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Shedding Light on the Risks
& Benefits of Medications Non-Hormonal Options for Perimenopause Symptoms
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New FDA-approved medications and older repurposed drugs are expanding treatment choices for women seeking relief from hot flashes, sleep problems, mood changes, and other symptoms
July 15, 2026
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Natural Approaches to Managing Perimenopause
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Each year, about two million women in the United States begin perimenopause, yet many are caught off guard by how wide-ranging the symptoms can be.
“Most people, and honestly, a fair number of clinicians, still picture perimenopause as hot flashes, mood changes, and poor sleep,” says Melinda Ring, M.D., clinical professor of Medicine and Medical Social Sciences at Northwestern University Feinberg School of Medicine in Chicago. “These are real, but they’re only part of it. I see women with new histamine reactions, joint and muscle pain, even frozen shoulder, all tied to shifting hormones.”
Treating these and other symptoms has traditionally meant hormone therapy (HT), the cornerstone of treatment for perimenopause. But HT is not medically suitable or desirable for everyone, and researchers have continued to search for safe and effective nonhormonal alternatives. Today, renewed attention to women’s health is yielding a new generation of targeted medications designed to improve well-being during perimenopause.
“For a long time, women who couldn’t take hormone therapy were left with very little,” says Dr. Ring, who also serves as director of the Osher Center for Integrative Health at Northwestern. “Now we have targeted nonhormonal options. They’re a genuine advance.”
What Is Perimenopause?
Perimenopause is the transitional stage before menopause, when the body begins shifting toward the end of menstrual periods and hormone levels start to fluctuate. Sometimes called the menopausal transition, perimenopause typically begins in the mid-40s, though it can start earlier, and lasts an average of six years (although for some women it continues much longer).
The perimenopause transition officially ends after a woman has gone 12 consecutive months without a menstrual period, marking menopause.
During perimenopause, estrogen and progesterone levels fluctuate unpredictably, triggering a wide range of symptoms. Periods may become heavier, lighter, more frequent, or farther apart. Some women experience hot flashes and night sweats, while others notice mood changes, sleep disruption, vaginal dryness, headaches, weight gain, bladder symptoms, or difficulty concentrating.
“Estrogen affects every tissue and organ system in the body,” says Stephanie S. Faubion, M.D., director of Mayo Clinic’s Center for Women’s Health and medical director of The Menopause Society. “And when you lose it, you have effects in pretty much every tissue and organ system.”
Although hot flashes and night sweats, also called vasomotor symptoms, affect as many as 80% of women and are the best-known symptoms of perimenopause, according to recent research, they are not the most common complaint among perimenopausal women. A study published in January 2026 in the journal Menopause, analyzing data from nearly 17,500 women globally, found that physical and mental exhaustion, fatigue, irritability, sleep problems, and depression were reported even more frequently.
Because symptoms often develop gradually and may not initially seem connected to hormonal changes, many women do not immediately recognize what is happening.
“The provider may say, ‘Oh, but you are still getting a period,’ or ‘Your hormone levels are normal or high — it’s not that,’” says Monica Christmas, M.D., director of the Center for Women’s Integrated Health and the Menopause Program at the University of Chicago Medicine and associate medical director of The Menopause Society.
To manage these symptoms, some women benefit from continuous hormonal birth control, which can help regulate symptoms while providing contraception. For others, hormone therapy remains one of the most effective treatments for vasomotor symptoms and related sleep disruption.
However, these treatments are not a universal option. HT is generally not recommended for women with prior or current estrogen-dependent cancers, including breast and endometrial cancer, or for those with a history of heart attack, stroke, blood clots, or pulmonary embolism. Others remain hesitant because of lingering concerns stemming from the 2002 Women’s Health Initiative (WHI) report claiming that increased risks of cardiovascular disease and breast cancer are associated with hormone therapy.
While subsequent research has provided a more nuanced and reassuring picture than the one painted by the initial WHI study, HT’s risks and benefits vary depending on age, timing, medical history, and the type of therapy used, says Dr. Faubion.
Nonhormonal Medications
For women who cannot or prefer not to use hormone therapy, evidence-based nonhormonal treatment options have expanded in recent years. Certain medications are Food and Drug Administration (FDA)-approved specifically for vasomotor symptoms, while others are prescribed as off-label, meaning they are used in ways not specifically approved by the FDA.
Off-label use of these medications for menopause may also help address related problems such as anxiety, depression, sleep disruption, chronic pain, or bladder symptoms. Clinicians sometimes describe them as “twofers” because they may improve more than one symptom at the same time.
“We try to do double duty with these medications,” says Dr. Faubion. “They address both the primary symptom and the broader range of symptoms that occur during the menopausal transition.”
Fezolinetant (Veozah)
The ongoing effort to develop safe and effective nonhormonal alternatives reached a significant milestone with the 2023 FDA approval of fezolinetant (Veozah), the first in a new class of medications known as neurokinin 3 (NK3) receptor antagonists for moderate-to-severe hot flashes and night sweats.
The drug acts on the brain’s thermoregulatory center, targeting neurons in the hypothalamus that help regulate body temperature. By stabilizing the body’s internal “thermostat,” it can reduce hot flashes without the use of hormones.
Because fezolinetant is FDA-approved for vasomotor symptoms associated with menopause, prescribing it during perimenopause is technically off-label.
