This is a study explaining the effect of iron overload on testosterone production and obesity, both a mouse study and a human study. It is a free paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139764/

Antioxidants (Basel)

. 2020 Mar 22;9(3):261.

doi: 10.3390/antiox9030261.

Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity

Seu-Hwa Chen ¹, Kuo-Ching Yuan ², Yu-Chieh Lee ³, Chun-Kuang Shih ⁴, Sung-Hui Tseng ^{5 6}, Alexey A Tinkov ^{7 8 9}, Anatoly V Skalny ^{7 8 9}, Jung-Su Chang ^{4 10 11 12}

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• PMID: 32235809

PMCID: PMC7139764 DOI: 10.3390/antiox9030261Free PMC article

Abstract

The literature suggests a bidirectional relationship between testosterone (T) and iron, but mechanisms underlying this relationship remain unclear. We investigated effects of iron on advanced glycation end products (AGEs) in obesity-related androgen deficiency. In total, 111 men were recruited, and iron biomarkers and N(ɛ)-(carboxymethyl)lysine (CML) were measured. In an animal study, rats were fed a 50% high-fat diet (HFD) with (0.25, 1, and 2 g ferric iron/kg diet) or without ferric citrate for 12 weeks. Obese rats supplemented with >1 g iron/kg diet had decreased testicular total T compared to HFD alone. Immunohistochemical staining showed that >1 g of ferric iron increased iron and AGE retention in testicular interstitial tissues, which is associated with increased expression of the receptor for AGEs (RAGE), tumor necrosis factor-α, and nitric oxide. Compared with normal weight, overweight/obese men had lower T levels and higher rates of hypogonadism (19% vs. 11.3%) and iron overload (29.8% vs.15.9%). A correlation analysis showed serum total T was positively correlated with transferrin saturation (r = 0.242, p = 0.007) and cathepsin D (r = 0.330, p = 0.001), but negatively correlated with red blood cell aggregation (r = -0.419, p<0.0001) and CML (r = -0.209, p < 0.05). In conclusion, AGEs may partially explain the underlying relationship between dysregulated iron and T deficiency.