Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women (SHAPE)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00608062
First received: January 31, 2008
Last updated: June 26, 2013
Last verified: June 2013
  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

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

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

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, Interleukin 6 (IL6), C-Reactive Protein (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 ]

Enrollment: 92
Study Start Date: March 2007
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre1
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
Other Name: Ganirelix
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)
Placebo Comparator: Pre2
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
Other Name: Ganirelix
Drug: Transdermal placebo patch
Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Experimental: Peri1
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
Other Name: Ganirelix
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)
Placebo Comparator: Peri2
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
Other Name: Ganirelix
Drug: Transdermal placebo patch
Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Experimental: Peri3
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
Other Name: Ganirelix
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)
Placebo Comparator: Peri4
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
Other Name: Ganirelix
Drug: Transdermal placebo patch
Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Experimental: Post1
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
Other Name: Ganirelix
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)
Placebo Comparator: Post2
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
Other Name: Ganirelix
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:   18 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: 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Colorado
University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Kerrie L Moreau, PhD University of Colorado, Denver
  More Information

Publications:

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00608062     History of Changes
Other Study ID Numbers: 06-0537, R01AG027678
Study First Received: January 31, 2008
Last Updated: June 26, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Colorado, Denver:
endothelial function
women
female
estrogen deficiency
sex hormones
adiposity
oxidative stress
antioxidants

Additional relevant MeSH terms:
Estradiol
Polyestradiol phosphate
Estrogens
LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-
Ganirelix
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female
Hormone Antagonists

ClinicalTrials.gov processed this record on July 22, 2014