Typically taken once daily, fezolinetant demonstrated strong results in Phase 3 clinical trials (SKYLIGHT 1 and 2). These multicenter trials enrolled 1,022 women, aged 40 to 65, across 146 sites in the U.S., Canada, and Europe. Participants experiencing at least seven moderate-to-severe hot flashes per day received either 30 mg or 45 mg of fezolinetant or placebo. By week 12, those on the 45 mg dose experienced more than a 60% reduction on average in hot flash frequency and severity compared with placebo, with improvements often beginning as early as week four..
Because Veozah has been linked to rare but serious liver injury, it carries an FDA boxed warning. Current prescribing guidelines require liver function testing before treatment begins, monthly for the first three months, and again at months 6 and 9. Other side effects may include abdominal pain, diarrhea, insomnia, headache, and back pain.
Natural Approaches to Managing Perimenopause
Many women look for ways to manage perimenopause symptoms without prescription medications. Some natural approaches that may help ease symptoms for some include:
Mediterranean-style eating. Rich in fruits, vegetables, whole grains, nuts, legumes, fish, and healthy fats, the Mediterranean diet has anti-inflammatory properties and may help reduce hot flashes while supporting a healthy weight, says Dr. Nakhoul.
Regular exercise. Cardio exercise combined with strength training can help maintain bone density, improve mood, and support overall health. Research suggests exercise may be particularly helpful for managing mild to moderate perimenopausal symptoms.
Better sleep habits. Since hot flashes often disrupt sleep, maintaining a consistent sleep schedule and creating a cool, comfortable sleep environment can help. Breathable bedding, a fan, or a cooling mattress pad may improve comfort and sleep quality.
Mind-body practices. Yoga, meditation, and mindfulness techniques may help reduce stress, improve sleep, and lessen the impact of hot flashes. Studies suggest these approaches may also improve anxiety and fatigue while improving overall quality of life.
Acupuncture. Some studies suggest acupuncture may help reduce hot flashes and improve overall well-being, although results vary.
Supplements and herbal remedies. Black cohosh is among the most studied supplements for hot flashes. Other commonly used options include red clover, flaxseed, evening primrose oil, Korean red ginseng, and melatonin, though research findings are mixed. Because supplements are not regulated by the FDA in the same way as prescription drugs, quality and potency can vary. “Not everything that is ‘natural’ is necessarily safe,” says Dr. Nakhoul. For information about potential benefits, side effects, and precautions, visit the National Center for Complementary and Integrative Health’s “Herbs at a Glance” resource.
Elinzanetant (Lynkuet)
Following closely behind fezolinetant, elinzanetant is another new non-hormonal option for treating hot flashes. Approved by the FDA in late 2025, elinzanetant (Lynkuet) is the first dual neurokinin receptor antagonist developed to treat vasomotor symptoms associated with menopause, though clinicians may also prescribe it during perimenopause.
Like fezolinetant, the drug targets the brain’s temperature-regulation system but blocks both NK1 and NK3 receptors, pathways believed to contribute to hot flashes, night sweats, and disrupted sleep. Researchers say that dual action may help explain why the medication appears to improve sleep quality alongside hot flash frequency.
“This is a strong option for many women,” says Dr. Christmas, noting that an internal clinical trial showed reductions in hot flashes of around 70%, along with sleep benefits.
In Phase 3 clinical trials (OASIS 1, 2, and 3) involving nearly 800 women with moderate-to-severe vasomotor symptoms, elinzanetant significantly reduced the frequency and severity of hot flashes within the first week compared with placebo. The OASIS 3 study specifically confirmed the drug’s long-term safety profile over 52 weeks.
The drug has also successfully undergone testing at UVA Health and other sites globally. Reported side effects have generally been mild, including headache and fatigue.
“These two newer drugs are very effective options for the treatment and management of vasomotor symptoms, and some patients describe them as feeling like ‘miracle drugs,’” says Marie R. Nakhoul, M.D., a board-certified obstetrician-gynecologist at the University of Maryland Medical Center in Baltimore. “They represent a meaningful advance for women, and they are really exciting.”
Beyond neurokinin receptor antagonists, several classes of older, repurposed medications are also used to treat vasomotor symptoms.
Venlafaxine (Effexor) and Desvenlafaxine (Pristiq)
Venlafaxine and desvenlafaxine are antidepressants known as serotonin-norepinephrine reuptake inhibitors (SNRIs). They are often prescribed off-label for women in perimenopause who are looking for relief from both hot flashes and escalating anxiety.
An older randomized, double-blind trial from 2009 involving 458 women published in the American Journal of Obstetrics & Gynecology, showed that desvenlafaxine effectively reduced vasomotor symptoms by up to 67%.
Additionally, a 2011 review published in Pharmacy Practice (Granada) and co-authored by researchers from the Auburn University Harrison School of Pharmacy found that venlafaxine reduced hot flash frequency and severity by 37% to 61%.
Researchers believe these medications help calm the brain’s temperature-regulation system by influencing serotonin and norepinephrine signaling, which appears to change as estrogen levels fluctuate during perimenopause and menopause.
Side effects may include nausea, insomnia, increased blood pressure, and sexual dysfunction (which can be life-altering for some people). Because abrupt discontinuation can trigger withdrawal symptoms, the medications should be tapered gradually.
Paroxetine (Brisdelle) and Escitalopram (Lexapro)
Selective serotonin reuptake inhibitors (SSRIs) are another class of antidepressants used to treat vasomotor symptoms. Low-dose paroxetine (7.5 mg) remains the only FDA-approved medication in this class.
