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A 67-year-old woman noted the appearance of several non-tender, rock-hard, purple-colored nodules on her legs. Her medical history was significant for distant non-Hodgkin lymphoma.

A 67-year-old woman noted the appearance of several non-tender, rock-hard, purple-colored nodules on her legs. Her medical history was significant for distant non-Hodgkin lymphoma. The violaceous color and configuration of the skin lesions suggests which of the following? 

Clinical Topics

Hard Purple Nodules: Your Dx?

Malignancy Risks of Neurokinin Receptor Antagonists

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

 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?

 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.

 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.

 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.

 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.

 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.

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

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

Panelists discuss clinical trial data suggesting a small but higher incidence of endometrial hyperplasia or malignancy with fezolinetant, while no cases of endometrial hyperplasia or malignancy were observed with elinzanetant in a long-term safety study.

VMS Treatment Guidelines

: I’d like to start by saying that Lisa and I are longtime friends, and we’ve had many conversations about this. We’re both strong proponents of estrogen therapy. So, let me be clear: we are not abandoning estrogen for these new medications, even though they are fabulous. The NK3 and NK1 receptor antagonists are groundbreaking, both in their biochemistry and their clinical results.

That said, these drugs are primarily for women who can’t or won’t take estrogen. They offer a fantastic option, particularly for patients who don’t tolerate estrogen or for whom it’s contraindicated. For example, in my oncology clinic, I see many breast cancer survivors devastated by vasomotor symptoms and sleep disturbances. These medications can be life-changing for them.

Lisa, as the immediate past president of the Menopause Society, can you talk about the society’s updated guidelines on hormonal and non-hormonal therapies? I’d also encourage our viewers to visit the Menopause Society’s website, 

, where you can access the 2022 hormonal therapy guidelines and the 2023 non-hormonal therapy guidelines for free.

: Absolutely. I strongly encourage everyone to read these guidelines, as they represent the gold standard for managing menopause.

As Dr Minkin said, we’ve both been shaped by the evolution of menopausal hormone therapy (MHT) over our careers. Unfortunately, many primary care clinicians, particularly those who entered the field after the 2002 Women’s Health Initiative (WHI) data, were taught to avoid hormone therapy entirely. For over two decades, there’s been a lack of education and a pervasive fear of hormones, stemming from concerns about stroke, heart attack, breast cancer, and dementia listed on package labels.

I recently saw a patient whose primary care doctor told her they ran a “hormone-free practice.” This highlights how misunderstood hormone therapy still is. However, today in 2024, we’ve gained a far better understanding of who benefits from hormone therapy, its advantages, and its risks.

Here’s what the current guidelines emphasize: for symptomatic women close to the menopause transition, MHT should be the first-line treatment. It’s highly effective for vasomotor symptoms, sleep issues, and more. Yet, fewer than 5% of appropriate candidates are even offered hormone therapy. That’s a huge disservice to these women.

Now, we do have exciting new non-hormonal drugs, but they’re primarily for women who can’t or won’t take hormones. While drugs like elinzanetant show promise for vasomotor symptoms and sleep, we don’t yet know their effects on other critical outcomes like cardiovascular risk, bone health, sexual function, or cognitive health. These areas remain unanswered.

So, for the majority of women, MHT remains the gold standard for managing menopausal symptoms. The guidelines make that clear.

: I agree, and to expand on Lisa’s point, there are other menopausal symptoms that estrogen helps with, even if they’re not part of the official indications. Let’s recap the primary indications for MHT: moderate to severe vasomotor symptoms, vaginal dryness, osteoporosis protection, and, for women with premature ovarian failure, comprehensive hormone replacement.

But estrogen benefits go beyond these. For example, many women report relief from joint aches and other discomforts. Vaginal dryness, bladder symptoms, and other aspects of genitourinary syndrome of menopause (GSM) are also areas where estrogen excels. These new drugs, while effective for hot flashes and sleep, don’t address GSM, bladder health, joint pain, or improvements in skin and hair.

So, while these medications are valuable, they don’t replace estrogen’s broader benefits. It’s about finding the right balance for each patient.

One final thought: menopause care takes time. These are complex conversations that require careful discussion with patients. You may not get rich as a menopause specialist, but you’ll make a real difference in your patients’ lives. And that’s what matters most.

Panelists discuss key considerations for women taking hormonal therapy, emphasizing the importance of individualized treatment plans and shared decision-making to evaluate the risk-benefit profile of therapy.

The lesion on this 6-year-old boy occupies almost the entire left side of his nose. The mother attributed it to an injury her son had sustained 2½ weeks earlier, when he was hit in the face by a baseball.

Is this lesion the result of an injury, as the boy’s mother suspected, or something else?

Scaly Plaque on the Nose

Johnathan S. Crane, MD

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