- Email: [email protected]
F099 metabolic effects of 12-month percutaneous DHEA replacement therapy in postmenopausal women
F097
F098
EFFECT OF HORMONE REPLACEMENT ON INSULIN SENSITIVITY IN WOMEN AFTER OOPHORECTOMY, R N Roberts, M A Lumsden, J Petlie*, S Monaghan, J M C Connell *, Departments of Obstetrics and Gynaecology and Medicine and Therapeutics*, University of Glasgow, UK.
EFFECTS OF ORAL OR T~NSDERMAL O~ST~DIOL COMBINED WITH CYCLICAL ORAL NORETHISTERONE ACETATE ON INSULIN AND GLUCOSE METABOLISM IN POSTMENOPAUSAL WOMEN CPSorncer, I F Godsland,AJ Cooper,D Ross,MI Whitehead,JC Stevenson, Wynn Division of Metabolic Medicine, Imperial College,London, NW8 9SQ,UK.
The incidenceof cardiovascular disease in women rises sharply after the menopause. Insulin resistance is a risk factor for cardiovascular disease Few data exist on the effects of postmenopausal HRT on which is all&ted by sex steroid concentrations. The aim of the study was to determinethe effect on insulinsensitivityof transdermal oestradiol, carbohydratemetabolism.We have comparedthe effects of oral alone and combinedwith no~~istemne,in healthywomenalter a 178-oestradiolwith cyclical oral NETA (TrisequensB) and with cyclical oral NETA (Es~pak~) surgicalmenopau~. Fourteenwomenentereda randomised, double- tr~sde~al 17R-oes~adiol blind, placebo-controlled study 3-6 weeksafter hysterectomyand over 12 months.intravenousglucosetolerancetests(IVGTTs) were bilatemloophorectomy.They receivedeither transdermal oestradiol performedat baseline,46 weeks (oestrogen-onlyphase)and 48 5Ong(E2) or placebopatches.After 6 weeksa secondrandomisation weeks(combinedphase). Mathematicalmodellinganalysisof the of insulin allocatedthemto receiveE2 combinedwith oral norethisterone 5mg IVGTT concentrationprofileswasusedto derive measures @JET)or a placebo tablet(Ptac)for a further6 weeks.Theythen‘crossed sensitivity, pancreaticinsulin secretionand the amountof newly over to receivethe oppositetherapy. H~erinsulinaemic, eugly~emi~ secretedinsulintaken up by the liver. A prelimin~ analysiswas clampswereperformedat initial~domisation(Basal)andaftereach6 unde~~enof 44 womencompIetingthe study. In womentaking TrisequensO(n=20), there was a 38% increase weektreatmentperiod. The meanage of the womenwas 42.9 years (range32-49) mean (~~0.05) in insulin sensitivity in the oestrogen-onlyphase. There body massindex was25 kg/m2(range20 - 30 ) Insulin sensitivity wasno changein insulin secretionand a 35% increase(p=O.Ol) in was expressedas the weight-correctedmeansteady-stateglucose the amountof newly secretedinsulintakenup by the liver. Addition of NETA diminishedthe improvementin insulinsensitivity. In the infusionrate M rn~k~hr (~ean~SEM). womentaking Es~apak~ (n=24), there was no changein insulin Basal Placebo E2+Plac Ez+NET E2 sensitivitybut insulinsecretionwasincreasedby 48% (~4.01) and (n=14) (n=6) (r-i=81 (n=121 (ik1Z.f a.0 kO.5 7.7 +0.6 8.5 k0.9 8.5 20.5 7.8 f0.7. uptakeof newly secretedinsulinby the liver wasincreasedby 17% In this pilot study neither E2 nor E2+NET had any statistically (p=O.O5).Addition of NETA hadlittle effect onthesechanges. andEstrapako. significanteffect on insulinsensitivity. A largerstudy is underway Insulineliminationis improvedwith bothTrisequens@ Insulinsensitivityis improvedduring the oestrogen-onlyphaseof to investigatethe underlyingtrends. Trisequens@ therapy. Thesechangesare consistentwith a reduced risk of arteriafdisease.
