Intratesticular testosterone is essential for spermatogenesis and can only be reliably measured with invasive testicular sampling. Previous studies have demonstrated good correlation between intratesticular testosterone and serum 17-hydroxyprogesterone (17-OHP) in men treated with human chorionic gonadotropin. Based on this observation we hypothesized that we can use serum 17-OHP as a serum biomarker for evaluating intratesticular testosterone in men receiving medications that alter serum testosterone.

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 used the Mann Whitney U or Wilcoxon tests.

In the initial cross-sectional analysis of 93 men, a total of 30 men received treatments that increase or maintain intratesticular testosterone concentrations, such as clomiphene citrate and/or human chorionic gonadotropin; 21 men received treatments that suppress intratesticular testosterone concentrations (various exogenous testosterone replacement therapy formulations) and 42 fertile men with normal serum testosterone (greater than 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 who received exogenous testosterone replacement therapy, as opposed to men receiving human chorionic gonadotropin and/or clomiphene citrate or fertile controls (p <0.05). In the prospective evaluation that ensued, 17-OHP values decreased in the 21 men who received testosterone replacement therapy (47.5 [21–70] to 13.5 [10—23] ng/dl, p <0.05). Conversely, 17-OHP increased in the 55 men who received human chorionic gonadotropin and/or clomiphene citrate when compared to their baseline levels (42 [24–72] to 88 [61–135] ng/dl, p <0.05).

Serum 17-OHP appears to be a reliable serum marker for intratesticular testosterone levels and could potentially be used to titrate or change medications that alter intratesticular testosterone.