Hormone therapy, neurokinin antagonists, and the evolving menopause treatment landscape

Clinicians managing vasomotor symptoms now have a broader and more effective toolkit than at any prior point—but translating that into individualized treatment decisions requires time, a thorough history, and a clear understanding of which contraindications to hormone therapy are real and which are not, according to Jill Liss, MD, MSCP, FACOG, an associate clinical professor of obstetrics and gynecology.

Hormone therapy remains the first-line recommendation for most patients.

"For most people, hormone therapies should be first line—they're safe, effective, and usually cost effective as well," Liss said during an interview with Contemporary OB/GYN at the 2026 American College of Obstetricians & Gynecologists (ACOG) Annual Clinical & Scientific Meeting. Her starting framework is straightforward: Assess candidacy for estrogen, and if the patient is a good candidate and willing, begin there. If not, move to non-hormonal options.

A critical part of that assessment is correcting misconceptions about contraindications.

"We've fallen into a trap of finding too many contraindications, some of which don't actually exist," Liss said. Migraine with aura is not a contraindication to hormone therapy. Neither is a family history of breast cancer. True contraindications include active liver disease, undiagnosed bleeding, stroke, and myocardial infarction. Liss noted that she is collaborating with a group of menopause specialists to develop a medical eligibility criteria grid for hormone and non-hormone therapies—a resource intended to help clinicians navigate more nuanced, intermediate-risk treatment decisions.

The rise of non-hormonal treatments

For patients who are not candidates for or prefer to avoid hormones, non-hormonal options have meaningfully improved. Liss identified the neurokinin receptor antagonists—fezolinetant (Veozah) and elinzanetant (Lynkuet)—as a significant advance.

"We finally have an FDA-approved non-hormone option that's really efficacious," she said. "It's like estrogen and then everything else—we finally really have something that can hold a candle to estrogen therapy for vasomotor symptoms."

Among older non-hormonal options, Liss described how secondary symptom profiles can guide selection. For patients whose vasomotor symptoms are accompanied by sleep disruption, gabapentin may offer dual benefit. For those with concurrent mood disturbance, an SNRI or SSRI is a reasonable choice—although she emphasized that the doses used for vasomotor symptoms are substantially lower than those used to treat depression or anxiety, a nuance clinicians should keep in mind.

Across all non-hormonal agents, Liss noted that estimates of efficacy vary widely but that an average reduction in severity and frequency of approximately 60% is a reasonable benchmark. Neurokinin antagonists are particularly well suited to patients who prefer not to use hormones, older patients who are not good hormone therapy candidates, and oncology patients for whom hormone therapy is contraindicated and who often experience the most severe vasomotor symptoms.

On the structure of clinical encounters, Liss was direct about the practical barrier.

"One of the biggest constraints is that there's too much to talk about in a short amount of time," she said. "This is really probably a 2-visit topic—one for a really good history, one for counseling and treatment decisions." She emphasized that taking the time to understand what patients have already tried and what their goals of care are is essential to making these conversations productive.