Hypogonadism
Conditions
Keywords
testosterone
Brief summary
Testosterone (T) replacement prevents bone loss and relieves symptoms associated with androgen deficiency in male patients with hypogonadism, but at the expense of an increase in prostate-related adverse events and in the hematocrit values above the normal which may lead to bad circulatory outcomes. Most of the effects of T on the male skeleton are mediated by its conversion to estradiol (E2) by the enzyme aromatase. Genetic variations in the aromatase (CYP19A1) gene result in enzymes with variable activity and variable levels of E2 and T. This project is designed to determine if genetic variations in the CYP19A1 gene will result in differences in the skeletal response and incidence of side effects from T treatment in patients with low T. A large number of male Veterans are on T. Results from this project will help identify patients who would benefit from the therapy from those at risk for side effects, and would definitely have an impact in the future care of these patients and male patients in general once genetic profiling becomes part of the standard of care.
Detailed description
Estrogen has been gaining recognition as the primary hormone that regulates the male skeleton. Estrogen in males is mainly derived from the conversion of testosterone to estradiol by the enzyme aromatase. Polymorphisms of the aromatase gene (CYP19A1) have been reported to result in variable enzyme activity resulting in variable hormonal profile and differences in bone mineral density (BMD) among the variants. These polymorphisms were also found to influence changes in BMD in response to hormone therapy in postmenopausal women and bone loss from aromatase inhibitors in women with breast cancer. It is possible that these same polymorphisms will also influence skeletal response to testosterone therapy in hypogonadal males given testosterone. Among the side effects described for testosterone therapy, prostate-related events and an increase in hematocrit represent as the more common and the potentially more serious side effects. However, these side effects do not affect everybody, suggesting that a certain subgroup of patients is predisposed to these side effects. Because polymorphisms in the CYP19A1 gene result differences in activity among variants leading in variable substrate and product accumulation, the investigators hypothesize that these polymorphisms will influence the skeletal response and perhaps susceptibility to side effects from testosterone therapy. Thus the objectives of this proposal are: (1) To evaluate the influence of polymorphisms in the CYP19A1 gene on the skeletal response to testosterone in male patients with low testosterone, (2) To evaluate the influence of polymorphisms in the CYP19A1 gene on the susceptibility to side effects from testosterone therapy, (3) To evaluate the changes in functional activity of the aromatase enzyme in clinically significant CYP19A1 gene polymorphisms. The investigators propose to treat 105 patients with testosterone cypionate 200 mg IM every 2 weeks for an 18-month treatment period. The investigators will do serial measurements of BMD by dual energy X-ray absorptiometry, markers of bone turnover, hematocrit, prostate-specific antigen (PSA), prostate volume and hormonal assays. Changes in BMD and markers of bone turnover with testosterone treatment will be compared among the different CYP19A1 genotypes. The investigators will also compare changes in hematocrit, PSA and prostate volume among the different CYP19A1 genotypes. Changes in functional activity among the variants will be evaluated by CYP19 gene expression studies on the adipose tissues obtained from periumbilical fat biopsies, and by changes the in estradiol to testosterone ratio, a surrogate marker for aromatase activity. The investigators anticipate that variants with increase in activity will have relatively higher estradiol levels than less active variants resulting in greater increments in BMD. Meanwhile, less active variants will have relatively higher levels of testosterone than other variants and have greater increments in hematocrit. On the other hand, variants associated with higher estradiol to testosterone ratio will experience greater increases in PSA and prostate volume with therapy. The incidence of testosterone deficiency goes up with aging and the presence of co-morbid conditions making male hypogonadism one of the common problems among patients attending the VA clinics who, are for the most part, elderly with various co-morbid conditions. Indeed, a large number of VA patients are already taking testosterone for hypogonadism, some of them primarily to prevent further bone loss. It is possible that some of these patients do not derive benefit from the drug while subjecting them to potential serious side effects. Results from this proposal will identify the genetic profiles of favorable responders from poor responders or those who might be more prone to serious side effects, thus, may impact the future care of male Veterans and hypogonadal patients in general, once genetic profiling becomes part of the standard of care.
Interventions
DRUGTestosterone Cypionate
Testosterone cypionate was administered at 200 mg by intramuscular injection every 2 weeks. DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the molecular weight of 412.61.
Sponsors
Baylor College of Medicine
VA Office of Research and Development
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Male Veterans with low total testosterone (\<300 ng/dl) as defined by the Endocrine Society, who are between 40-75 years of age. * These patients must be ambulatory; and be willing and able to provide written informed consent.
