Third Year Evaluation on Genistein Efficacy and Safety

Completed

• Conditions: Menopause; Osteopenia
• Interventions: Dietary Supplement: placebo; Dietary Supplement: aglycone genistein

• Registration Number: NCT00626769
• Lead Sponsor: University of Messina

Brief Summary

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

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.

Study Timeline

• Study Start: 2005-07
• Primary Completion: 2006-07
• Study Completion: 2006-09
• Study First Submitted: 2008-02-19
• Study First Submitted QC: 2008-02-28
• Study First Posted: 2008-02-29
• Status Verified: 2009-05
• Last Update Submitted: 2009-05-18
• Last Update Posted: 2009-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 138

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
2	placebo	Postmenopausal women with established osteopenia receiving placebo (Calcium and vitD) for 3 years
1	aglycone genistein	Postmenopausal women with established osteopenia receiving aglycone genistein 54 mg/day for 3 years

Primary Outcome Measures

Name	Time	Method
Bone Mineral Density	basal and after 1 year
Mammographic breast density	basal and after 3 years

Secondary Outcome Measures

Name	Time	Method
Thyroid status	basal and after 3 years
Insulin resistance	basal and after 3 years
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
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-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