- Email: [email protected]
P248 Combined continuous hormonal replacement therapy (CC-HRT) influence of progestagen doses (PD) on bleeding (B) patterns of postmenopausal women (PW)
P245
P246
LONG-TERM ADMINISTRATION OF TIBOLONE IS NOT ASSOCIATED WITH ENDOMETRIAL PROLIFERATION
TIBOLONE: DOSE-RESPONSE ANALYSIS OF UTERINE BLEEDINGS IN A MULTICENTRE PLACEBOCONTROLLED STUDY
PM Kicovic(1) and TP RolIason(2). (1) Reprod Med Section, MRDU, NV Organon, Oss, The Netherlands and (2) Dept of Histopathology, Birmingham Maternity Hospital, Birmingham, UK.
PM Kicovictl), S Empelen(2), HJT Coelingh Bennink(l). (1) Reprod Med Section and (2) Dept of Biometrics, MRDU, NV Organon, Oss, The Netherlands.
Two previous studies have shown that tibolone (Tib, Livial) does not induce endometrial proliferation. The present prospective study with 150 postmenopausal women (PMW) in 6 centres, was undertaken to assess the long-term effect of Tib on the endometrium. PMW presenting with an atrophic/inactive endometrium or no curettings at pretreatment received one tablet of Tib (2.5 mg) daily for 2 years. Repeated endometrial biopsies (EB) at 1 and 2 years were done by Novak’s curette and specimens evaluated by means of light microscopy. Of 150 subjects, 85 discontinued the study - 22 of them for reasons related and 63 for reasons not related to the study; EB were obtained in 115 and 65 subjects at 1 and 2 years, respectively. Data obtained showed a lack of endometrial Occasional stimulation, thus confirming previous reports. proliferation was found at all 3 times of assessment, most likely being related to fluctuations in endogenous estrogens. In one subject with hyperplasia at pretreatment, the same was found at 1 year, while an atrophic pattern was diagnosed at 2 years. Uterine bleeding and/or spotting was reported by 18 subjects. In conclusion, Tib administered for 2 years did not display a stimulatory effect on the endometrium in PMW. This makes Tib attractive for long-term menopausal therapy.
In a large randomized, placebo-controlled study (770 subjects, 28 centres) of effects of 4 doses (0.625 mg, 1.25 mg, 2.5 mg and 5.0 mg) of tibolone (Tib, Livial) on menopausal symptoms, a doseresponse analysis of uterine bleedings (UB) was carried out. Demographic data at baseline showed the 5 groups to be well matched. Diary cards were used for the record of bleeding and/or spotting. The relationship between UB and factors as age, time since menopause (TSM), BMI and previous use of HRT was investigated. The dose-related trend was tested using the Mantel-Haenszel statistic with one degree of freedom. Each of the dose groups was compared with the placebo (Pl) group by means of a log-rank test. Prognostic factors were analyzed by stepwise linear logistic regression. Results show occurrence of UB as follows: Pl 13.9%, 0.625 mg 18.2%, 1.25 mg 19.0%, 2.5 mg 25.0% and 5.0 mg 46.2% suggesting a highly significant (p
P247
P248
BLEEDING RATES-DURING A LONG-TERM PLACEBOCONTROLLED STUDY WITH TWO DOSES OF TIBOLONE B Bernin&& PM Kicovic(;Z), BCJM Fauserfl), HJT Coelingh Bennink(2). (l)Dept of Obs/Gyn, Dijkzigt University Hospital, Rotterdam, The Netherlands, (2)Reprod Med Section, MRDU, NV Organon, Oss, The Netherlands. Withdrawal bleedings during sequential regimens are among the main reasons for poor acceptance of long-term HRT. Tibolone (Tib, Livial) has no stimulant effect on endometrium and, therefore, addition of progestogen is obviated. In a 2-year placebo-controlled study 94 women, 1-3 years postmenopausal, were randomized to Tib 2.5 mg/d (n=35), Tib 1.25 mg/d (n=36) or placebo (Pl; n=23) to study effects on the skeleton. We report herewith on occurrence of uterine bleedings (UB). The chi-square test and test for linear trend were used to compare the 3 groups. Frequency distribution and number/percentage of women with UB/12 weeks were tabulated per group. Curettings obtained by D&C were evaluated histologically. Occurrence of UB during the 2-year study period was as follows: Tib 2.5 mg 18 (51.4%), Tib 1.25 mg 16 (44.4%) and Pl 5 (21.7%). Most UB started within 36 weeks of treatment. These bleedings were not perceived as disturbing since only one subject dropped out due to UB. In women that experienced UB, histological evaluation showed no curetting in 20, atrophic pattern in 12 and slight proliferation in 4 specimens (2 in Tib 1.25 mg and 2 in Pl group). In conclusion, UB occurred in all 3 groups, mostly from an atrophic endometrium. Occasional slight proliferation is related to residual endogenous estrogens.
