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Selective estrogen receptor modulators and vulvovaginal atrophy: can we improve the lives of our patients with new therapeutic options?

M enopausal transition harkens a profound change in the health and well-being of women. This profound and relative rapidly occurring change is associated with numerous physiological and clinical alterations, primarily (but not exclusively) associated with the loss of physiological levels of estrogen. Indeed, it has been the use of estrogen-based therapies that has been associated with the most consistent improvement in many of these symptoms. However, more recent studies have demonstrated that such therapies may not be associated with the complete amelioration of all estrogen-related menopausal symptoms. Taking into account the ongoing concerns regarding the safety of menopausal estrogen therapies, it behooves us to investigate and consider other therapeutic options that can improve the overall health and well-being of postmenopausal women. Vulvovaginal atrophy (VVA) is a relatively common menopausal problem and usually results from the loss of physiological levels of estradiol (E2) in surgically and naturally postmenopausal women. The loss of estrogen leads to a spectrum of vaginal symptoms including dryness, itching, burning, soreness, and irritation as well as urinary symptoms that can include urgency, frequency, and increasing frequency of urinary tract infections. In addition, women with VVA report a considerable increase in dyspareunia, frequently resulting in a reduction or cessation in sexual activity. Over-the-counter lubricants are frequently used by sexually active women with VVA; however, such remedies do not treat the mucosal changes that lead to the symptoms experienced by women with VVA and provide only situational relief from symptoms. Systemic and local estrogen therapies have been shown to be effective in reducing or reversing many of the problems associated with VVA, although local estrogen therapies have been shown to be equal to or more effective than systemic therapies and are appropriate options for women with symptomatic VVA who may otherwise not require or desire systemic hormone therapy. Various local estrogen therapies that provide effective relief from estrogen-related VVA are available; the variety of local estrogen regimens and delivery systems allows for women to choose a method that best suits their lifestyle and increases the likelihood of consistent and correct use for as long as they seek estrogen therapy for VVA. Despite the ready availability of multiple effective interventions, VVA seems to be highly underreported by postmenopausal women, thus hampering efforts by clinicians to identify and treat symptomatic VVA in postmenopausal women. It is unclear as to why VVA is underreported by affected postmenopausal women; Santoro and Komi recently reported that in a survey of almost 2,300 women aged 45 to 89 years, 45% were postmenopausal and currently or previously experienced VVA. In this study, approximately 60% of past or never users of hormone therapies reported one or more of the aforementioned vaginal symptoms, and more than 90% found these symptoms to be bothersome. In comparison, 82% of current users of estrogen therapies reported vulvovaginal symptoms before initiation of hormone therapy. Sexual activity played a role in the reporting of VVA symptoms; those women who were not sexually active reported VVA symptoms at a lower incidence and severity than did those who were sexually active. However, 85% of all respondents reported being aware of safety issues surrounding the use of menopausal hormone therapies. Although it may be perceived by clinicians and women that the risk of local hormone therapies is less than that associated with oral systemic therapeutic regimens given the lower systemic levels associated with local hormone therapy, there is still concern that any hormone therapy is associated with an adverse risk profile and that if hormone therapy cannot be avoided in the treatment of menopausal symptoms, the lowest effective dose used for the shortest period of time is the optimal therapeutic approach regarding hormone therapy during menopause. The recent development and approval of an ultralowdose intravaginal estrogen tablet (E2 hemihydrate 10.3 Kg [Vagifem 10 Kg]) corroborates the practice of many clinicians and the choice of many women to use the lowest effective hormone dose for the treatment of menopausal symptoms. This safety concern may be supported by the recent work of Labrie et al that showed that local therapies do increase systemic levels of measurable E2 after the initiation of local estrogen therapies. The findings of Santoro and Komi support this perception and show that safety concerns are an important factor associated with the nonuse or discontinuation of menopausal hormone therapy in women with symptomatic VVA. In this regard, the development of effective therapeutic interventions that do not carry the risk or even the perception of risk associated with estrogen therapies could increase the use of therapeutic interventions for VVA and improve the well-being of women experiencing the effects of VVA by reducing safety concerns among women and their clinicians.