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Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women

NCT ID: NCT00608062

Last Updated: 2020-12-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

155 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2012-10-25

Brief Summary

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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.

Detailed Description

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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

Conditions

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Arterial Stiffening Aging Menopause

Keywords

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endothelial function women female estrogen deficiency sex hormones adiposity oxidative stress antioxidants

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Pre1

Premenopausal - GnRHant plus estradiol

Group Type EXPERIMENTAL

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal estradiol patch

Intervention Type DRUG

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

Pre2

Premenopausal - GnRHant plus placebo

Group Type PLACEBO_COMPARATOR

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal placebo patch

Intervention Type DRUG

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

Peri1

Perimenopausal (early) - GnRHant plus estradiol

Group Type EXPERIMENTAL

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal estradiol patch

Intervention Type DRUG

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

Peri2

Perimenopausal (early) - GnRHant plus placebo

Group Type PLACEBO_COMPARATOR

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal placebo patch

Intervention Type DRUG

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

Peri3

Perimenopausal (late) - GnRHant plus estradiol

Group Type EXPERIMENTAL

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal estradiol patch

Intervention Type DRUG

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

Peri4

Perimenopausal (late) - GnRHant plus placebo

Group Type PLACEBO_COMPARATOR

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal placebo patch

Intervention Type DRUG

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

Post1

Postmenopausal - GnRHant plus estradiol

Group Type EXPERIMENTAL

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal estradiol patch

Intervention Type DRUG

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

Post2

Postmenopausal - GnRHant plus placebo

Group Type PLACEBO_COMPARATOR

GnRHant - Ganirelix acetate

Intervention Type DRUG

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

Transdermal placebo patch

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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)

Intervention Type DRUG

Transdermal placebo patch

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

Intervention Type DRUG

Other Intervention Names

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Ganirelix

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kerrie L Moreau, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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

Aurora, Colorado, United States

Site Status

Countries

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United States

References

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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. doi: 10.1016/s0008-6363(02)00777-0.

Reference Type BACKGROUND
PMID: 12618248 (View on PubMed)

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. doi: 10.1161/01.HYP.0000165678.63373.8c. Epub 2005 May 2.

Reference Type BACKGROUND
PMID: 15867135 (View on PubMed)

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. doi: 10.1161/01.cir.101.19.2258.

Reference Type BACKGROUND
PMID: 10811592 (View on PubMed)

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. doi: 10.1161/01.res.0000038304.62046.4c.

Reference Type BACKGROUND
PMID: 12411396 (View on PubMed)

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. doi: 10.1113/jphysiol.2003.057042. Epub 2004 Jan 30.

Reference Type BACKGROUND
PMID: 14754992 (View on PubMed)

Gavin 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.

Reference Type BACKGROUND
PMID: 22692329 (View on PubMed)

Moreau 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.

Reference Type BACKGROUND
PMID: 22245769 (View on PubMed)

Moreau 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.

Reference Type RESULT
PMID: 22969140 (View on PubMed)

Other Identifiers

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R01AG027678

Identifier Type: NIH

Identifier Source: secondary_id

View Link

06-0537

Identifier Type: -

Identifier Source: org_study_id