Menopause, Osteoporosis, Osteopenia
Conditions
Brief summary
The purpose of this study is to determine if soy-derived phytoestrogens (naturally occurring compounds similar to estrogen) can prevent bone loss and other menopausal symptoms in women who have recently gone through menopause. Study hypothesis: Tablets of high-dose, purified soy phytoestrogens spare the normally occurring spinal bone loss and improve biological and other emotional changes of menopause.
Detailed description
The risks of bone loss and osteoporosis increase significantly after menopause. Although hormone therapy (HT) can spare menopausal women from bone loss and other menopausal symptoms, Women's Health Initiative (WHI) findings indicate significant potential health risks associated with HT. This has prompted women to switch from HT to naturally occurring compounds similar to estrogen, such as those derived from soy, in the hope that estrogens from plant sources can provide benefits while sparing adverse effects caused by prescribed estrogens. However, the long-term efficacy and safety of plant estrogens are unknown. This study will evaluate the effectiveness of treatment using purified soy isoflavones, a dietary source of phytoestrogens, in preventing bone loss, menopausal symptoms, and other changes associated with estrogen deficiency in young menopausal women. The Soy Phytoestrogens As Replacement Estrogen (SPARE) study will provide a foundation of knowledge from which menopausal women and their doctors can begin to make more informed decisions regarding HT and other treatment options. Enrollment into the study will occur over 3 years, with each participant taking part in the study for a total of 2 years. Participants will be randomly assigned to one of two groups; the first group will receive a 200 mg dose of soy isoflavones daily and the second group will receive placebo daily. There will be 10 study visits: screening, study entry, randomization at Month 1, six follow-up visits at Months 2, 4, 8, 12, 16, 20, and a final visit at the end of active participation at Month 24. At each study visit, participants will have blood drawn, provide urine samples, answer questionnaires, and have mammograms and bone density tests.
Interventions
DIETARY_SUPPLEMENTSoy isoflavones
Purified soy isoflavones (phytoestrogens) in tablet form tablets; 200 mg.
DIETARY_SUPPLEMENTPlacebo
Placebo soy isoflavones
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Absence of menstrual period for 12 months but not more than 5 years, or absence of menstrual period for 6 to 12 months and follicle stimulating factor (FSH) greater than 40 IU/L
Exclusion criteria
* Treatment with estrogens, progesterone, raloxifene, or tamoxifen * Treatment with bisphosphonates, calcitonin, fluoride, or systemic corticosteroids * Use of soy/herbal supplements, including DHEA, within 3 months prior to study entry * Use of antibiotics in the month prior to study entry * Use of prescription medication to treat hot flashes * Chemical menopause, including post-chemotherapy * Hyperthyroidism * Hypothyroidism * Uncontrolled diabetes * Malabsorption syndromes or other chronic diseases * Body mass index (BMI) less than 20 or greater than 32 * Bone mineral density (BMD) T-score below -2.0 in lumbar spine or femoral neck
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Bone Mineral Density | baseline and 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Women's Health Questionnaire Score | baseline and 2 years | This self-administered questionnaire contains 23 items, distributed among 6 factors: anxiety and depressed mood (7 items), well-being (4 items), somatic symptoms (5 items), memory and concentration (3 items), vasomotor symptoms (2 items) and sleep problems (2 items). The instrument has a structured format and the response choices consist of 4-point Likert scales ('yes definitely' to 'no, not at all'). Item scores are collapsed into a dichotomous scale, where higher scores indicate a greater level of symptomatology or difficulty; i.e., if the response is 1 or 2 (positive response), the score = 1; if the response is 3 or 4 (negative response), the score is 0. Results can be reported as a total score, where the range is 0-23, but also for each dimension. Thus, the ranges of the subscales are: for anxiety and mood 0-7, for well-being 0-4, somatic symptoms 0-5, memory and concentration 0-3, vasomotor symptoms 0-2 and sleep problems 0-2. |
