AndroGel Variable Absorption Severity Grading: A Clinical Rubric

Is there an official severity grading system?

None was identified. The Teva testosterone gel 1% label says to confirm hypogonadism with morning serum testosterone measured on at least two separate days, both below the normal range, then start 50 mg once daily in the morning and adjust among 50, 75 and 100 mg based on serum total testosterone [1].

The label notes that topical testosterone products may have different doses, strengths or application instructions that can result in different systemic exposure, and that its dosage and administration differ from testosterone gel 1.62% [1].

How much of an applied dose is actually absorbed?

In a pharmacokinetic study of 227 hypogonadal men given two doses of a 1% hydroalcoholic testosterone gel or a testosterone patch, about 9 to 14% of the testosterone applied as the gel was bioavailable [2]. The gel was applied to the upper arms, shoulders and abdomen [2], the same sites the Teva label permits, with genitals, chest, armpits, knees and back excluded [1]. Mean serum testosterone stayed stable across 180 days of daily application, and free testosterone tracked total testosterone without a change in the free fraction [2]. The researchers reported that an earlier study found steady-state testosterone levels 48 to 72 hours after the first gel application [2].

What the dose-titration data show

After 90 days, the 227-man study titrated the dose up from 50 to 75 mg or down from 100 to 75 mg when preapplication serum testosterone fell outside the normal adult male range. Raising the dose from 50 to 75 mg per day did not significantly increase the group average 24-hour serum testosterone concentration, while lowering it from 100 to 75 mg brought levels into range for most patients [2]. That is one study, not a rule that applies to every man.

What the label lists for monitoring

The Teva label lists serum testosterone, PSA, hemoglobin, hematocrit, liver function tests and lipid concentrations as periodic checks. It calls for a hematocrit check before treatment, again 3 to 6 months in, and then annually, and notes that increased red blood cell mass may raise the risk of thromboembolic events [1]. It also says to measure blood pressure periodically and does not recommend the gel in men with uncontrolled hypertension; in an ambulatory monitoring study, gel 1% raised mean 24-hour systolic and diastolic pressure by 1.9 and 1.3 mm Hg at week 16 in the 169 patients with usable recordings [1].

Does switching to injections reduce variability?

No study identified compared the variability of gel and injections. A network meta-analysis of 29 placebo-controlled trials in 3,393 men found that both gel and intramuscular enanthate or cypionate raised mean hematocrit versus placebo, by 3.0% (95% CI 1.8 to 4.3) and 4.0% (95% CI 2.9 to 5.1) respectively; the difference between the two was not statistically significant [3].