Effects of menopause on artery health and fat gain in women

Cardiometabolic Consequences of the Loss of Ovarian Function

This study is testing how menopause and lower estrogen levels affect artery health and belly fat in women, and whether using an estrogen patch can help improve these issues.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 20 Years to 45 Years
• Sex: Female
• Sponsor: University of Colorado, Denver (Academic / other)
• Locations: 1 site (Aurora, Colorado)
• Trial ID: NCT06264882 on ClinicalTrials.gov

What this trial studies

This research investigates how the decrease in estrogen during menopause affects artery health and fat accumulation, particularly in the abdominal area, which may increase the risk of heart disease. The study aims to determine the relationship between low estrogen levels and vascular function in premenopausal women, as well as the impact of increased abdominal fat on vascular health. Additionally, it explores the role of the tryptophan-kynurenine pathway in these changes, which may be linked to aging and body fat regulation. Participants will receive either a transdermal estradiol patch or a placebo to assess these effects.

Who should consider this trial

Good fit: Ideal candidates are premenopausal women aged 20-45 with regular menstrual cycles and no recent hormonal contraceptive use.

Not a fit: Patients who are pregnant, lactating, or have irregular menstrual cycles may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of cardiovascular risks associated with menopause in women.

How similar studies have performed: Other studies have shown promising results in understanding the effects of estrogen on vascular health, but this specific approach is novel.

Eligibility criteria

Inclusion Criteria:

* Age criteria of 20-45 years: the investigators are determining the effects of ovarian suppression on adiposity and vascular in premenopausal women;
* Premenopausal defined as normal menstrual cycle function defined as no more than 1 missed cycle in the previous year: irregular menstrual or missed menstrual cycles could indicate that women are anovulatory and/or perimenopause;
* Not pregnant or planning to become pregnant;
* Not lactating in the last 3 months;
* Serum FSH \<10 IU/L measured during days 1-10 of the menstrual cycle: to ensure the woman is premenopausal and not perimenopausal;
* Not on hormonal contraception in the last 3 months;
* Sedentary or recreationally active (\<2 days/wk vigorous exercise);
* No use of medications that might influence vascular function (i.e., antihypertensives, lipid lowering medications, blood thinners);
* No use of antioxidant supplements or chronic NSAIDs or be willing to go off them for 4 weeks prior to enrollment in the study;

Exclusion Criteria:

* Diabetic or fasted glucose \>126 mg/dL;
* Body mass index (BMI) \>35 kg/m2;
* Weight change \>5 kg in the last 3 months;
* Use of glucocorticoids (inhaled, oral, topical) or drugs that affect glucocorticoid metabolism (e.g., ketoconazole) in the last 3 months;
* Excess alcohol consumption, defined as \>14 drinks per week by self-report;
* Known hypersensitivity to study medications;
* Depressive symptoms, defined as a CES-D score \>16;
* Resting blood pressure \>150/90 mmHg;
* Preexisting or active cardiac, renal, or hepatic disease: past or current history of these diseases or conditions;
* Active or chronic infection: inflammation associated with active or chronic infections impair vascular function;
* Thyroid dysfunction, defined as an ultrasensitive TSH \<0.5 or \>5.0 mU/L; volunteers with abnormal TSH values will be reconsidered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement;
* Smoking or Tobacco use within the previous 12 months;
* Severe low bone mass or osteoporosis, defined as a hip or lumbar spine T-score \<-2.0: safety reasons, women who are randomized to the ovarian suppression plus placebo group could see a decrease in bone mineral density due to the suppression of estrogen;
* History of venous thromboembolic event (VTE): safety reasons, estradiol therapy can increase the risk of VTE;
* History of breast cancer or other estrogen-dependent neoplasm: estradiol therapy is contraindicated;

Where this trial is running

Aurora, Colorado

• University of Colorado Anschutz Medical Campus — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Kerrie Moreau, PhD — University of Colorado Denver Anschutz Medical Campus
• Study coordinator: Kerrie Moreau, PhD

Conditions Menopause; Estrogen Deficiency; Aging; Adiposity; Vascular biology; Women's health; Women