Non-Hormonal Medications for Menopausal Symptoms

First-Line Non-Hormonal Options

The American College of Physicians recommends selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin, and clonidine as effective first-line non-hormonal pharmacological options for women experiencing menopausal symptoms who cannot or prefer not to use hormonal treatments 1, 2
Low-dose paroxetine (7.5 mg daily) significantly reduces both frequency and severity of vasomotor symptoms and decreases nighttime awakenings 3
For controlled-release formulations of paroxetine, 12.5 mg is considered the optimal dose 4, 3
Venlafaxine (37.5 mg daily, increasing to 75 mg daily after 1 week) is extensively studied and effective for vasomotor symptoms 4
Gabapentin is an effective alternative first-line treatment for hot flashes 4
Clonidine, a centrally acting α-adrenergic agonist, has mild to moderate efficacy in treating menopausal hot flashes and can reduce hot flashes by up to 46% 4

The mean reduction in daily hot flashes versus placebo is:
- Clonidine: -0.95 4
- SSRIs/SNRIs: -1.13 2
- Gabapentin: -2.05 4
SSRIs/SNRIs have side effects including dry mouth, nausea, constipation, headache, and sexual dysfunction (10-20% discontinuation rate) 4, 3
Gabapentin has side effects including dizziness, drowsiness, and unsteadiness (10% discontinuation rate) 4
Clonidine has side effects including dry mouth, insomnia or drowsiness (40% discontinuation rate) 4

The National Comprehensive Cancer Network recommends avoiding paroxetine and fluoxetine in women taking tamoxifen, as these drugs inhibit CYP2D6, blocking the conversion of tamoxifen to active metabolites 1, 3
Venlafaxine is the preferred SNRI for women on tamoxifen 3
Gabapentin is also a good option for breast cancer survivors 4

The American Cancer Society recommends lifestyle modifications such as rhythmic breathing, avoiding spicy foods, caffeine, and alcohol 2
Environmental modifications such as cool rooms and dressing in layers are also recommended 2
Acupuncture may reduce menopausal symptoms in some women 2
Cognitive behavioral therapy and clinical hypnosis may provide benefit 3

The American College of Obstetricians and Gynecologists recommends low-dose vaginal estrogen tablets or estradiol vaginal ring for urogenital atrophy, though safety in breast cancer survivors is not well established 2
Vaginal dilators or pelvic floor relaxation techniques may help with dyspareunia secondary to vaginal atrophy 2
Psychoeducational support, sexual counseling, and marital counseling should be offered to women with sexual complaints 2
Gabapentin should be considered over SSRIs/SNRIs if sexual dysfunction is a concern 4