Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women

Not Applicable

Completed

Interventions: Drug: GnRHant - Ganirelix acetate
Drug: Transdermal placebo patch
Drug: Transdermal estradiol patch

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.

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.

Pre-specified Outcome Measures were divided into unit-of-measurement specific Outcome Measure tables for the purposes of results reporting to ClinicalTrials.gov

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Pre1	GnRHant - Ganirelix acetate	Premenopausal - GnRHant plus estradiol
Pre2	Transdermal placebo patch	Premenopausal - GnRHant plus placebo
Peri1	GnRHant - Ganirelix acetate	Perimenopausal (early) - GnRHant plus estradiol
Peri2	GnRHant - Ganirelix acetate	Perimenopausal (early) - GnRHant plus placebo
Peri4	Transdermal placebo patch	Perimenopausal (late) - GnRHant plus placebo
Post1	Transdermal estradiol patch	Postmenopausal - GnRHant plus estradiol
Peri3	GnRHant - Ganirelix acetate	Perimenopausal (late) - GnRHant plus estradiol
Peri3	Transdermal estradiol patch	Perimenopausal (late) - GnRHant plus estradiol
Pre1	Transdermal estradiol patch	Premenopausal - GnRHant plus estradiol
Pre2	GnRHant - Ganirelix acetate	Premenopausal - GnRHant plus placebo
Peri2	Transdermal placebo patch	Perimenopausal (early) - GnRHant plus placebo
Peri4	GnRHant - Ganirelix acetate	Perimenopausal (late) - GnRHant plus placebo
Post2	Transdermal placebo patch	Postmenopausal - GnRHant plus placebo
Peri1	Transdermal estradiol patch	Perimenopausal (early) - GnRHant plus estradiol
Post1	GnRHant - Ganirelix acetate	Postmenopausal - GnRHant plus estradiol
Post2	GnRHant - Ganirelix acetate	Postmenopausal - GnRHant plus placebo

Primary Outcome Measures

Name	Time	Method
Arterial Stiffness (Carotid Artery Compliance) During Saline	Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment	Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure
Endothelial Function	Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment	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.

Secondary Outcome Measures

Name	Time	Method

Locations (1): University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory
🇺🇸
Aurora, Colorado, United States