Comparative Effects of Drospirenone and Tibolone on the Postmenopausal Endometrium
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- The endometrium thickness
研究概览
简要总结
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.
详细描述
Subjects
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 about the trial and signed the informed consent documents, eligibility was determined based on medical history, and on general physical and gynecological examination. All women were informed by a physician of the risks and possible benefits of Hormone Replacement Therapy (HRT). Upon inclusion, Transvaginal ultrasound (TV-US) 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 . Vital signs, blood pressure, weight, Pap smear, mammography, routine clinical chemistry assays (including, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides) and hematology will also be evaluated at screening.
Treatment Groups Of the 100 women initially evaluated, 32 did not meet the inclusion and exclusion criteria, while eight refused to participate, giving a final total of 60 patients for inclusion in the study. The sixty postmenopausal women were randomly allocated into three groups: Group I: control group comprising 20 patients (no hormonal treatment); Group II: also comprising 20 patients, to whom a continuous combined treatment with drospirenone 2 mg and 17β-estradiol 1 mg (DRSP/E2) will be administered daily; and Group III: also comprising 20 patients, to whom treatment with tibolone 1.25 mg (Tib) will be administered daily. All treatments will be administered for a 24-week period. DRSP/E2 was purchased from "Bayer Schering Pharma™", Brazil and Tib from "Biolab™", Brazil. The duration of the treatment will be 6 cycles, each lasting a period of 28 days (conducted for a total of 24 weeks). Randomization will be done with the aid of computer software in order to prevent bias in the selection process.
Objective: A prospective randomized controlled trial will be conducted to evaluate the effect of low dose of tibolone and estradiol/drospirenone on the histology, expression of estrogen (ER) and progesterone receptors (PR) and Bcl-2 protein, in endometrium of postmenopausal women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 45 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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.
- •Inclusion criteria will be:
- •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.
排除标准
- •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.
研究组 & 干预措施
Control
Control Group: Women without hormone replacement therapy. Transvaginal Ultrasound - Endometrial Thickness; Endometrial Biopsy. Endometrial Immunohistochemical Study
干预措施: Endometrial Biopsy (Procedure)
Control
Control Group: Women without hormone replacement therapy. Transvaginal Ultrasound - Endometrial Thickness; Endometrial Biopsy. Endometrial Immunohistochemical Study
干预措施: Transvaginal Ultrasound (Device)
Control
Control Group: Women without hormone replacement therapy. Transvaginal Ultrasound - Endometrial Thickness; Endometrial Biopsy. Endometrial Immunohistochemical Study
干预措施: Endometrial Immunohistochemical (Procedure)
Hormone treatment
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
干预措施: Endometrial Biopsy (Procedure)
Hormone treatment
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
干预措施: Transvaginal Ultrasound (Device)
Hormone treatment
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
干预措施: Endometrial Immunohistochemical (Procedure)
结局指标
主要结局
The endometrium thickness
时间窗: up to 24 weeks
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.
次要结局
- Estrogen and progestogen receptors in postmenopausal endometrium(24 weeks)
- Bcl-2 protein in postmenopausal endometrium(24 weeks)
研究者
Benedito Fabiano dos Reis
Professor
Universidade do Vale do Sapucai