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

NCT ID: NCT04050592

Last Updated: 2021-02-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-19
• Study Completion Date: 2022-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Group A, Abrupt Discontinuation

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.

Group Type: OTHER

Estradiol

Intervention Type: 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.

Placebo

Intervention Type: 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 B, Tapered Discontinuation

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

Group Type: OTHER

Estradiol

Intervention Type: 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.

Placebo

Intervention Type: 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 C, Control Group

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

Group Type: ACTIVE_COMPARATOR

Estradiol

Intervention Type: 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.

Interventions

Estradiol

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Southern California

OTHER

Sponsor Role: collaborator

Hanna Savolainen-Peltonen

OTHER

Sponsor Role: lead

Responsible Party

Hanna Savolainen-Peltonen

M.D., Ph.D., associate professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Tomi Mikkola, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Central Hospital

Locations

HUS Women's Hospital

Helsinki, , Finland

Site Status: RECRUITING

Countries

Finland

Central Contacts

Hanna Savolainen-Peltonen, MD, PhD

Role: CONTACT

hanna.savolainen-peltonen@hus.fi

+35894711

Other Identifiers

FINNHT1

Identifier Type: -

Identifier Source: org_study_id