S44 9th European Congress on Menopause and Andropause /Maturitas 71, Supplement 1 (2012) S1–S82

(range, 0%-0.4%). There was 1 venous thromboembolic event with MPA/CEand 1 cerebrovascular event with BZA 20 mg/CE 0.625 mg. The incidenceof breast pain for both BZA/CE doses was similar to that for placeboand significantly lower than that for MPA/CE (P<0.01). BZA/CE showedhigh rates of cumulative amenorrhea and low rates of bleeding/spottingsimilar to those for placebo and significantly better compared with MPA/CE(P<0.001).Conclusion: BZA/CE was associated with a favorable endometrial andoverall safety profile and showed improved tolerability compared withMPA/CE over 1 year in postmenopausal women.

68THE EFFECTS OF BAZEDOXIFENE/CONJUGATED ESTROGENS ON BREASTDENSITY IN POSTMENOPAUSALWOMEN

S. Mirkin1, J.A. Harvey2, J.V. Pinkerton3, K. Pan1, J.R. Thompson1,A.A. Chines1. 1Pfizer Inc, Collegeville, PA; 2Department of Radiology;3Department of Obstetrics and Gynecology, Division of Midlife Health,University of Virginia Health System, Charlottesville, VA, USA

Objective: To examine the effects of bazedoxifene/conjugated estrogens(BZA/CE) on mammographic breast density.Design: The Selective estrogens, Menopause, And Response to Ther-apy (SMART)-5 trial was a 1-year, randomized, double-blind, phase 3study in nonhysterectomized, postmenopausal women. Subjects wererandomized to BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, CE 0.45mg/medroxyprogesterone acetate (MPA) 1.5 mg, or placebo. Breast densitywas assessed in women meeting the inclusion criteria for the breastdensity substudy via digitized mammograms that were centrally read.Comparisons between active treatment and placebo groups were based ona non-inferiority test with a pre-defined margin of 1.5%.Results: This substudy included 940 participants (mean age±standarddeviation, 54.0±4.0 y): BZA 20 mg/CE 0.45 (n=231) or 0.625 mg (n=247),BZA 20 mg (n=122), CE 0.45 mg/MPA 1.5 mg (n=100), or placebo (n=240). At12 months, BZA 20 mg/CE 0.45 and 0.625 mg showed a decrease in breastdensity similar to placebo (not statistically different) and demonstratednon-inferiority versus placebo (Figure; upper bound of 95% confidence in-terval [CI], 0.51% and 0.44%, respectively). CE/MPA failed the non-inferioritytest and showed a significant increase in breast density versus placebo(P<0.001; upper bound of 95% CI, 2.7%).

Figure 1. Mean adjusted difference (95% CI) in percent breast density versus placebo at12 month.

Conclusion: BZA/CE did not increase breast density and showed non-inferiority versus placebo in contrast to CE/MPA, which increased breastdensity versus placebo.

69THE IMPACT OF MENOPAUSE AND HRT IN GINGIVAL TISSUE ANDALVEOLAR BONE

R. Qirko1, M. Qirko2, H. Kosova1, I. Heta1, E. Sadiku1, E. Demiraqi1.1Obstetrics and Gynecologic, “Queen Geraldine” Hospital; 2Operative Dentistry,Albanian University, Tirana, Albania

Introduction: Menopause is an unavoidable change that every woman willexperience, assuming she reaches middle age and beyond. Many womenarrive at their menopause transition years without knowing anything about

what they might expect. Hormonal changes during menopause influenceoral cavity and women may experience unpleasant symptoms. The aim ofthis study is to show the effect of HRT in preventing the changes in gingivaltissue and alveolar bone.Methods and materials: We examined 64 menopause women aged from49 to 64 years old. Half of them received HRT from 6 months to 2 years.We evaluated the gingival tissue, alveolar bone loss and by a questionnairethe mouth burning syndrome, xerostomia and altered taste perception.Osteoporosis evaluation was conducted by rheumatologic specialist.Results: The gingival atrophy was present in 19 patients untreated withHRT and 3 patients treated with HRT. Xerostomia was present in 18patients of the first group and in only 2 patients of the second group, whilemouth burning syndrome and altered taste perception were not present inpatients treated with HRT. We found a correlation between osteoporosisand alveolar bone loss. Hormonal changes during menopause may causehypertrophic inflammatory changes, which were noted in 5 patient of thefirst group and 2 patients of the second group.Conclusion: Hormonal changes during menopause effect gingival tissueand alveolar bone. HRT will improve significantly the clinical situation andsymptoms of oral cavity in general. Osteoporosis correlates with alveolarbone loss.

70EFFECTS OF TIBOLONE ON STEROID RECEPTORS AND BCL-2 ON THEBRAZILIAN POSTMENOPAUSAL ENDOMETRIUM

B.F. Reis1,2, S.M.R.R. Lima2, S.S. Yamada2, S. Postigo2, L.C.R. Barbosa1,S.C.V. Archangelo1, A.M.C. Francisco1. 1Obstetrician and Gynaecology,HCSL-UNIVAS, Santa Rita Sapucai-MG; 2Obstetrician and Gynaecology,FCMSCSP, Sao Paulo, Brazil

Introduction: Tibolone has been used many years for hormone replace-ment therapy in postmenopausal women. It exerts a tissue specific mode ofaction and effectively prevents bone loss and relieves climacteric symptomswithout stimulation of the endometrium.Objective: The aim of this study was to evaluate the effect of tibolone onthe histology and expression of estrogen and progesterone receptors andof Bcl-2 protein, in endometrium of postmenopausal women.Method: Forty postmenopausal women, including controls, participated inthis study evaluating oral hormone replacement treatment combining 2,5mg/day of tibolone administered for a 24-week period. The effect on theendometrium was assessed by histology and the apoptosis marker Bcl-2.The immunoexpression of estrogen (ER) and progesterone (PR) receptorsin the endometrium were also measured.Results: No increase in endometrial thickness was evident after both treat-ments, although endometrial histology was atrophic in most biopsies. Thetibolone group showed higher expression of ER and PR in glandular epithe-lium compared to stroma, but despite the Bcl-2 was more immunoreactivein glandular epithelium than in stroma, it was not significantly different.Compared to controls, tibolone users showed higher immunoexpression ofER, PR and Bcl-2 in both stroma and glandular epithelium.Conclusion: A twenty-four week course of tibolone resulted in low prolif-eration and was shown to lead to atrophic endometrium. Tibolone seemsto have favorable effects on the endometrium of postmenopausal womendue to its pro-apoptotic action in stroma.

71POSSIBLE MECHANISM FOR THE OBSERVED INCREASED BREAST CANCERRISK USING NORETHISTERONE IN HORMONE THERAPY

X. Ruan1, H. Neubauer2, H. Seeger2, T. Fehm2, A.O. Mueck2. 1GynecologicalEndocrinology, Beijing Ob/Gyn Hospital, Capital Medical University, Beijing,China; 2University Women’s Hospital, Tübingen, Germany

Objectives: Some clinical trials showed an increased risk especially duringHRT containing estrogen/norethisterone preparations. In the present workthe effect of a sequential estradiol/norethisterone combination was inves-tigated on the proliferation of MCF-7 breast cancer cells overexpressingthe progesterone receptor membrane component 1 (PGRMC1). Additionallythis combination was tested in a mouse transplantation model.Methods: MCF-7 cells were stably transfected with PGRMC1 expressionplasmid (WT-12 cells). In cell experiments estradiol (E2, 10−12 or 10−10 M)was sequentially combined with norethisterone (NET, 10−7 M). Proliferation