Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women - Full Text View

Sponsored by:	National Institute on Aging (NIA)
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00608062

Purpose

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.

Condition	Intervention
Arterial Stiffening Aging Menopause	Drug: GnRHant - Ganirelix acetate Drug: Transdermal estradiol patch Drug: Transdermal placebo patch

MedlinePlus related topics: Menopause

Drug Information available for: Depogen Estradiol Estradiol 3-benzoate Estradiol acetate Estradiol cypionate Estradiol dipropionate Estradiol valerate Polyestradiol phosphate Ganirelix Ganirelix acetate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Investigator), Parallel Assignment
Official Title:	Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:

Arterial stiffness (carotid artery compliance) during saline and ascorbic acid [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Endothelial function - brachial artery flow-mediated dilation [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
Endothelial cell protein expression [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
Serum or plasma blood samples - endothelin-1, catecholamines, angiotensin converting enzyme, oxidative stress markers, IL6, CRP, sex hormones, ascorbic acid, glucose, insulin [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
Carotid and brachial blood pressures [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	124
Study Start Date:	March 2007
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Pre1: Experimental Premenopausal - GnRHant plus estradiol	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)
Pre2: Placebo Comparator Premenopausal - GnRHant plus placebo	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 placebo patch Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Peri1: Experimental Perimenopausal (early) - GnRHant plus estradiol	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)
Peri2: Placebo Comparator Perimenopausal (early) - GnRHant plus placebo	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 placebo patch Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Peri3: Experimental Perimenopausal (late) - GnRHant plus estradiol	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)
Peri4: Placebo Comparator Perimenopausal (late) - GnRHant plus placebo	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 placebo patch Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Post1: Experimental Postmenopausal - GnRHant plus estradiol	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)
Post2: Placebo Comparator Postmenopausal - GnRHant plus placebo	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 placebo patch Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

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.

Eligibility

Ages Eligible for Study:	21 Years to 70 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy women of all races and ethnic backgrounds in one of the following groups:
- Premenopausal: 21-35 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 (PENN-5); 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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608062

Contacts

Contact: Kalen Abbott	720-848-6418	Kalen.Abbott@uchcs.edu
Contact: Nicole Hirsch	720-848-6396	Nicole.Hirsch@uchsc.edu

Locations

United States, Colorado
University of Colorado Denver General Clinical Research Center and Exercise Research Laboratory	Recruiting
Aurora, Colorado, United States, 80045
Contact: Tim Lockie, MS, MBA 720-848-6660 Tim.Lockie@uchsc.edu
Principal Investigator: Kerrie L Moreau, PhD
Sub-Investigator: Wendy M. Kohrt, PhD

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Kerrie L Moreau, PhD

University of Colorado Denver

More Information

SHAPE Study at the University of Colorado at Denver and Health Sciences Center This link exits the ClinicalTrials.gov site

Publications:

Moreau 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.

Moreau 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. Epub 2005 May 2.

Virdis 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.

Ihionkhan 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.

Eskurza 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. Epub 2004 Jan 30. Erratum in: J Physiol. 2004 May 1;556(Pt 3):1014.

Responsible Party:	University of Colorado Denver ( Kerrie L. Moreau, PhD, Assistant Research Professor )
Study ID Numbers:	AG0094, R01AG027678
Study First Received:	January 31, 2008
Last Updated:	January 31, 2008
ClinicalTrials.gov Identifier:	NCT00608062
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

endothelial function
women
female
estrogen deficiency

sex hormones
adiposity
oxidative stress
antioxidants

Study placed in the following topic categories:

Atherosclerosis
Obesity
Ganirelix
Estradiol 3-benzoate
Estradiol valerate

Stress
Estradiol 17 beta-cypionate
Polyestradiol phosphate
Estradiol
Menopause

Additional relevant MeSH terms:

Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009