Early dynamics and mechanisms of recovery of sex steroid disturbance after weight loss in obese men

Prevalence of obesity has risen sharply during the last decades and is considered to be a major
cause of chronic diseases such as diabetes, dyslipidemia, hypertension and sleep apnea. As such,
obesity leads to cardiovascular disease which is still the primary cause of death worldwide.
One of the clinical hallmarks in obese men is low serum testosterone levels. Whereas sex steroid
exposure is a major determinant of body composition, obesity itself is associated with important
changes in sex steroid metabolism (decreased production of sex-hormone binding globulin,
increased metabolisation at adipose tissue level, downregulation of the hypothalamic-pituitarygonadal
axis). Therefore, it is unclear whether this disturbed sex steroid profile in obese men
contributes to their phenotype or is mere a physiologic consequence of obesity or both.
Until now, interventions to augment testosterone levels in obese men have yielded limited and
conflicting results with respect to body composition and metabolic profile. Weight loss, on the other
hand, is associated with a variable improvement in testosterone levels – mostly relative to the
amount of weight lost.
To gain more insight in the pathogenesis of the disturbed sex steroid profile in obese men, we want
to evaluate early dynamics and mechanisms of recovery of sex steroid disturbance after weight loss.
If elucidated, this might contribute to the exploration of potential therapeutic targets in this
population with unmet medical needs.