STUDY QUESTION What is the incidence of premature ovarian insufficiency (POI), has the incidence of POI changed over time, and what is the risk of POI among relatives of POI women? SUMMARY ANSWER The incidence of POI increased among females aged 15–19 years from 2007 onwards and decreased in older age groups, and among relatives of women with POI the risk of POI is significantly increased. WHAT IS KNOWN ALREADY So far, there has been no good quality, nationwide studies of the incidence of POI. Early menopause has been associated with the elevated risk of early menopause among relatives, but the knowledge of the familial risk of POI is scarce. Lower socioeconomic status has been associated with lower age at natural menopause. STUDY DESIGN, SIZE, DURATION Population-based study with 5011 women diagnosed with POI in 1988–2017. The data were collected from national registries and covers POI subjects in entire Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with hormone replacement therapy reimbursement for POI were identified from Social Insurance Institution (SII). We calculated POI incidence in different age groups and studied the changes in the incidence rate over time in 5-year segments. Four population-based controls were selected from the Digital and Population Data Services Agency (DVV) for each POI woman. Family members of the POI cases and controls were identified from the DVV and linked to SII reimbursement data to identify POI diagnoses among them. The familial risk of POI was estimated with a logistical regression model. MAIN RESULTS AND THE ROLE OF CHANCE The incidence was highest in the 35–39 age group, ranging from 73.8/100 000 women-years in 1993–1997 to 39.9/100 000 women-years in 2013–2017. From 2007, the incidence among 15- to 19-year-olds rose from 7.0 to 10.0/100 000 women-years in 2015–2017. Cumulative incidence of POI for women under 40 years in 1988–2017 was 478/100 000 women. The relative risk of POI among relatives of women with POI was 4.6 (95% CI 3.3–6.5) compared to relatives of women without POI. POI women tended to have slightly lower socioeconomic status and level of education compared to controls. LIMITATIONS, REASONS FOR CAUTION For some women with POI, diagnosis or reimbursement may be lacking. However, we presume that these women represent a minority due to the nature of the disease and the economic benefits of reimbursement. Some changes in the incidence of POI can reflect changes in clinical practice and changing treatments and reimbursement criteria. WIDER IMPLICATIONS OF THE FINDINGS The risk of developing POI is significantly higher in women who have first-degree relatives diagnosed with POI. Raising awareness of the increased risk might lead to earlier diagnosis and initiation of hormonal replacement therapy, possibly preventing adverse effects of low oestrogen levels, such as osteoporosis. STUDY FUNDING/COMPETING INTEREST(S) This work was financially supported by the Oulu University Hospital. H.S. received a grant from Finnish Menopause Society. S.M.S. received a grant from the Finnish Menopause Society, the Finnish Medical Foundation and the Juho Vainio Foundation. The authors do not have any competing interests to declare. TRIAL REGISTRATION NUMBER N/A.

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Objective: To investigate whether early-onset menopausal transition associates with deteriorated glucose tolerance in women in their mid-forties. Methods:A cross-sectional analysis of a cohort study including 2632 women of the Northern Finland Birth Cohort 1966. The participants were divided into two groups by their menstrual history and follicle stimulating hormone values at age 46: climacteric and preclimacteric women. Glucose and insulin parameters, as well as mathematical indices derived from them to evaluate insulin sensitivity, were compared between the groups. The results were adjusted for measured body mass index and smoking. The possible effect of hormone therapy was investigated in subanalyses excluding hormone therapy users.Results: Climacteric women (n = 379) were more often current smokers at age 46 (P = 0.008), and their body mass indices increased more from 31 to 46 years (P = 0.013), compared to preclimacteric women (n = 2253). In a multivariable generalized linear model, being climacteric at age 46 was associated with several findings suggesting decreased insulin sensitivity: increase in glycated haemoglobin (P < 0.001), two-hour oral glucose tolerance test 30-and 60-minute insulin (P = 0.040 and 0.006, respectively) and area under the insulin curve (P = 0.005). Being climacteric also was associated with a decrease in the McAuley (P = 0.024) and Belfiore indices (P = 0.027) and glucose tolerance test 60-minute glucose (P = 0.015). In subanalyses excluding hormone therapy users (n = 94), the results did not change significantly.Conclusions: Earlier onset of climacteric transition associates with impaired insulin sensitivity in middle-aged women.