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


RESULTS
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.


CONCLUSIONS
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).


BACKGROUND
ClinicalTrials.gov NCT00152438.
Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, Vancouver, British Columbia, Canada ; Division of Endocrinology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada ; School of Population and Public Health, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
Jerilynn C
JC
Prior
Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, Vancouver, British Columbia, Canada ; Division of Endocrinology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Thomas G
TG
Elliott
Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, Vancouver, British Columbia, Canada.
Eric
E
Norman
Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, Vancouver, British Columbia, Canada.
Vesna
V
Stajic
Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, Vancouver, British Columbia, Canada.
Christine L
CL
Hitchcock
D001794:Blood Pressure; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008875:Middle Aged; D010991:Plethysmography; D017698:Postmenopause / Q000097:blood* / Q000187:drug effects; D011374:Progesterone / Q000008:administration & dosage*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005338:Fibrin Fibrinogen Degradation Products; D014280:Triglycerides; C036309:fibrin fragment D; D011374:Progesterone; D002097:C-Reactive Protein