Endocrine Abstracts

Background: Men with obesity often have low total and, with increasing adiposity, also free testosterone (T) levels, which can partially restore when they lose weight. Although this is in part explained by lower sex-hormone binding globulin (SHBG) production and hypothalamic-pituitary downregulation, it is still not fully unraveled whether changes in androgen metabolization contribute to this phenomenon.

Aim: Investigating metabolisation of sex steroids during weight loss in men with obesity.

SUBJECTS AND METHODS: Eleven obese men (age 49±10 years, BMI 44.9±5.0 kg/m²) were recruited prior to adhering dedicated lifestyle changes (n=1) or undergoing gastric bypass surgery (n=10). Before start of weight loss and 3 weeks, 6 weeks, 6 months and 1 year thereafter, 24h urine collections and fasting serum samples were collected. Serum T and estradiol (E₂) levels were analyzed using LC-MS/MS and serum SHBG concentrations using immunoassays. Urinary T, 3α-androstanediol, androsterone, 3α-etiocholanediol, etiocholanolone, estrone, E₂ and estriol levels were analyzed using gas chromatography coupled to mass spectroscopy. Statistical analyses were performed using linear mixed modelling.

Results: Obese men significantly reduced their BMI through this one-year follow-up study with a mean BMI of 30.3 kg/m² after one year (F(4, 9.173)=139.105, P<0.001). Serum T and SHBG concentrations increased by 102% and 87%, respectively (both P<0.001), while serum E₂ levels decreased non-significantly (P=0.129). A significant increase of total urinary T concentration was observed during follow-up (F(4, 29.112)=4.529, P=0.006), with a total increase of 101% one year after start of weight loss (P=0.001), while the ratios E₂/T and estriol/T decreased (P=0.001 and P=0.010; respectively) suggesting lower relative aromatization. In addition, T metabolisation by 5α-reductase and 3α-hydroxysteroid dehydrogenase (HSD) reflected by 3α-androstanediol/T- and androsterone/T-ratio, decreased during follow-up (P=0.006 and P=0.002; respectively) whereas 3α-etiocholanediol/T-ratio and etiocholanolone/T-ratio, reflecting T metabolisation from the 5β-reductase and 3α-HSD pathway, showed a non-significant decrease (P=0.065 and P=0.070; respectively).

Conclusion: Restoration of T levels into the eugonadal range during weight loss in men with obesity is not only brought about by normalization of circulating SHBG levels but also by increased T production per se as reflected by increased urinary secretion of T. In addition, changes in these men’s urinary steroid profile, suggest that alterations in T metabolization also contribute to this. More specifically, besides relatively higher aromatization, higher 5α-reductase and 3α-HSD activity might also play a role in the phenomenon of low T levels in men with obesity.