Type 2 diabetes and obesity have become global pandemics. Obesity is central to many cardiovascular disease risk factors such as insulin resistance, hypertension, type 2 diabetes, and sleep apnea. It has been shown that obese men, who are often accompanied by hypogonadism, have significantly lower testosterone levels. Testosterone promotes protein synthesis and increases male mobility. Insufficient testosterone adversely affects the metabolism of sugar, protein and fat. Several epidemiological research studies have shown that men with reduced testosterone levels are at significantly increased risk of developing type 2 diabetes in the future. Treatment that lowers testosterone as a result of prostate cancer treatment significantly increases the incidence of insulin resistance and type 2 diabetes. Currently, there is a lack of adequate attention to hypogonadal axis dysfunction (MOSH) associated with obesity in men. This article discusses the incidence, pathogenesis, and treatment measures for the disease. Disease definition: The function of the hypothalamic-pituitary-testicular axis in the human body is precisely regulated by many factors. The diagnosis of MOSH can be considered in obese men with significantly reduced testosterone levels and normal or mildly reduced gonadotropin (FSH and LH) levels, excluding hypothalamic pituitary occupational lesions and other chronic diseases affecting gonadal axis function.MOSH is often associated with clinical manifestations of testosterone deficiency, such as erectile dysfunction, decreased libido, fatigue, decreased memory, depressed mood, decreased bone mass/bone loss of bone mass/osteoporosis, and increased abdominal fat. The relationship between reduced testosterone levels and clinical manifestations is more ambiguous. In a community-based study of middle-aged and older men aged 40-79 years, total testosterone < 8 nmol/L was associated with decreased libido, testosterone < 8.5 nmol/L caused erectile dysfunction, testosterone < 11 nmol/L was associated with decreased morning erections, and testosterone < 13 nmol/L may cause decreased physical vigor. Therefore, testosterone levels <8 nmol/L or free testosterone <220 pmol/L are used as clinical criteria for the diagnosis of MOSH. Gonadotropin levels can be low or normal. The incidence of MOSH correlates with the severity of obesity. The more obese the population, the higher the prevalence of hypogonadism. A cross-sectional study in the Department of Endocrinology at Peking Union Medical College Hospital showed a negative correlation between testosterone levels and weight and waist circumference. In patients with waist circumference ≥2500px, the incidence of testosterone levels ≤10nmol/L was 85.7%. According to the current understanding of this disease, the diagnosis of MOSH includes the following points: (1) male BMI > 30 kg/m2; (2) symptoms of hypogonadism, including abnormal sexual function, gynecomastia, paroxysmal hot flashes, fatigue, and depression; (3) total blood testosterone levels less than 8 nmol/L in two repeated measurements with normal sex hormone-binding globulin; (4) gonadotropin levels less than 8 nmol/L in two repeated measurements with normal sex hormone binding globulin. (4) Reduced or decreased levels of gonadotropins FSH and LH; (5) Excluding other systemic diseases causing hypogonadism; Pathogenesis: The function of the hypothalamic-pituitary-testicular axis is precisely regulated by a variety of factors. By secreting GnRH, the hypothalamus regulates the secretion of gonadotropins (FSH and LH) by the pituitary gland, which in turn promotes androgen and sperm production by the testes. The testis regulates the secretory function of hypothalamic GnRH through multiple pathways of negative feedback. First, the supporting cells (also known as Sertoli cells) in the testis negatively inhibit hypothalamic GnRH secretion by secreting inhibin. Second, testosterone secreted by testicular interstitial cells (also known as Leydig cells) is converted to estradiol by aromatase action in peripheral adipose tissue. Many factors can affect the function of the gonadal axis, for example, acute inflammatory states, malnutrition or extreme wasting can cause a significant decrease in androgen production by the testes due to a decrease in hypothalamic GnRH secretion. Obese patients have a large amount of adipose tissue in their bodies. Aromatase is mainly expressed in adipose tissue. It converts testosterone to estradiol, leading to a decrease in the substrate (testosterone) and an increase in estradiol levels. Excessive levels of estradiol negatively feedback inhibits hypothalamic GnRH secretion and pituitary FSH and LH secretion, resulting in decreased androgen production by the testes. Excessive estradiol levels also cause gynecomastia. Other factors associated with obesity, such as hypoxia (sleep apnea), elevated blood glucose, and elevated levels of chronic inflammatory factors, may also inhibit hypothalamic GnRH secretion. Studies have shown that type 2 diabetic patients with significantly elevated blood glucose have a reduced pulse frequency of LH secretion, which can lead to lower testosterone production by the testes. Disease treatment: The pathogenesis of MOSH suggests that weight reduction may be the best treatment option for MOSH. It has been shown that with significant weight loss, whether through a low-calorie diet or through gastrointestinal bariatric surgery, the patient’s gonadotropin levels will increase, as will testosterone levels. In addition, aromatase inhibitors, block the conversion of testosterone to estradiol in peripheral tissues. The application of drugs in obese patients results in lower estradiol levels and reduced negative feedback inhibition of hypothalamic GnRH secretion by estradiol, leading to increased pituitary secretion of FSH and LH, which in turn promotes more androgen and sperm production by the testes. The results of a recent meta-analysis (n=479, observed over 28 weeks) showed that weight loss by different means elevated testosterone levels. A low calorie restricted diet resulted in a mean weight reduction of 9.8±4.5%; gastrointestinal surgery resulted in a mean weight reduction of 32±5.4%. Further subgroup analysis of patients who underwent gastrointestinal surgery for weight loss showed that biliopancreatic bypass (gastrointestinal diversion, which can cause malnutrition, has a stronger weight loss effect) and patients undergoing gastric banding, testosterone was elevated by 11.6 (95% CI 7.1C16.0) and 6.1 (2.4C9.8) nmol/l, respectively (p < 0.0001). Further meta-analysis showed that younger age of the patient, heavier preoperative weight and greater postoperative BMI reduction were favorable predictors of higher testosterone levels after surgery. After surgery, blood estradiol levels decreased by 8.9 (95% CI 15.2 - 2.5) pmol/L compared with preoperative levels (P<0.0001< span="">). FSH increased by 1.8 (95% CI 1.3 C2.3) U/L and LH increased by 1.3 (95% CI 0.8C1.8) U/L. Taken together, these results suggest that gonadotropins can increase significantly after bariatric surgery as body weight decreases and estradiol levels decrease; the greater the weight loss, the greater the increase in testosterone. Aromatase inhibitors are another drug that blocks the onset of MOSH disease. A study included 12 obese patients with a BMI of 45.7±3.0 kg/m2. 6 months of treatment with an aromatase inhibitor (letrozole) (dosing regimen, 2.5 mg once weekly): estradiol decreased from 123±11 pmol/L to 57±7 pmol/L, LH increased from 4.4±0.6 U/L to 11.1±1.5, FSH increased from 4.8 ± 0.8 to 12.1 ± 1.5 U/L, and total blood testosterone levels increased from 5.9 ± 0.5 to 19.6 ± 1.4 nmol/L. Other similar studies have suggested that aromatase inhibitors, by elevating gonadotropin levels, may increase spermatogenesis. The above clinical trial results and our clinical experience suggest that aromatase inhibitors can significantly increase testosterone levels. However, it is unclear whether long-term use of the drug can bring additional substance metabolism benefits to obese patients, as well as adverse effects on the skeleton.