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. 

 
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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.

 
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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. 


References

  • Avis et al. (2015) “Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition.” JAMA Intern Med 175(4): 531–539

  • Avis et al. (2003) “Health-Related Quality of Life in a Multiethnic Sample of Middle-Aged Women.” Medical Care 41(11) 1262–1276

  • Baker at al. (2018) “Sleep problems during the menopausal transition: prevalence, impact, and management challenges.” Nature and Science of Sleep: 10 73–95

  • Gartoulla et al. (2015) “Moderate to severe vasomotor and sexual symptoms remain problematic for women aged 60 to 65 years.” Menopause Vol. 22, No. 7, pp. 694-701

  • Genazzani et al. (2006) “The European Menopause Survey 2005: Women’s perceptions on the menopause and postmenopausal hormone therapy.” Gynecol Endocrinol. 22(7):369-75)

  • Howlader et al. (2014) “US Incidence of Breast Cancer Subtypes Defined by Joint Hormone Receptor and HER2 Status.” J Natl Cancer Inst. 28;106(5)

  • Jones et al. (2012) “Androgen deprivation therapy-associated vasomotor symptoms.” Asian J Androl. 14(2): 193-197

  • Kaiser Family Foundation, Prescription Drug Trends Report 2001

  • Kligman et al. (2010) “Management of hot flashes in women with breast cancer.” Curr Oncol. 17(1): 81-86

  • Thurston et al. (2011) “Vasomotor Symptoms and Menopause: Findings from the Study of Women’s Health Across the Nation.” Obstet Gynecol Clin North Am.38(3):489-501

  • Whiteley et al. (2013) “Impact of the severity of vasomotor symptoms on health status, resource use, and productivity.” Menopause 2(5), pp. 518-524

  • The American Congress of Obstetricians and Gynecologists: 2011 Women’s Health and Stats

  • Williams et al (2008) “Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States.” Climacteric 11:32–43

  • The North American Menopause Society, 11 October 2017 “Despite Effectiveness Women Remain Skeptical of Hormones at Menopause—What’s the Problem?” Press Release

  • Woyka et al. (2017) “Consensus statement for non-hormonal-based treatments for menopausal symptoms.” Post Reproductive Health, Vol. 23(2) 71–75