Conditions: Arterial Stiffening Aging Menopause
Keywords: endothelial function women female estrogen deficiency sex hormones adiposity oxidative stress antioxidants
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 155
Healthy volunteers: yes

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

Arms:
arm 1: Premenopausal - GnRHant plus estradiol arm 2: Premenopausal - GnRHant plus placebo arm 3: Perimenopausal (early) - GnRHant plus estradiol arm 4: Perimenopausal (early) - GnRHant plus placebo arm 5: Perimenopausal (late) - GnRHant plus estradiol arm 6: Perimenopausal (late) - GnRHant plus placebo arm 7: Postmenopausal - GnRHant plus estradiol arm 8: Postmenopausal - GnRHant plus placebo

Interventions: intervention 1: GnRHant - Ganirelix acetate intervention 2: Transdermal estradiol patch intervention 3: Transdermal placebo patch
Intervention descriptions: intervention 1: 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 2: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7) intervention 3: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Protocol document: