The effect of continuous combined HRT on glucose homeostasis and plasma lipids. A placebo-controlled study in postmenopausal women with type 2 diabetes.
BACKGROUND
Hyperandrogenicity in women is a risk factor for cardiovascular disease and noninsulin-dependent diabetes mellitus (NIDDM). Estradiol alone decreases hyperandrogenicity and have beneficial effects on glucose metabolism and plasma lipids in postmenopausal women with type 2 diabetes.


OBJECTIVE
To analyse effects on glucose homeostasis and plasma lipids by 2 mg estradiol and 1mg norethisterone acetate (NETA) given as a daily tablet during 6 months in postmenopausal women with type 2 diabetes.


METHODS
Randomised, double-blind, placebo-controlled, cross-over design.


METHODS
Thirty-one postmenopausal women with type 2 diabetes, glycosylated haemoglobin (HbA1c) of 6% or more and sex hormone-binding globulin (SHBG) values of 60 nmol/L or less were included. Anthropometric variables, blood pressure, sex steroid hormones, HbA1c, serum and lipoprotein lipids, plasminogen activator inhibitor 1 (PAI-1) and insulin-like growth factor 1 (IGF-1) were measured. An oral glucose tolerance test (OGTT) was performed and blood glucose, insulin and C-peptide were analysed. All measurements were taken at baseline and after each 6-month period.


RESULTS
An increase of SHBG and a decrease in free testosterone and PAI-1 levels was induced by the estradiol/NETA treatment compared with placebo. Lipoprotein(a) decreased but otherwise lipid metabolism was unaffected. No differences were recorded in glucose homeostasis between active treatment and placebo.


CONCLUSIONS
Estradiol/NETA therapy decreased hyperandrogenicity in postmenopausal women with type 2 diabetes. Lipoprotein(a) and PAI-1 which are independent risk factors for coronary heart disease decreased. No changes in glucose homeostasis were found.
Thunell
Louise
L
Department of Obstetrics and Gynecology, Sahlgrenska University Hospital/East, Göteborg, Sweden. louise.thunell@telia.com
Andersson
Björn
B
Glassell
Marie
M
Mattsson
Lars-Ake
LA
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004311:Double-Blind Method; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy* / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects*; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077563:Norethindrone Acetate; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects / Q000378:metabolism; D018709:Statistics, Nonparametric
D001786:Blood Glucose; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone