Female Hormone Therapy Not Associated With Increased Risk of Retinal Vein, Artery Occlusions

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Women filling a prescription for female hormone therapy (FHT), and presumably taking FHT, are not at increased risk of retinal artery or retinal vein occlusions.

Women filling a prescription for female hormone therapy (FHT), and presumably taking FHT, are not at increased risk of retinal artery occlusion (RAO) or retinal vein occlusion (RVO), according to a study published in JAMA Ophthalmology.

FHT, including oral contraceptive pills, has been shown to increase the risk of cardiovascular, venous thromboembolism, pulmonary embolism, and stroke, authors explained. Because RVOs have similar risk factors to those of cardiovascular and cerebrovascular diseases, FHT may predispose individuals to RVOs.

RVOs, or blockages in the retinal veins, can lead to permanent vision loss and are a leading cause of blindness from retinal vascular diseases. Both RAOs and RVOs are associated with systemic risk factors such as type 2 diabetes, hypertension, and hyperlipidemia.

Although there have been case reports associating oral estrogen use with development of RVO or RAO, only 1 large cohort study, conducted in 1998, has ever been published on the subject. To investigate the incidence of the ocular conditions in women who filled a prescription for FHT, researchers compared data with those on age- and race-matched control patients who were not prescribed estrogen products.


Data were gleaned from the Clinformatics Data Mart Database (OptumInsight). The data set included claims of all beneficiaries in a commercial and Medicare Advantage database obtained by a national insurance provider. All prescriptions were filled between January 2000 and June 2019. Patients with less than 2 years in the insurance plan or who did not visit an eye-care clinician prior to the index date (the earliest date a prescription was filled) were excluded from the study.

The final analysis included a total of 205,304 patients who filled prescriptions for FHT and 755,462 matched controls. Inverse probability of treatment weighting (IPTW) with propensity scores was applied to address residual confounding by baseline covariates between the groups after matching, researchers explained.

The weighted mean (SD) age of the FHT cohort was 47.2 (16.3) years, compared with 47.1 (16.7) years in the control cohort. No differences in baseline covariates were found between the groups, while the median time in plan after index date was much shorter for FHT patients (190 days) compared with control patients (719 days). This was due to the requirement that FHT patients continue to have an active prescription for the medication.

Data showed:

  • In the FHT group, 41 RAO cases (0.01%), 68 RVO cases (0.02%), and 111 combined outcomes (0.03%) were found.
  • 373 RAO cases (0.05%), 617 RVO cases (0.08%), and 1003 combined cases (0.13%) were found in the control cohort.
  • IPTW Kaplan-Meier (KM) event rates at 1 year were 0.00015 for patients who filled prescription of FHT and 0.00019 for the control group with regard to RAOs.
  • The RVO KM event rate was 0.00038 and 0.00033 for the FHT prescription group and control group, respectively.
  • The combined KM rate was 0.00053 for the FHT prescription cohort and 0.00054 in the control group.
  • No difference was seen in the hazard of developing RAO (HR, 1.17; 95% CI, 0.83-1.65; P = .36), RVO (HR, 1.07; 95% CI, 0.82-1.39; P = .65), or the combined outcome (HR, 1.10; 95% CI, 0.89-1.36; P = .37) when comparing patients who filled a prescription of FHT with control patients.

Researchers also found no significant differences between the 2 cohorts after stratifying for age, diabetes, and hypertension.

The results suggest that “a history of FHT use may not be relevant in the evaluation of an individual with a retinal artery or retinal vein occlusion. Nor do our results support considering cessation of FHT in an individual who develops an RAO or RVO,” authors wrote.

Third-generation oral contraceptives, or low-dose oral contraceptives, now account for the majority of oral contraceptive purchases in developed countries. It is likely this lower-dose formulation may confer less risk to patients compared with second-generation formulations.

Investigators were unable to confirm whether the medication was taken by the patient, marking a limitation to the study. In addition, a lack of mandated eye examinations after index date made it possible that asymptomatic RAOs and RVOs went undetected. Data also only reflected patients from a single large US insurer and results may not be generalizable to uninsured populations.


Song D, Nadelmann J, Yu Y, and VanderBeek BL. Association of retinal vascular occlusion with women filling a prescription for female hormone therapy. JAMA Ophthalmol. Published online November 12, 2020. doi:10.1001/jamaophthalmol.2020.4884