Abstract
Vitamin D status has been inconsistently associated with ovarian reserve and menopause. We used data from the Sister Study cohort to examine the associations of vitamin D supplement use, total 25-hydroxyvitamin D (25OHD) level, and calcium supplement use with the timing of natural menopause. Vitamin D and calcium supplement use were assessed on a questionnaire at baseline (mean age: 46) and two follow-up time points, and characterized in multiple ways based on type, dose, and duration of use. Serum samples from a random subset of participants were analyzed for total 25OHD (25OHD(3) + 25OHD(2) + epi-25OHD(3)) using liquid chromatography-mass spectrometry. Menopause was assessed at each yearly follow-up with the question "Have you had a menstrual period in the past 12 months?"; if the response was "no", age at last menstrual period was recorded. We censored women at time of hysterectomy or medically induced menopause, death, loss to follow-up or October 2020. We used multivariable Cox proportional hazard models with age as the time scale to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs), adjusting for race/ethnicity, education, body mass index, alcohol use, smoking status, and physical activity. Among the 13,102 eligible premenopausal participants, 8897 experienced natural menopause during follow-up. Concomitant use of a multivitamin and a vitamin D supplement was associated with slightly earlier menopause (HR(CI): 1.10 (0.98, 1.24)). None of the remaining vitamin D or calcium supplement variables (alone or in combination) were meaningfully associated with timing of natural menopause. In a subsample with 25OHD measurements (n = 906), neither total 25OHD nor 25OHD(3) was associated with timing of menopause. Our study includes, on average, 6 years of follow-up from an average age of 46 years and did not find associations between vitamin D or calcium supplement use and timing of menopause. Future studies should focus on a life course approach to this question and include 25OHD measures from early mid-life when examining menopause timing.