Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women

University of Colorado, Denver155 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

155

Conditions

Arterial Stiffening Aging Menopause

Interventions

GnRHant - Ganirelix acetateDRUG

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 patchDRUG

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

Transdermal placebo patchDRUG

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

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

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

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Arterial Stiffness (Carotid Artery Compliance) During Saline

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

Time frame: 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.

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

Data from ClinicalTrials.gov

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