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Obesity a Growing Issue for Male Fertility

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Obesity a Growing Issue for Male Fertility MEN'S HEALTH PEER REVIEWED Obesity A growing issue for male fertility MADHUNI HERATH MB BS, BMedSci(Hons), MPH, FRACP IE-WEN SIM MB BS(Hons), BMedSci, FRACP Obesity in men has been associated with besity is a growing health issue that causes substantial reduced fertility. The impact of paternal body morbidity and mortality. Epidemiological data mass index on fertility is multifactorial, with suggest an association between increasing body mass increased weight associated with endocrine index (BMI) and reduced fertility in men, with one Ostudy suggesting that a gain of 10 kg decreases male fertility dysregulation and impaired sexual desire and function. Weight loss may improve fertility by approximately 10%.1 The effect of BMI on male fertility is outcomes as well as conferring longer-term multifactorial, with increased weight associated with changes health benefits. in sex hormone profile and impaired sexual desire and function. Some studies also suggest poorer semen parameters in over- weight men. Despite the prevalence and costs of male subfertility, there are few data regarding the fertility benefits of weight loss in men. Although weight reduction may normalise the hormone profile, the extent that this improves fertility and the time course of any improvement are unclear. Factors Contributing to Subfertility in Obese Men Increased BMI is strongly associated with both hormonal dys- regulation and poorer sexual function in men, which can impair fertility, as outlined in the Flowchart. Hormonal dysregulation Excess body weight has numerous effects on the reproductive First published: MedicineToday 2014; 15(1): 49-53 Updated SEPTEMBER 2020 hormone profile in men, leading to: • a relative excess of oestrogen Dr Herath is the Andrology Fellow at Monash Health, which is supported by • resultant suppression of hypothalamic secretion of Healthy Male (formerly Andrology Australia). Dr Sim is a Consultant Andrologist -gonadotrophin-releasing hormone (GnRH) at Monash Health and Monash IVF, Expert Advisor to Healthy Male, and • reduced serum levels of gonadotrophins (luteinising Consultant Endocrinologist at Monash Health, Eastern Health and Western hormone and follicle stimulating hormone) © GETTY IMAGES/OF SCIENCE EYE. SPERM FERTILISING AN OVUM Health, Melbourne, Vic. • reduced serum testosterone levels. MedicineToday ❙ Collection: Obesity Awareness SEPTEMBER 2020 1 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2020. MEN'S Health continued POTENTIAL EFFECTS OF INCREASED BMI ON FERTILITY IN MEN Increased BMI in men Excessive alcohol, sedentary lifestyle Increased Increased aromatisation Obstructive Mood Psychosocial Cardiovascular testicular of androgens sleep apnoea disorders factors risk factors, temperature including diabetes Hypogonadotrophic hypogonadism Abnormal spermatogenesis Reduced libido Erectile dysfunction Subfertility Abbreviation: BMI = body mass index. Furthermore, there may be a feedback by the aromatase enzyme in adipose tis- and psychosocial factors. effect as there is a well-recognised asso- sue. In overweight men, the increased Obese men report poorer sexual desire ciation between hypogonadism and the adipose tissue mass and upregulation of and satisfaction compared with control metabolic syndrome, which itself is asso- aromatase activity lead to excess periph- subjects, which may contribute to avoid- ciated with increased weight. eral aromatisation of androgens. The ance of sexual encounters.3 Overweight resulting hyperoestrogenism exerts a individuals are more likely to have chronic Effects on testosterone negative feedback effect on hypothalamic medical comorbidities and to be of lower BMI is a strong predictor of low serum GnRH pulses, reducing stimulation of socioeconomic class with resulting finan- total testosterone concentrations in men, gonadotrophin secretion. Circulating cial or domestic problems that can reduce with a clear inverse correlation shown in oestrogens may also have a direct adverse libido. Depressive illness is also more many studies. BMI is also inversely pro- effect on testicular function. In addition, common, and correlates with both low portional to free testosterone concentra- circulating endogenous opioids are likely libido and ED. Low libido ultimately tions, suggesting an association even after to have a pathophysiological role in the results in reduced coital frequency, low- accounting for lower sex hormone bind- development of hypogonadotrophic ering fertility rates. ing globulin levels due to insulin hypogonadism in overweight men. In addition, sexual dysfunction is an resistance.2 important contributor to subfertility, with Reduced libido and erectile