Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women

NCT00608062 | Completed Results

• 2 other identifiers: 06-0537R01AG027678
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Arterial Stiffening; Aging; Menopause

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Arterial Stiffness (Carotid Artery Compliance) During Saline

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

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

• Endothelial Function

  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.

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

Other Outcomes (6)

• Supine Brachial Blood Pressures

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

• Estradiol

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

• Progesterone

  Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back

Study Arms (8)

Pre1

EXPERIMENTAL

Premenopausal - GnRHant plus estradiol

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch

Pre2

PLACEBO COMPARATOR

Premenopausal - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch

Peri1

EXPERIMENTAL

Perimenopausal (early) - GnRHant plus estradiol

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch

Peri2

PLACEBO COMPARATOR

Perimenopausal (early) - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch

Peri3

EXPERIMENTAL

Perimenopausal (late) - GnRHant plus estradiol

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch

Peri4

PLACEBO COMPARATOR

Perimenopausal (late) - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch

Post1

EXPERIMENTAL

Postmenopausal - GnRHant plus estradiol

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch

Post2

PLACEBO COMPARATOR

Postmenopausal - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch

Interventions

GnRHant - Ganirelix acetate 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

Also known as: Ganirelix

Peri1; Peri2; Peri3; Peri4; Post1; Post2; Pre1; Pre2

Transdermal estradiol patch DRUG

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

Peri1; Peri3; Post1; Pre1

Transdermal placebo patch DRUG

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

Peri2; Peri4; Post2; Pre2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

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

Aurora, Colorado, 80045, United States

Location

Related Publications (8)

• 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.

  PMID: 12618248 BACKGROUND

• 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.

  PMID: 15867135 BACKGROUND

• 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.

  PMID: 10811592 BACKGROUND

• 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.

  PMID: 12411396 BACKGROUND

• 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.

  PMID: 14754992 BACKGROUND

• 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.

  PMID: 22692329 BACKGROUND

• 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.

  PMID: 22245769 BACKGROUND

• 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.

  PMID: 22969140 RESULT

MeSH Terms

Conditions

Obesity

Interventions

ganirelix

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Budget cuts lead to: 1) endothelial cell protein expression outcome not analyzed and deleted; 2) small numbers of early and late perimenopausal groups, thus, it was collapsed into 1 peri group. Ultrasound image quality also lead to small numbers.

Results Point of Contact

• Title: Dr. Kerrie Moreau. PI
• Organization: University of Colorado Anschutz Medical Campus

kerrie.moreau@cuanschutz.edu

303-724-1914

Study Officials

• Kerrie L Moreau, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 6, 2008
• Study Start: March 1, 2007
• Primary Completion: October 25, 2012
• Study Completion: October 25, 2012
• Last Updated: December 24, 2020
• Results First Posted: December 24, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)