<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04453332</url>
  </required_header>
  <id_info>
    <org_study_id>2015-0363</org_study_id>
    <nct_id>NCT04453332</nct_id>
  </id_info>
  <brief_title>Effects of Hormone Replacement Therapy on Cardiovascular Risk and Body Composition Parameters</brief_title>
  <official_title>Effects of Oral and Non-oral Hormonal Therapy on Cardiovascular Risk and Body Composition Parameters in Postmenopausal Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Menopause is defined as the last episode of menstrual bleeding, resulting from the&#xD;
      interruption of ovarian function by follicular depletion. It is characterized by the presence&#xD;
      of amenorrhea associated with increased levels of FSH and low levels of estradiol. The&#xD;
      decline in estrogenic levels is associated with several organic changes, from vasomotor&#xD;
      symptoms to impaired bone mass and urogenital atrophy. Although for some patients menopause&#xD;
      is asymptomatic or oligosymptomatic, many women experience intense symptoms, which profoundly&#xD;
      affect quality of life.&#xD;
&#xD;
      Proper assessment and treatment of postmenopausal women can significantly improve climacteric&#xD;
      symptoms. Target tissue, hormone therapy regimen and variations between patients will&#xD;
      influence the effects of treatment. Regarding estrogen, the main factors that influence the&#xD;
      therapeutic response are the type of hormone used, the dose and the route of administration.&#xD;
      The skin metabolizes only a small part of estradiol. Thus, the transdermal route reaches&#xD;
      adequate therapeutic levels from a lower dose of estrogen.&#xD;
&#xD;
      The present study aims to evaluate and compare the effects of low dose of oral estradiol&#xD;
      associated with oral progesterone and transdermal estradiol associated with vaginal&#xD;
      progesterone on variables related to inflammation, coagulation and body composition&#xD;
      parameters.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hormone therapy (HT) was available since 1942 in tablets containing conjugated equine&#xD;
      estrogens. Since the 1970s, it has been recommended to add progestogens to the treatment of&#xD;
      women with a uterus to prevent endometrial hyperplasia. HT has been shown to be very&#xD;
      effective in climacteric syndrome, relieving 90% of hot flushes that affect women in the&#xD;
      menopausal transition.&#xD;
&#xD;
      Target tissue, HT regimen and variations between patients will influence the effects of&#xD;
      treatment. Regarding estrogen, the main factors that influence the therapeutic response are&#xD;
      the type of hormone used, the dose and the route of administration. The most physiological&#xD;
      type of estrogen is 17β estradiol, available in the form of gel and adhesive. The skin&#xD;
      metabolizes only a small part of estradiol. Thus, the transdermal route reaches adequate&#xD;
      therapeutic levels from a lower dose of estrogen. Also, the transdermal route prevents the&#xD;
      first hepatic passage, resulting in more stable levels of estradiol in the circulation,&#xD;
      without supraphysiological liver concentrations. The bioavailability of estrogen after&#xD;
      undergoing metabolism in the liver is approximately 2 to 10% of the total administered. This&#xD;
      hepatic passage can result in greater variability in hormone levels, as well as activation of&#xD;
      prothrombotic and inflammatory factors. In addition, hepatic metabolism can change the&#xD;
      therapeutic effects of estrogen and other pharmacological agents.&#xD;
&#xD;
      The present study aims to evaluate and compare the effects of low dose of oral estradiol&#xD;
      associated with oral progesterone and transdermal estradiol associated with vaginal&#xD;
      progesterone on variables related to inflammation, coagulation and body composition&#xD;
      parameters. This is a prospective randomized controlled study, and the study population&#xD;
      includes postmenopausal patients with climacteric symptoms, who have not been using hormone&#xD;
      therapy for at least three months. Patients will receive three months of oral hormonal&#xD;
      treatment (estradiol 1mg and micronized natural progesterone 200mg 14 days a month) and three&#xD;
      months of non-oral hormonal treatment (percutaneous estradiol gel 1.5mg and micronized&#xD;
      progesterone 200mg vaginal 14 days a month).&#xD;
&#xD;
      Patients with climacteric symptoms who meet the inclusion and the exclusion criteria will be&#xD;
      included in the study. The entire sample will receive both hormonal therapies sequentially&#xD;
      and the patients will be divided between the groups (oral therapy and non-oral therapy) to&#xD;
      start the study by random allocation. There will be no period of suspension between&#xD;
      treatments, that is, at the end of the first three months of the study, the group initially&#xD;
