Mechanisms of Obesity-induced Male Infertility

Karen P Phillips; Nongnuj Tanphaichitr


Expert Rev Endocrinol Metab. 2010;5(2):229-251. 

In This Article


Three main biological mechanisms can be used to explain the relationship between obesity and male infertility: hypogonadism; testicular heat-stress-/hypoxia-induced apoptosis and endocrine disruption by obesogens (Figure 14). Obesity-induced hypogonadism appears to be present in most morbidly obese men, driven by peripheral conversion of androgens to estrogens and leptin/insulin resistance. Obese men diagnosed with hypogonadism may have several treatment options, including weight loss and short-term aromatase inhibitor treatment. Similarly, testicular heat stress, although difficult to ascertain medically, could be anticipated following gradation of the pannus (suprapubic/abdominal fat overhang). Testicular heat stress may be alleviated through increased activity, weight loss and use of air-cooling devices during sleep. Future areas for investigation include the roles of adipocytokines and endocrine disrupters in male fertility and obesity. Prenatal exposures to endocrine disrupters may reprogram not only reproductive and endocrine pathways but also molecular modulation of adipocytes. Obesity is, therefore, a causal factor in male infertility, and for some individuals, prenatal exposures may confer additional risk via intersecting endocrine and adipogenic signaling pathways.

Figure 14.

Mechanisms of obesity-induced male infertility. (A) Normal-weight males. In normal-weight individuals, male reproduction is stimulated by the hypothalamus–pituitary–testis (HPT) axis, with negative feedback provided by testosterone. Increasing evidence points to the stimulatory roles of leptin and insulin in the HPT axis including testis functions. (B) Obese males. Male obesity is characterized by high serum estrogen, leptin and insulin levels. Testicular testosterone production is reduced, but may still provide negative feedback to the HPT axis (not shown), although to a lesser extent than in the normal-weight males. Three main biological mechanisms link obesity to impaired male reproductive function: (1) hypogonadism: hypogonadotropic hypogonadism caused by negative feedback by estrogens or insulin/leptin resistance, and hypergonadotropic hypogonadism caused by direct actions of leptin on the testis, (2) testicular heat-stress-/hypoxia-induced apoptosis, and (3) endocrine disruption by 'obesogens': environmental chemicals that may be stored in adipose tissue and have the potential to modulate both estrogenic and adipogenic pathways. Dotted lines indicate proposed mechanisms and solid lines indicate established mechanisms.
E2: Estradiol; FSH: Follicle-stimulating hormone; GnRH: Gonadotropin-releasing hormone; LH: Luteinizing hormone; T: Testosterone; t: Temperature.


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