Pathogenesis of the decreased androgen levels in obese men.

Abstract

In obese men, sex hormone-binding globulin levels (SHBG) as well as total plasma testosterone (T) levels are decreased. Data concerning the levels of nonprotein-bound testosterone (FT) are discordant, with some researchers reporting normal levels, and other reporting decreased levels. The latter imply an impairment of the feedback regulation mechanism of FT levels. We investigated whether an eventual decrease in FT levels and, hence, functional impairment of the gonadostat might occur only at a more severe degree of obesity than that required for a decrease in SHBG and total T levels. We, therefore, determined androgen and precursor levels in three groups of male subjects: nonobese controls [body mass index (BMI), G (kg)/L2 (m) < 26; n = 70]; moderately (BMI, 30-35; n = 18), and severely (BMI, > 40; n = 22) obese men, respectively. In a subgroup of these controls, moderately and severely obese subjects, respectively, we studied LH levels as well as LH pulsatility. Moreover, as a decrease in FT levels might affect the metabolic pattern of the androgens and, more specifically, 5 alpha-reductase activity, we determined the plasma levels of the major 5 alpha-reduced metabolites, androstanediol glucuronide and androsterone glucuronide (AG), as well as the urinary excretion of the major 5 alpha (androsterone glucuronide) and the major 5 beta (etiocholanolone glucuronide) metabolite of the androgens. In moderately obese men, T levels were decreased, which was the consequence of the decreased SHBG-binding capacity. FT levels, however, were normal as were LH levels and both pulse amplitude and frequency of LH pulses, suggesting a normal hypothalamic control of LH secretion. In severely obese men (BMI, > 40), total T, FT, and LH levels as well as LH pulse amplitude were decreased, indicating a functional impairment of the gonadostat. Even in massively obese subjects with decreased FT levels, androgen metabolism and 5 alpha-reductase activity appeared to be normal, as suggested by similar androstanediol glucuronide and AG levels, determined by RIA or calculated from the conversion rates of precursors obtained in nonobese subjects. This was confirmed by the similar AG/eticholanolone glucuronide ratios in obese and nonobese men.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypogonadotrophic Hypogonadism in Type 2 Diabetes, Obesity and the Metabolic Syndrome

“…FT concentrations correlated positively with the sum of LH pulse amplitudes in each individual. Further work from the same group showed low FT, LH and LH pulse amplitude in severely obese (BMI>40kg/m2) while these parameters were normal in milder obesity [27]. One study suggested that obesity can also blunt the responsiveness of pituitary gonadotropin secretion to GnRH stimulation [63].…”

“…Estradiol levels are increased in mild to moderate obesity but do not rise further in massive obesity [27,28]. However, free testosterone continues to fall as the obesity progresses.…”

“…It has been believed in the past that the low total T in obesity is due to low SHBG. However, studies in the past 15 years have shown FT concentrations to be low in the obese, especially those with BMI>40kg/m 2 [27,28].…”

Metabolic Syndrome, Androgens, and Hypertension

“…Morbidly obese men have normal luteinizing hormone (LH) pulsatility, but the LH amplitude is severely reduced [24]. However, this depends on the degree of obesity and is consistent only in the morbidly obese (BMI>40 kg/m 2 ) [25]. …”

For and against: The male menopause---does it exist? For Against

“…A history of orchitis, testicular trauma, or other pathology may be contributory. The presence of obesity is associated with lower concentrations of bioavailable testosterone, 19 and insulin concentrations have been found to be indirectly correlated with sex hormone binding globulin and testosterone concentrations 20. With respect to lifestyle, excess intake of alcohol and physical and psychological stress are all associated with lowered testosterone concentrations 21 22…”