NCT02384408

Brief Summary

Healthy postmenopausal women, amenorrheic for 1-10 years, aged 45-60 years and in use of follicle stimulating hormone \> 30 mille-International unit/milliliters (mIU/mL), will participate in the study. All women will be informed by a physician of the risks and possible benefits of Hormone Replacement Therapy (HRT). The continuous combined treatment with drospirenone 2 mg and 17β-estradiol 1 mg or tibolone 1.25 mg will be administered for a 24-week period. Transvaginal ultrasound was performed to evaluate the thickness of the endometrium at baseline. At study end-point, an endometrial biopsy will be performed with a Pipelle endometrial sampler to examine histological and immunohistochemical parameters. Immunohistochemical detection of Bcl-2 protein, estrogen and progesterone receptors will be performed in stroma and glandular epithelium.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
100

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Nov 2014

Shorter than P25 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

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

November 1, 2014

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

February 3, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 10, 2015

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2015

Completed
Last Updated

October 14, 2015

Status Verified

October 1, 2015

Enrollment Period

7 months

First QC Date

February 3, 2015

Last Update Submit

October 11, 2015

Conditions

Menopause

Keywords

menopausedrospirenonetiboloneBcl-2steroid receptors

Outcome Measures

Primary Outcomes (1)

  • The endometrium thickness

    Transvaginal ultrasound will be performed to evaluate the thickness of the endometrium in milimiters at baseline and the end of the study in postmenopausal women under use of drospirenone and tibolone. The results will be expressed as mean and standard deviation.

    up to 24 weeks

Secondary Outcomes (2)

  • Bcl-2 protein in postmenopausal endometrium

    24 weeks

  • Estrogen and progestogen receptors in postmenopausal endometrium

    24 weeks

Study Arms (2)

Control

PLACEBO COMPARATOR

Control Group: Women without hormone replacement therapy. Transvaginal Ultrasound - Endometrial Thickness; Endometrial Biopsy. Endometrial Immunohistochemical Study

Procedure: Endometrial BiopsyDevice: Transvaginal UltrasoundProcedure: Endometrial Immunohistochemical

Hormone treatment

EXPERIMENTAL

Group Drospirenone: To whom a continuous combined treatment with drospirenone 2 mg and 17β-estradiol 1 mg (DRSP/E2) will be administered daily for 24 weeks. Group Tibolone: To whom treatment with tibolone 1.25 mg (Tib) will be administered daily for 24 weeks. Transvaginal Ultrasound - Endometrial Thickness; Endometrial Biopsy. Endometrial Immunohistochemical Study

Procedure: Endometrial BiopsyDevice: Transvaginal UltrasoundProcedure: Endometrial Immunohistochemical

Interventions

Endometrial BiopsyPROCEDURE

Histological assessment

ControlHormone treatment
Transvaginal UltrasoundDEVICE

Endometrial Thickness made by ultrasound

Also known as: Endometrial Thickness
ControlHormone treatment
Endometrial ImmunohistochemicalPROCEDURE

Immunoexpression of estrogen (ER) and progesterone receptors (PR) and Bcl-2 protein

ControlHormone treatment

Eligibility Criteria

Age45 Years - 60 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy postmenopausal women, amenorrheic for 1-10 years,
  • aged 45-60 years and in use of follicle stimulating hormone \> 30 mIU/mL, participated in the study.
  • In all subjects, menopausal status will be confirmed by levels of serum follicle stimulating hormone and estradiol in the postmenopausal range.
  • an intact uterus,
  • a washout period of 8 weeks for oral estrogens with or without progestogens, androgens, or selective estrogen receptor modulators (SERMs), four weeks for transdermal or local sex steroids, and 20 weeks for injections of medroxyprogesterone acetate (MPA) containing contraceptives.

You may not qualify if:

  • neoplastic, metabolic and infectious diseases,
  • a uterine size greater than that consistent with a 12-week gestation,
  • any abnormality on bimanual pelvic examination,
  • concomitant use of any hormonal drug,
  • body mass index (BMI) \> 30 kg/m2,
  • cigarette smoking and an endometrial thickness \> 5 mm or the presence of any endometrial abnormalities on transvaginal ultrasound (TV-US).
  • No subjects have present or past history of venous thrombosis, cerebrovascular or cardiovascular disease, and
  • women were excluded if they had any condition that could alter the pharmacokinetics or hypersensitivity to drospirenone/estradiol and tibolone.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vale Do Sapucai University (Univas)

Pouso Alegre, Minas Gerais, 37550-000, Brazil

Location

Related Publications (7)

  • Klaassens AH, van Wijk FH, Hanifi-Moghaddam P, Sijmons B, Ewing PC, Ten Kate-Booij MJ, Kooi GS, Kloosterboer HJ, Blok LJ, Burger CW. Histological and immunohistochemical evaluation of postmenopausal endometrium after 3 weeks of treatment with tibolone, estrogen only, or estrogen plus progestagen. Fertil Steril. 2006 Aug;86(2):352-61. doi: 10.1016/j.fertnstert.2005.12.077. Epub 2006 Jul 7.

    PMID: 16828477RESULT

  • Lima SM, Reis BF, Yamada SS, Postigo S, Grande RM, Botogoski SR, Campaner AB, Hueb CK, Galvao MA. Effects of drospirenone/estradiol on steroid receptors and Bcl-2 in the postmenopausal endometrium. Climacteric. 2011 Oct;14(5):551-7. doi: 10.3109/13697137.2011.559604. Epub 2011 Apr 6.

    PMID: 21469974RESULT

  • Campaner AB, Longo Galvao MA. Application of an easy and useful morphometric technique for immunohistochemistry counting. Gynecol Oncol. 2009 Jan;112(1):282-3. doi: 10.1016/j.ygyno.2008.08.012. Epub 2008 Oct 19. No abstract available.

    PMID: 18937967RESULT

  • Kloosterboer HJ. Tissue-selectivity: the mechanism of action of tibolone. Maturitas. 2004 Aug 30;48 Suppl 1:S30-40. doi: 10.1016/j.maturitas.2004.02.012.

    PMID: 15337246RESULT

  • Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol. 1995 Feb;85(2):304-13. doi: 10.1016/0029-7844(94)00383-O.

    PMID: 7824251RESULT

  • Smith-Bindman R, Kerlikowske K, Feldstein VA, Subak L, Scheidler J, Segal M, Brand R, Grady D. Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA. 1998 Nov 4;280(17):1510-7. doi: 10.1001/jama.280.17.1510.

    PMID: 9809732RESULT

  • Gokaslan H, Oktem O, Durmusoglu F, Eren F. Apoptosis in the endometrium of postmenopausal women receiving tibolone. Gynecol Obstet Invest. 2003;56(3):124-7. doi: 10.1159/000073624. Epub 2003 Sep 22.

    PMID: 14504425RESULT

Study Officials

  • Benedito F Reis, Prof

    Faculdade de Ciências Médicas da Santa Casa de São Paulo

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

February 3, 2015

First Posted

March 10, 2015

Study Start

November 1, 2014

Primary Completion

June 1, 2015

Study Completion

July 1, 2015

Last Updated

October 14, 2015

Record last verified: 2015-10

Locations

BR(1)