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P012 Long term effects of kliogest® (kliofem®) on bone turnover in postmenopausal women
PO09
PO10
COMPARISON OF THE EFFECT OF DIVIGEL, A PERCUTANEOUS ESTRADIOL GEL AND ESTRADERM (TTS) TREATMENT ON TOTAL BODY BONE MINERAL DENSITY AND LIPID METABOLISM IN MENOPAUSE Kivinen, S*, Hirvonen, E 4 Wilen-Rosenqvist,
G*, Kanta-Hdme
CentralHospital*,, Hameenlinna,KalevankatuMedical Center n, Helsinki,Orion Pharma,Espoo*,Finland.
CONJUGATED ESTROGEN AT A DAILY DOSE OF 0.625 MG AND 0.3 MG HAD ALMOST THE SAME IMPACT ON THE CHANGES OF BONE MINERAL DENSITY AND BONE METABOLISM IN POSTMENOPAUSAL WOMEN. LT. Chen, K. Hasumi, E. Ogata
Departmentof Gynecology,CancerInstitute Hospital,Toshima-Ku, Tokyo, 170,Japan.
The effect of an estradiolgel (Divigel) anda transdermal therapeutic We comparedthe changesin bonemineraldensity andmetabolism system(TTS)(Estradermpatch) on total body bonemineraldensity treated by the two-year study of hormonereplacementtherapy (TBBMD) and lipid metabolismwas investigatedin an open, (HRT) with the two different dosesof conjugatedestrogen.40 controlled,parallel-groupstudy. 120 postmenopausal womenwere patientswithin 10 years after menopausewere divided into two allocatedat randomto the two treatmentgroupsfor twelve anda half groups;(A):E 0.625mg + medroxyprogesterone acetate(MPA) 2.5 months.60 patientsweretreatedwith 1.0 mg of estradiolgel daily. mg/day;20 cases,(B):E 0.3mg+ MPA 1.25mg/day;20 cases.We The gel wasappliedin the eveningon the skin of the lower trunk, measured L2-4BMD(DPXL;Lunar), E2, Ca, P, Al-p, belowthenavel, or on the skinof the thighs.61 patientsweretreated Osteocalcin(Cis) N-terminalosteocalcin(Teijin), intact osteocalcin with Estradermpatch of 50 yg/24 h, changedtwice a week. Both (Teijin), Urinary pyridinoline/Cr, deoxypyridinoline/Cr,before, 6, groupsreceiveddydrogesterone (Terolut) 1 0 mg daily for the first 12, 18 and 24 months after HRT. There were no statistical 12daysof everymonth. differencesin age,body massindex, postmenopausal periods, and Serumtriglycerides,total cholesterol,HDL-cholesterolandalkaline L2-4BMD before HRT. Betweenthe two groups, we found no phosphatase (s-APHOS) concentrationswere determinedfi-om all statisticaldifferences(mean+SE;A vs. B) in % baselineBMD patientsat the onsetof the study and at 12 months.(TBBMD) was changes(103.3+0.2; 103.2kO.9;6M, 104.1+0.7;104.6+1.1; 12M, measuredin both groupsfrom the first 30 includedpatientswith 106.350.7; 107.421.1; 24M), deoxypyridinoline/Cr (63.753.5; Lunar DBX dualphotonabsorptiometryat onsetof the study andat 58.8t3.8; 6M, 55.9i4.0; 59.025.5;12M, 52.522.4;57.2255; 24M), 6 and 12 months. Theseparameterswere alsomeasuredfrom a Al-p 87.5253; 81.724.3;6M, 79.4k5.7; 75.125.5; 12M, 79.8~4.5; referencegroupof 25 postmenopausal women. 76.7k6.1;24M). Incidenceof abnormaluterinebleedingwasmuch Total cholesterol decreased in bothtreatmentgroupsbut not statistically lessin B. Thesedata indicatedthat E at 0.625 mg and 0.3 mg/day significantly. HI&cholesterol and s-triglyceride concentrations hadalmostsameimpacton the changesof bonemineraldensityand remainedunchangedin both groups. There were no statistically metabolism, however,the bettercomplianceis expectedin the lower significantchanges in theTBBMD duringthestudyin eithergroupwhile dose of conjugatedestrogenregimen due to the lower uterine TBBMD decreased by 1% in the referencegroup. S-APHOS, a bleedingincidence. parameterthat reflects bone formation, decreasedmore in the Divigel group(p < 0.001)than in the Estradermgroup(p < 0.01).
