Vasomotor Symptoms During Menopause: A Practical Guide on Current Treatments and Future Perspectives Original paper

What was reviewed?

This review explains menopause vasomotor symptoms treatment by summarizing pathophysiology, first-line hormone therapy, effective nonhormone options, and emerging agents. It describes how estrogen withdrawal narrows the hypothalamic thermoregulatory neutral zone through KNDy neuron signaling and how this neurobiology supports both hormone therapy and neurokinin receptor antagonists. It details the efficacy of systemic menopausal hormone therapy for hot flashes and night sweats, the importance of timing near menopause, and the risk differences by route and progestogen choice. In addition, it outlines practical prescribing, including when to choose transdermal estradiol, how to pair progestogen for endometrial protection, and how to handle bleeding and contraindications.

Who was reviewed?

The review focuses on midlife women with bothersome vasomotor symptoms, particularly those under 60 years of age or within 10 years of their final menstrual period. It addresses women with cardiometabolic risks, venous thromboembolism risks, obesity, diabetes, or prior coronary disease, and it highlights when transdermal routes and lower doses fit better. It also considers women with an intact uterus who require a progestogen with systemic estrogen, women after hysterectomy who may use estrogen alone, women with a history of breast cancer who should avoid systemic hormone therapy, and diverse groups who prefer or need nonhormone options such as SSRIs/SNRIs, gabapentin, oxybutynin, clonidine, or mind-body therapies. The review includes evidence that informs care for breast cancer survivors on tamoxifen, in whom paroxetine can interact, while venlafaxine does not.

Most important findings

Hormone therapy remains the most effective treatment for vasomotor symptoms and can reduce frequency and severity by about 90%, with the benefit greatest when initiated before age 60 or within 10 years of menopause. Transdermal estradiol limits first-pass hepatic effects and does not raise venous thromboembolism or ischemic stroke risk to the same degree as oral estrogen, which makes it preferable in women with vascular or metabolic risk. Progestogen choice matters for safety, with micronized progesterone or dydrogesterone showing more favorable thrombosis and breast profiles than several synthetic agents. Low-dose vaginal estrogen treats genitourinary syndrome of menopause but does not treat vasomotor symptoms, which underscores a separation between VMS control and local vaginal care that has downstream microbiome implications, even though this review presents no taxa.

Nonhormone options help many women who avoid or cannot use hormones. Low-dose paroxetine 7.5 mg reduces vasomotor symptom frequency and improves sleep but can inhibit CYP2D6 and interact with tamoxifen, while venlafaxine 75 mg can reduce vasomotor symptoms comparably to low-dose estradiol and lacks that interaction. Gabapentin 900 mg/day reduces hot flash frequency and can help sleep and migraine comorbidity, while oxybutynin improves symptoms but can cause anticholinergic effects, especially in older women. Clonidine provides a modest benefit with frequent side effects. Stellate ganglion block can reduce symptom severity in selected women. Novel neurokinin pathway agents such as fezolinetant produce rapid relief within days, which aligns with KNDy neuron biology and offers a hormone-free path. Estetrol appears promising but remains under study for vasomotor use.

Key implications

Clinicians should start vasomotor symptom therapy near menopause when possible, prefer transdermal estradiol in higher-risk women, and pair estrogen with an appropriate progestogen when the uterus is intact. Clinicians should separate vasomotor care from genitourinary care and recognize that local vaginal estrogen targets genitourinary symptoms rather than vasomotor symptoms, which allows teams to track vaginal outcomes and microbiome-sensitive endpoints in parallel while using systemic or neurokinin-based strategies for hot flashes. This approach aligns symptom relief with safety and prepares a framework to link route, regimen, and mucosal outcomes in a microbiome database, even though the review itself reports no microbial profiling.