Various interventions for infertility in men with type II diabetes and hypogonadism

Background: Low levels of testosterone and sexual desire loss are common characteristics of hypogonadism, which is an endocrine disorder often occurring in men. Sexual dysfunction is an uncomfortable condition that both hypogonadal and diabetic men experience nowadays, however the diagnosis and treatment strategies are limited. Type II diabetes is a lifelong disorder of abnormal glucose metabolism with devastating health effects on patients. Sex-related hormones, that normally regulate the reproductive cycle, are found significantly reduced in conditions where the functional activity of the gonads is decreased. An imbalance in the levels of these hormones is also associated with metabolic abnormalities, such as hyperglycemia and insulin resistance. The effectiveness of the existing therapies for sexual dysfunction treatment and the restoration of reproductive hormones in hypogonadal men with type II diabetes remain unexplored. Methods: We searched the Cochrane Library, Scopus, Science Direct and the Web Search engine “Google Scholar” from January 2011 to July 2021. Randomized controlled trials (RCTs) were included, comparing the treatment of sexual dysfunction and the restoration of sex-related hormones in hypogonadal men with type II diabetes with testosterone replacement or administration of vardenafil or clomiphene citrate, versus placebo treatment. Fixed effect meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). Results: The review includes nine RCTs regarding: a) Testosterone replacement therapy (five RCTs) and administration of b) Vardenafil (one RCT) or c) Clomiphene citrate (three RCTs) for the treatment of sexual dysfunction in diabetic men with hypogonadism. The aspects of sexual function were evaluated by estimating the: a) Aging male’s symptoms’ (AMS) rating scale, b) Erectile Function, c) Intercourse Satisfaction, d) Orgasmic Function, e) Sexual Desire, f) Overall Sexual Satisfaction, g) levels of E2 (pg/mL), h) levels of FHS (mU/mL), i) levels of LH (mU/mL), j) levels of SHBG (nmol/L) and k) levels of free testosterone (nmol/L). Our findings suggest that a) testosterone replacement therapy or administration of vardenafil resulted in improved erectile function (95% Cl -0.485 to -0.165; 6 RCTs; I2=94,8%, p=6.5e-05), b) testosterone supplementation ameliorated intercourse satisfaction (95% Cl -0.4 to -0.064; 4 RCTs; I2=54,5%, p=0.006783), orgasmic function (95% Cl -0.674 to -0.325; 4 RCTs; I2=94,6%, p=0) and sexual desire (95% Cl -0.446 to -0.124; 5 RCTs; I2=94,3%, p=0.00509), but had no impact on AMS rating scale (95% Cl -0.286 to 0.057; 4 RCTs; I2=93,1%, p = 0.191643) and overall satisfaction (95% Cl 0.03 to 0.402; 3 RCTs; I2=95%, p=0.023112) and c) administration of clomiphene citrate led in elevated levels of E2 (95% Cl -1.531 to -0.756; 3 RCTs; I2=0%, p=0), LH (95% Cl -0.674 to -0.325; 3 RCTs; I2=0%, p=0), FSH (95% Cl -1.372 to -0.612; 3 RCTs; I2=0%, p=0), SHBG (95% Cl -0.938 to -0.207; 3 RCTs; I2=0%, p=0.002151) and free testosterone (95% Cl -1.864 to -1.204; 3 RCTs; I2=83.1%, p=0), compared to placebo treatment in hypogonadal men with type II diabetes. Conclusions: Hypogonadal males with type II diabetes receiving either testosterone supplementation, or the compounds vardenafil and clomiphene citrate, displayed improved sexual function and elevated levels of sex-related hormones, versus placebo treatment.