Abstract

AIMS--To study the effects of ovarian hormone replacement therapy (HRT) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis (RA). METHOD--A placebo controlled double-blind study was carried out on 62 patients with RA, 22 on placebo and 40 on HRT (transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinically indicated). Bone mineral density of spine, hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0, 12, 24 and 48 weeks. RESULTS--Thirteen of 22 (59%) of placebo and 31 of 40 (78%) of the HRT group completed 48 weeks in the study. At entry, bone mineral density (BMD) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups, whereas at the distal radius, BMD was significantly reduced to approximately 50% of control values (both p < 0.001 from controls). In the HRT group, spine BMD increased significantly by a median of +0.94% at 48 weeks (p = 0.024), but did not change significantly in the placebo group. BMD at the femoral neck and distal radius did not change in either group. In the HRT group, there was significant improvement in well being as assessed by the Nottingham Health Care Profile (p < 0.01) and in the articular index (p < 0.05). There were no significant changes in ESR or CRP in either group. CONCLUSION--Transdermal HRT was well tolerated, increased well being, reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA. Although no laboratory evidence was found of a disease modifying effect, the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA.

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Interaction with Estrogen Receptors as Treatment of Arthritis and Osteoporosis

Osteoimmunology

Advances in Experimental Medicine and Biology, 2007, Volume 602, 83-92, DOI: 10.1007/978-0-387-72009-8_11 http://www.springerlink.com/content/lg506007252607g0/

Abstract

Estrogen is a steroid hormone having, in addition to its effects on sexual differentiation and reproduction, important impact on the immune system and on bone. Estrogen exerts its effects via activation of its two receptors ERα and ERβ. Our knowledge of how estrogen manages to mediate its various properties in different organs has increased tremendously by studies of ER targeted mice (Matthews and Gustafsson 2003; Hewitt, Harrell and Korach 2005). It has been evident that the effects of estrogen on bone to a large extent are mediated via its action on immune cells. Estrogen has a dichotomous impact on the immune system by down regulation of inflammatory immune responses but simultaneous upregulation of immunoglobulin production. Consequently, immune mediated diseases in humans and in animal models are modulated by estrogen. Estrogen deficiency after ovarectomy in mice and menopause in women are associated with significant bone loss. In rheumatic diseases such as rheumatoid arthritis (RA) osteoporosis is frequent and in postmenopausal RA the degree of bone loss is dramatically increased. Hormone replacement therapy (HRT) in murine and human arthritis has, as expected beneficial effects on bone loss but it also ameliorates inflammation and inflammation triggered joint destruction (Holmdahl, Jansson, and Andersson 1986; Forsblad d’Elia, Larsen, Mattsson, et al. 2003b). RA is a chronic autoimmune disease with complex pathogenesis (Holmdahl, Bockermann, Backlund, et al. 2002) displaying a variety of inflammatory mechanisms resulting in joint destruction (Gravallese 2002) and generalized osteoporosis (Haugeberg, Orstavik and Kvien 2003). Hence, in order to understand the mechanisms for estrogen mediated effects on bone loss in inflammatory diseases it is necessary to dissect the different stages at which the estrogen has potential modulating properties. Long-term use of HRT has been associated with increased risk of breast cancer, thrombosis and possibly also stroke (Prelevic, Kocjan, and Markou 2005). Accordingly, there is great need for new activators of estrogen receptors (ERs) selectively reproducing only the beneficial effects of estrogen.

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HRT reduces pain 21.7% and morning stiffness 25.2%, and improved articulation among those who were good compliers (50 mg transdermal estradiol)

Ann Rheum Dis. 1994 Feb;53(2):112-6. At http://www.ncbi.nlm.nih.gov/pubmed/8129455?ordinalpos=1&itool=PPMCLayout.PPMCAppController.PPMCArticlePage.PPMCPubmedRA&linkpos=4

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

Hall GM, Daniels M, Huskisson EC, Spector TD.

Department of Rheumatology, St Bartholomew's Hospital, London, UK.

Abstract

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.