Current partner codePEPTIDESDE
NCT00608062·Not applicable·INTERVENTIONAL

Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women

Status

Completed

Phase

Not applicable

Enrollment

155

Locations

1

Results

Posted

Publications

8

Study summary

What the protocol is testing.

The purpose of this study is to find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because the arteries lose their ability to expand, or dilate.

Full detailed description

As women get older and go through menopause, estradiol levels decrease. Also with aging, the arteries that are located around the heart get stiffer. Over time this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study we want to find out if a short-term drop in estrogen levels in premenopausal and perimenopausal women can cause arteries to become stiffer, and why this happens. Additionally, in postmenopausal women, we want to find out if a short-term increase in estrogen levels causes their arteries to become more flexible (less stiff). Arterial health (i.e., stiffness) will be examined in premenopausal, perimenopausal and postmenopausal women before and after they are given a drug called Ganirelix™ (for 7 days), which will markedly lower their reproductive hormones. After the first 4 days of taking Ganirelix™, the women will be randomly placed into 1 of 2 treatment groups to take either estrogen (0.075 mg/d skin patch) replacement or placebo for the rest of the Ganirelix treatment. This is to increase estrogen levels back to the normal level. After having the patch on for 4 days, arterial health will be examined again. Pre-specified Outcome Measures were divided into unit-of-measurement specific Outcome Measure tables for the purposes of results reporting to ClinicalTrials.gov

Interventions

Treatment arms and agents.

DRUG

GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

DRUG

Transdermal estradiol patch

0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

DRUG

Transdermal placebo patch

Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Timeline

From registration to results.

  1. First posted

    Feb 6, 2008

  2. Study start

    Mar 2007

  3. Primary completion

    Oct 25, 2012

  4. Study completion

    Oct 25, 2012

  5. Results posted

    Dec 24, 2020

  6. Registry updated

    Dec 24, 2020

Outcomes

What the study measures.

Primary outcomes

Arterial Stiffness (Carotid Artery Compliance) During Saline

Time frame · Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment

Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure

Endothelial Function

Time frame · Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment

Brachial artery flow-mediated dilation (FMD) assessed by ultrasound. This other outcome measure was originally specified as "Secondary" in error and has been updated to "Primary" to be consistent with the protocol.

Secondary outcomes

Not reported in the indexed record.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
70 Years
Sex
FEMALE
Healthy volunteers
Yes

Inclusion Criteria: * Healthy women of all races and ethnic backgrounds in one of the following groups: * Premenopausal: 18-49 years, regular menstrual cycles with no change in observed cycle length (21-35 days) * Perimenopausal: 40-55 years, categorized as either early (at least 2 cycles with cycle length changes of at least 7 days) or late (more than 3 months of amenorrhea) transition * Postmenopausal: 45-70 years, more than 12 months of amenorrhea as defined by the menopausal staging system (STRAW); additionally, postmenopausal women will be categorized into early and late stages as defined by the STRAW definition, specifically, women who are less than 5 years postmenopause will be considered early, and women more than 6 years will be categorized as late * All postmenopausal women will have undergone natural menopause * No oral contraceptive or Hormone Replacement Therapy (HRT) use for at least 6 months * Resting blood pressure less than 140/90 mmHg * Plasma glucose concentrations less than 110 mg/dl under fasting conditions * Sedentary or recreationally active (less than 3 days of vigorous aerobic exercise) * No use of medications that might influence cardiovascular function * Nonsmokers * No use of vitamin supplements or willing to stop use for duration of the study Exclusion Criteria: * History of or active estrogen-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia, and cardiovascular disease * Known allergy to transdermal patch or GnRHant * Other contraindications to HRT and GnRHant

Study locations

1 registered sites.

United States. Showing up to 24 locations stored in the fast local snapshot.

University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory

Aurora, Colorado, United States

Publications

Results and literature.

PMID 12618248Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res. 2003 Mar;57(3):861-8. doi: 10.1016/s0008-6363(02)00777-0.PMID 15867135Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery compliance in postmenopausal women. Hypertension. 2005 Jun;45(6):1107-12. doi: 10.1161/01.HYP.0000165678.63373.8c. Epub 2005 May 2.PMID 10811592Virdis A, Ghiadoni L, Pinto S, Lombardo M, Petraglia F, Gennazzani A, Buralli S, Taddei S, Salvetti A. Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women. Circulation. 2000 May 16;101(19):2258-63. doi: 10.1161/01.cir.101.19.2258.PMID 12411396Ihionkhan CE, Chambliss KL, Gibson LL, Hahner LD, Mendelsohn ME, Shaul PW. Estrogen causes dynamic alterations in endothelial estrogen receptor expression. Circ Res. 2002 Nov 1;91(9):814-20. doi: 10.1161/01.res.0000038304.62046.4c.PMID 14754992Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol. 2004 Apr 1;556(Pt 1):315-24. doi: 10.1113/jphysiol.2003.057042. Epub 2004 Jan 30.PMID 22692329Gavin KM, Jankowski C, Kohrt WM, Stauffer BL, Seals DR, Moreau KL. Hysterectomy is associated with large artery stiffening in estrogen-deficient postmenopausal women. Menopause. 2012 Sep;19(9):1000-7. doi: 10.1097/gme.0b013e31825040f9.PMID 22245769Moreau KL, Meditz A, Deane KD, Kohrt WM. Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1211-8. doi: 10.1152/ajpheart.01065.2011. Epub 2012 Jan 13.PMID 22969140Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab. 2012 Dec;97(12):4692-700. doi: 10.1210/jc.2012-2244. Epub 2012 Sep 11.

Primary links

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Related trials

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