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IDENTIFICATION OF SUBJECTS AT INCREASED RISK OF FRACTURE USING FRAX TOOL
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
S15
National Society Symposia
Swiss Menopause Society
can be defined as the fracture probability at which an intervention becomes acceptable. Treatment decisions depend not only upon the fracture probability, but also the efficacy, costs and side effects of treatment and the willingness to pay. All these differ between countries, so that intervention threshold will differ accordingly.
51 CURRENT SWISS TRENDS IN HRT
53 A. Bodmer, C. Bodmer, M. Litschgi, D. Widmer, M. Birkhäuser. Division of Gynaecological Endocrinology and Reproductive Medicine, Frauenklinik, Inselspital Bern, Bern, Switzerland All over the world, physicians’ confidence in the use of HRT as a treatment for the relief of menopausal symptoms has been negatively impacted since the publication of the WHI study in 2002. In 2008, a survey has been done by mailed questionnaires among Swiss physicians with a particular interest in Menopause to ascertain their attitudes towards HRT and their current prescribing trends towards. 2218 questionnaires have been sent to Swiss menopause specialists. 550 physicians did answer (24.8%). Gynaecologists and GPs perceptions were evaluated in relation to the impact of menopausal symptoms on a woman’s quality of life, benefits of HRT, attitudes to prescribing HRT and awareness of new guidelines on dosing. The overriding message from the survey was that there was strong support for the use of HRT in suitable patients. More than seventy percent of physicians strongly agreed that the menopause significantly impacts on the Quality of Life of its sufferers. Physicians felt that the negative media coverage of HRT was unjustified. Dosing, time of initiation and duration of treatment are important factors that must be taken into account when prescribing HRT. Virtually all physicians claimed awareness of the new thinking around HRT dosing and understand that the current guidelines are the lowest possible dose of oestrogen and progestogen. The general consensus among those surveyed was that HRT is an effective treatment option for the relief of menopausal symptoms in suitable patients.
52
NEW INSIGHTS ON ACTIONS OF ESTROGEN ON VASCULAR ENDOTHELIUM R.K. Dubey. University Hospital Zurich, Clinic for Reproductive Endocrinology, Department of Obstetrics and Gynecology, Zürich, Switzerland Estrogen is known to induce vasoprotective and antivasooccluisve actions by stimulating the release of vasodilatory molecules from endothelial cells (ECs) and promoting EC growth. Recent studies suggest that circulating progenitor endothelial cells (PECs) play a critical role in repairing damaged endothelial layer. Because estradiol protects against vascular damage by stimulating EC growth, it may also induce vascular endothelium recovery by promoting PEC adhesion and proliferation. Using human PECs isolated from cord or peripheral blood we observed that estradiol selectively promotes adhesion of early-, but not differentiated-PECs, to ECs, moreover, this adhesion is enhanced in ECs primed with estradiol. Increase in endogenous estradiol promotes PEC colony formation and proliferation in mononuclear cells. Importantly, PECs expressed functional ER-α and ER-β, moreover, estradiol induced PEC growth. Studies using ER agonists and antagonists suggest the mitogenic effects of estrogen on PEC are ERa mediated. Similarly, via ER-a, estradiol stimulates signal-transduction pathways that positively regulate cell growth (ERK1/2 phosphorylation, cyclin D1, cyclin A, cyclin B and cyclin E), and suppresses p21, a negative growth regulator. These findings provide evidence that estradiol may promote vascular endothelium repair by activating adhesion of circulating PECs and subsequently promoting their proliferation via ER-α activation. Because priming of ECs facilitates the adhesion process, lack of estrogen during menopause would render this repair mechanism inactive. More importantly our results suggest that estradiol can channel adult stem cells/PECs to repair the vascular endothelium and protect women against cardiovascular disease.
IDENTIFICATION OF SUBJECTS AT INCREASED RISK OF FRACTURE USING FRAX TOOL R. Rizzoli. Geneva University Hospitals and Faculty of Medicine, Division of Bone Diseases [WHO Collaborating Center for Osteoporosis Prevention], Department of Rehabilitation and Geriatrics, Geneva, Switzerland During aging, bone cortex becomes thinner. This, together with an increased cortical porosity, a destruction of trabecular tridimentional structure through trabeculae thinning and perforation, and modifications of intrinsic tissue properties, account for age-dependent bone mineral loss, and increased bone fragility. Extraskeletal factors, such as muscle weakness or increased propensity to falling, also determine whether a bone will fracture in response to a given mechanical load. Osteoporosis diagnosis is based on the determination of areal bone mineral density, at spine and hip, using dual energy x-ray absorptiometry. This method captures mineral mass, but not alterations in bone microstructure, which significantly contribute to bone fragility. Osteoporosis diagnosis threshold is expressed in standard deviations from values recorded in young healthy individuals. Areal BMD predicts fracture risk, but nearly 50% of patients with hip fracture have BMD values above the osteoporosis threshold, implying a major role of BMD-independent clinical risk factors for predicting fracture risk. The WHO FRAX algorith provides a country-specific, estimate of fracture probability by taking into consideration remaining lifetime and absolute 10-year probabilities for osteoporotic fractures by gender, age and BMD. Clinical risk factors used in the FRAX algorith include prevalent fracture, family history of fracture, glucocorticoid therapy, smoking and drinking together with conditions causing secondary osteoporosis. Using this approach, it is now possible to determine fracture probability at which antiosteoprosis intervention may be recommended. Intervention thresholds
Groupe d’Etude sur la Ménopause et le Vieillissement Horman (GEMVI)
54 HORMONE DEPENDENCY OF BREAST TISSUE IN BRCA1/BRCA2 MUTATION CARRIERS A. Gompel 1 , L. Desreumaux 2 . 1 APHP Hôtel-Dieu, Université Paris Descartes, INSERM UMRS 893, Gynécologie, Paris, France; 2 INSERM UMRS 893, Hôpital St Antoine, Paris, France Brca1 and Brca2 are two genes involved in DNA repair and other biological functions. Mutations in these genes are associated with a dramatic increase risk of breast and ovarian cancers. Although it is well established that women with germ-line mutations in the BRCA1 gene have a greatly increased lifetime incidence of breast and ovarian cancer, the molecular mechanisms responsible for this tissue-specific carcinogenesis remain undefined. Whereas the BRCA2 mutation related tumours have a luminal epithelial phenotype with ER+, PR+, HER2 negative, the BRCA1 inactivation is associated with predominantly a triple negative tumor phenotype suggesting a different origin of these tumors. Paradoxically, the reproductive factors known to influence the sporadic breast cancer risk, are also active in women with BRCA1 mutation as well as prophylactic oophorectomy in addition to the ovarian cancer also reduces the risk of breast cancer in mutation carriers. There is an interplay between estradiol receptor (ER)
S15
National Society Symposia
Swiss Menopause Society
can be defined as the fracture probability at which an intervention becomes acceptable. Treatment decisions depend not only upon the fracture probability, but also the efficacy, costs and side effects of treatment and the willingness to pay. All these differ between countries, so that intervention threshold will differ accordingly.
51 CURRENT SWISS TRENDS IN HRT
53 A. Bodmer, C. Bodmer, M. Litschgi, D. Widmer, M. Birkhäuser. Division of Gynaecological Endocrinology and Reproductive Medicine, Frauenklinik, Inselspital Bern, Bern, Switzerland All over the world, physicians’ confidence in the use of HRT as a treatment for the relief of menopausal symptoms has been negatively impacted since the publication of the WHI study in 2002. In 2008, a survey has been done by mailed questionnaires among Swiss physicians with a particular interest in Menopause to ascertain their attitudes towards HRT and their current prescribing trends towards. 2218 questionnaires have been sent to Swiss menopause specialists. 550 physicians did answer (24.8%). Gynaecologists and GPs perceptions were evaluated in relation to the impact of menopausal symptoms on a woman’s quality of life, benefits of HRT, attitudes to prescribing HRT and awareness of new guidelines on dosing. The overriding message from the survey was that there was strong support for the use of HRT in suitable patients. More than seventy percent of physicians strongly agreed that the menopause significantly impacts on the Quality of Life of its sufferers. Physicians felt that the negative media coverage of HRT was unjustified. Dosing, time of initiation and duration of treatment are important factors that must be taken into account when prescribing HRT. Virtually all physicians claimed awareness of the new thinking around HRT dosing and understand that the current guidelines are the lowest possible dose of oestrogen and progestogen. The general consensus among those surveyed was that HRT is an effective treatment option for the relief of menopausal symptoms in suitable patients.
