Understanding how Age-Related Decline in Testosterone Affects Male Sexual Behavior: Neurosteroids as the Missing Piece

Abstract

Age-related declines in male sexual behavior are often attributed to a well-documented decline in circulating androgens. Yet, several recent studies and metanalyses have suggested a weak relationship between circulating androgen levels and sexual behaviors, indicating that despite decreases in circulating androgens many men maintain moderate levels of sexual behavior. The lack of a strong relationship between circulating androgens and sexual dysfunction may be due to age-related changes in steroid signaling in the brain, which may be independent of circulating androgens. Androgen concentrations, synthesis, and signaling in the aging brain have been understudied. The purpose of this review is to briefly summarize our understanding of how age-related decreases in circulating androgens influence neural circuits that mediate sexual behavior and reward, and to highlight recent findings in our understanding of androgen receptors, neuroandrogens, and sexual function in healthy aged men. Age-related declines in circulating androgens weakly correlate with declines in sexual behavior, but androgen decline does not account for all the variance in sexual behavior observed among subjects. Evidence now suggests that neural nodes of the consummatory and appetitive sexual behavior circuits are capable of synthesizing androgens, independent of circulating levels of androgens. However, there remains a lack of controlled studies on neural markers of androgen signaling in healthy aged men. This ability to locally regulate androgens may compensate for lower circulating androgen levels to maintain proper sexual functioning. To better understand age-related declines in sexual behavior, compensatory androgen synthesis in the brains of aged males should be explored further in humans and animal models. A greater understanding of these mechanisms can inform the development of pharmacotherapies that can be used to ameliorate age-related sexual dysfunction.