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.

Evaluation of a serum 17-hydroxyprogesterone as a predictor of semen parameter improvement in men undergoing medical treatment for infertility.

INTRODUCTION: The goal of medical therapy for infertile men with testosterone deficiency (TD) is to improve intratesticular testosterone (ITT). There is a gap in knowledge to identify those who will respond with semen parameter(s) improvement. We hypothesized that serum 17-hydroxyprogesterone (17-OHP) - a marker of ITT - can be used to predict improvement of semen parameter(s). METHODS: Between July 2018 and January 2020, we conducted a prospective study of 31 men with primary infertility, TD, and secondary hypogonadism receiving clomiphene citrate (CC) and/or human chorionic gonadotropin (hCG) for three months. We assessed baseline and followup hormones, including testosterone, 17-OHP, semen parameter(s), and demographics. Semen quality upgrading was based on assisted reproduction eligibility: in-vitro fertilization (<5 million), intrauterine insemination (IUI) (5-9 million), and natural pregnancy (>9 million). Variables were compared using the Mann-Whitney U or Wilcoxon rank test. RESULTS: Twenty-one men received CC and 10 received CC/hCG. Median followup was 3.7 (3.3-5.1) months. Sixteen men upgraded semen quality. Six of 10 men with baseline total motile sperm count (TMSC) of 0 had motile sperm after treatment, and 11/20 men with TMSC <5 upgraded semen quality into TMSC >5 range. Low 17-OHP was the only factor that predicted semen quality upgrading. Men with 17-OHP ≤55 ng/dL upgraded semen quality and improved hormones, whereas men with 17-OHP >55 ng/dL did not upgrade semen quality. CONCLUSIONS: Medical therapy for infertile men with TD resulted in the improvement of sperm concentration, TMSC, testosterone, and 17-OHP. Semen quality upgrading appears to be more significant in patients with low 17-OHP, suggesting that ITT can be used as a biomarker to predict semen parameter(s) improvement.

Association of Leptin with Total and Free Testosterone: Results from the National Health and Nutrition Examination Surveys.

INTRODUCTION: Obese men can have testosterone deficiency (TD) but the etiology is uncertain. Leptin is a 16-kDa protein produced primarily by adipose tissue and, therefore, is positively associated with the amount of body fat and can affect testosterone (T) production. We hypothesized that increased leptin can be independently associated with low T. MATERIALS AND METHODS: We performed a cross-sectional analysis of men from National Health and Nutrition Examination III database to evaluate the association of leptin with serum T and calculated free testosterone (cFT). Linear regression was performed with leptin, age, waist circumference, hypertension, and diabetes as independent variables predicting cFT/T. Multiple linear regression was used to determine predictors for cFT and T using variables previously significant in the univariate analysis. RESULTS: A total of 1193 men were analyzed. As expected, older and obese men were associated with having lower T. Interestingly, increasing leptin levels were an independent predictor of decreasing T and cFT on multivariable analysis. Increasing 1ng/mL in leptin resulted in a decrease of 5.13 and 0.11 ng/dL of T and cFT, respectively (p < 0.05). Also, every additional year of life led to a T and cFT reduction of 2.87 and 0.13 ng/dL, respectively, and increasing 1 cm in waist circumference corresponded to decrease of 4ng/dL in T (p < 0.05). CONCLUSIONS: We concluded that increasing leptin, age, and waist circumference were associated with decreasing of T and cFT. Elevated leptin levels could be one of the potential etiologies of TD.