- Central Serous Chorioretinopathy (CSCR) Overview:
- CSCR is characterized by subretinal fluid accumulation due to increased choriocapillaris blood flow and permeability, often linked to elevated cortisol or corticosteroid use.
- Emerging evidence suggests a potential association between elevated testosterone levels and CSCR, though prior studies are inconclusive.
- Study Design and Population:
- Cross-sectional study using the TriNetX Analytics platform (over 100 million patients) to assess CSCR prevalence in patients with exogenous androgen exposure, female-to-male (FTM) transgender individuals, and polycystic ovary syndrome (PCOS).
- Exclusions: Patients with prior steroid prescriptions, anxiety disorders, or fluticasone use to minimize confounding factors.
- Patients were identified via ICD-10 codes and procedural codes, with prevalence and odds ratios (ORs) calculated using RStudio.
- Prevalence and Associations:
- Among 21,056 CSCR patients (mean age 61 years, 67.95% male), the highest CSCR prevalence was in the exogenous androgen therapy cohort (24.13 per 1000; OR: 5.84, 95% CI: 5.35–6.37).
- FTM surgery (OR: 3.04, 95% CI: 2.30–4.019) and sex-discordant hormone therapy (OR: 5.32, 95% CI: 4.097–6.90) showed significant associations with CSCR.
- PCOS had a modest but significant association (OR: 1.23, 95% CI: 1.013–1.49), likely due to only 60%–80% of PCOS patients having elevated testosterone.
- Gender identity disorder (GID) showed no significant association (OR: 1.29, 95% CI: 0.90–1.85), supporting the role of androgen exposure over gender identity.
- Exogenous androgen therapy and sex-discordant hormone therapy are strongly linked to CSCR, emphasizing testosterone’s role.
- Mechanistic Insights:
- Elevated testosterone may increase choriocapillaris blood flow and permeability, contributing to CSCR’s characteristic subretinal fluid.
- The exact mechanism linking androgens to CSCR is not fully understood, and this study did not measure testosterone levels directly.
- Clinical Implications:
- Findings underscore the need for ophthalmic screenings in patients on long-term testosterone therapy, particularly FTM transgender individuals and those on exogenous androgens.
- PCOS patients may require further investigation due to variable testosterone elevation, ideally with confirmed laboratory tests.
- Vigilant monitoring for CSCR symptoms is critical in transgender healthcare communities using hormone therapy.
- Study Strengths and Limitations:
- Strengths: Large sample size via TriNetX, unique focus on FTM transgender and PCOS cohorts, and robust statistical analysis.
- Limitations:
- Exploratory analysis with potential unaccounted confounders (e.g., obstructive sleep apnea, uncontrolled hypertension, alcohol use).
- Inability to capture over-the-counter topical steroids, which may affect results.
- Lack of temporality, dosage, or duration data for androgen therapy.
- Reliance on ICD-10 coding accuracy, introducing potential bias.
- Coding inconsistencies and unmeasured confounders are critical limitations for interpreting real-world data studies.
- Future Directions:
- Further studies are needed to elucidate the mechanistic link between androgens and CSCR, particularly in PCOS patients with confirmed elevated testosterone.
- Investigation into the impact of modifying or discontinuing androgen therapy in CSCR patients is warranted.
- High-yield for OKAP: Longitudinal studies with detailed hormone level measurements and therapy duration are essential to confirm causality.
Citation Address
Shirian JD, Shaia JK, Das N, Talcott KE, Singh RP, Mammo DA. Associations between Androgen Exposure, Polycystic Ovary Syndrome, and Transmasculine Individuals with Central Serous Chorioretinopathy. Ophthalmology Retina. 2025;9(5):460-464. https://doi.org/10.1016/j.oret.2024.10.026