Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN

Abstract

We tested the hypothesis that higher serum osteocalcin and urinary N-telopeptide of type I collagen (NTx) concentrations would be found in women with increasing cycle irregularity or increased follicle stimulating hormone concentrations. We studied 2,375 pre- and early perimenopausal women from the Study of Women's Health Across the Nation (SWAN), aged 42-52 years, who self-identified their race/ethnic origin as African-American (28.3%), Caucasian (49.4%), Japanese (10.5%) or Chinese (11.8%). Outcome measures were serum osteocalcin, a measure of bone formation, and NTx, a measure of bone resorption. The explanatory variables were menopausal status, based on self-reported regularity of menstrual bleeding, and circulating endogenous hormone concentrations including estradiol (E(2)), testosterone (T), sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) concentrations. Additionally, we evaluated the association of the bone turnover markers with the Free Androgen Index (FAI) and the Free Estradiol Index (FEI), ratios of total testosterone and estradiol concentrations to SHBG, respectively. Higher FSH concentrations were associated with higher NTx concentrations ( beta=0.003, partial r2=2.1%, p<0.0001), both before and after adjusting for other covariates (total explained variability of 9%). Higher FSH concentrations were also associated with higher osteocalcin concentrations ( beta=-0.216, partial r2=4.1%, p<0.0001, total explained variability of 15.4%). There were no significant associations of the bone turnover markers with other endogenous hormones, following adjustment for covariates. Mean osteocalcin and NTx values were not significantly different in premenopausal women compared to early perimenopausal women. In these pre- and early perimenopausal women, higher FSH concentrations, but not other serum reproductive hormone concentrations, are positively associated with greater bone turnover prior to the last menstrual period.