In a 2011 randomized placebo-controlled trial published in JAMA, part of the NIH-funded MsFLASH (Menopause Strategies-Finding Lasting Answers for Symptoms and Health) network, researchers at the University of Pennsylvania Perelman School of Medicine studied 205 women. They found that escitalopram reduced hot flashes by 47% compared with 33% in the placebo group after eight weeks.
Both medications are generally well tolerated, though side effects may include nausea, sleep disturbance, and sexual dysfunction. Paroxetine should not be used with tamoxifen because it can interfere with how the body processes the breast cancer drug, potentially making it less effective.
Gabapentin (Neurontin)
Originally developed as an anti-seizure medication, gabapentin is now frequently used off-label to reduce hot flashes, particularly those that disrupt sleep.
The drug appears to influence temperature-regulation pathways in the central nervous system and can have sedating effects. As a result, clinicians often consider it for people whose hot flashes are disrupting sleep, particularly when chronic pain is also present.
Several randomized trials have shown that gabapentin can reduce both the frequency and severity of hot flashes, particularly at night. A study from 2006 published in The Lancet found that 420 breast cancer survivors taking 900 mg daily experienced a 41% reduction in hot flashes after four weeks, compared with just 17% in the placebo group.
Because gabapentin has sedating effects, daytime drowsiness, dizziness, and fatigue are common side effects. It should not be combined with alcohol, opioids, or other sedatives because of the risk of excessive sedation.
Oxybutynin (Ditropan)
Traditionally prescribed for overactive bladder, which is a common problem during perimenopause and menopause that can leave women feeling the frequent or sudden need to urinate, oxybutynin (Ditropan) is increasingly being used off-label to help reduce hot flashes. The medication blocks acetylcholine, a neurotransmitter involved in both bladder contractions and sweating. As a result, it may be particularly helpful for women dealing with urinary urgency or frequency alongside vasomotor symptoms.
Available in both immediate-release and extended-release formulations, oxybutynin has shown meaningful reductions in hot flash frequency and severity in clinical studies. A major 2020 multicenter trial known as ACCRU SC-1603, led by researchers at the Mayo Clinic and published in JNCI Cancer Spectrum, found that oxybutynin reduced hot flashes by 70% to 86% depending on the dose.
However, side effects can be limiting. “I rarely use it,” says Dr. Nakhoul, who also serves as an assistant professor of Obstetrics, Gynecology and Reproductive Sciences at the University of Maryland School of Medicine. She notes that, in her experience, oxybutynin is generally less effective than paroxetine and raises additional concerns about its cognitive effects, particularly with long-term use in older adults.
Beyond dry mouth and constipation, clinicians monitor for “anticholinergic burden”— the cumulative effect of drugs like oxybutynin that block acetylcholine, a neurotransmitter involved in memory and learning. Because a high anticholinergic burden has been linked in longitudinal studies to an increased risk of cognitive decline and dementia in older adults, clinicians emphasize using the lowest effective dose while monitoring for changes in memory or thinking.
Finding the Right Approach
The growing number of nonhormonal therapies has broadened treatment discussions for women who need or prefer alternatives to hormone therapy. “The newer drugs haven’t replaced the conversation for me,” says Dr. Ring. “They have widened it. The new medications simply give me one more good tool for the women who need a different path.”
For many women, that expanding treatment landscape is welcome news.
“The gift of this day is that we have so many options,” says Lisa Taylor-Swanson, Ph.D., associate professor in the College of Nursing and adjunct associate professor in the Department of Obstetrics & Gynecology at the University of Utah. She says many women tell her they are interested in starting with lifestyle or natural approaches and then considering other treatments if those strategies do not provide enough relief.
Ultimately, the right approach looks different for every woman, depending on her symptoms, health history, and preferences. “It’s not about surviving perimenopause,” says Dr. Christmas. “It’s thriving through perimenopause.”
Disclosure: Several experts interviewed for this article are affiliated with The Menopause Society. The nonprofit organization reports receiving support from corporate sponsors, including pharmaceutical companies that participate in its Corporate Liaison Council.
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If you’ve experienced side effects or medication issues related to this topic, we want to hear from you.
Submit Your Story- Avis, N. E., Crawford, S. L., & Green, R. (2018). Vasomotor symptoms across the menopause transition: Differences among women. Obstetrics and Gynecology Clinics of North America, 45(4), 629–640
- Bluming, A. Z., & Tavris, C. (2023). ‘Tis but a scratch: A critical review of the Women’s Health Initiative evidence against hormone replacement therapy. Menopause, 30(12), 1219–1226.
- Columbia University Irving Medical Center. (n.d.). Everything you need to know about perimenopause.
- Dodin, S., Blanchet, C., Marc, I., Ernst, E., Wu, T., Vaillancourt, C., Paquette, J., & Maunsell, E. (2013). Acupuncture for menopausal hot flushes. Cochrane Database of Systematic Reviews, 2013(7), CD007410
- Food and Drug Administration. (2023, May 12). FDA approves novel drug to treat moderate to severe hot flashes caused by menopause.
- Food and Drug Administration. (2024, December 17). FDA adds warning about rare occurrence of serious liver injury with use of Veozah (fezolinetant) for hot flashes due to menopause.
- Food and Drug Administration. (2025). Drug trials snapshots: Lynkuet.
