- Email: [email protected]
F222 Antiresorptive effect of transdermal estradiol on bone mass in healthy, osteoporotic and fractured postmenopausal women
F222
F223 NOR~THISTER~NE COMPARABLE
~~SO~~E EFFECT OF T~SDE~AL ESTRADIOL ON BONE MASS IN HEALTHY, OSTEOPOROTIC AND FRACTURED POSTMENOPAUSAL WOMEN
AND PROGESTERONE ARE POTENT INDUCERS OF ENDOMETRIAL PAIACTIVITY
T Moskovic, S Runic, Z Vukasinovic,
Cussi& Bertil, Hedlund
University Hospitalof Obstetricand Gynecology“NarodniFront”, Departmentof Menopauseand Family Planning,N. Fronta 62, Belgrade,Yugoslavia
Departmentof Obstretrics& Gynecology,Lund University Hospital. Lund,Sweden
86 womenin artificial menopause were allocatedin one of 5 group accordingto baselinebonemineraldensity(BMD) andadministered therapy. A: I7 healthy women without therapy; B: 19 healthy women receiving transdermal 17Bestradiol SOugrlday C: I 1 osteoporoticwomenreceiving Calcium 1~OOm~day;group D: 24 osteoporoticwomenreceivingtransdermalI7R-estradiol5Ougrlday + Calcium IOOOmg/day;E:15 womenwith at leastone vertebral osteoporoticfracture receivingtransdermal17l3-estradiol 5Oygr/day + Calcium lOOOmg/day + Calcitriol 0.25ugr/day.BMD of lumbar spine(L2-L4) at baselineand alter 12 monthswasmeasured using DEXA. In group A mean BMD has decreased(1.38+0.2%) (p
F224
Hemostasis in the endometrium is regulatedby the ovarianhormones. Fibrinolytic enzymeactivity, which is associatedwith endometrial hemorrhage, isreducedin thesecretory phase,asa resultof up-regulation of plasminogen activatorinhibitor-I (PAI-I ) by progesterone. Sinceit is relevantto hemostasis. we usedthe inductionof PAI-I in endometrial stromalcells to comparethe doseresponseof norethisterone and progesterone. Primaryculturesof endometrial stromalcellsweregrownto confluency in mediacontainingIO%FBS,andstimulated with progesterone (PR)or norethisterone (NET) for four days in mediumcontaining2% FBS. Conditioned mediumwascollecteddaily,replaced by freshmediumwith thehormones, andstoredat -20°Cuntil assayed with ImulysePAI- lTM (Biopol, Ume%Sweden). ~ndom~tr~al tissuewasrecoveredfrom 6 patientsundergoing hysterectomy.Alter incubationdupticatesamples wererunseparately at 5 concentration stepswith PRandNET. Therelease of PAI- I wasincreased bothby PRandNET. The response was time and dosedependentfor both compounds.There was a significantincrease of PAI-I in response to NET andPR at IO nmoVL andhighercon~entmtions. Theresponse wassli~tly higherto NETthan to PRin equimotar con~en~tions. Primarycultureof endometrial stromalcellsisa relevmtbioassay system for the endorganeffectsof progestagen steroids. The PAI-I geneis inducedby progesterone receptorstimulation,andPAI- I antigencan easilybe assayed.We foundcomparableresponses to PRandNET. with NET beingslightlymoreeffectiveat equimclarconcentrations.
IF225
TLBOLONE IN CLIMACTERIUM: EFFECT ON THE UTERINE ENDOMETRIUM OF POSTMENOPAUSAL WOMEN N. Klear~~ou **, M. KanelIaki-K~~~issi*~ V. K~raviann~s**, Koti~ou *, G. Vlassis * *, A. K~~ogero~ou~os * *
Tove and Samsioe G&an
PERIMENOPAUSAL ENDOMETRIUM: IRREGULAR HISTOLOGIC DEVELOPMENT K.