COMBINED CONTINUOUS HORMONAL REPLACEMENT THERAPY (CC-HRT) INFLUENCE OF PROGESTAGEN DOSES (PD) ON BLEEDING (B) PATTERNS OF POSTMENOPAUSAL WOMEN (PW). D Rodripuez Vidal, M Martino, M Paciocco, M Aguirre, E Gil Deza, A Mirkin. Department of Climateric & Gynecology. School of Medicine. Rosario. Argentina. The aim of this randomized crossover study was to evaluate the influence of PD on B patems in PW treated with a CCHRT regimen with two different opposed PD. 99 PW were randomized in two groups: a=49 mean age 53,5 and b=50 mean age 52,3. All PW received two courses of 6 months CC-HRT, with one month washout period between them. All PW received fixed-doses of 17b estradiol (E2) Zmg/day in both periods. Medroxyprogesterone acetate (MAP) was given as follows: a: 5mg followed by 2,5mg (ala2) or b: 2,5mg followed by 5mg (bl-b2). The Body Mass Index (BMI) was calculated at 0-12months and B score was used to evaluate the B patems at 6-12 months. Endometrial biopsies were performed at O-6-12 month. Wilcoxon test was used for statistical analysis. Results: 14199patients (14.1%) withdrawn before starting the 2nd course, 6/14 due to unacceptable B (a=1 and b=5). B intensity (score 2-5) was increased with MAP 2.5mg (p=O.O023). B frequency was increased also on MAP 2.5mg (bl-a2), but without statisticalsignificancein the wholegroup. In a subsetof PW with BMI >= 25 there were more frequencyof B (69 vs 22 p=O.O06) without relationshipwith MAP doses. Continued
193
P248 (cord)
P249 THE EFFECT FIBROUS
4-5: > mfalstma period o-1 5 VI 2.5 K” 0.012
OF TIBOLONE @VIAL} IN POST~NOPAUSAL
ON UTERINE WOMEN.
0. Greporiou, C. Papadias, S. Konidaris, N. Vitoratos, V. Antonaki, D. Costometros 2nd Departmentof Obstetricsand Gynecology Athens Unive~i~ “Areteion” Hospital,Athens,Greece.
16 O-l VJ 2-3 VI 44 in 5 vs 2.5 P” 0.023
Regardingendometrialbiopsies,40/49 in group al and 39150in group bl shown atrophic epitheliumbefore treatment. After 1st course.9140in al and 17139in bl changedto trophic morphology (p= 0.045). After 2nd course 6 patients in each group(aZb2) changedto trophicmorphology(p=NS). In conclusion1) 5 mg MAP duringCC-HRT appearsto be more~propriate in orderto decrease B intensity and to support endometriumatrophia. 2) PW with BMI>=25 seems to increaseB occurrency.
