Excess and Body Composition: Clinical Studies
Three scenarios can be considered when describing the effect of androgen excess on body composition: in women, FtoM and PCOS; in both men and women, doping.
FtoM is the most common gender dysphoria; in this condition, a person with a female gender at birth has a male identity. It has a prevalence of 1:30,400 females, which is one third when compared to the prevalence of the MtoF transsexualism (1:11,900 males), based on the Netherlands and Belgium data [89]. Medical management is based on T administration; the following effects on body composition have been consistently reported: increase in body weight and muscle mass; quick depletion of SAT, with slower accumulation of VAT occurring in 1–3 years. Interestingly morphological changes include enlarged ovaries with a polycystic morphology [30, 89–91].
PCOS is the most common ovarian disorder associated with androgen excess in women. According to Rotterdam criteria, it can be diagnosed when 2 criteria are found between chronic oligo/anovulation, clinical or biochemical hyperandrogenism and polycystic ovaries on US, after excluding other aetiologies such as congenital adrenal hyperplasia, androgen-secreting tumours, Cushing syndrome, thyroid dysfunction, and hyperprolactinaemia; based on the combination of criteria, 4 phenotypes can be further classified [92]. Clinical series reported an association between PCOS and being overweight or obese; obesity is associated with insulin resistance; insulin has been shown to increase androgen synthesis by ovaries acting synergistically with LH and by adrenal glands with adrenocorticotropin (androgens further boosts VAT gain [93–95]. Other authors reported an increased androgens production by theca cells even when isolated in culture. The reciprocal association between insulin resistance and hyperandrogenism/ovulatory dysfunction are supported by the following evidence: metformin and bariatric surgery induce insulin sensitizing and weight loss, which are usually associated with decreased Ferriman-Gallwey score, androgen levels and in some patients to the resolution of PCOS; flutamide (a pure anti-androgen indicated for hirsutism) is associated with decreased VAT and insulin resistance [96].
Doping is a technique or the use of substances to improve exercise performance and/or body image of an athlete illegally. The most common drugs are androgens that exert their effect on both of the aspects mentioned above; this explains the reason behind their wide diffusion reported in almost 10% of adult gym users, 40% of body builders and 70% of power lifters. A randomized trial evaluated the effects of supraphysiological doses of exogenous testosterone among 43 healthy young men: those given T had greater increases in muscle size in their arms and legs and in strength in the bench-press and squatting exercises than those given placebo, independently from training [97]. It is worth noting that T exerts its effect on all types of muscular fibres, including the heart: chronic exposure to doping is associated with concentric cardiac hypertrophy, dilated cardiomyopathy, fibrosis, and increased risk of acute myocardial infarction and fatal ventricular arrhythmias [98].
Conclusions
Androgens exert a relevant role in determining body weight and composition, as confirmed by preclinical and clinical studies. In animal models and cell cultures, androgens have been shown to inhibit adipogenic lineage and lipid storage, while favouring muscle cell hypertrophy. In clinical studies in men, low androgens have been associated with increased FM and reduced FFM, both corrected after T replacement therapy; high androgen levels lead to increase FFM and reduce FM. Differences are described depending on sex and the type of adipose tissue (VAT or SAT).
Disclosure Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed a potential conflict of interest.
Author Contributions
V.A.G. and M.C. performed the literature search, analysis and manuscript drafting. All authors critically reviewed and approved the final version.
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