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

Ciaffi J1van Leeuwen NM2Schoones JW3Huizinga TWJ4de Vries-Bouwstra JK5.

Semin Arthritis Rheum. 2019 Jul 20. pii: S0049-0172(19)30298-7. doi: 10.1016/j.semarthrit.2019.07.007. [Epub ahead of print]

 

Abstract

BACKGROUND:

The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women, a contribution of sex hormones has been proposed.

OBJECTIVES:

We undertook this systematic literature review to investigate: (1) the role played by male and female sex hormones in the pathogenesis of SSc; (2) how sex hormone levels change in SSc patients and how hormonal variations modify the progression of SSc; (3) the effect of therapies targeting sex hormones on the disease course.

METHODS:

A literature search was performed in Pubmed, Embase, Web of Science, and Cochrane library databases. Given the heterogeneity in study design, different quality assessment tools were applied where appropriate.

RESULTS:

We retrieved 300 articles and 30 were included in the review. The available evidence points to a fibrogenic, but also a vasodilatory, role of estrogens in SSc. With the limitation of small sample sizes, women with SSc tend to have lower levels of androgens and non-significantly higher levels of estradiol compared to healthy controls, while in men we found increased levels of estradiol and discordant results for androgens. After menopause the skin score seems to decrease and prevalence of pulmonary artery hypertension seems to rise, which might be prevented by the use of hormone replacement therapy. No recent high-quality trial evaluated the efficacy of hormone-targeting therapies in SSc.

CONCLUSIONS:

Few translational studies of varying quality evaluated the role of sex hormones in SSc showing possible profibrotic and vasodilatatory effects of estrogens, but more research is needed to elucidate the extent of this contribution. Insights on the influence of sex hormones, along with the availability of new compounds acting on estrogen pathways, might provide ideas for additional studies on the application of sex hormone-targeting therapies in SSc.

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