52
NEW INSIGHTS ON ACTIONS OF ESTROGEN ON VASCULAR ENDOTHELIUM R.K. Dubey. University Hospital Zurich, Clinic for Reproductive Endocrinology, Department of Obstetrics and Gynecology, Zürich, Switzerland Estrogen is known to induce vasoprotective and antivasooccluisve actions by stimulating the release of vasodilatory molecules from endothelial cells (ECs) and promoting EC growth. Recent studies suggest that circulating progenitor endothelial cells (PECs) play a critical role in repairing damaged endothelial layer. Because estradiol protects against vascular damage by stimulating EC growth, it may also induce vascular endothelium recovery by promoting PEC adhesion and proliferation. Using human PECs isolated from cord or peripheral blood we observed that estradiol selectively promotes adhesion of early-, but not differentiated-PECs, to ECs, moreover, this adhesion is enhanced in ECs primed with estradiol. Increase in endogenous estradiol promotes PEC colony formation and proliferation in mononuclear cells. Importantly, PECs expressed functional ER-α and ER-β, moreover, estradiol induced PEC growth. Studies using ER agonists and antagonists suggest the mitogenic effects of estrogen on PEC are ERa mediated. Similarly, via ER-a, estradiol stimulates signal-transduction pathways that positively regulate cell growth (ERK1/2 phosphorylation, cyclin D1, cyclin A, cyclin B and cyclin E), and suppresses p21, a negative growth regulator. These findings provide evidence that estradiol may promote vascular endothelium repair by activating adhesion of circulating PECs and subsequently promoting their proliferation via ER-α activation. Because priming of ECs facilitates the adhesion process, lack of estrogen during menopause would render this repair mechanism inactive. More importantly our results suggest that estradiol can channel adult stem cells/PECs to repair the vascular endothelium and protect women against cardiovascular disease.
IDENTIFICATION OF SUBJECTS AT INCREASED RISK OF FRACTURE USING FRAX TOOL R. Rizzoli. Geneva University Hospitals and Faculty of Medicine, Division of Bone Diseases [WHO Collaborating Center for Osteoporosis Prevention], Department of Rehabilitation and Geriatrics, Geneva, Switzerland During aging, bone cortex becomes thinner. This, together with an increased cortical porosity, a destruction of trabecular tridimentional structure through trabeculae thinning and perforation, and modifications of intrinsic tissue properties, account for age-dependent bone mineral loss, and increased bone fragility. Extraskeletal factors, such as muscle weakness or increased propensity to falling, also determine whether a bone will fracture in response to a given mechanical load. Osteoporosis diagnosis is based on the determination of areal bone mineral density, at spine and hip, using dual energy x-ray absorptiometry. This method captures mineral mass, but not alterations in bone microstructure, which significantly contribute to bone fragility. Osteoporosis diagnosis threshold is expressed in standard deviations from values recorded in young healthy individuals. Areal BMD predicts fracture risk, but nearly 50% of patients with hip fracture have BMD values above the osteoporosis threshold, implying a major role of BMD-independent clinical risk factors for predicting fracture risk. The WHO FRAX algorith provides a country-specific, estimate of fracture probability by taking into consideration remaining lifetime and absolute 10-year probabilities for osteoporotic fractures by gender, age and BMD. Clinical risk factors used in the FRAX algorith include prevalent fracture, family history of fracture, glucocorticoid therapy, smoking and drinking together with conditions causing secondary osteoporosis. Using this approach, it is now possible to determine fracture probability at which antiosteoprosis intervention may be recommended. Intervention thresholds
Groupe d’Etude sur la Ménopause et le Vieillissement Horman (GEMVI)
54 HORMONE DEPENDENCY OF BREAST TISSUE IN BRCA1/BRCA2 MUTATION CARRIERS A. Gompel 1 , L. Desreumaux 2 . 1 APHP Hôtel-Dieu, Université Paris Descartes, INSERM UMRS 893, Gynécologie, Paris, France; 2 INSERM UMRS 893, Hôpital St Antoine, Paris, France Brca1 and Brca2 are two genes involved in DNA repair and other biological functions. Mutations in these genes are associated with a dramatic increase risk of breast and ovarian cancers. Although it is well established that women with germ-line mutations in the BRCA1 gene have a greatly increased lifetime incidence of breast and ovarian cancer, the molecular mechanisms responsible for this tissue-specific carcinogenesis remain undefined. Whereas the BRCA2 mutation related tumours have a luminal epithelial phenotype with ER+, PR+, HER2 negative, the BRCA1 inactivation is associated with predominantly a triple negative tumor phenotype suggesting a different origin of these tumors. Paradoxically, the reproductive factors known to influence the sporadic breast cancer risk, are also active in women with BRCA1 mutation as well as prophylactic oophorectomy in addition to the ovarian cancer also reduces the risk of breast cancer in mutation carriers. There is an interplay between estradiol receptor (ER)