NCT04453332

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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Oct 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 9, 2015

Completed
4.7 years until next milestone

First Submitted

Initial submission to the registry

June 23, 2020

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 1, 2020

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2021

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2021

Completed
Last Updated

July 1, 2020

Status Verified

June 1, 2020

Enrollment Period

5.6 years

First QC Date

June 23, 2020

Last Update Submit

June 26, 2020

Conditions

MenopauseHormone Replacement Therapy

Keywords

MenopauseHormone therapyBody compositionMetabolism

Outcome Measures

Primary Outcomes (2)

  • Change in body composition parameters

    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

    Fat mass (kilograms) evaluated by dual energy X-ray absorptiometry (DXA)

    Before hormone therapy and after 3 and 6 months of treatment

Secondary Outcomes (7)

  • Lipid profile

    Before hormone therapy and after 3 and 6 months of treatment

  • Serum glucose

    Before hormone therapy and after 3 and 6 months of treatment

  • 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

  • Physical activity

    Before hormone therapy and after 3 and 6 months of treatment

  • +2 more secondary outcomes

Study Arms (2)

Oral hormone therapy

ACTIVE COMPARATOR

Estradiol 1mg and micronized natural progesterone 200mg 14 days a month (oral)

Drug: Oral hormone therapy (estradiol and micronized natural progesterone)

Non-oral hormone therapy

ACTIVE COMPARATOR

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)

Interventions

Oral hormone therapy (estradiol and micronized natural progesterone)DRUG

Oral hormone therapy - estradiol 1mg every day and micronized natural progesterone 200mg only 14 days a month

Oral hormone therapy
Non-oral hormone therapy (estradiol and micronized natural progesterone)DRUG

Percutaneous estradiol gel 1.5mg every day and micronized progesterone 200mg vaginal only 14 days a month

Non-oral hormone therapy

Eligibility Criteria

Age40 Years - 58 Years
Sexfemale(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital de ClĂ­nicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035903, Brazil

RECRUITING

Related Publications (10)

  • 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: 21467283BACKGROUND

  • 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: 18775609BACKGROUND

  • 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: 29936403BACKGROUND

  • 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: 15963666BACKGROUND

  • 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: 18706557BACKGROUND

  • 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: 23046709BACKGROUND

  • 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: 20189290BACKGROUND

  • 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: 25514104BACKGROUND

  • 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: 22011208BACKGROUND

  • 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: 12117397BACKGROUND

MeSH Terms

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

EstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Poli Mara Spritzer, PhD

    Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tayane M Fighera, PhD

CONTACT

+55 51 998004004tfighera@hcpa.edu.br

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: Prospective randomized controlled study
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 23, 2020

First Posted

July 1, 2020

Study Start

October 9, 2015

Primary Completion

June 1, 2021

Study Completion

December 1, 2021

Last Updated

July 1, 2020

Record last verified: 2020-06

Data Sharing

IPD Sharing
Will not share

Locations

BR(1)