Making Sense of the 2023 North American Menopause Society (NAMS) Nonhormone Therapy Position Statement

It's all about context

My Friends...
Here it is! ... hot off the press from the North American Menopause Society (NAMS): The 2023 Position Statement on nonhormonal therapy. As we would expect, NAMS presents a thorough review of current and past literature. But the messaging behind the recommendations is a real head-scratcher. 
See what you think! 
-Carla 

Hot Flashes and night sweats (a.k.a vasomotor symptoms (VMS)) are the most common symptoms women experience during the menopause transition and after menopause onset. They can range in severity from mild to outright debilitating, resulting in lost sleep which can lead to poor recovery, mood lability, poor health, and quality of life. VMS can last on average, 7-9 years, and in one-third of women, last more than 10 years.

Hormone therapy (HT) typically encompasses estrogen alone or estrogen plus progestogen as the mainstay of pharmacologic treatment with a long history of high-quality studies supporting its safety and efficacy for VMS. However, the debate about the safety of HT has been raging since the Women’s Health Initiative (WHI) discontinued the Estrogen/Progestin arm of their study due to a statistically greater incidence of breast cancer compared to the placebo and estrogen-only arms of the study back in 2002. Following the release of this data, HT use by women and prescriptions from healthcare providers have declined precipitously leaving many women untreated for their debilitating symptoms for fear of the risk of breast cancer. In the last 30 years, more study has emerged that has revealed the safety of HT for treating VMS in women <60 and within 10 years of menopause and even beyond in low-risk patients. However, apprehension still remains and many women prefer non-hormonal alternatives to treating their menopausal symptoms and some women have medical conditions where HT is not a safe or viable option.

NAMS recognizes the demand for non-hormonal treatment options for VMS and created its first position statement specifically addressing nonhormonal therapy for VMS in 2015. This year, NAMS published an update to the 2015 statement which was published in the June 2023 issue of Menopause.

Although I generally applaud NAMS for their rigorous and objective review of the vast body of literature surrounding menopause health, the messaging behind these two position statements on nonhormonal therapy does not do justice for the holistic and integrated approach required for effective menopause care. Further, the recommendations in these two statements are in direct conflict with their own patient information publication, MenoNotes on Hot Flashes, which was published at the same time as the original Position Statement on nonhormonal therapy published in 2015.

Below is a summary of the key points from the 2015 and 2023 Position Statements and my personal analysis to follow.

Definitions

Level I evidence: Good quality, randomized controlled trial (RCT)

Level II evidence: Moderate or poor RCT, good quality cohort study

Level III evidence: Moderate or poor quality cohort study, Case-control study

Level IV evidence: Case series

The 2023 nonhormone therapy position statement of The North American Menopause Society

Menopause. Volume 30 No. 6 pp 573-590

Both the 2015 and 2023 Statements break down their analysis of the literature into categories of nonhormonal therapy to include lifestyle modifications, mind-body techniques, nonhormonal pharmacologic treatment, and dietary supplements.

NAMS on nonhormonal prescription therapies

• Anti-depressant medications - Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are two classes of commonly used anti-depressant medications that have also shown benefits for reducing VMS. Paroxetine salt is the only anti-depressant that is FDA-approved for the treatment of VMS, however, other medications in this class including escitalopram, citalopram, venlafaxine, and desvenlafaxine that have all been shown to significantly reduce VMS in large, double-blinded RCTs.

  • Conclusion: Anti-depressant medications in the SSRI and SNRI classes are an effective treatment for VMS. Level I evidence; Recommend.

• Gabapentiniods. Gabapentin is FDA-approved as an anti-epileptic drug that is commonly used to treat diabetic neuropathy and post-herpetic nerve pain. However, several trials have shown that 300mg three times daily can improve the frequency and severity of VMS. Adverse events at this dose include dizziness, headache, and disorientation, which can limit its utility. Gabapentin is often prescribed at night if there is also difficulty with sleep.

