Third Year Evaluation on Genistein Efficacy and Safety

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Menopause, Osteopenia

Intervention / Treatment
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* Dietary Supplement: aglycone genistein
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 49 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Postmenopausal women with established osteopenia receiving aglycone genistein 54 mg/day for 3 years | Dietary Supplement: aglycone genistein<br>* 2 capsules per day containing 27 mg of aglycone genistein, calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period.<br>* Other names: Fosteum;|
| 2<br>Postmenopausal women with established osteopenia receiving placebo (Calcium and vitD) for 3 years | Dietary Supplement: placebo<br>* 2 capsules per day containing calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density |  | basal and after 1 year | 
| Mammographic breast density |  | basal and after 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone-specific alkaline phosphatase (B-ALP) |  | basal and after 1 year | 
| Insulin-like growth factor 1 (IGF-1) |  | basal and after 1 year | 
| Pyridinium cross-links (pyridinoline and deoxypyridinoline) |  | basal and after 1 year | 
| carboxy-terminal cross-linking telopeptide (CTX) |  | basal and after 1 year | 
| Osteoprotegerin and soluble receptor activator of NF-kB ligand (s-RANKL) |  | basal and after 1 year | 
| 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 | 
| hot flushes |  | basal and after 3 years | 
| Thyroid status |  | basal and after 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genistein, Bone mineral density, digital mammography, safety