Menopausal Vasomotor Symptoms (VMS) or “Hot Flashes”
Vasomotor Symptoms and Epidemiology
Vasomotor symptoms are characterized by sudden and recurrent sensations of heat or “hot flashes,” often accompanied by elevated heart rate, profuse sweating, skin reddening and chills. VMS often cause disruption of daily activities and sleep disturbances when they occur at night. Higher frequency of hot flashes has been associated with increased rates of depression, pain and insomnia, impairing quality of life.
The morbidity and overall healthcare burden of vasomotor symptoms is well documented. Several studies have demonstrated lower quality of life scores and an increased use of medical resources, including more frequent physician visits and associated escalations in healthcare costs, among women experiencing vasomotor symptoms.
Millions of women enter menopause each year and a majority of these women experience vasomotor symptoms. In the U.S. alone, an estimated 6,000 women reach menopause every day (over two million each year) and approximately 75% of these women experience vasomotor symptoms at some point during their menopausal transition and about two-thirds of postmenopausal women experience hot flashes. The median duration of vasomotor symptoms is approximately 7 years, while some women report VMS for decades after the menopause transition.
Current Treatments and Unmet Medical Needs in VMS
While hormone therapy is considered an effective treatment for VMS, many women choose to avoid hormone therapy due to concerns about safety risks highlighted in the product labels of hormone therapy products, including potential increased risk of myocardial infarction, stroke, invasive breast cancer (for combined estrogen/progestin products), pulmonary embolism and deep vein thrombosis. FDA labels for hormone therapy products also indicate they should be used at the lowest possible dose for the shortest time. In addition, hormone therapy is contraindicated in women who have a history of certain medical conditions, including vaginal bleeding, certain cancers, blood clots, stroke, heart attack, bleeding disorders and liver disease.
Highlighting the size of the VMS market opportunity, products containing conjugated estrogens, a form of hormone therapy, accounted for the largest number of prescriptions of all drugs sold in the U.S. in 2000. After results from the Women’s Health Initiative clinical study describing hormone therapy safety concerns were published in 2002, approximately 65% of women on hormones stopped therapy, creating a significant treatment gap.
The currently-available non-hormonal options are known to have limited efficacy and none can match the efficacy of hormone therapy in the treatment of vasomotor symptoms due to menopause.
Given today’s treatment options, women seeking relief from VMS today face a difficult choice. On the one hand, hormone therapy offers strong efficacy in treating hot flashes but the labels for hormone containing products include boxed warnings related to elevated safety risks. On the other hand, non-hormonal classes of compounds, such as anti-depressants, have limited efficacy. As a result, there is a well-recognized and significant unmet medical need for a new non-hormonal treatment capable of providing the same powerful efficacy as hormone therapy.
Other Conditions Associated with Vasomotor Symptoms
While menopausal women are the largest population suffering from VMS, women taking aromatase inhibitors or tamoxifen for breast cancer often experience them, as do men on androgen deprivation therapy for prostate cancer. These patients may experience an abrupt change in hormone signaling due to these therapies, often leading to a sudden onset of VMS, making it challenging for many of these patients to adhere to their cancer treatment. A study from the Journal of the National Cancer Institute indicates that approximately 75% of the incident breast cancer population is HR+/HER2-, a subset most commonly treated with aromatase inhibitors or tamoxifen, and of those patients, a significant portion experience VMS as a side effect of treatment. Estrogen is contraindicated in women with breast cancer and therefore not a treatment option for VMS in this population. Similarly, approximately 33% of the prevalent prostate cancer population has received androgen deprivation therapy (ADT) at some point during the course of their disease and up to 80% of men on ADT will experience VMS.
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