- Freeman, E. W., Guthrie, K. A., Caan, B., Sternfeld, B., Cohen, L. S., Joffe, H., Carpenter, J. S., Anderson, G. L., Larson, J. C., Ensrud, K. E., Reed, S. D., & Newton, K. M. (2011). Efficacy of escitalopram for hot flashes in healthy menopausal women: A randomized controlled trial. JAMA, 305(3), 267–274
- Gonçalves, C., et al. (2024). Systematic review of Mediterranean diet interventions in menopausal women. Nutrients, 16
- Hedges, M. S., et al. (2026). Global perspectives on perimenopause: A digital survey of knowledge and symptoms using the Flo app. Menopause.
- Johnson, E. D., Carroll, D. G., & Belding, M. A. (2011). Venlafaxine and desvenlafaxine in the management of menopausal hot flashes. Pharmacy Practice, 9(3), 117–121.
- Johnson, K. A., et al. (2023). Efficacy and safety of fezolinetant in moderate to severe vasomotor symptoms associated with menopause: A phase 3 randomized clinical trial. The Lancet, 401(10382), 1091–1102
- Leon-Ferre, R. A., Novotny, P. J., Wolfe, E. G., Faubion, S. S., Ruddy, K. J., Flora, D., Dakhil, C. S. R., Rowland, K. M., Graham, M. L., Le-Lindqwister, N., Smith, T. J., & Loprinzi, C. L. (2020). Oxybutynin vs placebo for hot flashes in women with or without breast cancer: A randomized, double-blind clinical trial (ACCRU SC-1603). JNCI Cancer Spectrum, 4(1), pkz088
- Mayo Clinic. (n.d.). Perimenopause: Symptoms and causes.
- National Center for Complementary and Integrative Health. (n.d.). Herbs at a glance.
- National Institutes of Health, Office of Dietary Supplements. (n.d.). Black cohosh: Fact sheet for health professionals.
- Panay, N., et al. (2025). Elinzanetant for the treatment of vasomotor symptoms associated with menopause. JAMA Internal Medicine.
- Pandya, K. J., Morrow, G. R., Roscoe, J. A., Zhao, H., Hickok, J. T., Pajon, E., Sweeney, T. J., Banerjee, T. K., & Flynn, P. J. (2005). Gabapentin for hot flashes in 420 women with breast cancer: A randomised double-blind placebo-controlled trial. The Lancet, 366(9488), 818–824.
- Philip, A. E., et al. (2025). Impact of exercise on perimenopausal syndrome: A systematic review. Cureus.
- Sood, R., Kuhle, C. L., Kapoor, E., Thielen, J. M., Frohmader, K. S., Mara, K. C., & Faubion, S. S. (2019). Association of mindfulness and stress with menopausal symptoms in midlife women. Climacteric, 22(4), 377–382.
- Wegrzynowicz, A. K., et al. (2025). Insights into perimenopause: A survey of perceptions, symptoms, and healthcare experiences. Women’s Health Reports.
- World Health Organization. (2024, October 17). Menopause.
- Xu, H., et al. (2024). Effects of mind-body exercise on perimenopausal and postmenopausal women: A systematic review and meta-analysis. Frontiers in Public Health.
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<p>Each year,<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC12014197/"> about two million women </a>in the United States begin perimenopause, yet many are caught off guard by how wide-ranging the symptoms can be. </p>
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<p>"Most people, and honestly, a fair number of clinicians, still picture perimenopause as hot flashes, mood changes, and poor sleep," says <a href="https://www.nm.org/doctors/1245348333/melinda-r-ring-md">Melinda Ring, M.D.,</a> clinical professor of Medicine and Medical Social Sciences at Northwestern University Feinberg School of Medicine in Chicago. "These are real, but they're only part of it. I see women with new histamine reactions, joint and muscle pain, even frozen shoulder, all tied to shifting hormones.”</p>
<!-- /wp:paragraph --><!-- wp:paragraph -->
<p>Treating these and other symptoms has traditionally meant hormone therapy (HT), the cornerstone of treatment for perimenopause. But HT is not medically suitable or desirable for everyone, and researchers have continued to search for safe and effective nonhormonal alternatives. Today, renewed attention to women's health is yielding a new generation of targeted medications designed to improve well-being during perimenopause.</p>
<!-- /wp:paragraph --><!-- wp:paragraph -->
<p>“For a long time, women who couldn’t take hormone therapy were left with very little,” says Dr. Ring, who also serves as director of the <a href="https://www.feinberg.northwestern.edu/sites/ocih/">Osher Center for Integrative Health at Northwestern</a>. “Now we have targeted nonhormonal options. They’re a genuine advance.”</p>
<!-- /wp:paragraph --><!-- wp:heading -->
<h2 class="wp-block-heading"><strong>What Is Perimenopause? </strong></h2>
<!-- /wp:heading --><!-- wp:paragraph -->
<p>Perimenopause is the transitional stage before menopause, when the body begins shifting toward the end of menstrual periods and hormone levels start to fluctuate. Sometimes called <a href="https://www.mayoclinic.org/diseases-conditions/perimenopause/symptoms-causes/syc-20354666">the menopausal transition</a>, perimenopause typically begins in the mid-40s, though it can start earlier, and lasts an average of <a href="https://menopause.org/press-releases/international-differences-exist-in-knowledge-gaps-and-most-common-perimenopause-symptoms">six years</a> (although for some women it continues much longer). </p>
<!-- /wp:paragraph --><!-- wp:paragraph -->
<p>The perimenopause transition officially ends<a href="https://www.who.int/news-room/fact-sheets/detail/menopause#:~:text=Natural%20menopause%20is%20deemed%20to,the%20absence%20of%20clinical%20intervention."> after a woman has gone 12 consecutive months</a> without a menstrual period, marking menopause.</p>
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<p>During perimenopause, estrogen and progesterone levels fluctuate unpredictably, triggering a wide range of symptoms. <a href="https://www.cuimc.columbia.edu/news/everything-you-need-know-about-perimenopause">Periods may become heavier, </a>lighter, more frequent, or farther apart. Some women experience hot flashes and night sweats, while others notice mood changes, sleep disruption, vaginal dryness, headaches, weight gain, bladder symptoms, or difficulty concentrating.</p>
