A randomised controlled trial of the effect of hormone replacement therapy on disease activity in postmenopausal rheumatoid arthritis.

OBJECTIVE--To assess the effects of hormone replacement therapy (HRT) on disease activity in postmenopausal rheumatoid arthritis (RA). METHODS--Two hundred postmenopausal outpatients (aged 45-65 years) were admitted into a single blind randomised placebo controlled trial of transdermal oestradiol (50 micrograms daily) over six months. Patients continued with routine antirheumatic medications. Compliance with HRT was monitored using serum oestradiol (E2) levels. Disease activity was monitored at entry, three and six months using erythrocyte sedimentation rate (ESR), articular index (AI), visual analogue pain scale (VPS) and early morning stiffness (EMS). RESULTS--Ninety one and 77 patients completed six months treatment with placebo and HRT respectively. There were no significant differences in baseline characteristics between the groups and no overall effects of treatment. However, 35 patients (41.6%), who completed HRT, failed to achieve serum E2 levels > 100 pmol/l at either three or six months and were considered 'poor-compliers'. In the remaining HRT 'compliers' (58.4%) there were significant improvements after six months in articular index (28.9%; p < 0.01) and pain score (21.7%; p < 0.05) compared with placebo, as well as reductions in ESR (8.9%; NS) and morning stiffness (25.2%; NS). Comparisons between HRT 'compliers' and 'poor-compliers' confirmed significant improvements in articular index (p < 0.001), pain score (p < 0.05) and morning stiffness (p < 0.001) in the 'compliers'. CONCLUSIONS--This study did not show an overall effect of HRT on disease activity when used as an adjunct therapy in postmenopausal patients. A subgroup of patients, who had greater increments in serum E2 whilst taking HRT, demonstrated improvements in some parameters of disease activity, suggesting a potential beneficial effect with good compliance and higher dose HRT. Most importantly, in the treatment of RA associated bone loss, HRT can be prescribed without fear of a disease flare up.

[1]  J. Stevenson,et al.  Compliance with hormone replacement therapy (HRT) after screening for post menopausal osteoporosis , 1993, British journal of obstetrics and gynaecology.

[2]  J. Bijlsma,et al.  Adjuvant oestrogen treatment increases bone mineral density in postmenopausal women with rheumatoid arthritis. , 1993, Annals of the rheumatic diseases.

[3]  T. Spector,et al.  Risk of vertebral fracture in women with rheumatoid arthritis. , 1993, BMJ.

[4]  G. Blake,et al.  Compliance with hormone replacement therapy (HRT) after screening for post menopausal osteoporosis , 1992, British journal of obstetrics and gynaecology.

[5]  T. Spector,et al.  Carpal tunnel syndrome and hormone replacement therapy. , 1992, BMJ.

[6]  E. Barrett-Connor,et al.  Exogenous Estrogen and Endogenous Sex Hormones , 1992, Medicine.

[7]  J. A. P. Silva,et al.  Heat shock proteins: the missing link between hormonal and reproductive factors and rheumatoid arthritis? , 1991, Annals of the rheumatic diseases.

[8]  R. Holmdahl,et al.  Maintained pregnancy levels of oestrogen afford complete protection from post‐partum exacerbation of collagen‐induced arthritis , 1991, Clinical and experimental immunology.

[9]  C. Dinarello.  Interleukin-1 and interleukin-1 antagonism. , 1991, Blood.

[10]  D. Remick,et al.  In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta and tumor necrosis factor during experimental endotoxemia. Kinetics, Kupffer cell expression, and glucocorticoid effects. , 1991, The American journal of pathology.

[11]  G. Colditz,et al.  Estrogen replacement therapy and coronary heart disease: A quantitative assessment of the epidemiologic evidence☆☆☆ , 1991 .

[12]  T. Spector,et al.  The protective effect of the oral contraceptive pill on rheumatoid arthritis: an overview of the analytic epidemiological studies using meta-analysis. , 1990, Journal of clinical epidemiology.

[13]  R. Holmdahl,et al.  Oestrogen is a potent immunomodulator of murine experimental rheumatoid disease. , 1989, British journal of rheumatology.

