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

Cardiovascular Diseases Clinical Trial

Official title:

Randomized Comparative Trial Between Abrupt and Tapered Discontinuation of Postmenopausal Hormone Therapy: Impact on Endothelial Function, Recurrence of Vasomotor Symptoms and Quality of Life

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04050592
• Other study ID #: FINNHT1
• Status: Recruiting
• Phase: Phase 4
• Start date: February 19, 2020
• Est. completion date: December 2022

Study information

• Verified date: February 2021
• Source: Helsinki University Central Hospital
• Contact: Hanna Savolainen-Peltonen, MD, PhD
• Phone: +35894711
• Email: hanna.savolainen-peltonen[@]hus.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Estrogen Replacement Therapy
• Menopause

Intervention

Drug:
• 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.

Other:
• 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.

Locations

Country	Name	City	State
Finland	HUS Women's Hospital	Helsinki

Sponsors (2)

Lead Sponsor	Collaborator
Hanna Savolainen-Peltonen	University of Southern California

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Symptom diary	Participants will keep a symptom diary reporting the exact number, severity and timing of hot flashes during three periods each lasting three weeks: the first period at baseline, the second starting on the 10th week and the third starting on the 18th week. Based on the diary notes, we can assess, how frequent, severe and durable the symptoms are during each period.	5 and 13 weeks
Secondary	Women's Health Questionnaire	Women's Health Questionnaire measures emotional and physical health. WHQ includes 37 questions that are answered based on the momentary feeling on a four-point scale (Yes, definitely; Yes, sometimes; No, not so much; No, not at all). The participant receives 37 points at minimum and 148 points at maximum.	5 and 13 weeks
Secondary	Symptom questionnaire	The symptom questionnaire includes 19 questions about the frequency of menopausal symptoms (such as hot flashes, night sweats and insomnia) experienced during the past two weeks, and each question is evaluated on a four-point scale (never or seldom; once a month; once a week; almost daily).The participant receives 19 points at minimum and 76 points at maximum.	5 and 13 weeks
Secondary	European Quality of Life Instrument	EuroQoL includes a health classification index that covers five dimensions of HRQL (mobility, self-care, usual activities, pain/discomfort, anxiety/depression).The participant receives 5 points at minimum and 15 points at maximum.; In the second part of the questionnaire, there is a visual analogue scale ranging from 0, "worst imaginable health state", to 100, "best imaginable health state". Thus, the participant receives from 0 to 100 points from this part of the questionnaire.	5 and 13 weeks
Secondary	Female Sexual Function Index	This questionnaire includes 19 questions about sexuality. The questions are answered on a five-point scale (almost always or always; most times; sometimes; a few times; almost never or never). The participant receives 19 points at minimum and 95 points at maximum.	5 and 13 weeks
Secondary	Biomarker: Concentration of endothelin-1	Concentration of endothelin-1 (ET-1, a vasoconstrictive marker, unit pmol/l)	5 and 8 weeks
Secondary	Biomarker: Concentration of nitrite and nitrate	Concentration of nitrite and nitrate (markers of released nitric oxide and consequent vasodilation, unit µmol/l)	5 and 8 weeks
Secondary	Biomarker: Concentration of Asymmetric Dimethylarginine	Concentration of asymmetric Dimethylarginine (ADMA, inhibitor of NO synthesis and indicator of endothelial dysfunction, unit µmol/l)	5 and 8 weeks
Secondary	Biomarker: concentration of sex hormones	Concentration of sex hormones: Follicle-stimulating hormone (FSH, unit IU/l), luteinizing hormone (LH, unit IU/l), estrone (pmol/l), estradiol (nmol/l) and sex hormone-binding globulin (SHBG, unit nmol/l)	2, 5 and 8 weeks
Secondary	Biomarker: Concentration of coagulation factors	Concentration of coagulation factors: fibrinogen (g/l), plasminogen activator inhibitor-1 (IU/ml), D-dimer (mg/l)	5 and 8 weeks
Secondary	Biomarker: Concentration of lipids	Concentration of lipids: high-density lipoprotein cholesterol (HDL, unit mmol/l), low-density lipoprotein cholesterol (LDL, unit mmol/l), very low-density lipoprotein cholesterol (VLDL, unit mmol/l), triglycerides (mmol/l) and lipoprotein A (g/l)	5 and 8 weeks
Secondary	Biomarker: Concentration of carbohydrate metabolism	Concentration of carbohydrate metabolism: fasting glucose (mmol/l) and insulin (mU/l)	5 and 8 weeks
Secondary	Biomarker: Concentration of oxidative stress	Concentration of oxidative stress: oxidized LDL (U/l)	5 and 8 weeks
Secondary	Biomarker: Concentration of inflammatory factors	Concentration of interferon-? (IFN-?, unit ng/ml), monocyte chemoattractant (MCP-1, unit pg/ml), macrophage inflammatory protein 1a (MIP-1a, unit pg/ml), tumor necrosis factor a (TNF-a, unit pg/ml) and high-sensitivity C-reactive protein (hs-CRP, unit mg/l)	5 and 8 weeks
Secondary	Biomarker: Concentration of advanced glycation end products and soluble form of their receptor	Concentration of advanced glycation end products (AGE, unit U/ml) and soluble form of their receptor (sRAGE, unit pg/ml)	5 and 8 weeks
Secondary	Biomarker: Concentration of cellular adhesion molecules	Concentration of cellular adhesion molecules: E selectin (mg/dl), intracellular cell-adhesion molecule-1 (ICAM-1, unit ng/ml), vascular cell adhesion molecule-1 (VCAM-1, unit ng/ml)	5 and 8 weeks
Secondary	Concentration of matrix metalloproteinases	Concentration of matrix metalloproteinases (MMPs, unit µM)	5 and 8 weeks
Secondary	Rey Auditory Verbal Learning Test (RAVLT)	RAVLT evaluates a wide diversity of cognitive functions. Participant is given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the client must again repeat the original list of 15 words and then again after 30 minutes.	1 and 19 weeks