Differential Effects of Estradiol and Progesterone on Cardiovascular Risk Factors in Postmenopausal Women.

Context: Controlled, blinded studies of sex-hormone replacement in postmenopausal women using natural estradiol (E) and native progesterone (P) are few.

Objective: To delineate the effect of E alone or with P on lipids and inflammatory markers.

Design: A placebo-controlled, double-masked, prospectively randomized study of 40 healthy, postmenopausal volunteers assigned to four treatment groups: placebo, intramuscular E, and/or micronized oral P for 23 (±2) days.

Results: Treatment with E alone compared with placebo lowered total cholesterol (TC; = 0.006), non-high-density lipoprotein cholesterol (nonHDL-C; = 0.004), low-density lipoprotein cholesterol (LDL-C; = 0.012), and apolipoprotein B (Apo B; = 0.02) levels, and raised HDL-C levels ( = 0.03 the 3 other groups). Conversely, addition of P to E reduced HDL-C levels ( = 0.015). Triglyceride concentrations manifested no effect on E or P. High-sensitivity C-reactive protein (hsCRP) level was highest in women with E and P replacement ( = 0.018 placebo). Leptin and IL-6 concentrations did not vary. P treatment decreased adiponectin levels ( = 0.019). Serum E levels correlated linearly with TC, LDL-C, nonHDL-C, Apo B (all negatively), and SHBG (positively) concentrations. P level correlated negatively with TC ( = 0.029), HDL-C ( = 0.002), and adiponectin ( = 0.002) levels.

Conclusion: In this study, there were individual and interactive effects of E and P on key lipids in postmenopausal individuals.