Progesterone therapy, endothelial function and cardiovascular risk factors: a 3-month randomized, placebo-controlled trial in healthy early postmenopausal women

• Published in: PloS one 2014-01, Vol.9 (1), p.e84698
• Main Authors: Prior, Jerilynn C, Elliott, Thomas G, Norman, Eric, Stajic, Vesna, Hitchcock, Christine L
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Albumin; Blood; Blood flow; Blood Pressure; Body mass; Body Mass Index; Body size; C-reactive protein; C-Reactive Protein - metabolism; Cardiovascular diseases; Cardiovascular Diseases - prevention & control; Cholesterol; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Clinical trials; Coagulation; Coronary artery disease; Diabetes mellitus; Double-Blind Method; EKG; Electrocardiography; Endothelium; Estradiol; Estrogens; Fasting; Female; Fibrin Fibrinogen Degradation Products - metabolism; Forearm; Forearm - blood supply; Glucose; Health risk assessment; Health risks; Heart diseases; Heart rate; High density lipoprotein; Hormone replacement therapy; Hormones; Humans; Hypertension; Laboratory testing; Lipid metabolism; Lipids; Low density lipoproteins; Medicine; Menopause; Menstruation; Metabolism; Middle Aged; Occlusion; Physiological aspects; Plethysmography; Post-menopause; Postmenopausal women; Postmenopause - blood; Postmenopause - drug effects; Progesterone; Progesterone - administration & dosage; Randomization; Risk analysis; Risk assessment; Risk Factors; Sex hormones; Smoking; Statistical analysis; Therapy; Triglycerides; Triglycerides - blood; Waist Circumference; Women's health; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084698

Progesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation. We conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily) among 133 healthy postmenopausal women in Vancouver, Canada from 2003-2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1-11 y since last menstruation, not using hormones (for >6 months), non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1) women (55 ± 4 years, body mass index 25 ± 3) initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline) was not changed with progesterone (487 ± 189%, n = 18) compared with placebo (408 ± 278%, n = 16) (95% CI diff [-74 to 232], P = 0.30). Progesterone (n = 65) and placebo (n = 47) groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (-0.14 mmol/L, P = 0.001) on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo. Results indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change). ClinicalTrials.gov NCT00152438.