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Third Year Evaluation on Genistein Efficacy and Safety

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00626769
Recruitment Status : Completed
First Posted : February 29, 2008
Last Update Posted : May 19, 2009
Primus Pharmaceuticals
Information provided by:
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).

Condition or disease Intervention/treatment
Menopause Osteopenia Dietary Supplement: aglycone genistein Dietary Supplement: placebo

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.

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Study Type : Observational
Actual Enrollment : 138 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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
Study Start Date : July 2005
Actual Primary Completion Date : July 2006
Actual Study Completion Date : September 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Genistein

Group/Cohort Intervention/treatment
Postmenopausal women with established osteopenia receiving aglycone genistein 54 mg/day for 3 years
Dietary Supplement: aglycone genistein
2 capsules per day containing 27 mg of aglycone genistein, calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period.
Other Names:
  • Genivis
  • Fosteum

Postmenopausal women with established osteopenia receiving placebo (Calcium and vitD) for 3 years
Dietary Supplement: placebo
2 capsules per day containing calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period.

Primary Outcome Measures :
  1. Bone Mineral Density [ Time Frame: basal and after 1 year ]
  2. Mammographic breast density [ Time Frame: basal and after 3 years ]

Secondary Outcome Measures :
  1. Bone-specific alkaline phosphatase (B-ALP) [ Time Frame: basal and after 1 year ]
  2. Insulin-like growth factor 1 (IGF-1) [ Time Frame: basal and after 1 year ]
  3. Pyridinium cross-links (pyridinoline and deoxypyridinoline) [ Time Frame: basal and after 1 year ]
  4. carboxy-terminal cross-linking telopeptide (CTX) [ Time Frame: basal and after 1 year ]
  5. Osteoprotegerin and soluble receptor activator of NF-kB ligand (s-RANKL) [ Time Frame: basal and after 1 year ]
  6. BRCA1 and BRCA2 mRNA levels [ Time Frame: basal and after 3 years ]
  7. Sister Chromatid exchanges [ Time Frame: basal and after 3 years ]
  8. Endometrial thickness [ Time Frame: basal and after 3 years ]
  9. Insulin resistance [ Time Frame: basal and after 3 years ]
  10. hot flushes [ Time Frame: basal and after 3 years ]
  11. Thyroid status [ Time Frame: basal and after 3 years ]

Biospecimen Retention:   Samples With DNA
whole blood, serum, plasma, urine.

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Ages Eligible for Study:   49 Years to 67 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Postmenopausal women (age 49-67 yrs)

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00626769

Sponsors and Collaborators
University of Messina
Primus Pharmaceuticals
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Principal Investigator: Francesco Squadrito, MD University of Messina
Study Director: Rosario D'Anna, MD University of Messina
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Prof. Francesco Squadrito, University of Messina Identifier: NCT00626769    
Other Study ID Numbers: 2005-07
First Posted: February 29, 2008    Key Record Dates
Last Update Posted: May 19, 2009
Last Verified: May 2009
Keywords provided by University of Messina:
Bone mineral density
digital mammography
Additional relevant MeSH terms:
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Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogens, Non-Steroidal
Hormones, Hormone Substitutes, and Hormone Antagonists