Lipoproteins and low-dose estradiol replacement therapy in post-menopausal Type 2 diabetic patients: the effect of addition of norethisterone acetate.
OBJECTIVE
Low-dose continuous oestrogen/progestogen may increase patient compliance long-term but the cardioprotective effects in diabetes are unknown. The aim of this study was to compare the effect of low-dose oral oestrogen (1 mg, 17-beta-estradiol) treatment with oestrogen (1 mg 17-beta-estradiol) in combination with low-dose (0.5 mg) continuous norethisterone acetate (NETA) on lipoproteins in Type 2 diabetic patients.


METHODS
Thirty-four post-menopausal Type 2 diabetic patients in moderate control (mean haemoglobin A1c 7.7%) who had a serum oestradiol level of < 50 pg/ml were examined over a 6-month period. Serum lipids, and lipoprotein composition of very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were measured. Serum lipoprotein(a) was determined by an ELISA method, LDL fatty acids by gas-liquid chromatography and LDL oxidizability by thiobarbituric acid reactive substances (TBARS assay). Cholesteryl ester transfer protein (CETP), and cell cholesterol were measured.


RESULTS
There was a reduction in serum cholesterol on both treatments but no significant difference between treatment groups. LDL cholesterol decreased by 17% in each group. There was a no significant difference between the groups in serum VLDL or HDL cholesterol or serum triglycerides during the study. The change in lipoprotein(a) during the study was not significantly different between the groups. There was no significant difference in 4 h LDL oxidizability between groups. Although CETP increased with time in both groups there was no significant difference in the change between the groups.


CONCLUSIONS
In this small study, the addition of continuous low-dose NETA did not reduce the potentially beneficial effects of low-dose 17-beta-estradiol on the progression of atherosclerosis in diabetes.
Owens
D
D
Department of Clinical Medicine, Trinity College, Dublin, Ireland.
Collins
P B
PB
Johnson
A
A
Tomkin
G H
GH
D000368:Aged; D002352:Carrier Proteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006023:Glycoproteins; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D017698:Postmenopause; D014280:Triglycerides / Q000097:blood
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D004958:Estradiol; D002784:Cholesterol; D000077563:Norethindrone Acetate; D009640:Norethindrone