Use of testosterone in older woman with hypoactive sexual-desire disorder (HSDD) is controversial. One concern about existing testosterone therapies for HSDD is the common recommendation to concomitantly administer estradiol because of the known risks of such therapy in postmenopausal women. This large, year-long, double-blind, placebo-controlled trial of testosterone therapy in postmenopausal women examined the hypothesis that testosterone alone would be efficacious in improving HSDD. The results of this trial confirm the improvement in sexual function for postmenopausal women seen in earlier studies using testosterone in combination with estradiol, implying that estradiol administration may not be essential for the beneficial effects of testosterone. However, this study raised some concerns regarding testosterone therapy on the risk of breast and endometrial cancer, highlighting the need for further long-term trials to better assess the long-term safety of this approach for the treatment of HSDD in women.