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Metabolic syndrome and infertility in men

https://doi.org/10.1016/j.bpobgyn.2014.10.006Get rights and content

Highlights

  • Metabolic syndrome is a compilation of symptoms including central obesity, insulin resistance, dyslipidemia, and hypertension.

  • The molecular and physiologic abnormalities seen in metabolic syndrome extend well beyond the cardiovascular system.

  • Growing evidence has linked metabolic syndrome and its individual symptoms to the increasing prevalence of male infertility.

  • We review the recent evidence connecting metabolic syndrome to male infertility as well as the underlying pathophysiology.

Metabolic syndrome is a compilation of symptoms including central obesity, insulin resistance, dyslipidemia, and hypertension. Initially used to predict cardiovascular disease, it is now clear that the molecular and physiologic abnormalities seen in metabolic syndrome extend well beyond the cardiovascular system. Growing evidence has linked metabolic syndrome and its individual symptoms to the increasing prevalence of male infertility. This manuscript reviews the recent evidence connecting metabolic syndrome to male infertility as well as the underlying pathophysiology. Currently, there are limited prospective studies examining the effects of treating metabolic syndrome on male reproduction and these relationships will need to be a focus of further investigation.

Introduction

Infertility, defined by the World Health Organization as the inability to achieve a clinical pregnancy despite 12 months of unprotected intercourse, is estimated to affect 48.5 million couples worldwide [1]. Based on data collected through the National Survey of Family Growth, the prevalence of infertility in the United States is estimated between 12% and 15% [2], [3]. Both male and/or female factors can contribute to infertility. Male factor infertility is estimated to be the causative or a contributing factor in 20–50% of couples [4]. Interestingly, there is some evidence that the prevalence of male factor infertility may be increasing. A New England Journal of Medicine publication in 1995 reported the decline in semen quality received by a single sperm bank in Paris, France, between 1973 and 1992. While the semen volume remained unchanged overtime, the mean concentration of sperm and the percentage of motile sperm decreased over the course of 20 years [5]. Furthermore, a review of 61 papers from 1938 to 1990 also documented declining sperm parameters over time [6]. What could explain this decline in semen quality?

With the increasing prevalence of obesity and diabetes, metabolic syndrome has been postulated to be a potential contributing factor for the decline in semen quality and a contributing factor to male infertility. Metabolic syndrome is a cluster of physiologic abnormalities associated with an increased risk for cardiovascular disease. As defined by the Adult Treatment Panel III (ATPIII), metabolic syndrome is the presence of three or more of the following risk factors: abdominal obesity, elevated fasting glucose, elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, and elevated blood pressure [7] (Table 1). Although not strictly included in the diagnosis, patients with metabolic syndrome frequently have a pro-inflammatory state, often with elevated cytokines and acute phase reactants, such as C-reactive protein (CRP) [8]. In a study of more than 3000 adults aged 20 and over between 2003 and 2006, 34% of subjects met the criteria for metabolic syndrome. Furthermore, the likelihood of meeting criteria for metabolic syndrome increased with age and body mass index (BMI) [9]. This paper reviews the recent literature linking obesity, insulin resistance, dyslipidemia, inflammation, and metabolic syndrome as a whole to male infertility. While hypertension is one of the criteria for the diagnosis of metabolic syndrome, to our knowledge, there is little, if any, evidence directly linking hypertension to male infertility and thus will not be addressed in this chapter.

Section snippets

Abdominal obesity and infertility

Obesity is a cardinal feature of metabolic syndrome and has been increasing in prevalence [10]. Female obesity has already been well established as a cause of female infertility [11]. More recently, however, there has been considerable research examining the links between obesity and male factor infertility. In a 2007 study from Norway examining over 26,000 planned pregnancies and the length of time required to achieve pregnancy, after adjusting for female BMI and smoking habits, it was

Insulin resistance, diabetes, and infertility

The prevalence of diabetes was estimated at 347 million individuals worldwide in 2008 and is expected to continue to rise [33]. Insulin resistance and diabetes appear to negatively affect male infertility through similar pathophysiologic processes as obesity. Studies have demonstrated a relationship between hypogonadism and insulin resistance. The Massachusetts Male Aging Study followed 1156 men over 7–10 years. In this prospective study, the risk of developing diabetes was significantly

Dyslipidemia and infertility

Dyslipidemia, defined by elevated triglycerides and/or low HDL, is another key component of metabolic syndrome. While the volume of research is less compared to that of obesity and diabetes, there are animal and human studies that correlate dyslipidemia with male infertility. In an animal study by Yamamoto and colleagues in 1999, 20 rabbits were given either a diet containing 3% cholesterol or a normal diet. The authors found that the sperm concentration and the percentage of motile spermatozoa

Inflammation and infertility

Although not a specific ATP III criteria for the diagnosis of metabolic syndrome, an association between inflammation and metabolic syndrome has been well established [8]. Adipose tissue in obese males has been shown to express higher levels of inflammatory molecules such as TNF-α, IL-6, and CRP [48]. A study in 2003 by Weisberg and colleagues analyzed perigonadal, perirenal, mesenteric, and subcutaneous fat from both obese and lean mice. The authors found that obese mice had higher percentages

Metabolic syndrome and infertility

As detailed above, individual components of metabolic syndrome have been associated with male infertility. More recently, there has been an increase in studies examining metabolic syndrome as a whole and male infertility. In a 2005 cross-sectional study, Muller and colleagues found that decreasing levels of total testosterone, SHBG, and DHEA-S were associated with increasing risk factors for metabolic syndrome. The authors also found that low total testosterone and SHBG levels were associated

Summary

Metabolic syndrome is a complex constellation of symptoms that was originally described to identify patients at an increased risk for cardiovascular disease. Research over the past decade has demonstrated that the effects of metabolic syndrome extend well beyond the heart and into other organ systems, including the male reproductive system. Obesity has been shown to disrupt the hypothalamic–pituitary–gonadal axis, increase scrotal temperatures, and negatively affect sperm development,

Conflict of interest

The authors have no conflicts of interest.

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