PO11 EFFECT OF 12-MONTH DHEA REPLACEMENT THERAPY ON BONE MINERAL DENSITY IN 60- TO 70-YEAR-OLD WOMEN F Labrie, P Diamonrt, L Cusan, J L Gomez, A Belanger,
Laboratory of Molecular Endocrinology,CHUL ResearchCenter andLava1University, Quebec,Canada
PO12 LONG TERM EFFECTS OF KLIOGEST@ (KLIOFEMQ) ON BONE TURNOVER IN POSTMENOPAUSAL WOMEN D McKav Spowart,
Hart,
E Farish,
K Ekevall,
A Brown,
D Nolan,
K
MenopauseClinic, Stobhill NHS Trust and the WesternInfirmary, Glasgow,UK.
The effect of 1Zmonth DHEA replacementtherapy has been evaluatedin fifteen 60- to 70- year-old women who had daily 52 postmenopausal womenwerefollowedinitially in a double-blind, applicationsof a 10%DHEA cream. Vaginal epitheliummaturation randomised, parallelgroupstudy to examinethe effectsof addition/ wasstimulatedby DHEA administrationin 8 out of 10 womenwho withdrawal of oestriol on bone and lipid metabolismin the had a maturationvalue of zero at the onset of therapy while a continuouscombinedHRT, Kliogest(Kliofem, 170oestradiol,2 mg stimulatory effect was also seenin the three women who had and norethisteroneacetate, 1 mg). Patients were subsequently intermediatevaginalmaturationbeforetherapy. No estrogeniceffect followed in an open, prospectivestudy using Kliogest (Kliofem) of DHEA was observed in the endometriumwhich remained without oestriol.35 patientscompleted4 yrs of treatmentand 27 completely atrophic in all women treated with DHEA. Most patientswere ongoingat 10 yrs, when the meanage was44.6 yrs interestingly,bone mineral density increasedby 2.3% at the hip, (28-53 yrs). BMD determinationswere performedat 6 month 3.75%at the hip Ward’striangle,and2.2% at the lumbarspinelevel intervalsup to 10 yrs. No significantdifferenceswere found for (pcO.05at all sites). Thesechangesin bonemineraldensitywere BMD in the different groupsat baseline.Major increases in BMD associated with decreases at 12 monthsof 38%, 22%, and20% in were observedinitially, and remainedsignificant(p>O.O22)at all urinaryhydroxyproline,and N-telopeptides of type 1 bonecollagen, visits. Thisrepresented an increaseof up to 5% higherthanbaseline andplasmabonealkalinephosphatase, respectively(~~0.05for all lumbarspine(L2-L4) evenup to 10yrs. When statisticalmodelling effects). An increaseof 135% over control (pcO.05) in plasma wasappliedto investigatethe possibilityof a decrease following the osteocalcinwasconcomitantlyobserved.The presentdatadescribe initial rise in BMD, resultsshowedthe increasein BMD wasnot for the first time a seriesof medicallyimportantbeneficialeffectsof compromised overall.Theseobservationsdemonstrate the long term DHEA therapyin postmenopausal womenthroughtransformationof beneficialeffectsof Kliogest(Kliofem) in the preservationof bone the precursorsteroidDHEA without significantadverseeffects. The loss,thusaffordingprotectionagainstosteoporoticfracture. stimulatory effect on the vaginal epithelium in the absenceof stimulationof the endometriumeliminatesthe needfor progestin replacementtherapy. The stimulatory effects on bone mineral densityaccompanied by an increasein serumosteocalcin,a marker of boneformation,indicatestimulationof boneformationby DHEA, a finding of particularinterestfor both the preventionandtreatment ofosteoeorosis. 119
PO10
COMPARISON OF THE EFFECT OF DIVIGEL, A PERCUTANEOUS ESTRADIOL GEL AND ESTRADERM (TTS) TREATMENT ON TOTAL BODY BONE MINERAL DENSITY AND LIPID METABOLISM IN MENOPAUSE Kivinen, S*, Hirvonen, E 4 Wilen-Rosenqvist,
G*, Kanta-Hdme
CentralHospital*,, Hameenlinna,KalevankatuMedical Center n, Helsinki,Orion Pharma,Espoo*,Finland.
