Commentary on “Correlation between weight loss and testosterone restoration after sleeve gastrectomy in patients with biochemical male obesity-associated secondary hypogonadism”

Obesity stands as a main public health challenge in the recent century. The World Obesity Atlas 2024 projected that by 2035, more than 1.5 billion adults globally will be overweight or obese. Obesity is strongly related to many comorbid conditions like metabolic syndrome, non-alcoholic fatty liver disease, diabetes, cardiovascular disease, and obstructive sleep apnea. The latest epidemiological data indicate that the prevalence of overweight and obesity was almost 2 times higher in men than that in women of all ages, especially in reproductive age. They cause endocrine disorders, negatively affect reproductive capacity, and are a risk factor for associated comorbidities leading to increased mortality. Therefore, it is currently extremely important to prevent obesity and treat it effectively.1

A very common and significant consequence of obesity in men is male obesity-associated secondary hypogonadism (MOSH). Its symptoms include reduced muscle and bone mass, sexual dysfunction, decreased quality of life, and an increased risk of prediabetes, type 2 diabetes, and metabolic syndrome.2

In the recent article of the Asian Journal of Andrology, Zhao et al.3 presented the efficacy of laparoscopic sleeve gastrectomy (LSG) on MOSH remission and testosterone levels and explored the associations between weight loss and serum testosterone levels changes. This retrospective study was conducted in 186 patients with a mean age of 33.1 years and a mean body mass index (BMI) of 43.0 kg m⁻². MOSH remission rates at 12 months and 24 months post-LSG were 79.7% and 89.5%, respectively, accompanied by substantial increases of total testosterone levels (from 7.0 nmol l⁻¹ to 18.4 nmol l⁻¹) and free testosterone levels (from 0.2 nmol l⁻¹ to 0.4 nmol l⁻¹) at respective time points. Total weight loss percentage (TWL%) reached 34.4% and 32.3% at respective time points. Men with MOSH had luteinizing hormone (LH; 5.1 IU l⁻¹) and follicle-stimulating hormone (FSH; 4.2 IU l⁻¹) concentrations within the normal range before treatment and they did not change after 24 months, while estradiol levels decreased from 146.0 pmol l⁻¹ to 118.2 pmol l⁻¹.

On the one hand, the results obtained are extremely spectacular and prove that testosterone deficiency in men with obesity can be effectively treated surgically, but on the other hand, they raise a few questions. MOSH, often called functional hypogonadism (FH), is caused by obesity, age, exercise, stress, drugs, co-occurring diseases, and opioids; and in approximately 30% of cases, the cause is unknown.4 FH is defined as the coexistence of low testosterone and signs of hypogonadism occurring in the absence of structural pathology of hypothalamic-pituitary-testis (HPT) axis. So the main role is attributed to partial suppression of hypothalamic and pituitary function caused by excess estradiol produced by aromatization in adipocytes. Other mechanisms that impair gonadotropin-releasing hormone (GnRH) secretion (through kisspeptin suppression) include insulin and leptin resistance, and proinflammatory cytokines.4 However, the authors did not observe a reduction in gonadotropin secretion in men with obesity (despite low testosterone levels), and these levels did not increase after surgery. Whereas, estradiol levels were significantly reduced after treatment. We also know that obesity is associated with low sex hormone binding globulin (SHBG) levels, and these levels increased after surgery. Increasing SHBG levels can, in turn, result in decreased free testosterone levels. However, in the study cohort, free testosterone levels also increased significantly.

The hormonal changes described by the authors after surgical treatment indicate that the pathomechanism of testosterone deficiency in men with obesity is complex and the specific causes are not fully understood. But, the fact that bariatric treatment leads to the resolution of MOSH is extremely important for the health of men with obesity. It should be emphasized, however, that hypogonadism in men, regardless of the cause, is a coincidence of low testosterone levels and clinical symptoms. Although the authors of the discussed studies did not evaluate these symptoms (which were usually nonspecific), it appears that increasing testosterone levels in these patients must have had a beneficial effect on their well-being, quality of life, and sexual activity, and not just reduced the risk of metabolic disorders. Weight loss likely also has a beneficial effect on male fertility.

According to the European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males, the diagnosis of functional hypogonadism is based on the presence of clinical symptoms of testosterone deficiency in combination with low serum testosterone levels, and after exclusion of organic causes of hypogonadism.5 In men with MOSH and a BMI >40 kg m⁻², bariatric surgery seems to be the most effective method,6 but the first-line treatment should be lifestyle changes, physical exercise, modification of drugs (e.g., opiates and anabolic steroids), and treatment of chronic diseases. FH (also MOSH) can be diagnosed after excluding primary and secondary hypogonadism, and after eliminating the factors causing androgen deficiency. Testosterone replacement therapy is not the treatment of choice for weight loss, and is contraindicated in men who desire fertility.

COMPETING INTERESTS

All authors declare no competing interests.