Evidence for Hypogonadism in Massively Obese Males Due to Decreased Free Testosterone

Abstract

In obese male subjects with 160 - 200% of ideal body weight (IBW = 100%) the decrease in total plasma testosterone is biologically ineffective since SHBG is concomitantly decreased from 30.0 +/- 3.6 to 20.0 +/- 3.4 nM/l. Conversely, in massively obese males with greater than 250% of IBW, the decrease in SHBG (to 10.6 +/- 1.8 nM/l) is too small to compensate for total testosterone decrease (from 6.04 +/- 0.57 to 1.72 +/- 0.32 ng/Ml). Therefore, free testosterone is markedly less in the massively obese patients (55 +/- 8 vs. 127 +/- 15 pg/ml in the controls). Despite this significant difference in free testosterone concentrations (p less than 0.01), plasma LH is even lower in the obese (6.8 +/- 0.8 mU/ml) than in the controls (10.0 +/- 1.0 mU/ml). This may be an effect of free estradiol, which rises from 0.48 to 1.52 pg/ml in the massively obese subjects. These alterations are clearly demonstrated by the imbalance of the estradiol/testosterone ratios, which increase 10-fold and 7-fold for the total and for the free sex hormones, respectively. We conclude that the decrease in SHBG, which prevents obese males from developing hypogonadism, is not sufficiently effective in the massively obese patients to compensate the marked decrease in testosterone. This, in connection with the observed increase of free estradiol, may cause hypogonadism and hyperestrogenism in these subjects.

Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome

“…Free testosterone levels, however, are normal as were LH levels, suggesting a normal hypothalamic control of LH secretion. In morbidly obese men (BMI Ͼ 40), total and free testosterone and FSH and LH levels were decreased, indicating a functional impairment of the gonadostat responsible for the decreased free testosterone and hypogonadism (335,336). This suggests a syndrome of hypogonadotropic hypogonadism only in the most obese men.…”

Reproductive ecology and life history of the human male

“…For example, increases in E2 levels due to greater testosterone conversion within adipocytes by the enzyme aromatase, a process known as aromatization, were suspected to underlie low testosterone levels and hypogonadism in obese men (Kley et al, 1981). Indeed, a genetic mutation resulting in abnormally high aromatase levels is associated with hypogonadism in human males (Stratakis et al, 1998).…”

The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study

“…Other investigations that included small samples of selected men with severe obesity reported that obese men had low free testosterone (FT) levels (13). One hypothesis to explain the association between extreme adiposity and low FT levels (true androgen deficiency) suggests that high estrogen levels are the culprit.…”

“…One hypothesis to explain the association between extreme adiposity and low FT levels (true androgen deficiency) suggests that high estrogen levels are the culprit. Some speculate that in extremely obese men, high estradiol levels, generated by aromatization of testosterone in the adipose tissue (14,15), suppress gonadotropinreleasing hormone and luteinizing hormone levels thereby suppressing testicular testosterone production (13,16,17).…”