Impact of hormonal contraceptives on urinary steroid profile in relation to serum hormone changes and CYP17A1 polymorphism

Abstract

To detect doping with endogenous steroids, six urinary steroids are longitudinally monitored in the athlete biological passport (ABP). These steroids include testosterone, etiocholanolone, androsterone, 5α‐androstane‐3α,17β‐diol, 5β‐androstane‐3α,17β‐diol, and the testosterone isomer epitestosterone. It is known that the intake of hormonal contraceptives may interfere with the ABP biomarkers. A previous study showed that athletes using hormonal contraceptives (HCs) display lower urinary epitestosterone concentrations than non‐using athletes. In this study, we analyzed the urinary steroid profile prior to and three months after administration of an oral HC including levonorgestrel and ethinylestradiol (n = 55). The urinary concentrations of all the ABP metabolites decreased after three months, with epitestosterone showing the largest decline (median 6.78 to 3.04 ng/mL, p˂0.0001) followed by 5α‐androstane‐3α,17β‐diol (median 23.5 to 12.83 ng/mL, p˂0.0001), and testosterone (median 5.32 to 3.66, p˂0.0001). Epitestosterone is included in two of the five ratios in the ABP (T/E and 5αAdiol/E), and consequently these ratios increased 1.7‐fold (range 0.27 to 8.50) and 1.26‐fold (range 0.14 to 5.91), respectively. Some of these changes may mimic the changes seen after administration of endogenous steroids leading to atypical findings. Notably, even though participants used the same contraceptive treatment schedule, the HC‐mediated epitestosterone change varied to a large extent (median 0.43‐fold, range 0.06 to 6.5) and were associated with a functional T˃C promoter polymorphism in CYP17A1. Moreover, the epitestosterone changes correlated with HC‐induced testosterone and gonadotropins changes in serum, indicating that urinary epitestosterone reflects the androgen load in HC‐using women.

Urinary steroid profile in relation to the menstrual cycle

“…During the follicular phase, the urinary E concentration was suppressed in all the women in the study (Figure 2a). The suppression of E was almost as profound as seen in women taking hormonal contraceptives 9,23,25 . Hormonal contraceptives are not one of the confounding factors that the laboratories have to analyze and report according to TD2018EAAS 14 .…”

“…The reason why urinary E increases in the later phase of the cycle is not known but may be associated with the increase of LH and P in the ovulation and luteal phase, respectively. We have seen that hormonal contraceptives (HC) mediated E changes exhibit strong correlation with the gonadotropins to a much larger extent than the other ABP metabolites, 9 whereas no studies have investigated the correlation between urinary E and the other female hormones P and E2. Here, we aim to study if the concentrations of the urinary steroid metabolites differ between the different biological phases of the menstrual cycle.…”

The Specificities of Elite Female Athletes: A Multidisciplinary Approach

“…Studies have been performed with COC and emergency (i.e., progestin-only, levonorgestrel) contraceptives in healthy women [ 415 ] or elite athletes [ 416 ]. One of the main results was that E concentrations were significantly lower in COC users vs. non-users, whereas T showed no difference, leading to a higher T/E ratio.…”

In vitro and in vivo investigation of the therapeutic mechanism of Lycium Chinense and Cuscutae Semen on oligoasthenozoospermia

“…We found that LC‐CS enhanced the expression of hormone‐related CYP17A1, CYP19A1, AR and SRD5A2. It has been suggested that CYP17A1 encodes cytochrome p450‐17 and is a key enzyme in the steroid hormone synthesis pathway (Ekström et al., 2019).…”