Circulating Sex Hormones and Risk of Uterine Fibroids: Study of Women's Health Across the Nation (SWAN)

Context: Estrogen has been implicated in the development of uterine fibroids. However, the contribution of androgen in women is unknown. Objective: Our objective was to assess the longitudinal relations of circulating androgens and estradiol (E2) and their joint effects to the risk of developing fibroids. Design: This is a 13-year longitudinal study in the Study of Women's Health Across the Nation. Setting: This study was conducted in seven sites across the United States (1997–2013). Participants: At baseline, 3240 pre- or early peri-menopausal women with an intact uterus, ages 45–52 years were included; 43.6% completed the follow-up. There were 512 incident and 478 recurrent fibroid cases. Exposures: We measured near-annual time-varying serum levels of bioavailable E2 and bioavailable T, dichotomized at the median (high vs low). Main Outcomes and Measures: We estimated the conditional odds ratio (OR) of fibroids in the ensuing year using discrete-time proportional odds models adjusted for race/ethnicity/site, age, body mass index, menopausal stage, reproductive factors, smoking, timing of blood draw, and FSH. Results: Women with high T had a statistically significant increased risk of incident fibroids (OR, 1.33; 95% confidence interval [CI], 1.01–1.76; P = .04), but not recurrent fibroids. This risk was further elevated in those with high T and E2 (OR, 1.52; 95% CI, 1.07–2.17; P = .02). High E2 and T was associated with lower risk of recurrent fibroids (OR, 0.50; 95% CI, 0.26–0.96; P = .04). Conclusions: High T with high E2 was associated with an elevated risk of incident fibroids in midlife women who never reported fibroids before baseline. Conversely, the risk of recurrent fibroids was mitigated in women with high E2 and high T.