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<p>“Estrogen affects every tissue and organ system in the body,” says <a href="https://www.mayoclinic.org/biographies/faubion-stephanie-s-m-d-m-b-a/bio-20054845">Stephanie S. Faubion, M.D.,</a> director of Mayo Clinic's Center for Women's Health and medical director of The Menopause Society. “And when you lose it, you have effects in pretty much every tissue and organ system.”</p>
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<p>Although hot flashes and night sweats, also called vasomotor symptoms, affect<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6226273/"> as many as 80%</a> of women and are the best-known symptoms of perimenopause, according to recent research, they are not the most common complaint among perimenopausal women. <a href="https://pubmed.ncbi.nlm.nih.gov/41603602/#:~:text=The%20study%20%22Global%20perspectives%20on%20perimenopause:%20a,Depressive%20mood%20(77%25)%20*%20Digestive%20issues%20(76%25)">A study published in January 2026</a> in the journal <em>Menopause</em>, analyzing data from nearly 17,500 women globally, found that physical and mental exhaustion, fatigue, irritability, sleep problems, and depression were<a href="https://menopause.org/wp-content/uploads/press-release/MENO-D-25-00377.pdf"> reported even more frequently</a>.</p>
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<p>Because symptoms often develop gradually and may not initially seem connected to hormonal changes, many women do not immediately recognize what is happening. </p>
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<p>“The provider may say, ‘Oh, but you are still getting a period,’ or ‘Your hormone levels are normal or high — it’s not that,’” says <a href="https://www.uchicagomedicine.org/find-a-physician/physician/monica-christmas">Monica Christmas, M.D</a>., director of the Center for Women’s Integrated Health and the Menopause Program at the University of Chicago Medicine and associate medical director of The Menopause Society.</p>
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<p>To manage these symptoms, some women benefit from continuous hormonal birth control, which can help regulate symptoms while providing contraception. For others, hormone therapy remains <a href="https://menopause.org/press-releases/when-women-initiate-estrogen-therapy-matters">one of the most effective treatments </a>for vasomotor symptoms and related sleep disruption.</p>
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<p>However, these <a href="https://medshadow.org/conditions-treatments/hormone-therapy/why-is-hormone-therapy-still-so-misunderstood/">treatments are not a universal option.</a> HT is generally not recommended for women with prior or current estrogen-dependent cancers, including breast and endometrial cancer, or for those with a history of heart attack, stroke, blood clots, or pulmonary embolism. Others remain hesitant because of lingering concerns stemming from the <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10758198/#:~:text=Use%20of%20menopausal%20hormone%20therapy,not%20improve%20quality%20of%20life">2002 Women’s Health Initiative (WHI)</a> report claiming that increased risks of cardiovascular disease and breast cancer are associated with hormone therapy.</p>
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<p>While subsequent research <a href="https://medshadow.org/conditions-treatments/hormone-therapy/why-is-hormone-therapy-still-so-misunderstood/">has provided a more nuanced and reassuring picture</a> than the one painted by the initial WHI study, HT’s risks and benefits vary depending on age, timing, medical history, and the type of therapy used, says Dr. Faubion.</p>
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<h2 class="wp-block-heading"><strong>Nonhormonal Medications</strong></h2>
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<p>For women who cannot or prefer not to use hormone therapy, evidence-based nonhormonal treatment options have expanded in recent years. Certain medications are Food and Drug Administration (FDA)-approved specifically for vasomotor symptoms, while others are prescribed as off-label, meaning they are used in ways not specifically approved by the FDA. </p>
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<p>Off-label use of these medications for menopause may also help address related problems such as anxiety, depression, sleep disruption, chronic pain, or bladder symptoms. Clinicians sometimes describe them as “<a href="https://www.mayoclinicproceedings.org/action/showPdf?pii=S0025-6196(24)00245-3">twofers</a>” because they may improve more than one symptom at the same time. </p>
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<p>“We try to do double duty with these medications,” says Dr. Faubion. “They address both the primary symptom and the broader range of symptoms that occur during the menopausal transition.”</p>
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<h3 class="wp-block-heading"><strong>Fezolinetant (Veozah)</strong></h3>
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<p>The ongoing effort to develop safe and effective nonhormonal alternatives reached a significant milestone with the<a href="https://www.fda.gov/news-events/press-announcements/fda-approves-novel-drug-treat-moderate-severe-hot-flashes-caused-menopause"> 2023 FDA </a>approval of <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11623885/">fezolinetant (Veozah)</a>, the first in a new class of medications known as neurokinin 3 (NK3) receptor antagonists for moderate-to-severe hot flashes and night sweats. </p>
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<p><a href="https://medshadow.org/drug-updates-recalls/drug-safety/how-safe-is-veozah-the-fda-approved-hot-flash-treatment/">The drug acts on the brain’s thermoregulatory center,</a> targeting neurons in the hypothalamus that help regulate body temperature. By stabilizing the body's internal "thermostat," it can reduce hot flashes without the use of hormones.</p>
