Obesity is strongly linked to hypogonadism in males regardless of age

Obesity is strongly linked to hypogonadism in males regardless of age

Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Camacho EM, Huhtaniemi IT, O’Neill TW, et al. Eur J Endocrinol 2013;168(3):445-455.

Determinants of testosterone recovery after bariatric surgery: is it only a matter of reduction of body mass index? Luconi M, Samavat J, Seghieri G, et al. Fertil Steril 2013;99(7):1872-1879.

Testosterone concentrations in young pubertal and post-pubertal obese males. Mogri M, Dhindsa S, Quattrin T, et al. Clin Endocrinol (Oxf) 2013;78(4):593-599.

The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Saboor Aftab SA, Kumar S, Barber TM. Clin Endocrinol (Oxf) 2013;78(3):330-337.

This summary presents an overview of four published papers that describe the relationship between obesity and decreased testosterone levels (hypogonadism): one review focusing on the association between obesity, type 2 diabetes mellitus (T2DM) and secondary hypogonadism1 and three clinical studies.2-4 The three clinical studies included a cross-sectional survey assessing the correlation between body mass index (BMI) and sex steroid hormone levels in a general population of 161 males, as well as a longitudinal study investigating the effects of weight loss on sex hormone levels in 24 morbidly obese (BMI >40 kg/m2) males undergoing bariatric surgery;2 a cross-sectional observational study evaluating the impact of obesity on pubertal and post-pubertal males (n=50) aged 14–20 years;3 and a community-based longitudinal survey of 2736 men (baseline age 40–79 years) recruited from eight centers across Europe which aimed to assess the relationship between health and lifestyle factors and reproductive hormone levels in aging men.4

Key Points

  • Obesity is a major cause of hypogonadism, and while there are several diseases which may result in secondary hypogonadism in obese males, obesity itself is a well-known cause of the condition1

    • The relationship between hypogonadism and body composition is complex and not completely understood1
    • In the general male population, the prevalence of hypogonadism increases with BMI: in the cross-sectional survey of 161 male patients, the prevalence of hypogonadism (circulating total testosterone <12.1 nmol/L) in men with a normal BMI (<30 kg/m2) and in men considered obese (≥30 kg/m2) was 7% and 32%, respectively2
    • In the longitudinal phase of the study, the prevalence of hypogonadism in morbidly obese (BMI >40 kg/m2) patients who underwent bariatric surgery was 75%2
  • The association between obesity and low testosterone levels is not restricted to adult males3

    • In the study of young men aged 14–20 years (Tanner stage ≥4), those considered obese (BMI ≥95th percentile for age; n=25) had significantly lower total and calculated free testosterone versus those considered non-obese (BMI <85th percentile for age; n = 25) (10.5 vs. 21.4 nmol/L and 0.26 vs. 0.44 nmol/L; p<0.001 for all)
  • Weight loss in obese patients is associated with an increase in testosterone levels2

    • In a longitudinal study of patients undergoing bariatric surgery, patients had a median weight loss of 24.6% and 27.0% at 6 and 12 months post-surgery, respectively; this weight loss was associated with significantly increased total testosterone levels versus baseline at both time points (14.80 and 13.90 vs. 8.75 nmol/L, respectively; p<0.001 for both)
    • These increases in total testosterone levels were significantly greater than those expected based on the cross-sectional survey results
  • The decrease in testosterone seen in older males is not due to age, but to a concomitant increase in body weight, and weight loss or gain can result in significant changes in testosterone levels4

    • In a large, community-based study, over time men had a mean annualized decrease in total and free testosterone levels of 0.1 nmol/L and 3.83 pmol/L per year
    • Men who lost ≥10% of their baseline body weight over the study period had an increase in testosterone levels of 2.9 nmol/L, a change that was significantly different from that seen in men whose body weight remained within 10% of baseline (-0.4 nmol/L; p<0.01)
    • Similarly, men who gained ≥10% of their baseline body weight over the study period had a decrease in testosterone that was significantly more than those whose body weight remained ‘stable’ (-2.4 nmol/L vs. -0.4 nmol/L; p<0.01)
    • A loss of ≥5% of baseline body weight resulted in a significant increase in testosterone, and further weight loss resulted in additional increases. Weight gain resulted in progressive decreases in testosterone (Figure 1)
    • In contrast, free testosterone levels only changed significantly when the body weight lost or gained was ≥15%

