AndroGel Plateau & Non-Response Troubleshooting: A Clinical Guide

What the gel trials measured

TRAVERSE randomized 5,246 men aged 45 to 80 with hypogonadism and existing or high cardiovascular risk to daily 1.62% testosterone gel or placebo gel, with the dose adjusted to keep total testosterone at 350 to 750 ng/dL [3]. Mean treatment lasted 21.7 months, and the primary cardiovascular endpoint occurred in 7.0% on testosterone versus 7.3% on placebo (hazard ratio 0.96, 95% CI 0.78 to 1.17) [3]. The Testosterone Trials gave gel or placebo for one year to 790 men aged 65 or older with testosterone below 275 ng/dL and raised levels into the mid-normal range for men aged 19 to 40 [4]. Both are group averages, not an individual trajectory.

Does the gel product and strength change exposure?

In a randomized crossover study, 29 hypogonadal men received a single 50 mg dose of two 1% testosterone gels, Testim and AndroGel, seven days apart [1]. Total testosterone peak concentration and 24-hour exposure were each about 30% higher with Testim, and the confidence intervals fell outside bioequivalence limits [1]. The AndroGel 1% label makes the general point that topical testosterone products may have different doses, strengths or application instructions that may result in different systemic exposure [5].

How the label adjusts the dose

The AndroGel 1% label says the starting dose is 50 mg applied once daily in the morning, and that serum testosterone should be measured at intervals to ensure proper dosing: if it is below the normal range the daily dose may be increased from 50 to 75 mg and from 75 to 100 mg, and if it exceeds the normal range the dose may be decreased [5]. The label also reports no differences in average daily serum testosterone at steady state based on age, cause of hypogonadism or body mass index [5]. The label further says to confirm the diagnosis before starting, with serum testosterone measured in the morning on at least two separate days and below the normal range [5]. The 1.62% gel has its own dosing instructions, which the 1% label does not give [5].

What to check when the level stays low

The first question is whether hypogonadism was confirmed. The Endocrine Society recommends making the diagnosis only in men with symptoms and signs consistent with testosterone deficiency and unequivocally and consistently low serum testosterone, confirmed by repeating the morning fasting total testosterone measurement [6]. It also recommends monitoring symptoms, serum testosterone, hematocrit and prostate cancer risk in the first year [6].

Age trends are a separate consideration. In the Massachusetts Male Aging Study, total testosterone declined about 0.8% per year of age across men and 1.6% per year within men followed over 7 to 10 years, while SHBG rose about 1.6% per year across men [7]. Those are cohort trends and do not establish the cause of any one man's low level.