P250
Tibolone (Livial) is a synthetic steroid that exhibits estrogenic, progestagenic and androgenicactivity. It is given continuouslyfor the relief of menopausal symptoms.However,prescribingLivial to postmenopausal womenwith uterinefibroids is a dilemma,because the commonbelief is that uterine fibroids tend to grow after exposureto estrogenandprogesterone. The purposeof our study was to evaluatethe elect of Livial on uterinefibroidsin postmenopausal women. The study included20 naturally postmenopausal womenwith small asymptomaticuterine fibroids. All of them were scannedby tr~svaginal ul~~onography. Pos~enopausalstatuswasdefinedas a minimumperiodof 1 l/2 to 2 yearsof amennorhea.All patients weretreatedwith tibolonefor a periodof oneyear andon the endof the treatmentthe size of the uterine fibroids was reevaluated ultrasonographically. No statisticallysignificantdifferencewasfound, suggesting thusthat treating menopausalsymptomswith tiboione does not affect preexistingasymptomatic uterinefibroids.
P251
VAGINAL SQNOGRAPHY OF THE ENDOMETRIUM IN POSTMENOPAUSAL WOMEN ON TILOBONE OR LOWDOSE ESTROGEN TREATMENT : A COMPARISON.
TRANSVAGINAL ULTRASOUND AND TRANSVAGINAL ~STEROSONOG~~ (SALINE IN~SIO~ IN THE EVALUATION OF THE E~OME~M IN FIBROID UTERUS
Boais D. , K~~an~~ D. , K~~g~rouA , Anton&m G., ViforafosN., Anton&w D. 2nd Departmentof Obstetricsand Gynecology Athens University “Areteion” Hospital,Athens,Greece. A six monthcomparativerandomisedprospectivestudy to compare the efftcacy of locally administeredlow-doseestrogens,and orally administeredtibolone in post menopausalwomen with signs of atrophicvaginitis. Transvaginalultrasonography wasperformedfor the evaluationof endometrialor ovarianabnormalities.Seventytwo postmenopausal womenwith symptomsof atrophicvaginitis were examinedwith transvaginalultrasound.The endometrialthickness, the endometrialvolume, the uterusand the ovariesweremeasured before andafter 6 monthsof detent with low-doseestrogensor tibolone. In group A (low dose estrogenstreatment)the mean endometrialthickness,before and after treatment,was 3.MO.l mm and 2.wO.8 mm, respectively. The meanovarianvolumewas 3.9 ml. There were no changesin uterinevolume during the reagent period. In groupB (treatedwith tibolone)endometrialthicknesswas 3.2a.3 mmand3.20.7 mmrespectively. Two womenexperienced vaginalbleeding. The volume of corpusuteri wasunchangedafter treatment. The volume of both ovaries waw 4.2 ml and 3.9 ml respectively. Our study, using transvaginalultrasonography,has shownthat either hormonereplacementtherapy with tibolone or s~ptomatic treatmentwith low doseestrogens,gives no sign of endometrialproliferationmeasured asendometrialthickness.
G Surko~~,G Kubersz-Adamska, JSuzin MadurowiczHospital,Medical University Of Lodz (Lodz), Institute of obstetricsandGynecology,UltrasoundDepartment,Lddz (Lodz) 94-029,37Wilenskastreet,Poland If we providetransvaginalsonographyexaminationto womanwith uterine fibroids we can have problemswith preciseevaluationof endometrium.Thereis possibilityto makeit muchmoreprecise- if wehavefluid in the uterinecavity. Usuallyit is not a big problemto makesalineinfusionby specialcatheterinto the endometrialcavity. In our results(83 women)sometimes we had big differencesin widthness and echogenicity of endometrium in transvaginal ul~ound beforeand after salinein~sion. I think that this is the answerwhy sometimes previouslywe have seenabnormallywide endometrium duringthe transvaginalultrasound,decidedto provide hysteroscopyand D&C and sometimes there was no pathology sometimeswe measured and evaluated not endome~ium. Transvaginalhysterosonography gives us possibility not only to measurepreciselythe width of the endometriumbut to evaluate contentsof uterinecavity aswell, for examplepolyps, submuco~ fibroids,irregular,inhomogenous masses.
