Background/Purpose: Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive extracellular matrix deposition (ECM), leading to dermal and internal organ fibrosis. As in other autoimmune diseases, SSc is more prevalent in women. However, men have more severe disease. Considering the sex-based disparity in disease severity, estradiol (E2), an estrogen form with pro-fibrotic effects in different organs, may play a role in SSc pathogenesis. We previously reported that post-menopausal women with diffuse cutaneous (dc)SSc have higher serum E2 levels compared to healthy controls of similar age. Our objective was to examine serum E2 levels in dcSSc males in relation to disease characteristics (i.e. autoantibody profile and internal organ involvement) and its impact on survival.

Methods: We measured serum E2 levels in 83 dcSSc men >50 years old from the University of Pittsburgh Scleroderma Center and healthy controls of similar age. Using statistical modeling, we examined the associations between circulating E2 levels, internal organ involvement, autoantibody profiles, and survival.

Results: Male dcSSc patients had significantly higher serum E2 levels compared to healthy male controls. Male dcSSc patients also had higher serum E2 levels compared to dcSSc post-menopausal women of similar age. Male dcSSc patients with high serum E2 levels had significantly more heart involvement and worse survival. Using Cox regression modeling for risk of death, increasing serum E2 levels in anti-Scl-70 antibody positive dcSSc males were associated with an increased risk of death.

Conclusion: DcSSc male patients have higher levels of E2 compared to healthy controls and dcSSc post-menopausal women. Elevated serum E2 levels in dcSSc males >50 are associated with heart involvement and, if anti-Scl-70 antibody positive, worse survival. Our current study expands on our previous work, implicating E2 in the pathogenesis of SSc-associated fibrosis and extends our findings to an association between E2 levels, internal organ involvement, and overall survival. These data suggest an important role for estrogen imbalance in SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/estradiol-levels-are-elevated-in-older-men-with-diffuse-cutaneous-ssc-and-are-associated-with-decreased-survival/