Abstract
IntroductionWe aimed to evaluate the effect of menopause on skin thickening, as measured by the modified Rodnan skin score (mRSS), in women with systemic sclerosis (SSc).MethodsWe identified women with either limited or diffuse SSc, aged ≥ 18 years, enrolled within the Canadian Scleroderma Research Group (CSRG) cohort, between 2004 and 2011. As part of the CSRG cohort, subjects undergo annual assessments with standardized questionnaires and physical examinations. We performed multivariate regression analyses using generalized estimating equation (GEE) to determine the effect of menopause on the mRSS, adjusting for relevant covariates including notably age, follow-up time, and disease duration.ResultsWe identified 1070 women with SSc, contributing a total of 3546 observations over the study period. Of these women, at baseline, 65% had limited disease and 35% diffuse disease. In multivariate analyses, we observed a substantial effect of postmenopausal status on the mean mRSS in women with diffuse disease subtype [−2.62 units, 95% confidence interval (CI) -4.44, −0.80] and significant interaction between menopausal status and disease subtype (2.04 units, 95% CI 0.20, 3.88). The effect of postmenopausal status on the mean mRSS was smaller in women with limited SSc (−0.58, 95% CI −1.50, 0.34).ConclusionsOur results suggest that menopause has a substantial effect on skin thickening in diffuse SSc, with postmenopausal status being associated with a lower mean mRSS compared to premenopausal status.
Highlights
We aimed to evaluate the effect of menopause on skin thickening, as measured by the modified Rodnan skin score, in women with systemic sclerosis (SSc)
Investigators have shown that estrogen induced a significant increase of fibronectin, collagen type I, and laminin synthesis in SSc fibroblasts compared to untreated fibroblasts
Medication exposures were collected by physicians and included information on exposure to oral contraceptive pills (OCP), hormone replacement therapy (HRT), disease-modifying antirheumatic drugs (DMARDs), and exposure to cyclophosphamide
Summary
We aimed to evaluate the effect of menopause on skin thickening, as measured by the modified Rodnan skin score (mRSS), in women with systemic sclerosis (SSc). Skin thickening is a defining feature of SSc, which is characterized by excessive production of extracellular matrix proteins (for example, collagen, laminin, fibronectin) by fibroblasts, resulting in skin thickening and internal organ fibrosis [1,2]. Cyclophosphamide, a potent cytotoxic drug, was observed to have an effect on skin thickening when used for the Recent experimental evidence suggests that estrogen increases synthesis of extracellular matrix proteins in cultures of SSc skin fibroblasts [9]. Investigators have shown that estrogen induced a significant increase of fibronectin, collagen type I, and laminin synthesis in SSc fibroblasts compared to untreated fibroblasts. An estrogen-receptor inhibitor (that is, tamoxifen) induced a significant decrease of these extracellular matrix proteins in cultures of SSc skin fibroblasts [9]
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