Leptin and androgens in male obesity: Evidence for leptin contribution to reduced androgen levels

Andrea M. Isidori, Massimiliano Caprio, Felice Strollo, Costanzo Moretti, Gaetano Frajese, Aldo Isidori, Andrea Fabbri

Research output: Contribution to journalArticlepeer-review


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 (E 2) 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 im) 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 E 2 levels or in the E 2/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 E 2 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.

Original languageEnglish
Pages (from-to)3673-3680
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number10
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Leptin and androgens in male obesity: Evidence for leptin contribution to reduced androgen levels'. Together they form a unique fingerprint.

Cite this