madman
Super Moderator
ABSTRACT
Objective: Men with obesity often have low total and, with increasing adiposity, also low free testosterone (T) levels, which can partially restore during weight loss. Although this is partly explained by lower sex hormone-binding globulin (SHBG) production and hypothalamic-pituitary downregulation, it is still not unraveled whether changes in androgen metabolism contribute to this phenomenon. Therefore, early changes in urinary excretion of T and its metabolites, during weight loss, in men with obesity are investigated.
Design: Longitudinal study.
Methods: Fourteen men with obesity (age 52 (45–60)years, BMI 42.6 (41.8–44.8)kg/) underwent gastric bypass surgery (GBS). Before surgery and 3 weeks, 6 weeks, 6 months, and 1 year thereafter, 24 h urine and fasting serum samples were collected. Serum T and estradiol (E2) levels were analyzed using LC-MS/MS and urinary metabolites of T with GC-MS/MS.
Results: Already three weeks after GBS, serum SHBG and total T levels increased and remained increased as compared to baseline (all,p < 0.0125). Gonadotropins and (free) E2 levels were unchanged, serum E2/T ratio decreased (p < 0.0125). The total amount of urinary T increased non-significantly with a mean increase of 53 % one year after GBS (p = 0.026). Urinary E2/T, estrone/T, 3α-androstanediol/T and androsterone/T ratios decreased after GBS (p < 0.0125).
Conclusions: Restoration of circulating T levels during weight loss in this population is not only brought about by normalization of circulating SHBG levels, but increased production of and alterations in T metabolism also contribute. More specifically, relative decreases in aromatization and lower 5α-reductase activity might also be involved in restoring T levels in men with obesity.
1. Introduction
Men with obesity are known to have disturbed sex steroid profiles, especially lower total serum testosterone (T) levels compared to healthy men [1–6]. However, with increasing adiposity, free T levels are also decreased. Many hypotheses have been put forward explaining these lower total and free T levels, such as lower sex hormone-binding globulin (SHBG) production, downregulation of the hypothalamic-pituitary-gonadal (HPG) axis and/or increased aromatization [2,5–11]. However, aromatase is not the only enzyme metabolizing T, as almost half of the secreted T is hepatically metabolized by 5α-reductase and 5β-reductase enzymes to the 17-ketosteroids androsterone and etiocholanolone (Fig. 1). These metabolites can then be glucuronidated or sulfated and are mainly excreted in urine [12,13]. To date, it is not clear whether changes in androgen metabolism, besides aromatization, contribute to the lower T levels in men with obesity.
Remarkably, this disturbed serum sex steroid profile in men with obesity is (partially) restored when these men lose weight and some studies even showed increases in urinary T suggesting increased T production per se [14–18]. As the prevalence of obesity keeps rising and sex steroids are involved in the regulation of muscle mass [19], bone [20] and adipose tissue [21], there is a need to better understand how this
In conclusion, restoration of total T levels into the eugonadal range during massive weight loss in men with obesity after GBS is not only brought about by normalization of circulating SHBG levels, but increased production of and alterations in T metabolism also contribute. More specifically, decreases in aromatization and lower 5α-reductase activity might also be involved in restoring T levels in men with obesity.
Objective: Men with obesity often have low total and, with increasing adiposity, also low free testosterone (T) levels, which can partially restore during weight loss. Although this is partly explained by lower sex hormone-binding globulin (SHBG) production and hypothalamic-pituitary downregulation, it is still not unraveled whether changes in androgen metabolism contribute to this phenomenon. Therefore, early changes in urinary excretion of T and its metabolites, during weight loss, in men with obesity are investigated.
Design: Longitudinal study.
Methods: Fourteen men with obesity (age 52 (45–60)years, BMI 42.6 (41.8–44.8)kg/) underwent gastric bypass surgery (GBS). Before surgery and 3 weeks, 6 weeks, 6 months, and 1 year thereafter, 24 h urine and fasting serum samples were collected. Serum T and estradiol (E2) levels were analyzed using LC-MS/MS and urinary metabolites of T with GC-MS/MS.
Results: Already three weeks after GBS, serum SHBG and total T levels increased and remained increased as compared to baseline (all,p < 0.0125). Gonadotropins and (free) E2 levels were unchanged, serum E2/T ratio decreased (p < 0.0125). The total amount of urinary T increased non-significantly with a mean increase of 53 % one year after GBS (p = 0.026). Urinary E2/T, estrone/T, 3α-androstanediol/T and androsterone/T ratios decreased after GBS (p < 0.0125).
Conclusions: Restoration of circulating T levels during weight loss in this population is not only brought about by normalization of circulating SHBG levels, but increased production of and alterations in T metabolism also contribute. More specifically, relative decreases in aromatization and lower 5α-reductase activity might also be involved in restoring T levels in men with obesity.
1. Introduction
Men with obesity are known to have disturbed sex steroid profiles, especially lower total serum testosterone (T) levels compared to healthy men [1–6]. However, with increasing adiposity, free T levels are also decreased. Many hypotheses have been put forward explaining these lower total and free T levels, such as lower sex hormone-binding globulin (SHBG) production, downregulation of the hypothalamic-pituitary-gonadal (HPG) axis and/or increased aromatization [2,5–11]. However, aromatase is not the only enzyme metabolizing T, as almost half of the secreted T is hepatically metabolized by 5α-reductase and 5β-reductase enzymes to the 17-ketosteroids androsterone and etiocholanolone (Fig. 1). These metabolites can then be glucuronidated or sulfated and are mainly excreted in urine [12,13]. To date, it is not clear whether changes in androgen metabolism, besides aromatization, contribute to the lower T levels in men with obesity.
Remarkably, this disturbed serum sex steroid profile in men with obesity is (partially) restored when these men lose weight and some studies even showed increases in urinary T suggesting increased T production per se [14–18]. As the prevalence of obesity keeps rising and sex steroids are involved in the regulation of muscle mass [19], bone [20] and adipose tissue [21], there is a need to better understand how this
In conclusion, restoration of total T levels into the eugonadal range during massive weight loss in men with obesity after GBS is not only brought about by normalization of circulating SHBG levels, but increased production of and alterations in T metabolism also contribute. More specifically, decreases in aromatization and lower 5α-reductase activity might also be involved in restoring T levels in men with obesity.
