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.

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 4 ng/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.

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