J. Boon, B. vdPWe, AP. Heinh, P.S~~olte~, R.Euser, A.~i~e~k~ve~
Ac.Hosp.Utrecht,PoBox85500,Holland. *3rd Dept. of Obstetricsand Gynecology Medical Faculty, and **Dept of Histology-Ebryology, Medical Faculty Aristotele’s Endometrialsamplesof perimenopausal womenshow severalcoUniversityThessaloniki,Greece existinghistologicalcharacteristicsinsteadof regulardevelopment seenin premenopausal women. During our study, 142 of 202 The useof tibolone in the treatmentof climacteriumhasbeenquite endometrialbiopsiesfrom Mmenopausal women(AD<12 months) si~i~c~t for several years. There have not however been couldbe analysed.The commonlyusedclassificationof endometrial published reports concerning the medication’s effect upon biopsiesaccordingto phaseof the cycle or evendate,is supposed to endometrium.This study was designedin order to determinethe be accurate.We found it wasnot possibleto classifyin 63 (44.4%) effect of tiboloneuponendometrium.The endometrium of fourteen postmenopausal womentreatedwith Tibolonefor a periodof I to 24 cases,which showedcharacteristicsof different phases. There months in comparisonwith the endometriumof 6 nontreated seemsto be a spectrumfrom atrophy to low activity whereupon pos~enopausal women, was studied by light and electron hormonal activity induces proliferative and/or secretory caracteristics.Secretorychanges dueto progesterone stimulationare microscope.Underinfluenceof Tibolone,the surfaceandgl~dular far morefrequentlyseenthan proliferative changes(73.2% vs 4%) epitheliumof the endometriumwas eniargedand the numberof We found no relationshipbetweenFSH- or E2-levelsand irregular stromal cells was increased. Ultrastructuraly, the cytoplasmic endometrialdevelopment.Timesincelastmenstrualbleedingis not structuresin the glandularepitheliumweredeveloped.The sizeand significantly for the sampleswith homogenousor irregular number of mitochondria, the number of free ribosomes,the development. The relationshipwith duration of perimenopause endoplasmicreticulum and the Golgi apparatuswere found increased,After prolongedtherapyof postmenopausal womenwith (characterisedby irregular hormonal production) is unknown. of this phenonomenare unknown. Tibolone,largeamountsof glycogenwere observedthroughoutthe Reasonsand consequences C/The histological classification for premenopausal womenis not cytoplasm, and especially near the nuclei of some glandular informative enough,and therefore a more detailed classification epithelialcells. Reticulatednucleoliwerealsofound in thesecases,The resultsof the should be created for endometria in perimenopausalwomen, presentwork suggesta combinationof estrogenicand progestogenic Consequenceof irregular endometrial developmentshould be influenceof Tiboloneon humanendome~u~ which is probably studiedmoreextensively. associated with its specialmoleculestructure. An analogous study, concerning Tibolone’s effectuponbreast,is in progress.
113
F223 NOR~THISTER~NE COMPARABLE
~~SO~~E EFFECT OF T~SDE~AL ESTRADIOL ON BONE MASS IN HEALTHY, OSTEOPOROTIC AND FRACTURED POSTMENOPAUSAL WOMEN
AND PROGESTERONE ARE POTENT INDUCERS OF ENDOMETRIAL PAIACTIVITY
T Moskovic, S Runic, Z Vukasinovic,
Cussi& Bertil, Hedlund
University Hospitalof Obstetricand Gynecology“NarodniFront”, Departmentof Menopauseand Family Planning,N. Fronta 62, Belgrade,Yugoslavia
Departmentof Obstretrics& Gynecology,Lund University Hospital. Lund,Sweden
86 womenin artificial menopause were allocatedin one of 5 group accordingto baselinebonemineraldensity(BMD) andadministered therapy. A: I7 healthy women without therapy; B: 19 healthy women receiving transdermal 17Bestradiol SOugrlday C: I 1 osteoporoticwomenreceiving Calcium 1~OOm~day;group D: 24 osteoporoticwomenreceivingtransdermalI7R-estradiol5Ougrlday + Calcium IOOOmg/day;E:15 womenwith at leastone vertebral osteoporoticfracture receivingtransdermal17l3-estradiol 5Oygr/day + Calcium lOOOmg/day + Calcitriol 0.25ugr/day.BMD of lumbar spine(L2-L4) at baselineand alter 12 monthswasmeasured using DEXA. In group A mean BMD has decreased(1.38+0.2%) (p
F224
Hemostasis in the endometrium is regulatedby the ovarianhormones. Fibrinolytic enzymeactivity, which is associatedwith endometrial hemorrhage, isreducedin thesecretory phase,asa resultof up-regulation of plasminogen activatorinhibitor-I (PAI-I ) by progesterone. Sinceit is relevantto hemostasis. we usedthe inductionof PAI-I in endometrial stromalcells to comparethe doseresponseof norethisterone and progesterone. Primaryculturesof endometrial stromalcellsweregrownto confluency in mediacontainingIO%FBS,andstimulated with progesterone (PR)or norethisterone (NET) for four days in mediumcontaining2% FBS. Conditioned mediumwascollecteddaily,replaced by freshmediumwith thehormones, andstoredat -20°Cuntil assayed with ImulysePAI- lTM (Biopol, Ume%Sweden). ~ndom~tr~al tissuewasrecoveredfrom 6 patientsundergoing hysterectomy.Alter incubationdupticatesamples wererunseparately at 5 concentration stepswith PRandNET. Therelease of PAI- I wasincreased bothby PRandNET. The response was time and dosedependentfor both compounds.There was a significantincrease of PAI-I in response to NET andPR at IO nmoVL andhighercon~entmtions. Theresponse wassli~tly higherto NETthan to PRin equimotar con~en~tions. Primarycultureof endometrial stromalcellsisa relevmtbioassay system for the endorganeffectsof progestagen steroids. The PAI-I geneis inducedby progesterone receptorstimulation,andPAI- I antigencan easilybe assayed.We foundcomparableresponses to PRandNET. with NET beingslightlymoreeffectiveat equimclarconcentrations.
