NAMS: Nonhormone Therapy Position Statement 2023

SUMMARY:

An advisory panel was selected to review current literature regarding nonhormone therapy based on levels of evidence. In the treatment of vasomotor symptoms in women within ten years of menopause and who are not candidates for or who decline hormone therapy, evidence-based nonhormone options such as behavioral therapies, medications such as SSRIs or gabapentin, and weight loss should be discussed and considered.  

Vasomotor Post Menopausal Symptoms  

• Vasomotor symptoms (VMS) 
  • Defined as hot flashes and night sweats  
• Incidence 
  • Mean 7 to 10 years 
  • 30% >10 years 
• Standard Management 
  • Hormone therapy 
  • First line recommended treatment 
  • Underutilized therapy 
• Contraindications 
  • Estrogen sensitive tumors 
  • Coronary artery disease/myocardial infarction history 
  • Stroke 
  • Venous thromboembolism 

Recommended Nonhormone Techniques and Therapies  

• Mind-Body Techniques 
  • Clinical hypnosis 
  • Cognitive behavior therapy 
• Prescription Medications 
  • SSRIs and SNRIs demonstrate mild to moderate improvement 
    • Ecitalopram 10 to 20 mgs/day 
    • Paroxetine salt 7.5 mg/day 
    • Paroxetine 10 to 25 mg/day 
    • Citalopram 10 to 20 mg/day 
    • Desvenlafaxine 100 to 150 mg/day (start at 25 to 50 mg/day) 
    • Venlafaxine 37.5 to 150 mg/day (start at 37.5 mg/day) 
  • Gabapentin 
    • 900 to 2400 mg/day in divided doses (start with 100 to 300 mg at night, add 300 mg at night, then an AM dose of 300 mg) 
  • Fezolinetant 
    • Neurokinin B antagonist 
    • 45 mg/day 
  • Oxybutynin 
    • 2.5 to 5.0 mg twice daily or 15 mg extended release daily 
    • Long term use may be associated with cognitive decline in older adults 
• Weight loss 

NOT Recommended 

• Yoga | Diet | Cooling techniques | Weight loss | Relaxation techniques  
• All dietary supplements/cannabinoids 
• Acupuncture 
• Chiropractic manipulations 
• Stellate ganglion block may alleviate moderate to severe VMS but is associated with risk of transient seizures or bleeding 
• Medical therapies not recommended 
  • Pregabalin 
  • Clonidine 
  • Suvorexant  

KEY POINTS: 

• Vasomotor symptoms occur in up to 80% of postmenopausal women 
• Mean duration 7 to 9 years 
  • >10 years for one third of women 
• Hormone therapy is underutilized in symptomatic women 
• Hormone therapy is the most effective treatment for vasomotor sympytoms and is indicated for  
  • Women younger than age <60 years 
  • Are within 10 years of menopause 
  • Are without contraindications including 
    • Estrogen sensitive malignancies 
    • Coronary artery disease/myocardial infarction 
    • Thromboembolism/stroke 
      • Inherited high risk for thromboembolic disease. 
• Recommended nonhormone therapies: Prescription 
  • SSRIs/SNRIs 
  • Gabapentin 
  • Oxybutynin 
  • Fezolinetant 
• Recommended therapies: Nonprescription 
  • Cognitive based therapy 
  • Clinical hypnosis 
  • Weight loss 
  • Stellate ganglion block 
• Not recommended or insufficient evidence  
  • Supplements or herbal remedies 
    • Soy extracts 
  • Yoga and exercise 
  • Cooling techniques 
  • Cannabinoids 
  • Acupuncture 
  • Chiropractic interventions 

Learn More – Primary Sources: (Level 3) 

The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society 

The WHI Randomized Trials: Is Menopausal Hormone Therapy Associated with Long-Term Mortality?

PURPOSE:

• The original WHI trials were designed to assess risk vs benefits of menopausal hormone therapy
• Double-blinded, placebo-controlled, randomized clinical trials, conducted among US postmenopausal women aged 50 to 79 years at enrollment using the following 2 drug regimens
  • Conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for women with an intact uterus
  • CEE alone for women with hysterectomy
• The CEE plus MPA trial was stopped early (after 5.6 years) due to an increased risk of breast cancer and overall risks exceeding benefits
• CEE-alone trial was stopped after 7.2 years due to an increased risk of stroke
• Postintervention follow up has been ongoing
• Manson et al. (JAMA, 2017) report the extended follow up on all-cause and cause-specific mortality with attention to age

METHODS:

• Postintervention follow up study of the two WHI studies (1993-1998)
• Total 27,347 postmenopausal women ages 50 to 79 years were recruited at 40 US clinical centers
  • 16,608 women with a uterus received daily oral CEE (0.625 mg) plus MPA (2.5 mg) or placebo
  • 10,739 women with hysterectomy received daily oral CEE (0.625 mg) alone or placebo
• Primary outcome: All-cause mortality
  • Cause-specific mortality (cardiovascular disease cancer and other major causes)
• 18 year follow up in 2 trials separately and combined (pooled)

RESULTS:

• All-cause mortality
  • Pooled cohort: 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03])
  • CEE plus MPA: HR 1.02 (95% CI, 0.96-1.08)
  • CEE alone: HR 0.94 (95% CI, 0.88-1.01)
• Cardiovascular mortality
  • Pooled cohort: HR 1.00 (95% CI, 0.92-1.08)
• Total cancer mortality
  • Pooled cohort: HR 1.03 (95% CI, 0.95-1.12)
• Other causes
  • Pooled cohort: HR 0.95 (95% CI, 0.88-1.02)
  • results did not differ significantly between trials
• Comparing younger women (50-59 years) to older women (70-79 years) in the pooled cohort for all-cause mortality
  • During intervention phase: all-cause mortality reduced compared to older women
    • ratios of HRs 0.61 (95% CI, 0.43-0.87)
  • During cumulative 18-year follow-up: no difference seen in all-cause mortality compared to older women
    • ratios of HRs 0.87 (95% CI, 0.76-1.00)
  • No significant difference between trials

CONCLUSION:

• There was no long-term association between hormone replacement and all-cause or cause-specific mortality during a follow up period of 18 years in women who used combination estrogen plus progestin for 5.6 or estrogen-alone group for 7.2 years
• Limitations include specific hormone replacement formulations and therefore results may not be generalizable
• Cause-specific mortality results should be considered exploratory because multiple smaller subgroups were analyzed
• The accompanying editorial states that this present study supports the recently released 2017 NAMS guidance and women should be reassured and hormone therapy appears “safe and efficacious”.

Learn More – Primary Sources:

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials

Menopausal Hormone Therapy: Understanding Long-term Risks and Benefits (JAMA Editorial)