Effect of hormonal replacement therapy on C-reactive protein and cell-adhesion molecules in postmenopausal women

A randomized, double-blind, placebo-controlled, crossover study comparing the effects of conjugated equine estrogen (CEE) and the combination of CEE and MPA in postmenopausal women, the most frequently prescribed progestin, on the regulation of cell-adhesion molecules and CRP levels is performed.

Abstract

Healthy postmenopausal women were enrolled in a placebo-controlled, double-blind, randomized, crossover study consisting of 3 different phases: (1) placebo, (2) CEE (0.625 mg/day), and (3) CEE (0.625 mg/day) and MPA (2.5 mg/day). Both CEE and MPA tablets had a matching placebo tablet, and during each phase of the study, patients took 2 tablets/day (1 tablet as active CEE or CEE placebo, and 1 tablet as active MPA or MPA placebo). Each phase of the study lasted 8 weeks. Phases were separated by a 4-week washout period. Postmenopausal women with coronary heart disease, liver or kidney disease, thyroid dysfunction, diabetes mellitus, and women who were smoking or were taking medications known to affect lipid levels and metabolism, or with a history of clotting disorders, thromboembolism, cancer of the breast, uterus, or cervix were excluded from the study. The study protocol was approved by the Human Investigation Review Committee of New England Medical Center and Tufts University. Study subjects provided informed consent and underwent a screening visit consisting of an interview including medical history, physical examination, vital signs, electrocardiogram, and laboratory tests. In all, 14 postmenopausal women were enrolled and completed the 3 phases of the study (age 57 ± 6 years, weight 69.9 ± 12.3 kg, and body mass index 27.26 ± 5.11 kg/m2). Subjects were asked to maintain the same lifestyle (diet, physical exercise) throughout the study. At weeks 7 and 8 of each phase, blood was drawn after a 12-hour fast in all subjects. In the first 6 subjects, an additional fasting blood draw was also obtained at week 6 of each phase. Blood was drawn in a 10-ml tube containing ethylenediaminetetraacetic acid to a final concentration of 0.15%, and in a regular 10-ml tube. Plasma and serum were separated at 2,500 rpm for 30 minutes at 4°C, and aliquots were stored at −80°C until time of assay.