[14]  L. Avioli,et al.  Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[15]  W. H. Stimson.  Oestrogen and Human T Lymphocytes: Presence of Specific Receptors in the T‐Suppressor/Cytotoxic Subset , 1988, Scandinavian journal of immunology.

[16]  L. Klareskog,et al.  Oestrogen induced suppression of collagen arthritis: I. Long term oestradiol treatment of DBA/1 mice reduces severity and incidence of arthritis and decreases the anti type II collagen immune response. , 1987, Clinical and experimental immunology.

[17]  J. Bijlsma,et al.  Effect of oestrogen treatment on clinical and laboratory manifestations of rheumatoid arthritis. , 1987, Annals of the rheumatic diseases.

[18]  M. Peacock,et al.  Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women. , 1987, British medical journal.

[19]  R. Holmdahl,et al.  Female sex hormones suppress development of collagen-induced arthritis in mice. , 1986, Arthritis and rheumatism.

[20]  M. Blankenstein,et al.  Presence of oestrogen receptors in human blood mononuclear cells and thymocytes. , 1986, Acta endocrinologica.

[21]  J. Fries,et al.  The development of disability in rheumatoid arthritis. , 1986, Arthritis and rheumatism.

[22]  W. Good,et al.  Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement. , 1985, American journal of obstetrics and gynecology.

[23]  L. Andersson,et al.  The oestrogen antagonists, tamoxifen and FC-1157a, display oestrogen like effects on human lymphocyte functions in vitro. , 1985, Clinical and experimental immunology.

[24]  A. N. Tucker,et al.  Estrogen immunosuppression is regulated through estrogenic responses in the thymus. , 1984, Journal of immunology.

[25]  G. Weissmann,et al.  Female hormones reduce neutrophil responsiveness in vitro. , 1984, Arthritis and rheumatism.

[26]  J. Revillard,et al.  Sex steroid receptors in peripheral T cells: absence of androgen receptors and restriction of estrogen receptors to OKT8-positive cells. , 1983, Journal of immunology.

[27]  R. Pope,et al.  Effect of pregnancy on immune complexes and rheumatoid factors in patients with rheumatoid arthritis. , 1983, The American journal of medicine.

[28]  M. Ostensen,et al.  Effect of pregnancy and hormonal changes on the activity of rheumatoid arthritis. , 1983, Scandinavian journal of rheumatology.

[29]  D. Mishell,et al.  The effects of estrogen on adrenal androgens in oophorectomized women. , 1982, American journal of obstetrics and gynecology.

[30]  H. Adlercreutz,et al.  Sex hormone regulation of in vitro immune response. Estradiol enhances human B cell maturation via inhibition of suppressor T cells in pokeweed mitogen-stimulated cultures , 1981, The Journal of experimental medicine.

[31]  B. Henderson,et al.  Menopausal estrogen therapy and hip fractures. , 1981, Annals of internal medicine.

[32]  Stimson Wh,et al.  Oestrogen-induced immunoregulation mediated through the thymus. , 1980 .

[33]  W. Stimson,et al.  Oestrogen-induced immunoregulation mediated through the thymus. , 1980, Journal of clinical & laboratory immunology.

[34]  T. Hutchinson,et al.  POST-MENOPAUSAL ŒSTROGENS PROTECT AGAINST FRACTURES OF HIP AND DISTAL RADIUS A Case-control Study , 1979, The Lancet.

[35]  W. Seaman,et al.  beta-Estradiol reduces natural killer cells in mice. , 1978, Journal of immunology.

[36]  M. Oka,et al.  Effect of pregnancy on the prognosis and serology of rheumatoid arthritis. , 1966, Acta rheumatologica Scandinavica.

[37]  I. Estrin,et al.  NORETHYNODREL WITH MESTRANOL IN TREATMENT OF RHEUMATOID ARTHRITIS. , 1964, JAMA.

[38]  J. Duthie,et al.  Course and Prognosis in Rheumatoid Arthritis , 1964, Annals of the rheumatic diseases.

[39]  A. Cohen,et al.  The Treatment of Atrophic Arthritis with Estrogenic Substance , 1940 .