Prospective Double Blind Evaluation of Bioidentical Hormones
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Number of Participants Without Change in Baseline and Follow up Mammograms
研究概览
简要总结
Prospective double blind pilot study comparing bioidentical 'natural' hormones to low-dose PremPro. Forty participants will be enrolled. The purpose of this study is to try to gather early information about safety when "natural" or bioidentical hormones are used during early menopause.
详细描述
In spite of warnings regarding safety and adverse events widely publicized after the Women's Health Initiative (WHI), women continue to seek hormone replacement therapy for a variety of reasons. Increased cardiovascular events identified in WHI are an important concern for considering menopausal hormone replacement. There is the belief the 'natural' or bioidentical hormone replacement therapy could provide a safe alternative to widely used synthetic hormone replacement therapy. However, this has never been studied with any rigor and health care providers can not adequately advise patients seeking 'natural' bioidentical hormone therapy.
This feasibility pilot study is designed as a prospective double blind study comparing 4 groups of women who are within 7 years of menopause. There will be 10 women in each of the 4 groups with a total of 40 women enrolled and these women will be treated for 12 months.
The Long-Term Goal is to provide health care practitioners and consumers with evidence-based recommendations for the use of bioidentical hormone replacement. The Short-Term Goal of this pilot study is to determine if it is feasible to conduct a study in bioidentical hormones and obtain information that could lead to a larger more definitive study. We would like to provide safety information for bioidentical hormone use by evaluating surrogate markers for cardiovascular disease (lipid levels), with secondary evaluation of breast (mammogram) and uterus (endovaginal ultrasound), and to collect information about bone preservation.
The information gained from this trial will provide information for a future trial to test the hypothesis that bioidentical hormone replacement therapy provides a safe alternative to standard hormone replacement therapy: To determine if bioidentical hormone replacement therapy is associated with improved lipid profiles (surrogate marker for cardiovascular disease) when compared to Prempro. This will be determined by evaluating lipid levels at baseline and during the 12-month treatment period.
Secondary hypotheses will also be evaluated in the future to include:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Ambulatory
- •Within 7 years post menopause
- •Positive history of menopausal symptoms such as vasomotor symptoms or osteoporosis in a study subject unable to tolerate bisphosphonates
- •FSH greater than 20 mIU/mL
- •Intact uterus and at least one intact ovary
- •Amenorrhea for 3 months or greater up to 7 years
- •Normal pap smear results within 12 months
- •Normal mammogram result within 12 months
- •Agreeable to a 3 month washout period with no hormones prior to entering the trial
- •Women who have no language barrier, are cooperative, and who can give informed consent before entering this study
排除标准
- •Unwilling to take hormone replacement for the 12 month period
- •Evidence of clinically significant psychiatric disorder by history/examination that would prevent the patient from completing the study.
- •Active deep venous thrombosis, pulmonary embolism, or a history of these conditions
- •Active or recent arterial thromboembolic disease
- •Undiagnosed vaginal bleeding
- •Hypersensitivity to ingredients in Prempro
- •Patients with known current bone disorders other than primary osteoporosis
- •Patients with pathological fractures
- •Patients with suspected or history of carcinoma of the breast or estrogen dependent neoplasms such as endometrial carcinoma.
- •Patients who have ≥ 5mm endometrial thickness by endovaginal (transvaginal) ultrasound.
- •Patients who have impaired renal function evidenced by serum creatinine greater than 2.5 mg/dL.
- •Patients who have impaired hepatic function evidenced by transaminase (AST/ALT) ≥2.5X upper limit
- •Patients with severe malabsorption syndromes.
- •Patients who consume an excess of alcohol or abuse drugs (an excess of alcohol is defined as more than four of any one or combination of the following per day: 30 mL distilled spirits, 340 mL beer, or 120 mL wine).
- •Treatment with therapeutic doses of any of the following medications more recently than 3 months:
- •Calcitonin
- •Corticosteroids
- •Progestins
- •Progesterone
- •Herbal menopause treatments
- •Fluorides
- •Phosphate binding antacids
- •Bisphosphonates
- •Vitamin D 50,000IU
- •Anticonvulsants
- •Patients who received any investigational drug within the proceeding month
- •Tobacco use will not be allowed
研究组 & 干预措施
1 equine estrogens m-progesteroneacetate
Menopausal women in first seven years of menopause randomized to arm 1 receive conjugated equine estrogens 0.45 mg combined with medroxyprogesteroneacetate 1.5 mg placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
干预措施: equine estrogens m-progesteroneacetate (Drug)
2 estradiol estriol progesterone
Menopausal women in first seven years of menopause randomized to arm 2 estradiol .5mg, estriol 2.0mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
干预措施: Estradiol , estriol , progesterone (Drug)
4 estradiol progesterone
Menopausal women in first seven years of menopause randomized to arm 4 estradiol 0.5 mg, progesterone 100 mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
干预措施: estradiol, progesterone (Drug)
3 estriol progesterone
Menopausal women in first seven years of menopause randomized to arm 3 estriol 2.5mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
干预措施: estriol, progesterone (Drug)
结局指标
主要结局
Number of Participants Without Change in Baseline and Follow up Mammograms
时间窗: baseline and month 12
Comparison at baseline and month 12 by descriptive analysis of breast mammograms. Assessing for changes in density and/or lesions for risk of breast stimulation from hormone replacement therapy. Mammogram readings for participants completing study in descriptive terms. Looking for significant change in breast tissue while on hormone therapy for 12 months. Those who had no change are counted below.
Change in Total Cholesterol
时间窗: Baseline and month 12
To determine if bioidentical hormone replacement therapy is associated with change in lipid profiles (surrogate marker for cardiovascular disease) when compared to Prempro and provide safety data to proceed to larger trial. This was determined by evaluating lipid levels at baseline and during the 12-month treatment period. Participants' values were averaged at baseline and again at 12 months; the average of the baseline value was subtracted from the average at completion.
Endometrial Measurement
时间窗: Baseline and month 12
Baseline and 12 month follow up endovaginal ultrasound(completed at study site only) to evaluate endometrial stripe thickness for change on hormone therapy for all 4 arms. Endometrial thickness was measured in millimeters at baseline and again at 12 month completion. The average of the baseline value was subtracted from the average at completion for each group and reported in mm. Single participant in Arm 2: compared baseline to completion.
次要结局
- Number of Participants Without Change in Baseline and Follow up Bone Density(baseline and 12 months)
研究者
Jeanne Drisko, MD, CNS, FACN
Director Integrative Medicine
University of Kansas Medical Center