hazard ratio; HRT, hormone replacement therapy; MI, myocardial infarction; MRR, mortality rate ratio; Menopause; Mortality; NAMS, North American Menopause Society; NDI, National Death Index; REGARDS; REGARDS, REasons for Geographic and Racial Differences in Stroke; RR, relative risk; Race; SD, standard deviation; Smoking; U.S., United States; Women.

Grants and funding

K01 HL138273/HL/NHLBI NIH HHS/United States