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Many breast cancer survivors (BCS) suffer the consequences of antineoplastic treatments that induce a hypoestrogenic state, leading to chronic climacteric symptoms such as genitourinary syndrome of menopause (GSM), arousing significant alteration in their quality of life. Non-hormonal therapies (NHT) are first-line treatments, safe but with mild efficacy. When facing moderate-severe GSM, the options for BCS are limited: local estrogen therapy, considered the 'gold standard' but with concerns about safety; vaginal androgens and prasterone, which seem to trigger an activation of estrogen and androgen receptors of the vaginal epithelium layers, without activating estrogen receptors on other tissues, being potentially safe but still without strong evidence in favor of BCS; vaginal lasers, which appear to improve vascularization of vaginal mucosa by stimulating the remodeling of the underlying connective tissue, but with contradictory results of efficacy in recent randomized clinical trials; and ospemifene, an oral selective estrogen receptor modulator presenting mild vaginal estrogenic potency and anti-estrogenic effect at the endometrial and breast level, but still not recommended for use in BCS in recent North American Menopause Society guidelines. There is a need for further studies evaluating objectively the efficacy and safety of these promising therapeutic options. On the other hand, sexuality must be seen as a multifactorial issue, where GSM is only part of the problem; evidence shows that sexual counseling improves the quality of life of BCS. Finally, there is a need to limit the underdiagnosis and undertreatment of GSM in BCS; the primary goal of physicians treating BCS regarding this issue has to be the provision of information of what to expect regarding genital and sexual symptoms to BCS and to counsel on early first-line treatments that may help prevent more severe GSM.

Background: Due to safety concerns on estrogen-based treatments for genitourinary syndrome of menopause (GSM) in breast cancer survivors (BCS), new options are appearing, such as androgen-based treatments, which according to proprieties would not be transformed systemically to estrogens in patients receiving aromatase inhibitors (AIs)., Objective: The aim of this pilot study is to assess the security and efficacy of vaginal prasterone (dehydroepiandrostenedione [DHEA]) in BCS treated with AIs., Methods: This open, prospective, pilot study included 10 BCS treated with AIs. All participants complained of severe GSM. DHEA was administrated as a vaginal ovule. Participants were instructed to use one ovule every night during the first month, and one ovule every two nights for the entire five remaining months. The patients were requested to attend seriated visits after the beginning of the prasterone treatment to evaluate symptoms, physical improvement and serum estradiol., Results: Mean serum estradiol remained low from 3.4 pg/ml to 4.3 pg/ml ( p  = 0.9136) after 6 months of follow-up. The visual analog scale of dyspareunia improved from 8.5 to mean values after treatment of 0.4 ( p  = 0.0178). The Vaginal Health Index (VHI) scale and Female Sexual Function Index improved from 9.75 to 15.8 ( p  = 0.0277) and from an initial score of 11.2 to 20.6 ( p  = 0.0277), respectively. Vaginal pH changed from basal 8.1 to final 6.5 ( p  = 0.0330)., Conclusion: Symptoms and physical examination regarding sexuality and vaginal health improved significantly, while serum estradiol remained at low levels. Prasterone seems a safe and effective option to treat GSM in BCS receiving AIs.