Body fat distribution predicts the development of obesity-related complications in patients with obesity, and ectopic fat accumulation, namely visceral adipose tissue and epicardial fat (EF), is associated with higher cardiovascular risk. Functional hypogonadism (FG) represents either cause and consequence of obesity, with the two conditions often coexistent; Testosterone replacement therapy (TRT) in patients with obesity and classical hypogonadism predisposes to better outcomes in terms of body weight reduction/distribution and cardiometabolic status. However, in clinical routine patients suffering with obesity and concomitant FG are often left untreated. Our hypothesis is that male individuals with obesity and FG may derive greater benefit from TRT in association with nutritional intervention (NI) in terms of body fat mass decrease and EF reduction compared to controls undergoing NI alone. Our aim is to investigate the impact of TRT in association with NI on body fat mass and distribution, cardiac ultrasound-derived EF thickness (EFT), metabolic status in patients with obesity and FG. In this open-label randomized pilot study, 40 male patients with obesity and FG will be randomized in 2 groups. 20 patients enrolled in the NI-group will follow a hypocaloric diet, whereas 20 patients enrolled in the TRT+NI group will follow a TRT in addition to the same dietary intervention for 6 months. At the baseline and at the end of the study, Cardiac Ultrasound Examination-derived EFT will be calculated, body composition through dual-energy-X-ray absorptiometry will be performed and blood samples for hormonal and metabolic parameters will be collected. If our hypothesis will be confirmed, we expect patients in the TRT+NI group to show greater body weight reduction, body fat composition amelioration, EFT reduction compared to control. Considering the high prevalence of both conditions, this knowledge would help clinicians achieve a more personalized management of obesity.
The dramatic increase in the prevalence of obesity worldwide represents an urgent public health issue, considering its strong association with cardiometabolic disease and increased mortality. To date, few pharmacological therapeutic strategies promoting body weight reduction and body fat distribution amelioration are available, and clinicians¿ awareness of the need of a valid therapy personalization is raising. Functional hypogonadism is a common comorbidity associated with obesity in a bidirectional and vicious relationship; in fact, on the one hand, adipose tissue expansion may be considered as a cause of androgen deficiency and inactivity, while on the other hand lower TT levels contributes to body fat accumulation and visceral fat expansion. Noteworthy, although international guidelines for the treatment of hypogonadism recommend testosterone replacement therapy (TRT) in those patients suffering from classical hypogonadism, which is the correct timing to start TRT in functional hypogonadism is a matter of debate. In clinical routine, patients suffering with obesity and concomitant functional hypogonadism are often left untreated because body fat reduction is commonly associated with hypogonadism resolution. However, clinical and preclinical studies suggest that individuals with obesity may derive significant benefit in terms of body weight reduction and body fat distribution improvement from TRT.
In the current study, we will aim at evaluating the effectiveness of TRT in addition to nutritional intervention to achieve body weight reduction and body fat distribution amelioration, with a special focus on EFT reduction. Considering the strong association between EFT and cardiovascular diseases, if our hypothesis will prove true, we will identify TRT as a valid therapeutic strategy to reduce cardiometabolic risk in patients suffering from obesity and functional hypogonadism.
Considering the heterogeneity of obesity, the identification of the multitude of factors driving its most dangerous complications with subsequent therapy personalization is fundamental. Individuals with obesity suffering from functional hypogonadism may be considered as a particular subgroup of patients who may derive particular benefit by TRT. Considering the high prevalence of both conditions in general population, this knowledge would significantly help clinicians achieve a better and more personalized management of obesity as whole.