Healthy
Conditions
Keywords
HDL, Insulin sensitivity, testosterone, estradiol, cholesterol
Brief summary
The original purpose of this research study was to understand the effects of testosterone (T) and estrogen on stem cells in the blood. The knowledge would be used to help understand the effects of T and estrogen on cardiovascular (heart and blood vessel) disease, and to help in the development of a safe male hormonal contraceptive. The effect of androgens on the number of circulating endothelial progenitor (CEP) cells would best be observed in group 1 (placebo). Upon observation of group 1 under original protocol, changes in CEP cells were not significant but there were changes in markers of inflammation, lipids, and HDL protein composition. A modification to the protocol and title were made to reflect this for groups 2 and 3: Hormonal regulation of HDL-C in Men.
Detailed description
We will be administering three drugs: testosterone gel (T), anastrozole, and acyline. We want to see their effects on stem cells and hormone levels in the blood. Acyline suppress luteinizing hormone(LH) and follicle-stimulating hormone(FSH), which are hormones made by the pituitary gland, thus blocking the signal from the brain that causes the testes to make testosterone. Therefore acyline blocks testosterone production. Some men may experience side effects such as hot flashes or irritability from the low levels of T caused by acyline. We are studying whether adding T to acyline will reduce or eliminate these side effects. Since heart disease is a common problem in men we want to know about the effects of male hormonal contraception on the cardiovascular system. One way to evaluate these risks is to measure the number of progenitor cells and the types of cholesterol in the blood. Progenitor cells are cells that travel in the blood and go to areas of blood vessel injury to help repair the damage amd may help prevent heart attacks and stokes. Some studies suggest that T administration may increase the number of these cells in the blood but other studies have shown that estrogen may be responsible for this effect. In addition, T and estrogen may affect the amount and type of HDL cholesterol in the blood. This is the good cholesterol that is thought to protect people from heart attacks and strokes. Therefore, more studies to test the effects of T and estrogen on progenitor cells in the blood and to understand HDL cholesterol in men receiving testosterone are needed. Acyline is an experimental drug. The FDA allows its use only in research with a small number of volunteers. So far, over 125 men have received acyline. Anastrozole is a drug that blocks the production of estrogen from testosterone. Anastrozole has been given to men safely in the past. Anastrozole is not approved for use in men and is also an experimental drug. Testosterone gel will also be used in this study. It is FDA approved for use in men with low testosterone levels.
Interventions
DRUGAcyline
Acyline 300 μg/kg injections every two weeks (2 doses) for 28 days + placebo Testosterone gel daily for 28 days + placebo oral anastrozole pill daily for 28 days
DRUGAcyline + Testosterone gel
Acyline 300 μg/kg injections every two weeks (2 doses) for 28 days + Testosterone gel 100 mg daily for 28 days + placebo oral pill 1 mg daily for 28 days
DRUGAcyline + testosterone gel + anastrozole
Acyline 300 μg/kg injections every two weeks (2 doses) for 28 days + Testosterone gel 100 mg daily for 28 days + oral anastrozole pill 1 mg daily for 28 days
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Males age 18-55 years * Normal serum total testosterone (300 ng/dl-1000 ng/dl) * Normal LH and FSH levels * Taking no regular medications * Normal baseline serum hematology, chemistry and liver function tests * Agrees not to donate blood during the study * Agrees to use a form of contraception during the study * Subject must be able to comply with all study procedures
Exclusion criteria
* Clinically significant screening assessments or other relevant disease, allergy or surgery, as revealed by history, physical examination and/or laboratory assessments, which may limit participation or prevent completion of the study * History of prostate cancer, breast cancer, or benign prostatic hypertrophy * Prostate-specific antigen (PSA) \> 3.0 * History of regular, chronic testosterone or anabolic steroid use in the past year * Chronic medical illness, prostate disease, or cardiovascular disease * History of a bleeding disorder or need for anticoagulation * Skin condition that might interfere with or be exacerbated by T gel use * Sitting systolic blood pressure \> 180mm Hg or \<90 mm Hg or sitting diastolic blood pressure \>110 mm Hg or \< 60 mm Hg. * History of clinically significant, untreated sleep apnea * Participation in another drug-related research study within the past 2 months * Participating in a regular physical relationship with a pregnant woman * History of hypersensitivity to any of the study medications (T gel, anastrozole, acyline) * History of medical or surgical therapy for benign prostatic hypertrophy * Hematocrit \> 55% * History of drug or alcohol abuse within last 6 months * Abnormal digital rectal exam at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Progenitor Cells | Baseline, Day 28 | Number of CD33 + CD134+ cells as a percentage of all lymphocytes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Homeostasis Model of Insulin Resistance (HOMA-IR) | Baseline, Day 28, Day 56 | HOMA IR is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher HOMA IR numbers are associated with increased insulin resistance and decreased insulin sensitivity. |
| Fasting Serum Insulin | Baseline, Day 28, Day 56 | — |
| Fasting Lipid Levels | Baseline, Day 28, Day 56 | — |
| Follicle Stimulating Hormone (FSH) | Baseline, 28 days | — |
| Luteinizing Hormone Concentration (LH) | Baseline, Day 28 | — |
| Testosterone Concentration | Baseline, Day 28 | — |
| Estradiol Concentration | Baseline, Day 28 | — |
| Sex Hormone Binding Globulin (SHBG) | Baseline, Day 28 | — |
| Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline, Day 28, Day 56 | QUICKI is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher QUICKI are associated with decreased insulin resistance and increased insulin sensitivity. |
Participant flow
Recruitment details
Subjects were recruited using rosters from prior research studies, newspaper and online advertisements. Recruitment began December 2008 and ended March 2010.