194
P246
LONG-TERM ADMINISTRATION OF TIBOLONE IS NOT ASSOCIATED WITH ENDOMETRIAL PROLIFERATION
TIBOLONE: DOSE-RESPONSE ANALYSIS OF UTERINE BLEEDINGS IN A MULTICENTRE PLACEBOCONTROLLED STUDY
PM Kicovic(1) and TP RolIason(2). (1) Reprod Med Section, MRDU, NV Organon, Oss, The Netherlands and (2) Dept of Histopathology, Birmingham Maternity Hospital, Birmingham, UK.
PM Kicovictl), S Empelen(2), HJT Coelingh Bennink(l). (1) Reprod Med Section and (2) Dept of Biometrics, MRDU, NV Organon, Oss, The Netherlands.
Two previous studies have shown that tibolone (Tib, Livial) does not induce endometrial proliferation. The present prospective study with 150 postmenopausal women (PMW) in 6 centres, was undertaken to assess the long-term effect of Tib on the endometrium. PMW presenting with an atrophic/inactive endometrium or no curettings at pretreatment received one tablet of Tib (2.5 mg) daily for 2 years. Repeated endometrial biopsies (EB) at 1 and 2 years were done by Novak’s curette and specimens evaluated by means of light microscopy. Of 150 subjects, 85 discontinued the study - 22 of them for reasons related and 63 for reasons not related to the study; EB were obtained in 115 and 65 subjects at 1 and 2 years, respectively. Data obtained showed a lack of endometrial Occasional stimulation, thus confirming previous reports. proliferation was found at all 3 times of assessment, most likely being related to fluctuations in endogenous estrogens. In one subject with hyperplasia at pretreatment, the same was found at 1 year, while an atrophic pattern was diagnosed at 2 years. Uterine bleeding and/or spotting was reported by 18 subjects. In conclusion, Tib administered for 2 years did not display a stimulatory effect on the endometrium in PMW. This makes Tib attractive for long-term menopausal therapy.
In a large randomized, placebo-controlled study (770 subjects, 28 centres) of effects of 4 doses (0.625 mg, 1.25 mg, 2.5 mg and 5.0 mg) of tibolone (Tib, Livial) on menopausal symptoms, a doseresponse analysis of uterine bleedings (UB) was carried out. Demographic data at baseline showed the 5 groups to be well matched. Diary cards were used for the record of bleeding and/or spotting. The relationship between UB and factors as age, time since menopause (TSM), BMI and previous use of HRT was investigated. The dose-related trend was tested using the Mantel-Haenszel statistic with one degree of freedom. Each of the dose groups was compared with the placebo (Pl) group by means of a log-rank test. Prognostic factors were analyzed by stepwise linear logistic regression. Results show occurrence of UB as follows: Pl 13.9%, 0.625 mg 18.2%, 1.25 mg 19.0%, 2.5 mg 25.0% and 5.0 mg 46.2% suggesting a highly significant (p
P247
P248
BLEEDING RATES-DURING A LONG-TERM PLACEBOCONTROLLED STUDY WITH TWO DOSES OF TIBOLONE B Bernin&& PM Kicovic(;Z), BCJM Fauserfl), HJT Coelingh Bennink(2). (l)Dept of Obs/Gyn, Dijkzigt University Hospital, Rotterdam, The Netherlands, (2)Reprod Med Section, MRDU, NV Organon, Oss, The Netherlands. Withdrawal bleedings during sequential regimens are among the main reasons for poor acceptance of long-term HRT. Tibolone (Tib, Livial) has no stimulant effect on endometrium and, therefore, addition of progestogen is obviated. In a 2-year placebo-controlled study 94 women, 1-3 years postmenopausal, were randomized to Tib 2.5 mg/d (n=35), Tib 1.25 mg/d (n=36) or placebo (Pl; n=23) to study effects on the skeleton. We report herewith on occurrence of uterine bleedings (UB). The chi-square test and test for linear trend were used to compare the 3 groups. Frequency distribution and number/percentage of women with UB/12 weeks were tabulated per group. Curettings obtained by D&C were evaluated histologically. Occurrence of UB during the 2-year study period was as follows: Tib 2.5 mg 18 (51.4%), Tib 1.25 mg 16 (44.4%) and Pl 5 (21.7%). Most UB started within 36 weeks of treatment. These bleedings were not perceived as disturbing since only one subject dropped out due to UB. In women that experienced UB, histological evaluation showed no curetting in 20, atrophic pattern in 12 and slight proliferation in 4 specimens (2 in Tib 1.25 mg and 2 in Pl group). In conclusion, UB occurred in all 3 groups, mostly from an atrophic endometrium. Occasional slight proliferation is related to residual endogenous estrogens.
