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Hypogonadism is a chronic clinical condition. What are the potential harms when a patient does not adhere to a regimen of chronic testosterone therapy?
Response by Wayne J.G. Hellstrom, MD, Posted 06/02/08

Hypogonadism, affecting 4 to 5 million American men, is a consequence of low testosterone production resulting from primary or secondary causes. Low testosterone has been associated with signs and symptoms that include diminished libido, erectile dysfunction, reduced bone and muscle mass, increased body fat, decreased physical performance, and poor concentration and memory.1 Furthermore, low testosterone levels are associated with chronic comorbid conditions, including diabetes, coronary artery disease, hypothyroidism, and hyperlipidemia.2-6 In 2006, the Endocrine Society released a clinical practice guideline on the administration of testosterone therapy for men with androgen deficiency syndromes.1 The guideline supports the use of testosterone therapy to treat the signs and symptoms of androgen deficiency. Testosterone therapy has been a mainstay of hypogonadism management for decades, and therapeutic delivery systems include short-acting injections, buccal systems, gels, patches, and long-acting depot formulations.

Experience has shown that testosterone therapy mitigates many of the signs and symptoms of hypogonadism, however, little is known about the potential harm of interrupting chronic treatment. As with treatment for other chronic conditions, when testosterone therapy for hypogonadism is interrupted or discontinued, underlying signs and symptoms may return. A study by Yialamas and colleagues assessed the effects of acute testosterone withdrawal on insulin sensitivity of otherwise healthy men with idiopathic hypogonadotropic hypogonadism. Twelve subjects discontinued chronic testosterone therapy (gel), which resulted in reduced insulin sensitivity. Two weeks after cessation of testosterone therapy, fasting glucose levels increased from 86.7±1.3 to 90.8±1.7 mg/dL (P<.09).7 Likewise, in a model involving 58 healthy men, Lee and colleagues demonstrated that acute withdrawal of testosterone (gel), estradiol (patch), or both resulted in increased bone resorption (accelerated loss of bone density) in as little as 6 weeks.8

Cessation of testosterone therapy is likely to cause erectile problems and an overall feeling of lethargy soon after discontinuing therapy. Changes in serum lipid levels, impact on glycosylated hemoglobin levels, and increase in body mass index may take longer to manifest. Nonadherence to chronic therapy or missed doses of therapeutic preparations with short half-lives, such as gels, which require daily application, may cause a more acute impact or daily fluctuations in testosterone levels. A long-acting depot formulation, testosterone undecanoate (which is available in Europe and 70 countries worldwide), has a longer half-life and provides consistent, daily delivery of testosterone. This preparation may benefit men who are at risk for nonadherence or inconvenienced by daily application of testosterone gel.

 

References

  1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2006;91(6):1995-2010.
  2. Hak AE, Witteman JCM, de Jong FH, Geerlings MI, Hofman A, Pols HAP. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam Study. J Clin Endocrinol Metab. 2002;87(8):3632-3639.
  3. Kupelian V, Page ST, Araujo AB, Travison TG, Bremer WJ, McKinlay JB. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab. 2006;91(3):843-850.
  4. Meikle AW. The interrelationships between thyroid dysfunction and hypogonadism in men and boys. Thyroid. 2004;14(suppl 1):S-17-S-25.
  5. Oppenheim DS, Greenspan SL, Zervas NT, Schoenfeld DA, Klibanski A. Elevated serum lipids in hypogonadal men with and without hyperprolactinemia. Ann Intern Med. 1989;111(4):288-292.
  6. Rosano GMC, Sheiban I, Massaro R, et al. Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res. 2007;19(2):176-182.
  7. Yialamas MA, Dwyer AA, Hanley E, Lee H, Pitteloud N, Hayes FJ. Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2007;92(11):4254-4259.
  8. Lee H, Finkelstein JS, Miller M, Comeaux SJ, Cohen RI, Leder BZ. Effects of selective testosterone and estradiol withdrawal on skeletal sensitivity to parathyroid hormone in men. J Clin Endocrinol Metab. 2006;91(3):1069-1075.

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