Follicle stimulating hormone and its rate of change in defining menopause transition stages

Abstract

Context/objective: The objective of the study was to identify menopause transition stages using acceleration or deceleration patterns of FSH rates of change from the late reproductive years to postmenopause.

Setting/participants: Participants were the Michigan Bone Health and Metabolism Study cohort of 629 women, aged 24-44 yr (in 1992/3), with 5757 annual FSH data points over a 14-yr period. DESIGN/MAIN OUTCOME MEASURES: The study was designed to relate acceleration/deceleration patterns in FSH rate of change to time to final menstrual period (FMP) and chronological age using nonparametric and piecewise regression modeling.

Results: Four major FSH stages, based on rate of FSH change patterns, were identifiable in relation to the FMP. In FSH stage 1, the rate of FSH change increased modestly up to -7 yr prior to the FMP; in FSH stage 2 (-7 to -2 yr prior to FMP), there was a major acceleration in FSH rate of change. FSH stage 3 had an acute increase in FSH rate of change (-2 to +1 yr around the FMP), with average FSH level of 34 mIU/ml. The fourth, or plateau, FSH stage began at 1 yr after FMP when the average FSH level was 54 mIU/ml. During the yr 28-60, there were eight age-specific epochs defined by significant changes of FSH trajectory accelerations or decelerations and rate of change.

Conclusions: Four menopause transition stages bounding the FMP and eight epochs in chronological aging from age 28 to 60 yr were defined by changes of FSH trajectory accelerations/decelerations and rates of change. This timing information, combined with knowledge of FSH levels and menstrual cycle characteristics, can help discern the likely status of women with respect to their reproductive viability and menopause transition stage.

Figure 1

The mean population logFSH (milliinternational units per milliliter), with 95% upper (UCI) and lower confidence intervals (LCI), in relation to years before and after the FMP depicting two modeling approaches, a nonparametric stochastic model (black solid line) or a four-segment piece-wise model (shown with nodes). Vertical reference lines shows the critical nodes associated with time (years) around FMP.

Figure 2

Four FSH stages (S1–S4) defined by critical changes in the _logFSH (milliinternational units per milliliter) acceleration and rate of change in relation to the FMP. The acute increasing of _logFSH (milliinternational units per milliliter; and thus FSH due to the monotonicity of logarithm) occurs between 2 yr prior and 1 yr after FMP. The major acceleration in _logFSH rate of change occurs around 2 yr before FMP and the major deceleration in _logFSH rate of change occurs at 1 yr after FMP.

Figure 3

The mean population _logFSH (milliinternational units per milliliter), with 95% upper (UCI) and lower confidence intervals (LCI), according to chronological age using two modeling approaches, a nonparametric stochastic model (black solid line) or an eight-segment piece-wise model, with the ages at the nodes at which there are critical changes in the line.

Figure 4

Eight age-related FSH segments (A1–A8) defined by critical changes in the _logFSH (milliinternational units per milliliter) acceleration and rate of change. The major acceleration in _logFSH rate of change occurs at 45 yr of age, and the major deceleration in _logFSH rate of change occurs at age 55 yr.