COMBINED CONTINUOUS HORMONAL REPLACEMENT THERAPY (CC-HRT) INFLUENCE OF PROGESTAGEN DOSES (PD) ON BLEEDING (B) PATTERNS OF POSTMENOPAUSAL WOMEN (PW). D Rodripuez Vidal, M Martino, M Paciocco, M Aguirre, E Gil Deza, A Mirkin. Department of Climateric & Gynecology. School of Medicine. Rosario. Argentina. The aim of this randomized crossover study was to evaluate the influence of PD on B patems in PW treated with a CCHRT regimen with two different opposed PD. 99 PW were randomized in two groups: a=49 mean age 53,5 and b=50 mean age 52,3. All PW received two courses of 6 months CC-HRT, with one month washout period between them. All PW received fixed-doses of 17b estradiol (E2) Zmg/day in both periods. Medroxyprogesterone acetate (MAP) was given as follows: a: 5mg followed by 2,5mg (ala2) or b: 2,5mg followed by 5mg (bl-b2). The Body Mass Index (BMI) was calculated at 0-12months and B score was used to evaluate the B patems at 6-12 months. Endometrial biopsies were performed at O-6-12 month. Wilcoxon test was used for statistical analysis. Results: 14199patients (14.1%) withdrawn before starting the 2nd course, 6/14 due to unacceptable B (a=1 and b=5). B intensity (score 2-5) was increased with MAP 2.5mg (p=O.O023). B frequency was increased also on MAP 2.5mg (bl-a2), but without statisticalsignificancein the wholegroup. In a subsetof PW with BMI >= 25 there were more frequencyof B (69 vs 22 p=O.O06) without relationshipwith MAP doses. Continued
193
P248 (cord)
P249 THE EFFECT FIBROUS
4-5: > mfalstma period o-1 5 VI 2.5 K” 0.012
OF TIBOLONE @VIAL} IN POST~NOPAUSAL
ON UTERINE WOMEN.
0. Greporiou, C. Papadias, S. Konidaris, N. Vitoratos, V. Antonaki, D. Costometros 2nd Departmentof Obstetricsand Gynecology Athens Unive~i~ “Areteion” Hospital,Athens,Greece.
16 O-l VJ 2-3 VI 44 in 5 vs 2.5 P” 0.023
Regardingendometrialbiopsies,40/49 in group al and 39150in group bl shown atrophic epitheliumbefore treatment. After 1st course.9140in al and 17139in bl changedto trophic morphology (p= 0.045). After 2nd course 6 patients in each group(aZb2) changedto trophicmorphology(p=NS). In conclusion1) 5 mg MAP duringCC-HRT appearsto be more~propriate in orderto decrease B intensity and to support endometriumatrophia. 2) PW with BMI>=25 seems to increaseB occurrency.