| Change in Vaginal Maturation Value | baseline and 2 years | The Vaginal Maturation Value (VMV) describes the proportion of the three vaginal epithelial cell types (parabasal, intermediate and superficial) obtained from a swab of the vaginal walls. The changes in the proportion of each type of cells reflects the degree of exposure to estrogen of the vaginal epithelium. The VMV lists the percentage of each type of cell appearing on the smear, with the total of all three values equaling 100%. The index is read from left to right; i.e. VMI of 5/40/55 represents 5% parabasal cells, 40% intermediate cells and 55% superficial cells. Exposure to estrogens results in some parabasal cells, a greater proportion of intermediate cells and few superficial cells. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Soy Isoflavone Group A total of 122 participants were randomized to receive a 200-mg dose of soy isoflavones in tablet form daily by mouth, over 2 years. The medication was delivered in four tablets that had to be taken fasting in the morning. | 122 |
| Placebo Group A total of 126 participants were randomized to receive placebo tablets by mouth daily over 2 years.The medication was delivered in four tablets that had to be taken fasting in the morning. | 126 |
| Total | 248 |
Baseline characteristics
| Characteristic | Total | Soy Isoflavone Group | Placebo Group |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 248 Participants | 122 Participants | 126 Participants |
| Age, Continuous | 52.5 years STANDARD_DEVIATION 3.3 | 53 years STANDARD_DEVIATION 3.3 | 52 years STANDARD_DEVIATION 3.3 |
| Region of Enrollment United States | 248 participants | 122 participants | 126 participants |
| Sex: Female, Male Female | 248 Participants | 122 Participants | 126 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 121 / 122 | 122 / 126 |
| serious Total, serious adverse events | 9 / 122 | 3 / 126 |
Outcome results
Primary
Change From Baseline in Bone Mineral Density
Time frame: baseline and 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Isoflavone Group | Change From Baseline in Bone Mineral Density | 1.146 g/cm2 | Standard Deviation 0.125 |
| Placebo Group | Change From Baseline in Bone Mineral Density | 1.132 g/cm2 | Standard Deviation 0.124 |
Secondary
Change in Vaginal Maturation Value
The Vaginal Maturation Value (VMV) describes the proportion of the three vaginal epithelial cell types (parabasal, intermediate and superficial) obtained from a swab of the vaginal walls. The changes in the proportion of each type of cells reflects the degree of exposure to estrogen of the vaginal epithelium. The VMV lists the percentage of each type of cell appearing on the smear, with the total of all three values equaling 100%. The index is read from left to right; i.e. VMI of 5/40/55 represents 5% parabasal cells, 40% intermediate cells and 55% superficial cells. Exposure to estrogens results in some parabasal cells, a greater proportion of intermediate cells and few superficial cells.
Time frame: baseline and 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Isoflavone Group | Change in Vaginal Maturation Value | 0.20 score | Standard Error 2.53 |
| Placebo Group | Change in Vaginal Maturation Value | -1.78 score | Standard Error 2.86 |
Secondary
Changes in Women's Health Questionnaire Score
This self-administered questionnaire contains 23 items, distributed among 6 factors: anxiety and depressed mood (7 items), well-being (4 items), somatic symptoms (5 items), memory and concentration (3 items), vasomotor symptoms (2 items) and sleep problems (2 items). The instrument has a structured format and the response choices consist of 4-point Likert scales ('yes definitely' to 'no, not at all'). Item scores are collapsed into a dichotomous scale, where higher scores indicate a greater level of symptomatology or difficulty; i.e., if the response is 1 or 2 (positive response), the score = 1; if the response is 3 or 4 (negative response), the score is 0. Results can be reported as a total score, where the range is 0-23, but also for each dimension. Thus, the ranges of the subscales are: for anxiety and mood 0-7, for well-being 0-4, somatic symptoms 0-5, memory and concentration 0-3, vasomotor symptoms 0-2 and sleep problems 0-2.
Time frame: baseline and 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Soy Isoflavone Group | Changes in Women's Health Questionnaire Score | -0.73 change in score | Standard Error 0.54 |
| Placebo Group | Changes in Women's Health Questionnaire Score | -0.34 change in score | Standard Error 0.77 |