Menopausal Symptoms: What Works? What Doesn't?

This transcript has been edited for clarity.

I'm Dr Neil Skolnik, and today I'm going to talk about the 2023 nonhormone therapy position statement of the North American Menopause Society (NAMS). Up to 80% of menopausal women have hot flashes and night sweats, called vasomotor symptoms (VMS), and they last a lot longer than many of us appreciate, with a mean duration of 7-9 years. They can interrupt activities, interfere with sleep, and diminish quality of life. In one third of women, VMS can last longer than 10 years, so this is an important issue.

Estrogen Therapy

While postmenopausal estrogen therapy is the most effective treatment for VMS and is considered first-line therapy, many women and many practitioners are concerned about the evidence-based adverse effects of estrogen therapy, and so many patients choose not to use it. For women with an intact uterus, estrogen is combined with progestin to prevent endometrial hyperplasia and cancer.

The risks associated with estrogen-progestin therapy include an increased risk for venous thrombotic disease (deep vein thrombosis and pulmonary embolism) and — most concerning to many women — an increase in the risk for breast cancer, in the range of 30%-60% (up to 100%, a doubling of the risk). Those numbers vary depending on which dataset is used, with risk increasing with duration of use (Collaborative Group on Hormonal Factors in Breast Cancer, Chlebowski et al).

The effects of estrogen on the development of coronary heart disease have been debated. Benefits of estrogen include a decline in genitourinary symptoms and a slowing of the postmenopausal reduction in bone mineral density.

Because of the concerns of many women about the adverse effects, and because some women are not candidates for hormone therapy, it is important to understand nonhormonal options for the treatment of VMS.

Some of these options work and some don't. These latter therapies don't have demonstrated evidence of efficacy and therefore are not recommended by NAMS.

Lifestyle Interventions

Recommended as effective are:

Weight loss, which reduces the frequency and severity of VMS;
Cognitive-behavioral therapy, which reduces the degree to which VMS are bothersome (although does not affect the frequency of VMS); and
Hypnosis; a randomized trial showed decreased frequency and severity of hot flashes.

Not recommended due to lack of evidence of efficacy are cooling techniques, exercise and yoga, dietary modifications, mindfulness-based interventions, paced respirations, relaxation exercises, and acupuncture. If an individual finds any of these helpful, I don't see a reason to discourage them; you can't argue with general health benefits of exercise and yoga. But none of these have demonstrated clinical trial evidence of efficacy for VMS.

Supplements

Supplements are a commonly used approach, but well-done trials that have actually looked at supplements for VMS are limited, and so none of these are recommended: soy and soy derivatives, pollen extract, ammonium succinate (Amberen), lactobacillus, rhubarb, black cohosh (the most commonly used botanical for VMS, but it has reports of hepatotoxicity, so patients need to be particularly careful here), evening primrose, vitamin E, and others.

Medications

Among prescription medications, two have been FDA approved: paroxetine 7.5 mg daily and fezolinetant 45 mg daily.

Fezolinetant, approved this year, is the first of a new class of medication — a neurokinin B antagonist — which works directly in the thermoregulatory area of the brain, targeting the neural mechanisms that cause VMS. It produces little in the way of adverse effects, although liver enzymes should be checked before starting the medicine and periodically thereafter. Fezolinetant decreases both the frequency and the severity of hot flashes and improves both sleep quality and quality of life.

Paroxetine, at a low dose of 7.5 mg daily, modestly decreases both the frequency and severity of hot flashes, along with improving sleep disruption.

Among non–FDA-approved medications that are recommended based on the evidence are SSRIs, SNRIs, gabapentin (at a significant dose, usually 300 mg three times daily or higher) and oxybutynin.

NAMS gives a "not recommended" designation to pregabalin and clonidine.

In summary, we are fortunate to have some nonhormonal, evidence-based approaches to VMS that work. There are two FDA-approved medications: paroxetine and fezolinetant. There are non–FDA-approved medications which have evidence of efficacy: SSRIs, SNRIs, gabapentin, and oxybutynin. There are also nonpharmacologic approaches, including weight loss and cognitive-behavioral therapy.

VMS of menopause are common and there is a lot we can do about them. This guideline offers helpful advice. I'm interested in your thoughts; please leave them in the comments section.

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