11-oxygenated androgens in healthy young adults: Does use of hormonal contraceptives matter? The Fit Futures Study

Increasing evidence suggests a role of 11-oxygenated adrenal androgens (11-OxyA) (11-ketotestosterone, 11KT; 11β-hydroxytestosterone, 11OHT; 11-ketoandrostenedione, 11KA4; 11β-hydroxyandrostenedione, 11OHA4) in several hyperandrogenic disorders. This study aimed to describe distributions of 11-OxyA in a healthy young adult population and explore the relation between hormonal contraceptives and 11-OxyA.

This study utilized cross-sectional data from the third Fit Futures Study conducted in Norway. 11-OxyA in fasting blood samples were analyzed by liquid chromatography tandem mass spectrometry technique (LC-MS/MS). Contraceptive use was registered and categorized as combined hormonal contraceptives (CHC) or gestagen-only contraceptives. Descriptive statistics were used to report 11-OxyA distributions. Independent t-tests and ANOVA were used to compare biomarker concentrations between groups.

The study included 289 males and 337 females with median age of 27 years. Males had 9-30% higher 11-OxyA concentrations than females (all p's < 0.01). Among the females, 25.5% used CHC, 36.7% used gestagen-only contraceptives, and 37.8% used non-hormonal contraceptives or no contraceptives. As concentrations of 11-OxyA in gestagen-only contraceptives users were similar to non-users, these groups were combined. CHC users had 25-29% lower concentrations of 11KT, 11OHT, and 11KA4 than non-CHC users (all p's < 0.001). After exclusion of CHC users, sex differences attenuated and was no longer significant for 11KT.

Females had lower concentrations of 11-OxyA than males, partly explained by use of CHC, as users had significantly lower concentrations of 11-OxyA than non-CHC users, except 11OHA4. These findings suggest an additional mechanism for CHC in treatment of hyperandrogenic conditions, in which 11-OxyA are elevated.