Beyond Hormone Therapy: Effective Alternatives for Managing Menopausal Symptoms

EP: 1.Understanding VMS in Menopause: Prevalence and Impact

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EP: 2.Beyond Hormone Therapy: Effective Alternatives for Managing Menopausal Symptoms

EP: 3.Breaking Down the Science: Mechanisms of Action for New VMS Therapies

EP: 4.How Primary Providers Can Prevent the Broader Health Impacts of VMS

EP: 5.Liver Safety and Monitoring in VMS Treatment

EP: 6.Long-Term Safety of New VMS Agents: What We Know So Far

EP: 7.Understanding the Link Between Elinzanetant and Somnolence

EP: 8.Educating Patients and Providers: Key Takeaways for Better VMS Management

Episode 2

The following transcript has been edited for clarity, style, and length.

Tara K. Iyer, MD: That brings us to an important question—what treatment options are available to help women manage vasomotor symptoms (VMS)? Many patients are familiar with menopausal hormone therapy (MHT), but what about those who are ineligible due to contraindications, experience side effects, or simply prefer not to use it? What alternatives do we have for these patients?

Alexa Fiffick, DO, MBS, MSCP: This is a great question because many assume that most non-hormonal options are FDA-approved, and unfortunately, that is not the case. Many treatments we use for patients who are ineligible or choose not to use hormone therapy are off-label. However, we do have several evidence-based alternatives. Non-medication approaches include cognitive behavioral therapy (CBT) and clinical hypnosis, which have shown effectiveness. Additionally, external devices like the Ember Wave bracelet offer some symptom relief.

When it comes to medications, we have selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin, and oxybutynin. Clonidine has been used in the past but is not commonly recommended anymore. Until recently, only one non-hormonal medication—paroxetine mesylate (7.5 mg)—was FDA-approved specifically for VMS. Fortunately, newer treatments are now emerging to fill this gap.

Iyer: Absolutely, and I think one challenge many clinicians face is that these medications aren’t always as simple as prescribing and expecting immediate relief. Many patients try different options but discontinue them due to side effects or limited efficacy. In many cases, we have to layer treatments to achieve meaningful symptom control. Historically, this has been frustrating for both patients and providers due to the limited number of approved options.

Thankfully, we now have new interventions on the horizon. That brings me to my next question: What are the 2 neurokinin receptor antagonists currently available or awaiting FDA approval for the treatment of VMS due to menopause?

Fiffick: Great question. The most well-known is fezolinetant, which is FDA-approved under the brand name Veoza. Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that works by blocking the NK3 receptor in the hypothalamus, where the body's thermostat is regulated. In menopause, estrogen loss leads to receptor hypertrophy, triggering VMS. Fezolinetant helps counteract this process by preventing NK3 activation.

A second medication, elinzanetant, is currently under FDA review. It is a dual NK1 and NK3 receptor antagonist, meaning it not only blocks NK3 like fezolinetant but also targets NK1 receptors, which may offer additional benefits for sleep and mood disturbances associated with menopause. Both medications represent a significant advancement by directly addressing the underlying mechanism of VMS rather than just managing symptoms.