Serum 17-Hydroxyprogesterone is a Potential Biomarker for Evaluating Intratesticular Testosterone.

INTRODUCTION AND OBJECTIVE: Intratesticular testosterone (ITT) is essential for spermatogenesis and can only be reliably measured with invasive testicular sampling. Previous studies have demonstrated good correlation between ITT and serum 17-hydroxyprogesterone (17-OHP) in men treated with human chorionic gonadotropin (hCG). Based on this observation, we hypothesized that we can use serum 17-OHP as a serum biomarker for evaluating ITT in men receiving medications that alter serum testosterone. METHODS: Initially, we conducted a cross-sectional analysis of men with a single serum 17-OHP evaluation from July 2018 to March 2019. We followed this with a prospective analysis from July 2018 to October 2019 with evaluation of 140 men including fertile controls, and those receiving treatments that alter serum testosterone at baseline and after 3 months of therapy. According to the data distribution, we reported the median and interquartile ranges and utilized the Mann Whitney U or Wilcoxon tests. RESULTS: In the initial cross-sectional analysis of 93 men, a total of 30 men received treatments that increase or maintain ITT concentrations, such as clomiphene citrate (CC) and/or hCG; 21 men received treatments that suppress ITT concentrations (various exogenous testosterone replacement therapy (TRT) formulations); and 42 fertile men with normal serum testosterone (>300 ng/dL) were used as control. We demonstrated that serum testosterone levels were within normal range among men receiving the various therapies. In contrast, we found that serum 17-OHP was undetectable in men that received exogenous TRT, as opposed to men receiving hCG and/or CC or fertile controls (p < 0.05). In the prospective evaluation that ensued, 17-OHP values decreased in the 21 men who received TRT (47.5 [21-70] ng/dL to 13.5 [10 - 23] ng/dL, p < 0.05). Conversely, 17-OHP increased in the 55 men who received hCG and/or CC when compared to their baseline levels (42 [24-72] ng/dL to 88 [61-135] ng/dL, p < 0.05). CONCLUSION: Serum 17-OHP appears to be a reliable serum marker for ITT levels and could potentially be used to titrate or change medications that alter ITT.