Safety Profile and Bone Efficacy of the Phytoestrogen Genistein in a Cohort of Osteopenic, Postmenopausal Women After Three Years of Treatment: a Follow-up Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 138
- 主要终点
- Bone Mineral Density
研究概览
简要总结
BACKGROUND: Recent evidences showed that the phytoestrogen genistein positively affects bone metabolism with no clinically significant adverse effects in a cohort of osteopenic, postmenopausal women. However, there is still a knowledge gap regarding the long-term safety of genistein on the breast, the uterus, the thyroid gland and its efficacy in postmenopausal women.
OBJECTIVE: To assess the safety profile of genistein on mammary and thyroid glands and endometrium and cardiovascular apparatus and its effects on bone metabolism after a 3-year therapy with pure, standardized genistein (54 mg/day).
详细描述
DESIGN: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24 months. After the 24-month visit, a sub-population (138 patients) accepted to continue the intervention until 36 months, thus generating a follow-up study.
SETTING: 3 Italian university medical centers. INTERVENTIONS: Participants received 54 mg of genistein, daily, (n=71) or placebo (n=67). Both intervention and placebo contained calcium and vitamin D3. All patients also received dietary instruction in an isocaloric fat-reduced diet.
MEASUREMENTS: Mammographic breast density at baseline and after 24 and 36 months was assessed by visual classification scale and by digitized quantification. BRCA1 and BRCA2 molecular message, sister chromatid exchanges and endometrial thickness were also evaluated at the same time points. Measurements of lumbar spine and femoral neck BMD and QUS t-score were assayed in our patients. Secondary outcomes were serum levels of B-ALP, IGF-I, sRANKL, osteoprotegerin and urinary excretion of CTX, pyridinoline and deoxypyridinoline. Furthermore insulin resistance (HOMA-IR), glucose levels, homocysteine and hot flushes were also evaluated. In addition for thyroid safety TSH, fT3, fT4, thyroid autoantibodies, and mRNA for thyroid and retinoid receptors were evaluated.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 49 Years 至 67 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Good general health
- •Have not had a menstrual period in the preceding year
- •Had not undergone surgically induced menopause
- •Had a follicle-stimulating hormone level > 50 IU/liter and a serum 17 beta-estradiol level ≤ 100 pmol/liter
- •Established osteopenia (-1<T-score<-2.5 SD)
排除标准
- •Clinical or laboratory evidence of confounding systemic diseases, such as cardiovascular, hepatic, or renal disorders
- •Coagulopathy, use of oral or transdermal estrogen, progestin, androgen or other steroids
- •Biphosphonates, cholesterol-lowering therapy or cardiovascular medications in the preceding six months
- •Smoking habit of more than two cigarettes per day
- •Previous treatment with any drug that could affect the skeleton in the preceding year
- •A family history of estrogen-dependent cancer
- •BMD at femoral neck > 0.795 g/cm2; this BMD value corresponds to a T score of -1 standard deviation
结局指标
主要结局
Bone Mineral Density
时间窗: basal and after 1 year
Mammographic breast density
时间窗: basal and after 3 years
次要结局
- Pyridinium cross-links (pyridinoline and deoxypyridinoline)(basal and after 1 year)
- Osteoprotegerin and soluble receptor activator of NF-kB ligand (s-RANKL)(basal and after 1 year)
- Bone-specific alkaline phosphatase (B-ALP)(basal and after 1 year)
- Thyroid status(basal and after 3 years)
- Insulin-like growth factor 1 (IGF-1)(basal and after 1 year)
- carboxy-terminal cross-linking telopeptide (CTX)(basal and after 1 year)
- hot flushes(basal and after 3 years)
- BRCA1 and BRCA2 mRNA levels(basal and after 3 years)
- Sister Chromatid exchanges(basal and after 3 years)
- Endometrial thickness(basal and after 3 years)
- Insulin resistance(basal and after 3 years)