CONJUGATED ESTROGEN AT A DAILY DOSE OF 0.625 MG AND 0.3 MG HAD ALMOST THE SAME IMPACT ON THE CHANGES OF BONE MINERAL DENSITY AND BONE METABOLISM IN POSTMENOPAUSAL WOMEN. LT. Chen, K. Hasumi, E. Ogata
Departmentof Gynecology,CancerInstitute Hospital,Toshima-Ku, Tokyo, 170,Japan.
The effect of an estradiolgel (Divigel) anda transdermal therapeutic We comparedthe changesin bonemineraldensity andmetabolism system(TTS)(Estradermpatch) on total body bonemineraldensity treated by the two-year study of hormonereplacementtherapy (TBBMD) and lipid metabolismwas investigatedin an open, (HRT) with the two different dosesof conjugatedestrogen.40 controlled,parallel-groupstudy. 120 postmenopausal womenwere patientswithin 10 years after menopausewere divided into two allocatedat randomto the two treatmentgroupsfor twelve anda half groups;(A):E 0.625mg + medroxyprogesterone acetate(MPA) 2.5 months.60 patientsweretreatedwith 1.0 mg of estradiolgel daily. mg/day;20 cases,(B):E 0.3mg+ MPA 1.25mg/day;20 cases.We The gel wasappliedin the eveningon the skin of the lower trunk, measured L2-4BMD(DPXL;Lunar), E2, Ca, P, Al-p, belowthenavel, or on the skinof the thighs.61 patientsweretreated Osteocalcin(Cis) N-terminalosteocalcin(Teijin), intact osteocalcin with Estradermpatch of 50 yg/24 h, changedtwice a week. Both (Teijin), Urinary pyridinoline/Cr, deoxypyridinoline/Cr,before, 6, groupsreceiveddydrogesterone (Terolut) 1 0 mg daily for the first 12, 18 and 24 months after HRT. There were no statistical 12daysof everymonth. differencesin age,body massindex, postmenopausal periods, and Serumtriglycerides,total cholesterol,HDL-cholesterolandalkaline L2-4BMD before HRT. Betweenthe two groups, we found no phosphatase (s-APHOS) concentrationswere determinedfi-om all statisticaldifferences(mean+SE;A vs. B) in % baselineBMD patientsat the onsetof the study and at 12 months.(TBBMD) was changes(103.3+0.2; 103.2kO.9;6M, 104.1+0.7;104.6+1.1; 12M, measuredin both groupsfrom the first 30 includedpatientswith 106.350.7; 107.421.1; 24M), deoxypyridinoline/Cr (63.753.5; Lunar DBX dualphotonabsorptiometryat onsetof the study andat 58.8t3.8; 6M, 55.9i4.0; 59.025.5;12M, 52.522.4;57.2255; 24M), 6 and 12 months. Theseparameterswere alsomeasuredfrom a Al-p 87.5253; 81.724.3;6M, 79.4k5.7; 75.125.5; 12M, 79.8~4.5; referencegroupof 25 postmenopausal women. 76.7k6.1;24M). Incidenceof abnormaluterinebleedingwasmuch Total cholesterol decreased in bothtreatmentgroupsbut not statistically lessin B. Thesedata indicatedthat E at 0.625 mg and 0.3 mg/day significantly. HI&cholesterol and s-triglyceride concentrations hadalmostsameimpacton the changesof bonemineraldensityand remainedunchangedin both groups. There were no statistically metabolism, however,the bettercomplianceis expectedin the lower significantchanges in theTBBMD duringthestudyin eithergroupwhile dose of conjugatedestrogenregimen due to the lower uterine TBBMD decreased by 1% in the referencegroup. S-APHOS, a bleedingincidence. parameterthat reflects bone formation, decreasedmore in the Divigel group(p < 0.001)than in the Estradermgroup(p < 0.01).
