Objective Limited data exist on the association between menopause and atrial fibrillation (AF). We sought to examine the relationship between menopausal age, postmenopausal hormone therapy (PHT) use and incident AF.
Methods The Women’s Health Study (WHS) enrolled 39 876 female health professionals between 1992 and 1995. We prospectively examined 30 034 women in WHS using Cox proportional-hazard models. Participants were free of cardiovascular disease and AF at baseline and had not undergone hysterectomy without bilateral oophorectomy prior to menopause. Incident AF was confirmed by medical record review.
Results At baseline, median age was 53 years (IQR 49–60), median menopausal age was 50 years (IQR 46–52) and 14 415 (48.0%) had prior PHT use. Over a median follow-up of 20.5 years, 1350 AF events occurred. In multivariable analysis, relative hazards for AF were lower among women with younger age at menopause but did not differ significantly from women with the oldest menopausal age (<45: HR 0.82, 95% CI 0.67 to 1.02; 45–49: HR 0.90, 95% CI 0.74 to 1.08; 50–54: HR 0.89, 95% CI 0.75 to 1.06; >54 years: referent). Use of oestrogen-alone PHT, but not oestrogen and progesterone, was independently associated with AF risk (HR 1.22; 95% CI 1.02 to 1.45 vs HR 1.04; 95% CI 0.86 to 1.26). This relationship was not attenuated by intermediary cardiovascular events.
Conclusions In this large prospective study, menopausal age was not significantly related to incident AF, while use of oestrogen monotherapy was associated with increased AF risk. Our findings suggest a pathophysiological link between unopposed oestrogen exposure and AF in women.
Clinical trial registration NCT000000479; Post-results.
- Atrial fibrillation
- Menopausal Age
- Post-menopausal Hormone Therapy
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Contributors JAW is the first and corresponding author. He was involved in study design and conception, data analysis and interpretation, drafting and revising of the manuscript, and final approval. He is the guarantor. CMA is the senior author and was involved in study design and conception, data analysis and interpretation, manuscript revision and final approval. KMR and DC were involved in study design, data interpretation, manuscript revision and final approval. RKS was involved in data interpretation, manuscript revision and final approval. MVM was involved in data analysis, manuscript revision and final approval.
Funding This study was supported by grant HL-093613 from the NHLBI to CMA. The WHS was supported by grants HL-043851, HL-080467 and HL-099355 from the NHLBI and grant CA-047988 from the National Cancer Institute. JAW is supported by a Canadian Institutes of Health Research Fellowship award and the Arthur J.E. Child Cardiology Fellowship. DC was supported by a grant of the Swiss National Science Foundation (PP00P3_133681 and PP00P3_159322).
Competing interests None declared.
Ethics approval Brigham and Women’s Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.