Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence

Androgens are deemed critical for penile-tissue development, growth, and maintenance of erectile function, however, their role in erection, especially in humans, remains controversial. In this review, we summarize information from clinical and animal model studies to provide a comprehensive and rational argument for the role of androgens, or lack thereof, on penile erection ability in humans. The goal of this review is to present the clinical and preclinical evidence available in the literature with regard to testosterone and erectile physiology and engage the reader in this discussion. Ultimately, each reader will have to form his or her own conclusions based on the existing evidence. In humans, androgen-deficiency manifestations are noted in clinical situations such as: (i) inadequate development of the penis; and (ii) loss of erectile function in prostate cancer and benign prostatic hyperplasia patients managed with medical or surgical castration or antiandrogen therapy. Androgen treatment causes: (i) improvement in sexual function in hypogonadal patients treated with androgen supplementation; (ii) improvement in nocturnal penile tumescence in hypogonadal patients treated with androgens; (iii) improvement in erectile function with androgen supplementation in patients who did not respond to phosphodiesterase type 5 inhibitor therapy initially; and (iv) improvement in the well-being, mood, energy, and sexual function in aging men who have testosterone deficiency treated with androgen therapy. In contrast to animals, especially rodents in which the adrenal cortex does not synthesize androgens, the human adrenal is a source of peripherally circulating androgen precursors, thus, complete androgen insufficiency may not be observed in men at a younger age. Furthermore, in light of the concept that a threshold of androgen levels exists in animals and humans below which sexual function is diminished, further contributes to the complexity of understanding androgens role in erections, especially in humans. Nevertheless, based on the preclinical and clinical data available in the literature, to date, we infer that androgens play a critical role in maintaining erectile physiology in humans.