Gender differences in leptin, ghrelin, and adiponectin levels have been described in a normal population. This is important for understanding differences between males and females in the regulation of food intake, weight gain, body fat distribution, and cardiovascular risk. It is unclear how endogenous and exogenous sex hormones may regulate circulating levels of these factors. Transsexuals during hormonal treatment may represent an ideal model to ascertain the role of exogenous sex hormones on these parameters. In this study, our objective was to evaluate adiponectin, ghrelin, and leptin levels in transsexual subjects during hormone therapy and to compare the results of males and females. Subjects were 26 nondiabetic transsexuals, which included 15 male-to-female (M-to-F, group 3) and 11 female-to-male (F-to-M, group 4) individuals, and 29 age- and BMI-matched controls, which included 15 males (group 1) and 14 females (group 2). Results showed that leptin levels were significantly lower in group 1 compared with group 2 (P = .04) and group 3 (P = .01); no differences were recorded between the other groups. Adiponectin levels were significantly higher in group 3 compared with group 4 (P = .03). No differences were found between the 4 groups for ghrelin levels. In conclusion, our data confirm the sexual dimorphism in serum leptin levels in normal subjects and demonstrate an increase in M-to-F transsexuals. While ghrelin does not show any sexual differences and seems not to be influenced by exogenous sex hormone administration, the lower adiponectin levels in F-to-M transsexuals during treatment confirm that androgens may decrease plasma adiponectin levels. This latter observation suggests that F-to-M transsexual patients could have a higher cardiovascular risk.

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