Higher serum total testosterone levels correlate with increased risk of depressive symptoms in Caucasian women through the entire menopausal transition

Abstract

Background: Despite the high prevalence of depressive symptoms in women, the precise role of sex hormones in mood changes during the menopausal transition is unclear. Previous studies have been inconsistent with regard to identifying the association of androgens, namely total testosterone, with depressive symptoms.

Objective: The objectives of this study were to evaluate changes in serum total testosterone levels and depressive symptoms during the entire menopausal transition, and examine the impact of covariates on the association between concurrent serum total testosterone levels and depressive symptoms during this time period.

Methods: A longitudinal cohort study (428 women at baseline with 3634 repeated measures) using data from the Penn Ovarian Aging Study, a population-based cohort of late reproductive-aged women, followed through the menopausal transition. Serum hormone parameters and depression scores using the Center for Epidemiological Studies of Depression scale (CES-D) were measured at each annual visit over a 14-year period. General linear (for testosterone) and a generalized negative-binomial model (for depressive symptoms) for repeated measures were used for analysis.

Results: Serum total testosterone levels increased progressively over the study period and were significantly associated with older age and with current smoking (p<0.001, respectively). In the post menopause total testosterone levels were significantly higher in African Americans compared to Caucasians (p=0.012). The proportion of women with CES-D ≥16 significantly decreased with increasing age and in the post-menopausal period, and were higher in women with a history of depression and hot flashes (p<0.001). The association between concurrent testosterone levels and high depressive symptoms (CES-D ≥16) differed by race (p=0.008). In Caucasians, but not African Americans, higher serum testosterone levels were associated with increased depressive symptoms after controlling for several variables including age, obesity status, hot flashes and menopausal status (RR 1.09, 95% CI 1.00-1.17, p=0.042).

Conclusion: In our cohort, testosterone levels were low but progressively increased from premenopause through post menopause. In addition to age and history of depression, we identified race to have a significant interaction between the association of testosterone levels and depressive symptoms. This study further supports the associations between sex hormones and increased risk of having depressive symptoms, although the precise underlying mechanisms for this association remain unclear.

Keywords: Androgens; Depressive symptoms; Menopausal transition; Menopause; Testosterone.