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Female Hormonal Therapy Makes Only Small Contribution to Risk of Noninfectious Uveitis

Key findings

  • In the first study of its kind, Lucia Sobrin, MD, MPH, and John H. Kempen, MD, PhD, of the Mass Eye and Ear/Massachusetts General Hospital Department of Ophthalmology, and colleagues found a low risk of noninfectious uveitis among women using hormonal contraceptives or menopausal hormone replacement therapy
  • This retrospective analysis of nationwide private insurance data compared 217,653 women exposed to female hormonal therapy (FHT, hormonal contraceptives or menopausal hormone replacement therapy) with 928,408 matched unexposed women
  • There was no difference between the exposed and unexposed groups when incident noninfectious uveitis was defined as the assignment of a diagnosis code at least twice, without any requirement for corticosteroid treatment
  • The increased risk remained in subanalyses for the anterior subtype of uveitis and for women 45 or older
  • The absolute risk was low—a rate of 0.001 events per year according to the alternative analysis—suggesting FHT is safe with regard to uveitis risk for most women

Most cases of uveitis in the U.S. are noninfectious, and like other immune-mediated diseases, noninfectious uveitis is more prevalent among women than men. This suggests a need to investigate whether hormone-containing contraceptives and/or menopausal hormonal replacement therapy (HRT) might be risk factors for this vision-threatening disease.

In the first study on this topic, Lucia Sobrin, MD, MPH, associate chief of clinical data science at Massachusetts Eye and Ear and associate professor of ophthalmology at Harvard Medical School, and John H. Kempen, MD, MPH, PhD, MHS, director of epidemiology for Ophthalmology at Mass Eye and Ear and professor of Ophthalmology, part-time at Harvard Medical School, and colleagues from the University of Pennsylvania led by Dr. Brian VanderBeek, found that female hormone therapy (FHT) makes only a small contribution to the risk of noninfectious uveitis. Their report appears in Ophthalmology.

Study Methods

The researchers used a nationwide database maintained by a private insurance plan. 217,653 adult women filled at least one prescription for FHT between January 1, 2000 and December 31, 2016. Women who were 44 or younger at the time of first FHT prescription were presumed to be using hormonal contraceptives and those 45 or older were assumed to be using HRT.

Each FHT-exposed patient was matched with up to five women who did not fill a prescription for FHT, for a total of 928,408. Matching was based on age, race and start date of insurance eligibility.

Primary Analysis

The primary outcome was a new diagnosis code for noninfectious uveitis followed by a second instance of a diagnosis code within 120 days. With this definition, the incidence of noninfectious uveitis did not differ between the FHT and unexposed cohorts (HR, 0.99; 95% CI, 0.83–1.17; P=NS).

The result was similar when the outcome was limited to anterior uveitis. There were no incident cases of intermediate or posterior uveitis in the FHT cohort, so the HR for incident uveitis could not be calculated for those subtypes.

In a model that stratified by age (to address use of contraceptives vs. HRT), the risk of incident noninfectious uveitis was not significant in either category.

Alternative Analysis

The researchers also used an alternative primary outcome: prescription for a corticosteroid or a procedure code for intraocular/periocular corticosteroid injection within 120 days of the first uveitis diagnosis instead of requiring a second uveitis diagnosis. (Some patients may have improved enough with corticosteroid treatment that they didn't return for a second visit.)

In this analysis, the FHT cohort had a higher risk of developing incident noninfectious uveitis:

  • Overall—HR, 1.21 (95% CI, 1.04–1.41; P=0.01)
  • Anterior uveitis—HR, 1.23 (95% CI, 1.05–1.45; P=0.01)

Guidance for Clinicians

  • In the alternative analysis, differences between the exposed and unexposed groups didn't begin to be apparent until about 180 days after initiation of FHT, indicating its effects on the immune system take some time to manifest. Still, the absolute risk was low according to the alternative analysis. This suggests FHT is safe with regard to uveitis risk for most women
  • Women 45 or older at the time of FHT prescription were more likely to develop incident noninfectious uveitis (HR, 1.23; 95% CI, 1.03–1.47; P=0.03)

higher risk of noninfectious uveitis in users of female hormonal therapy than controls

higher risk of noninfectious anterior uveitis in users of female hormonal therapy than controls

higher risk of noninfectious anterior uveitis in users of female hormonal therapy who were age ≥45 years compared with controls ≥45 years

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