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<p>Because fezolinetant is FDA-approved for vasomotor symptoms associated with menopause, prescribing it during perimenopause is technically off-label. </p>
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<p>Typically taken once daily, fezolinetant demonstrated strong results in <a href="https://www.endocrine.org/news-and-advocacy/news-room/2022/phase-3-study-finds-fezolinetant-reduces-the-frequency-and-severity-of-menopausal-hot-flashes">Phase 3 clinical trials (SKYLIGHT 1 and 2).</a> These multicenter trials enrolled 1,022 women, aged 40 to 65, across 146 sites in the U.S., Canada, and Europe. Participants experiencing at least seven moderate-to-severe hot flashes per day received either 30 mg or 45 mg of fezolinetant or placebo. By week 12, those on the 45 mg dose experienced more than<a href="https://www.contemporaryobgyn.net/view/nonhormonal-therapies-transform-menopause-care-in-2025#:~:text=Nonhormonal%20therapies%20transform%20menopause%20care%20in%202025%20%7C%20Contemporary%20OB/GYN"> a 60% reduction</a> on average in hot flash frequency and severity compared with placebo, with improvements often beginning as early as week four.. </p>
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<p>Because Veozah has been linked to rare but serious liver injury, it carries <a href="https://www.fda.gov/drugs/drug-safety-communications/fda-adds-warning-about-rare-occurrence-serious-liver-injury-use-veozah-fezolinetant-hot-flashes-due">an FDA boxed warning</a>. Current prescribing guidelines require liver function testing before treatment begins, monthly for the first three months, and again at months 6 and 9. Other side effects may include abdominal pain, diarrhea, insomnia, headache, and back pain.</p>
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<div class="wp-block-myplugin-custom-alignment-block alignright"><h2><strong>Natural Approaches to Managing Perimenopause</strong><br></h2><p>Many women look for ways to manage perimenopause symptoms without prescription medications. Some natural approaches that may help ease symptoms for some include:<br><br><strong>Mediterranean-style eating</strong>. Rich in fruits, vegetables, whole grains, nuts, legumes, fish, and healthy fats, the <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11007410/">Mediterranean diet</a> has anti-inflammatory properties and may <a href="https://www.news-medical.net/news/20250901/How-a-Mediterranean-diet-helps-women-manage-menopausal-symptoms.aspx">help reduce hot flashes</a> while supporting a healthy weight, says Dr. Nakhoul. <br><br><strong>Regular exercise</strong>. Cardio exercise combined with strength training can help maintain bone density, improve mood, and support overall health<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC12008710/">. Research suggests exercise </a>may be particularly helpful for managing mild to moderate perimenopausal symptoms.<br><br><strong>Better sleep habits</strong>. Since hot flashes often disrupt sleep, maintaining a consistent sleep schedule and creating a cool, comfortable sleep environment can help. Breathable bedding, <a href="https://store.mayoclinic.com/education/perimenopause-and-sleep-why-it-changes-and-what-can-help/">a fan, or a cooling mattress pad</a> may improve comfort and sleep quality. <br><br><strong>Mind-body practices</strong>. Yoga, meditation, and mindfulness techniques may help reduce stress, improve sleep, and lessen the impact of hot flashes. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11465887/">Studies suggest </a>these approaches may also improve anxiety and fatigue while improving overall quality of life.<br><br><strong>Acupuncture</strong>. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7478674/">Some studies</a> suggest <a href="https://medshadow.org/integrative-health/other-treatments/can-acupuncture-help-osteoarthritis-pain/">acupuncture</a> may help reduce hot flashes and improve overall well-being, although results vary.<br><br><strong>Supplements and herbal remedies.</strong> <a href="https://ods.od.nih.gov/factsheets/BlackCohosh-HealthProfessional/">Black cohosh </a>is among the most studied supplements for hot flashes. Other commonly used options include red clover, flaxseed, <a href="https://pubmed.ncbi.nlm.nih.gov/41498229/">evening primrose oil</a>, Korean red ginseng, and melatonin, though <a href="https://www.sciencedirect.com/science/article/abs/pii/S1555415523003756">research findings are mixed</a>. Because supplements are not regulated by the FDA in the same way as prescription drugs, quality and potency can vary. “Not everything that is ‘natural’ is necessarily safe,” says Dr. Nakhoul. For information about potential benefits, side effects, and precautions, visit the National Center for Complementary and Integrative Health’s <a href="https://www.nccih.nih.gov/health/herbsataglance">“Herbs at a Glance</a>" resource. </p></div>
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<h3 class="wp-block-heading"><strong>Elinzanetant (Lynkuet)</strong></h3>
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<p>Following closely behind fezolinetant, <a href="https://medshadow.org/drug-updates-recalls/drug-safety/what-to-know-about-lynkuet-the-new-hot-flash-drug/">elinzanetant</a> is another new non-hormonal option for treating hot flashes. Approved by the FDA in late 2025, <a href="https://www.fda.gov/drugs/drug-trials-snapshots/drug-trials-snapshots-lynkuet">elinzanetant (Lynkuet) is the first dual neurokinin receptor antagonis</a>t developed to treat vasomotor symptoms associated with menopause, though clinicians may also prescribe it during perimenopause.</p>
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<p>Like fezolinetant, the drug targets the brain’s temperature-regulation system but blocks both NK1 and NK3 receptors, pathways believed to contribute to hot flashes, night sweats, and disrupted sleep. Researchers say that dual action may help explain why the medication appears to improve sleep quality alongside hot flash frequency.</p>
