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

Jerilynn C Prior; Thomas G Elliott; Norman E; Vesna Stajic; Christine L Hitchcock

doi:10.1371/journal.pone.0084698

Therapeutics · Hormonal Agents

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

Prior JC, Elliott TG, Norman E, Stajic V, Hitchcock CL

Published January 28, 2014 PloS One, 9(1), e84698

DOI 10.1371/journal.pone.0084698 PMID 24465425 PMC PMC3897380

RRM Academy Synopsis

Progesterone changed few heart markers in healthy postmenopausal women

In a randomized, double-blind, placebo-controlled trial of 133 healthy women after menopause, three months of progesterone left blood pressure, weight and waist size similar to placebo. HDL cholesterol was lower on progesterone than on placebo. Heart risk scores stayed low in both groups.

Key Findings

Women taking progesterone (n = 65) and women taking placebo (n = 47) had similar changes in blood pressure, heart rate, weight, body mass index and waist circumference.
HDL cholesterol was lower on progesterone than on placebo (P = 0.001), while total cholesterol, LDL cholesterol and triglycerides changed similarly in the two groups.
Endothelial (blood vessel) function, a main planned outcome, did not differ significantly between progesterone (n = 18) and placebo (n = 16): 95% CI -74 to 232, P = 0.30.
Changes in glucose, C-reactive protein, albumin and D-dimer were comparable to placebo, and Framingham 10-year risk scores stayed low in both arms (P = 0.53).
The 133 participants were randomized to progesterone or placebo for 3 months in Vancouver, Canada between 2003 and 2009 and were 1 to 11 years past their last menstruation.

Interpretation

The trial randomized healthy women after menopause who had no diabetes, high blood pressure or heart disease. The outcomes were body measures and blood tests of heart and blood vessel health. The authors conclude that progesterone showed short-term cardiovascular safety. They judge the HDL difference clinically unimportant because the risk score did not change. The authors also note that 34 women had blood vessel testing and that the study used surrogate markers.

RRM Context

RRM is built on ovulation, the event that makes the body's own progesterone. The authors state that evidence suggests normal estradiol with normal progesterone before menopause may provide later heart protection. NaProTechnology protocols time the use of progesterone to the cycle.

Our editorial summary of this paper, not the article's abstract.

Abstract

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.

Methods and 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).

Trial Registration

ClinicalTrials.gov NCT00152438.

Topics

Therapeutics › Hormonal Agents › Progesterone and Progestins · Perimenopause and Menopause › Hormone Therapy › Benefits and Risks · Reproductive Endocrinology › Ovarian Hormones › Progesterone

Jerilynn C Prior, Thomas G Elliott, Christine L Hitchcock, Eric G Norman, Vesna Stajic

J Prior, Tom Elliott, T Elliott, Chris Hitchcock, C Hitchcock, E Norman, V Stajic

PMID 24465425 24465425 DOI 10.1371/journal.pone.0084698 10.1371/journal.pone.0084698 Prior et al. 2014, Prior 2014

Keywords

Cholesterol, HDL, Cholesterol, LDL, Fibrin Fibrinogen Degradation Products, Triglycerides, Fibrin Fragment D, Progesterone, C-Reactive Protein