Incidence and familial risk of premature ovarian insufficiency in the Finnish female population

Abstract

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.

Previous cancers in women diagnosed with premature ovarian insufficiency: A nationwide population‐based case–control study

“…In a recent register‐based study, we found that 15.9% of POI patients had a genetic disorder or congenital malformation. The overall prevalence of Turner syndrome in our study was 5.13% 9 . Among lifestyle‐based risk factors of POI, cigarette smoking has been confirmed to be an independent risk factor for POI in multiple studies 10–12 .…”

“…The reimbursement is applied by the treating physician at the time of POI diagnosis, regardless of whether the patient initiates HRT treatment at that time or not. The reimbursement criteria and their changes over time have been described in detail in a previous article 2 . These requirements have always been aligned with international diagnostic criteria.…”

“…The reimbursement criteria and their changes over time have been described in detail in a previous article. 2 These requirements have always been aligned with international diagnostic criteria. We identified 5221 women who were granted the right to POI medication reimbursement between 1988 and 2017 at ages less than 40 years.…”

“…1 The prevalence of POI is reported to be 1%-3%, and in a recent study, we reported a cumulative incidence of approximately 0.5%. 2,3 The impact of POI on women's health is far-reaching, causing fertility impairment and longterm bone, cardiovascular, and cognitive health deterioration. 4,5 Genetic, iatrogenic, or autoimmune causes can lead to POI.…”

“…Premature ovarian insufficiency (POI) is defined as amenorrhea for at least 4 months and high follicle‐stimulating hormone levels in two separate samples from a woman younger than 40 years 1 . The prevalence of POI is reported to be 1%–3%, and in a recent study, we reported a cumulative incidence of approximately 0.5% 2,3 . The impact of POI on women's health is far‐reaching, causing fertility impairment and long‐term bone, cardiovascular, and cognitive health deterioration 4,5 …”