Change in follicle stimulating hormone and estradiol across the menopausal transition: effect of age at the final menstrual period

Menopausal transition (MT) is a gradual loss of competent oocytes, cumulating in a final menstrual period (FMP) as a result of progressive dysregulation of the hypothalamic–pituitary–ovarian system. In previous studies it has been demonstrated that, on average, concentrations of follicle stimulating hormone (FSH) increase and oestradiol (E₂) decrease during MT with the midpoint of the FSH rise occurring a year before the midpoint E₂ fall. It has also been reported that women with a later FMP have a shorter MT. The aim of this paper was to determine whether patterns of change in serum E₂ and FSH concentrations across the MT were associated with age at the FMP.

Data were collected from The Study of Women's Health across the Nation (SWAN), a seven-site, multiethnic longitudinal study of MT conducted in 3302 menstruating women aged 42–52 y. At the 1996 baseline, they had an intact uterus and were not on any medication known to affect ovarian function. Annual serum collections were analysed for E₂ and FSH concentrations and patterns of change in serum E₂ and FSH were evaluated in 1215 women with natural FMP at a follow-up visit in 2006. Semiparametric stochastic and piecewise linear mixed modelling was used for this purpose. FSH was measured by chemiluminometric and E₂ by modified ACS-180 E₂–6 immunoassays on a Bayer ACS-180 automated analyser.

Data from 9435 samples were stratified to examine the effects of obesity, smoking and ethnicity on age at FMP. The FSH concentration began to gradually increase 6.1 y before FMP with a rapid increase 2.1 y before FMP. The FSH rise was delayed by obesity to 5.5 y before FMP but was independent of smoking and ethnicity. The E₂ concentration began to decrease 2.0 y before FMP. Obesity and smoking did not affect the pattern of E₂ change, although the decrease occurred 1.3–1.6 y earlier in Chinese and Japanese women. FSH and E₂ attained stable levels by 2.0 and 2.2 y, respectively, after FMP. Overall FSH and E₂ patterns across MT were not related to age at FMP or smoking but were related to obesity and ethnicity.