The Benefits and Risks of Different Menopausal Hormone Replacement Therapy Regimes in the Treatment of Menopause Syndrome

The Effect and Risk of Conjugated Estrogens Combined With Different Types of Progestin in the Treatment of Menopause Syndrome During Window Phase

A prospective, open-label, randomized controlled clinical trial to compare the benefits and risks of half-dose or standard-dose conjugated equine estrogens(CEE) plus natural progesterone or dydrogesterone in menopausal hormone therapy .

Study Overview

• Status: Unknown
• Conditions: Menopause Syndrome
• Intervention / Treatment: Drug: CEE 0.625 mg/MP 100mg; Drug: CEE 0.3 mg/MP 100mg; Drug: CEE 0.625mg/dydrogesterone

Detailed Description

This is a prospective, open-label, randomized controlled clinical trial compare the benefits and risks of half-dose or standard-dose conjugated equine estrogens(CEE) plus natural progesterone or dydrogesterone in menopausal hormone therapy during window phase. 120 Healthy postmenopausal women with intact uterus seeking treatment for menopausal symptoms are enrolled in this study.Participants are randomized into three groups, the CEE 0.3 mg/micronized progesterone (MP) 100 mg group; CEE 0.625 mg/MP 100 mg group; CEE 0.625 mg/dydrogesterone 10 mg group,metabolic parameters,body composition,bone mineral density,breast cancer risk factors and life quality will be measure at baseline,one year and two year intervention.The investigators hypothesize there may be differences of these parameters measured among three groups after intervention.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • China/Beiing
    • Beijing, China/Beiing, China, 100000
      • Lei Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. 40 and 60 years old;
2. natural amenorrhea for more than 6 months but less than 5 years;
3. suffered by menopause symptoms and seeking for treatment;
4. serum follicle-stimulating hormone levels >40 IU/L and serum estradiol <30 pg/ml.

Exclusion Criteria:

1. contraindications for menopausal hormone therapy;
2. complications including: uterine myoma more than 3 centimeter in diameter, endometriosis, uncontrolled hypertension or diabetes mellitus, thromboembolic disease history or high risk for developing thromboembolic disease, epilepsy, asthma, hyperprolactinemia, first degree relative has breast cancer;
3. cardiovascular, chronic liver, thyroid or kidney diseases; a history of cancer; a disease or condition that could influence the participants' ability to follow the study protocol;
4. alcohol or drug abuse within the last 3 months;
5. use of hormone therapy in the past 3months;
6. endometrial thickness more than 5mm even after progestin withdrawal;
7. abnormal cervical scraping smear;
8. allergic to any ingredient of the drugs;
9. participation in other clinical trials within the last 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CEE 0.625 mg/MP 100mg; CEE 0.625 mg/micronized progesterone (MP) 100 mg daily for the last 12 days of every 28 days for two years	Drug: CEE 0.625 mg/MP 100mg; CEE 0.625 mg daily/MP 100mg daily for the last 12 days of every 28 days for two years
Experimental: CEE 0.3 mg/MP 100mg; CEE 0.3mg/micronized progesterone (MP) 100 mg daily for the last 12 days of every 28 days for two years	Drug: CEE 0.3 mg/MP 100mg; CEE 0.3 mg daily/MP 100mg daily for the last 12 days of every 28 days for two years
Experimental: CEE 0.625 mg/dydrogesterone 10mg; CEE 0.625 mg/dydrogesterone 10 mg daily for the last 12 days of every 28 days for two years	Drug: CEE 0.625mg/dydrogesterone; CEE 0.3 mg/dydrogesterone 10mg daily for the last 12 days of every 28 days for two years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-cholesterol		5 minutes
body fat mass percentage	DEXA method	5 minutes
breast mammography		5 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glucose		5 minutes
bone mineral density		5 minutes
Mini-mental State Examination score	Questionnaire.The score range is 0-30.Total score greater than or equal to 24 points indicates a normal cognition,below this, scores can indicate cognitive impairment.	5 minutes
HAD scale	questionnaire to evaluate anxiety and depression.The total score is 0-20.Total score 0-7 is normal,8-10 maybe borderline anxiety or depression,11-20 indicates obvious anxiety or depression.	5 minutes
modified Kupperman score	questionnaire to evaluate the menopause symptom.The total score range is 0-63.Total score below 6 is normal,6-15 is mild,16-30 is moderate, above 30 is severe	5 minutes
Endometrial thickness	ultrasound	5 minutes
weight		5 minutes
serum creatinine		5 minutes
serum glutamic pyretic transaminase		5 minutes

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Aijun Sun, MD, Peking Union Medical College Hospital,Peking Union Medical College, Chinese Academy of Medicine Sciences

Publications and helpful links

General Publications

• Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, Bassford T, Burke G, Torrens J, Howard BV; Women's Health Initiative Investigators. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004 Jul;47(7):1175-1187. doi: 10.1007/s00125-004-1448-x. Epub 2004 Jul 14.
• Thorneycroft IH, Lindsay R, Pickar JH. Body composition during treatment with conjugated estrogens with and without medroxyprogesterone acetate: analysis of the women's Health, Osteoporosis, Progestin, Estrogen (HOPE) trial. Am J Obstet Gynecol. 2007 Aug;197(2):137.e1-7. doi: 10.1016/j.ajog.2007.05.042.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: February 2, 2018
• First Submitted That Met QC Criteria: February 10, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): February 19, 2018
• Last Update Submitted That Met QC Criteria: February 10, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: progestin; Menopause Syndrome; low dose estrogen
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Dydrogesterone
• Other Study ID Numbers: HRT14021808

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Network platform, and the website will be attached later.
• IPD Sharing Time Frame: Within 2 months after the trial complete
• IPD Sharing Access Criteria: Data access requests will be reviewed by an external independent review panel.Requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No