Dose adjustments of AndroGel for older men with hypogonadism should not be based on a single, post-application serum testosterone measurement, as serum concentrations can vary throughout the day, according to research in The Journal of Clinical Endocrinology & Metabolism.
In a randomized double blind, placebo-controlled trial with older men assigned either AndroGel 1% (transdermal testosterone gel, AbbVie) a matched placebo gel to treat symptoms of hypogonadism, researchers found a wide variation in serum testosterone (T) levels among participants; serum levels collected 2 hours after T gel application in two separate, ambulatory visits did not reflect serum T levels collected at multiple points throughout the day during a third, inpatient visit.
“After T gel application, the between- and within-subject variations in the serum T levels were large,” the researchers wrote. “The 2-hour ambulatory serum T level after T gel application was neither a good indicator of timed serum T concentration nor [average serum concentration] with the same dose on another inpatient day.”
Ronald S. Swerdloff
, MD, chief of the division of endocrinology and metabolism at Habor-UCLA Medical Center and director of the WHO Collaborative Center in Reproduction, and colleagues from other institutions analyzed data from 47 men aged 65 years or older with symptoms of low testosterone (morning testosterone concentration of less than 275 ng/dL) participating in The Testosterone Trials at five academic medical centers. Participants were randomly assigned to receive either T gel (n = 27; mean age, 71 years) or an identical placebo gel (n = 20; mean age, 70 years). Researchers assigned participants an initial daily dose of 5 grams of gel applied to shoulders and upper arms; researchers adjusted the dose monthly in the first 3 months to achieve a serum T level between 400 and 800 ng/dL, later changed to between 500 and 800 ng/dL. To maintain study blinding, researchers assigned an adjusted dose to a man in the placebo arm if a man in the T gel arm required an adjusted dose.
Researchers measured serum T variability in participants over three separate visits following 16 weeks of T gel application. During the first two visits (visits A and B), researchers drew blood 2 hours after men applied T gel; for a third visit participants went to a clinical research unit for a 24-hour multiple blood sampling survey (visit C).
Researchers found that T levels varied substantially among participants over the three visits, and the T concentrations at visits A and B were not correlated with the serum T levels drawn at the same time (2 hours post-application) or at any other time during the 24-hour monitoring in visit C. Within the cohort, 22.2% of men in the T gel arm had an average serum concentration within the target range of 500 to 800 ng/dL; 81.5% had a serum concentration within the broader range of 300 to 1,000 ng/dL.
“In older men administered a given dose of T gel, one or two measurements of serum T at any time after T gel application may be inadequate for attaining a serum concentration within a target range much narrower but within the population reference range,” the researchers wrote. “However, our results do suggest that one of two T measurements may be sufficient for monitoring of treatment aimed at maintaining serum concentration within the broader normal reference range.”
– by Regina Schaffer
Disclosure: Swerdloff reports receiving grant support from Antares, Clarus Therapeutics and Novartis, as well as consultant fees from Clarus Therapeutics, Quest Diagnostics and TesoRx. Please see the full study for the other authors’ relevant financial disclosures.