- Email: [email protected]
F019 A longitudinal, comparative study of the effect of kliogest and livial on plasma lipids in post-menopausal women
F017 ADVERSE CYCLE
F017 (cant) ENDOMETRIAL EFFECTS HORMONE REPLACEMENT
DURING LONG THERAPY
A. Cerin, K. Bjarnason, K. Heldaas, H. Klem Thomsen, B. Moelier, Depts of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden, Telemark Central Hospital, Porsgrunn, Norway, Novo Nordisk A/S, Bagsvaerd, Denmark, Institute of Pathology, Bispbjerg Hospital, Denmark, Dept of Obstetrics and Gynecology, Odense Hospital, Denmark. On behalf of the Scandinavian Long Cycle Study Group Different Long Cycle HRT regimens where progestogens are administered less than monthly are used in clinical practice. The study was an open, randomised, prospective multicenter trial comprising 240 healthy, early postmenopausal women. 120 of them received HRT with a daily dose of 2 mg 17R estradiol (E2) and with an extended cycle of 84 days ended by addition of Img norethisterone acetate (NETA) for IO days and reduced E2 (1 mg) for another 6 days. 120 women received the reference drug Trisequens, Novo Nordisk A/S, i.e. the same regimen and progestogen dose but with a 28 day cycle. The planned duration of treatment was 5 years. Endometrial biopsies were obtained prior to therapy and once a year during the last four days of progestogen addition. All endometrial biopsies were analysed by one experienced pathologist blinded to treatment.
Preliminary results of the endometrial biopsies during 2-3 years of treatment showed 8 simple and 5 complex hyperplasias, one complex hyperplasia with atypia and one endometrial cancer in the Long Cycle group, whereas in the Trisequens group one simple and one complex hyperplasia were recorded. The total incidence of endometrial hyperplasia, atypia. and cancer was significantly higher in the Long Cycle group (P=O.O038, exact Kruskal-Wallis test). The trial had to be discontinued due to a dissatisfactory endometrial safety profile. We conclude that caution using Long Cycle HRT regimens is advisable. Careful monitoring of the endometrium during treatment is recommended.
Continued
F018
F019
INTERNATIONAL LONG-TERM RANDOMISED CONTROLLED TRIAL OF HORMONE REPLACEMENT THERAPY - UK FEASIBILITY STUDY M R Vickers, T W Meade, H C Wilkes, MRC Epidemiology and Medical Care Unit, Charterhouse London EC I M 6BQ, UK.
A LONGITUDINAL, COMPARATIVE EFFECT OF KLIOGEST AND LIVIAL IN POST-MENOPAUSAL
Square,
The balance of risks and benefits of long-term hormone replacement therapy (HRT) needs to be established through randomised controlled trials. Pilot studies in the UK (and other countries) have determined recruitment and withdrawal rates and addressed the practicalities of conducting a full multi-centre trial. 830 post-menopausal women were recruited from 18 general practices and two hospital clinics. Initially, two approaches were piloted and then combined into a single design. Women with a uterus were randomised to combined oestrogen and cyclical progestogen or placebo, hysterectomised women to oestrogen alone, combined oestrogen and cyclical progestogen or placebo. Hysterectomised women definitely wishing to take HRT were randomised to oestrogen alone or combined oestrogen and cyclical progestogen. Around 50% of those invited for screening attended and one-third of those eligible entered the trial. Without a run-in period early withdrawal rates were fairly high, 18% at six months and 35% at three yew. but have been taken into account in sample size calculations. Many, women with a uterus withdrew because of the return of periods which will be avoided in a main trial by using a continuous combined preparation. The pilot studies show a full-scale trial to be feasible. A trial involving 34.000 women treated for ten years is proposed. the main outcomes being cardiovascular disease, f?actures and breast cancer. Funding for the UK contribution of 18.000 women has been approved by the UK Medical Research Council. lnternational collaborators are seeking funding. 48
STUDY OF THE ON PLASMA LIPIDS WOMEN.
B. L.Shemard, N. O’Keeffe, M. Joyce, LA. Norris and J. Bonnar. University Dept. Obstetrics & Gynaecology, Trinity College Centre, St. James’s Hospital and Coombe Women’s Hospital, Dublin 8, Ireland. HRT in the menopause may modify the risk of coronary heart disease by altering plasma lipid concentrations. We report here on plasma triglycerides, total cholesterol, HDL, LDL, VLDL, apolipoprotein (a) and lipoprotein (a) measured in 80 postmenopausal women prior to and following 3, 6 and 12 months randomly allocated treatment with either 2mg 17-beta-oestradiol + Img norethisterone (Kliogest) or 2.5mg tibolone (Livial). Treatment reduced circulating lipid levels within three months with a reduction in total cholesterol, HDL, LDL and apolipoprotein (a) occurring with both preparations. Significant differences between treatment with Kliogest and Livial were seen in levels of HDL (p=O.O036) and apolipoprotein (a) (p=O.OOOl). Overall these changes show an improved lipid profile in women on Kliogest and Livial.
