Dataset Information

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

ABSTRACT:

Context

Controlled, blinded studies of sex-hormone replacement in postmenopausal women using natural estradiol (E₂) and native progesterone (P) are few.

Objective

To delineate the effect of E₂ 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 E₂, and/or micronized oral P for 23 (±2) days.

Results

Treatment with E₂ alone compared with placebo lowered total cholesterol (TC; P = 0.006), non-high-density lipoprotein cholesterol (nonHDL-C; P = 0.004), low-density lipoprotein cholesterol (LDL-C; P = 0.012), and apolipoprotein B (Apo B; P = 0.02) levels, and raised HDL-C levels (P = 0.03 vs the 3 other groups). Conversely, addition of P to E₂ reduced HDL-C levels (P = 0.015). Triglyceride concentrations manifested no effect on E₂ or P. High-sensitivity C-reactive protein (hsCRP) level was highest in women with E₂ and P replacement (P = 0.018 vs placebo). Leptin and IL-6 concentrations did not vary. P treatment decreased adiponectin levels (P = 0.019). Serum E₂ levels correlated linearly with TC, LDL-C, nonHDL-C, Apo B (all negatively), and SHBG (positively) concentrations. P level correlated negatively with TC (P = 0.029), HDL-C (P = 0.002), and adiponectin (P = 0.002) levels.

Conclusion

In this study, there were individual and interactive effects of E₂ and P on key lipids in postmenopausal individuals.

SUBMITTER: Roelfsema F

PROVIDER: S-EPMC6030831 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Roelfsema Ferdinand F Yang Rebecca J RJ Veldhuis Johannes D JD

Journal of the Endocrine Society 20180614 7

<h4>Context</h4>Controlled, blinded studies of sex-hormone replacement in postmenopausal women using natural estradiol (E<sub>2</sub>) and native progesterone (P) are few.<h4>Objective</h4>To delineate the effect of E<sub>2</sub> alone or with P on lipids and inflammatory markers.<h4>Design</h4>A placebo-controlled, double-masked, prospectively randomized study of 40 healthy, postmenopausal volunteers assigned to four treatment groups: placebo, intramuscular E<sub>2</sub>, and/or micronized oral ...[more]

PMID: 29978153

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Project description:ContextThe effect of the female sex steroids, estradiol and progesterone, on muscle protein turnover is unclear. Therefore, it is unknown whether the changes in the hormonal milieu throughout the life span in women contribute to the changes in muscle protein turnover and muscle mass (eg, age associated muscle loss).ObjectiveThe objective of this study was to provide a comprehensive evaluation of the effect of sex hormones on muscle protein synthesis and gene expression of growth-regulatory factors [ie, myogenic differentiation 1 (MYOD1), myostatin (MSTN), follistatin (FST), and forkhead box O3 (FOXO3)].Subjects and designWe measured the basal rate of muscle protein synthesis and the expression of muscle growth-regulatory genes in 12 premenopausal women and four groups of postmenopausal women (n=24 total) who were studied before and after treatment with T, estradiol, or progesterone or no intervention (control group). All women were healthy, and pre- and postmenopausal women were carefully matched on body mass, body composition, and insulin sensitivity.ResultsThe muscle protein fractional synthesis rate was approximately 20% faster, and MYOD1, FST, and FOXO3 mRNA expressions were approximately 40%-90% greater (all P<.05) in postmenopausal than premenopausal women. In postmenopausal women, both T and progesterone treatment increased the muscle protein fractional synthesis rate by approximately 50% (both P<.01), whereas it was not affected by estradiol treatment and was unchanged in the control group. Progesterone treatment increased MYOD1 mRNA expression (P<.05) but had no effect on MSTN, FST, and FOXO3 mRNA expression. T and estradiol treatment had no effect on skeletal muscle MYOD1, MSTN, FST, and FOXO3 mRNA expression.ConclusionMuscle protein turnover is faster in older, postmenopausal women compared with younger, premenopausal women, but these age-related differences do not appear to be explained by the age- and menopause-related changes in the plasma sex hormone milieu.

Project description:BackgroundProgesterone 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 resultsWe 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.ConclusionsResults 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 registrationClinicalTrials.gov NCT00152438.

Project description:Much attention has been drawn to the deleterious effects of adding progestins to estrogen as hormone therapy (HT) in postmenopausal women. Some widely prescribed progestins have been shown to partially oppose the beneficial effects of estrogens on surrogate markers of cardiovascular disease (CVD) risk. Progestins with higher androgenic activity may interfere with lipid profile and glucose tolerance, and could affect mechanisms of estrogen-induced C-reactive protein (CRP) stimulation. Recent data have shown that norpregnane derivatives, but not micronized progesterone, increase the risk of venous thromboembolism among transdermal estrogens users. The aim of the present study was to assess the effects of combining micronized progesterone with non-oral estrogen therapy on lipid profile and cardiovascular risk factors in a sample of early postmenopausal women.Clinical trial including 40 women receiving intranasal 17? estradiol 3 mg/day for two months and 46 women receiving percutaneous 17? estradiol gel 1.5 mg/day for three months (E2). Both groups received an additional 200 mg/day of micronized progesterone by vaginal route 14 days/month (E2+P). Outcome measures included body weight, waist circumference, body mass index (BMI), lipid profile and ultra-sensitive C-reactive protein (usCRP) at baseline and during the E2 or E2+P portions of treatment.Mean age was 51±3 years. Mean time since menopause was 22.2±10 months. Most participants were overweight; HT did not change BMI. E2 and E2+P did not affect waist circumference and weight. Menopausal symptoms improved after HT. The effects of intranasal and percutaneous estradiol were similar, regardless of the addition of progesterone. Similarly, for the overall group of 86 women, micronized progesterone did not alter the response to E2. Blood pressure, glucose, insulin, HDL-c, triglycerides, and usCRP remained constant with or without micronized progesterone. Total cholesterol decreased after E2, and progesterone maintained this reduction. LDL-c levels were similar at baseline and with E2, and lower during E2+P in relation to baseline.Cyclic, short term exposure to vaginal micronized progesterone did not alter the metabolic and cardiovascular effects of non-oral E2 in early, apparently healthy, postmenopausal women.ClinicalTrials.gov NCT01432028.

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Dataset Information

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

Context

Objective

Design

Results

Conclusion

Publications

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

Similar Datasets

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