Exclusion criteria
* history of prostate cancer, breast cancer * history of testicular disease * untreated sleep apnea * any ongoing illness that, in the opinion of the investigator, could prevent the subject from completing the study * patients with a hematocrit of more than 50% (2010 Endocrine Society Guidelines) * prostate-related findings of a palpable prostate nodule on exam, a serum PSA of 4.0 ng/ml or more, International Prostate Symptom Score \>8(9), urinary postvoid residual by ultrasound of \>149 ml, or an abnormal transrectal ultrasound * patients who are on androgen replacement therapy, selective androgen receptor modulator, or finasteride * patients currently on medications that affects bone metabolism such as: * estrogen * the selective estrogen receptor modulator (SERM) as raloxifene * use of bisphosphonates (i.e. risedronate, alendronate, zoledronic acid and pamidronate) * within two years of study entry * aromatase inhibitors * GnRH analogs * glucocorticoids of at least 5 mg daily for one month or more * anabolic steroids * dilantin * warfarin * patients with diseases known to interfere with bone metabolism as hyperparathyroidism, untreated hyperthyroidism, osteomalacia, chronic liver disease, renal failure, hypercortisolism, malabsorption and immobilization * those with current alcohol use of more than 3 drinks per day (62). * history of documented coronary artery disease at high risk for recurrence * Subjects with osteoporosis or a BMD T-score of -2.5 in the lumbar spine, total femur or femoral neck as well as those patients with a history of osteoporosis-related fractures (spine, hip or wrist) or vertebral deformities on lateral spine radiographs deemed as fragility fractures by the team principal investigator. * history of documented coronary artery disease at high risk for recurrence, history of deep vein thrombosis and cerebrovascular event.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | form baseline to 18 months | Percent change in bone mineral density from baseline to 18 months |
| Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | baseline to 18 months | Percent change in bone mineral density from baseline to 18 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene | from baseline to 18 months | Percent change in PSA from baseline at 18 months |
| Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene | baseline to 18 months | Percent change in hematocrit from baseline to 18 months |
| Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene | Baseline to 18 months | Percent change in hematocrit from baseline to 18 months |
| Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene | Baseline to 6 months | Percent change in gene expression from baseline to 18 months |
| Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | baseline to 18 months | Percent changes in bone mineral density from baseline |
| Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene | Baseline to 18 months | Percent change in bone turnover markers |
| Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus | Baseline to 18 months | Percent change in bone mineral density from baseline to 18 months |
| Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus | Baseline to 18 months | Percent change in bone turnover markers from baseline to 18 months. |
| Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene | Baseline to 18 months | Percent change in bone turnover from baseline to 18 months. |
| Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene | From baseline to 18 months | Percent change in PSA from baseline to 18 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Testosterone Cypionate All patients who qualify for the study will receive testosterone cypionate
Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone.
Subjects were divided into different groups of BMI.
Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-,
(178)-. Its molecular formula is CvH400a, and the mole | 105 |
| Total | 105 |
Baseline characteristics
| Characteristic | Arm 1: Testosterone Cypionate |
|---|---|
| Age, Continuous BMI group 1 | 61.7 years STANDARD_DEVIATION 8.5 |
| Age, Continuous BMI group 2 | 57.3 years STANDARD_DEVIATION 8.7 |
| Age, Continuous BMI group 3 | 60.0 years STANDARD_DEVIATION 7.4 |
| aromatase activity as assessed using estradiol to testosterone ratio Tertile 1 | 0.069 estradiol to testosterone ratio STANDARD_DEVIATION 0.04 |
| aromatase activity as assessed using estradiol to testosterone ratio Tertile 2 | 0.25 estradiol to testosterone ratio STANDARD_DEVIATION 0.07 |
| aromatase activity as assessed using estradiol to testosterone ratio Tertile 3 | 1.37 estradiol to testosterone ratio STANDARD_DEVIATION 1.12 |
| Body mass index BMI group 1 | 27.2 kg/m2 STANDARD_DEVIATION 1.9 |
| Body mass index BMI group 2 | 32.1 kg/m2 STANDARD_DEVIATION 1.4 |
| Body mass index BMI group 3 | 39.8 kg/m2 STANDARD_DEVIATION 3.9 |
| patients with diabetes mellitus patients with diabetes mellitus | 49 Participants |
| patients with diabetes mellitus patients without diabetes mellitus | 56 Participants |
| Race/Ethnicity, Customized American Indian | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Blacks | 11 Participants |
| Race/Ethnicity, Customized Caucasians | 45 Participants |
| Race/Ethnicity, Customized Hispanics | 33 Participants |
| Race/Ethnicity, Customized Not reported | 14 Participants |
| Region of Enrollment United States | 105 Participants |
| Sex: Female, Male BMI group 1 Female | 0 Participants |
| Sex: Female, Male BMI group 1 Male | 38 Participants |
| Sex: Female, Male BMI group 2 Female | 0 Participants |
| Sex: Female, Male BMI group 2 Male | 40 Participants |
| Sex: Female, Male BMI group 3 Female | 0 Participants |
| Sex: Female, Male BMI group 3 Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 105 |
| other Total, other adverse events | 51 / 105 |
| serious Total, serious adverse events | 18 / 105 |
Outcome results
Primary
Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene
Percent change in bone mineral density from baseline to 18 months
