women wishing to avoid monthly withdrawal bleeding while receiving natural progesterone non-orally for limited side effects.

P-282

Bone Mineral Density Response to Unopposed Es- terified Estrogens; Group BMD Changes vs Individ- ual Responses. 1j. Mortola, 2R. Emkey, 3S. Silfen, 8j. C. Nolan, 3j. Brennan. 1Cook County Hospital, Chicago, IL, 2Bone Research Center, Reading, PA, 3Solvay Pharmaceu- ticals, Inc., Marietta, GA, for the ESTRATAB® Osteoporo- sis Study Group.

Objectives: Esterified estrogens (ESE) were shown to prevent postmenopausal bone loss in doses as low as 0.3 mg/day. In an at tempt to define a response threshold, bone mineral density (BMD) changes for individual patients were compared to mean ESE t reatment group changes. Associations (correlations/regressions) were constructed between the mean % BMD change and the number of pa- tients who achieved a specific response threshold.

Design: A two-year, placebo-controlled (PBO), random- ized clinical study was conducted in 406 postmenopausal women to determine the effects of unopposed ESE in the prevention of postmenopausal bone loss. BMD changes were determined for all subjects on PBO and ESE (0.3, 0.625, or 1.25 rag) at 6, 12, 18, and 24 mos of treatment.

Material and Methods: Lumbar spine and hip BMD out- comes after 24 mos of t reatment (% change from baseline) for individual patients in this study were categorized into 'responder' or 'non-responder' classes based on a specific threshold response. Regression analyses were conducted using the % BMD data and the responder data.

Results: All doses of E SE caused statistically significant increases in lumbar spine BMD compared to PBO at 6, 12, 18, and 24 months. At 24 mos, the percent changes in lumbar spine BMD (visit-wise analysis) from baseline for the t reatments were: PBO, -2.52% (n = 64); 0.3 mg ESE, +1.76% (n = 66), 0.625 mg ESE, +2.81% (n = 57), and 1.25 mg ESE, +5.10% (n =- 38). The definition of BMD responder had an impact on the % of the women catego- rized as a responder. In defining BMD responders as those women having a lumbar BMD change > than the mean placebo response (-2.52%) at 24 months, 86-89% of the women on the lower ESE doses were 'responders', and 100% of the women on 1.25 mg ESE were 'responders'. When the definition of 'responder ' was changed to include all women whose lumbar BMD change was > 2 SE above the placebo response (-1.5%), 82-84% of the women on lower ESE doses were still categorized as 'responders', while 60% of the placebo women were 'non-responders'.

Conclusions: While all doses of ESE caused statistically significant increases in lumbar spine and total hip BMD compared to PBO 24 months, the definition of responder impacts the number of patients who were categorized as 'BMD responders', when using a definition that included women as 'responders' if their BMD change was more than 2 SE above the placebo response, 82-100% of the patients on ESE were responders. While mean t reatment group changes help define effective doses, the individual re- sponses to t reatment are more difficult to interpret.

P-283

Increased Bone Mineral Density in Surgically Meno- pausal Women Treated With Oral Estrogen-Andro- gen: A Two-year Double-blind Study Comparing Two Doses Each of Conjugated Estrogens and Estro- gen-androgen. 1R. Young, 2E. Barrett-Connor, ~R. Grimm, 4M. C. Timmons, 5j. Nolan, 5H. M. Yang, ~B. Wiita. 1Baylor Univ., 2UC San Diego, 3Berman Ctr. Clin. Res., 4Gerigyn, 5Solvay Pharmaceuticals, Inc.

Objective: The effects of estrogens on the prevention of postmenopausal bone loss are well known, while the ef- fects of androgens on postmenopausal bone loss are less- well characterized. This study was designed to compare the effect of combined estrogen-androgen therapy to that of estrogen therapy on bone mineral density changes in surgically menopausal women.

Design: A two-year double-blind randomized multicen- ter study was conducted in 311 surgically menopausal women to compare the effects of two doses of estrogens and two doses of estrogen + androgen given continuously with no added progestin.

Materials and Methods: Patients received one of four treatments: Estrogen (E) groups received daily doses of either conjugated estrogens (Premarin ®) 0.625mg or 1.25 mg, and estrogen-androgen (E+A) groups received daily doses ofesterified estrogens 0.625 mg or 1.25 mg combined with methyltestosterone 1.25 mg or 2.5 mg (Estratest HS ® or Estratest ® respectively. Bone mineral density (BMD) of the lumbar spine and hip was measured by Dual-energy X-ray absorptiometry (DEXA) at baseline, 12 and 24 months, and values for BMD were quality-assured by a central group.

Results: The average age of the patients was 45.7 years and their mean duration of menopause was 2.7 years. After 24 months of treatment, the lumbar spine BMD changes of the lower dose E and E + A groups were not significantly different (0.5% and 1.1%, respectively) from each other, but the changes induced by the higher doses were statisically different from each other (E, 2.1% and E + A, 4.2%, p < 0.014). Total hip BMD increased by 1.4% and 3.5% (P < 0.002) at 24 months in the higher dose E and E+A groups respectively. All medications relieved somatic, psychosomatic, and psychological symptoms of menopause and were well tolerated; the incidence of dis- continuation was comparable in all groups.

Conclusions: While the effects of low dose E and E+A treatment on lumbar spine and hip BMD changes in surgi- cally menopausal were comparable, high dose E+A pro- duced a significantly greater increase in lumbar spine and hip BMD (4.2% and 3.5%) than did high dose E alone (2.1% and 1.4%). High-dose E+A therapy may be appropriate for women at high risk for osteoporotic fractures.

P-284

Changes in Plasma Steroids, Parathyroid Hormone (PTH) and Calcitonin (CAL) During the Year Follow- ing Hip Fracture in Postmenopausal Women. 1N. H. Dubin, 1L. K. Monahan, 2j. A. Yu-Yahiro, 3K. S. Fox, 2M. Sachs, 2R. H. Michael, sS. I. Zimmerman, 2j. Magaziner.

8228 Abstracts