What medications are used to treat hot flashes in menopausal women?

Medications for Menopausal Hot Flashes

For menopausal women with moderate to severe hot flashes, start with nonhormonal pharmacologic therapy—specifically gabapentin 900 mg/day at bedtime or venlafaxine 37.5-75 mg daily—as first-line treatment, reserving hormone therapy only for women who fail nonhormonal options and have no contraindications. 1, 2, 3

First-Line Nonhormonal Medications

Gabapentin (Preferred for Most Patients)

• Gabapentin 900 mg/day at bedtime is the preferred first-line agent, reducing hot flash severity by 46% compared to 15% with placebo, with efficacy equivalent to estrogen. 1, 2, 3
• This medication has no known drug interactions and no absolute contraindications, making it safer than SSRIs/SNRIs in complex medication regimens. 1
• Gabapentin is particularly advantageous for women with concurrent sleep disturbance from hot flashes, those on multiple medications, or those taking tamoxifen. 1
• Side effects (somnolence, dizziness, fatigue) affect up to 20% of patients but improve after the first week and largely resolve by week 4. 1
• Assess efficacy at 4-6 weeks; if ineffective, switch to an alternative nonhormonal agent. 1

Venlafaxine (Alternative First-Line)

• Venlafaxine 37.5 mg daily, increasing to 75 mg after 1 week, reduces hot flash scores by 37-61% with rapid onset within 1 week. 1, 2, 3
• Venlafaxine is preferred when rapid symptom control is prioritized or when gabapentin is ineffective or not tolerated. 1
• Patients prefer venlafaxine over gabapentin 68% vs 32% despite similar efficacy, likely due to tolerability profile. 1
• Assess efficacy at 2-4 weeks; if no response, switch to another agent. 1
• Common side effects include dry mouth, decreased appetite, fatigue, nausea, and constipation, with approximately 10-20% discontinuing due to adverse effects. 2, 3

Paroxetine (Second-Line SSRI)

• Paroxetine 7.5-20 mg daily reduces hot flash frequency, severity, and nighttime awakenings by 62-65%. 1, 3
• Critical contraindication: Avoid paroxetine (and fluoxetine) in women taking tamoxifen due to CYP2D6 inhibition, which reduces conversion of tamoxifen to active metabolites. 1, 2, 3
• Use citalopram, venlafaxine, or gabapentin instead for women on tamoxifen. 1, 3
• Do not screen patients for CYP2D6 despite theoretical concerns, as negative impact on breast cancer outcomes has not been conclusively demonstrated. 1

Important Prescribing Considerations for SSRIs/SNRIs

• These medications are contraindicated in women taking monoamine oxidase inhibitors and should be avoided in bipolar disorder due to risk of inducing mania. 1
• Require gradual taper on discontinuation to minimize withdrawal symptoms. 1, 3
• Consider gabapentin if sexual dysfunction is a concern before starting SSRIs/SNRIs or if it develops during therapy. 3
• There is no benefit to adding gabapentin to SSRI/SNRI therapy. 3

Second-Line Nonhormonal Options

Clonidine

• Clonidine (centrally acting α-adrenergic agonist) reduces hot flash frequency and severity by up to 46%. 1, 3
• It may have slower effect than venlafaxine but is often better tolerated. 1
• Common side effects include dry mouth and insomnia. 3

Vitamin E (Limited Efficacy)

• Vitamin E 800 IU daily has limited efficacy but is reasonable for patients requesting "natural" treatment with mild symptoms. 1, 3
• Critical warning: Doses >400 IU/day are linked to increased all-cause mortality and should be avoided. 1

Hormone Therapy (Reserved for Refractory Cases)

When to Consider Hormone Therapy

• Menopausal hormone therapy (MHT) is the most effective treatment, reducing hot flashes by approximately 75-90% compared to placebo. 1, 4, 5, 6
• MHT should only be used when nonhormonal options fail, using the lowest effective dose for the shortest duration possible (not more than 3-5 years). 1, 7
• Estradiol reduces moderate to severe hot flashes effectively. 8

Formulation Preferences

• Transdermal estrogen formulations are preferred due to lower rates of venous thromboembolism and stroke compared to oral preparations. 1, 9
• Women with a uterus must receive concurrent progestogen to reduce the risk of endometrial cancer. 4, 7
• Micronized progesterone may be preferred over medroxyprogesterone acetate due to lower rates of VTE and breast cancer risk. 1

Absolute Contraindications to Hormone Therapy

• History of hormone-related cancers (breast, endometrial) 1, 2, 8
• Abnormal vaginal bleeding (must be evaluated first) 1, 2, 8
• Active or recent thromboembolic events 1, 2, 8
• Active liver disease 1, 2, 8
• Pregnancy 1, 8

Important Safety Warnings

• Combined estrogen/progestogen therapy increases breast cancer risk when used for more than 3-5 years. 1, 4
• MHT increases the risk of stroke and venous thromboembolism. 1
• Do not use estrogens with or without progestins to prevent heart disease, heart attacks, or strokes. 8
• Using estrogens with progestins may increase risk of dementia. 8

Nonpharmacologic Adjuncts

• Weight loss ≥10% of body weight may eliminate hot flash symptoms. 1
• Smoking cessation improves frequency and severity of hot flashes. 1
• Acupuncture is safe and effective, with some studies showing equivalence or superiority to venlafaxine or gabapentin. 1
• Cognitive behavioral therapy (CBT) may reduce perceived burden of hot flashes even if frequency remains unchanged. 1
• Paced respiration training (structured breathing exercises for 20 minutes daily) shows significant benefit. 1
• Environmental adjustments: dressing in layers, maintaining cool room temperatures, wearing natural fibers, using cold packs intermittently, and avoiding identified triggers (including limiting alcohol intake). 1

Treatment Algorithm Summary

1. Start with gabapentin 900 mg/day at bedtime for most patients, especially those with sleep disturbance, multiple medications, or taking tamoxifen. 1, 2, 3
2. Alternative: Start with venlafaxine 37.5-75 mg daily if rapid onset is prioritized or patient preference based on tolerability profile. 1, 2, 3
3. Assess response at 2-4 weeks for SSRIs/SNRIs or 4-6 weeks for gabapentin; switch to alternative nonhormonal agent if ineffective or not tolerated. 1
4. Consider hormone therapy only after nonhormonal options fail, using lowest effective dose for shortest duration, with careful screening for contraindications. 1, 7
5. Encourage nonpharmacologic adjuncts (weight loss, smoking cessation, environmental modifications) alongside pharmacologic therapy. 1