Non-Hormonal Treatments for Menopausal Symptoms – NA Menopause Society 2023 Position Statement

SUMMARY: It is estimated that the 50 million women will attain menopause annually. Natural menopause occurs in women between age 49-52 years. Vasomotor symptoms (VMS) manifesting as hot flashes and night sweats are the most common symptoms of menopause. These symptoms occur in up to 80% of menopausal women lasting from 7-10 years and sometimes even longer, significantly impacting their quality of life. Compared to other ethnic groups, menopausal symptoms tend to be less severe in Asian women and more severe in African American women.

Hormone Replacement Therapy remains the most effective treatment and should be considered in menopausal women younger than 60 years, within 10 years of their final menstrual periods, with no contraindications. However, the use of Hormone Replacement Therapy has declined substantially, following the Women’s Health Initiative (WHI) hormone therapy trials recommendation, not to prescribe menopausal hormone therapy for chronic disease prevention due to the complex pattern of risks and benefits, including increases in invasive breast cancer, stroke and pulmonary embolism.

Nonhormonal interventions have therefore been important considerations for symptomatic menopausal women. The North American Menopause Society convened an advisory panel of clinicians and research experts in the field of women’s health, to review and evaluate the literature published after the Position Statement of The North American Menopause Society in 2015.

This advisory panel assessed the most current and available literature to recommend or not recommend use, with the level of evidence assigned, on the basis of these categories:

• Level I: Good and consistent scientific evidence.
• Level II: Limited or inconsistent scientific evidence.
• Level III: Consensus and expert opinion

The following are the evidence-based updated guidelines:

Level I
Cognitive-Behavioral Therapy: CBT has been shown to reduce the bother and interference associated with VMS.
Clinical hypnosis: Clinical hypnosis has been shown to reduce VMS frequency and severity.
Selective Serotonin Reuptake Inhibitors (SSRIs)/ Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SSRIs and SNRIs are associated with mild to moderate improvements in vasomotor symptoms.
SSRIs: Paroxetine 7.5 mg daily is approved by the FDA for the treatment of moderate to severe vasomotor symptoms. Paroxetine however should be avoided in women taking Tamoxifen to treat or prevent breast cancer. Other SSRIs include Citalopram and Escitalopram which have less of an effect on the CYP2D6 enzyme.
SNRIs: Venlafaxine may be a safer choice in women using Tamoxifen as coadministration of SSRIs such as Paroxetine or Fluoxetine with Tamoxifen may lead to inhibition of CYP2D6 (the enzyme that converts Tamoxifen to its most active metabolite, endoxifen).
Gabapentin: Gabapentin is approved by the FDA as an antiepileptic drug, and is often used to treat diabetic neuropathy and postherpetic neuralgia. However, several trials studying the dose of 900 mg (300 mg three times/day) show that this has improved the frequency and severity of vasomotor symptoms.
Fezolinetant (VEOZAH®): Fezolinetant is a first-in-class neurokinin B antagonist that is FDA approved for management of vasomotor symptoms. It modulates the neuronal activity in the thermoregulatory center of the brain.
Oxybutynin: Oxybutynin is an antimuscarinic, anticholinergic therapy that is used for the treatment of overactive bladder and urinary urge incontinence. Oxybutynin has been shown to reduce moderate to severe vasomotor symptoms, although in older adults, long-term use may be associated with cognitive decline
Pregabalin and Clonidine are not recommended for vasomotor symptoms

Level II-III
Weight Loss: The limited available evidence suggests that weight loss may be used to improve vasomotor symptoms for some women.
Stellate ganglion blockade: This procedure is a widely used to treat migraine and complex regional pain syndrome by injecting an anesthetic agent at the lower cervical or upper thoracic region. This blockade might help alleviate moderate to very severe vasomotor symptoms in select women. Because of the potential risks and adverse events, its potential use for vasomotor symptoms should be carefully evaluated.

The following interventions have NOT BEEN PROVEN beneficial and NOT RECOMMENDED interventions:
Paced respiration, Supplements/Herbal remedies, avoiding triggers such as alcohol, caffeine, spicy foods or hot foods, Cooling techniques, Exercise, Yoga, Mindfulness-based intervention such as meditation, Relaxation, Suvorexant, Soy foods and Soy extracts, Soy metabolite equol, Cannabinoids, Acupuncture, Calibration of neural oscillations, Chiropractic interventions, and Dietary modification.

The panel concluded that the most effective treatment for vasomotor symptoms is hormonal therapy and should be considered in menopausal women within 10 years of their final menstrual periods. For women who are not candidates for hormone therapy because of contraindications (estrogen-dependent cancers or cardiovascular disease) or personal preference, it is important for healthcare professionals to be well informed about the evidence-based nonhormone treatment options, for reducing vasomotor symptoms.

NAMS POSITION STATEMENT: The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause: The Journal of The North American Menopause Society 2023;30:573-590. DOI: 10.1097/GME.0000000000002200