  • Conclusion: Gabapentin at doses of 900mg - 2400mg daily can be an effective treatment for VMS, although caution should be used due to side effects at these doses. Level I evidence; Recommend.

• Neurokinin B antagonists. Fezolinetant is a new therapy that was FDA-approved in May 2023 as a nonhormonal treatment for VMS. Its mechanism of action targets nerve pathways in the hypothalamus of the brain (a.k.a the “thermostat”) thus acting directly on the neural mechanisms underlying VMS. Phase 3 trials report headache as the most common side effect and rarely, elevation of liver enzymes. The effect of neurokinin B antagonists on other symptoms that commonly occur with VMS remains to be studied.

  • Conclusion: Fezolinetant is a first-in-class neurokinin B antagonist that is FDA approved for the management of VMS. Level I evidence; Recommend.

NAMS on dietary supplements

Assessing dietary supplements pertaining to the management of VMS is challenging because dietary supplements are unregulated and thus not standardized with respect to purity and safety. Further, there is limited, rigorous RCT data studying the effects of these supplements for the management of VMS.

• Conclusion: Of the dietary supplements reviewed in the position statement, none are recommended for the treatment of VMS with Level I-III evidence.

Below is a partial list of the most commonly used supplements that were reviewed in the Position Statement

• Soy foods and extracts

• Equol (soy metabolite)

• Black Cohosh

• Wild Yam

• Don Quai

• Evening Primrose

• Maca

• Ginseng

• Chasteberry

• Milk thistle

• Omega-3 fatty acid

• Vitamin E

• Cannabinoids

NAMS on mind-body techniques

• Cognitive behavioral therapy (CBT). CBT includes psychoeducation (physiology of VMS), training in relaxation and paced breathing techniques, and cognitive behavioral strategies to manage VMS. CBT has been shown to reduce the degree to which VMS is rated as a problem. Evidence of this began to emerge a decade ago with two randomized control trials (RCTs) in cancer survivors and subsequent follow-up studies extended the benefits to other populations.

  • Conclusion: The body of literature as a whole supports that CBT alleviates bothersome VMS for both survivors of breast cancer and menopausal women (Level I evidence; Recommended)

• Clinical hypnosis. Clinical hypnosis is a mind-body therapy that involves a deeply relaxed state and individualized mental imagery and suggestion. It has been widely used to manage pain and anxiety. The application of hypnosis to VMS has been studied in two RCTs involving breast cancer survivors. In both trials, 5 weekly, in-person sessions were compared to at-home self-hypnosis. These two studies and another involving 60 breast cancer survivors showed improvement in VMS as compared to no treatment.

  • Conclusion: Clinical hypnosis was better at reducing VMS and improving mood and sleep than no treatment. (Level I evidence; Recommended)

• Relaxation and Paced Respiration. Paced respiration was shown to be beneficial for reducing VMS in several small studies, however, in larger studies including a randomized trial involving 200 women, no benefit was found. There is limited and inconsistent evidence that relaxation techniques improve VMS.

  • Conclusion: Paced respiration and relaxation techniques did not show significant benefits for improving VMS. (Level I-II evidence; Not Recommended.)

NAMS on lifestyle modification

• Cooling techniques. These techniques include dressing in layers, breathable clothing, adjusting room temperature, and cooling aids such as fans, cold packs, and cooling mattresses. One small uncontrolled trial showed the benefit of using a forehead-cooling device and sleep hygiene instruction. In another 4-week randomized study of night-time comfort interventions, no improvements were seen in VMS, however, there were some self-reported improvements in sleep.

  • Conclusion: Cooling interventions must be tested in larger, randomized-placebo-sham controlled trials. Level II evidence; Not recommended.

