Hormonal Contraception and Retinal Vascular Occlusion Risk

PURPOSE: To investigate the association between hormonal contraceptive use and the risk of retinal vascular occlusions in women of reproductive age.

DESIGN: Register-based, nationwide cohort study.

PARTICIPANTS: A total of 2,208,172 women aged 15-49 years were followed from January 1, 1996, to June 30, 2021, excluding those with prior venous or arterial thrombosis, thrombophilia, cancer (except non-melanoma skin cancer), liver disease, chronic kidney disease, hysterectomy, bilateral oophorectomy, hormone therapy, infertility treatment, endometriosis, or polycystic ovary syndrome.

METHODS: Women were followed until study end, age 50, emigration, death, or occurrence of exclusion criteria. Individual-level, time-updated hormonal contraception use was identified through prescription records; retinal vascular occlusion events were detected through hospital diagnoses. Poisson regression models estimated incidence rate ratios of retinal vascular occlusion by duration, dosage, and type of hormonal contraceptives, adjusting for age, educational level, hypertension, diabetes, hypercholesterolemia, atrial fibrillation/flutter during observation.

MAIN OUTCOME MEASURES: Adjusted incidence rate ratios (AIRR) and standardized incidence rate differences (SIRD) of retinal vein occlusion and retinal artery occlusion with hormonal contraceptive use compared to non-use.

RESULTS: The cohort contributed 23,882,016 person-years with a median follow-up time of 10 years (1st to 3rd quartile: 4 to 17). Compared to non-use, current hormonal contraception use was associated with a 40% increased rate of retinal vein occlusion (AIRR 1.4, 95% Confidence Interval (95% CI): 1.1-1.8), corresponding to SIRD of 4.6 (95% CI: 0.9-8.4) additional cases per 1,000,000 person-years. AIRR of retinal artery occlusion was 1.2 (95% CI: 0.8-1.7) with current hormonal contraception use compared to non-use. The increased rate of retinal vein occlusion persisted with use of combined oral contraceptives containing 30-40 µg of estrogen (AIRR 1.6, 95% CI: 1.2-2.3), while no increased rate was observed with the low-dose 20 µg combined contraceptives (AIRR 0.7, 95% CI: 0.3-1.5). No increase observed with use of hormonal intrauterine devices.

CONCLUSION: Combined oral contraceptives containing 30-40 µg estrogen were associated with an increased rate of retinal vein occlusion compared to non-use, although the absolute increase was low. No increased rate was observed for retinal artery occlusions.