Time frame: form baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data from 84 subjects were available for analysis; 15 in the GG, 44 in the GA and 25 in the AA genotype.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Total hip | 0.38 percent change | Standard Deviation 0.93 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Lumbar spine | 3.69 percent change | Standard Deviation 0.87 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Femoral neck | -1.09 percent change | Standard Deviation 1.28 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Total hip | 0.93 percent change | Standard Deviation 0.49 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Lumbar spine | 4.13 percent change | Standard Deviation 0.52 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Femoral neck | 1.51 percent change | Standard Deviation 0.69 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Lumbar spine | 3.82 percent change | Standard Deviation 0.7 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Femoral neck | -1.25 percent change | Standard Deviation 0.91 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene | Total hip | 0.08 percent change | Standard Deviation 0.66 |
Comparison: Analysis by intention to treat with last value carry forward.p-value: <0.05ANOVA
Primary
Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene
Percent change in bone mineral density from baseline to 18 months.
Time frame: baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis . The data of 82 subjects were available for analysis; 14 in the GG, 38 in the GC and 32 in the CC genotype.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | FEMORAL NECK | -1.04 PERCENT CHANGE | Standard Deviation 1.31 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | LUMBAR SPINE | 4.72 PERCENT CHANGE | Standard Deviation 0.91 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | TOTAL HIP | 0.33 PERCENT CHANGE | Standard Deviation 0.84 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | FEMORAL NECK | 0.64 PERCENT CHANGE | Standard Deviation 0.81 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | LUMBAR SPINE | 2.85 PERCENT CHANGE | Standard Deviation 0.56 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | TOTAL HIP | 0.70 PERCENT CHANGE | Standard Deviation 0.5 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | LUMBAR SPINE | 3.74 PERCENT CHANGE | Standard Deviation 0.63 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | TOTAL HIP | 0.64 PERCENT CHANGE | Standard Deviation 0.56 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene | FEMORAL NECK | 0.22 PERCENT CHANGE | Standard Deviation 0.96 |
Comparison: Analysis by intention to treat with the last value carry forwardp-value: <0.05ANOVA
Secondary
Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene
Percent change in gene expression from baseline to 18 months
Time frame: Baseline to 6 months
Population: Gene expression studies were successful in 27 samples; 6 in the GG, 17 in the GA and 4 in the AA genotype.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene | 25.0 percent change | Standard Deviation 120 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene | 65.25 percent change | Standard Deviation 71.29 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene | 113.33 percent change | Standard Deviation 146.97 |
Secondary
Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus
Percent change in bone mineral density from baseline to 18 months
Time frame: Baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Thirty-nine subjects with diabetes mellitus group and 45 without diabetes mellitus have complete dataset available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus | LUMBAR SPINE | 4.05 Percent change | Standard Deviation 0.6 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus | TOTAL HIP | 1.81 Percent change | Standard Deviation 0.61 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus | FEMORAL NECK | 1.63 Percent change | Standard Deviation 0.95 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus | FEMORAL NECK | -0.55 Percent change | Standard Deviation 0.79 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus | LUMBAR SPINE | 3.28 Percent change | Standard Deviation 0.51 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus | TOTAL HIP | 0.53 Percent change | Standard Deviation 0.49 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA
Secondary
Percent Change in Bone Mineral Density According to Body Mass Index (BMI)
Percent changes in bone mineral density from baseline
Time frame: baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Thirty subjects in BMI group 1, 31 in BMI group 2 and 23 subjects in BMI groups 3 have complete dataset available for analysis. There were a total 84 patients who were able to provide data for this outcome at 18 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | Total hip | 0.14 Percent change | Standard Error 0.56 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | lumbar spine | 3.00 Percent change | Standard Error 0.97 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | femoral neck | 0.71 Percent change | Standard Error 0.83 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | Total hip | 1.74 Percent change | Standard Error 0.55 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | femoral neck | -0.33 Percent change | Standard Error 0.86 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | lumbar spine | 4.90 Percent change | Standard Error 0.96 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | Total hip | -0.27 Percent change | Standard Error 0.64 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | femoral neck | 0.16 Percent change | Standard Error 0.97 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Mineral Density According to Body Mass Index (BMI) | lumbar spine | 3.90 Percent change | Standard Error 1.24 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA
Secondary
Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus
Percent change in bone turnover markers from baseline to 18 months.
