Estradiol rates of change in relation to the final menstrual period in a population-based cohort of women

Abstract

Context/objective: The aim was to characterize rates of change in serum estradiol (E2) levels across the menopausal transition and into early postmenopause.

Setting/participants: We studied the Michigan Bone Health and Metabolism Study cohort of 629 women with median age of 38 yr (interquartile range, 7) at the 1992-1993 baseline with annual assessment of E2 levels over the subsequent 15-yr period. DESIGN/MAIN OUTCOME MEASURES: The purpose was to describe patterns of acceleration/deceleration in (log)E2 rates of change before and after the final menstrual period (FMP) using nonparametric and piecewise regression modeling.

Results: Between -10 to -2 yr to the FMP, mean fitted serum E2 population values were relatively stable. The 95% confidence bands around the slight increase in E2 rate of change 5 yr prior to the FMP included the value of no change. The fitted population mean E2 value declined 67% from 64.5 pg/ml (se = 3.6) to 21 pg/ml (se = 1.2) in the 4 yr between -2 < FMP < +2. A second significant mean E2 rate of change was identified from 6-8 yr after FMP. Fitted population mean E2 values declined 18% from 18.1 pg/ml (se = 1.3) at FMP = 6 to 14.8 pg/ml (se = 1.3) at FMP = 8. In nonobese women, the mean E2 percent decline was 42% from FMP = 6 to FMP = 8, whereas in obese women, the mean E2 percent decline over this time was 31%.

Conclusions: Population mean serum E2 levels were sustained until approximately 2 yr prior to the FMP. In the ensuing 4-yr period, E2 levels declined 67%. A secondary E2 decline, commencing about 6 yr after the FMP, was observed in nonobese but not obese women.

Figure 1

Population mean backtransformed _logE2 levels (pg/ml), both nonparametric and piece-wise fitted models, and upper and lower 95% confidence bands around the nonparametric fitted line for the 20-yr period around the FMP. The vertical reference lines (−2 to +2 and 6 to 8) identify the two time periods in which there are significant declines according to rate of change. LCI, Lower confidence interval; UCI, upper confidence interval.

Figure 2

Significant declines in the instantaneous rates of change occur in _logE2 levels at −2, 2, 6, and 8 yr before and after the FMP as identified, with broken vertical lines indicating where the 95% confidence intervals (95% CI) in gray shaded bands exclude the null value of no change.

Figure 3

The association of BMI was inconsistent across the menopause transition, with _logE2 rate of change declining among nonobese women (<30 kg/m²) in 6 < FMP < 9.5 in contrast to no decline in obese women (≥30 kg/m²). CI, Confidence intervals.