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<p>“This is a strong option for many women,” says Dr. Christmas, noting that an internal clinical trial showed <a href="https://news.med.virginia.edu/research/menopause-drug-reduces-hot-flashes-by-more-than-70-in-international-clinical-trial/">reductions in hot flashes of around 70%, along </a>with sleep benefits.</p>
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<p>In Phase 3 clinical trials (<a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2838538">OASIS 1, 2, and 3)</a> involving nearly 800 women with moderate-to-severe vasomotor symptoms, elinzanetant significantly reduced the frequency and severity of hot flashes within the first week compared with placebo. The OASIS 3 study specifically confirmed the drug’s long-term safety profile over 52 weeks.</p>
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<p>The drug has also successfully undergone testing at UVA Health and other sites globally. Reported side effects have generally been mild, including headache and fatigue.</p>
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<p>“These two newer drugs are very effective options for the treatment and management of vasomotor symptoms, and some patients describe them as feeling like ‘miracle drugs,’” says <a href="https://www.umms.org/find-a-doctor/profiles/dr-marie-ramez-nakhoul-md-1235634999">Marie R. Nakhoul, M.D., a board-certified obstetrician-gynecologis</a>t at the University of Maryland Medical Center in Baltimore. “They represent a meaningful advance for women, and they are really exciting.” </p>
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<p>Beyond neurokinin receptor antagonists, several classes of older, repurposed medications are also used to treat vasomotor symptoms. </p>
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<h3 class="wp-block-heading"><strong>Venlafaxine (Effexor) and Desvenlafaxine (Pristiq) </strong></h3>
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<p>Venlafaxine and desvenlafaxine are antidepressants known as serotonin-norepinephrine reuptake inhibitors (SNRIs). They are often prescribed off-label for women in perimenopause who are looking for relief from both hot flashes and escalating anxiety.<br><br>An older randomized, double-blind trial from 2009 involving 458 women published in the <a href="https://www.sciencedirect.com/science/article/abs/pii/S0002937808020012"><em>American Journal of Obstetrics & Gynecology,</em></a> showed that desvenlafaxine effectively reduced vasomotor symptoms <a href="https://www.pharmacypractice.org/index.php/pp/article/view/60">by up to 67%.</a> </p>
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<p>Additionally, a 2011 review published in <a href="https://www.pharmacypractice.org/index.php/pp/article/view/60"><em>Pharmacy Practice (Granada)</em></a> and co-authored by researchers from the Auburn University Harrison School of Pharmacy found that venlafaxine reduced hot flash frequency and<a href="https://www.pharmacypractice.org/index.php/pp/article/view/60"> severity by 37% to 61%.</a> </p>
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<p>Researchers believe these medications help calm the brain’s temperature-regulation system by influencing serotonin and norepinephrine signaling, which appears to change as estrogen levels fluctuate during perimenopause and menopause.</p>
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<p>Side effects may include nausea, insomnia, increased blood pressure, and sexual dysfunction (<a href="https://medshadow.org/conditions-treatments/sexual-health/post-ssri-sexual-dysfunction-how-to-protect-yourself-from-this-side-effect/">which can be life-altering for some people</a>). Because abrupt discontinuation can trigger withdrawal symptoms, the medications should be tapered gradually.</p>
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<h3 class="wp-block-heading"><strong>Paroxetine (Brisdelle) and Escitalopram (Lexapro)</strong></h3>
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<p>Selective serotonin reuptake inhibitors (SSRIs) are another class of antidepressants used to treat vasomotor symptoms. Low-dose paroxetine (7.5 mg) remains the only FDA-approved medication in this class. </p>
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<p>In a 2011 randomized placebo-controlled trial published in <a href="https://jamanetwork.com/journals/jama/fullarticle/645171"><em>JAMA</em></a>, part of the NIH-funded <a href="https://pubmed.ncbi.nlm.nih.gov/33217253/">MsFLASH </a>(Menopause Strategies-Finding Lasting Answers for Symptoms and Health) network, researchers at the<a href="https://womensmentalhealth.org/posts/new-research-from-the-cwmh-escitalopram-lexapro-for-hot-flashes/#:~:text=At%208%20weeks,%20the%20mean,hot%20flash%20frequency%20and%20severity."> University of Pennsylvania Perelman School of Medicine</a> studied 205 women. They found that <a href="https://womensmentalhealth.org/posts/new-research-from-the-cwmh-escitalopram-lexapro-for-hot-flashes/#:~:text=At%208%20weeks,%20the%20mean,hot%20flash%20frequency%20and%20severity.">escitalopram reduced hot flashes by 47% </a>compared with 33% in the placebo group after eight weeks.</p>
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<p>Both medications are generally well tolerated, though side effects may include nausea, sleep disturbance, and sexual dysfunction. Paroxetine should not be used with tamoxifen because it can interfere with how the body processes the breast cancer drug, potentially making it less effective.</p>
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<h3 class="wp-block-heading"><strong>Gabapentin (Neurontin)</strong></h3>
