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

Sponsor

Hospital de Clinicas de Porto Alegre (Other)

Overall Status

Unknown status

CT.gov ID

NCT04453332

Collaborator

(none)

Enrollment

Location

Arms

73.8

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Menopause Hormone Replacement Therapy	Drug: Oral hormone therapy (estradiol and micronized natural progesterone) Drug: Non-oral hormone therapy (estradiol and micronized natural progesterone)	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Prospective randomized controlled studyProspective randomized controlled study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 9, 2015

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in body composition parameters [Before hormone therapy and after 3 and 6 months of treatment]
Lean mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)
Change in body composition parameters [Before hormone therapy and after 3 and 6 months of treatment]
Fat mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 58 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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).