What are the treatment options for hot flashes?

Treatment for Hot Flashes

Start with nonhormonal pharmacologic therapy as first-line treatment, specifically gabapentin 900 mg at bedtime for women with sleep disturbance or those on tamoxifen, or venlafaxine 37.5-75 mg daily for rapid symptom control, as these agents reduce hot flash severity by 46% and 37-61% respectively. 1

First-Line Nonhormonal Pharmacologic Options

The National Comprehensive Cancer Network recommends nonhormonal pharmacologic treatments as first-line therapy for menopausal hot flashes. 1 Here's how to choose:

Gabapentin (Preferred in Specific Situations)

• Dose: 900 mg/day at bedtime 1
• Efficacy: Reduces hot flash severity score by 46% compared to 15% with placebo 2, 1
• Equivalent efficacy to estrogen 1
• Choose gabapentin when:
  • Patient has concurrent sleep disturbance from hot flashes 1
  • Patient is taking tamoxifen (no drug interactions) 1
  • Patient is on multiple medications (no known drug interactions) 1
• Side effects: Affect up to 20% of patients but improve after the first week and largely resolve by week 4 1
• No absolute contraindications 1

Venlafaxine (Preferred for Rapid Onset)

• Dose: Start 37.5 mg daily, increase to 75 mg after 1 week 1, 3
• Efficacy: Reduces hot flash scores by 37-61% depending on dose 1, 4
• Faster onset than gabapentin 1
• Preferred by 68% of patients over gabapentin despite similar efficacy 1
• Choose venlafaxine when:
  • Rapid onset is prioritized 1
  • Patient prefers it based on tolerability profile 1
  • Gabapentin is ineffective or not tolerated 1
• Must taper gradually on discontinuation to minimize withdrawal symptoms 1

Paroxetine (Use with Caution)

• Dose: 7.5 mg daily 1
• Efficacy: Reduces frequency, severity, and nighttime awakenings by 62-65% 1, 3
• CRITICAL WARNING: Avoid in women taking tamoxifen due to CYP2D6 inhibition, which reduces conversion of tamoxifen to active metabolites 1
• Also avoid fluoxetine in women on tamoxifen 1
• Alternative SSRIs/SNRIs safe with tamoxifen: venlafaxine, citalopram 1

Clonidine (Alternative Option)

• Reduces hot flash frequency and severity 1
• Slower effect than venlafaxine but often better tolerated 1
• Particularly useful for women taking tamoxifen 1

Treatment Monitoring Algorithm

1. Assess efficacy at 2-4 weeks for SSRIs/SNRIs 1
2. Assess efficacy at 4-6 weeks for gabapentin 1
3. If intolerant or ineffective, switch to another nonhormonal agent 1
4. Recognize the robust placebo response (up to 70% in some studies) when evaluating treatment 1

Nonpharmacologic Approaches (Adjunctive)

Highly Effective Options

• Acupuncture: Safe and effective, with some studies showing equivalence or superiority to venlafaxine or gabapentin 1, 3
  • Contraindication: Not recommended for breast cancer survivors with prior axillary surgery on the affected arm 1
• Cognitive Behavioral Therapy (CBT): Significantly reduces perceived burden of hot flashes even if frequency remains unchanged 1, 3
• Hypnosis: Showed 59% decrease in daily hot flashes and significant improvement in quality of life measures 1

Lifestyle Modifications

• Weight loss ≥10% of body weight may eliminate hot flash symptoms entirely 2, 1, 3
• Smoking cessation improves frequency and severity of hot flashes 2, 1, 3
• Limiting alcohol intake if it triggers symptoms 2, 1
• Environmental adjustments: Dress in layers, maintain cool room temperatures, wear natural fibers, use cold packs intermittently, avoid identified triggers (spicy food, hairdryers, caffeine) 1, 3
• Paced respiration training: 20 minutes daily shows significant benefit 1

Exercise

• Evidence is inconclusive for hot flash reduction 2
• However, recommend exercise for overall health benefits despite lack of specific hot flash benefit 2

Hormonal Therapy (When Nonhormonal Options Fail)

Menopausal hormone therapy (MHT) is the most effective treatment, reducing hot flashes by approximately 75-80% compared to placebo, but should only be used when nonhormonal options fail. 1, 5, 4, 6

Estrogen-Alone Therapy (Post-Hysterectomy)

• Preferred formulation: Transdermal estradiol 50-100 µg daily (lower rates of venous thromboembolism and stroke) 1, 3
• Use lowest effective dose for shortest duration possible 1
• In women younger than 60 years post-hysterectomy, estrogen-alone therapy has lower long-term cardiovascular and breast cancer risks compared to combined estrogen-progestin therapy 1

Absolute Contraindications to Estrogen 1, 5

• History of hormone-related cancers (breast, endometrial)
• Abnormal vaginal bleeding (must be evaluated first)
• Active or recent thromboembolic events
• Active liver disease
• Pregnancy
• Stroke or heart attack in the past year

Relative Contraindications/Use with Caution 1

• Coronary heart disease
• Hypertension
• Current smokers
• Increased genetic cancer risk

Special Population: Breast Cancer Survivors

For breast cancer survivors, avoid estrogen and tibolone due to potential increased recurrence risk. 1

Treatment Hierarchy for Breast Cancer Survivors 1

1. Lifestyle modifications (weight loss, smoking cessation, environmental adjustments)
2. First-line pharmacologic: Venlafaxine, gabapentin, or citalopram (avoid paroxetine if on tamoxifen)
3. Adjunctive: Acupuncture or CBT
4. Consider switching endocrine therapy: From aromatase inhibitor to tamoxifen or vice versa if appropriate from disease treatment standpoint 2
5. For advanced breast cancer or severe symptoms affecting quality of life: Estrogen may be considered after fully informed discussion of risks, with decision ultimately resting with patient 2

Important Note on Tamoxifen Interactions

• 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 1
• However, avoid paroxetine and fluoxetine in women taking tamoxifen 1

Treatments to AVOID

Ineffective or Unsafe Options

• Black cohosh: No benefit in randomized trials and reports of liver failure 2, 1
• Multibotanicals with soy: Worsened symptoms in randomized trials 2, 1
• Soy isoflavones and phytoestrogens: Show minimal to no benefit compared to placebo 3
• Vitamin E 800 IU daily: Limited efficacy, and doses >400 IU/day linked to increased all-cause mortality 2, 1, 4
  • Exception: Reasonable for patients requesting "natural" treatment with mild symptoms, but keep dose ≤400 IU/day 1

Common Pitfalls to Avoid

1. Prescribing paroxetine to women on tamoxifen - this reduces tamoxifen efficacy 1
2. Failing to recognize venlafaxine-induced night sweats - these are dose-dependent side effects that may mimic hot flashes; consider gradual dose reduction 1
3. Abrupt discontinuation of SSRIs/SNRIs - always taper gradually to avoid withdrawal syndrome 1
4. Using MHT as first-line therapy - nonhormonal options should be tried first unless contraindications exist 1
5. Ignoring spontaneous improvement - many hot flashes improve over time with ongoing treatment 2, 1
6. Recommending complementary therapies without evidence - stick to acupuncture, CBT, and hypnosis which have demonstrated benefit 1

Practical Treatment Algorithm

Step 1: Implement lifestyle modifications (4-6 weeks trial) 3

• Weight loss if overweight
• Smoking cessation
• Environmental adjustments
• Identify and avoid triggers

Step 2: Add nonpharmacologic therapy if symptoms persist 3

• Acupuncture or CBT based on availability and patient preference

Step 3: Initiate pharmacologic therapy based on patient characteristics 1

• If sleep disturbance or on tamoxifen: Gabapentin 900 mg at bedtime
• If rapid onset needed: Venlafaxine 37.5-75 mg daily
• If neither works: Try clonidine or switch between agents

Step 4: Consider hormonal therapy only if nonhormonal options fail and no contraindications exist 1, 3

• Transdermal estradiol (post-hysterectomy)
• Combined estrogen-progestin (with intact uterus)

Step 5: Reassess annually to determine if treatment can be discontinued, as symptoms often decrease naturally over time 3