The Effect of Hypogonadism and Testosterone Replacement Therapy on Components of the Cardio-Metabolic Syndrome and Diabetes Mellitus

Introduction

Hypogonadism in patients with type 2 diabetes mellitus (T2DM) is an underestimated medical problem that is associated with decreased sexual function, bone mineral density, and sense of well-being. It is also associated with increased incidence of T2DM and the cardiac metabolic syndrome (CMS).13 Usually, hypogonadism in patients with T2DM remains undiagnosed until patients complain of erectile dysfunction (ED), which affects one-third of all patients.4, 5 The etiology of ED in diabetic patients is often secondary to vascular disease or autonomic neuropathy. However, hypogonadism is also playing a role in the etiology of ED in patients with DM as well as in the metabolic derangements that these patients are suffering from. The current Endocrine Society guidelines for testosterone therapy in adult men with androgen deficiency syndromes recommend testosterone treatment to maintain secondary sex characteristics, improve sexual function, sense of well-being, and bone mineral density.6 However, the actual benefit of testosterone replacement therapy in patients with T2DM may go beyond these effects.

Abstract

There is increased awareness of the association between hypogonadotropic hypogonadism (HH) and the components of the cardiac metabolic syndrome (CMS) and type 2 diabetes mellitus (T2DM). The indications for treatment, as established by the Endocrine Society, focus on addressing the decreased sexual function, bone mineral density, and on improving the sense of well-being of those patients with biochemical evidence of HH. Recent studies, however, suggest that treating HH also improves insulin resistance in T2DM and each of the components of the CMS. Larger studies of testosterone administration need to be conducted to more clearly outline benefits and balance them against the risks of prostatic and cardiovascular disease (CV) as well as other adverse outcomes. The present article explains the pathophysiology of HH, reviews the articles highlighting this association, and discusses the clinical evidence supporting the effects of testosterone replacement therapy and its potential adverse effects in patients with T2DM and CMS.

Keywords

cardiac metabolic syndrome, type 2 diabetes mellitus, obesity, hypogonadotropic hypogonadism, insulin resistance, testosterone