What are the non-hormonal therapy options for managing perimenopausal symptoms?

Non-Hormonal Therapy for Perimenopause

For perimenopausal women with bothersome vasomotor symptoms, start with SNRIs/SSRIs (venlafaxine, paroxetine, escitalopram, or citalopram) or gabapentin as first-line pharmacologic therapy, which reduce hot flashes by 40-65%. 1, 2

Pharmacologic Options for Vasomotor Symptoms

First-Line Medications

• SNRIs/SSRIs are the preferred non-hormonal medications, with venlafaxine showing particular efficacy in reducing hot flashes by approximately 40-65% 1, 2
• Paroxetine is FDA-approved specifically for vasomotor symptoms and reduces hot flash frequency by 40-65% 2, 3
• Escitalopram and citalopram are effective alternatives with similar efficacy 1, 2
• Desvenlafaxine (SNRI) also reduces vasomotor symptoms by 40-65% 2

Critical caveat: Do not use SSRIs (particularly paroxetine) in women taking tamoxifen, as SSRIs interfere with tamoxifen metabolism and reduce its efficacy 3

Second-Line Medications

• Gabapentin effectively reduces hot flashes and is particularly useful for women with sleep disturbances related to night sweats 1, 2
• Pregabalin was previously recommended but is no longer advised per The Menopause Society's 2025 updated guidelines 4
• Clonidine can be used but is no longer a primary recommendation per updated 2025 guidelines 1, 4

Emerging Therapies

• Neurokinin B antagonists represent a new medication class specifically targeting vasomotor symptoms, with additional benefits for sleep and mood disturbances 4

Non-Pharmacologic Interventions

Lifestyle Modifications (First-Line Approach)

• Environmental modifications: Keep rooms cool, dress in layers, use fans 1, 3
• Avoid triggers: Hot beverages, spicy foods, alcohol, caffeine, and stress 1
• Regular physical activity helps reduce symptom severity 1

Evidence-Based Behavioral Therapies

• Cognitive behavioral therapy (CBT) is effective for short-term reduction of vasomotor symptoms and associated sleep disturbances 5, 3
• Clinical hypnosis shows efficacy for short-term vasomotor symptom reduction 3
• Mind-body interventions are effective non-pharmacological options 5
• Acupuncture has demonstrated some efficacy in reducing hot flashes 5, 1

Important limitation: Data are lacking to support herbal/botanical supplements, and phytoestrogens show no convincing evidence of benefit 5

Management of Genitourinary Symptoms

Vaginal Dryness and Dyspareunia

• Hormone-free vaginal lubricants and moisturizers are first-line therapy: water-based gels, silicone-based lubricants, hyaluronic acid gel 5, 1, 3
• Non-hormonal vaginal moisturizers are noninferior to estrogen-based therapies for treating genitourinary syndrome of menopause 3
• Vaginal dilators can be used for dyspareunia secondary to vaginal atrophy 1
• Topical vitamin D or E may provide comfort 5

When Non-Hormonal Measures Fail

• Low-dose vaginal estrogen (rings, suppositories, creams) improves symptom severity by 60-80% and does not increase breast cancer recurrence risk 5, 1, 2
• Ospemifene (oral SERM) improves GSM symptom severity by 30-50% 2
• Intravaginal dehydroepiandrosterone (DHEA/prasterone) improves symptom severity by 40-80% 2

Sleep Disturbances

• Melatonin is recommended for sleep disturbances associated with perimenopause 5
• Gabapentin addresses both vasomotor symptoms and sleep disruption 1, 2
• CBT effectively treats sleep disturbances related to menopausal symptoms 5, 3

Assessment Before Treatment

Essential Evaluations

• Screen for medical causes: thyroid disease, diabetes that may mimic or exacerbate menopausal symptoms 5, 1
• Assess hormone levels as clinically indicated: estradiol, FSH, LH, prolactin 5, 1
• Note: FSH is unreliable in women with prior chemotherapy, pelvic radiation, or those taking tamoxifen 5

Risk Assessment

• Bone density assessment should be considered, especially with early menopause or osteoporosis risk factors 1
• Evaluate for contraindications to hormone therapy: history of hormone-dependent cancers, recent breast cancer, active liver disease, abnormal vaginal bleeding, thromboembolic events 5, 1

Treatment Algorithm

1. Start with lifestyle modifications and environmental controls for all women 1, 3
2. For bothersome vasomotor symptoms: Initiate SNRI/SSRI (venlafaxine or paroxetine preferred) or gabapentin 1, 2
3. For vaginal symptoms: Begin with non-hormonal lubricants and moisturizers 5, 3
4. Add behavioral therapies: CBT or clinical hypnosis for additional symptom control 3
5. Consider neurokinin B antagonists as emerging option for refractory vasomotor symptoms 4
6. For persistent genitourinary symptoms: Consider low-dose vaginal estrogen, ospemifene, or vaginal DHEA 2, 3

Key principle: Non-hormonal therapies show moderate efficacy (40-65% reduction) compared to hormone therapy (75% reduction), but are appropriate for women with contraindications to hormones or those who prefer non-hormonal approaches 5, 2