F017 (cant) ENDOMETRIAL EFFECTS HORMONE REPLACEMENT
DURING LONG THERAPY
A. Cerin, K. Bjarnason, K. Heldaas, H. Klem Thomsen, B. Moelier, Depts of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden, Telemark Central Hospital, Porsgrunn, Norway, Novo Nordisk A/S, Bagsvaerd, Denmark, Institute of Pathology, Bispbjerg Hospital, Denmark, Dept of Obstetrics and Gynecology, Odense Hospital, Denmark. On behalf of the Scandinavian Long Cycle Study Group Different Long Cycle HRT regimens where progestogens are administered less than monthly are used in clinical practice. The study was an open, randomised, prospective multicenter trial comprising 240 healthy, early postmenopausal women. 120 of them received HRT with a daily dose of 2 mg 17R estradiol (E2) and with an extended cycle of 84 days ended by addition of Img norethisterone acetate (NETA) for IO days and reduced E2 (1 mg) for another 6 days. 120 women received the reference drug Trisequens, Novo Nordisk A/S, i.e. the same regimen and progestogen dose but with a 28 day cycle. The planned duration of treatment was 5 years. Endometrial biopsies were obtained prior to therapy and once a year during the last four days of progestogen addition. All endometrial biopsies were analysed by one experienced pathologist blinded to treatment.
Preliminary results of the endometrial biopsies during 2-3 years of treatment showed 8 simple and 5 complex hyperplasias, one complex hyperplasia with atypia and one endometrial cancer in the Long Cycle group, whereas in the Trisequens group one simple and one complex hyperplasia were recorded. The total incidence of endometrial hyperplasia, atypia. and cancer was significantly higher in the Long Cycle group (P=O.O038, exact Kruskal-Wallis test). The trial had to be discontinued due to a dissatisfactory endometrial safety profile. We conclude that caution using Long Cycle HRT regimens is advisable. Careful monitoring of the endometrium during treatment is recommended.
Continued
F018
F019
INTERNATIONAL LONG-TERM RANDOMISED CONTROLLED TRIAL OF HORMONE REPLACEMENT THERAPY - UK FEASIBILITY STUDY M R Vickers, T W Meade, H C Wilkes, MRC Epidemiology and Medical Care Unit, Charterhouse London EC I M 6BQ, UK.
A LONGITUDINAL, COMPARATIVE EFFECT OF KLIOGEST AND LIVIAL IN POST-MENOPAUSAL
Square,
The balance of risks and benefits of long-term hormone replacement therapy (HRT) needs to be established through randomised controlled trials. Pilot studies in the UK (and other countries) have determined recruitment and withdrawal rates and addressed the practicalities of conducting a full multi-centre trial. 830 post-menopausal women were recruited from 18 general practices and two hospital clinics. Initially, two approaches were piloted and then combined into a single design. Women with a uterus were randomised to combined oestrogen and cyclical progestogen or placebo, hysterectomised women to oestrogen alone, combined oestrogen and cyclical progestogen or placebo. Hysterectomised women definitely wishing to take HRT were randomised to oestrogen alone or combined oestrogen and cyclical progestogen. Around 50% of those invited for screening attended and one-third of those eligible entered the trial. Without a run-in period early withdrawal rates were fairly high, 18% at six months and 35% at three yew. but have been taken into account in sample size calculations. Many, women with a uterus withdrew because of the return of periods which will be avoided in a main trial by using a continuous combined preparation. The pilot studies show a full-scale trial to be feasible. A trial involving 34.000 women treated for ten years is proposed. the main outcomes being cardiovascular disease, f?actures and breast cancer. Funding for the UK contribution of 18.000 women has been approved by the UK Medical Research Council. lnternational collaborators are seeking funding. 48
STUDY OF THE ON PLASMA LIPIDS WOMEN.
B. L.Shemard, N. O’Keeffe, M. Joyce, LA. Norris and J. Bonnar. University Dept. Obstetrics & Gynaecology, Trinity College Centre, St. James’s Hospital and Coombe Women’s Hospital, Dublin 8, Ireland. HRT in the menopause may modify the risk of coronary heart disease by altering plasma lipid concentrations. We report here on plasma triglycerides, total cholesterol, HDL, LDL, VLDL, apolipoprotein (a) and lipoprotein (a) measured in 80 postmenopausal women prior to and following 3, 6 and 12 months randomly allocated treatment with either 2mg 17-beta-oestradiol + Img norethisterone (Kliogest) or 2.5mg tibolone (Livial). Treatment reduced circulating lipid levels within three months with a reduction in total cholesterol, HDL, LDL and apolipoprotein (a) occurring with both preparations. Significant differences between treatment with Kliogest and Livial were seen in levels of HDL (p=O.O036) and apolipoprotein (a) (p=O.OOOl). Overall these changes show an improved lipid profile in women on Kliogest and Livial.