C ertain groups of breast cancer survivors are at greaterthan-average risk for sexual problems compared with age-matched controls without a history of cancer. Although body image disturbance is related to sexual dysfunction after cancer treatment, breast loss or alteration per se is not the most reliable determinant of sexual function outcomes. Rather, having received chemotherapyVand, most importantly, having experienced premature ovarian failure as a resultVis a consistent treatment-specific risk factor for sexual maladjustment across studies of women with breast cancer. Attention has turned increasingly to the additional effect of endocrine therapy on sexual outcomes, as use of selective estrogen receptor modulators and aromatase inhibitors (AIs) in the adjuvant setting has become the standard of care for women with estrogen-sensitive tumors, who make up most breast cancer survivors. In light of the frequent use of endocrine therapies for breast cancer and the growing acceptance of these drugs as chemopreventive agents in high-risk women with no cancer history, more critical attention to treatment effects on quality of life is warranted. In this issue of Menopause, Baumgart et al’s study on breast cancer survivors undergoing endocrine therapy lends weight to a growing consensus that AIs are more strongly associated with sexual problems than tamoxifen and other selective estrogen receptor modulators. Whereas data on sexual outcomes with tamoxifen have been mixed but largely reassuring, the sexual adverse effects of AIs may have been underestimated initially. Baumgart et al compared four groups of postmenopausal women: healthy women not undergoing estrogen therapy, healthy women taking estrogen, breast cancer survivors taking tamoxifen, and breast cancer survivors taking an AI. An important population not represented in this study are breast cancer survivors who did not receive adjuvant endocrine therapy. However, previous studies suggest that this group has sexual function outcomes similar to those in women treated with tamoxifen, with all other factors being equal. Given the similarities between tamoxifen-treated women and age-matched controls in this study, it is improbable that breast cancer survivors not undergoing endocrine therapy fared significantly better. Another subgroup that was not examined consists of younger women who became menopausal because of their breast cancer treatment. These women tend to have more severe and distressing problems with sexual function than those who were already postmenopausal at the time of diagnosis. Younger women may also experience greater distress because of sexual problems. Incidentally, women in younger age groups are also considerably less likely to adhere to AI therapy, but it is not known to what extent sexual adverse effects predict AI discontinuation or nonadherence. Although controls matched on age and postmenopausal status were important to the objectives of this study, future studies of AI-related adverse effects should explicitly document the experiences of younger survivors. The results of this study are congruent with the clinical observation that women taking AIs tend to report global sexual problems, including not only dyspareunia but also reduced sexual desire, difficulty becoming sexually aroused, and problems with orgasm. They may complain of persistent dyspareunia despite the use of lubricant for sexual activity. Existing data are insufficient to draw conclusions about the independent effects of AIs on sexual desire, apart from their effects on vulvovaginal symptoms. At present, low sexual desire is perhaps best understood as an adaptation to an activity that has become aversive owing to pain. With compelling evidence suggesting that AIs are linked to sexual problems, attention should be turned to interventions that address these adverse effects. The risks and benefits of hormonal treatment, although controversial, merit cautious study. The use of low-dose topical hormonal treatments to reverse vulvovaginal symptoms in breast cancer survivors is one strategy for which outcome data are scarce and long-term data are lacking. As of this writing, Clinicaltrials.gov lists one trial of low-dose vaginal estradiol and three trials (one suspended) of testosterone for breast cancer survivors who are currently taking AIs. Meanwhile, Baumgart et al’s findings remind us that, in the general population, estrogen therapy does not always prevent or reverse sexual dysfunction in postmenopausal women. Even when the onset of a sexual problem seems to be tied to a discrete event or condition, clinicians must consider additional factors that may be involved in the maintenance or exacerbation of the problem. In the case of AIs, the long-term ramifications of estrogen deprivation can be both physical and psychosocial. For example, women who experience severe dyspareunia may avoid not only vaginal intercourse but also other forms of intimate contact. Over
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