Trajectory clustering of estradiol and follicle-stimulating hormone during the menopausal transition among women in the Study of Women's Health across the Nation (SWAN)

Abstract

Context: Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined.

Objective: The current study aimed to determine whether different trajectories of E2 and FSH could be identified and whether race/ethnicity and body mass index were related to the different trajectories.

Design: The Study of Women's Health Across the Nation is a longitudinal observational study of the menopausal transition.

Setting: Women aged 42-52 yr from seven participating sites were recruited and underwent up to 11 annual visits.

Participants: Postmenopausal women with 12 or more months of amenorrhea that was not due to hysterectomy/oophorectomy and who were not using hormone therapy before the final menstrual period participated in the study.

Main outcome measures: Annual serum E2 and FSH levels anchored to final menstrual period were measured.

Results: Four distinct E2 trajectories and three distinct FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%), flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns. Obesity increased the likelihood of a flat E2 and low FSH trajectory for all race/ethnic groups. Normal-weight Caucasian and African-American women tended to follow the rise/steep decline E2 and high FSH trajectories. Normal-weight Chinese/Japanese women tended to follow the slow decline E2 and the high/medium FSH trajectories.

Conclusions: E2 and FSH trajectories over the menopausal transition are not uniform across the population of women. Race/ethnicity and body mass index affect the trajectory of both E2 and FSH change over the menopausal transition.

Fig. 1.

Trajectory of E2 across the FMP. Significant predictors for trajectory separation were race/ethnicity and BMI (see Supplemental Table 2 for modeling details). E2 levels were the average observed serum E2 levels at each time point. Time-varying age, SHBG, and cycle day of blood draw were adjusted in the model. The model accuracy diagnostics showed that the capacity of the model to separate women among the groups was good. The AvePP ranged from 0.72 to 0.81 and the OCC ranged from 6.44 to 10.98.

Fig. 2.

Distribution of E2 trajectory subgroups by race/ethnicity and BMI. BMI was analyzed as normal weight (<25 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). The percentages represented the percent of E2 trajectory subgroups within each race/ethnicity or BMI category. The total percentage within each race/ethnicity or BMI category was 100%. Overall P values based on χ² tests for the distribution of E2 trajectory subgroups by race/ethnicity and BMI were both less than 0.0001.

Fig. 3.

Trajectory of FSH across the FMP. Significant predictors for trajectory separation were race/ethnicity and BMI (see Supplemental Table 3 for modeling details). FSH levels were the average observed serum FSH levels at each time point. Time-varying age and cycle day of blood draw were adjusted in the model. The model accuracy diagnostics showed that the capacity of the model to separate women among the groups was very good. The AvePP ranged from 0.87 to 0.92 and the OCC ranged from 7.00 to 105.51.

Fig. 4.

Distribution of FSH trajectory subgroups by race/ethnicity and BMI. BMI was analyzed as normal weight (<25 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). Percentages represented the percent of FSH trajectory subgroups within each race/ethnicity or BMI category. The total percentage within each race/ethnicity or BMI category was 100%. Overall P values based on χ² tests for the distribution of FSH trajectory subgroups by race/ethnicity and BMI were both less than 0.0001.