A common question among hypogonadal men is how long they should stay on testosterone therapy.
The answer is - it depends on what is causing a man’s testosterone deficiency..
Traditionally, two types of testosterone deficiency have been acknowledged: [1]
1. Primary hypogonadism (also known as hypergonadotropic hypogonadism):
- Low testosterone with elevated LH, due primarily to insufficient testicular function.
2. Secondary hypogonadism (also known as hypogonadotropic hypogonadism)
- Low testosterone with low-normal LH, due primarily to insufficient hypothalamic-pituitary function.
Primary hypogonadism (caused by testicular insufficiency) is most common in older men, and its prevalence increases with age.[1] These men will require lifelong testosterone therapy due to aging-related impairment of testicular function.
In contrast, secondary hypogonadism (hypothalamic/pituitary insufficiency) is most often caused by obesity [2-4] and stress [5-7], and is more commonly seen in younger men.[1] Most people, including typical doctors, think that testosterone deficiency is only an old man’s problem. This is very wrong, as obesity is a stronger risk factor for testosterone deficiency (secondary hypogonadism) than age per se.[4] It is notable that non-obese men who become obese may experience a decline of testosterone levels comparable to that of 10 years of aging.[8]
Further evidence that obesity can cause hypogonadism comes from studies of weight/fat loss (induced by either low-calorie dieting or bariatric surgery), which show increases in testosterone levels proportional to the amount of fat loss.[9] However, this requires a very large weight loss, which most men won’t be able to achieve and maintain.
For example, in a study of obese men (mean age 46 years old), body weight 256 lb (116 kg), waist circumference 48 in (121 cm) and BMI 36, a very low-calorie diet resulted in a weight loss of 36 lb (16.3 kg) after 9-weeks, and 32 lb (14.3 kg) after a 12-month maintenance period.[10] Waist was reduced by 5 in, to 43 in (108 cm), at both the 9 week and 12 month time points. This increased total testosterone levels from approx. 332 ng/dL (11.5 nmol/L) to 461 ng/dL (16 nmol/L) and 404 ng/dL (14 nmol/L), respectively.[10] This fat loss-induced increase in testosterone – even if maintained - is unlikely to provide the whole array of health benefits seen with long-term testosterone therapy. However, fat loss in younger obese men in their 20-30s will likely raise testosterone levels more than what is seen in middle-age and older obese men.
Even when weight loss is successfully achieved with a strict calorie reduced diet, testosterone therapy during the diet shifts weight loss to almost exclusive fat loss, while diet alone causes loss of both fat mass and lean mass.[11]
Thus, men with secondary hypogonadism will also benefit from testosterone therapy. Whether lifelong testosterone treatment is needed in this population can only be answered by regular blood work.
References:
1. Tajar, A., et al., Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab, 2010. 95(4): p. 1810-8.
2. Cohen, P.G., The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone-estradiol shunt--a major factor in the genesis of morbid obesity. Med Hypotheses, 1999. 52(1): p. 49-51.
3. Ng Tang Fui, M., P. Dupuis, and M. Grossmann, Lowered testosterone in male obesity: mechanisms, morbidity and management. Asian J Androl, 2014. 16(2): p. 223-31.
4. Wu, F.C., et al., Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab, 2008. 93(7): p. 2737-45.
5. Kyrou, I. and C. Tsigos, Chronic stress, visceral obesity and gonadal dysfunction. Hormones (Athens), 2008. 7(4): p. 287-93.
6. Nargund, V.H., Effects of psychological stress on male fertility. Nat Rev Urol, 2015. 12(7): p. 373-382.
7. Bhongade, M.B., et al., Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples. Andrologia, 2015. 47(3): p. 336-42.
8. Travison, T.G., et al., The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metab, 2007. 92(2): p. 549-55.
9. Corona, G., et al., Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol, 2013. 168(6): p. 829-43.
10. Niskanen, L., et al., Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab, 2004. 6(3): p. 208-15.
11. Ng Tang Fui, M., et al., Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial. BMC Med, 2016. 14(1): p. 153.