P250
Tibolone (Livial) is a synthetic steroid that exhibits estrogenic, progestagenic and androgenicactivity. It is given continuouslyfor the relief of menopausal symptoms.However,prescribingLivial to postmenopausal womenwith uterinefibroids is a dilemma,because the commonbelief is that uterine fibroids tend to grow after exposureto estrogenandprogesterone. The purposeof our study was to evaluatethe elect of Livial on uterinefibroidsin postmenopausal women. The study included20 naturally postmenopausal womenwith small asymptomaticuterine fibroids. All of them were scannedby tr~svaginal ul~~onography. Pos~enopausalstatuswasdefinedas a minimumperiodof 1 l/2 to 2 yearsof amennorhea.All patients weretreatedwith tibolonefor a periodof oneyear andon the endof the treatmentthe size of the uterine fibroids was reevaluated ultrasonographically. No statisticallysignificantdifferencewasfound, suggesting thusthat treating menopausalsymptomswith tiboione does not affect preexistingasymptomatic uterinefibroids.
P251
VAGINAL SQNOGRAPHY OF THE ENDOMETRIUM IN POSTMENOPAUSAL WOMEN ON TILOBONE OR LOWDOSE ESTROGEN TREATMENT : A COMPARISON.
TRANSVAGINAL ULTRASOUND AND TRANSVAGINAL ~STEROSONOG~~ (SALINE IN~SIO~ IN THE EVALUATION OF THE E~OME~M IN FIBROID UTERUS
Boais D. , K~~an~~ D. , K~~g~rouA , Anton&m G., ViforafosN., Anton&w D. 2nd Departmentof Obstetricsand Gynecology Athens University “Areteion” Hospital,Athens,Greece. A six monthcomparativerandomisedprospectivestudy to compare the efftcacy of locally administeredlow-doseestrogens,and orally administeredtibolone in post menopausalwomen with signs of atrophicvaginitis. Transvaginalultrasonography wasperformedfor the evaluationof endometrialor ovarianabnormalities.Seventytwo postmenopausal womenwith symptomsof atrophicvaginitis were examinedwith transvaginalultrasound.The endometrialthickness, the endometrialvolume, the uterusand the ovariesweremeasured before andafter 6 monthsof detent with low-doseestrogensor tibolone. In group A (low dose estrogenstreatment)the mean endometrialthickness,before and after treatment,was 3.MO.l mm and 2.wO.8 mm, respectively. The meanovarianvolumewas 3.9 ml. There were no changesin uterinevolume during the reagent period. In groupB (treatedwith tibolone)endometrialthicknesswas 3.2a.3 mmand3.20.7 mmrespectively. Two womenexperienced vaginalbleeding. The volume of corpusuteri wasunchangedafter treatment. The volume of both ovaries waw 4.2 ml and 3.9 ml respectively. Our study, using transvaginalultrasonography,has shownthat either hormonereplacementtherapy with tibolone or s~ptomatic treatmentwith low doseestrogens,gives no sign of endometrialproliferationmeasured asendometrialthickness.
G Surko~~,G Kubersz-Adamska, JSuzin MadurowiczHospital,Medical University Of Lodz (Lodz), Institute of obstetricsandGynecology,UltrasoundDepartment,Lddz (Lodz) 94-029,37Wilenskastreet,Poland If we providetransvaginalsonographyexaminationto womanwith uterine fibroids we can have problemswith preciseevaluationof endometrium.Thereis possibilityto makeit muchmoreprecise- if wehavefluid in the uterinecavity. Usuallyit is not a big problemto makesalineinfusionby specialcatheterinto the endometrialcavity. In our results(83 women)sometimes we had big differencesin widthness and echogenicity of endometrium in transvaginal ul~ound beforeand after salinein~sion. I think that this is the answerwhy sometimes previouslywe have seenabnormallywide endometrium duringthe transvaginalultrasound,decidedto provide hysteroscopyand D&C and sometimes there was no pathology sometimeswe measured and evaluated not endome~ium. Transvaginalhysterosonography gives us possibility not only to measurepreciselythe width of the endometriumbut to evaluate contentsof uterinecavity aswell, for examplepolyps, submuco~ fibroids,irregular,inhomogenous masses.
194