Diabetes and Hypogonadism in Males

Objectives: The spectrum of metabolic disease, including obesity, prediabetes and Type 2 diabetes mellitus (T2DM), is increasing globally at an alarming rate. In addition to the vascular complications classically associated with diabetes, other ‘non-classical’ comorbidities like psychological distress, osteoporosis and sarcopenia are getting increasingly reported with diabetes. Hypogonadism in males has been reported to be associated with diabetes from the early 1990s. Around one-fourth of male subjects with diabetes mellitus were found to have decreased testosterone levels by several studies from both India and other countries. There is apparently a bidirectional link between T2DM and hypogonadism, with each contributing to and adversely affecting the other. This article briefly reviews the literature related to diabetes and hypogonadism, including the burden in an Indian setting, the pathophysiological link between the two, clinical evaluation and the evidence for and against testosterone replacement therapy. Methodology: Literature and information regarding this topic were collected from various original articles, review articles, systematic reviews and meta-analyses available on various platforms such as Google Scholar and PubMed. Results: The caveat here for clinicians is whether this low testosterone in a diabetic male who is more than 50 years old is due to late-onset hypogonadism (andropause) or is it a consequence per se due to diabetes. Physicians should remind themselves that a diabetic patient may also harbour other conditions directly leading to hypogonadism (like hypothalamo-pituitary lesions or primary testicular conditions). Thus, it is imperative that a thorough history and physical examination are mandatory in all diabetes suspected to have hypogonadism. Judicious use of relevant hormonal tests, including FSH, LH, testosterone and sex hormone binding globulin (SHBG), may be warranted to confirm hypogonadism. Conclusions: Appropriate referral to endocrine specialists for further endocrine evaluation of aetiology and management may be required in a subset of patients. In these patients with diabetes with a clear organic aetiology of hypogonadism, the latter is managed with testosterone replacement at age-appropriate doses. However, in the larger group of diabetes patients with functional hypogonadism with or without symptoms of androgen deficiency, testosterone replacement therapy is controversial. There are studies that show improvement in metabolic metrics of body composition, glucose, lipid and inflammatory parameters. However, the main concern of aggravating an underlying androgen-dependent occult malignancy (prostate), rise in haematocrit-related potential thrombotic tendencies, including cardio- and cerebrovascular events, is to be weighed against the potential benefits. Thus, the Endocrine Society guidelines currently recommend against testosterone treatment for improving the metabolic status (glucose levels, dyslipidaemia) alone in a diabetic patient. However, the Indian consensus (Integrated Diabetes and Endocrine Academy [IDEA] group) suggests individualising testosterone replacement after discussing it with the patient.