Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.
This study evaluated the effect of Cenestin, a synthetic conjugated estrogens product, on the maintenance of trabecular bone microarchitecture, bone strength, and of bone turnover in the ovariectomized (ovx) rat model. Two doses of Cenestin were chosen in an attempt to approximate the equivalent human oral doses of 0.3 mg and 0.625 mg. Forty-nine 6-month-old retired female breeder Sprague-Dawley rats were randomly assigned to one of four groups: (1) sham-operated + vehicle; (2) ovx + vehicle; (3) ovx + day 1 post-ovariectomy Cenestin (8.12 mg/kg); (4) ovx + day 1 post-ovariectomy Cenestin (16.24 mg/kg) for 8 weeks. Trabecular structure of the right proximal tibia of each rat was imaged noninvasively by microCT. A compression test to induce a tibial plateau fracture was performed to determine the mechanical properties of the proximal tibia. Urine was collected on days 0, 14, 28, 42 and 56 and serum on days 0, 28 and 56 to assess biochemical markers of bone turnover including deoxypyridinoline crosslinks and osteocalcin. Both biochemical markers of bone turnover were analyzed by ELISA. Trabecular bone mass, structure, and connectivity density in the Cenestin-treated groups did not differ statistically ( p>0.05) from those of the sham-operated + vehicle-treated rats, but all were significantly higher ( p<0.05) than in the ovx + vehicle-treated rats. Structure Model Index, a measure of trabecular plate morphometry, in Cenestin-treated rats maintained a more equal mix of plate- and rod-like structures similar to the sham group, whereas the ovx group had predominantly rod-like trabeculae. Fracture load in the Cenestin (16.24 mg/kg) treated group was 31% ( p<0.01) higher than in the sham + vehicle-treated group and 61% ( p<0.05) higher than in the ovx + vehicle-treated group. Both the sham-operated + vehicle-treated and Cenestin-treated groups showed significantly lower urinary deoxypyridinoline crosslink excretion at all timepoints and serum osteocalcin at day 56 compared with the ovx + vehicle-treated group. In summary, Cenestin maintained trabecular bone microarchitecture and strength in an ovariectomized rat model of estrogen deficiency.
Recent studies have indicated that estrogen users have a lower than expected rate of concurrent osteoarthritis. We assessed the association between estrogen replacement therapy and incident symptomatic osteoarthritis, using a nested case-control design. We identified all incident cases of hand, hip, and knee osteoarthritis in women members of the Fallon Community Health Plan, age 20-89 years, from January 1, 1990, to December 31, 1993. For each case, we selected a control woman matched by closest date of birth. We used pharmacy records to classify women as new users, past users, ongoing users (past and new users), and never-users of estrogen replacement therapy. There were 60 informative case-control pairs. After controlling for obesity and health care utilization, we found that new use of estrogen replacement therapy was a predictor of new osteoarthritis diagnosis. Past use was inversely associated with risk of osteoarthritis [adjusted odds ratio = 0.7; 95% confidence interval (CI) = 0.3-1.9]. For ongoing use of estrogen replacement therapy and osteoarthritis, the adjusted odds ratio was 1.4 (95% CI = 0.6-3.3). The associations between osteoarthritis and both new use of estrogen replacement therapy and utilization of services suggest that frequent medical care increases the likelihood of diagnosis of osteoarthritis.
A bone mineral density test, regardless of the result, had a significant effect on women's decisions to accept HRT. Within the group having the test, women with lower bone mineral density were more likely to choose HRT.
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