Incidence and etiologic factors of premature ovarian insufficiency. Register-based nationwide study.

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Auditorium 4, Oulu University Hospital

Topic of the dissertation

Incidence and etiologic factors of premature ovarian insufficiency. Register-based nationwide study.

Doctoral candidate

Medical Doctor Heidi Silvén

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Research Unit of Clinical Medicine

Subject of study

Obstetrics and gynecology


professor Angelica Lindén Hirschberg, Karolinska University Hospital, Stockholm, Sweden


docent Maarit Niinimäki, Oulu University Hospilta, University of Oulu

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Premature ovarian insufficiency is associated with a significant familial risk.

Premature ovarian insufficiency (POI) is the cessation of ovarian function before the age of 40. The underlying factors of POI can include hereditary syndromes, previous cancer treatments, autoimmune diseases, and ovarian removal, but for the majority of patients, the cause remains unknown. POI causes infertility and predisposes individuals to several diseases such as osteoporosis and cardiovascular diseases. Symptoms and morbidity can be reduced by hormone replacement therapy. Previous studies indicate that POI affects approximately one percent of the female population, but further information on changes in the incidence of POI, underlying factors, and the risk of relatives contracting the condition is needed.

In this doctoral thesis research, we investigated data of all women diagnosed with POI in Finland from 1988 to 2017 using national health registers. Diagnosed women were identified based on the reimbursement code from the Social Insurance Institution of Finland (Kela). The study included 5011 women with POI and four controls for each of them.

The study found that first-degree relatives (sisters, daughters) of women with POI had about a 4.5 times higher risk of developing POI compared to women whose relatives were not diagnosed with POI. The cumulative incidence of POI by the age of 40 was 0.5%.

Additionally, the doctoral thesis research delved into the background factors of POI. Among those diagnosed with POI, 15.9% were found to have at least one genetic or congenital malformation diagnosis (GD/CM diagnosis). The younger the age at which POI was diagnosed, the more likely the patient was to have a GD/CM diagnosis. Moreover, the more GD/CM diagnoses a woman had, the more likely she was to be diagnosed with POI.

Cancer treatments are known to cause ovarian insufficiency, but population-level data on the contribution of cancer treatments to all POI cases have not been previously studied. In the research, a previous cancer diagnosis was found in up to one-fifth (21.9%) of those with POI compared to 0.8% of matched controls. Following cancer treatment, the risk of receiving a POI diagnosis was highest within the first two years, but the risk remained elevated even more than 10 years after the cancer diagnosis.

POI poses an increased health risk for women, emphasizing the importance of its diagnosis and appropriate hormone replacement therapy initiation. The study provides new insights into the increased risk of POI among first-degree relatives of women with POI and the background factors of POI. If POI is diagnosed at a young age, special attention should be paid to the possibility of hereditary diseases. Additionally, the risk of POI should be remembered if a woman has multiple congenital malformations or developmental delays. Cancer treatments are a significant background factor for POI in the Finnish population, and the risk of developing POI remains elevated even more than 10 years after a cancer diagnosis.
Last updated: 7.5.2024