Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males.

Abstract

Several aspects of the regulation of androgen secretion and plasma levels in males remain controversial. Among these, we cite the problem of whether the age-related decrease in testosterone (T) levels is an intrinsic aging phenomenon or is a sequel of previous illness, the mechanisms underlying the increase in sex hormone-binding globulin (SHBG)-binding capacity in aging men and the supranormal capacity observed immediately after a weight-reducing diet, and the role of insulin in the age-associated decrease in dehydroepiandrosterone (sulfate) [DHEA (DHEAS)] levels. To gain further insight into these issues, we investigated the influence of age, smoking, body mass index (BMI), serum albumin, insulin, GH, and insulin-like growth factor I (IGF-I) levels, respectively, on androgen levels and SHBG-binding capacity in a nonobese healthy population (n = 250) as well as in an obese population (n = 50) before and after weight loss. The influence of GH supplementation on SHBG, DHEAS, DHEA, and insulin levels was studied in a small group of men (n = 8) with isolated GH deficiency. In nonobese healthy men, age was inversely correlated with serum levels of all androgens studied (although total T levels stayed relatively stable until age 55 yr) as well as with albumin, GH, and IGF-I levels and positively correlated with BMI, insulin levels, and SHBG-binding capacity. Nevertheless, SHBG levels were significantly negatively correlated with insulin levels (P < 0.001) as well as with mean 24-h GH and IGF-I levels. Among possible confounding factors affecting (free) T [(FT)] levels in healthy men, smoking appeared to be accompanied by higher (F)T levels than those in nonsmokers. BMI increased with age, but although BMI was negatively correlated with T, FT, and SHBG, respectively, the age-dependent decrease in T levels persisted after correction for BMI. Data not corrected for BMI may, nevertheless, overestimate the age-associated decrease in T levels. The albumin concentration decreased with age, and if FT is the feedback regulator of plasma T levels, albumin concentration might be a codeterminant (although, evidently, less important than SHBG) of T levels and contribute to the age-associated decrease in T levels. In any case, albumin concentration is a codeterminant of DHEAS concentration. T, DHEA, and DHEAS levels were significantly correlated, but this correlation disappeared after controlling for age; hence, there is no evidence for an adrenal-gonadal interaction in men. In obese men, T, FT, and SHBG levels were significantly lower than those in the nonobese men and inversely correlated with BMI; DHEAS levels were slightly lower than those in the nonobese controls, but no significant correlation between DHEA or DHEAS, and insulin levels was observed. After a weight-reducing, protein-rich diet, resulting in a mean weight loss of +/- 15 kg, SHBG-binding capacity increased to normal values notwithstanding the fact that the subjects were still obese and that the insulin levels remained higher than those in the nonobese controls. Co...

Hormone levels and sexual development in Flemish adolescents residing in areas differing in pollution pressure

“…Arithmetic and geometric means with 95% confidence intervals (CI) or median with 10th and 90th percentile values are reported. Analysis of Covariance (Ancova) or multiple regression were used to adjust the raw data for some pre-specified, literature based confounders (Ukkola et al, 2001;Vermeulen et al, 1999a;Zitzmann and Nieschlag, 2001). Statistical analysis of data on sexual development comprised adjustment for age and BMI for boys and for girls also for use of oral contraception.…”

Are declining testosterone levels a major risk factor for ill-health in aging men?

“…15 At constant total testosterone, increased SHBG by providing more binding sites for testosterone would be expected to reduce the fraction of free testosterone and SHBG levels rise with increasing age. [16][17][18] Thus, even though total testosterone and SHBG remain correlated in older men, the age-related increase in SHBG could modulate levels of free testosterone in a setting where total testosterone is relatively preserved. 13,14 However, multiple mechanisms are likely to influence the decline in testosterone levels in aging men.…”

Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review

“…The progressive uncoupling of the coregulation between SHBG and total plasma T with increasing age may be explained by the parallel, age-related decline in pituitary GH production, and in total IGF-1 levels. 178,210 Associations of bioavailable androgens with overweight and obesity…”

“…221,223,224 One such additional mechanism may be a decrease in pituitary GH secretion and total IGF-1 levels, which is generally observed in obese men. 178,225,226 Another possible mechanism is the inhibition of androgen synthesis by leptin, a hormone formed predominantly in adipose tissue, which is central to the regulation of food intake, as well as to regulation of reproductive function in women and men. 227 In overweight to mildly obese men (25`BMI`30), total T is decreased, but not dramatically so, and moderate overweight or obesity usually is not associated with a state of hypogonadotropic hypogonadism.…”