Sex hormones and sex hormone-targeting therapies in systemic sclerosis: A systematic literature review

Ciaffi, Jacopo; Leeuwen, Nina M van; Schoones, Jan W.; Huizinga, Tom W J; Vries-Bouwstra, Jeska K de

doi:10.1016/j.semarthrit.2019.07.007

Cited by 16 publications

(13 citation statements)

References 53 publications

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“…A recent systematic review of the literature conducted on the role of sex hormones in SSc reported that estrogens may be simultaneously fibrogenic and vasodilatory. Within the limitation of the small numbers of individuals studied, compared to healthy controls women with SSc tended to have lower levels of androgens, non-significantly higher levels of estradiol, while men had increased levels of estradiol [ 50 ].…”

Section: Sex Bias In Sscmentioning

confidence: 99%

Current Concepts on the Pathogenesis of Systemic Sclerosis

Truchetet

Brembilla²,

Chizzolini³

2021

Clinic Rev Allerg Immunol

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From the clinical standpoint, systemic sclerosis (SSc) is characterized by skin and internal organ fibrosis, diffuse fibroproliferative vascular modifications, and autoimmunity. Clinical presentation and course are highly heterogenous and life expectancy variably affected mostly dependent on lung and heart involvement. SSc touches more women than men with differences in disease severity and environmental exposure. Pathogenetic events originate from altered homeostasis favored by genetic predisposition, environmental cues and a variety of endogenous and exogenous triggers. Epigenetic modifications modulate SSc pathogenesis which strikingly associate profound immune-inflammatory dysregulation, abnormal endothelial cell behavior, and cell trans-differentiation into myofibroblasts. SSc myofibroblasts show enhanced survival and enhanced extracellular matrix deposition presenting altered structure and altered physicochemical properties. Additional cell types of likely pathogenic importance are pericytes, platelets, and keratinocytes in conjunction with their relationship with vessel wall cells and fibroblasts. In SSc, the profibrotic milieu is favored by cell signaling initiated in the one hand by transforming growth factor-beta and related cytokines and in the other hand by innate and adaptive type 2 immune responses. Radical oxygen species and invariant receptors sensing danger participate to altered cell behavior. Conventional and SSc-specific T cell subsets modulate both fibroblasts as well as endothelial cell dysfunction. Beside autoantibodies directed against ubiquitous antigens important for enhanced clinical classification, antigen-specific agonistic autoantibodies may have a pathogenic role. Recent studies based on single-cell RNAseq and multi-omics approaches are revealing unforeseen heterogeneity in SSc cell differentiation and functional states. Advances in system biology applied to the wealth of data generated by unbiased screening are allowing to subgroup patients based on distinct pathogenic mechanisms. Deciphering heterogeneity in pathogenic mechanisms will pave the way to highly needed personalized therapeutic approaches.

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Section: Sex Bias In Sscmentioning

confidence: 99%

Current Concepts on the Pathogenesis of Systemic Sclerosis

Truchetet

Brembilla²,

Chizzolini³

2021

Clinic Rev Allerg Immunol

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“…A recent systematic literature of the sex hormones and sex hormone-targeting therapies literature concluded that oestrogens (particularly oestradiol) may have important pro-fibrotic but vasculoprotective properties in SSc (20). Apparent differences in clinical phenotype in females presenting before and after the menopause (21,22) also indicated a link between sex hormone levels and clinical phenotype (with lower fibrosis but higher rates of PAH associated with hypo-oestrogenic states (20). These findings have been challenged by recent work suggesting an anti-fibrotic role of oestrogens in pre-clinical models of SSc (23), which is consistent with the more severe clinical phenotype in males (see below).…”

Section: Pathogenesis (Jp)mentioning

confidence: 99%

Gender-related differences in systemic sclerosis

Hughes

Pauling

Armstrong-James

et al. 2020

Autoimmunity Reviews

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Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease which is characterised by widespread tissue fibrosis of the skin and internal organs, widespread vasculopathic alterations and immune system abnormalities. The condition is more common in women, but has a more severe expression of disease and higher mortality in men. Although the aetiopathogenesis of SSc is not yet fully understood, there is emerging evidence of important differences between men and women with the disease. This review brings together the current evidence on sex differences in SSc including epidemiology, pathophysiology, clinical expression of disease, mortality, SSc in transgender individuals, and psychosocial aspects of disease.

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“…Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by microvascular dysfunction and excessive collagen deposition leading to fibrosis of skin and internal organs [ 1 ]. SSc is considered a rare disease [ 2 ] and its pathogenesis is poorly understood, with a possible role of genetic, hormonal, environmental and occupational factors [ 1 , 3 , 4 ]. The extent of skin involvement defines two major clinical subtypes, namely limited cutaneous (lcSSc) and diffuse cutaneous SSc (dcSSc) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Whole body insulin sensitivity is increased in systemic sclerosis

et al. 2023

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Objectives In the present study, we aimed to evaluate whole-body insulin sensitivity in systemic sclerosis (SSc) patients and to compare the results with controls with no autoimmune rheumatic disease (non-ARD) and with patients affected by rheumatoid arthritis (RA). Methods In all patients and controls, oral glucose tolerance test (OGTT) was performed according to the World Health Organization (WHO) recommendations. Plasma glucose and insulin concentrations were measured at time 0 and then after 30, 60, 90, and 120 minutes. Whole-body insulin sensitivity (ISI), insulinogenic index (IGI), oral disposition index (ODI), and insulin resistance (HOMA-IR) were estimated accordingly. Results A total of 41 SSc patients were evaluated and, for comparison, 41 individuals with RA and 82 non-ARD control patients were recruited. OGTT yielded a proportion of normotolerant individuals among SSc patients higher than in RA controls (p = 0.040) but lower than in the non-ARD group (p = 0.028). The ISI was significantly higher in SSc patients compared with RA controls (p <0.001) and with non-ARD patients (p <0.001). Significant differences emerged also when analysing the HOMA-IR, which was lower in SSc patients than in RA (p <0.001) and non-ARD (p <0.001) groups. Additionally, IGI was lower in SSc patients compared with RA (p = 0.011) and with non-ARD controls (p <0.001), whereas ODI was not significantly different between groups. Conclusions Interestingly, we found that SSc patients are more insulin sensitive than those with RA and even than individuals without inflammatory diseases. In contrast, no significant difference was found in terms of β-cell function.

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Sex hormones and sex hormone-targeting therapies in systemic sclerosis: A systematic literature review

Cited by 16 publications

References 53 publications

Current Concepts on the Pathogenesis of Systemic Sclerosis

Current Concepts on the Pathogenesis of Systemic Sclerosis

Gender-related differences in systemic sclerosis

Whole body insulin sensitivity is increased in systemic sclerosis

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