Effects of Hormone Replacement Therapy on Arthralgia in Postmenopausal Women

Effects of Hormone Replacement Therapy on Arthralgia in Postmenopausal Women: a Randomized, Double-blind Controlled Trial

Arthralgia has been a common complaint in postmenopausal period which seems to be involved with estrogen depletion, although, its pathophysiology isn´t completely clarified. It seems to relate with the level of physical activity, climacteric symptoms and pain catastrophizing. In view of the multiple dimensions involved in arthralgia in postmenopausal women which characterize it as a complex phenomenon, this study aims to describe the effects of hormone replacement therapy in women aged between 45 and 55 years, considering estrogen as a possible anti-nociceptive factor.

Study Overview

• Status: Unknown
• Conditions: Arthralgia
• Intervention / Treatment: Drug: Conjugated Equine Estrogen; Drug: Placebo

Detailed Description

This study is a randomized double-blind controlled clinical trial with postmenopausal women aged between 45 and 55 years with chronic arthralgia related to climacteric. They will be evaluated climacteric symptoms, pain intensity, level of physical activity, pain catastrophising, depression, anxiety, quality of sleep and quality of life. The volunteers will be randomized, in the proportion 1:1, to treatment with either 0,625 mg conjugated equine estrogen, via oral administration, for 12 weeks or placebo, via oral administration, for 12 weeks. The randomization will be performed by a computer-generated random numbers list. The investigators will be blinded until completion of 12 weeks. Evaluation of climacteric symptoms, pain intensity, level of physical activity, pain catastrophising, depression, anxiety, quality of sleep and quality of life will be performed in the hospital at baseline, 1, 2, 3, 6 months and 15 days. In each visit, participants will be evaluated about adverse effects such as diarrhea, nausea and vomit.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maria Celeste Osório Wender, Ph.D; Phone Number: 55 51 3359-8117; Email: mceleste@ufrgs.br
• Study Contact Backup: Name: Fernanda Vargas Ferreira, Ph.D; Phone Number: 55 51 3359-8117; Email: fernandaferreira@unipampa.edu.br

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Recruiting
      • Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre
      • Contact: Maria Celeste Osório Wender, Ph.D; Phone Number: +55513359-8117; Email: mceleste@ufrgs.br
      • Contact: Fernanda Vargas Ferreira, Ph.D; Phone Number: +55513359-8117; Email: fernandaferreira@unipampa.edu.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• age between 45 and 55 years
• chronic arthralgia related to climacteric
• regular mammography and pap smear test in the last twelve months
• availability to attend hormone replacement therapy
• maximum of ten years of amenorrhea according to the criteria of Stages of Reproductive Aging Workshop (STRAW)
• without use of hormone replacement therapy, at least, previous six months
• no contraindication to hormone replacement therapy (current or past of breast and / or cervical cancer, severe current or recent heart disease, thromboembolism, hypertension with no control, metabolic diseases (but stable thyroid disease) and endometrial hyperplasia to be enlightened
• Informed consent

Exclusion Criteria:

• autoimmune diseases
• visceral pain (chronic pelvic pain, dyspareunia, irritable bowel syndrome)
• systemic diseases (rheumatic, neurological, oncology, sexually transmitted infection)
• body mass index of 30 or greater
• soy diet
• abuse of alcohol and drugs
• large surgeries

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conjugated Equine Estrogen; Thirty-six healthy postmenopausal women aged between 45 and 55 years will receive 0,625 mg/day conjugated equine estrogen (CEE) for 12 weeks. These 1 active pill containing conjugated equine estrogen, 0,625 mg will be provided by a laboratory with no trademark identification. The bottles will be numbered in code by a pharmaceutist not involved directly in study and they will donated to volunteers. During the intervening period, use of conjugated equine estrogen, there will be blinding. After this phase, blinding will be interrupted in order to identify volunteers who used the active drug.	Drug: Conjugated Equine Estrogen; Use of conjugated equine estrogen for 12 weeks. Adherence will be monitored during periodical hospital visits in order to receive pills.; Other Names: Drug active
Placebo Comparator: Placebo; Thirty-six healthy postmenopausal women aged between 45 and 55 years will receive placebo pills, identical in size, shape and color to the active drug, via oral administration, for 12 weeks. The bottles, without trademark identification, will be numbered in code by a pharmaceutist not involved directly in study and they will donated to volunteers. During the intervening period, use of placebo, there will be blinding. After this phase, blinding will be interrupted in order to identify volunteers who used the active drug and placebo.	Drug: Placebo; Use of placebo for 12 weeks. Adherence will be monitored during periodical hospital visits in order to receive pills.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arthralgia	Arthralgia´ll be measured by numeric scale (0-10).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Climacteric symptoms	Climacteric symptoms´ll be evaluated by Menopause Rating Scale - Brazilian Version. The score increases point by point with increasing severity of subjectively perceived symptoms in each of the 11 items.	6 months
Level of physical activity	Level of physical activity´ll be evaluated by International Physical Activity Questionnaire - Brazilian Version whose three levels of physical activity are low, moderate and high.	6 months
Pain Catastrophizing	Pain Catastrophizing´ll be evaluated by Pain Catastrophizing - Brazilian Version into three subscales being magnification, rumination, and helplessness. The higher the score, the more catastrophizing thoughts are present.	6 months
Health-related quality of life	Quality of life´ll be evaluated by Women´s Health Questionnaire - Brazilian Version (somatic symptoms, depressed mood, cognitive difficulties, anxiety and fear, sexual functioning, vasomotor symptoms, sleep problems, menstrual problems, and self-perceived attraction). The higher the score, the more pronounced the suffering and dysfunction.	6 months
Depression	Depression´ll be evaluated by Beck Depression Inventory - Brazilian Version. The standard cut-off scores are minimal, mild, moderate and severe depression.	6 months
Anxiety	Anxiety´ll be evaluated by Beck Anxiety Inventory - Brazilian Version. The standard cut-off scores are minimal, mild, moderate and severe depression.	6 months
Quality of sleep	Quality of sleep´ll be evaluated by Pittsburgh Sleep Quality Index - Brazilian Version. Lower scores denote a healthier sleep quality.	6 months

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Maria Celeste Osório Wender, Ph.D, Hospital de Clinicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): December 2, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: July 15, 2016
• First Posted (Estimate): July 20, 2016

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Arthralgia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: 16-0235

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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