Vasomotor symptoms (VMS), commonly known as hot flashes and night sweats, are the most frequent symptoms experienced during the menopause transition. Hot flashes are sudden, intense heat sensations that affect the face, chest, and other body parts. They can be accompanied by an increased heart rate, dizziness, and followed by chills. Night sweats are hot flashes that happen at night, causing intense sweating that can wake you up and require changing clothes and bed sheets. (1, 2) 

Studies have shown that as women age, their estrogen levels decline, and their ovaries shrink, leading to problems with the body's temperature control system. VMS can also cause feelings of agitation, anxiety, and depression. These symptoms can negatively impact quality of life, affecting sleep, mood, productivity, and relationships. (2)

Hormone therapy (HT) is the most effective treatment for VMS, but it isn't suitable or preferred by everyone. Recently, interest in nonhormonal medications for these menopause related symptoms has increased. (2)

Nonhormonal VMS Treatment: Who's Eligible?

Individuals who prefer to avoid HT or have contraindications such as hormone-dependent cancer, unexplained vaginal bleeding, liver disease, deep vein thrombosis, migraines with aura, or heart disease, may benefit from nonhormonal medications. (2)

When choosing a treatment, whether it's HT or nonhormonal, consult a medical doctor specializing in menopause care. The decision should take into consideration your symptoms, family and medical history, and the risks versus benefits.

Non-Hormonal Treatments for VMS

Effective nonhormonal treatments include FDA-approved options for VMS and other medications that doctors recommend for off-label use, says Barbra Hanna, DO, gynecologist, menopause specialist, and co-founder and Chief Executive Officer at MyMenopauseRx, a virtual clinic specializing in menopause care. These medications include some antidepressants, gabapentin, oxybutynin, and a new class of drugs for VMS called neurokinin B antagonists, explains Dr. Hanna.

Gabapentin

Gabapentinoids were initially used for seizures but are now also prescribed for neuropathic pain and mood disorders. Although their effect on VMS isn't fully understood, they are believed to calm the body's hyperactive response and help the brain's temperature control. Gabapentin, a type of gabapentinoid, has been shown to reduce the frequency and severity of hot flashes. Common side effects include dizziness, unsteadiness, and drowsiness. (3, 5)

Neurokinin B Antagonists

Neurokinin B antagonists are a new class of nonhormonal medications that block certain signals in the brain to help reduce hot flashes. Fezolinetant is one example and is one of only two FDA-approved medications specifically for VMS. It has shown effectiveness in treating moderate to severe hot flashes. Common side effects include abdominal pain, diarrhea, insomnia, back pain, hot flush, and elevated liver enzymes. (3, 6) 

Another neurokinin B antagonist, elinzanetant, is in late-phase clinical trials and has shown effectiveness in treating moderate to severe VMS and improving sleep and quality of life, says Dr. Hanna. Headache is the most common side effect. (3, 7)

Oxybutynin

 Oxybutynin treats overactive bladder and urinary urge incontinence. In women with VMS, it has been shown to improve symptoms, sleep, and quality of life. Side effects are usually dose-dependent and include dry mouth and urinary issues. (3, 5)

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs are antidepressants that boost levels of serotonin and norepinephrine in the brain. These neurotransmitters help regulate mood, sleep, memory, social behavior, sexual desire, arousal, and attention. Two SNRIs — desvenlafaxine and venlafaxine — can help lessen the severity and frequency of hot flashes. (2, 3, 4)

Desvenlafaxine side effects may include raised blood pressure, pulse rate, and lipid levels, along with diarrhea, fatigue, and drowsiness. Both desvenlafaxine and venlafaxine can lead to dry mouth, nausea, and constipation. SNRIs can also worsen sexual function by affecting orgasm potential, lubrication, and sexual desire. (2)

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are antidepressants that may help lessen the frequency and intensity of hot flashes. As estrogen levels decline during menopause, serotonin — a key mood regulator — also drops. This drop in serotonin may be connected to symptoms like hot flashes and mood issues, such as depression and anxiety. (2)

Paroxetine, an SSRI, is one of only two FDA-approved nonhormonal treatments for VMS. Citalopram and escitalopram are also effective SSRIs for managing VMS. (2,3)

The side effects of SSRIs are usually mild and can include nausea, vomiting, diarrhea, headaches, agitation, sexual issues, and insomnia. (2)

Questions to Ask Your Doctor About Nonhormonal VMS

Each class of medication may offer additional benefits beyond treating VMS. A Menopause Society Certified Practitioner can help guide you on all your options and with shared decision-making, says Dr. Hanna. Here are questions you can ask your doctor about nonhormonal VMS medications:

• What nonhormonal medication options are available to me?

• What options does my insurance cover?

• How effective are these nonhormonal treatments compared to hormone therapy?

• How will nonhormonal treatments affect my overall health and other menopause symptoms?

• What are the potential side effects of the nonhormonal medications you recommend and how long do they last?

• Will these medications interact with any other medications or supplements I am currently taking?

• How long will it take to see improvements in my VMS symptoms with this treatment?

The symptoms associated with the menopause transition can last for 7-10 years on average, notes Dr. Hanna. Treating these symptoms may require one therapeutic approach or a combination of several. Dr. Hanna advises being open-minded about a bit of trial and error to find what works best for you. Communication and exploring treatment options with your healthcare provider is key. What VMS treatments have worked for you? Let’s talk about it.

Written by: Johna Burdeos

Resources:

1. WebMD. What are Vasomotor Symptoms (Hot Flashes)?

2. Witten T, Staszkiewicz J, Gold L, Granier MA, Klapper RJ, Lavespere G, Dorius B, Allampalli V, Ahmadzadeh S, Shekoohi S, Kaye AD, Varrassi G. Nonhormonal Pharmacotherapies for the Treatment of Postmenopausal Vasomotor Symptoms. Cureus. 2024 Jan 17;16(1):e52467. doi: 10.7759/cureus.52467.

3. “The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause. 2023 Jun 1;30(6):573-590. doi: 10.1097/GME.0000000000002200.

4. Cleveland Clinic. SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors).

5. Khan SJ, Kapoor E, Faubion SS, Kling JM. Vasomotor Symptoms During Menopause: A Practical Guide on Current Treatments and Future Perspectives. Int J Womens Health. 2023 Feb 14;15:273-287. doi: 10.2147/IJWH.S365808.

6. U.S. Food and Drug Administration. FDA Approves Novel Drug to Treat Moderate to Severe Hot Flashes Caused by Menopause.

7. Sassarini J, Anderson RA. Elinzanetant: a phase III therapy for postmenopausal patients with vasomotor symptoms. Expert Opin Investig Drugs. 2024 Jan;33(1):19-26. doi: 10.1080/13543784.2024.2305122.