Menopause and Neurology: Clinical Essentials

Menopause is a neurobiological transition with important implications for neurologic care. This review summarizes the physiology and hormonal changes of spontaneous menopause and its treatment as applied to cognition, epilepsy, migraine, multiple sclerosis (MS), and stroke. It aims to serve as a resource for neurologists when managing patients in this transitional life stage.

Hormonal shifts associated with menopause, particularly declining estrogen and fluctuating estrogen-to-progesterone ratios, influence symptoms, disease expression, and treatment across multiple neurologic conditions. Perimenopause is often associated with subjective cognitive complaints, in part attributed to hypoestrogenism, along with secondary effects from sleep disturbance, vasomotor symptoms, and mood changes. Cognitive symptoms are often transient and rarely with objective neuropsychological deficits or progression. In epilepsy, menopause-related endogenous and exogenous hormones may influence seizure susceptibility and alter antiseizure medication metabolism. Migraine may worsen during perimenopause, especially in estrogen-sensitive phenotypes, with postmenopause stabilization once hormones plateau. In MS, perimenopause and postmenopause contribute to overlapping age-related and MS-related symptoms and is a period of high clinical need with potential acceleration in disability progression despite reduced relapse rate. Ischemic stroke risk rises sharply in postmenopausal women driven by advancing age, accumulation of cardiometabolic risk, and loss of estrogen's protective effects. Oral estrogen-containing systemic menopause hormone therapy (MHT) is associated with increased thromboembolic events (including stroke), whereas transdermal regimens seem safer and are preferred at low or standard doses (≤50 mcg estradiol patch or ≤1.5 mg [or 2 pumps] per day of 0.06% estradiol gel). Timing of initiation also modulates this risk and plays a critical role with a favorable risk:benefit window when initiated in women younger than 60 years or within 10 years of menopause onset.

Neurologists should routinely consider reproductive history, menopausal stage, symptom burden, and disease risk factors when evaluating midlife and older female patients. When appropriately selected, MHT can be safely used in many neurologic populations, with nonoral routes for estrogen and nonhormonal options generally preferred. Incorporating menopausal considerations into neurologic practice offers an important opportunity to optimize care and advance precision medicine.