Menopausal transition and cardiovascular risk factor trajectories: a Japanese annual health checkup cohort

Background The menopausal transition is associated with adverse shifts in cardiometabolic risk factors and increased cardiovascular disease (CVD) risk in women. However, the timing and magnitude of changes in cardiovascular risk factors across the menopausal transition remain unclear. Therefore, we aim to characterize longitudinal changes in cardiovascular risk factors across the menopausal transition using serial measurements collected over two decades in midlife women. Methods This longitudinal cohort study (2004–2024) used data from an annual health checkup program including women who experienced menopause during follow-up. Women with unknown menopause timing, hormone therapy use, or surgical menopause were excluded. Menopause status was self-reported via standardized questionnaires at each visit. Transition stages were categorized as premenopause (>5 years before menopause), perimenopause (0–5 years before), and postmenopause (≥0 years after). The primary outcomes were cardiovascular risk factors (systolic and diastolic blood pressure [SBP and DBP], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides, and hemoglobin A1c [HbA1c]), and the predicted 30-year CVD risk using PREVENT equations, assessed at each visit. Longitudinal changes were evaluated using adjusted interrupted time-series analyses. Results 8,172 women (93,545 visits; median follow-up, 14 years; median age at menopause, 52 years) were included in this analysis. During perimenopause, mean SBP showed an additional annual increase of 0.55 mmHg/year (95%CI, 0.46–0.64) beyond the premenopausal slope of 0.46 mmHg/year (95%CI, 0.41–0.51), resulting in an increase from 112.3 mmHg to 116.8 mmHg over the 5-year perimenopausal period (Figure and Table). DBP followed a similar pattern. LDL-C also demonstrated accelerated worsening during perimenopause (premenopausal slope: 0.76 mg/dL/year [95%CI 0.68–0.85]; additional perimenopausal slope change: 2.69 mg/dL/year [95%CI 2.54–2.83]) and increased from 109.5 mg/dL to 124.1 mg/dL over this period. HDL-C and triglycerides showed parallel trajectories. Mean HbA1c increased from 5.4% to 5.6%, with the slope doubling during perimenopause (premenopausal slope: 0.02%/year [95%CI 0.02–0.02]; additional perimenopausal slope change: 0.02%/year [95%CI 0.02–0.02]). The predicted total 30-year CVD risk showed an accelerated increase across menopausal transition, changing from 9.8% to 14.7% during perimenopause. Conclusion Accelerated worsening of multiple cardiovascular risk factors was observed beginning approximately five years before menopause, indicating that the menopausal transition is a clinically actionable window for cardiometabolic monitoring and preventive interventions in midlife women.