Third Year Evaluation on Genistein Efficacy and Safety

University of Messina

Status

Completed

Conditions

Osteopenia

Menopause

Treatments

Dietary Supplement: placebo

Dietary Supplement: aglycone genistein

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT00626769

2005-07

Details and patient eligibility

About

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).

Full 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.

Enrollment

138 patients

Sex

Female

Ages

49 to 67 years old

Volunteers

No Healthy Volunteers

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