IF225
TLBOLONE IN CLIMACTERIUM: EFFECT ON THE UTERINE ENDOMETRIUM OF POSTMENOPAUSAL WOMEN N. Klear~~ou **, M. KanelIaki-K~~~issi*~ V. K~raviann~s**, Koti~ou *, G. Vlassis * *, A. K~~ogero~ou~os * *
Tove and Samsioe G&an
PERIMENOPAUSAL ENDOMETRIUM: IRREGULAR HISTOLOGIC DEVELOPMENT K.
J. Boon, B. vdPWe, AP. Heinh, P.S~~olte~, R.Euser, A.~i~e~k~ve~
Ac.Hosp.Utrecht,PoBox85500,Holland. *3rd Dept. of Obstetricsand Gynecology Medical Faculty, and **Dept of Histology-Ebryology, Medical Faculty Aristotele’s Endometrialsamplesof perimenopausal womenshow severalcoUniversityThessaloniki,Greece existinghistologicalcharacteristicsinsteadof regulardevelopment seenin premenopausal women. During our study, 142 of 202 The useof tibolone in the treatmentof climacteriumhasbeenquite endometrialbiopsiesfrom Mmenopausal women(AD<12 months) si~i~c~t for several years. There have not however been couldbe analysed.The commonlyusedclassificationof endometrial published reports concerning the medication’s effect upon biopsiesaccordingto phaseof the cycle or evendate,is supposed to endometrium.This study was designedin order to determinethe be accurate.We found it wasnot possibleto classifyin 63 (44.4%) effect of tiboloneuponendometrium.The endometrium of fourteen postmenopausal womentreatedwith Tibolonefor a periodof I to 24 cases,which showedcharacteristicsof different phases. There months in comparisonwith the endometriumof 6 nontreated seemsto be a spectrumfrom atrophy to low activity whereupon pos~enopausal women, was studied by light and electron hormonal activity induces proliferative and/or secretory caracteristics.Secretorychanges dueto progesterone stimulationare microscope.Underinfluenceof Tibolone,the surfaceandgl~dular far morefrequentlyseenthan proliferative changes(73.2% vs 4%) epitheliumof the endometriumwas eniargedand the numberof We found no relationshipbetweenFSH- or E2-levelsand irregular stromal cells was increased. Ultrastructuraly, the cytoplasmic endometrialdevelopment.Timesincelastmenstrualbleedingis not structuresin the glandularepitheliumweredeveloped.The sizeand significantly for the sampleswith homogenousor irregular number of mitochondria, the number of free ribosomes,the development. The relationshipwith duration of perimenopause endoplasmicreticulum and the Golgi apparatuswere found increased,After prolongedtherapyof postmenopausal womenwith (characterisedby irregular hormonal production) is unknown. of this phenonomenare unknown. Tibolone,largeamountsof glycogenwere observedthroughoutthe Reasonsand consequences C/The histological classification for premenopausal womenis not cytoplasm, and especially near the nuclei of some glandular informative enough,and therefore a more detailed classification epithelialcells. Reticulatednucleoliwerealsofound in thesecases,The resultsof the should be created for endometria in perimenopausalwomen, presentwork suggesta combinationof estrogenicand progestogenic Consequenceof irregular endometrial developmentshould be influenceof Tiboloneon humanendome~u~ which is probably studiedmoreextensively. associated with its specialmoleculestructure. An analogous study, concerning Tibolone’s effectuponbreast,is in progress.
113