Nonhormone therapies for vasomotor symptom management

Tara K. Iyer; Alexa N. Fiffick; Pelin Batur

doi:10.3949/ccjm.91a.23067

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TABLE 1

Contraindications to hormone therapy

Contraindications	Pertinent considerations
Prior history of coronary heart disease, stroke, myocardial infarction, or unprovoked venous thromboembolism or inherited high risk of thromboembolic disease, or significantly high risk for cardiovascular disease	Relative contraindication: hormone therapy can be considered on a case-by-case basis
Unexplained vaginal bleeding	Relative contraindication: unexplained vaginal bleeding should be evaluated before hormone therapy is considered
End-stage liver disease	Relative contraindication: hormone therapy can be considered on a case-by-case basis
Prior history of estrogen-receptor-positive cancer	Absolute contraindication

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TABLE 2

Nonhormone pharmacologic agents currently available for management of vasomotor symptoms

Class	Medication	Dosing for VMS^a	Clinical pearls
SSRIs	Paroxetine salt^10,11,23,24 Paroxetine^10,11,23,24 Fluoxetine^11,23,24,26 Sertraline^11,23,24,27 Citalopram^10,11,23,24 Escitalopram^{10,11,23–25}	7.5 mg daily at bedtime 10–25 mg daily 10–30 mg daily 25–100 mg daily 10–20 mg daily 10–20 mg daily	Potent cytochrome P450 CYP2D6 enzyme inhibitors; do not use with tamoxifen as SSRIs reduce tamoxifen bioavailability and efficacy Paroxetine mesylate 7.5 mg was the first and only US Food and Drug Administration–approved nonhormone medication for moderate to severe menopausal VMS until the development of neurokinin-receptor antagonists Fluoxetine and sertraline are not recommended for VMS reduction owing to inconsistent data regarding efficacy in hot flash frequency and severity reduction Sertraline has a moderate effect on the CYP2D6 enzyme Citalopram and escitalopram may cause QT prolongation
SNRIs	Desvenlafaxine^10,11,23,24 Venlafaxine^10,11,23,24 Duloxetine^11,23,25	100–150 mg daily 37.5–75 mg daily 30–60 mg daily	SNRIs may increase blood pressure, use with caution in patients with hypertension Venlafaxine is the most well studied SNRI in combination with tamoxifen Duloxetine has a moderate effect on the CYP2D6 enzyme
Gabapentinoid	Gabapentin^{10,11,28–31}	300–2,400 mg daily (divided doses)	Consider for patients with a history of neuropathic pain or sleep concerns Consider nightly dosing (starting dose of 100–300 mg at bedtime) to minimize any adverse effects of daytime fatigue
Antimuscarinic	Oxybutynin^11,24,31,32	2.5–5 mg twice a day (immediate release), up to 15 mg/day (extended release)	Consider for patients with concurrent overactive bladder or hyperhidrosis Use caution in older adults (≥ 65 years); avoid altogether in patients ≥ 65 years taking concomitant anticholinergic medications
Alpha-2 adrenergic agonist	Clonidine^11,32,33	0.05–0.1 mg once or twice a day	Consider for patients with hypertension, especially if improved blood pressure control is desired Avoid in older adult patients (≥ 65 years) Less often used and no longer recommended by the Menopause Society owing to modest efficacy vs placebo and side-effect profile
Neurokinin-receptor antagonist	Fezolinetant^11,34,35	45 mg daily	Exercise caution in patients taking concomitant CYP1A2 enzyme inhibitors, which increase potency of fezolinetant Check transaminase levels at baseline, 3 months, 6 months, and 9 months

↵a Based on clinical efficacy demonstrated in randomized controlled trials and the Menopause Society recommendations.^10,11
SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitors; VMS = vasomotor symptoms