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)
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Severe obesity (BMI>38) is characterized by reduction of serum testosterone, its free fraction, and quality and quantity of LH secretion.
“especially the severe form of obesity (BMI>38) is characterized by reduction of serum T, its free fraction and quality and quantity of LH secretion (26).”
From Effects of liraglutide on obesity-associated functional hypogonadism in men (2019) · cites this paper as [26]
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- Authors
- Giagulli, V. A., Kaufman, J. M., & Vermeulen, A.
- Affiliations
- Ghent University Hospital (BE)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1994-10
- Volume
- 79
- Issue
- 4
- Pages
- 997-1000
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2036011095
- Cited by
- 215
- References
- 15
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 10 · 2020: 11 · 2019: 13 · 2018: 11 · 2017: 15 · 2016: 12 · 2015: 13 · 2014: 17 · 2013: 7 · 2012: 12
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- obesity, male hypogonadism, androgen deficiency, sex hormone-binding globulin, free testosterone, LH pulsatility, luteinizing hormone secretion, androstanediol glucuronide, androsterone glucuronide, androgen metabolism, hypothalamic-pituitary-gonadal axis
- MeSH terms
- Adult, Androgens, Androsterone, Humans, Luteinizing Hormone, Male, Middle Aged, Obesity, Testosterone, Androstane-3,17-diol, Body Mass Index
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