Pre-assignment details
Before study procedures,2 withdrew consent and 1 was withdrawn by the investigator for missing appointments.4 failed inclusion criteria(1-anemia,1-low testosterone,1-high BMI,1-medications. 31 men enrolled. 22 men completed.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Acyline + Placebo Gel, Placebo Pill Acyline 300 µg/kg injections Day 0 & 14 + placebo (no active ingredients) transdermal gel daily for 28 days + oral placebo daily for 28 days | 8 |
| Group 2: Acyline, Testosterone Gel, Placebo Pill Acyline 300 µg/kg injections Day 0 & 14 + Testosterone gel (Testim) 10g 1% daily for 28 days + oral placebo daily for 28 days | 8 |
| Group 3: Acyline, Testosterone Gel, Anastrazole Pill Acyline 300 μg/kg injections Day 0 & 14 + 1% Testosterone gel 10g transdermal daily for 28 days + oral anastrozole 1 mg (Arimidex) daily for 28 days | 8 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1: Acyline + Placebo Gel, Placebo Pill | Group 2: Acyline, Testosterone Gel, Placebo Pill | Group 3: Acyline, Testosterone Gel, Anastrazole Pill | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Age Continuous | 38.5 years STANDARD_DEVIATION 10.6 | 24.3 years STANDARD_DEVIATION 4 | 25.8 years STANDARD_DEVIATION 8.4 | 30.0 years STANDARD_DEVIATION 10.5 |
| Body Mass Index (BMI) | 26.2 kg/m^2 STANDARD_DEVIATION 2.5 | 27.1 kg/m^2 STANDARD_DEVIATION 3.8 | 23.7 kg/m^2 STANDARD_DEVIATION 2.1 | 25.5 kg/m^2 STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 7 Participants | 7 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 7 Participants | 21 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 1 / 6 | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Endothelial Progenitor Cells
Number of CD33 + CD134+ cells as a percentage of all lymphocytes
Time frame: Baseline, Day 28
Population: Statistical analyses were limited to changes from baseline within a given group and between-group comparisons were not performed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Endothelial Progenitor Cells | Baseline | 0.101 percentage of all lymphocytes | Standard Deviation 0.032 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Endothelial Progenitor Cells | Day 28 | 0.081 percentage of all lymphocytes | Standard Deviation 0.04 |
Comparison: p value for the difference = 0.28p-value: 0.2895% CI: [0.005, 0.035]paired t-test
Secondary
Estradiol Concentration
Time frame: Baseline, Day 28
Population: Per protocol, the first 8 subjects were assigned to Group 1. Subsequent subjects were randomly assigned to Group 2 or Group 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Estradiol Concentration | Baseline | 95.4 pmol/L | Standard Deviation 18.2 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Estradiol Concentration | Day 28 | 31.9 pmol/L | Standard Deviation 11.2 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Estradiol Concentration | Baseline | 117.8 pmol/L | Standard Deviation 28.6 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Estradiol Concentration | Day 28 | 109.0 pmol/L | Standard Deviation 28.8 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Estradiol Concentration | Baseline | 96.3 pmol/L | Standard Deviation 21.9 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Estradiol Concentration | Day 28 | 36.5 pmol/L | Standard Deviation 14.3 |
Secondary
Fasting Lipid Levels
Time frame: Baseline, Day 28, Day 56
Population: per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | Total cholesterol Day 0 | 4.97 mmol/L | Standard Deviation 1.1 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | HDL cholesterol Day 0 | 1.19 mmol/L | Standard Deviation 0.2 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | HDL cholesterol Day 28 | 1.37 mmol/L | Standard Deviation 0.2 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | Triglycerides Day 0 | 1.79 mmol/L | Standard Deviation 2.1 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | Triglycerides Day 28 | 1.73 mmol/L | Standard Deviation 1.4 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | Total cholesterol Day 28 | 5.44 mmol/L | Standard Deviation 1.2 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | Total cholesterol Day 56 | 4.95 mmol/L | Standard Deviation 1.1 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | LDL choesterol Day 0 | 2.95 mmol/L | Standard Deviation 0.8 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | LDL cholesterol Day 28 | 3.29 mmol/L | Standard Deviation 0.7 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | LDL cholesterol Day 56 | 2.87 mmol/L | Standard Deviation 0.5 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | HDL cholesterol Day 56 | 1.19 mmol/L | Standard Deviation 0.2 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Lipid Levels | Triglycerides Day 56 | 1.89 mmol/L | Standard Deviation 2.3 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | Triglycerides Day 56 | 0.80 mmol/L | Standard Deviation 0.4 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | LDL cholesterol Day 56 | 