Malignancy Risks of Neurokinin Receptor Antagonists

EP: 1.Overview of KNDy neurons

EP: 2.VMS Symptoms and Neurokinin Receptor Antagonists

EP: 3.Neurokinin and Estrogen Balance in Menopausal Hot Flashes for Primary Care

EP: 4.Fezolinetant Guidelines and Emerging Data on Menopause and Liver Health

EP: 5.Molecular Comparison and Safety Profiles of Fezolinetant and Elinzanetant

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EP: 6.Malignancy Risks of Neurokinin Receptor Antagonists

EP: 7.VMS Treatment Guidelines

EP: 8.Nonestrogen Treatments for Menopause

EP: 9.Guidance for PCPs: Streamlining Menopause Care

Episode 7

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

Mary Jane Minkin, MD: Lisa, one thing we’re always concerned about, and our patients are appropriately concerned about, is whether there’s any difference in the risk of malignancies between fezolinetant and elinzanetant. What do your findings suggest?

Lisa Larkin, MD: That’s a great question. First, I want to emphasize that neither fezolinetant nor elinzanetant are hormones; they are non-hormonal therapies. However, the FDA required endometrial safety monitoring for both, reflecting a standard practice established for managing vasomotor symptoms with hormone therapy.

In the trials that led to the approval of fezolinetant, there was a very small signal of concern for endometrial hyperplasia and endometrial cancer, but it was minimal. So far, we haven’t seen similar findings in the elinzanetant data. That said, I wouldn’t consider these findings to exceed the normal rates of endometrial hyperplasia or cancer expected in the general population. It’s important to remember that these issues naturally occur in aging women, and the monitoring requirements are precautionary.

Minkin: Exactly. There’s often a misconception that anything related to female organs must involve estrogen. These drugs do not exert a direct estrogen effect, but because we’re dealing with the uterus and endometrium, there’s a presumption of risk. This connection drives the safety monitoring requirements, even though these medications are non-hormonal.

Larkin: I agree. And to add, elinzanetant hasn’t been approved yet, and fezolinetant has only been available for about 18 months. We need to contextualize these concerns appropriately. I wouldn’t overstate the risks of endometrial hyperplasia or cancer with either medication at this stage.

Minkin: Right, we haven’t seen significant problems so far. On another note, Lisa, I’d like to highlight the potential for these drugs to be adopted more widely—not just by OBGYNs but also by primary care providers and internal medicine practitioners. Women suffering from vasomotor symptoms deserve access to effective interventions, regardless of which type of provider they see.

One common concern among primary care practitioners is vaginal bleeding, which often makes them hesitant to prescribe certain therapies. Fortunately, with this class of medications, vaginal bleeding isn’t an issue. That’s a significant advantage.

Larkin: Absolutely, but I’d like to add another perspective. While some primary care colleagues are excited about these drugs because they don’t involve hormones, I’ve heard a troubling narrative. Some see these medications as a way to completely replace hormone therapy. That’s a misconception that really concerns me.

Menopausal hormone therapy remains the gold standard for many patients. These medications are fantastic options for women who can’t or shouldn’t take hormones, but they shouldn’t lead to the abandonment of hormone therapy altogether.

Minkin: I couldn’t agree more. Hormone therapy still plays a crucial role, and these medications are complementary, not replacements.

Larkin: Exactly. They’re valuable additions to our toolkit, but they don’t render menopausal hormone therapy obsolete.

Minkin: Absolutely.