Male reproductive function disorders in metabolic syndrome and approaches to pharmacological correction

Abstract

Metabolic syndrome (MS) is one of the most urgent problems of modern medicine associated with an unhealthy lifestyle: physical activity restriction, a typical Western diet, accepted all over the world due to its taste and price, increased emotional stress, and a tendency to bad habits. Epidemiological data clearly indicate that an increase in the frequency of male infertility today occurs against the background of «non­ communicable epidemics» of the 21st century: MS, obesity, and type 2 diabetes mellitus (DM­2). Despite the fact that the basis of the treatment of MS and obesity should be a combination of the diet therapy and sufficient physical activity, in practice, the use of only non­drug methods of body weight correction is ineffective and short­term lasting, which necessitates some patients to pharmacotherapy. At the same time, not all mechanisms of the MS effect on male fertility are fully disclosed, and approaches to pharmacological correction are not fully defined.

The aim of the study is to summarize and critically discuss the available experimental and clinical studies of MS mechanisms involved in male fertility disorders and the modern methods of pharmacological treatment. To identify relevant publications an extensive search was carried out in ScienceDirect, PubMed, Scopus, Google Scholar, and related databases.

According to current concepts, obesity and insulin resistance (IR)/DM­2 are key components of MS. A decrease in testosterone levels (androgen deficiency) is a new pathogenetically important component of MS in men. In addition, among the mechanisms involved in the development of male reproductive function disorders, hyperinsulinemia, hyperleptinemia, oxidative stress and nitric oxide deficiency, systemic chronic inflammation, and renal lipotoxicity, induced by cytokines autoimmune local inflammation of the testes and epididymis are recalled.

Scientific publications evidenced the potential role of metformin in the correction of male reproductive disorders with MS; however, data on this drug's effects (protective or harmful) on testicular function are somewhat contradictory. The same applies to testosterone preparations. Considering that MS is associated with oxidative stress and a pro­inflammatory state, it seems pathogenetically substantiated to use drugs with powerful antioxidant properties in all cases of impaired fertility against the background of IR.

Based on the fact that human reproductive health is an important prerequisite for favorable demographic prospects of the nation, the establishment of the age­related mechanisms of male reproductive dysfunction as a consequence of MS, as well as the experimental substantiation for the prevention and treatment of such disorders are urgent problems today. This determines the need for both further experimental studies and clinical analysis of the MS effect on male reproductive function at different ages and also the development of approaches to timely appropriate pharmacological treatment.