Female Hormone Therapy Not Linked to Increased Retinal Disease

Photo taken in Thai Mueang, Thailand
Despite previous suspicions, oral contraceptives and hormone therapies are not linked to risk.

The incidence of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) for women on female hormone therapy is very low, and not associated with a prescription for hormone supplements, according to researchers at the University of Pennsylvania.

Female hormone therapy includes oral contraceptive pills for women of reproductive age and hormone therapy for postmenopausal women. Previous research has linked the use of oral contraceptives with cardiovascular disease, venous thromboembolism, pulmonary embolism, and stroke, the researchers say. Because RVOs and these cardiovascular and cerebrovascular diseases share similar risk factors, investigators suspected that hormone therapy may predispose women to RVO.

Several studies have associated oral estrogen use with developing RVO or RAO, according to the researchers. However, no large cohort studies have been published on this topic since 1998, and the pre-1980 studies that have been published involved oral contraceptive pills that contained 80 μg or 100 μg of estrogen, significantly higher than the current types most frequently used in the United States, which contain only 30 μg or 35 μg of estrogen. Low-dose oral contraceptives appear to be less associated with an increased risk of cerebrovascular diseases.

To investigate the incidence of RVO and RAO in patients who filled a prescription for female hormone therapy, a multiple-cohort study was conducted using an administrative claims insurance database comparing women who filled a prescription with matched control individuals. Subjects enrolled in the plan for less than 2 years, those with no prior ophthalmologic examination, and those with a history of an RAO/RVO, systemic diseases/medications that affect estrogen levels, or a disease associated with an increased risk for thromboembolism were excluded from the study. 

A total of 205,304 women who filled a prescription for female hormone therapy were matched with 755,462 control subjects with a mean age of 47.2 years. The primary outcome measurement was the incidence of a new diagnosis of RAO or RVO.  The team’s analysis found 41 cases (0.01%) of RAO and 68 cases of RVO (0.02%) in the hormone cohort compared with 373 cases of RAO (0.05%) and 617 cases of RVO (0.08%) in the control cohort. After applying inverse probability of treatment weight, they found no difference in risk for RAO, RVO, or combined outcomes in the hormone cohort compared with the control cohort (RAO HR, 1.17; 95% CI, 0.83-1.65; P =.36; RVO HR, 1.07; 95% CI, 0.82-1.39; P =.65; combined HR, 1.10; 95% CI, 0.89-1.36; P =.37). After stratifying by age, diabetes, and hypertension, the data showed no significant link between the prescription cohort and all outcomes, according to the study.

These findings suggest that filling a prescription for female hormone treatment—and presumably taking it—does not increase the risk of RAO or RVO. As such, having a history of female hormone therapy use may not be relevant when evaluating a patient with a retinal artery or retinal vein occlusion, according to the researchers. The results also don’t support discontinuing female hormone therapy for patients who develop an RAO or RVO, say investigators.

“Despite many forms of oral contraceptives and female hormonal therapy being recognized as a risk factor for thromboembolisms, these hormones do not appear to affect the eye as they do in other areas of the body,” explains Delu Song, MD, the study’s co-author.

Researchers note several limitations to the study, including that filling a prescription does not confirm that the medication was taken by the patient. Also, claims data did not link a pharmacy prescription with a specific diagnosis and investigators could not verify diagnosis codes with medical record data. Further, researchers note that it’s possible that the risk for RAO/RVO is dose-dependent and the follow-up time within the database was not long enough to confer an identifiable risk to hormone users. Another issue that may have affected the study was a lack of mandated eye examinations after the index date. Lastly, the data came from a single large insurer in the United States and may or may not reflect patients from other insurers or the uninsured.


Song D, Nadelmann J, Yu Y, 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