Effects of Hormone Replacement Therapy on Cardiovascular Risk and Body Composition Parameters

June 26, 2020 updated by: Hospital de Clinicas de Porto Alegre

Effects of Oral and Non-oral Hormonal Therapy on Cardiovascular Risk and Body Composition Parameters in Postmenopausal Women

Menopause is defined as the last episode of menstrual bleeding, resulting from the interruption of ovarian function by follicular depletion. It is characterized by the presence of amenorrhea associated with increased levels of FSH and low levels of estradiol. The decline in estrogenic levels is associated with several organic changes, from vasomotor symptoms to impaired bone mass and urogenital atrophy. Although for some patients menopause is asymptomatic or oligosymptomatic, many women experience intense symptoms, which profoundly affect quality of life.

Proper assessment and treatment of postmenopausal women can significantly improve climacteric symptoms. Target tissue, hormone therapy regimen and variations between patients will influence the effects of treatment. Regarding estrogen, the main factors that influence the therapeutic response are the type of hormone used, the dose and the route of administration. The skin metabolizes only a small part of estradiol. Thus, the transdermal route reaches adequate therapeutic levels from a lower dose of estrogen.

The present study aims to evaluate and compare the effects of low dose of oral estradiol associated with oral progesterone and transdermal estradiol associated with vaginal progesterone on variables related to inflammation, coagulation and body composition parameters.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hormone therapy (HT) was available since 1942 in tablets containing conjugated equine estrogens. Since the 1970s, it has been recommended to add progestogens to the treatment of women with a uterus to prevent endometrial hyperplasia. HT has been shown to be very effective in climacteric syndrome, relieving 90% of hot flushes that affect women in the menopausal transition.

Target tissue, HT regimen and variations between patients will influence the effects of treatment. Regarding estrogen, the main factors that influence the therapeutic response are the type of hormone used, the dose and the route of administration. The most physiological type of estrogen is 17β estradiol, available in the form of gel and adhesive. The skin metabolizes only a small part of estradiol. Thus, the transdermal route reaches adequate therapeutic levels from a lower dose of estrogen. Also, the transdermal route prevents the first hepatic passage, resulting in more stable levels of estradiol in the circulation, without supraphysiological liver concentrations. The bioavailability of estrogen after undergoing metabolism in the liver is approximately 2 to 10% of the total administered. This hepatic passage can result in greater variability in hormone levels, as well as activation of prothrombotic and inflammatory factors. In addition, hepatic metabolism can change the therapeutic effects of estrogen and other pharmacological agents.

The present study aims to evaluate and compare the effects of low dose of oral estradiol associated with oral progesterone and transdermal estradiol associated with vaginal progesterone on variables related to inflammation, coagulation and body composition parameters. This is a prospective randomized controlled study, and the study population includes postmenopausal patients with climacteric symptoms, who have not been using hormone therapy for at least three months. Patients will receive three months of oral hormonal treatment (estradiol 1mg and micronized natural progesterone 200mg 14 days a month) and three months of non-oral hormonal treatment (percutaneous estradiol gel 1.5mg and micronized progesterone 200mg vaginal 14 days a month).

Patients with climacteric symptoms who meet the inclusion and the exclusion criteria will be included in the study. The entire sample will receive both hormonal therapies sequentially and the patients will be divided between the groups (oral therapy and non-oral therapy) to start the study by random allocation. There will be no period of suspension between treatments, that is, at the end of the first three months of the study, the group initially treated with oral therapy starts receiving non-oral treatment for another three months, and the group initially treated with non-oral therapy starts to receive oral therapy also for another three months.

This project has already been approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre. Post-informed written consent will be obtained from all patients, in accordance with health research standards.

The results will be presented as means and standard deviation or medians and interquartile range. Analysis of variance for latin square will be used to evaluate carryover effect. Two-way ANOVA for repeated samples will be used to compare baseline conditions and the two treatments. Bonferroni's adjustment will be used for multiple comparisons. Bivariate correlations between continuous numerical variables will be examined using Pearson or Spearman correlation coefficients, according to the Gaussian or non-Gaussian nature of the variable, respectively. Statistical analysis will be performed using Statistical Package for Social Sciences (SPSS, Chicago, IL, USA), with a value of p <0.05 being considered significant.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90035903
        • Recruiting
        • Hospital de Clinicas de Porto Alegre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 58 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Six months or more of amenorrhea and FSH levels> or = at 35 mIU / ml;
  • Menopause for a maximum of three years;
  • Mammography and cytology of recent cervix (from the last 12 months);
  • Signature of the Informed Consent Form.

Exclusion Criteria:

  • Menopause age below 40 years;
  • Use of hormonal therapy in the three months preceding the study;
  • Uncontrolled diabetes mellitus;
  • Endometrial thickening (endometrial thickness greater than 0.5 cm);
  • Neoplasm of breast, colon or endometrium;
  • History of thromboembolism or established cardiovascular disease;
  • Previous hysterectomy;
  • Active smoking;
  • Use of medication to treat osteoporosis in the last 12 months: bisphosphonates, denosumab, teriparatide, SERMs (selective estrogen receptor agonist).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Oral hormone therapy
Estradiol 1mg and micronized natural progesterone 200mg 14 days a month (oral)
Drug: Oral hormone therapy (estradiol and micronized natural progesterone)
Oral hormone therapy - estradiol 1mg every day and micronized natural progesterone 200mg only 14 days a month
ACTIVE_COMPARATOR: Non-oral hormone therapy
Percutaneous estradiol gel 1.5mg and micronized progesterone 200mg vaginal 14 days a month (non-oral)
Drug: Non-oral hormone therapy (estradiol and micronized natural progesterone)
Percutaneous estradiol gel 1.5mg every day and micronized progesterone 200mg vaginal only 14 days a month

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in body composition parameters
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
Lean mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)
Before hormone therapy and after 3 and 6 months of treatment
Change in body composition parameters
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
Fat mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)
Before hormone therapy and after 3 and 6 months of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lipid profile
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
HDL, LDL, triglycerides (evaluated by blood sample)
Before hormone therapy and after 3 and 6 months of treatment
Serum glucose
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
(evaluated by blood sample)
Before hormone therapy and after 3 and 6 months of treatment
Blood pressure
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
Before hormone therapy and after 3 and 6 months of treatment
Weight
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
With body mass index (kg/m²)
Before hormone therapy and after 3 and 6 months of treatment
Physical activity
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
Evaluated by pedometer
Before hormone therapy and after 3 and 6 months of treatment
Bone mineral density (g/cm²)
Time Frame: Before hormone therapy and after 3 and 6 months of treatment
Evaluated by dual energy X-ray absorptiometry (DXA)
Before hormone therapy and after 3 and 6 months of treatment
Bone metabolism
Time Frame: Before hormone therapy
Calcium, phosphorus, PTH, albumin, 25 OH vitamin D (evaluated by blood sample)
Before hormone therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital de Clinicas de Porto Alegre

Investigators

  • Principal Investigator: Poli Mara Spritzer, PhD, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 9, 2015

Primary Completion (ANTICIPATED)

June 1, 2021

Study Completion (ANTICIPATED)

December 1, 2021

Study Registration Dates

First Submitted

June 23, 2020

First Submitted That Met QC Criteria

June 26, 2020

First Posted (ACTUAL)

July 1, 2020

Study Record Updates

Last Update Posted (ACTUAL)

July 1, 2020

Last Update Submitted That Met QC Criteria

June 26, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-0363

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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