Testosterone therapy in men with obesity "Classical" vs. "Functional" hypogonadism


Prof. Zitzmann presents data on testosterone therapy in obese men. The prevalence of obesity is 30-35% in many Western countries. Obesity in men is strongly associated with low testosterone levels. Over half of obese men have hypogonadism. A Similarly high prevalence of hypogonadism is seen in men with type 2 diabetes, hypertension and dyslipidemia.

The kind of hypogonadism seen in obese men is often called functional hypogonadism, and is caused by disturbed testicular (Leydig Cell) function and hypothalamic/pituitary regulation. A main characteristic of functional hypogonadism is that it is age-independent and frequently occurs in younger obese men. In contrast, primary hypogonadism is caused by testicular damage, while secondary hypogonadism is caused by hypothalamic/pituitary damage. The reduction in testosterone levels seen in older non-obese men is commonly due to impaired testicular function, and is irreversible.

In men, testosterone deficiency may contribute to the development of visceral obesity and the metabolic syndrome. Visceral fat disturbs the hypothalamic-pituitary-gonadal axis by production of proinflammatory cytokines.

Testosterone has reciprocal effects on the generation of muscle and visceral adipose tissue by influencing the commitment of pluripotent stem cells to myogenic cells, and by inhibiting the development of preadipocytes. Testosterone increases insulin sensitivity of muscle cells by augmenting mitochondrial capacity and fostering expression of oxidative phosphorylation genes.

Among hypogonadal patients seeking medical care for erectile dysfunction, the prevalence of primary and secondary hypogonadism is 3.2% and 17.4%, respectively. In 10% of men with secondary hypogonadism, the underlying cause was drugs, trauma, surgery/CT, empty sella or prolactin adenoma. Notably, in 90% of men with secondary hypogonadism, the underlying cause was unexplained.

Interestingly, among men with unexplained secondary hypogonadism, 72% were obese and/or had the metabolic syndrome or type 2 diabetes. The remaining 28% presented with chronic inflammatory conditions.

There are limited data about the long-term effects of testosterone therapy in hypogonadal men and clinical value of this treatment in men with functional (late-onset) hypogonadism vs. classical remains hotly debated. Prof. Zitzmann presents new data from a registry study of testosterone therapy for 9 years in men with classical (primary and secondary) and functional hypogonadism. The study was large enough to analyze potential differences in effects of testosterone therapy between the various kinds of hypogonadism.

At baseline, before start of testosterone therapy, the prevalence of obesity was greater among men with functional hypogonadism (52%) compared to classical hypogonadism (36%). Men with functional hypogonadism also had worse cholesterol profile and hyperglycemia.

During testosterone therapy, analysis of changes over time revealed some differences between types of hypogonadism in regards to obesity and metabolic outcomes: men with functional hypogonadism were more likely to lose 10% of initial body weight and 5% of initial waist circumference, and had greater improvements in cholesterol parameters and glucose control. There was no difference for increase in hematocrit. This study provides major new findings regarding effects and safety of testosterone therapy in men with different types of hypogonadism. Patients with functional hypogonadism may experience greater benefits from testosterone therapy; this is a function of their initially worse status in cardiovascular risk factors compared to men with classical forms of hypogonadism.

In accordance with these data, the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) clinical practice guidelines for medical care of patients with obesity recommend that men with obesity and/or type 2 diabetes should be screened for hypogonadism.



Prof. Dr. Michael Zitzmann

Prof. Dr. Michael Zitzmann
Fellow of the Royal Society of Medicine
Andrologist, Endocrinologist, Diabetologist
Specialist for Sexual Medicine (FECSM)
Clinical Andrology / Centre for Reproductive Medicine and Andrology
University Clinics, Muenster, Germany