Time frame: Baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Thirty-seven subjects with diabetes mellitus group and 41 without diabetes mellitus have complete dataset available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus | C-telopeptide | 73.55 Percentage Changes | Standard Error 22.88 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus | Osteocalcin | 20.54 Percentage Changes | Standard Error 15.64 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus | C-telopeptide | 2.05 Percentage Changes | Standard Error 16.22 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus | Osteocalcin | -6.62 Percentage Changes | Standard Error 10.54 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA
Secondary
Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene
Percent change in bone turnover markers
Time frame: Baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 79 subjects with acceptable assay coefficient of variability were available for analysis; 15 subjects in the GG, 37 in the GC and 27 in the CC genotype.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene | C-telopeptide | 48.96 Percent change | Standard Deviation 98.42 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene | Osteocalcin | 33.59 Percent change | Standard Deviation 118.59 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene | C-telopeptide | 5.89 Percent change | Standard Deviation 48.82 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene | Osteocalcin | -20.59 Percent change | Standard Deviation 128.37 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene | C-telopeptide | -14.49 Percent change | Standard Deviation 51.05 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene | Osteocalcin | -26.96 Percent change | Standard Deviation 144.48 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA
Secondary
Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene
Percent change in bone turnover from baseline to 18 months.
Time frame: Baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 79 subjects were analyzed; 15 in the GG, 43 in the GA and 21 in the AA genotype.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene | C-teloepetide | 41.47 perecent change | Standard Deviation 16.33 |
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene | Osteocalcin | 12.40 perecent change | Standard Deviation 133.13 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene | C-teloepetide | 3.35 perecent change | Standard Deviation 9.64 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene | Osteocalcin | -31.22 perecent change | Standard Deviation 148 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene | Osteocalcin | -7.27 perecent change | Standard Deviation 112.06 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene | C-teloepetide | -9.75 perecent change | Standard Deviation 13.8 |
Comparison: Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline and with acceptable assay coefficient of variability were included in the analysis. The data of 79 subjects were analyzed; 15 in the GG, 43 in the GA and 21 in the AA genotype.p-value: <0.05ANOVA
Secondary
Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene
Percent change in hematocrit from baseline to 18 months
Time frame: Baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 85 subjects were available for analysis; 15 subjects in the GG, 37 in the GC and 33 subjects in the CC genotype.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene | 11.56 percent change | Standard Deviation 2.28 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene | 9.67 percent change | Standard Deviation 1.45 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene | 9.46 percent change | Standard Deviation 1.54 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA
Secondary
Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene
Percent change in hematocrit from baseline to 18 months
Time frame: baseline to 18 months
Population: Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 85 subjects were available for analysis; 16 subjects in the GG, 43 in the GC and 26 subjects in the CC genotype.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene | 11.32 Percent change | Standard Deviation 2.21 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene | 9.71 Percent change | Standard Deviation 1.35 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene | 9.41 Percent change | Standard Deviation 1.73 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA
Secondary
Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene
Percent change in PSA from baseline at 18 months
Time frame: from baseline to 18 months
Population: More participants came for their 6-month blood test than for other outcomes e.g. BMD. Since our analysis was intention to treat with the last value carry forward, there were more patients with evaluable PSA data at 18 months, as some patients who had PSA but had no BMD testing etc. who dropped out of the study were also included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene | 85.15 precent change | Standard Deviation 23.84 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene | 62.86 precent change | Standard Deviation 15.74 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene | 52.93 precent change | Standard Deviation 17.11 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA
Secondary
Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene
Percent change in PSA from baseline to 18 months
Time frame: From baseline to 18 months
Population: More participants came for their 6-month blood test than for other outcomes e.g. BMD. Since our analysis was intention to treat with the last value carry forward, there were more patients with evaluable PSA data at 18 months, as some patients who had PSA but had no BMD testing etc. who dropped out of the study were also included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene | Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene | 105.78 percent change | Standard Deviation 167.93 |
| GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene | Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene | 58.52 percent change | Standard Deviation 76.14 |
| AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene | Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene | 44.44 percent change | Standard Deviation 59.92 |
Comparison: Analysis by intention to treat with the last value carry forward.p-value: <0.05ANOVA