According to this hypothesis, obesity drives inflammation, insulin resistance, and diabetes. Too much fat storage activates aromatase, a protein that converts testosterone into estradiol. The cause-and-effect link between testosterone and obesity is complex, and it goes both ways. In general, weekly exercise of 160 minutes for 6 months can improve erectile function in obese physically inactive men.64 Weight loss achieved by lifestyle modification can improve erectile dysfunction as measured by International Index of Erectile Function (IIEF). A recently proposed GELDING (Gut Endotoxin Leading to a Decline IN Gonadal function) theory suggests that high-calorie, high-fat diet breaks down integrity of this mucosal barrier and results in metabolic endotoxaemia, a pro-inflammatory state, and consequential hypogonadism.45 Androgen receptors are present in adipose tissue, the density of which is positively regulated by testosterone. Catecholamines are the major hormones controlling lipolysis in adipose tissue, acting via the adrenoreceptors. Lipoprotein lipase present on the extracellular surface of adipocytes hydrolyses circulating triglyceride-rich lipoproteins to free fatty acids which are taken up by the adipocytes and then esterified back into triglycerides for storage. In contrast, relatively little is known about the role of androgens in brown fat, since its potential role in energy expenditure in humans has been recognized only more recently. In addition, local, tissue-specific increases of E2 may not be reflected in circulatory concentrations. Interestingly, diacylglycerol O-acyltransferase 2 (DGAT2), mechanistically implicated in this differential storage,10 is regulated by dihydrotestosterone,11 suggesting a potential role for androgens to influence the genetic predisposition to either the MHO or MONW phenotype. Therefore, the "obesity paradox" remains a hotly debated, but currently still unresolved issue. By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. In our study of 255 hypogonadal men, we noted 71% of men were obese and 14.1% had obesity grade III, using a testosterone cut-off of 12.1 nmol/l 23▪▪. Furthermore, a number of Food and Drug Administration (FDA)-approved drugs for treatment of obesity have serious adverse side-effects and were taken off the market 12,17. Although lifestyle modifications are highly recommended, as integral part of strategies designed for treatment and management of obesity 5–7, in most patients, such strategies are not always successful in the long term because of high rate of recidivism, in part due to lack of adherence to prescribed regimen 8–11. These findings support a role for testosterone therapy in management of obesity. Testosterone therapy for 12 months in men with testosterone deficiency and spinal cord injury significantly improved LBM and resting energy and percentage basal energy expenditure . One of the key observations in testosterone therapy is that testosterone increases LBM, thus increasing resting energy expenditure. Similarly, even mildly high levels of prolactin imbalance can affect the hormonal signals that are required for ovulation. Bakshi further added that over time, higher insulin can also badly affect the egg quality and overall ovarian reserve. Insulin resistance, in particular, can interfere with ovulation and also lead to higher androgen levels, which over time may affect ovarian reserve. Dr Sugata Mishra, Fertility Specialist, Birla Fertility & IVF, Kolkata, said, "When we talk about obesity and fertility, BMI doesn’t always give us the complete picture. This broader lens helps identify "metabolically unhealthy" individuals who may otherwise be overlooked. This makes early intervention crucial—not just for weight management, but for preserving reproductive potential.