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<p>Originally developed as an <a href="https://womensmentalhealth.org/posts/gabapentin-for-menopausal-vasomotor-symptoms/#:~:text=January%2027,%202026-,Gabapentin:%20A%20Non-Hormonal%20Option%20for%20the%20Treatment%20of%20Menopausal,up%20to%2060%E2%80%9380%25">anti-seizure medication</a>, gabapentin is now frequently used off-label to reduce hot flashes, particularly those that disrupt sleep.</p>
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<p>The drug appears to influence temperature-regulation pathways in the central nervous system and can have sedating effects. As a result, clinicians often consider it for people whose hot flashes are disrupting sleep, particularly when chronic pain is also present.</p>
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<p>Several randomized trials have shown that gabapentin can reduce both the frequency and severity of hot flashes, particularly at night. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC1627210/">A study from 2006</a> published in <em>The Lancet</em> found that 420 breast cancer survivors taking 900 mg daily experienced a 41% reduction in hot flashes after four weeks, compared with just 17% in the placebo group.</p>
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<p>Because gabapentin has sedating effects, daytime drowsiness, dizziness, and fatigue are common side effects. It should not be combined with alcohol, opioids, or other sedatives because of the risk of excessive sedation.</p>
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<h3 class="wp-block-heading"><strong>Oxybutynin (Ditropan)</strong></h3>
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<p>Traditionally prescribed for<a href="https://www.ncbi.nlm.nih.gov/books/NBK499985/#:~:text=Go%20to:-,Mechanism%20of%20Action,Pharmacokinetics"> overactive bladder,</a> which is a common problem during perimenopause and menopause that can leave women feeling the frequent or sudden need to urinate, oxybutynin (Ditropan) is increasingly being used off-label to help reduce hot flashes. The medication blocks acetylcholine, a neurotransmitter involved in both bladder contractions and sweating. As a result, it may be particularly helpful for women dealing with urinary urgency or frequency alongside vasomotor symptoms.</p>
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<p>Available in both immediate-release and extended-release formulations, oxybutynin has shown meaningful reductions in hot flash frequency and severity in clinical studies. A major 2020 multicenter trial known as <a href="https://academic.oup.com/jncics/article/4/1/pkz088/5601603?login=false">ACCRU SC-1603, </a>led by researchers at the Mayo Clinic and published in <a href="https://academic.oup.com/jncics/article/4/1/pkz088/5601603?login=false"><em>JNCI Cancer Spectrum,</em></a> found that oxybutynin reduced hot flashes by 70% to 86% depending on the dose. </p>
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<p>However, side effects can be limiting. “I rarely use it,” says <a href="https://www.medschool.umaryland.edu/profiles/nakhoul-marie/#:~:text=Marie%20Nakhoul,%20MD%20was%20born,the%20American%20University%20of%20Beirut.">Dr. Nakhoul, who also serves as an assistant professor of </a>Obstetrics, Gynecology and Reproductive Sciences at the University of Maryland School of Medicine. She notes that, in her experience, oxybutynin is generally less effective than paroxetine and raises additional concerns about its cognitive effects, particularly with long-term use in older adults.</p>
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<p>Beyond dry mouth and constipation, clinicians monitor for “anticholinergic burden”— the cumulative effect of drugs like oxybutynin that <a href="https://www.ncbi.nlm.nih.gov/books/NBK499985/">block acetylcholine</a>, a neurotransmitter involved in memory and learning. Because a high anticholinergic burden has been linked in longitudinal studies to an increased risk of <a href="https://www.ncbi.nlm.nih.gov/books/NBK499985/">cognitive decline and dementia in older adult</a>s, clinicians emphasize using the lowest effective dose while monitoring for changes in memory or thinking. </p>
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<h2 class="wp-block-heading"><strong>Finding the Right Approach</strong></h2>
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<p>The growing number of nonhormonal therapies has broadened treatment discussions for women who need or prefer alternatives to hormone therapy. “The newer drugs haven’t replaced the conversation for me,” says Dr. Ring. “They have widened it. The new medications simply give me one more good tool for the women who need a different path.”</p>
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<p>For many women, that expanding treatment landscape is welcome news. </p>
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<p>“The gift of this day is that we have so many options,” says <a href="https://profiles.faculty.utah.edu/u0108900">Lisa Taylor-Swanson, Ph.D.</a>, associate professor in the College of Nursing and adjunct associate professor in the Department of Obstetrics & Gynecology at the University of Utah. She says many women tell her they are interested in starting with lifestyle or natural approaches and then considering other treatments if those strategies do not provide enough relief.</p>
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<p>Ultimately, the right approach looks different for every woman, depending on her symptoms, health history, and preferences. “It’s not about surviving perimenopause,” says Dr. Christmas. “It’s thriving through perimenopause.”</p>
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<p><strong><em>Disclosure</em></strong><em>: Several experts interviewed for this article are affiliated with The Menopause Society. The nonprofit organization </em><a href="https://menopause.org/how-to-support-us/corporate-liaison-council"><em>reports receiving</em></a><em> support from corporate sponsors, including pharmaceutical companies that participate in its Corporate Liaison Council.</em></p>
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