      treated with oral therapy starts receiving non-oral treatment for another three months, and&#xD;
      the group initially treated with non-oral therapy starts to receive oral therapy also for&#xD;
      another three months.&#xD;
&#xD;
      This project has already been approved by the Research Ethics Committee of the Hospital de&#xD;
      Clínicas de Porto Alegre. Post-informed written consent will be obtained from all patients,&#xD;
      in accordance with health research standards.&#xD;
&#xD;
      The results will be presented as means and standard deviation or medians and interquartile&#xD;
      range. Analysis of variance for latin square will be used to evaluate carryover effect.&#xD;
      Two-way ANOVA for repeated samples will be used to compare baseline conditions and the two&#xD;
      treatments. Bonferroni's adjustment will be used for multiple comparisons. Bivariate&#xD;
      correlations between continuous numerical variables will be examined using Pearson or&#xD;
      Spearman correlation coefficients, according to the Gaussian or non-Gaussian nature of the&#xD;
      variable, respectively. Statistical analysis will be performed using Statistical Package for&#xD;
      Social Sciences (SPSS, Chicago, IL, USA), with a value of p &lt;0.05 being considered&#xD;
      significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 9, 2015</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">June 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Prospective randomized controlled study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in body composition parameters</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
    <description>Lean mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in body composition parameters</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
    <description>Fat mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
    <description>HDL, LDL, triglycerides (evaluated by blood sample)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum glucose</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
    <description>(evaluated by blood sample)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
    <description>With body mass index (kg/m²)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical activity</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
    <description>Evaluated by pedometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone mineral density (g/cm²)</measure>
    <time_frame>Before hormone therapy and after 3 and 6 months of treatment</time_frame>
    <description>Evaluated by dual energy X-ray absorptiometry (DXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone metabolism</measure>
    <time_frame>Before hormone therapy</time_frame>
    <description>Calcium, phosphorus, PTH, albumin, 25 OH vitamin D (evaluated by blood sample)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Menopause</condition>
  <condition>Hormone Replacement Therapy</condition>
  <arm_group>
    <arm_group_label>Oral hormone therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Estradiol 1mg and micronized natural progesterone 200mg 14 days a month (oral)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-oral hormone therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Percutaneous estradiol gel 1.5mg and micronized progesterone 200mg vaginal 14 days a month (non-oral)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral hormone therapy (estradiol and micronized natural progesterone)</intervention_name>
    <description>Oral hormone therapy - estradiol 1mg every day and micronized natural progesterone 200mg only 14 days a month</description>
    <arm_group_label>Oral hormone therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Non-oral hormone therapy (estradiol and micronized natural progesterone)</intervention_name>
    <description>Percutaneous estradiol gel 1.5mg every day and micronized progesterone 200mg vaginal only 14 days a month</description>
    <arm_group_label>Non-oral hormone therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Six months or more of amenorrhea and FSH levels&gt; or = at 35 mIU / ml;&#xD;
&#xD;
          -  Menopause for a maximum of three years;&#xD;
&#xD;
          -  Mammography and cytology of recent cervix (from the last 12 months);&#xD;
&#xD;
          -  Signature of the Informed Consent Form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Menopause age below 40 years;&#xD;
&#xD;
          -  Use of hormonal therapy in the three months preceding the study;&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus;&#xD;
&#xD;
          -  Endometrial thickening (endometrial thickness greater than 0.5 cm);&#xD;
&#xD;
          -  Neoplasm of breast, colon or endometrium;&#xD;
&#xD;
          -  History of thromboembolism or established cardiovascular disease;&#xD;
&#xD;
          -  Previous hysterectomy;&#xD;
&#xD;
          -  Active smoking;&#xD;
&#xD;
          -  Use of medication to treat osteoporosis in the last 12 months: bisphosphonates,&#xD;
