Special Report: How neurokinin receptor antagonists are reshaping the VMS treatment landscape

In the eighth episode of the Contemporary OB/GYN Special Report series, JoAnn V. Pinkerton, MD, and Jill Liss, MD, MSCP, FACOG, discussed how neurokinin receptor antagonists are transforming the management of vasomotor symptoms (VMS) by offering a highly effective, nonhormonal therapeutic option.

Pinkerton described this as “one of the most exciting areas right now,” noting that for many years, hormone therapy was the only reliable treatment for hot flashes and night sweats. “We now have an understanding of the central role of neurokinin receptors in the pathogenesis of VMS,” she explained. Declining estrogen levels trigger overactivity in certain hypothalamic neurons—known as the KNDy (kisspeptin, neurokinin B, dynorphin) system—causing thermoregulatory instability. Neurokinin receptor antagonists work by interrupting this process, effectively reducing hot flashes without the use of estrogen.

Pinkerton highlighted fezolinetant, an NK3 receptor antagonist currently approved in the United States,¹ and elinzanetant, a dual NK1/NK3 receptor antagonist under FDA review but already available internationally.² She noted that the dual-action mechanism of elinzanetant may confer added benefits for mood and sleep, as NK1 receptor modulation affects substance P pathways. “It’s very exciting to have new therapies that work almost as well as estrogen and are non-estrogen,” she said.

Liss agreed, calling these developments a major step forward in menopause management. “It is just so, so exciting to feel like there’s something on the playing field of hormone therapy,” she said, noting that previous nonhormonal options often felt less effective.

Addressing onset and durability of response, Pinkerton explained that fezolinetant and elinzanetant begin working within days. “Within a week, it’s documented—and probably even within the first day or 2, they start to see a benefit,” she said. Both drugs have demonstrated sustained efficacy through 52 weeks in clinical trials, including the OASIS-4 study in breast cancer survivors on endocrine therapy. She added that longer-term safety data are still accumulating, but early findings are encouraging.

Our Experts:
JoAnn V. Pinkerton, MD, division director, Midlife Health Center, University of Virginia.

Jill Liss, MD, MSCP, FACOG, associate clinical professor of Obstetrics and Gynecology, University of Colorado School of Medicine.

Liss has no relevant disclosures to report. Relevant disclosures for Pinkerton include Bayer.

References:

1. FDA Approves Novel Drug to Treat Moderate to Severe Hot Flashes Caused by Menopause. FDA. May 16, 2023. Accessed October 17, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-drug-treat-moderate-severe-hot-flashes-caused-menopause
2. Bayer. Regulatory Update on Elinzanetant. Bayer.com. July 25, 2025. Accessed October 17, 2025. https://www.bayer.com/en/us/news-stories/regulatory-update-on-elinzanetant