Effects of Tibolone Treatment on the Endometrium

NCT00294463 | Completed Phase 4

• 1 other identifier: MEC 217.640/2002/220
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Tibolone, a tissue-selective compound with a combination of estrogenic, progestogenic and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares endometrial histology, biochemistry (hormone levels) and gene-expression profiles after short-term (21-days) treatment with tibolone, to the findings after treatment with estradiol-only (E2) and E2+Medroxyprogesterone Acetate (MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolaps. Since short-term tibolone use results in increased spotting and bleeding but long-term treatment with tibolone has been shown to lead to an atrophic endometrium our hypothesis is that tibolone first displays a more estrogenic mode of action, which over time, is counterbalanced by tibolone's progestagenic properties

Conditions

Postmenopause; Osteoporosis

Keywords

postmenopause; endometrium; Gene Expression Profiling; Histology, Comparative; Hormone Replacement Therapy; Hormones

Outcome Measures

Primary Outcomes (4)

• Histologic evaluation of the endometrium at the end of treatment

• Biochemical evaluation (hormone measurements) of uterine tissue at the end of treatment

• Biochemical evaluation of sera, obtained just prior to treatment and at surgery

• Molecular assessment of gene expression

Interventions

Tibolone DRUG

Estradiol DRUG

Estradiol + Medroxy Progesterone Acetate DRUG

Eligibility Criteria

• Age: 0 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy postmenopausal women with a uterus. "Postmenopausal'' was defined as amenorrhoeic for at least one year prior to screening, or amenorrhoeic for at least six months prior to screening with a serum E2 concentration of \< 20 pg/ml and a serum FSH concentration of \> 40 IU/L at screening. If the patient used any kind of steroid hormone therapy prior to the study, a washout period of 6 months (for intra-uterine progesterone and oral estrogen+progestagen combination therapy) or 12 months (for progesterone implants or injections and injected estrogen+progestagen combination therapy) was applied.

You may not qualify if:

• Histological diagnosis by a local pathologist of an endometrial biopsy (with the Pipelle suction curette) taken before treatment, as proliferative, secretory or menstrual type endometrium, endometrial metaplasia, endometrial or endocervical polyp(s), endometrial hyperplasia, cancer or any other histological abnormality (leiomyoma(ta), stromal nodules or mesenchymal or (endo)cervical neoplasia(s)).
• Double-layer endometrium thickness \> 4 mm as assessed by transvaginal ultrasound, immediately before endometrial biopsy.
• History or presence of any malignancy, except successfully treated non-melanoma skin cancers.
• Any unexpected vaginal bleeding following the menopause.
• Liver disease, except cholecystectomy.
• Abnormal cervical Pap smear test result, or abnormal mammography result obtained within one year prior to the start of the trial
• Deep vein thrombosis, thrombophlebitis, thromboembolic disease, or suspicions of having hereditary predisposition for developing venous thromboembolic disease.
• Use of one or more of the following drugs within the last two months: hepatic microsomal enzyme-inducing anticonvulsant drugs known to affect or interfere with the pharmacokinetics of steroids (e.g. hydantoins, barbiturates such as Phenobarbital (alone or in combinations, such as Bellergal) rifampicin, griseofulvin, primidone or carbamazepine).

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Organon: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, 3000 CA, Netherlands

Location

Related Publications (1)

• Hanifi-Moghaddam P, Boers-Sijmons B, Klaassens AH, van Wijk FH, Van Ijcken WF, Van der Spek P, Verheul HA, Kloosterboer HJ, Burger CW, Blok LJ. Difference in signalling between various hormone therapies in endometrium, myometrium and upper part of the vagina. Hum Reprod. 2008 Feb;23(2):298-305. doi: 10.1093/humrep/dem366. Epub 2007 Dec 11.

  PMID: 18077316 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

tibolone; Estradiol

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Curt W Burger, MD, PhD

  Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands

  PRINCIPAL INVESTIGATOR

• Leen J Blok, PhD

  Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 17, 2006
• First Posted: February 22, 2006
• Study Start: February 1, 2003
• Study Completion: March 1, 2005
• Last Updated: February 22, 2006

Record last verified: 2006-02

Locations

NL (1)