Double-blind placebo controlled trial of tibolone and oestrogen hormone therapy on oxidative stress associated to postmenopausal disturbances in women with early postmenopause: MOS study

ISRCTN ISRCTN14939779
DOI https://doi.org/10.1186/ISRCTN14939779
Secondary identifying numbers N/A
Submission date
08/09/2017
Registration date
19/09/2017
Last edited
11/10/2023
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Menopause is an expected event in a woman’s life due to ovarian aging. Ovarian aging is produced by a series of hormonal changes that leads to the erratic production of estrogens that eventually leads to low estrogen levels (menopause). Menopause is associated with multiple symptoms that affects self-esteem and quality of life of the women. The marked reduction in estrogens has been shown to increase levels of oxidative stress (OS) in the body. Oxidative stress is an imbalance between the production of free radicals and the body’s ability to neutralize them by antioxidans. Therefore menopause is a risk factor for OS, which may be due to an estrogenic deficiency and severity of symptoms. Hormone therapy (HT) with estrogen with or without progestin (synthetic progestogens), is a therapeutic alternative for women seeking help to ease their symptoms that occur after menopause, also with antioxidant effect. However, this type of therapy is controversial and can have negative short-term and long-term effects, even leading to treatment withdrawal. An alternative to HT has been the use of tibolone, a molecule with selective activity as estrogen, progestin and androgen, that has effect over postmenopausal symptoms and has not shown side effects, but it has not been clear whether it is an antioxidant molecule. The aim of this study is to determine the effect of tibolone on OS associated with mood disorders, climacteric symptoms, loss of muscle function and bone mineral density, that modify self-esteem and quality of life in postmenopausal women, compared with HT and placebo.

Who can participate?
Women aged 45-59 who have not had menstruation in 12 months.

What does the study involve?
Participants are randomly allocated to one of three groups. Those in the first group receive 2.5 mg/d of tibolone daily for 18 months. Those in the second group receive 0.625 mg/g of synthetic conjugated estrogen as well as 5 mg/10 g of medroxyprogesterone. Those in the last group receive a placebo (a dummy medication). Participants are followed up at six months to measure their oxidative stress and other symptoms.

What are the possible benefits and risks of participating?
The treatment may improve participant’s women postmenopausal symptoms and quality of life. There are no risks to the health for participants with hormone treatment or placebo.

Where is the study run from?
National Autonomous University of Mexico (Mexico)

When is the study starting and how long is it expected to run for?
November 2016 to April 2020 (updated 10/07/2020, previously: July 2019)

Who is funding the study?
National Autonomous University of Mexico (Mexico)

Who is the main contact?
Dr Martha A. Sanchez-Rodriguez
masanrod@yahoo.com.mx

Contact information

Dr Martha A. Sanchez-Rodriguez
Scientific

Av. Guelatao No. 66 Col
Ejercito de Oriente
Mexico City
09230
Mexico

ORCiD logoORCID ID 0000-0002-7130-4074
Phone +52 15556230750
Email masanrod@yahoo.com.mx

Study information

Study designProspective randomized double-blind trial single-centre
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Community
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleMenopause and Oxidative Stress Study (MOS): Effects of tibolone and oestrogen hormone therapy on oxidative stress associated to mood disturbances, insomnia, loss of muscle function and bone mineral density, that affect self-esteem and quality of life in postmenopausal women
Study acronymMOS
Study objectivesConsidering that tibolone improves the symptoms present in postmenopausal period, and has a possible antioxidant activity, we assume that women with tibolone therapy will have a decrease in oxidative stress associated with postmenopausal disturbances, improving their quality of life and self-esteem, as well as those taking oestrogen therapy, and with an opposite effect to women receiving placebo.
Ethics approval(s)Ethics Committee of the Universidad Nacional Autonoma de Mexico, 12/01/2017, ref: FESZ/DEPI/CI/004/17;
Health condition(s) or problem(s) studiedPostmenopausal women with or without mood disturbances, insomnia, loss of muscle function and bone mineral density, that affect self-esteem and quality of life.
InterventionThe treatment allocation is done using the simple random method with a scientific calculator.

