|Testosterone replacement remains controversial due to a shortage of large clinical trials demonstrating the benefits and adverse effects of treatment in boys and men of all ages. However, available evidence and published clinical experience may help physicians determine for whom this therapy is appropriate.|
“Treatment of testosterone deficiency due to classical diseases affecting the hypothalamus, pituitary and/or testes has been accepted for decades, although there were no multicenter trials,”Glenn R. Cunningham, MD, and Shivani M. Toma, MD, both of the Baylor College of Medicine and St. Luke’s Episcopal Hospital in Houston, wrote in a recent review.
Cunningham, who is also an Endocrine Today editorial board member, and Toma analyzed the currently available data more closely to gain better insight into the treatment’s use.
“Most clinicians do not have the time or the expertise to critically review the literature on a complicated medical issue,” Cunningham said in an interview. “A review of this type in a reputable journal should highlight the issues and address them in an informative manner.”
Challenges of diagnosis, age
Physicians may have trouble determining whether testosterone therapy is appropriate because diagnosing androgen deficiency is complicated, according to the authors. Although several symptoms, including incomplete sexual development and loss of body hair, are apparent, others, such as fatigue, are nonspecific. Serum testosterone levels are also not necessarily reliable as thresholds for different tests vary widely. Moreover, these levels naturally decline with age.
“The assumption is that older men who fall below this reference range for younger men will also benefit from replacement testosterone treatment. This argument ignores the fact that we have limited data to assess relative benefit at specific serum testosterone windows,” Ronald Swerdloff, MD, and Christina Wang, MD, both of Harbor-UCLA Medical Center, wrote in an accompanying editorial published in The New England Journal of Medicine.
Generally, physicians deem testosterone treatment suitable for boys aged 14 years with delayed puberty and men aged 20 to 49 years as benefits outweigh the risks in these populations. In men aged 50 to 60 years, however, true androgen deficiency is difficult to detect due to common comorbidities, such as obesity and type 2 diabetes, that may lower testosterone levels. For men aged older than 60 years, the debate revolves around whether aging organs are as responsive to testosterone therapy, the researchers said.
Cunningham and Toma said several randomized, placebo-controlled trials back well-known advantages of testosterone therapy, including improvements in body composition, bone mineral density, libido and sexual function.
Although linked with various side effects, increased risk for prostate cancer and benign prostatic hyperplasia, and cardiovascular issues are most concerning, Cunningham and Toma said.
Current clinical trials indicate little risk for prostate cancer, but the researchers noted that exposure time to testosterone was limited in these studies. Similarly, two meta-analyses suggest no increased risk for CV events, but one study of testosterone use in men aged 65 and older yielded data to the contrary.
“An ongoing National Institute of Aging-sponsored clinical trial should provide definitive answers regarding potential benefits [of testosterone replacement therapy],” Cunningham said, noting that if the results confirm benefits, then a larger more expensive trial that can better assess the risks, as well as benefits, will be warranted.
Currently, however, Cunningham and Toma advise physicians to proceed with caution.
“For now, clinicians should discuss the available efficacy and risk data for testosterone replacement and should help each patient make the decision that is best for him,” they wrote.
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