Review
Obesity and testicular function

https://doi.org/10.1016/j.mce.2009.06.007Get rights and content

Abstract

Obesity in men, particularly when central, is associated with lower total testosterone [TT], free testosterone [FT] and sex hormone-binding globulin [SHBG], and a greater decline in TT and FT with increasing age compared with lean men. Obesity-related conditions such as obstructive sleep apnea, insulin resistance and type 2 diabetes mellitus are independently associated with decreased plasma testosterone. Possible mechanisms include decreased LH pulse amplitude, inhibitory effects of oestrogen at the hypothalamus and pituitary and the effects of leptin and other peptides centrally and on Leydig cells. Obese men have reduced sperm concentration and total sperm count compared to lean men but sperm motility and morphology appear unaffected. The cause and effect relationships between low plasma androgen levels, obesity and the metabolic syndrome, and associated cardiometabolic risk remain unclear. While weight loss normalizes TT and FT in obese men, androgen replacement in the short term does not significantly improve cardiometabolic risk profile despite reducing fat mass.

Introduction

Obesity has increased dramatically worldwide over the past 20–30 years. The risk of developing common chronic diseases such as diabetes mellitus, hypertension, heart disease and stroke increased with the severity of overweight in both men and women, particularly with predominant accumulation of visceral fat. Obese men and women with body mass index [BMI] over 35 kg/m2 have approximately 20 times higher likelihood of developing diabetes mellitus (Field et al., 2001). Obesity has also been shown to be associated with alterations in sex steroid hormone concentrations. Low plasma testosterone concentrations are associated with visceral obesity and the metabolic syndrome and increased cardiovascular risk (Haffner et al., 1993); the cause and effect relationship remain unresolved. In this review, we discuss the effects of obesity on the hypothalamic–pituitary–testicular axis, plasma androgen levels and spermatogenesis, as well as the effects of weight loss on androgen levels and the effects of androgen replacement therapy in this population.

Section snippets

Hypothalamic–pituitary–gonadal (HPG) axis

In a normal adult male, the preoptic area and the medial basal region of the hypothalamus secrete gonadotropin-releasing hormone [GnRH] in a pulsatile manner. GnRH interacts with cell-surface receptors coupled to G proteins on the plasma membrane of pituitary gonadotrophs stimulating the release of luteinizing hormone [LH] and follicle-stimulating hormone [FSH]. LH binds to the LH receptor on the plasma membrane of Leydig cells resulting in the synthesis of the enzymes of testosterone

Circulating testosterone levels

Testosterone is present in plasma as free or unbound testosterone, albumin-bound and sex hormone-binding globulin [SHBG]-bound. In lean men, about 2% of testosterone is unbound, 44% is bound to SHBG and 50% is bound to albumin and other proteins (Pardridge, 1986). The proportion of testosterone that is free together with the albumin-bound fraction have been considered to be the biologically active component that is readily available to the tissues and are collectively known as bioavailable

Obesity and the HPG axis

Obesity is associated with a reduction in serum total testosterone and SHBG levels (Gray et al., 1991, Kaufman and Vermeulen, 2005). In the Massachusetts Male Ageing Study, men who were obese at baseline and at follow-up, whether measured by BMI or central obesity (waist–hip ratio or waist circumference) had a greater decline of free and total testosterone and SHBG compared to men who were never classified as obese (Derby et al., 2006). The mechanism/s by which obesity affects the HPG axis

Effect of distribution of adipose tissue on plasma androgen levels

There is an inverse relationship between plasma total testosterone, free testosterone and SHBG with visceral fat (Haffner, 2000) that is considerably stronger than inverse relationship between plasma total testosterone, free testosterone and SHBG with BMI (Svartberg et al., 2004). Plasma levels of free testosterone and SHBG (Abate et al., 2002) correlate inversely with both truncal and peripheral adiposity in men with and without diabetes. Nielsen et al. investigated the role of visceral

Obesity, obstructive sleep apnea and hypogonadism

Obstructive sleep apnea [OSA] is associated with severe intermittent hypoxia and sleep fragmentation. Although obesity is not essential for the development of OSA, about two-thirds of patients with OSA are obese (Wittels, 1985). Patients with OSA have been found to have lower free and total testosterone and SHBG independent of ageing and adiposity. Taken together the available data suggests that OSA produces a reversible dysfunction of the hypothalamic–pituitary–gonadal axis, the magnitude of

Ageing, obesity and plasma testosterone

Normal ageing is characterized by changes in body composition, including a preferential increase in abdominal fat and a loss of skeletal muscle mass (Seidell and Visscher, 2000). Ageing is associated with decreased levels of testosterone and dihydrotestosterone, however age-related differences in androgen levels are partly mediated by variation in fat distribution (Couillard et al., 2000). The prevalence of the metabolic syndrome increases with age and is independently associated with lower

Obesity and spermatogenesis

Obesity is associated with alterations in spermatogenesis. In subfertile men, obesity was three times more prevalent compared to male partners of couples with idiopathic or female factor infertility (Hammoud et al., 2006).

A cross-sectional study of 1558 Danish men found that men with both a low BMI [<20 kg/m2] and a high BMI [>25 kg/m2] had a reduction in sperm concentration and total sperm count compared to men with BMI between 20 and 25 kg/m2 after correction for disorders of reproductive

Obesity and hypogonadism: cause or effect?

The cause and effect relationship between obesity, insulin resistance, the metabolic syndrome, type 2 diabetes mellitus and androgen deficiency remains unclear. Data from the Massachusetts Male Aging Study showed that lower levels of total testosterone and SHBG were predictive of the development of the metabolic syndrome, particularly in men with BMI < 25 kg/m2 (Kupelian et al., 2006). In contrast other data suggests that the metabolic syndrome is an independent risk factor for hypogonadism in

Conclusion

Obesity, the metabolic syndrome, and type 2 diabetes mellitus are associated with low plasma testosterone levels which should be regarded as a marker of, and possibly risk factor for progression of disordered metabolism. The mechanisms and cause and effect relationships remain to be determined. In addition although there is an association between obesity and abnormalities of spermatozoa, the prevalence and functional consequences, similarly remain to be determined.

Lifestyle intervention is of

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