Cardiometabolic Consequences of the Loss of Ovarian Function

Summary

The menopause transition is associated with a decrease in artery health and an increased risk for weight gain in storing fat in the stomach area which may increase the risk for heart disease. The purpose of this research is to study how the decrease in estrogen at menopause changes artery health and fat gain, and risk of disease in women as they age. The first aim in this study will determine whether short term and long term low estrogen levels in premenopausal women decreases artery function and whether this is related to an increase in fat in the stomach area. The second aim will determine whether the changes in artery health and body fat are related to changes in a pathway that breaks down an important amino acid called tryptophan. This pathway is thought to play a role in regulating the aging process. Therefore, the investigators will determine whether the decrease in artery health and the increase in body fat in the stomach region with low estrogen is related to changes in this pathway in the blood, in vascular cells and fat tissue. Because estrogen levels fluctuate in premenopausal women, the investigators will use an approach (intervention) that controls estrogen levels to address these aims. The investigators will use a medication that is typically used to treat endometriosis or uterine fibroids to lower estrogen levels and an estrogen patch to increase estrogen in some women. Some women will receive a patch that has no estrogen (called a placebo patch). The intervention period will be 20 weeks. The study will provide us with new knowledge on how low estrogen with menopause affects artery health and fat gain estrogen.

Conditions

• Menopause
• Estrogen Deficiency
• Aging
• Adiposity

Interventions

DRUG

Degarelix

After first undergoing a pregnancy test, a clinician will administer an 80-mg subcutaneous injection of degarelix acetate (20 mg/mL; Ferring Pharmaceuticals Inc, Parsippany, NJ) to the women. A second injection will occur at 10 weeks. Compliance to the intervention will be ensured by having participants receive injections in the Clinical and Translational Research Center (CTRC), where all study visits will take place.

DRUG

Transdermal Estradiol Patch

Treatment will be a weekly transdermal patch (0.075 mg) administered in a double-blinded manner. This estradiol dose increases serum estradiol to \~90 pg/mL. Compliance to the intervention will be monitored by having participants keep a log that tracks patch use.

DRUG

Transdermal Placebo Patch

Treatment will be a weekly transdermal patch (placebo inactive) administered in a double-blinded manner. Compliance to the intervention will be monitored by having participants keep a log that tracks patch use.

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• University of Colorado, Denver

  lead OTHER

Principal Investigators

• Kerrie Moreau, PhD · University of Colorado Denver Anschutz Medical Campus

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-06-01

Primary Completion

2028-05-31

Completion

2028-08-31

FDA Drug

Yes

Countries

• United States

Study Locations