What are the treatment options for hot flushes in menopause?

Treatment of Hot Flushes in Menopause

For most women with menopausal hot flushes, start with nonhormonal pharmacologic therapy—specifically venlafaxine 37.5-75 mg daily or gabapentin 900 mg/day at bedtime—as first-line treatment, reserving hormone therapy for severe cases unresponsive to nonhormonal options. 1

First-Line Nonhormonal Pharmacologic Options

The National Comprehensive Cancer Network recommends nonhormonal pharmacologic treatments as first-line therapy for menopausal hot flashes 1. The two most effective options are:

Venlafaxine (SNRI)

• Start at 37.5 mg daily, increase to 75 mg after 1 week 1
• Reduces hot flash scores by 37% at 37.5 mg/day and 61% at 75 mg/day (compared to 27% placebo reduction) 2
• Preferred by 68% of patients over gabapentin despite similar efficacy 1
• Side effects include dry mouth, decreased appetite, nausea, and constipation (dose-related) 2
• Must be tapered gradually on discontinuation to prevent withdrawal symptoms 2

Gabapentin (Anticonvulsant)

• Dose: 900 mg/day, preferably at bedtime 1
• Decreases hot flash severity score by 46% compared to 15% with placebo 2, 1
• Particularly useful when taken at bedtime for patients whose sleep is disturbed by hot flashes 2, 1
• Has no known drug interactions and no absolute contraindications, making it safer than SSRIs/SNRIs in complex medication regimens 1
• Side effects affect up to 20% of patients but improve after the first week and largely resolve by week 4 1
• Equivalent efficacy to estrogen 1

Treatment Algorithm for Choosing Between Venlafaxine and Gabapentin

Choose gabapentin 900 mg/day at bedtime if: 1

• Patient has concurrent sleep disturbance from hot flashes
• Patient is on multiple medications (no drug interactions)
• Patient is taking tamoxifen (see below)

Choose venlafaxine 37.5-75 mg daily if: 1

• Rapid onset is prioritized
• Patient prefers it based on tolerability profile
• Gabapentin is ineffective or not tolerated

SSRIs as Alternative Options

• Paroxetine 7.5-12.5 mg daily (controlled release) reduces hot flash composite score by 62-65% 2, 1
• CRITICAL WARNING: Avoid paroxetine and fluoxetine in women taking tamoxifen due to CYP2D6 inhibition, which reduces tamoxifen efficacy 1, 3
• Sertraline 50 mg daily is superior to placebo in tamoxifen users and has weak or no effects on CYP2D6 4
• Citalopram is another alternative with minimal CYP2D6 effects 4
• All SSRIs/SNRIs must be tapered gradually on discontinuation 2, 4

Clonidine (Alpha-Agonist)

• Can reduce hot flash frequency and severity 1
• May have slower effect than venlafaxine but often better tolerated 1

Timing of Efficacy Assessment

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

Hormone Replacement Therapy (HRT)

When to Consider HRT

HRT is the most effective treatment for vasomotor symptoms, reducing hot flashes by approximately 75% compared to placebo 1, 5, 6, but should be reserved for:

• Severe symptoms unresponsive to nonhormonal options 1
• Women without contraindications after thorough risk-benefit discussion 1, 7

HRT Prescribing Guidelines

• Use transdermal estrogen formulations preferentially due to lower rates of venous thromboembolism and stroke 1
• Use the lowest effective dose for the shortest duration possible 1, 7
• Estradiol gel 0.5-1.0 grams daily (0.5-1.0 mg estradiol) shows statistically significant reductions in frequency and severity at 4 weeks 8
• Conjugated estrogens 0.3-0.625 mg daily are effective at 4 weeks 9

Progestogen Requirements

• Women with an intact uterus must take progestogen with estrogen to reduce endometrial cancer risk 7, 10
• Micronized progestin is preferred over medroxyprogesterone acetate due to lower rates of VTE and breast cancer risk 1

Absolute Contraindications to HRT

HRT is contraindicated in: 1

• History of hormonally mediated cancers
• Abnormal vaginal bleeding
• Active or recent history of thromboembolic events
• Pregnancy
• Active liver disease

Important Safety Warnings

• Combined estrogen/progestogen therapy increases breast cancer risk when used for more than 3-5 years 1, 7
• Increases risk of stroke and venous thromboembolism 1, 7
• Use with caution in women with coronary heart disease, hypertension, current smokers, and increased genetic cancer risk 1

Nonpharmacologic Approaches

Lifestyle Modifications (First-Line Adjuncts)

• Weight loss of ≥10% of body weight may eliminate hot flash symptoms 1, 3
• Smoking cessation significantly improves both frequency and severity 3
• Limit alcohol intake 1
• Avoid triggers: spicy foods, caffeine, hot drinks 3
• Maintain cool room temperatures, dress in layers, use fans and cooling pillows 3

Evidence-Based Complementary Therapies

• Acupuncture is 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) reduces perceived burden of hot flashes 1, 3
• Yoga may improve quality of life associated with menopause 1, 3
• Paced respiration training and structured relaxation (20 minutes daily) show significant benefit 1

Limited or Ineffective Options

• Vitamin E 800 IU daily has limited efficacy but reasonable for patients requesting "natural" treatment; doses >400 IU/day linked to increased all-cause mortality 1
• Black cohosh has limited data showing possible benefit in general population but no benefit in breast cancer survivors 3
• Phytoestrogens, botanicals, and dietary supplements have mixed or limited evidence 3

Special Population: Breast Cancer Survivors

Breast cancer survivors should avoid estrogen and tibolone as they may increase recurrence risk 1. Recommended alternatives include:

• Venlafaxine (preferred SNRI) 1
• Gabapentin 1
• Sertraline (if on tamoxifen, due to minimal CYP2D6 interaction) 4
• Avoid paroxetine if on tamoxifen 1, 3

For women with advanced breast cancer or severe symptoms affecting quality of life, estrogen may be considered after fully informed discussion of risks, with the decision ultimately resting with the patient 1.