Testosterone Substitution Normalizes Elevated Serum Leptin Levels in Hypogonadal Men

Abstract

The ob gene product leptin (OB) is a feedback signal from the adipocyte to the hypothalamus and is involved in regulation of food intake and energy expenditure in rodents. A major determinant of serum OB levels is fat mass. Several studies suggest that men have lower OB levels than women even after adjustment for percent body fat. We, therefore, investigated the influence of testosterone (T) substitution in hypogonadal men on serum OB levels. Hypogonadal men with T levels of 3.6 nmol/L or less and off substitution therapy for at least 3 months were assigned to two treatment groups: testosterone enanthate (TE; 250 mg, i.m., every 21 days; n = 10) or a single s.c. implantation of 1200 mg crystalline T (TPEL; n = 12). Blood samples for determination of T, 5 alpha-dihydrotestosterone (DHT), sex hormone-binding globulin, and 17 beta-estradiol were obtained before therapy and then every 21 days until day 189 and at follow-up visits on days 246 and 300. Serum OB levels were assessed on days 0, 42, 84, 126, 168, and 300. OB levels were referred to a normal range for men based on the analysis of OB levels in 393 adult men. Substitution with T led to a large rise in T and DHT in both groups compared to baseline values (average T, days 21-189: TE, 14.33 +/- 2.63 nmol/L; TPEL, 24.98 +/- 1.64; average DHT, days 21-189: TE, 4.20 +/- 0.57 nmol/L; TPEL, 5.11 +/- 0.56; P < or = 0.05). Concomitantly, 17 beta-estradiol increased in both groups, and sex hormone-binding globulin levels were significantly decreased. At baseline, serum OB levels in hypogonadal men were 3-fold elevated compared to those in normal men (12.39 +/- 2.93 micrograms/L vs. 4.28 +/- 0.52; P < 0.01) and not different between groups (TE, 13.7 +/- 5.6; TPEL, 11.3 +/- 2.9 micrograms/L). This elevation was retained after adjustment for body mass index in the normal control group [TE, 1.45 +/- 0.51 SD score (P < 0.0001); TPEL, 0.98 +/- 0.35 SD score (P < 0.0008)]. During T substitution serum OB was completely normalized (trough levels: TE, 4.6 +/- 1.0 micrograms/L; TPEL 4.3 +/- 0.9 micrograms/L). In multiple regression analysis, the androgen (T plus DHT)/estrogen ratio was the only significant determinant of OB levels (r = -0.32; P < 0.01). At baseline, OB levels did not correlate with body mass index, but during substitution, the correlation was considerably improved. We conclude that hypogonadal men exhibit elevated OB levels that are normalized by substitution with T. The only determinant of OB levels was the androgen/estrogen ratio, indicating a major influence of sex steroids on OB production. The interaction of T and OB might be part of a hypothalamic-pituitary-gonadal-adipose tissue axis that is involved in body weight maintenance and reproductive function.

Year round plasma leptin and androgen concentrations in a tropical bat

“…Photoperiod and other hormones may also be involved in modulating reproductive activity as suggested in recent reviews (Cunningham et al 1999, Foster andNagatani 1999). It has been reported that testosterone suppresses leptin production by adipose tissue (Bedrak et al 1983, Gemmell et al 1985, Jockenhovel et al 1997. The present study support this hypothesis because in T. longimanus the increase in testosterone during January has been reported (Singh and Krishna, 2002).…”

Semen parameters and hormonal profile in obese fertile and infertile males

“…Elevated serum leptin in hypogonadal men (33,34) and elderly men (35) was shown to decrease during T replacement therapy. Giovambattista et al (36) suggested that leptin could affect both Leydig and Sertoli cells in the testis, but its direct effect might be only through Leydig cells.…”

Increased Body Adiposity and Serum Leptin Concentrations in Very Long-Term Adult Male Survivors of Childhood Acute Lymphoblastic Leukemia

“…In the present study, very high levels of leptin were observed among obese ALL survivors, and even more remarkable increases in leptin levels were observed when the values were adjusted for the BMI. It has been shown that hypogonadal men have increased leptin levels and that testosterone substitution therapy can normalize elevated serum leptin levels [31]. The mechanisms by which testosterone reduces leptin levels are uncertain but may include the capacity of testosterone to reduce adipose tissue mass [32].…”