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Is Testosterone Replacement Therapy a Lifelong Treatment?

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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.
 
 
For more details on the relation betweenestosterone deficiency and obesity, see my previous article “Testosterone and Fat Loss - the Evidence”.
 
For more information about the different types testosterone deficiency, see my previous article “Health Consequences of Subclinical Hypogonadism - riskier than previously thought

 

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.

Last modified on Tuesday, 18 October 2016 00:23
Monica

Medical Writer & Nutritionist

MSc Nutrition

University of Stockholm & Karolinska Institute, Sweden 

   Baylor University, TX, USA

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