Body Size and Ethnicity Are Associated With Menstrual Cycle Alterations in Women in the Early Menopausal Transition: The Study of Women???s Health Across the Nation (SWAN) Daily Hormone Study

Abstract

The SWAN is a multiethnic, community-based, longitudinal cohort study of 3302 women at 7 sites who initially were 42 to 52 years of age. Daily patterns of reproductive hormones have been studied in a subgroup of 848 women. A total of 833 menstrual cycles were evaluated. Urinary levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone conjugate (E1c), and pregnanediol glucuronide (Pdg) were used in algorithms to evaluate menstrual cycles for features of folliculogenesis, ovulation, and corpus luteum function. A significant rise in Pdg was taken as evidence of luteal activity (ELA), which is consistent with ovulation. A 60% decrease in the E1c to Pdg ratio indicated a luteal shift (DLT). Phase-specific lengths of cycles with ELA were estimated using the DLT as day 0, excluding day 0 from both follicular and luteal phase lengths. Hormone levels were summed over the total cycle and over the follicular and luteal phases for cycles with ELA. Participants were 43–53 years of age. Just over one third had smoked, and more than half were either overweight or obese. Just over one fourth of women were premenopausal; the rest were in the early perimenopausal phase. Approximately 81% of cycles had ELA, and these were the ones used in the following comparisons. Hispanic women had more long cycles exceeding 33 days and fewer short ones less than 22 days. Both longer and shorter cycles were most frequent in women aged 49 and older. Women whose body mass index (BMI) exceeded 25 kg/m2 had longer cycles on average than those with lower values. Early perimenopausal women were likelier than premenopausal women to have long cycles. On multivariate analysis, only age was significantly associated with total cycle length. BMI was the strongest predictor of phase lengths, larger women having longer follicular phases and shorter luteal phases. The differences remained significant on multivariate analysis. The follicular phase was significantly longer on average in early perimenopausal than in premenopausal women. Neither age nor smoking status influenced phase lengths. Hispanic women had longer luteal phases than other ethnic groups, but there were no significant ethnic differences after adjusting for BMI. Apart from E1c, daily hormone levels were highest in women whose BMI was 25 kg/m2 or less. Lower BMI correlated with higher total-cycle E1c values. Chinese and Japanese women had higher Pdg and lower E1c levels, largely because of the influence of BMI. Women over age 49 years had higher total-cycle FSH levels but lower total-cycle PdG values than did younger women. Smoking did not predict Pdg on multivariate analysis. Total-cycle FSH was higher in early perimenopausal than in premenopausal women, partly because of age differences. Total-cycle hormone levels were related to BMI in this study, and ethnicity seems to play a role independently of body size. It is not clear whether the observed differences are the result of differing rates of progress through the menopausal transition related to body size or ethnicity, or whether the differences will persist with longer follow up.