Endogenous Steroid Hormone Concentrations and Risk of Endometriosis in the Nurses’ Health Study II


 Few studies have assessed endogenous steroid hormone levels and subsequent endometriosis diagnosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically-confirmed endometriosis in a nested case-control study within the Nurses’ Health Study II. Between blood collection (1996-1999) and 2009, we ascertained 446 women with incident endometriosis and matched them to 878 controls through risk-set sampling. We conducted multivariable conditional logistic regression accounting for matching and confounders to estimate relative risks (RR) and 95% confidence intervals (CI). Women with greater early follicular total or free estradiol levels had a non-linear increased risk of endometriosis (early follicular total estradiol: 2nd quartile vs 1st, RR=2.23(CI=1.44-3.47); 3rd quartile, RR=1.83(CI=1.16-2.88); 4th quartile, RR=1.68(CI=1.05-2.68); early follicular free estradiol: 2nd quartile vs 1st, RR=1.63(CI=1.05-2.54); 3rd quartile, RR=2.02(CI=1.31-3.12); 4th quartile, RR=1.04(CI=0.66-1.65)). Free testosterone assessed in quartile categories was not associated with endometriosis, although a threshold effect was observed with a positive association among women in the top 2% of free testosterone levels. Mid-luteal total and free estradiol, follicular and luteal estrone, total testosterone, progesterone, and sex hormone binding globulin levels were not associated with endometriosis risk. These results support the role of sex steroids in endometriosis etiology, although the relationships suggest complex threshold effects.