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.
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
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
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.
For more information:
Disclosure: Dr. Cunningham has received consulting, advising and
lecturing fees, and research support from various pharmaceutical companies. Dr.
Toma reports no relevant financial disclosures. Drs. Swerdloff and Wang have
received consulting and lecturing fees, and research support from various
pharmaceutical companies. For a full list of disclosures, see the study.