Menopause and Hormone Therapy

Menopause is the permanent end of ovarian follicular activity. As follicles are depleted, estradiol and inhibin production fall; the loss of ovarian negative feedback allows pituitary FSH to rise. FSH is therefore a marker of declining ovarian function, not the primary cause of the symptoms. Vasomotor symptoms (VMS)—hot flashes and night sweats—occur because estrogen withdrawal alters the hypothalamic thermoregulatory network. KNDy neurons, named for kisspeptin, neurokinin B, and dynorphin, become more influential as estrogen falls. The thermoneutral zone narrows, so a small change in core temperature triggers heat dissipation: cutaneous vasodilation, sweating, and sometimes palpitations followed by chills. Neurokinin-3 receptor antagonists reduce this signalling, which explains how fezolinetant treats VMS without supplying estrogen. Genitourinary syndrome of menopause (GSM) has a different clinical emphasis. Estrogen-sensitive vulvovaginal and lower urinary tract tissues become thinner, less elastic, and less lubricated. Patients may report dryness, burning, dyspareunia, urinary urgency, dysuria, or recurrent urinary symptoms. These symptoms can persist or progress even when hot flashes have settled. The estrogen decline also accelerates bone resorption. Hormone therapy can prevent bone loss and reduce fracture risk while...