             denosumab, teriparatide, SERMs (selective estrogen receptor agonist).&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>58 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Poli Mara Spritzer, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Rio Grande do Sul, Porto Alegre, Brazil</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tayane M Fighera, PhD</last_name>
    <phone>+55 51 998004004</phone>
    <email>tfighera@hcpa.edu.br</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital de Clínicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90035903</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>LaCroix AZ, Chlebowski RT, Manson JE, Aragaki AK, Johnson KC, Martin L, Margolis KL, Stefanick ML, Brzyski R, Curb JD, Howard BV, Lewis CE, Wactawski-Wende J; WHI Investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011 Apr 6;305(13):1305-14. doi: 10.1001/jama.2011.382.</citation>
    <PMID>21467283</PMID>
  </reference>
  <reference>
    <citation>L'hermite M, Simoncini T, Fuller S, Genazzani AR. Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review. Maturitas. 2008 Jul-Aug;60(3-4):185-201. doi: 10.1016/j.maturitas.2008.07.007. Epub 2008 Sep 5.</citation>
    <PMID>18775609</PMID>
  </reference>
  <reference>
    <citation>Rovinski D, Ramos RB, Fighera TM, Casanova GK, Spritzer PM. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis. Thromb Res. 2018 Aug;168:83-95. doi: 10.1016/j.thromres.2018.06.014. Epub 2018 Jun 19.</citation>
    <PMID>29936403</PMID>
  </reference>
  <reference>
    <citation>Modena MG, Sismondi P, Mueck AO, Kuttenn F, Lignieres Bd, Verhaeghe J, Foidart JM, Caufriez A, Genazzani AR; TREAT. New evidence regarding hormone replacement therapies is urgently required transdermal postmenopausal hormone therapy differs from oral hormone therapy in risks and benefits. Maturitas. 2005 Sep 16;52(1):1-10. doi: 10.1016/j.maturitas.2005.05.003.</citation>
    <PMID>15963666</PMID>
  </reference>
  <reference>
    <citation>Casanova G, Radavelli S, Lhullier F, Spritzer PM. Effects of nonoral estradiol-micronized progesterone or low-dose oral estradiol-drospirenone therapy on metabolic variables and markers of endothelial function in early postmenopause. Fertil Steril. 2009 Aug;92(2):605-12. doi: 10.1016/j.fertnstert.2008.06.049. Epub 2008 Aug 15.</citation>
    <PMID>18706557</PMID>
  </reference>
  <reference>
    <citation>Casanova G, Spritzer PM. Effects of micronized progesterone added to non-oral estradiol on lipids and cardiovascular risk factors in early postmenopause: a clinical trial. Lipids Health Dis. 2012 Oct 9;11:133. doi: 10.1186/1476-511X-11-133.</citation>
    <PMID>23046709</PMID>
  </reference>
  <reference>
    <citation>Lara S, Casanova G, Spritzer PM. Influence of habitual physical activity on body composition, fat distribution and metabolic variables in early postmenopausal women receiving hormonal therapy. Eur J Obstet Gynecol Reprod Biol. 2010 May;150(1):52-6. doi: 10.1016/j.ejogrb.2010.02.007. Epub 2010 Feb 26.</citation>
    <PMID>20189290</PMID>
  </reference>
  <reference>
    <citation>Casanova G, Bossardi Ramos R, Ziegelmann P, Spritzer PM. Effects of low-dose versus placebo or conventional-dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials. J Clin Endocrinol Metab. 2015 Mar;100(3):1028-37. doi: 10.1210/jc.2014-3301. Epub 2014 Dec 16.</citation>
    <PMID>25514104</PMID>
  </reference>
  <reference>
    <citation>Goodman MP. Are all estrogens created equal? A review of oral vs. transdermal therapy. J Womens Health (Larchmt). 2012 Feb;21(2):161-9. doi: 10.1089/jwh.2011.2839. Epub 2011 Oct 19.</citation>
    <PMID>22011208</PMID>
  </reference>
  <reference>
    <citation>Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321.</citation>
    <PMID>12117397</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>June 26, 2020</last_update_submitted>
  <last_update_submitted_qc>June 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Menopause</keyword>
  <keyword>Hormone therapy</keyword>
  <keyword>Body composition</keyword>
  <keyword>Metabolism</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol 17 beta-cypionate</mesh_term>
    <mesh_term>Estradiol 3-benzoate</mesh_term>
    <mesh_term>Hormones</mesh_term>
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Polyestradiol phosphate</mesh_term>
    <mesh_term>Progesterone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04453332
org study id: 2015-0363
nct id: NCT04453332
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Prospective randomized controlled study
primary purpose: Treatment
masking: None (Open Label)
measure: Change in body composition parameters
time frame: Before hormone therapy and after 3 and 6 months of treatment
description: Lean mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)
measure: Change in body composition parameters
time frame: Before hormone therapy and after 3 and 6 months of treatment
description: Fat mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)
measure: Lipid profile
time frame: Before hormone therapy and after 3 and 6 months of treatment
