Premature ovarian insufficiency and early menopause: understanding the aetiology, protecting long-term health and what to expect from future research.

Abstract

Abstract: Premature ovarian insufficiency (POI) and early menopause, defined as ovarian failure before the age of 40 years and menopause between the ages of 40 and 45 years, respectively, affect a considerably higher proportion of people than previously estimated, with a worldwide prevalence of approximately 3.7 and 12%, respectively. Their aetiology is multifactorial, encompassing genetic causes, such as Turner's syndrome and FMR1 premutation carrier status; autoimmune conditions; iatrogenic factors, including chemotherapy, radiotherapy and pelvic surgery; and environmental and lifestyle influences, although a substantial proportion of cases remain idiopathic. POI and early menopause are associated with elevated risks of cardiovascular disease, osteoporosis, cognitive decline and dementia, as well as considerable psychological morbidity, including depression, anxiety and fertility-related distress. Many women also experience genitourinary syndrome of menopause (GSM), comprising vulvovaginal and lower urinary tract symptoms arising from hypo-oestrogenism, such as dryness, dyspareunia and recurrent urinary tract infections, alongside reduced libido, with important consequences for quality of life and sexual health. Prompt diagnosis of POI, requiring clinical suspicion alongside biochemical confirmation with elevated follicle-stimulating hormone (FSH) measurement, is important, as diagnostic delays can be associated with a greater bone mineral density loss. Hormonal therapy is the mainstay of management and should be continued until the average age of natural menopause. A comprehensive management approach should include lifestyle interventions and psychosocial support. Significant research gaps remain, including the identification of optimal hormonal regimens or validated biomarkers for early detection. Addressing these and other priorities is essential to improve long-term outcomes and quality of life for people affected by POI and early menopause.

Lay summary: Premature ovarian insufficiency (POI) occurs when the ovaries stop working normally before the age of 40 years. Early menopause means menopause happens between the ages of 40 and 45 years. These conditions are more common than previously thought. In addition to causing menopausal symptoms, such as hot flushes, mood changes and sleep disturbances, these conditions can have serious long-term effects on heart health, bone strength, memory and mental well-being. They can also have a profound emotional impact, particularly on patients who had hoped to have children. Hormone therapy is the main treatment for these conditions and is usually continued until the average age of natural menopause. Care should also include lifestyle support and psychological support. More research is still needed to identify the best hormone therapy options and better ways to detect these conditions early. Addressing these gaps could improve long-term health and quality of life for people with POI or early menopause.