the presence of ED being correlated with Effects on other reproductive dysfunction lower fertility rates in men. ED is more hormones Although hormonal dysregulation may prevalent in men with higher BMI. Its Low serum testosterone in overweight affect semen quality, as described below, aetiology in this setting is multifactorial, men is associated with inappropriately the primary reasons for the reduced fer- including androgen deficiency and low-to-normal levels of gonadotrophins. tility rate observed in obese men may be vasculogenic dysfunction. This reversible hypogonadotrophic hypo- decreased sexual desire and impaired Medical comorbidities such as the gonadism includes hyperoestrogenism sexual function. Potential contributing metabolic syndrome are significantly as a significant component. Androgens factors include androgen deficiency, associated with ED. Both diabetes and are converted to oestrone and oestradiol organic causes of erectile dysfunction (ED) hypertension are associated with vascular 2 MedicineToday ❙ Collection: Obesity Awareness SEPTEMBER 2020 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2020. dysfunction, and diabetes may also lead TABLE. FERTILITY ASSESSMENT OF OVERWEIGHT MEN to neuropathic complications. Further- more, obstructive sleep apnoea (OSA) is History more common in obese men and is strongly independently linked with both Risk factors for male • Previous history of infertility infertility ED and androgen deficiency. • Family history of infertility • Genital trauma or infection (e.g. orchitis) Reduced sperm quality • Cryptorchidism, testicular tumours Effect of BMI on semen parameters • Previous inguinal or pelvic surgery The relationship between BMI and sub- • Previous chemotherapy or radiotherapy fertility is not completely explained by • Occupational or environmental toxin exposure obesity-associated sexual dysfunction • Current medications and reduced frequency of intercourse. • Tobacco, alcohol, anabolic steroid use Changes with increased BMI, including hormonal imbalance and increased tes- Symptoms of androgen • Decreased sexual desire deficiency ticular temperature, may impair semen • Decreased sexual function parameters. • Reduced sense of wellbeing, energy, mood A recent systematic review and Comorbidities • History of cardiovascular disease, stroke meta-analysis demonstrated an associa- • Diabetes mellitus, dyslipidaemia, hypertension tion between increased BMI and modest • Obstructive sleep apnoea decreases in sperm motility, sperm mor- phology and concentration,4 whereas Physical examination earlier reviews have failed to establish this General examination • Height, weight, waist circumference 7 correlation. The association between BMI • Blood pressure and sperm DNA fragmentation has also been investigated. DNA fragmentation Genital examination • Testicular volume may correlate with poorer sperm quality • Epididymis, vas deferens and integrity, and consequently be asso- • Signs of androgen deficiency ciated with reduced fertility and an • Secondary sexual characteristics increased incidence of subsequent mis- • Gynaecomastia carriage. Although some studies have • Hair distribution demonstrated increased fragmentation in men with severe obesity,5,6 other studies Investigations have not reliably reproduced these find- Reproductive and other • Total and calculated free testosterone and SHBG levels 5,6,8 ings. Additionally, mouse models sug- hormones • FSH, LH and prolactin levels; thyroid function tests gest that paternal obesity may have met- abolic sequelae and lead to subfertility and Semen analysis • Sperm concentration, motility, morphology other metabolic effects in offspring Cardiovascular risk • Diabetes screen 9 through epigenetic effects. • Lipid profile Effect of BMI on assisted reproductive Other • Liver function tests (to exclude nonalcoholic fatty liver disease) technology outcomes • Sleep study (if symptoms of obstructive sleep apnoea) With the increasing use of assisted repro- ductive technology, the impact of paternal ABBREVIATIONS: FSH = follicle stimulating hormone; LH = luteinising hormone; SHBG = sex hormone binding BMI on their outcomes is pertinent. globulin. Increased paternal BMI has been associ- ated with reduced chemical and clinical on implantation and pregnancy rates, Lifestyle and environmental factors pregnancy rates, as well as lower live-birth there have also been suggestions that A range of potentially remediable lifestyle rates.8,10,11 This may be a result of sperm paternal obesity may have an impact on factors can affect fertility and should be dysfunction that is not detectable by blastocyst development, possibly as a con- addressed in all men with subfertility. standard analysis. In addition to effects sequence of sperm DNA damage. Some of these factors,
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