description: HDL, LDL, triglycerides (evaluated by blood sample)
measure: Serum glucose
time frame: Before hormone therapy and after 3 and 6 months of treatment
description: (evaluated by blood sample)
measure: Blood pressure
time frame: Before hormone therapy and after 3 and 6 months of treatment
measure: Weight
time frame: Before hormone therapy and after 3 and 6 months of treatment
description: With body mass index (kg/m²)
measure: Physical activity
time frame: Before hormone therapy and after 3 and 6 months of treatment
description: Evaluated by pedometer
measure: Bone mineral density (g/cm²)
time frame: Before hormone therapy and after 3 and 6 months of treatment
description: Evaluated by dual energy X-ray absorptiometry (DXA)
measure: Bone metabolism
time frame: Before hormone therapy
description: Calcium, phosphorus, PTH, albumin, 25 OH vitamin D (evaluated by blood sample)
arm group label: Oral hormone therapy
arm group type: Active Comparator
description: Estradiol 1mg and micronized natural progesterone 200mg 14 days a month (oral)
arm group label: Non-oral hormone therapy
arm group type: Active Comparator
description: Percutaneous estradiol gel 1.5mg and micronized progesterone 200mg vaginal 14 days a month (non-oral)
intervention type: Drug
intervention name: Oral hormone therapy (estradiol and micronized natural progesterone)
description: Oral hormone therapy - estradiol 1mg every day and micronized natural progesterone 200mg only 14 days a month
arm group label: Oral hormone therapy
intervention type: Drug
intervention name: Non-oral hormone therapy (estradiol and micronized natural progesterone)
description: Percutaneous estradiol gel 1.5mg every day and micronized progesterone 200mg vaginal only 14 days a month
arm group label: Non-oral hormone therapy
criteria: 
gender: Female
gender based: Yes
minimum age: 40 Years
maximum age: 58 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Poli Mara Spritzer, PhD
role: Principal Investigator
affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil
last name: Tayane M Fighera, PhD
phone: +55 51 998004004
email: tfighera@hcpa.edu.br
facility: 
status: Recruiting
country: Brazil
citation: LaCroix AZ, Chlebowski RT, Manson JE, Aragaki AK, Johnson KC, Martin L, Margolis KL, Stefanick ML, Brzyski R, Curb JD, Howard BV, Lewis CE, Wactawski-Wende J; WHI Investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011 Apr 6;305(13):1305-14. doi: 10.1001/jama.2011.382.
PMID: 21467283
citation: L'hermite M, Simoncini T, Fuller S, Genazzani AR. Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review. Maturitas. 2008 Jul-Aug;60(3-4):185-201. doi: 10.1016/j.maturitas.2008.07.007. Epub 2008 Sep 5.
PMID: 18775609
citation: Rovinski D, Ramos RB, Fighera TM, Casanova GK, Spritzer PM. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis. Thromb Res. 2018 Aug;168:83-95. doi: 10.1016/j.thromres.2018.06.014. Epub 2018 Jun 19.
PMID: 29936403
citation: Modena MG, Sismondi P, Mueck AO, Kuttenn F, Lignieres Bd, Verhaeghe J, Foidart JM, Caufriez A, Genazzani AR; TREAT. New evidence regarding hormone replacement therapies is urgently required transdermal postmenopausal hormone therapy differs from oral hormone therapy in risks and benefits. Maturitas. 2005 Sep 16;52(1):1-10. doi: 10.1016/j.maturitas.2005.05.003.
PMID: 15963666
citation: Casanova G, Radavelli S, Lhullier F, Spritzer PM. Effects of nonoral estradiol-micronized progesterone or low-dose oral estradiol-drospirenone therapy on metabolic variables and markers of endothelial function in early postmenopause. Fertil Steril. 2009 Aug;92(2):605-12. doi: 10.1016/j.fertnstert.2008.06.049. Epub 2008 Aug 15.
PMID: 18706557
citation: Casanova G, Spritzer PM. Effects of micronized progesterone added to non-oral estradiol on lipids and cardiovascular risk factors in early postmenopause: a clinical trial. Lipids Health Dis. 2012 Oct 9;11:133. doi: 10.1186/1476-511X-11-133.
PMID: 23046709
citation: Lara S, Casanova G, Spritzer PM. Influence of habitual physical activity on body composition, fat distribution and metabolic variables in early postmenopausal women receiving hormonal therapy. Eur J Obstet Gynecol Reprod Biol. 2010 May;150(1):52-6. doi: 10.1016/j.ejogrb.2010.02.007. Epub 2010 Feb 26.
PMID: 20189290
citation: Casanova G, Bossardi Ramos R, Ziegelmann P, Spritzer PM. Effects of low-dose versus placebo or conventional-dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials. J Clin Endocrinol Metab. 2015 Mar;100(3):1028-37. doi: 10.1210/jc.2014-3301. Epub 2014 Dec 16.
PMID: 25514104
citation: Goodman MP. Are all estrogens created equal? A review of oral vs. transdermal therapy. J Womens Health (Larchmt). 2012 Feb;21(2):161-9. doi: 10.1089/jwh.2011.2839. Epub 2011 Oct 19.
PMID: 22011208
citation: Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321.
PMID: 12117397
responsible party type: Sponsor
mesh term: Estradiol 17 beta-cypionate
mesh term: Estradiol 3-benzoate
mesh term: Hormones
mesh term: Estradiol
mesh term: Polyestradiol phosphate
mesh term: Progesterone
sharing ipd: No