Background Oral contraceptive (OC) and hormone replacement therapy (HRT) have been reported to have a protective and preventive effect on the progression of rheumatoid arthritis (RA). Although these observations are controversial, progression of undifferentiated arthritis (UA) to RA in pre- and post-menopausal women is largely unreported.

Objectives Over a 10 year period, we followed patients with undifferentiated arthritis (UA) who were referred to rheumatologists and did not fulfil classification or diagnostic criteria for RA or other connective tissue disease. We studied the efficacy of hormone replacement therapy (HRT) in this setting. In this study, the primary objective was to determine whether HRT reduces joint pain and/or decreased the progression of UA to RA.

Methods From 2007 to 2016, 1076 patients (male:60, female:1016) classified as UA were referred to one of two clinics because of complaints of joint pains and were enrolled in this study. Beginning in 2012, premenstrual, perimenstrual and postmenstrual women with UA were prescribed ultra-low dose tocopherol (600 mg/day) and HRT. A reduction of over 70% joint pain on a p-visual analogue scale (p-VAS) was set as the criterion of a favourable outcome. Each patient was assigned into one primary disease category. For example, primary SjS was regarded as a disease category but if a patient had secondary SjS, they were assigned to the primary (RA, SLE, SSc) disease category.

Results During the 5 year observation period, 213/343 (62.1%) had postmenopausal arthralgia (PoMA), 46/112 (41.1%) with perimenopausal arthralgia (PeMA), 17/25 (68%) with premenopausal arthralgia (PrMA). In the RA patients, 10.2%, had RF alone, 73.1% (250/342) had ACPA and/RF or ACPA alone and 16.7% had neither ACPA or RF. The specificity of ACPA was 93.2%. Regarding efficacy of HRT, the incidence of RA in RF positive individuals was 9.1% (5/55) in patients undergoing HRT (current and past user), which was significantly lower (p<0.01) than the 48.4% (30/62) in those never treated with HRT. Likely due to low numbers in the cohort, the incidence of RA in ACPA positive females was 22.2% (2/9) in those receiving HRT was not statistically significantly lower than the 70% (7/10) in those with without HRT.

Figure 1 Postmenopausal women responded to conventional HRT in 2013–2015

Conclusions The progression of UA to RA is apparently ameliorated in RF positive females who received conventional HRT and oral E3 treatment. Although the numbers were smaller, a significant protective effect was not observed in ACPA positive UA females. because they developed RA before menopause. Our observations suggest that HRT in peri- and post-menopausal and oestrogen (E3) in pre-menopausal females with RF and ACPA positive UA may be important in ameliorating the progression of UA to RA.

References [1] Orellana C, Saevarsdottir S, Klareskog L, Karlson EW, Alfredsson L, Bengtsson C.Postmenopausal hormone therapy and the risk of rheumatoid arthritis: results from the Swedish EIRA population-based case-control study.Eur J Epidemiol2015;30(5):449–57.

[2] Walitt B, Pettinger M, Weinstein A, Katz J, Torner J, Wasko MC, et al.Walitt B, Pettinger M, Weinstein A, et al. Effects of postmenopausal hormone therapy on rheumatoid arthritis: the women’s health initiative randomized controlled trials.Arthritis Rheum2008;59(3):302–10.

Acknowledgements We thank Dr Koyama for his advices and encouragement.

Disclosure of Interest None declared