What non-HRT treatment options are available for a perimenopausal woman with mild to severe hot flashes and night sweats?

Non-HRT Treatment for Perimenopausal Hot Flashes and Night Sweats

For perimenopausal women with mild to severe vasomotor symptoms, start with either venlafaxine 37.5-75 mg daily or gabapentin 900 mg/day at bedtime as first-line nonhormonal therapy, as these reduce hot flash frequency and severity by 37-65% and are recommended by major guidelines. 1, 2

First-Line Pharmacologic Options

SNRIs/SSRIs

• Venlafaxine is the preferred SNRI, starting at 37.5 mg daily and increasing to 75 mg after one week, reducing hot flash scores by 37-61% depending on dose 2, 3
• Venlafaxine is often preferred over gabapentin (68% vs 32% patient preference) despite similar efficacy, likely due to tolerability profile 2
• Common side effects include nausea (32-58% depending on dose), dry mouth (22%), dizziness (19-24%), and insomnia (14-23%) 4
• Avoid paroxetine in women taking tamoxifen due to CYP2D6 inhibition that reduces tamoxifen conversion to active metabolites, though breast cancer outcomes have not been conclusively affected 1, 2
• Citalopram and escitalopram are alternative SSRIs that reduce vasomotor symptoms by 40-65% without significant CYP2D6 interactions 3

Gabapentin

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

Clonidine

• Clonidine can reduce hot flash frequency and severity, with slower effect than venlafaxine but often better tolerated 2
• However, The Menopause Society recently removed clonidine from their recommendations due to benefits often being offset by adverse events 5, 6

Treatment Algorithm

Start with gabapentin 900 mg/day at bedtime if:

• Patient has concurrent sleep disturbance from hot flashes 2
• Patient is on multiple medications (no drug interactions) 2
• Patient is taking tamoxifen (avoid SSRIs with CYP2D6 inhibition) 2

Start with venlafaxine 37.5-75 mg daily if:

• Rapid onset is prioritized 2
• Patient prefers it based on tolerability profile 2
• Gabapentin is ineffective or not tolerated 2

Review efficacy at 2-4 weeks for SSRIs/SNRIs and 4-6 weeks for gabapentin; if intolerant or ineffective, switch to another nonhormonal agent 2

Nonpharmacologic Approaches

Lifestyle Modifications

• Weight loss of ≥10% of body weight may eliminate hot flash symptoms in postmenopausal women 1, 2
• Smoking cessation improves frequency and severity of hot flashes 1, 2
• Limiting alcohol intake if it triggers individual hot flashes 1
• Avoiding spicy foods and caffeine (variable results) 1
• Environmental modifications: cool rooms, dressing in layers 1

Mind-Body Interventions

• Cognitive behavioral therapy (CBT) reduces the perceived burden of hot flashes and has been studied specifically in breast cancer survivors 1, 2
• Paced respiration training (structured breathing exercises for 20 minutes daily) shows significant benefit compared to biofeedback control 2
• Hypnosis showed a 59% decrease in daily hot flashes with significant improvement in quality of life measures 2
• Yoga may improve quality of life associated with menopause, though effects on hot flash frequency are inconsistent 2

Acupuncture

• Acupuncture is safe and effective for managing vasomotor symptoms, with some studies finding it equivalent to or better than venlafaxine or gabapentin 1, 2
• Avoid acupuncture in breast cancer survivors with prior axillary surgery on the affected arm 2

Complementary Therapies

Vitamin E

• Vitamin E 800 IU daily has limited efficacy but is reasonable for patients requesting "natural" treatment 2
• However, doses >400 IU/day are linked to increased all-cause mortality and should be avoided 2

Phytoestrogens

• Preparations containing isoflavones (soy extract, red clover) are popular but scientific support for efficacy does not equal their popularity 7
• Black cohosh (Actaea racemosa) has variable evidence and has been found minimally effective 1, 7

Important Contraindications and Warnings

SSRI/SNRI Precautions

• Contraindicated in women taking monoamine oxidase inhibitors 2
• Avoid in bipolar disorder due to risk of inducing mania 2
• Gradual taper required on discontinuation to minimize withdrawal symptoms 2
• Monitor blood pressure with venlafaxine, as dose-dependent increases in diastolic blood pressure (0.7-2.5 mm Hg) and pulse rate (2-8 beats per minute) can occur 4

Special Populations

Breast Cancer Survivors

• Systemic hormone therapy is given rarely, if ever, to patients with breast cancer to control menopausal symptoms 1
• First-line options remain SNRIs (avoiding paroxetine if on tamoxifen), gabapentin, and lifestyle modifications 1, 2
• 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 2

Emerging Therapies

• Neurokinin B antagonists are a new class of medication now available to target vasomotor symptoms and show promise in addressing sleep and mood issues 5
• Pregabalin is no longer recommended by The Menopause Society 5

Key Clinical Pearls

• Recognize the robust placebo response (up to 70% in some studies) when evaluating treatment efficacy 2
• Nonhormonal medications reduce vasomotor symptoms by approximately 40-65%, which is about half as effective as estrogen (70-80% reduction) but significantly better than placebo 3, 7
• Vasomotor symptoms typically last more than 7 years, so long-term treatment strategies should be considered 3
• Menopausal symptoms remain substantially undertreated by healthcare providers, so proactive assessment and treatment is essential 8