Three groups are formed:
1. Women with 2.5 mg/d of tibolone
2. Women with 0.625 mg/d of synthetic conjugated oestrogens + 5 mg/10 d of medroxyprogesterone
3. Women taking placebo (pharmaceutical presentation similar to the treatment)
All the treatments are taken by oral administration.

The therapy follow up will be during 18 months with assessments at baseline and ever 6 months.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)tibolone
Primary outcome measureOxidative stress is measured using lipoperoxide levels by TBARS assay, erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx), total plasma antioxidant status and uric acid, using Randox Laboratories kits, at baseline measurement prior to initiation of therapy, and every 3 months.
Secondary outcome measures1. Hot flashes is measured using women's self-report diaries regarding how many total hot flashes they had per day during a week as well as information regarding the severity of each of these hot flashes (mild, moderate, severe, or very severe). The diaries are picked up at baseline and every 3 months.
2. Insomnia is measured using the Athens Insomnia Scale (Spanish version) at baseline and every 3 months
3. Depression is measured using the Zung Self-Rating Depression Scale (Spanish version) at baseline and every 3 months
4. Anxiety is measured using the Zung Self-Rating Anxiety Scale (Spanish version) at baseline and every 3 months
5. Quality of life and self-esteem is measured using the WHO Quality of Life-brief and the Coopersmith Self-Esteem Inventory (Spanish version), respectively, at baseline and every 3 months
6. Handgrip strength is measured with a dynamometer and the muscle mass by bioimpedance analysis, as muscle function tests, at baseline and every 6 months
7. Bone mineral density is measured using at the peripheral DXA in hip and column at baseline and every 6 months
Overall study start date28/11/2016
Completion date30/04/2020

Eligibility

Participant type(s)Healthy volunteer
Age groupAdult
SexFemale
Target number of participantsn= 150, 50 by group
Key inclusion criteria1. Women aged 45-59 with intact uterus
2. At least 12 months of spontaneous amenorrhea and/or serum estradiol levels less 25 pg/mL and follicle stimulating hormone (FSH) levels higher 50 mU/mL
Key exclusion criteria1. Women with cardiovascular, renal, hepatic or cancer disease
2. Antioxidant supplement intake for at least six months prior to the beginning of the study
2. Previous hormone therapy
3. Those who do not agree to participate in the study
Date of first enrolment02/10/2017
Date of final enrolment01/04/2020

Locations

Countries of recruitment

  • Mexico

Study participating centre

National Autonomous University of Mexico
Faculty of Higher Studies-Zaragoza
Guelatao # 66
Mexico City
09230
Mexico

Sponsor information

National Autonomous University of Mexico
University/education

Av. Universidad 3000
Universidad Nacional Autónoma de México CU
Mexico City
04510
Mexico

Website http://www.zaragoza.unam.mx/
ROR logo "ROR" https://ror.org/01tmp8f25

Funders

Funder type

University/education

National Autonomous University of Mexico

No information available

Results and Publications

Intention to publish date30/04/2021
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned publication in a high-impact peer reviewed journal.The study protocol is in Spanish and it is not available on line. Please contact the author to request a copy.
IPD sharing planThe datasets generated during and/or analysed during the current study are/will be available upon request from Dr. Martha A. Sanchez-Rodriguez, e-mail: masanrod@yahoo.com.mx or request a copy in the institutional website: http://condor.zaragoza.unam.mx/fesz_website_2011/?page_id=4004.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Other publications Oxidative Stress Risk Is Increased with a Sedentary Lifestyle during Aging in Mexican Women 25/10/2021 11/10/2023 Yes No

Editorial Notes

11/10/2023: Publication reference added.
10/07/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 15/12/2017 to 01/04/2020.
2. The overall end date was changed from 30/07/2019 to 30/04/2020.
3. The intention to publish date was changed from 15/10/2019 to 30/04/2021.
4. The plain English summary was updated to reflect these changes.