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

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• Cardiovascular Diseases 4,904
• Atherosclerosis 1,567

Keywords

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

Cardiovascular Diseases

4,904 studies on the registry are indexed under Cardiovascular Diseases; 919 are open to participants now.

This study's planned enrollment of 150 is above the median of 100 across 2,738 interventional studies indexed under Cardiovascular Diseases.

Lead sponsor

This is the only study on the registry with Hanna Savolainen-Peltonen as lead sponsor.

Study arms

• Other
  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.

  Drug: Estradiol · Other: Placebo

• Other
  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

  Drug: Estradiol · Other: Placebo

• Active comparator
  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.

  Drug: Estradiol

Interventions

• DrugEstradiol

  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.

• OtherPlacebo

  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.

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).

   Time frame: 8 and 14 weeks

Secondary outcomes

1. 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.

   Time frame: 5 and 13 weeks

2. 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.

   Time frame: 5 and 13 weeks

3. 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.

   Time frame: 5 and 13 weeks

4. 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.

   Time frame: 5 and 13 weeks

5. 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.

   Time frame: 5 and 13 weeks

6. Biomarker: Concentration of endothelin-1

   Concentration of endothelin-1 (ET-1, a vasoconstrictive marker, unit pmol/l)

   Time frame: 5 and 8 weeks

7. Biomarker: Concentration of nitrite and nitrate

   Concentration of nitrite and nitrate (markers of released nitric oxide and consequent vasodilation, unit µmol/l)

   Time frame: 5 and 8 weeks

8. Biomarker: Concentration of Asymmetric Dimethylarginine

   Concentration of asymmetric Dimethylarginine (ADMA, inhibitor of NO synthesis and indicator of endothelial dysfunction, unit µmol/l)

   Time frame: 5 and 8 weeks

9. 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)

   Time frame: 2, 5 and 8 weeks

10. Biomarker: Concentration of coagulation factors

    Concentration of coagulation factors: fibrinogen (g/l), plasminogen activator inhibitor-1 (IU/ml), D-dimer (mg/l)

    Time frame: 5 and 8 weeks

11. 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)

    Time frame: 5 and 8 weeks

12. Biomarker: Concentration of carbohydrate metabolism

    Concentration of carbohydrate metabolism: fasting glucose (mmol/l) and insulin (mU/l)

    Time frame: 5 and 8 weeks

13. Biomarker: Concentration of oxidative stress

    Concentration of oxidative stress: oxidized LDL (U/l)

    Time frame: 5 and 8 weeks

14. Biomarker: Concentration of inflammatory factors

    Concentration of interferon-γ (IFN-γ, unit ng/ml), monocyte chemoattractant (MCP-1, unit pg/ml), macrophage inflammatory protein 1α (MIP-1α, unit pg/ml), tumor necrosis factor α (TNF-α, unit pg/ml) and high-sensitivity C-reactive protein (hs-CRP, unit mg/l)

    Time frame: 5 and 8 weeks

15. 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)

    Time frame: 5 and 8 weeks

16. 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)

    Time frame: 5 and 8 weeks

17. Concentration of matrix metalloproteinases

    Concentration of matrix metalloproteinases (MMPs, unit µM)

    Time frame: 5 and 8 weeks

18. 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.

    Time frame: 1 and 19 weeks