2.49 mmol/L | Standard Deviation 0.5 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | Total cholesterol Day 56 | 4.14 mmol/L | Standard Deviation 0.6 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | LDL cholesterol Day 28 | 2.80 mmol/L | Standard Deviation 0.2 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | HDL cholesterol Day 0 | 1.32 mmol/L | Standard Deviation 0.2 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | Total cholesterol Day 28 | 4.51 mmol/L | Standard Deviation 0.3 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | Triglycerides Day 28 | 0.86 mmol/L | Standard Deviation 0.3 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | HDL cholesterol Day 56 | 1.32 mmol/L | Standard Deviation 0.2 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | LDL choesterol Day 0 | 2.77 mmol/L | Standard Deviation 0.3 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | Total cholesterol Day 0 | 4.48 mmol/L | Standard Deviation 0.4 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | Triglycerides Day 0 | 0.82 mmol/L | Standard Deviation 0.2 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Lipid Levels | HDL cholesterol Day 28 | 1.32 mmol/L | Standard Deviation 0.1 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | Triglycerides Day 0 | 1.08 mmol/L | Standard Deviation 0.5 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | Total cholesterol Day 0 | 4.56 mmol/L | Standard Deviation 1.5 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | HDL cholesterol Day 28 | 1.32 mmol/L | Standard Deviation 0.2 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | Total cholesterol Day 28 | 4.56 mmol/L | Standard Deviation 0.9 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | Total cholesterol Day 56 | 4.27 mmol/L | Standard Deviation 1.2 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | LDL choesterol Day 0 | 2.67 mmol/L | Standard Deviation 1.3 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | Triglycerides Day 28 | 1.08 mmol/L | Standard Deviation 0.4 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | LDL cholesterol Day 56 | 2.51 mmol/L | Standard Deviation 1 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | HDL cholesterol Day 0 | 1.40 mmol/L | Standard Deviation 0.2 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | LDL cholesterol Day 28 | 2.75 mmol/L | Standard Deviation 0.8 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | HDL cholesterol Day 56 | 1.30 mmol/L | Standard Deviation 0.2 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Lipid Levels | Triglycerides Day 56 | 1.02 mmol/L | Standard Deviation 0.3 |
Secondary
Fasting Serum Insulin
Time frame: Baseline, Day 28, Day 56
Population: per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Serum Insulin | Day 28 | 69 picomolar | Standard Deviation 25 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Serum Insulin | Baseline | 54 picomolar | Standard Deviation 26 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Fasting Serum Insulin | Day 56 | 54 picomolar | Standard Deviation 26 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Serum Insulin | Day 28 | 59 picomolar | Standard Deviation 26 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Serum Insulin | Day 56 | 64 picomolar | Standard Deviation 27 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Fasting Serum Insulin | Baseline | 65 picomolar | Standard Deviation 28 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Serum Insulin | Baseline | 50 picomolar | Standard Deviation 16 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Serum Insulin | Day 56 | 50 picomolar | Standard Deviation 16 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Fasting Serum Insulin | Day 28 | 42 picomolar | Standard Deviation 23 |
Secondary
Follicle Stimulating Hormone (FSH)
Time frame: Baseline, 28 days
Population: Per protocol, the first 8 subjects were assigned to Group 1. Subsequent subjects were randomly assigned to Group 2 or Group 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Follicle Stimulating Hormone (FSH) | Baseline | 4.2 IU/L | Standard Deviation 2.4 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Follicle Stimulating Hormone (FSH) | Day 28 | 0.42 IU/L | Standard Deviation 0.7 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Follicle Stimulating Hormone (FSH) | Baseline | 2.9 IU/L | Standard Deviation 1.3 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Follicle Stimulating Hormone (FSH) | Day 28 | 0.39 IU/L | Standard Deviation 0.5 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Follicle Stimulating Hormone (FSH) | Baseline | 2.5 IU/L | Standard Deviation 0.9 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Follicle Stimulating Hormone (FSH) | Day 28 | 0.87 IU/L | Standard Deviation 0.8 |
Secondary
Homeostasis Model of Insulin Resistance (HOMA-IR)
HOMA IR is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher HOMA IR numbers are associated with increased insulin resistance and decreased insulin sensitivity.
