Obesity and reproductive hormone levels in the transition to menopause

Abstract

Objective: The aim of this study was to estimate associations of obesity with reproductive hormone levels as women progress from premenopausal to postmenopausal status.

Methods: This was a longitudinal study conducted in the population-based Penn Ovarian Aging Cohort (N = 436). At cohort enrollment, the women were premenopausal, ages 35 to 47 years, with equal numbers of African Americans and whites. Anthropometric measures, menopause status, and reproductive hormone measures were evaluated for 12 years. Associations of the anthropometric measures with estradiol, follicle-stimulating hormone, and inhibin B in the menopausal transition were estimated using generalized linear regression models for repeated measures.

Results: Associations between obesity and hormone levels differed by menopause status as indicated by significant interactions between each hormone and menopausal stage. Premenopausal obese and overweight women had significantly lower estradiol levels compared with nonobese women, independent of age, race, and smoking (obese: 32.8 pg/mL [95% CI, 30.6-35.2] vs nonobese: 39.8 pg/mL [95% CI, 37.0-42.8], P < 0.001). The associations reversed postmenopause, with obese women having the highest estradiol levels (obese: 20.6 pg/mL [95% CI, 17.2-24.7] vs nonobese: 12.2 pg/mL [95% CI, 10.1-14.8], P < 0.001). Inhibin B levels were significantly lower in premenopausal obese compared with nonobese women but reversed in the late transition stage. Follicle-stimulating hormone levels were lowest in postmenopausal obese compared with nonobese women (P < 0.001). Measures of waist circumference (central adiposity) and waist-to-hip ratio paralleled the body mass index results.

Conclusion: Obesity is an important factor in hormone dynamics independent of age, race, and smoking in midlife women, although the mechanisms remain unclear.

Figure 1

Interaction between body mass index (BMI) and menopausal stage for (A) estradiol (P<0.001), (B) FSH (P=0.008), and (C) inhibin b (P=0.004) from the full multivariable models. Hormone values are the geometric mean with 95% confidence interval, estimated from multivariable models that adjusted for race, age and smoking and within women correlation due to repeated measurements. The reduced significance level with the Bonferroni correction for within-group comparisons at each menopausal stage is P=0.003. N=436 with 3,581 observations for estradiol, 3,578 observations for FSH and 3,051 observations for inhibin b.

Figure 1

Interaction between body mass index (BMI) and menopausal stage for (A) estradiol (P<0.001), (B) FSH (P=0.008), and (C) inhibin b (P=0.004) from the full multivariable models. Hormone values are the geometric mean with 95% confidence interval, estimated from multivariable models that adjusted for race, age and smoking and within women correlation due to repeated measurements. The reduced significance level with the Bonferroni correction for within-group comparisons at each menopausal stage is P=0.003. N=436 with 3,581 observations for estradiol, 3,578 observations for FSH and 3,051 observations for inhibin b.

Figure 1

Interaction between body mass index (BMI) and menopausal stage for (A) estradiol (P<0.001), (B) FSH (P=0.008), and (C) inhibin b (P=0.004) from the full multivariable models. Hormone values are the geometric mean with 95% confidence interval, estimated from multivariable models that adjusted for race, age and smoking and within women correlation due to repeated measurements. The reduced significance level with the Bonferroni correction for within-group comparisons at each menopausal stage is P=0.003. N=436 with 3,581 observations for estradiol, 3,578 observations for FSH and 3,051 observations for inhibin b.

Figure 2

Interaction between waist circumference (WC) and menopausal stage for estradiol (P<0.001) from the full multivariable model. See legend details in Figure 1.