Studies on CYP3A activity during the menstrual cycle as measured by urinary 6β-hydroxycortisol/cortisol

Abstract

The 6β-OH-cortisol/cortisol ratio (6β-OHC/C) in urine is an endogenous marker of drug-metabolizing enzyme cytochrome P450 3A (CYP3A). The primary aim of this single center, prospective, non-interventional cohort study, was to investigate the variability of 6β-OHC/C during the menstrual cycle. In addition, possible associations between the CYP3A activity and sex hormones, gut microbiota metabolite trimethylamine-N-Oxide (TMAO) and microRNA-27b, respectively, were investigated. Serum and urinary samples from healthy, regularly menstruating women followed for two menstrual cycles were analyzed. Twenty-six complete menstrual cycles including follicular, ovulatory, and luteal phase were defined based on hormone analyses in serum. 6β-OHC/C were analyzed in urine and sex hormones, TMAO and miRNA-27b were analyzed in serum at the same time points. 6β-OHC/C did not vary between the follicular, ovulatory, or luteal phases. There was a difference in the relative miRNA-27b expression between the follicular and ovulatory phase (p =.03). A significant association was found between 6β-OHC/C and progesterone during the follicular (p =.005) and ovulatory (p =.01) phases (n = 26 for each phase). In addition, a significant association was found between the ratio and TMAO during the ovulatory (p =.02) and luteal (p =.002) phases. 6β-OHC/C and gut microbiota TMAO were significantly associated (p =.003) when evaluating all values, for all phases (n = 78). Interestingly, the finding of an association between 6β-OHC/C in urine and levels of TMAO in serum suggest that gut microbiota may affect CYP3A activity.