Why AndroGel Causes Skin Irritation: The Biology Behind Testosterone Gel Reactions

What the AndroGel 1% data show

In a study of AndroGel 1%, 163 hypogonadal men applied 5, 7.5 or 10 g daily for up to 42 months. Mild local skin irritation occurred in 12 of them and led to discontinuation in one [1].

What a testosterone gel 1% label records

The Teva testosterone gel 1% label is not the AndroGel label, so its rates are not AndroGel's own. It shows how a regulator records these reactions. The label lists acne, application-site reaction, abnormal lab tests and prostatic disorders as the most common adverse reactions, at 5% or more [2].

In the label's 180-day phase 3 trial, application-site reaction was reported by 5% of the 77 men on 50 mg, 3% of the 40 on 75 mg and 4% of the 78 on 100 mg. The label says none of the skin reactions was severe enough to require treatment or discontinuation [2]. In the 3-year extension of 162 men, application-site reaction was 5.6%, dry skin 1.9% and itching 1.9%, and two men discontinued for application-site reactions [2].

The gel itself

A study comparing two doses of 1% testosterone gel with a testosterone patch enrolled 227 hypogonadal men. The gel was hydroalcoholic and dried within a few minutes on the upper arms, shoulders and abdomen. The authors noted that skin irritation had limited acceptance of testosterone patches and that gels had been proposed to minimize that problem [3]. None of the trials above separates an effect of the alcohol vehicle from an effect of testosterone on the skin.

Androgens and skin

Androgens act through the nuclear androgen receptor, and a review of sex hormones in skin describes androgen effects on sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing [4]. In the gel 1% trial, acne was reported by 1% of men at 50 mg, 3% at 75 mg and 8% at 100 mg [2]. That is consistent with an androgen effect on sebaceous glands, though the trial did not test the reason.