Back Back
Beyond the Symptoms of Menopause
Beyond the Symptoms of Menopause: A New Era of Individualized Care

Released: March 25, 2025

Expiration: March 24, 2026

Lila E. Nachtigall
Lila E. Nachtigall, MD, MSCP
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • Vasomotor symptoms (VMS) are linked to increased risk for cardiovascular disease, sleep and mood disorders, and poor metabolic health.
  • Nonhormonal neurokinin-3 receptor antagonists like fezolinetant directly address the root cause of VMS. 
  • Primary care has an emerging and critical role in menopause management—from implementing proactive screening practices to treating women with moderate to severe VMS.

For too long, vasomotor symptoms (VMS)—the hallmark symptoms of menopause—have been dismissed as mere uncomfortable issues rather than signals of broader health concerns. But hot flashes and night sweats are not just transient nuisances, they are linked to increased risk for cardiovascular disease and overall poor health outcomes. Treating these symptoms effectively should address patients’ comfort and prioritize their long-term health.

With an evolving understanding of the pathophysiology behind VMS, healthcare professionals (HCPs) should now recognize that these symptoms result from instability in thermoregulation, which is driven by the kisspeptin, neurokinin B, and dynorphin (or KNDy) neurons in the hypothalamus. A hot flash is not just a hot flash. Although many view VMS as simple temperature fluctuations, research has revealed critical links between persistent hot flashes and cardiovascular disease. Women who experience frequent and severe VMS are at a higher risk for hypertension, stroke, and poor metabolic health.

Beyond cardiovascular concerns, sleep disturbances caused by VMS can contribute to fatigue and cognitive dysfunction, as well as sleep and mood disorders. Sleep deprivation is well known to increase risk for diabetes, obesity, and overall mortality. Therefore, it is crucial to recognize that treating VMS is about far more than just addressing comfort—it is about disease prevention and promoting long-term health.

The Emerging Role of Primary Care in Menopause Management
In the past, menopause management often was considered within the sole domain of women’s health, that is obstetrics and gynecology (OB/GYN). However, with new treatment options emerging, primary care providers (PCPs), internists, and other HCPs must also take an active role in identifying and treating VMS. Internists and PCPs are often the first HCPs women approach when experiencing increased fatigue, sleep disturbances, or mood changes, which are frequently indirect manifestations of menopause. Because many women do not immediately associate these symptoms with age-related hormonal changes, it is critical that PCPs recognize the broader implications of menopause and its symptoms and engage in early intervention.

Furthermore, not all patients feel comfortable discussing menopause with their OB/GYN, and some may not see one regularly. Ensuring that PCPs are equipped to discuss and manage menopause treatment options, including hormonal and nonhormonal therapies, is an essential step toward expanding access to appropriate care.

A New Era of VMS Treatment
Until recently, hormone therapy was the only effective treatment available for VMS. However, hormone therapy with estrogen is not a viable option for all women, particularly those with a history of breast cancer, thromboembolic disease, or other contraindications. In addition, low-dose paroxetine (a selective serotonin reuptake inhibitor) was, for years, the only FDA-approved nonhormonal treatment and showed modest efficacy.

The recent breakthrough in understanding the neurobiology of VMS has changed this landscape. Researchers identified the KNDy neurons in the hypothalamus, which play a pivotal role in the body’s temperature regulation. These neurons usually are suppressed by estrogen, but their hyperactivity disrupts thermoregulation in menopause, leading to vasomotor instability.

This insight has led to the development of neurokinin 3 receptor antagonists, a class of nonhormonal therapies that directly target the underlying cause of VMS vs merely alleviating symptoms. Fezolinetant was the first FDA-approved medication in this class and blocks neurokinin B receptors, thereby reducing the hyperactivity of KNDy neurons and dramatically improving VMS within weeks. Further, fezolinetant demonstrated rapid, significant reductions in VMS severity, even among women with frequent and debilitating symptoms. This novel mechanism of action represents a true paradigm shift in menopause treatment, offering a powerful and nonhormonal alternative for women who either cannot or prefer not to take hormone therapy.

Although the introduction of neurokinin 3 receptor antagonists has been a major advancement, it is important to address safety concerns. Early trials of fezolinetant revealed a high incidence of abnormal liver function tests, leading to modifications in its formulation. Abnormal liver enzyme elevations were rare and comparable to placebo in phase III trials, but the FDA recommends routine liver monitoring for patients receiving this agent. HCPs should monitor women’s liver function at 3, 6, and 9 months following treatment initiation or when symptoms suggest liver injury. While long-term safety data continue to be collected, HCPs must weigh risks and benefits when prescribing this therapy.

Another key factor in treatment selection is patient preference. Some women are open to hormone therapy, but others may opt for nonhormonal options due to their own personal beliefs or concerns, past medical history, or culture-related factors. Having multiple effective choices allows for a truly individualized treatment approach that considers women’s symptoms, health status, and personal preferences.

A Call to Action for Primary Care
Given the expanding treatment landscape and recognition of menopause as a critical period to address long-term health, PCPs must feel empowered to take a more proactive role in menopause management. Women experiencing VMS should not have to wait for a referral to a specialist to receive treatment. Internists and PCPs should incorporate routine menopause-related screening into their visits with middle-aged women, particularly when they present with complaints of fatigue, sleep disturbances, or mood changes. In addition, these HCPs can order simple blood tests (ie, follicle-stimulating hormone, estradiol levels) to confirm menopause status in cases where a diagnosis is unclear.

By recognizing VMS as a significant health issue rather than a mere inconvenience, we can raise the standard of menopause care—ensuring more women receive the effective and evidence-based treatments they need.

Your Thoughts?
How often are you prescribing fezolinetant in women with moderate to severe VMS due to menopause? To learn more about VMS management, join us at our upcoming live program at ACP either in person or online via simulcast. Use this link to access program online: clinicaloptions.com/menopause2025NewOrleans.

You can get involved in the conversation by answering the polling question or posting a comment below.

Continue

Poll

1.

How often are you prescribing fezolinetant in women with moderate to severe VMS due to menopause?

Submit