Endocrine Abstracts

Introduction/Purpose: Despite some evidence that women with premature ovarian insufficiency (POI, loss of ovarian activity<40 years of age) are at risk for diminished life expectancy, large scale population-based studies are still scarce. The evidence on whether hormone replacement therapy (HRT) use decreases the mortality risk among women with POI are lacking. The aim of our study was to explore mortality among women with spontaneous POI and their controls in a large national cohort and whether HRT use modifies the mortality risk among them.

Methods: All spontaneous POI cases diagnosed in Finland between 1988-2017 were identified by their reimbursement right for HRT, from Social Insurance Institution medicine reimbursement registry. We explored mortality among women with spontaneous POI, compared to age and municipality matched controls (four/each POI case, n=22859). Cox regression analysis was used to compare mortality hazard ratio (HR) between women with POI and their controls in different causes of death. Women with cancer or cardiovascular morbidity before the index day were excluded from the analysis. Women with POI were classified as HRT users if they had purchased systemic HRT for ≥6 months. The data on mortality, causes of death and death ages were collected from Cause of Death Registry.

Results: The mean follow-up time for all groups was 17.5 years (standard deviation 8.5). At the end of the follow-up, 9.8% of women with spontaneous POI and 2.9% of controls were deceased. Compared to control women, age-standardized all-cause mortality was increased among women with spontaneous POI, among those without HRT (HR 1.60 95% Confidence Interval, CI 1.07-2.37) and those with HRT (HR 2.27 95% CI 1.46-3.5). Cancer mortality was also increased among spontaneous POI cases without HRT use, (HR 4.04 95% CI 3.04-5.37) and with HRT (HR 1.78 95%CI 1.27-2.48), as well as cardiovascular mortality (HR 2.30 95% CI 1.34-3.97) and (2.53 95% CI 1.58-4.06), respectively.

Conclusions: Women with spontaneous POI are at increased risk for all-cause, cardiovascular and cancer mortality, and HRT use of ≥6 months did not eliminate the risk. Future studies should focus on whether longer use of HRT associates with diminished mortality risk among women with POI. Specific attention should be paid to health of women with spontaneous POI to decrease excess mortality.