F099
FlOO
METABOLIC EFFECTS OF 12”MONTH PERCUTANEOUS DHEA REPLACEMENT THERAPY IN POSTMENOPAUSAL WOMEN
THE INFLUENCE OF POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY ON BODY COMPOSITION
P Diamond?L Casart, J L Gomez, A B&anger and F Lab& Laboratory of Molecular Endocrinology and Clinical Endocrine ResearchUnit, CHUL ResearchCenter and Lava] University, Quebec,CanadaG1V 4G2
W ~~n~gi (0, R L~puner~2~~F ~orber~3~,MH Birkh~aser~~,P Jdiger(2). (l)Departmentof Obstetricsand Gynecology and (2)Policlinic of Medicine, University of Bern, Bern, and (3)Schlossklinik, Mammem,Switzerland.
We have evaluatedthe effect of dehydroepi~drosterone (DHEA) We comparedthe effects on body compositionof two types of replacement therapyin GO-70-ye~~ldwomen(N-15) who receiveda conventionalHRT with that of tibolone, a sex steroidwith mixed singledaily percutaneous applicationof a 10%DHEA creamfor 12- estrogenic, progestogenic and mild androgenic activity. month.Whileanthropometric measurements showednochangein body Postmenopausal womenwere enrolled in (1) a control group, or weight.weobserveda 9.8%decrease in subcutaneous skinfoldthickness randomizedto (2) tibolone2.5 mg/day,(3) oral micronizedestradiol at 12months(pcO.05).Thiswasconfirmedby measurements of midthigh (E2) 2 mg/dayplussequentialdydrogesterone (DYD) IO mg/dayfor fat andmuscleareasby computedtomographywherea 3.8%decrease 14of 28 days,or (4) transdermal E2 patchreleasing50 mcgidayplus (pcO.05)in femoralfat and a 3.5%increase (~~0.05)in femoralmuscular oral sequentialDYD 10 mglday for I4 of 28 days. Body areaswereobserved at 12months.Thesechanges wereassociated with a compositionwas measuredat baselineand every 6 monthsfor 2 1I% decrease (~~0.05)in fastingplasmaglucoseanda 17%decrease yearsby DXA (Hologic QDR IOOOW).‘Total body fat mass(TBF) (~~0.05)in fastinginsulinlevels.An overalltrendtowardsa decrease in increased(~~0.05)in controls(+3.6*1.5%) and in the transdermal totalcholesterol anditslipoproteintractionswasobserved.Theindexof I$ group (+4.7*2.2%) but not in the oral E2 (-1.2*2.4%) and Tib sehumsecretion showeda 73%increase (p
F098
EFFECT OF HORMONE REPLACEMENT ON INSULIN SENSITIVITY IN WOMEN AFTER OOPHORECTOMY, R N Roberts, M A Lumsden, J Petlie*, S Monaghan, J M C Connell *, Departments of Obstetrics and Gynaecology and Medicine and Therapeutics*, University of Glasgow, UK.
EFFECTS OF ORAL OR T~NSDERMAL O~ST~DIOL COMBINED WITH CYCLICAL ORAL NORETHISTERONE ACETATE ON INSULIN AND GLUCOSE METABOLISM IN POSTMENOPAUSAL WOMEN CPSorncer, I F Godsland,AJ Cooper,D Ross,MI Whitehead,JC Stevenson, Wynn Division of Metabolic Medicine, Imperial College,London, NW8 9SQ,UK.