• Avoiding triggers. VMS are sometimes reported by women to be associated with things like alcohol, stress, and spicy foods among other elements or circumstances. One study of more than 4500 Chinese women found a positive association between alcohol intake and VMS, however, this finding has not been reported in other studies.

  • Conclusion: There are no clinical trials assessing the effects of avoiding triggers for the relief of VMS. Level II evidence; Not recommended.

• Exercise and yoga. Observational studies report that women who exercise regularly report fewer VMS. Others have found no relationship and in some cases, exercise can be a trigger for VMS. Several Cochrane reviews have concluded that there is insufficient or poor evidence to consider exercise as a treatment for VMS. A systemic review of 12 randomized trials comparing yoga to no intervention, health education, exercise, and acupressure was difficult to interpret due to limitations of the study design. Yoga had limited benefits compared with exercise for the treatment of VMS and there was no benefit compared with no treatment.

  • Conclusion: Although there are other health benefits associated with exercise or yoga, the evidence supporting those interventions for the treatment of VMS is sparse. Level II evidence; Not recommended.

• Weight loss. Studies have found that women who struggle with obesity are more likely to report more frequent and severe hot flashes than women of normal weight. Randomized trials have found that weight loss from behavioral interventions is associated with a decrease in VMS. Evidence suggests that the role of adiposity and weight loss in VMS may vary depending on age or menopausal stage.

  • Conclusion: The limited available evidence suggests that weight loss may be used to improve VMS in some women. Level II-III evidence; Recommended.

In my humble opinion…..

The brilliant minds at NAMS have always been a reliable source of objective and thorough literature review to help guide clinical decision-making. The 2023 Position Statement on nonhormonal therapy for VMS is no different. However, what is sorely lacking in this statement is a perspective that applies these research findings in a common sense way to the holistic approach that is needed to manage not just VMS, but the menopausal woman as a whole person.

When I see menopausal patients, it is rare that they are seeking care for a single symptom. Invariably - even if VMS is the main complaint - there is a constellation of physical experiences that she is concerned about as well as her overall concern for her general health that are typically addressed at any client visit. Although the statement presented a methodical review of the literature speaking to the specific question of what nonhormonal means were effective for treating VMS, the messaging surrounding the recommendations was as if nothing else about the whole patient mattered except the VMS.

The best example of this is the recommendation against physical exercise and dietary modification (not specifically discussed here) as treatments for hot flashes. This is interesting because weight loss was seen, in this statement, as potentially beneficial for improving VMS. It is well-accepted that dietary modification and physical exercise are the cornerstones of effective weight loss strategies. Given that more than 50% of menopausal women in the US are overweight, how do recommendations against dietary modification and physical exercise make sense in the holistic approach to symptom management and overall health? My friend, professional writer, and esteemed host of the Hit Play Not Pause podcast, Selene Yeager, nailed this and other excellent points in her recent blog, NAMS Releases 2023 Position Statement on Nonhormone Therapies.

The other head-scratchers are the recommendations against, yoga, paced breathing, and cooling techniques as a way to manage VMS. At first glance, the question is what is the harm in trying these techniques? The 2015 Position Statement speaks to this question and states “Some therapies appear risk-free but do not have any evidence testing their effects on VMS and their use may lead to delay in receipt of more appropriate and efficacious treatment. These include cooling techniques and avoidance of triggers.”

Although there may be some logic behind this argument, NAMS's own MenoNotes patient information sheet entitled Treating Hot Flashes published the same year as the 2015 statement specifically recommends these same techniques that are not recommended in the 2015 and 2023 nonhormonal therapy Position Statements.

Although it seems like AI published this statement before the Humans had a chance to message it properly, let’s not throw the baby out with the bathwater. The data summary and background review are excellent and serve as useful foundational elements upon which patients and providers can apply these studies to their individual clients’ personal situations in a holistic, common-sense way. It is also a firm reminder that providers and patients alike need to approach these and any recommendations from even the most esteemed sources with a critical eye and not just take them at face value.