Pathophysiologic Challenges in Rheumatoid Arthritis

*Rheumatoid Arthritis - Other Perspectives towards a Better Practice*

and active disease in rheumatoid arthritis: Defining criteria for disease activity states. Arthritis and Rheumatism. 2005;**52**(9):2625-2636

[30] Aletaha D, Alasti F, Smolen JS. Rheumatoid arthritis near remission: Clinical rather than laboratory inflammation is associated with radiographic progression. Annals of the Rheumatic Diseases. 2011;**70**(11):1975-1980

[31] Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Care & Research (Hoboken).

[32] Lau CS, Chia F, Harrison A,

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[33] Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR,

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Diseases. June 2020;**79**(6):685-699. DOI: 10.1136/annrheumdis-2019-216655.

Hsieh TY, Jain R, Jung SM, et al. APLAR

2016;**68**(1):1-25

2015;**18**(7):685-713

[Epub 2020 Jan 22]

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**Chapter 2**

**Abstract**

The Role of Estrogens in

*Maria Fernanda Romo-García, Martín Zapata-Zuñiga,*

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease that can lead to irreversible disability. It affects women in a higher proportion than men (3:1 cases). Several reports suggest a link between female sexual hormones (estrogens) and RA features. It's been described that biological processes where basal estrogen levels are altered like in menstruation, pregnancy, and menopause modifies RA onset, flare, disease severity, and inflammation. Estrogens have a direct action upon the immune system though ERα and ERβ receptors, which have distinct affinity to estrogen concentrations and modifications and have effects upon RA in a dose and receptor dependent manner. The studies focused on dose dependent response at experimental settings reveal a wide (from 25 pg/L to several μg/L) and even contradictory spectrum of effects in patients and cells. This chapter summarizes the contributions and effects of estrogens in RA physiopathology, clinical features, and discusses the possible contributions of estrogen administration and concentration of hormone replacement therapy (HRT) to improve the quality of life and reduce the symptoms of RA patients based on the knowledge of the biology of these hormones.

**Keywords:** rheumatoid arthritis, physiopathology, immune function, estrogen

Rheumatoid arthritis (RA) is defined as a chronic, inflammatory joint disease that without effective and timely treatment can lead to irreversible disability by cumulative joint damage. This autoimmune disease is characterized in most cases by autoantibodies against immunoglobulin G (RF) and citrullinated proteins (ACPAs) [1–3]. The alterations in the immune response is only one face of the disease since it has been described as a heterogeneous disease [4, 5]. This is supported by the wide variation in responsiveness to different rheumatic treatments [6]. Research suggests this might be due to variations in the distribution/expression of estrogen receptors (ERs) in immune cells; ERs often bind to promoter regions in the DNA associated with transcription factors (e.g., NF-κB, SP1, AP-1, C/EBPb) that are important for

Rheumatoid Arthritis

*and Julio Enrique Castañeda-Delgado*

Physiopathology

*José Antonio Enciso-Moreno*

**1. The RA-gender-hormones link**

immune cell function [7].

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### **Chapter 2**