The incidenceof cardiovascular disease in women rises sharply after the menopause. Insulin resistance is a risk factor for cardiovascular disease Few data exist on the effects of postmenopausal HRT on which is all&ted by sex steroid concentrations. The aim of the study was to determinethe effect on insulinsensitivityof transdermal oestradiol, carbohydratemetabolism.We have comparedthe effects of oral alone and combinedwith no~~istemne,in healthywomenalter a 178-oestradiolwith cyclical oral NETA (TrisequensB) and with cyclical oral NETA (Es~pak~) surgicalmenopau~. Fourteenwomenentereda randomised, double- tr~sde~al 17R-oes~adiol blind, placebo-controlled study 3-6 weeksafter hysterectomyand over 12 months.intravenousglucosetolerancetests(IVGTTs) were bilatemloophorectomy.They receivedeither transdermal oestradiol performedat baseline,46 weeks (oestrogen-onlyphase)and 48 5Ong(E2) or placebopatches.After 6 weeksa secondrandomisation weeks(combinedphase). Mathematicalmodellinganalysisof the of insulin allocatedthemto receiveE2 combinedwith oral norethisterone 5mg IVGTT concentrationprofileswasusedto derive measures @JET)or a placebo tablet(Ptac)for a further6 weeks.Theythen‘crossed sensitivity, pancreaticinsulin secretionand the amountof newly over to receivethe oppositetherapy. H~erinsulinaemic, eugly~emi~ secretedinsulintaken up by the liver. A prelimin~ analysiswas clampswereperformedat initial~domisation(Basal)andaftereach6 unde~~enof 44 womencompIetingthe study. In womentaking TrisequensO(n=20), there was a 38% increase weektreatmentperiod. The meanage of the womenwas 42.9 years (range32-49) mean (~~0.05) in insulin sensitivity in the oestrogen-onlyphase. There body massindex was25 kg/m2(range20 - 30 ) Insulin sensitivity wasno changein insulin secretionand a 35% increase(p=O.Ol) in was expressedas the weight-correctedmeansteady-stateglucose the amountof newly secretedinsulintakenup by the liver. Addition of NETA diminishedthe improvementin insulinsensitivity. In the infusionrate M rn~k~hr (~ean~SEM). womentaking Es~apak~ (n=24), there was no changein insulin Basal Placebo E2+Plac Ez+NET E2 sensitivitybut insulinsecretionwasincreasedby 48% (~4.01) and (n=14) (n=6) (r-i=81 (n=121 (ik1Z.f a.0 kO.5 7.7 +0.6 8.5 k0.9 8.5 20.5 7.8 f0.7. uptakeof newly secretedinsulinby the liver wasincreasedby 17% In this pilot study neither E2 nor E2+NET had any statistically (p=O.O5).Addition of NETA hadlittle effect onthesechanges. andEstrapako. significanteffect on insulinsensitivity. A largerstudy is underway Insulineliminationis improvedwith bothTrisequens@ Insulinsensitivityis improvedduring the oestrogen-onlyphaseof to investigatethe underlyingtrends. Trisequens@ therapy. Thesechangesare consistentwith a reduced risk of arteriafdisease.
F099
FlOO
METABOLIC EFFECTS OF 12”MONTH PERCUTANEOUS DHEA REPLACEMENT THERAPY IN POSTMENOPAUSAL WOMEN
THE INFLUENCE OF POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY ON BODY COMPOSITION
P Diamond?L Casart, J L Gomez, A B&anger and F Lab& Laboratory of Molecular Endocrinology and Clinical Endocrine ResearchUnit, CHUL ResearchCenter and Lava] University, Quebec,CanadaG1V 4G2
W ~~n~gi (0, R L~puner~2~~F ~orber~3~,MH Birkh~aser~~,P Jdiger(2). (l)Departmentof Obstetricsand Gynecology and (2)Policlinic of Medicine, University of Bern, Bern, and (3)Schlossklinik, Mammem,Switzerland.
We have evaluatedthe effect of dehydroepi~drosterone (DHEA) We comparedthe effects on body compositionof two types of replacement therapyin GO-70-ye~~ldwomen(N-15) who receiveda conventionalHRT with that of tibolone, a sex steroidwith mixed singledaily percutaneous applicationof a 10%DHEA creamfor 12- estrogenic, progestogenic and mild androgenic activity. month.Whileanthropometric measurements showednochangein body Postmenopausal womenwere enrolled in (1) a control group, or weight.weobserveda 9.8%decrease in subcutaneous skinfoldthickness randomizedto (2) tibolone2.5 mg/day,(3) oral micronizedestradiol at 12months(pcO.05).Thiswasconfirmedby measurements of midthigh (E2) 2 mg/dayplussequentialdydrogesterone (DYD) IO mg/dayfor fat andmuscleareasby computedtomographywherea 3.8%decrease 14of 28 days,or (4) transdermal E2 patchreleasing50 mcgidayplus (pcO.05)in femoralfat and a 3.5%increase (~~0.05)in femoralmuscular oral sequentialDYD 10 mglday for I4 of 28 days. Body areaswereobserved at 12months.Thesechanges wereassociated with a compositionwas measuredat baselineand every 6 monthsfor 2 1I% decrease (~~0.05)in fastingplasmaglucoseanda 17%decrease yearsby DXA (Hologic QDR IOOOW).‘Total body fat mass(TBF) (~~0.05)in fastinginsulinlevels.An overalltrendtowardsa decrease in increased(~~0.05)in controls(+3.6*1.5%) and in the transdermal totalcholesterol anditslipoproteintractionswasobserved.Theindexof I$ group (+4.7*2.2%) but not in the oral E2 (-1.2*2.4%) and Tib sehumsecretion showeda 73%increase (p