Acute effects of estradiol and progesterone on insulin, lipids and lipoproteins in postmenopausal women: a pilot study

Objectives: To examine the acute effects of estradiol-17 beta (E-2) and pro gesterone (P) on serum levels of insulin, lipids and lipoproteins in estrog en-deficient postmenopausal women, whereby, a direct cause-effect relations hip could be established without the influence of lifestyle changes. Materi als and Methods: Nine postmenopausal women were given oral E-2 (Estrace(TM) ) 2 mg/day for 28 days and oral micronized P (Prometrium(TM)) 200 mg/day in the last 14 days or E-2 treatment. Fasting blood samples were obtained bef ore starting E-2 (day 1) and P (day 15) and on day 29. Serum levels of insu lin, triglycerides (TG), total cholesterol (TC), low density lipoprotein (L DL), high density lipoprotein (HDL) and lipoprotein (a) (Lp(a)) at the thre e time points were compared by Friedman analysis of variance (ANOVA). Corre sponding levels of glucose, the apolipoproteins (Apo) Al and B and serum an drogen levels were also evaluated. Results: E-2 decreased while P increased fasting levels of insulin (32.45 +/- 3.57, 26.36 +/- 2.90 and 37.36 +/- 3. 67 pmol/l on day 1, 15 and 29 respectively; P < 0.01). Fasting glucose to i nsulin ratios changed inversely (P < 0.01). E-2 increased HDL from 1.07 +/- 0.05 mmol/l on day 1 to 1.17 +/- 0.07 mmol/l on day 29 but decreased corre sponding levels of Lp(a) from 261 +/- 93 to 211 +/- 83 U/l (P = 0.03 for bo th). TC and LDL levels fell significantly after 14 days of E-2 treatment wi th no further decrease when P was added. Androgen levels remained unchanged during hormone treatment. Conclusion: The sequential, acute effects of E-2 and micronized P on insulin and lipids confirm a direct cause-effect relat ionship. The acute effects of P on insulin in particular, highlights the im portance of standardizing the medication days according to estrogen and pro gestin in the clinical evaluation of their true metabolic impact in longer- term studies and may influence the choice of progestin type, dose and durat ion in hormone replacement (C) 2000 Elsevier Science Ireland Ltd. All right s reserved.