What is known

There is a well-established link between obesity and testosterone deficiency (hypogonadism), and although there appears to be a complex interplay between body composition, obesity, androgen levels, vascular disease and T2DM,1 the exact mechanisms which lead to hypogonadism in obese men have yet to be determined.5-10 It is also well-known that there is a decrease in testosterone levels in men as they age;4,11-13 in younger men, there exists a relationship between T2DM and hypogonadism, with over half of all men with T2DM aged 18–35 years being diagnosed with hypogonadism, with free testosterone levels being negatively related to BMI in this population.3,14 This suggests a possible link between obesity and hormone levels in younger men. However, a large number of the clinical trials investigating the links between obesity and sex hormone concentrations suffer from recruitment biases, and there remain large gaps in the knowledge base, with very few randomized controlled trials conducted to date.2 Further research is required to fully elucidate the mechanisms behind obesity-related hypogonadism and determine potential treatment options.1

What these studies add

The results of the bariatric surgery study confirm the association between hypogonadism and adiposity, with the prevalence of hypogonadism found being similar to that seen in other studies.15,16 A novel result from the study is the demonstration of a non-linear relationship between BMI and sex hormones.2 While previous studies investigating testosterone in adolescents have been conducted,17-20 they did not measure testosterone levels using liquid chromatography tandem mass spectrometry, a sensitive and specific method that is now considered the gold standard method for measuring testosterone.21 The results of the community-based aging study show for the first time that moderate weight loss in males in the general population leads to testosterone increases, and that weight loss of >15% results in increases in both total and free testosterone, demonstrating that in an aging population, obesity prevention is an important factor in maintaining hypothalamic-pituitary-testicular axis functioning, and that weight loss can reverse changes in sex hormone levels.4

Figure 1: Mean change in testosterone levels with bodyweight changes in community-dwelling men

References

1. Saboor Aftab SA, Kumar S, Barber TM. The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Clin Endocrinol (Oxf) 2013;78(3):330-337.
2. Luconi M, Samavat J, Seghieri G, et al. Determinants of testosterone recovery after bariatric surgery: is it only a matter of reduction of body mass index? Fertil Steril 2013;99(7):1872-1879.
3. Mogri M, Dhindsa S, Quattrin T, et al. Testosterone concentrations in young pubertal and post-pubertal obese males. Clin Endocrinol (Oxf) 2013;78(4):593-599.
4. Camacho EM, Huhtaniemi IT, O'Neill TW, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol 2013;168(3):445-455.
5. Grossmann M. Low testosterone in men with type 2 diabetes: significance and treatment. J Clin Endocrinol Metab 2011;96(8):2341-2353.
6. Hammoud A, Gibson M, Hunt SC, et al. Effect of Roux-en-Y gastric bypass surgery on the sex steroids and quality of life in obese men. J Clin Endocrinol Metab 2009;94(4):1329-1332.
7. Hammoud AO, Gibson M, Peterson CM, et al. Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril 2008;90(4):897-904.
8. MacDonald AA, Herbison GP, Showell M, et al. The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis. Hum Reprod Update 2010;16(3):293-311.
9. Pellitero S, Olaizola I, Alastrue A, et al. Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery. Obes Surg 2012;22(12):1835-1842.
10. Saad F, Aversa A, Isidori AM, et al. Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr Diabetes Rev 2012;8(2):131-143.
11. Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 2002;87(2):589-598.
12. Mohr BA, Bhasin S, Link CL, et al. The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Eur J Endocrinol 2006;155(3):443-452.
13. Travison TG, Araujo AB, Kupelian V, et al. The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metab 2007;92(2):549-555.
14. Chandel A, Dhindsa S, Topiwala S, et al. Testosterone concentration in young patients with diabetes. Diabetes Care 2008;31(10):2013-2017.
15. Corona G, Rastrelli G, Monami M, et al. Body mass index regulates hypogonadism-associated CV risk: results from a cohort of subjects with erectile dysfunction. J Sex Med 2011;8(7):2098-2105.
16. Dhindsa S, Miller MG, McWhirter CL, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care 2010;33(6):1186-1192.
17. Denzer C, Weibel A, Muche R, et al. Pubertal development in obese children and adolescents. Int J Obes (Lond) 2007;31(10):1509-1519.
18. Moriarty-Kelsey M, Harwood JE, Travers SH, et al. Testosterone, obesity and insulin resistance in young males: evidence for an association between gonadal dysfunction and insulin resistance during puberty. J Pediatr Endocrinol Metab 2010;23(12):1281-1287.
19. Reinehr T, de Sousa G, Roth CL, et al. Androgens before and after weight loss in obese children. J Clin Endocrinol Metab 2005;90(10):5588-5595.
20. Taneli F, Ersoy B, Ozhan B, et al. The effect of obesity on testicular function by insulin-like factor 3, inhibin B, and leptin concentrations in obese adolescents according to pubertal stages. Clin Biochem 2010;43(15):1236-1240.
21. Rosner W, Auchus RJ, Azziz R, et al. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007;92(2):405-413.

Last updated: 2018
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