PO11 EFFECT OF 12-MONTH DHEA REPLACEMENT THERAPY ON BONE MINERAL DENSITY IN 60- TO 70-YEAR-OLD WOMEN F Labrie, P Diamonrt, L Cusan, J L Gomez, A Belanger,
Laboratory of Molecular Endocrinology,CHUL ResearchCenter andLava1University, Quebec,Canada
PO12 LONG TERM EFFECTS OF KLIOGEST@ (KLIOFEMQ) ON BONE TURNOVER IN POSTMENOPAUSAL WOMEN D McKav Spowart,
Hart,
E Farish,
K Ekevall,
A Brown,
D Nolan,
K
MenopauseClinic, Stobhill NHS Trust and the WesternInfirmary, Glasgow,UK.
The effect of 1Zmonth DHEA replacementtherapy has been evaluatedin fifteen 60- to 70- year-old women who had daily 52 postmenopausal womenwerefollowedinitially in a double-blind, applicationsof a 10%DHEA cream. Vaginal epitheliummaturation randomised, parallelgroupstudy to examinethe effectsof addition/ wasstimulatedby DHEA administrationin 8 out of 10 womenwho withdrawal of oestriol on bone and lipid metabolismin the had a maturationvalue of zero at the onset of therapy while a continuouscombinedHRT, Kliogest(Kliofem, 170oestradiol,2 mg stimulatory effect was also seenin the three women who had and norethisteroneacetate, 1 mg). Patients were subsequently intermediatevaginalmaturationbeforetherapy. No estrogeniceffect followed in an open, prospectivestudy using Kliogest (Kliofem) of DHEA was observed in the endometriumwhich remained without oestriol.35 patientscompleted4 yrs of treatmentand 27 completely atrophic in all women treated with DHEA. Most patientswere ongoingat 10 yrs, when the meanage was44.6 yrs interestingly,bone mineral density increasedby 2.3% at the hip, (28-53 yrs). BMD determinationswere performedat 6 month 3.75%at the hip Ward’striangle,and2.2% at the lumbarspinelevel intervalsup to 10 yrs. No significantdifferenceswere found for (pcO.05at all sites). Thesechangesin bonemineraldensitywere BMD in the different groupsat baseline.Major increases in BMD associated with decreases at 12 monthsof 38%, 22%, and20% in were observedinitially, and remainedsignificant(p>O.O22)at all urinaryhydroxyproline,and N-telopeptides of type 1 bonecollagen, visits. Thisrepresented an increaseof up to 5% higherthanbaseline andplasmabonealkalinephosphatase, respectively(~~0.05for all lumbarspine(L2-L4) evenup to 10yrs. When statisticalmodelling effects). An increaseof 135% over control (pcO.05) in plasma wasappliedto investigatethe possibilityof a decrease following the osteocalcinwasconcomitantlyobserved.The presentdatadescribe initial rise in BMD, resultsshowedthe increasein BMD wasnot for the first time a seriesof medicallyimportantbeneficialeffectsof compromised overall.Theseobservationsdemonstrate the long term DHEA therapyin postmenopausal womenthroughtransformationof beneficialeffectsof Kliogest(Kliofem) in the preservationof bone the precursorsteroidDHEA without significantadverseeffects. The loss,thusaffordingprotectionagainstosteoporoticfracture. stimulatory effect on the vaginal epithelium in the absenceof stimulationof the endometriumeliminatesthe needfor progestin replacementtherapy. The stimulatory effects on bone mineral densityaccompanied by an increasein serumosteocalcin,a marker of boneformation,indicatestimulationof boneformationby DHEA, a finding of particularinterestfor both the preventionandtreatment ofosteoeorosis. 119