The role of leptin and obesity on male infertility

Abstract

Purpose of review Several studies suggest a strong association between leptin, obesity, and infertility with respect to the hypothalamic–pituitary–gonadal (HPG) axis, androgen regulation, and sperm production, but the direct mechanistic association between these is still largely unexplored. This review focuses on understanding the association between leptin, obesity, and male infertility. Recent findings Obesity is linked to fertility dysfunction in both genders. Obesity in men may affect their fertility by impaired spermatogenesis, reduced testosterone levels, erectile dysfunction, and poor libido by putatively targeting the HPG and hypothalamic–pituitary–adrenal axes. Leptin plays key roles in many metabolic functions, including reproduction. High concentrations of leptin have been found in infertile men with disorders affecting the testicular parenchyma, including nonobstructive azoospermia, oligozoospermia, and oligo-astheno-teratozoospermia. Additionally, serum leptin levels have negative associations with serum testosterone levels and sperm parameters and positive associations with serum follicle-stimulating hormone and luteinizing hormone levels and abnormal sperm morphology. Summary Excessive leptin production may be a significant contributor to the development of androgen insufficiency and reduced reproductive function in obese men. Understanding the relation between leptin, obesity, and reproduction may shed light on future targeted treatments for male infertility.

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

“…30 It is likely that the high leptin levels in obese patients play a role independent of the other factors involved in obesity on comorbid hypoandrogenism. 31 In contrast, another study suggested that low T could impact leptin levels. 32 In this study, castrated rats presented with the highest levels of leptin when compared with controls and those receiving exogenous T. 33 Since the majority of men in this study had normal serum T, low T was not a predictor of elevated leptin levels (Table 4).…”

Diet and Nutritional Factors in Male (In)fertility—Underestimated Factors

“…It is therefore suggested that excessive leptin production may constitute a significant factor in the development of androgen deficiency and deterioration of male reproductive function. Nevertheless, the mechanisms binding leptin to the HPG axis and obesity are still not fully understood and the research results on the role of leptin in infertility development remains unclear [65][66][67]. In addition, in obese individuals, disorders on the hypothalamic-pituitary-gonads (HPG) axis have been observed.…”

Mechanisms of Central Hypogonadism

“…Analogous to the context of hypoleptinaemia, the development of hyperleptinaemia also results in suppression of the HPG axis with resultant CH. However, unlike hypoleptinaemia, the mechanisms that mediate the effects of hyperleptinaemia on suppression of the HPG axis remain incompletely understood [ 83 ]. Obesity, particularly in the context of type 2 diabetes (T2D), is related to the development of resistance to the effects of leptin.…”