Association of aging and obesity with decreased 17-hydroxyprogesterone, a serum biomarker of intratesticular testosterone

Obesity’s negative association with serum testosterone can be explained by either decreasing luteinizing hormone (LH) production from the pituitary gland and/or directly impacting intratesticular testosterone production. We hypothesize that obesity will negatively impact intratesticular testosterone levels when compared to those of non-obese men. We performed a cross-sectional analysis of men with symptoms of testosterone deficiency and male infertility between July 2018 and April 2020 to evaluate the association between body mass index (BMI) and age with intratesticular testosterone (using serum 17-hydroxyprogesterone (17-OHP) as a biomarker), and between BMI with LH. Univariable and multiple linear regression analysis were performed using confounding variables to predict 17-OHP and testosterone. A total of 340 men were selected. Median age was 38 [33–44] years, BMI 27.8 [25.4–31.1] kg/m², serum testosterone 363 [256.3–469.6] ng/dl, 17-OHP 60.5 [39.3–85.8] ng/dl, and LH 4.2 [2.8–5.7] mIU/ml. Older and obese men had lower testosterone compared to younger and non-obese men. Interestingly, increasing age and higher BMI were associated with lower 17-OHP (p < 0.001). Contrarily, age and BMI were not associated with LH levels (p = 0.478). In conclusion, obesity and aging negatively affected 17-OHP independent of LH, suggesting a possible direct effect on testicular function, rather than a secondary effect from a decline in pituitary signaling.