What are the treatment options for a menopausal woman experiencing hot flashes?

Treatment of Menopausal Hot Flashes

For menopausal women experiencing hot flashes, begin with lifestyle modifications (weight loss ≥10% if overweight and smoking cessation), then escalate to nonhormonal pharmacotherapy with venlafaxine 37.5-75 mg daily or gabapentin 900 mg/day as first-line medications, reserving hormone therapy only for severe refractory symptoms in women without contraindications. 1, 2, 3

Stepwise Treatment Algorithm

Step 1: Lifestyle Modifications (First-Line for All Patients)

Weight management is the priority intervention for overweight women, as losing ≥10% of body weight significantly increases the likelihood of eliminating hot flash symptoms entirely. 1, 2, 3

• Smoking cessation substantially improves both frequency and severity of hot flashes, as symptoms are markedly worse in active smokers. 1, 2, 3
• Environmental adjustments include dressing in layers, maintaining cool room temperatures, wearing natural fibers, using cold packs intermittently, and avoiding identified triggers (spicy foods, caffeine, alcohol). 4, 2

Step 2: Nonpharmacologic Mind-Body Interventions

If lifestyle modifications are insufficient, consider these evidence-based nonpharmacologic approaches before medications:

• Acupuncture is safe and effective, with multiple studies showing equivalence or superiority to venlafaxine or gabapentin for managing vasomotor symptoms. 1, 2 However, avoid acupuncture in breast cancer survivors with prior axillary surgery on the affected arm. 1
• Cognitive Behavioral Therapy (CBT) reduces the perceived burden of hot flashes and significantly improves hot flash problem ratings, even if frequency remains unchanged. 1, 2
• Hypnosis demonstrated a 59% decrease in daily hot flashes with significant improvement in quality of life measures including sleep, mood, and concentration. 1, 2
• Paced respiration training (structured breathing exercises for 20 minutes daily) shows significant benefit compared to control interventions. 1, 2

Step 3: Nonhormonal Pharmacotherapy (First-Line Medications)

When nonpharmacologic approaches fail or symptoms are moderate to severe, initiate nonhormonal medications:

Primary Choice: Venlafaxine or Gabapentin

Venlafaxine 37.5 mg daily, increasing to 75 mg after 1 week, reduces hot flash scores by 37-61% and is preferred by 68% of patients over gabapentin despite similar efficacy. 1, 2, 3 Choose venlafaxine when rapid onset is prioritized or based on patient preference for tolerability profile. 1

Gabapentin 900 mg/day at bedtime reduces hot flash severity by 46% compared to 15% with placebo, with equivalent efficacy to estrogen. 1, 2, 3 Gabapentin is the preferred choice when:

• The patient has concurrent sleep disturbance from hot flashes 1
• The patient is on multiple medications (gabapentin has no known drug interactions) 1
• The patient is taking tamoxifen (avoiding SSRI/SNRI interactions) 1

Side effects affect up to 20% of patients but improve after the first week and largely resolve by week 4. 1

Alternative: Paroxetine (with Critical Caveat)

Paroxetine 7.5 mg daily reduces frequency, severity, and nighttime awakenings by 62-65%. 1, 2 However, paroxetine must be avoided in women taking tamoxifen due to CYP2D6 inhibition that reduces tamoxifen conversion to active metabolites. 4, 1, 2

Other Options

• Clonidine can reduce hot flash frequency and severity, with slower effect than venlafaxine but often better tolerated. 1
• Review efficacy at 2-4 weeks for SSRIs/SNRIs and 4-6 weeks for gabapentin; if intolerant or ineffective, switch to another nonhormonal agent. 1

Step 4: Hormone Therapy (Reserved for Refractory Cases)

Menopausal Hormone Therapy (MHT) is the most effective treatment, reducing hot flashes by approximately 75% compared to placebo and achieving 80-90% symptom relief. 1, 3, 5 However, it should only be used when nonhormonal options fail after adequate trials. 2

When prescribing MHT:

• Use transdermal estrogen formulations preferentially due to lower rates of venous thromboembolism and stroke compared to oral preparations. 1, 3
• Use the lowest effective dose for the shortest duration possible (not more than 4-5 years). 1, 5
• Initiate soon after menopause onset in women with good cardiovascular health, as initiation many years after menopause is associated with excess coronary risk. 5
• Use micronized progestin rather than medroxyprogesterone acetate due to lower rates of VTE and breast cancer risk. 1

Absolute contraindications to MHT include: 1, 3

• History of hormone-related cancers
• Abnormal vaginal bleeding of unknown etiology
• Active or recent thromboembolic events
• Active liver disease
• Pregnancy

Use with caution in: coronary heart disease, hypertension, current smokers, and increased genetic cancer risk. 1

Special Population: Breast Cancer Survivors

For women with breast cancer history, systemic hormone therapy is rarely if ever given. 4, 3 Instead, the American Cancer Society/American Society of Clinical Oncology recommends: 4

• SNRIs (venlafaxine), SSRIs (avoiding paroxetine if on tamoxifen), gabapentin, lifestyle modifications, and environmental modifications as first-line options. 4, 1
• Venlafaxine has been found to be safe and effective in reducing hot flashes in this population. 4
• Do not screen patients for CYP2D6 despite theoretical concerns about SSRI-tamoxifen interactions, as negative impact on breast cancer outcomes has not been conclusively demonstrated. 4

What NOT to Recommend

Avoid these commonly requested but ineffective treatments:

• Black cohosh is not recommended due to lack of efficacy in randomized trials and reports of liver failure. 2
• Soy isoflavones and phytoestrogens are not recommended, as only 3 of 8 studies showed modest improvement lasting less than 6 weeks, with substantial placebo effect making them no better than placebo. 2
• Vitamin E 800 IU daily has limited efficacy and doses >400 IU/day are linked to increased all-cause mortality and should be avoided, despite being "natural." 1, 2
• Exercise, while beneficial for overall health, does not have strong evidence for reducing hot flash frequency specifically. 2

Important Clinical Caveats

• Recognize the robust placebo response (up to 70% in some studies) when evaluating any treatment efficacy. 1, 2
• SSRIs/SNRIs are contraindicated in women taking monoamine oxidase inhibitors and should be avoided in bipolar disorder due to risk of inducing mania. 1
• Gradual taper is required on discontinuation of SSRIs/SNRIs to minimize withdrawal symptoms. 1
• For younger women on endocrine therapies, 50-70% will likely experience hot flashes while on tamoxifen, and these symptoms are typically more severe due to abrupt hormonal changes. 4

Emerging Therapies

Fezolinetant is the first FDA-approved neurokinin-3 receptor antagonist for hot flashes, representing a new class of nonhormonal treatments free of untoward off-target effects, with demonstrated improvements in patient-reported sleep outcomes. 6 Elinzanetant is awaiting FDA approval. 6