Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels

Abstract

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

Low Serum Testosterone Concentration in Middle-aged Men with Type 2 Diabetes

“…In obese men there is a decrease in free testosterone concentration, resulting from the peripheral conversion of testosterone into estrogen, which decreases the amplitude of LH pulse, promoting central inhibition of androgenic production [14]. It is also possible that the decreased concentrations of testosterone in obese men result from an inhibitory effect of leptin on the hypothalamus-pituitarygonadal axis [15]. Obesity is associated with increased plasma levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, Creactive protein, and adhesion molecules [16].…”

Aging and pathogenesis of erectile dysfunction

“…41 Recent findings suggest a possible role of the adipocytesecreted hormone leptin, which increases with fat mass, 42 in this phenomenon. [43][44][45][46] Although it is generally assumed that testosterone enhances libido and frequency of sexual acts (see in Tenover 13 for review), recent studies 16,17 did not show any relationship between testosterone levels and ED prevalence and severity. In accordance with these latter studies, we did not find any correlation between testosterone levels and the severity of ED.…”

Aspectos neuroendócrinos da síndrome metabólica

“…Estes níveis diminuídos, entretanto, explicam apenas parcialmente a diminuição dos androgênios. A própria diminuição da produção de testosterona pelos testículos pode ocasionar diminuição da SHBG (74). Seria esperado, então, que a diminuição das proteínas de ligação levasse a um aumento da testosterona livre.…”