Aromatase inhibitors as a potential harm reduction strategy for men with low-normal testosterone at risk of non-prescribed androgen use

Abstract

Men with low-normal testosterone often present with symptoms such as low energy, reduced libido, and mood disturbances. However, guidelines restrict testosterone therapy (TTh) to men with confirmed hypogonadism, leaving this subgroup without clear treatment options. Frustrated, some turn to illicit testosterone, often at supraphysiological doses, risking long-term endocrine disruption, infertility, and cardiovascular disease. This perspective explores aromatase inhibitors (AIs) as a harm reduction strategy for such men. By inhibiting estrogen-mediated feedback, AIs stimulate endogenous testosterone production while preserving hypothalamic-pituitary-gonadal (HPG) axis integrity. In addition to potential symptom relief, AIs can be used diagnostically to assess HPG responsiveness and the relationship between testosterone levels and symptoms. They may also serve an educational role, helping patients better understand the hormonal contribution to their complaints and avoid premature self-treatment. The response to AIs is variable, and their long-term safety in men remains uncertain. In addition, the use of AIs is off-label and lacks robust clinical evidence. Well-designed trials are needed to determine whether AIs are truly a viable harm reduction strategy and eventually reduce the incidence of self-initiated TTh. Until then, a cautious, individualized approach is essential—yet in selected cases, AIs may offer a supervised alternative that prevents progression to unregulated testosterone use.