Discontinuation of Postmenopausal Hormone Therapy: Impact on the Cardiovascular System and Quality of Life

NCT04050592 | Unknown Phase 4

• 1 other identifier: FINNHT1
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Although the impact of postmenopausal hormone therapy (HT) on cardiovascular disease risk has been studied in several large randomized trials, little is known about the acute cardiovascular consequences of HT discontinuation. In this randomized, double-blind, placebo-controlled trial, the investigators will compare the cardiovascular consequences of abrupt and tapered modes of HT discontinuation in 150 Finnish healthy postmenopausal women under age 60 years. The primary outcome is brachial artery flow-mediated dilatation. In addition, biochemical markers will be measured during the study period of 20 weeks. Health-related quality of life, frequency of hot flush recurrence and other menopausal symptoms will be also assessed in these groups. The trial will provide new high-quality information about the cardiovascular safety as well as the correct timing and method of HT discontinuation.

Conditions

Menopause; Atherosclerosis; Cardiovascular Diseases; Estrogen Replacement Therapy

Keywords

Randomized Controlled Trial; Menopause; Hormone Therapy; Vasomotor symptoms; Quality of Life; Cardiovascular diseases; Endothelium

Outcome Measures

Primary Outcomes (1)

• Brachial artery flow-mediated dilation (FMD)

  The primary outcome in this study is brachial artery flow-mediated dilation (FMD) to assess endothelial function. To induce reactive hyperemia, a sphygmomanometer cuff is placed on the forearm and inflated to a suprasystolic pressure for five minutes, after which the cuff is deflated. The brachial artery diameter is measured at baseline and during reactive hyperemia, and the relative change in diameter (in millimeters) is calculated. We measure FMD at baseline (at study week 5) and after HT discontinuation (at study weeks 13 and 19).

  8 and 14 weeks

Secondary Outcomes (18)

• Symptom diary

  5 and 13 weeks

• Women's Health Questionnaire

  5 and 13 weeks

• Symptom questionnaire

  5 and 13 weeks

• European Quality of Life Instrument

  5 and 13 weeks

• Female Sexual Function Index

  5 and 13 weeks

Study Arms (3)

Group A, Abrupt Discontinuation

OTHER

Women in group A will discontinue HT (estradiol, 2 mg daily) abruptly after study week 9 and will continue with placebo for study weeks 10-20.

Drug: Estradiol; Other: Placebo

Group B, Tapered Discontinuation

OTHER

Women in group B will discontinue HT (estradiol, 2 mg daily) gradually during study weeks 7-9, as follows: * weeks 7-9: 1 mg estradiol daily for 10 days and then 1 mg estradiol every other day for 11 days. * weeks 10-20: placebo

Drug: Estradiol; Other: Placebo

Group C, Control Group

ACTIVE COMPARATOR

Women in Group C, the control group, will continue with HT (estradiol, 2 mg daily) throughout the whole study period of 20 weeks.

Drug: Estradiol

Interventions

Estradiol DRUG

Active intervention is estradiol. Hormone therapy (HT) of all 150 participants will be standardized to 2.0 mg of oral estradiol (E2) without progestogen for six weeks prior to randomization. After that participants will be randomized into three groups (A, B, C) of equal size.

Group A, Abrupt Discontinuation; Group B, Tapered Discontinuation; Group C, Control Group

Placebo OTHER

Those in groups A and B will switch from estradiol to placebo at the beginning of the 10th week after abrupt or tapered discontinuation of HT.

Group A, Abrupt Discontinuation; Group B, Tapered Discontinuation

Eligibility Criteria

• Age: Up to 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• healthy postmenopausal women
• age ≤ 60 years
• has used postmenopausal hormone therapy for at least 3 years

You may not qualify if:

• any clinically significant disease
• use of regular medication
• history of cardiovascular events
• history of smoking
• body mass index over 30 kg/m2
• thickness of endometrium over 6 millimeters

Sponsors & Collaborators

• Hanna Savolainen-Peltonen: lead
• University of Southern California: collaborator

Study Sites (1)

HUS Women's Hospital

Helsinki, 00290, Finland

RECRUITING

MeSH Terms

Conditions

Atherosclerosis; Cardiovascular Diseases

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

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

• Tomi Mikkola, MD, PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hanna Savolainen-Peltonen, MD, PhD

CONTACT

+35894711; hanna.savolainen-peltonen@hus.fi

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., Ph.D., associate professor

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: August 8, 2019
• Study Start: February 19, 2020
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: February 15, 2021

Record last verified: 2021-02

Locations

FI (1)