Diabetic Retinopathy Linked to Serum Progesterone in Men

Models. On Screen, A Fundus Oculi With A Diabetic Retinopathy. (Photo By BSIP/UIG Via Getty Images)
The majority of participants with nonproliferative and proliferative diabetic retinopathy had progesterone levels in the highest quartile.

Among hospitalized male patients with type 2 diabetes mellitus, high levels of serum progesterone are significantly associated with diabetic retinopathy (DR), according to study results published in the Journal of Diabetes Investigation.

Previous findings suggested that the male sex is an independent risk factor for DR among patients with type 2 diabetes, which raises concerns about hormones that might affect these outcomes. The relationship between gonadal hormones and DR has not been often studied and information on the interaction between serum progesterone and DR is scarce. 

A team of investigators in China conducted a cross-sectional study to determine whether there is an association between progesterone and DR in male patients with type 2 diabetes mellitus. 

A total of 1376 men with type 2 diabetes were included in the analysis; 838 patients did not have DR, 499 patients had nonproliferative DR, and 39 patients had proliferative DR. Serum progesterone levels were categorized into 4 quartiles (Q1: ≤0.425; Q2: 0.425–0.75; Q3: 0.75–1.27; Q4: ≥1.27) with the Q1 representing the lowest quartile and Q4 representing the highest quartile. There were 344 patients in Q1, 352 patients in Q2, 341 patients in Q3, and 339 patients in Q4. 

Compared with patients who did not have DR, the majority of patients with nonproliferative and proliferative DR had progesterone levels in Q4 (P <.001). Among patients with nonproliferative DR, the prevalence of DR in Q4 was significantly higher than in Q1 (odds ratio [OR], 1.85); results were similar among patients with proliferative DR (OR, 8.35; unadjusted P <.001). 

After adjusting for variables, the odds for DR in Q4 for patients with nonproliferative and proliferative DR were 2.13 and 8.44, respectively (adjusted P <.001). Adjusted logistic regression suggested a positive correlation between serum progesterone and risk for DR. 

“The relationship between [progesterone] and DR will open up a new research field, and large-scale clinical studies in the future might help to identify whether P therapy is sex-specific,” according to the study. “Therefore, [progesterone]  therapy still requires careful and comprehensive consideration. Prospective cohort studies are required to identify the causality,” the investigators concluded. 


Sun S, Wang Y, Zhou Y, et al. Serum progesterone and retinopathy in male patients with type 2 diabetes: a cross-sectional study. J Diabetes Investig. 2021;12(7):1228-1235. doi:10.1111/jdi.13463