PURPOSE: Patients with prostate cancer on androgen deprivation therapy with luteinizing hormone-releasing hormone agonists experience deleterious side effects, including sexual dysfunction, hot flashes and osteoporosis. Estrogen may relieve or reduce some of these side effects. We explore the role of estrogen in normal male function, emphasizing sexual interest and performance. MATERIALS AND METHODS: We reviewed the literature on androgen deprivation therapy, estrogen and sexual function in males using PubMed® and other sources. RESULTS: Estrogen receptors are present in tissues involved in sexual behavior including several brain centers and pelvic floor muscles. Exogenous estrogens can restore some sexual interest to greater than castrate level in castrated animals. This has also been reported for certain androgen deprived patients (eg voluntarily castrated men, male-to-female transsexuals) who take exogenous estrogens and others who are on high dose antiandrogens which increase endogenous estradiol levels. Estrogen also helps prevent hot flashes and bone mineral loss, which commonly occur with luteinizing hormone-releasing hormone agonist treatment. However, estrogen may cause gynecomastia and increases the risk of breast cancer. Thus, patients with prostate cancer should be informed about the pros and cons of estrogen therapy before starting androgen deprivation therapy. Based on these data estrogen is likely to have maximal benefits in men if initiated simultaneously with androgen deprivation therapy. Because estrogen autoregulates its own receptors, a constant dose of estrogen will not likely produce a constant serum concentration, suggesting that its effectiveness could be optimized if administered cyclically. CONCLUSIONS: Prospective studies on the ability of parenteral estrogen to preserve sexual interest at greater than castrate level in patients with prostate cancer are warranted.