Men with low testosterone should go for intramuscular rather than transdermal replacement formulations, according to a new clinical practice guideline from the American College of Physicians (ACP).
In the guideline, which was also endorsed by the American Academy of Family Physicians, the ACP recommends providers prescribe intramuscular testosterone when initiating treatment for men with age-related low testosterone or male hypogonadism — defined as a testosterone threshold of 300 ng/dL or less.
Although both types of testosterone proved effective with similar risk profiles for improving sexual functioning in men with low testosterone, cost was the major differentiating factor.
On average, using an intramuscular formulation of testosterone would cost approximately $156.32 per patient per year versus $2,135.32 for a transdermal formation, explained Amir Qaseem, MD, PhD, of the American College of Physicians in Philadelphia, and colleagues.
The guideline, appearing in Annals of Internal Medicine, (read study – IM Testosterone) also recommended that testosterone should only be prescribed to men with age-related low testosterone with sexual dysfunction. Based on low-certainty evidence, the guideline suggested providers introduce this conversation to patients to individually weigh the benefits and risks of initiating testosterone replacement specifically for improving sexual dysfunction.
In an accompanying editorial, E. Victor Adlin, MD, of the Lewis Katz School of Medicine at Temple University in Philadelphia, noted that these recommendations are largely in line with what the rest of the medical community recommends, including recent guidelines from the Endocrine Society and the American Urological Association.
However, Adlin wasn’t quite sold on the ACP’s recommendation for intramuscular over transdermal formulation solely based on cost, saying that this recommendation “will be questioned by many clinicians.”
“[T]he need for an intramuscular injection every 1 to 4 weeks is a potential barrier to adherence, and some patients require visits to a health care facility for the injections, which may add to the expense,” he explained, adding that “peak-and-valley blood levels after each injection may cause irregularity of symptom relief and difficulty achieving the desired blood level. Individual preference may vary widely in the choice of testosterone therapy.”
But ACP President Robert McLean, MD, pointed out in a statement that “[m]ost men are able to inject the intramuscular formulation at home and do not require a separate clinic or office visit for administration.”
In an accompanying systematic review, Susan Diem, MD, MPH, of the Minneapolis VA Health Care System in Minnesota, and colleagues, found little to no benefit of testosterone therapy for symptoms other than sexual dysfunction in this patient population.
Looking at 38 randomized controlled trials of either transdermal or intramuscular testosterone-replacement therapy versus no therapy, the researchers found that testosterone had a small improvement in global sexual function score based on moderate-certainty evidence (standardized mean differences 0.35, 95% CI 0.23-0.46, I2=0%). There was also a small improvement shown in erectile function with testosterone therapy (SMD 0.27, 95% CI 0.09-0.44).
However, testosterone therapy — regardless of formulation — did not improve other symptoms of age-related male hypogonadism including lack of energy or vitality, physical functioning, and cognition. The analysis was underpowered to draw conclusions regarding testosterone’s effect on mortality, the guideline authors pointed out.
Based on this evidence report data, the guideline recommends against initiating testosterone treatment for these particular symptoms.
Low certainty evidence also found little or no difference in adverse cardiovascular events with testosterone therapy, while moderate evidence found no evidence of any increased risk for serious adverse events.
“[M]en with age related low testosterone should not be prescribed testosterone treatment unless its purpose is to treat sexual function issues,” the guideline concluded.
“Given that testosterone’s effects were limited to small improvements in sexual and erectile function in men with low testosterone levels, it is unlikely that screening men for low testosterone levels or treating men without sexual or erectile dysfunction and low testosterone levels would be effective,” McLean added in his statement.
As for the length of treatment, the guideline suggests that healthcare providers reevaluate the patient’s symptoms of sexual dysfunction within 12 months of testosterone therapy, based on low-certainty evidence. For those patients who show no improvement in sexual dysfunction, therapy should be discontinued.
Ultimately, the guideline underscores that providers should give “full consideration of the patient’s values and wishes” when initiating testosterone therapy.