Phytoestrogens for controlling climacteric symptoms

• Register: REBEC
• Last refreshed on: 29 April 2013
• Main ID: RBR-76mm75
• Date of registration: 04/01/2012
• Primary sponsor: UNICAMP - Brazil
• Public title: Phytoestrogens for controlling climacteric symptoms
• Scientific title: The use of Phytoestrogens, low dose hormone therapy and placebo to treat psychological, somatic and urogenital symptoms in climacteric women: randomized, controlled, double-blind, clinical trial
• Date of first enrolment: 01/01/2010
• Target sample size: 60
• Recruitment status: recruitment completed
• URL: http://www.ensaiosclinicos.gov.br/rg/RBR-76mm75/
• Study design: Randomized, controlled, double-blind, therapeutic clinical trial, phase 4.

Countries of recruitment

Brazil

Contacts

• Name: AARÃO PINTO-NETO
• Affiliation: UNICAMP

• Name: Adriana Pedro
• Affiliation: UNICAMP

Key inclusion & exclusion criteria

Inclusion criteria: Inclusion criteria consisted of postmenopausal women between 40 and 60 years of age who had had their last menstrual period more than 12 months previously, had follicle-stimulating hormone (FSH) levels higher than 30mIU/mL and estradiol levels lower than 20 pg/ml, who were having more than 8 hot flashes in 24 hours, had not been using any form of hormonal treatment during the previous six months and were not currently using any lipid-lowering drugs, antidiabetic drugs, soybean derived products or herbal supplements.
Exclusion criteria: The exclusion criteria consisted of: previous hysterectomy, chronic gastrointestinal disorder, any contraindication to hormone therapy or patients participating in another clinical trial. Finally, women were excluded if they had a known allergy or hypersensitivity to soy or cow milk or were not willing to cease consumption of soy products for the 16 weeks of the study.

Age minimum: 40Y
Age maximum: 60Y
Gender: F

Health Condition(s) or Problem(s) studied

N00-N99

vasomotor symptoms, psychoemotional symptoms, urogenital symptoms
E28.3

Intervention(s)

The three treatment groups consisted of 20 participants in each group and followed during 16 weeks. The participants were randomized according to the following therapies:
Phytoestrogen group (n=20): one placebo tablet plus 2 portions/day of dietary soy supplementation powder containing 45 mg of isoflavone per portion, making a total of 90 mg of isoflavone/day (Previna, Sanavita Functional Foods, Piracicaba, São Paulo, Brazil).
Hormone therapy (n=20): one tablet containing 1 mg of estradiol and 0.5 mg of norethisterone acetate (Activelle, Medley Pharmaceuticals, Campinas, São Paulo, Brazil), in addition to 2 portions/day of placebo powder.

Placebo group (n=20): one placebo tablet and 2 portions/day of placebo powder.
The dietary soy supplement (Previna, Sanavita Functional Foods, Piracicaba, SP, Brazil) consisted of 20 g portions of a food powder containing 12 g of soy protein and a total of 45 mg of isoflavones (26.5 mg aglycons) to be mixed with 200 ml of water. The soy supplement contained approximately 8 mg of total daidzein, 15 mg total genistein and 3.5 mg total glycitein. The placebo powder (Sanavita Functional Foods) contained 20g of maltodextrin, was identical in appearance to the soy powder and contained the same nutrients and calories except for the isoflavones and soy protein. Both supplements also contained 488 mg of calcium carbonate and 1.2 mg of hydrolyzed collagen per portion. The supplement was taken twice a day for a total of 16 weeks.

Primary Outcome(s)

At the screening visit, women completed a standardized questionnaire designed to obtain information on their demographic characteristics including age, ethnicity, education level and social status. Women were also queried about their reproductive history, age at menopause, time since menopause, use of medication, history of cigarette smoking and frequency of alcohol consumption.
In all three groups, data were collected at baseline and after sixteen weeks of use of the respective medication. To examine the effects of the regime on endogenous hormone levels, follicle-stimulating hormone (FSH) and 17beta estradiol were measured.
The Menopause Rating Scale (MRS) was used to evaluate menopausal symptoms at baseline and after 16 weeks of treatment. The MRS is composed of 11 items assessing menopausal symptoms and is divided into three subscales [13]:
§ Somatic symptoms: hot flashes, heart discomfort, sleeping problems and muscle and joint problems (items 1-3 and 11, respectively).
§ Psychological symptoms: depressive mood, irritability, anxiety, physical and mental exhaustion (items 4-7, respectively).
§ Urogenital symptoms: sexual problems, bladder problems and vaginal dryness (items 8-10, respectively).
Each item is graded by the subject, scores ranging from zero (absent) to four (1=mild; 2=moderate; 3=severe; 4=very severe). The total score for each subscale is the sum of each item graded within that subscale. Total MRS score is composed of the sum of the scores obtained for each subscale.
Transvaginal sonography was performed to evaluate endometrial thickness.It will be considered the comparision of the endometrial thickness of baseline and after 16 weeks of treatment.
The vaginal trofism will be evaluated by vaginal smears. The maturation index was scored under a light microscope by a single cytopathologist blinded to the study group at the baseline and after treatment. The Maturation Value (MV) was calculated by the following way: Superficial cells were assigned a point value of 1.0, intermediate cells were assigned a point value of 0.5, and parabasal cells were assigned a point value of 0. The number of cells in each category was multiplied by the point value, and the three results were added to calculate the MV.

Secondary Outcome(s)

Analize the metabolic effects.
. Blood was drawn for measurement of total lipid levels, lipoprotein levels and glucose analysis after women had fasted for 12 hours overnight. Plasma glucose was measured by a glucose oxidase assay. Plasma total cholesterol and triglyceride levels were measured using enzymatic techniques. Lipoproteins were determined according to the Lipid Research Clinics (LRC) method run by the National Institute of Health using commercial kits (Roche). The inter-run coefficients of variation were 1.5% (TGs), 0.8% (TC) and 1.3% (HDLc). LDL cholesterol was calculated using the Friedwald Equation: LDL cholesterol = total cholesterol – HDL cholesterol – (triglycerides/5). The Castelli I index was calculated as the ratio between total cholesterol and HDL cholesterol. Castelli II index was calculated as the ratio between LDL cholesterol and HDL cholesterol.
Analize the safety profile.Side effects were analyzed according to the occurrence or exacerbation of an adverse event during the treatment period.

Quality of life was measured by the abbreviated version of the World Health Organization’s Quality of Life instrument (WHOQOL-BREF), 1998, at baseline (T1) and at 16 weeks of treatment (T2).

Secondary ID(s)

202/2004

CAAE0003.0.255.000.06

Source(s) of Monetary Support

FAPESP - Brazil

Secondary Sponsor(s)

UNICAMP - Brazil