Menopause Effects on Vascular Function

NCT03236545 | Completed

• 1 other identifier: 385453-18
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to identify the independent effect of estradiol (E2) on endothelin-1 (ET-1) mediated vasomotor function in women. The study is the first step in recognizing the impact of ovarian hormones on the mechanisms that regulate vascular function in women to provide a better understanding of the cardiovascular efficacy of hormone therapy.

Conditions

Cardiovascular Risk Factor

Outcome Measures

Primary Outcomes (1)

• Vascular endothelial function

  The capacity of the small and large blood vessels to dilate.

  3 years

Secondary Outcomes (1)

• Endothelin receptor expression

  3 years

Study Arms (2)

No to Low Endogenous Estrogen

EXPERIMENTAL

PMW and young women (YW) will receive medical study clearance after a detailed physical examination. YW will self-administer subcutaneous injections of the gonadotropin-releasing hormone (GnRH) antagonist, ganirelix acetate (Antagon, 0.25 mg/day in 0.5 ml of normal saline, Organon, Inc., West Orange, New Jersey,) daily to suppress endogenous ovarian hormone production (16, 17, 18). This will begin following a separate medical screening at Reproductive Associates of Delaware 48 hours prior to initiating the hormone intervention to rule out other contraindications prior to beginning the treatment. YW will begin using the antagonist on days 26-28 of their menstrual cycle, and continue daily for 10-12 days. The experimental protocol will be conducted in YW after 3-4 days of using the GnRH antagonist. PMW will complete the experimental protocol prior to use of the 17β-estradiol (E2, 0.1 mg/day patch, Vivelle dot; estradiol patch).

Other: No to Low Endogenous Estrogen

Estrogen Add-Back

EXPERIMENTAL

Estradiol (E2, 0.1 mg/day patch, Vivelle dot; estradiol patch) will be administered for 7 days to both young and PMW. Young women will use the E2 over the last 7 days of Antagon administration.

Other: No to Low Endogenous Estrogen; Other: Estradiol

Interventions

No to Low Endogenous Estrogen OTHER

Ganirelix acetate (Antagon) will be used to prevent endogenous production of ovarian hormones in young women. Ganirelix is derived from native GnRH, and acts by competitively blocking GnRH receptors on the pituitary and subsequent pathways. Thus, administration of the GnRH antagonist (GnRHant) suppresses steroidogenesis, leading to low or undetectable serum estrogen and progesterone concentrations, which occurs within two days of initiation of administration (Oberye, Mannaerts, Huisman \& Timmer, 1999; Oberye, Mannaerts, Kleijn, \& Timmer, 1999).

Estrogen Add-Back; No to Low Endogenous Estrogen

Estradiol OTHER

Short term estradiol administration elicits changes in vascular function in women, and 0.1mg/day patch is the upper recommended limit for hormone therapy in women (Wenner, Taylor, \& Stachenfeld, 2011; Moreau, Hildreth, Meditz, Deane \& Kohrt, 2012).

Also known as: Vivelle dot

Estrogen Add-Back

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Young women between 18-35 years of age with regular menstrual cycles
• Postmenopausal women between 50-65 years of age and no more than 10 years past menopause
• Non-smoking
• BMI \< 30 kg/m2
• Free from known disease (heart disease, cancer, diabetes)

You may not qualify if:

• Current use of hormone therapy or within the past year
• Women using Depo-provera or an intra-uterine device (IUD)
• Pregnant, are planning on becoming pregnant, or are breast- feeding.
• History of stable or unstable angina
• Diabetes
• Neurological disease
• Lung disease
• Kidney or liver disease
• Cancer
• Hysterectomy
• Peripheral vascular disease
• History of blood clots
• Heart disease
• Fibroids
• High blood pressure

Sponsors & Collaborators

• University of Delaware: lead
• American Heart Association: collaborator

Study Sites (1)

University of Delaware

Newark, Delaware, 19716, United States

Location

Related Publications (22)

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• Wenner MM, Taylor HS, Stachenfeld NS. Progesterone enhances adrenergic control of skin blood flow in women with high but not low orthostatic tolerance. J Physiol. 2011 Feb 15;589(Pt 4):975-86. doi: 10.1113/jphysiol.2010.194563. Epub 2010 Dec 20.

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• Oberye JJ, Mannaerts BM, Kleijn HJ, Timmer CJ. Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers. Fertil Steril. 1999 Dec;72(6):1001-5. doi: 10.1016/s0015-0282(99)00413-6.

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  PMID: 9458917 BACKGROUND

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MeSH Terms

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Megan Wenner, PhD

  University of Delaware

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 2, 2017
• Study Start: July 1, 2016
• Primary Completion: April 30, 2022
• Study Completion: November 1, 2022
• Last Updated: November 14, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: No later than June 30, 2020
• Access Criteria: upon request

Locations

US (1)