Abstract


Total testosterone levels in men decrease with ageing and in obesity and in particular, this has been related to accumulation of abdominal adipose tissue (1). However, less is known about the association of body composition with serum sex steroid levels in overweight to mildly obese men. view more

Total testosterone levels in men decrease with ageing and in obesity and in particular, this has been related to accumulation of abdominal adipose tissue (1). However, less is known about the association of body composition with serum sex steroid levels in overweight to mildly obese men. We analyzed concentrations of serum sex steroids by liquid chromatography-tandem mass spectrometry, together with body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging) from 18 male monozygotic (MZ) twin pairs, identified from ten birth cohorts of young adult Finnish twins (mean age, 32 years; range, 24-36 years). Gene expressions from subcutaneous adipose tissue were analyzed by the Affymetrix U133 Plus 2.0 chips. Nine of the 18 MZ twin pairs studied were discordant for weight (intra-pair difference in BMI ≥ 3 kg/m2) with a median BMI of 33.5 kg/m2 for the heavier and 26.8 kg/m2 for the leaner co-twins. Serum total testosterone was slightly but not significantly lower in the heavier co-twins and its variation was best explained by sex hormone-binding globulin (SHBG). In the discordant pairs, the serum concentration of 5α-dihydrotestosterone (DHT) was significantly lower in the heavier compared to the leaner co-twins, 1.9 (0.7) vs 2.4 (1.0) nmol/l (mean, SD; P=0.04, paired samples t-test). Moreover, the larger the within-pair difference in the subcutaneous fat mass the lower were the serum levels of DHT, total and free testosterone in the heavier co-twin (P<0.01 for all, Spearman’s correlation). Expression of AKR1C2, involved in androgen inactivation, was higher in heavier co-twins (P=0.021) and positively related to percentage body fat (r=0.562, P<0.001) and subcutaneous fat mass (r=0.547, P=0.001). In all twin pairs, mean serum 17β-estradiol (E2) and estrone were higher in the heavier compared to the leaner co-twins, 107 vs 90 pmol/l (P=0.014) and 123 vs 105 pmol/l (P=0.018). In the discordant pairs, the calculated concentration of free E2 was higher in the heavier compared to the leaner co-twins, 2.3 (0.5) vs 1.9 (0.5) pmol/l (P=0.026). The larger the within-pair difference in the subcutaneous fat mass the higher was the expression of CYP19A1 (aromatase) in the heavier co-twin (r=0.576, P=0.012). In conclusion, increased adiposity in young men was associated with decreased serum active androgens and increased free E2 completely independent of genomic differences and age, as studied in MZ twin pairs. We hypothesize that sex steroid metabolism in the subcutaneous adipose compartment is altered in male acquired obesity.

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