A recent study published in Translational Vision Science & Technology explored the association between hormone levels and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM), emphasizing potential sex-specific differences in disease prevalence and progression.
Give me some background first.
T2DM is a growing global health crisis, with an estimated 700 million cases expected by 2045—of which one-third will develop DR.
- To note: DR is a microvascular complication that remains the leading cause of vision loss in individuals with diabetes.
Prior data: While previous studies have reviewed the link between sex hormones to diabetes risk, their role in DR development remains not well understood.
- Even further: Some research suggests that testosterone and estradiol levels may influence diabetes progression, but these findings have been inconsistent.
As such: This study aimed to clarify how hormone levels— follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, progesterone, and testosterone—affect DR risk in both men and women with T2DM.
Now, talk about the study.
This cross-sectional study was conducted at Tianjin Medical University General Hospital in Tianjin, China, between 2016 and 2019.
What it entailed: Researchers studied the association between hormone levels and DR risk using logistic regression models while adjusting for potential confounding variables such as age, body mass index (BMI), smoking status, diabetes duration, and blood pressure.
- The goal: To determine whether sex hormones influence DR risk differently in men, premenopausal women, and postmenopausal women.
Who was included in the study?
A total of 2,432 adults with T2DM (aged 18 to 90) were enrolled.
Participants were classified into two groups:
- DR group (n = 953; 39%)
- No-DR group (n = 1,479; 61%)
Both men (n = 1,055) and women (n = 1,377) were included. Women were further split into premenopausal (35.84%) and postmenopausal (64.16%) groups.
To note: Pregnant women, type 1 diabetes patients, and individuals with acute complications, severe infections, or hormone-affecting medications in the past three months were excluded.
Next up: the findings.
Investigators found that hormone levels significantly influence DR risk—but their effects differ between men and women.
Case in point:
- In men: Higher testosterone levels increased DR risk by 64%, while higher prolactin levels lowered risk by 35%, suggesting that prolactin could have a protective role against DR
- For women: Higher FSH and LH levels were associated with greater DR risk, especially in postmenopausal women, where FSH more than doubled the likelihood of DR
- While testosterone was not generally a major factor in women, postmenopausal women with moderately high testosterone had a 53% increased risk of DR
What other factors were significant?
Aside from hormones, longer diabetes duration, higher systolic blood pressure, and smoking increased DR risk.
- Surprisingly: Lower BMI was linked to higher DR risk, possibly due to the "obesity paradox."
Breaking the data down: These findings highlighted the importance of hormonal balance, blood pressure control, and lifestyle factors in DR prevention, especially for men with high testosterone and postmenopausal women experiencing hormonal shifts.
What else was concluded?
The study authors noted that the findings suggested hormonal imbalances may contribute to the development of DR beyond traditional risk factors like blood pressure and the duration of diabetes.
- Even further: The differences between men and women emphasized the complex role of sex hormones in retinal health, particularly in postmenopausal women, where hormonal changes may increase their risk.
The study also suggests that regulating hormones could be a potential target for DR prevention, although further research is needed to explore this.
How about some limitations?
Quite a few were listed, including:
- The cross-sectional design meant the study could only show associations, not causation
- The study was conducted in a hospital-based population, which may not reflect trends in the general public
- DR severity was not classified into mild, moderate, or severe cases, limiting insights into disease progression
- Potential confounding factors such as medication use and lipid-lowering therapies were not accounted for
- Hormone levels were measured using immunoassays, which are less precise than mass spectrometry, especially for testosterone and estradiol
Expert opinion?
These findings support previous research suggesting that hormonal fluctuations affect men and women differently when it comes to diabetes.
The study authors noted that the role of testosterone remains disputed—as some studies suggest it protects against diabetes—while others have claimed it increases inflammation and vascular damage.
- Similarly, prolactin’s protective effect in men is unanticipated and warrants further investigation.
And for the future: Longitudinal studies could explore hormone-based therapies for DR prevention, especially in men and postmenopausal women.
What else do these findings support?
The concept of "obesity paradox,” where a lower BMI is linked to a higher risk of DR, contrary to expectations.
In regards to the study: This suggests that while obesity is known to increase the risk for diabetes, it may not necessarily worsen DR. Understanding this paradox could help in the development of personalized treatment options for patients with diabetic complications.
Finally: the take home.
This study offers strong evidence that sex hormones affect the risk of DR differently in men and women. High testosterone and low prolactin in men may contribute to DR development, while FSH and LH appear to increase the risk of DR in postmenopausal women.
- Although the exact mechanisms remain unclear, these findings could be the basis for hormone-focused research and potential treatments.
Lastly: Controlling blood pressure, managing diabetes duration, and avoiding smoking are still key to lowering the risk of DR.