Testosterone Therapy: Do you really need it?

A 2013 article published in JAMA stated that there has been a dramatic increase in inappropriate use of testosterone therapy in healthy middle-aged and older men. One possible reason for this is the rise in direct-to-consumer advertising encouraging the use of testosterone products for nonspecific symptoms such as decreased energy and sexual interest. In actuality, testosterone replacement should only really be administered to patients who are hypogonadal.

What is hypogonadism?

Hypogonadism is defined as a decrease in either of the two major functions of the testes: sperm production or testosterone production. It can be classified as a disease of the testes (primary hypogonadism) or a disease of the pituitary or hypothalamus (secondary hypogonadism). Signs and symptoms typically include low energy, low libido, and decreased mood; less common symptoms include decreased muscle mass, decreased body hair, small testes. It is more common in males than in females. It must be noted that hypogonadism manifests differently between the genders and can occur before or after the onset of puberty. Signs and symptoms would also differ between different age and sex groups, and testosterone therapy would only be one of many modalities to treating the condition.

How do we test for hypogonadism?

Based on the clinical presentation and if there is suspicion of hypogonadism, testosterone can be measured with a blood test in the morning on three separate occasions. If testosterone is found to be consistently low, serum LH and FSH levels will be drawn to destinguish between primary and secondary hypogonadism. Further testing can be done by looking into Adrenocorticotropic hormone (ACTH) stimulation testing: in patients in whom a form of congenital adrenal hyperplasia is suspected. Patient who are younger with signs of hypogonadism can also get a Luteinizing-hormone releasing hormone (LHRH) stimulation testing to distinguish between true hypogonadotropic hypogonadism and constitutional delay in growth and maturation. The goal of these tests is the verify that the patient's symptoms are not caused by any other conditions.

What scenarios would testosterone therapy be inappropriate?

As of right now the benefits of testosterone therapy have not been established in men who have a low testosterone for no apparent reason other than age. Furthermore, simply having a single but not repeatedly low serum testosterone concentration should not received testosterone therapy. Testosterone therapy when not warranted may eventually results in suppression of spermatogenesis and decreased testicular size.

What are the risks of testosterone therapy?

It is important to know the evidence regarding risks in testosterone therapy. A variety of studies have been done to see the consequences.

1. Blood Clots - Erythrocytosis is a common adverse effect of testosterone administration, which can elevate the risk of getting venous thromboembolisms. In 2014, the FDA has added general warning to testosterone products about potential for venous blood clots.

2. Prostate - A 2010 systematic review and meta-analysis found that testosterone therapy was not associated with a significant difference in the risk for prostate biopsy or prostate cancer. A more recent review in 2014 reached a similar conclusion and even found no significant association between the incidence of prostate nodules, prostate biopsy, or prostate cancer among different formulations of TT.

3. Cardiovascular Risk - Cardiovascular risk with testosterone therapy has been a large concern during this decade with differing conclusions occuring with different studies. The same study done in 2010 concluded that testosterone therapy had no significant effect on mortality or on prostate or CV outcomes. However, a large study done by the Veterans Affair in 2013 showed that patients receiving testosterone had a higher rate of myocardial infarctions. According to the study, the use of testosterone in men was found to be associated with an approximately 30% higher risk for death, MI, or ischemic stroke. In 2014, a study with the largest cohort with PLoS One, men aged 65 years and older had a 2-fold increase in the risk for MI in the 90 days after filling an initial testosterone prescription. The risk declined to baseline in the 91-180 days after initial testosterone prescription among those who did not refill their prescription. Risk was similarly increased in younger men with pre-existing diagnosed heart disease. Lastly, an article published in JAMA in 2015 showed that testosterone therapy did not accelerate progression of subclinical atherosclerosis in men ≥ 60 years with low or low-normal serum testosterone concentrations. Ultimately, the Endocrine Society calls for longer and larger studies on the effects of testosterone.

Other serious reactions to testosterone reported include:

  • Gynecomastia in males
  • Hepatocellular carcinoma (after prolonged high dose use)
  • Peliosis hepatis (after prolonged high dose use)
  • Cholestatic hepatitis (after prolonged high dose use)
  • hyperlipidemia
  • Worsening sleep apnea
  • Prostate hypertrophy
  • Acne
  • Headaches
  • Edema
  • Diarrhea and Vomiting
  • Emotional lability

Regardless of the controversies involving testosterone's risk, the best recommendation is to still have a thorough discussion with a physician prior to getting testosterone therapy. If you are interested in knowing more about the risks and benefits of testosterone therapy, we highly recommend you to call the office to schedule an appointment.

 

Albert Hsia, MS-IV

Dr. David Carfagno, DO,  CAQSM

References:

  1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95:2536.
  2. Baillargeon J, Urban RJ, Ottenbacher KJ, et al. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med 2013; 173:1465.
  3. Brambilla DJ, O'Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol (Oxf) 2007; 67:853.
  4. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One 2014; 9:e85805.
  5. Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829-1836.
  6. Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95:2560-75.
  7. Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108.
  8. Shores MM, Smith NL, Forsberg CW, et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012; 97:2050.
  9. Basaria S, Harman SM, Travison TG, et al. Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial. JAMA 2015; 314:570.
  10. Nainggolan L. Endocrine Society Calls for Longer, Larger Studies on Testosterone. Medscape. 2016. Available at: http://www.medscape.com/viewarticle/820383. Accessed January 16, 2016.
  11. Hypogonadism: Practice Essentials, Background, Pathophysiology. 2016. Available at: http://emedicine.medscape.com/article/922038-overview. Accessed January 16, 2016.

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