AndroGel Pregnancy and Lactation Safety: What Clinicians and Patients Must Know

Which product does this prescribing information cover?

This page draws on the AndroGel 1% prescribing information. The label says dosage and administration for AndroGel 1% differ from AndroGel 1.62%, which has its own prescribing information [1].

What does the label say about pregnancy?

Pregnancy is a contraindication. AndroGel 1% is contraindicated in women who are pregnant, and the label says it can cause virilization of the female fetus when administered to a pregnant woman [1]. The same section says pregnant women need to be aware of the potential for transfer of testosterone from men treated with AndroGel 1% [1]. If a pregnant woman is exposed, the label says she should be apprised of the potential hazard to the fetus [1].

What is the fetal risk?

The label calls testosterone teratogenic and says it may cause fetal harm when administered to a pregnant woman, based on animal studies and its mechanism of action [1]. Exposure of a female fetus to androgens may result in varying degrees of virilization [1]. In animal developmental studies, testosterone given during organogenesis produced structural impairments in female and male offspring; the label notes those studies did not meet current standards for nonclinical developmental toxicity studies [1].

How does secondary exposure happen?

The boxed warning is about secondary exposure to testosterone. It says virilization has been reported in children who were secondarily exposed to testosterone gel, and that children should avoid contact with unwashed or unclothed application sites in men using testosterone gel; it also tells healthcare providers to advise patients to strictly adhere to the recommended instructions for use [1].

The warnings section covers the same ground and extends the precaution to women: children and women should avoid contact with unwashed or unclothed application sites in men using AndroGel 1% [1]. That section lists the signs reported in children: enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior and advanced bone age [1]. In most cases these signs and symptoms regressed when exposure was removed; in a few cases enlarged genitalia did not fully return to age-appropriate size and bone age remained modestly greater than chronological age [1]. The label says the risk of transfer was increased in some of these cases by not adhering to precautions for appropriate use, and that testosterone gel should be promptly discontinued until the cause of virilization has been identified [1].

Does the label cover breastfeeding?

The label has a lactation section, and it says only that AndroGel 1% is not indicated for use in women; it does not discuss breast milk [1]. What the label does address is skin contact: children and women should avoid contact with unwashed or unclothed application sites in men using the gel [1].

Can a partner conceive while a man uses the gel?

The label warns that exogenous administration of androgens may lead to azoospermia, says reduced fertility is observed in some men taking testosterone replacement therapy, and says the impact on fertility may be irreversible [1]. Its listed indication is replacement therapy in males with hypogonadism [1]. The Endocrine Society guideline recommends against starting testosterone therapy in men planning fertility in the near term [3].

What is known about sperm recovery?

Recovery data come from men treated with fertility medicines after testosterone. In a retrospective case series of 49 men with azoospermia or severe oligospermia while on exogenous testosterone, 47 of 49 men (95.9%) had a return of sperm production or improved counts while receiving hCG 3,000 units subcutaneously every other day plus clomiphene, tamoxifen, anastrozole or recombinant FSH, at an average of 4.6 months, with a mean first density of 22.6 million/mL [2].

In a retrospective study of 66 men with infertility after testosterone use, high-dose hCG plus a selective estrogen receptor modulator led to a total motile count above 5 million within 12 months in 46 men (70%); older age and longer testosterone use predicted slower recovery [4]. These are treated series, not untreated recovery rates.