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Menopause associated VMS nonhormone treatment
Menopause-Associated VMS: Nonhormone Treatment Options to Meet Patients’ Needs

Released: May 30, 2025

Expiration: May 29, 2026

Sara Shihab
Sara Shihab, MD, MSCP, FACP
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Key Takeaways
  • Fezolinetant is an FDA-approved nonhormone treatment option for moderate to severe VMS (eg, night sweats, hot flashes) attributed to menopause.
  • Antidepressants like low-dose paroxetine and gabapentin can be used to treat menopause-associated VMS. 
  • Vaginal estrogen can be used safely with patients to treat genitourinary syndrome of menopause (GSM), including certain patients with breast cancer, because it is not a systemic hormone therapy.

Nonhormone therapies play a significant role in managing vasomotor symptoms (VMS) like hot flashes during menopause, especially when hormone therapy is not suitable or preferred, when there is a contraindication or new diagnosis (eg, breast cancer), or when the patient preference is to take nonhormone treatment. In this commentary, we provide answers to questions posed with a live audience that included physicians, nurse practitioners, and physician associates during a satellite symposium on VMS in menopause held on April 4, 2025. 

Hormone therapy is not an option for certain patients. With these cases review available nonhormone options with them, including pharmacologic agents and nonpharmacologic possibilities. Furthermore, I follow The Menopause Society’s recommendations, which include a succinct table that outlines dosing ranges for nonhormone prescription therapies. 

Fezolinetant for Menopause-Associated VMS
I usually start hormone therapy conversions with patients by telling them that there are prescription options. One is fezolinetant, a newer agent that has FDA approval to treat menopause-associated VMS that are moderate to severe. It is a neurokinin 3 receptor antagonist that regulates the body’s temperature. Patients take 1 pill daily, which helps reduce VMS severity. Although some patients experience comorbidities related to depression, anxiety, or sleep issues, this agent will not help alleviate those additional symptoms. However, if a patient’s only concerns are hot flashes or night sweats, fezolinetant is the first option that I recommend.

For patients interested in starting fezolinetant, healthcare professionals (HCPs) must check their liver lab values at baseline and periodically afterwards as outlined in its prescribing information. This is because clinical data for fezolinetant indicate a few cases where patients had elevated liver transaminases. These values normalized to baseline when they discontinued treatment, had a dose interruption, or stopped treatment altogether.

The Role of Antidepressants
Antidepressants (serotonin-norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors) are an option for treating menopause-associated VMS.  I clarify patients by saying that we don’t specifically prescribe these agents for depression as I find there is some stigma associated with antidepressants. Many patients are concerned about using an antidepressant when they are not depressed. In such cases, I ensure that patients understand that antidepressants are prescribed specifically for VMS.

For example, paroxetine 7.5 mg is a once-daily pill that has FDA approval to treat menopause-associated VMS. It was studied in clinical trials, which demonstrated its efficacy in reducing VMS severity and frequency. If paroxetine 7.5 mg is not covered by patients’ health insurance, I prescribe the generic form that is 10 mg. Paroxetine also can be a good option for those with anxiety and depression related to perimenopause. Ensure that patients understand that the most common adverse events with this agent are headache, nausea, and vomiting, but paroxetine 7.5 mg is usually tolerated well.

Then there is gabapentin, a nerve-stabilizing agent. I often prescribe this for patients to take at night because it causes sleepiness. So for those who have trouble sleeping, gabapentin may be a good option. Following The Menopause Society recommendations, I start patients at 100 mg and gradually titrate to 300 mg at night. Again, studies demonstrated efficacy in reducing the severity of hot flashes. In addition, I rarely see patients experience toxicities with this treatment.

When using antidepressants to treat menopause-associated VMS, I tell patients that I use these therapies to treat their symptoms. I tailor the treatment based on what their most concerning symptoms are, and I will combine therapies when needed. Of note, I do not start patients on 2 agents at the same time; rather, I start with 1 and bring patients in for follow-up to see how they are doing. Are they tolerating the agent? Are they noticing improvement in their targeted symptoms? Do I need to titrate? Do we need to shift gears? Regardless of the answer, treatment should be tailored based on the patient’s most bothersome symptoms.

HCPs should not prescribe a concomitant selective serotonin reuptake inhibitor relating to potential drug–drug interactions for patients with breast cancer receiving selective estrogen receptor modulators like tamoxifen. However, one can prescribe venlafaxine, a serotonin-norepinephrine reuptake inhibitor, which has little to no drug–drug interaction with tamoxifen. So HCPs must pay attention to these possibilities.

Vaginal Estrogen for GSM
When talking about hormone therapy, we are discussing the systemic hormone therapy that is used to treat bothersome VMS related to menopause. But hormone therapy is associated with other benefits, including improved bone health, sleep, and sexual function. Vaginal estrogen therapy has FDA approval to treat genitourinary syndrome of menopause (GSM). With menopause and a lack of estrogen, there are a lot of changes that happen in the urogenital tissue, vulva, vagina, and the tissue around the urethra. There is a loss of elasticity and a change in pH, which lead to different bacteria growth. When that protective barrier tissue is no longer there, patients may experience symptoms such as burning, itching, discomfort, and urinary urgency or infection.

Many patients may have these symptoms and think that they have a urinary tract infection (UTI). They are going to the bathroom more frequently and are only producing small amounts of urine. They get tested and are sometimes treated for UTIs or have frequent UTIs. And this is all because of the changes in the tissue and changes in the microbiota related to menopause.

Other GSM symptoms include painful intercourse and dyspareunia. Again, because of the dryness and nonstretchable tissue, penetration becomes painful. Many patients have told me that intercourse feels like shredded glass or sandpaper. It is incredibly painful for them. This is where low-dose vaginal estrogen is helpful. Because it is not a systemic estrogen most patients can be on it, including those with contraindications to estrogen (eg, patients with breast cancer). And I always involve the patient’s oncologist because there are safety nuances to consider for this treatment option.

Vaginal estrogen can be prescribed at any age or time once patients are in menopause. The reason we have this liberty with prescribing vaginal estrogen is because it is a local therapy. It is low-dose vaginal therapy that requires a small amount to reach the bloodstream. In long-term studies, patients did not see an increased risk for cardiovascular disease or cancer with vaginal estrogen use vs nonuse. Furthermore, HCPs often do not need to prescribe progesterone for endometrial protection because the low-dose local therapy of vaginal estrogen does not reach serum levels that could lead to endometrial hyperplasia.

Your Thoughts
How often do you prescribe nonhormone therapies to treat patients with menopause-associated VMS? You can get involved in the discussion by answering the poll question and posting a comment below.

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