Time frame: Baseline, Day 28, Day 56
Population: per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Homeostasis Model of Insulin Resistance (HOMA-IR) | Baseline | 1.8 HOMA score | Standard Deviation 0.9 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Homeostasis Model of Insulin Resistance (HOMA-IR) | Day 28 | 2.4 HOMA score | Standard Deviation 1 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Homeostasis Model of Insulin Resistance (HOMA-IR) | Day 56 | 2.2 HOMA score | Standard Deviation 0.9 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Homeostasis Model of Insulin Resistance (HOMA-IR) | Day 56 | 1.9 HOMA score | Standard Deviation 0.9 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Homeostasis Model of Insulin Resistance (HOMA-IR) | Baseline | 2.0 HOMA score | Standard Deviation 0.9 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Homeostasis Model of Insulin Resistance (HOMA-IR) | Day 28 | 1.9 HOMA score | Standard Deviation 0.9 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Homeostasis Model of Insulin Resistance (HOMA-IR) | Day 56 | 1.7 HOMA score | Standard Deviation 0.8 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Homeostasis Model of Insulin Resistance (HOMA-IR) | Day 28 | 1.4 HOMA score | Standard Deviation 0.8 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Homeostasis Model of Insulin Resistance (HOMA-IR) | Baseline | 1.6 HOMA score | Standard Deviation 0.6 |
Secondary
Luteinizing Hormone Concentration (LH)
Time frame: Baseline, Day 28
Population: The analysis was per protocol. Following screening, the first 8 subjects were assigned to group I, and subsequent subjects enrolled were randomly assigned to either group 2 or 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Luteinizing Hormone Concentration (LH) | Baseline | 4.3 IU/L | Standard Deviation 2.3 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Luteinizing Hormone Concentration (LH) | Day 28 | 0.31 IU/L | Standard Deviation 0.2 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Luteinizing Hormone Concentration (LH) | Baseline | 4.7 IU/L | Standard Deviation 1.9 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Luteinizing Hormone Concentration (LH) | Day 28 | 0.69 IU/L | Standard Deviation 1.2 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Luteinizing Hormone Concentration (LH) | Baseline | 4.4 IU/L | Standard Deviation 2.2 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Luteinizing Hormone Concentration (LH) | Day 28 | 1.55 IU/L | Standard Deviation 1.6 |
Secondary
Quantitative Insulin Sensitivity Check Index (QUICKI)
QUICKI is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher QUICKI are associated with decreased insulin resistance and increased insulin sensitivity.
Time frame: Baseline, Day 28, Day 56
Population: per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Quantitative Insulin Sensitivity Check Index (QUICKI) | Day 28 | 0.34 QUICKI index | Standard Deviation 0.03 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline | 0.36 QUICKI index | Standard Deviation 0.03 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Quantitative Insulin Sensitivity Check Index (QUICKI) | Day 56 | 0.35 QUICKI index | Standard Deviation 0.03 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Quantitative Insulin Sensitivity Check Index (QUICKI) | Day 28 | 0.35 QUICKI index | Standard Deviation 0.02 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline | 0.35 QUICKI index | Standard Deviation 0.02 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Quantitative Insulin Sensitivity Check Index (QUICKI) | Day 56 | 0.35 QUICKI index | Standard Deviation 0.02 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline | 0.36 QUICKI index | Standard Deviation 0.02 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Quantitative Insulin Sensitivity Check Index (QUICKI) | Day 56 | 0.36 QUICKI index | Standard Deviation 0.02 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Quantitative Insulin Sensitivity Check Index (QUICKI) | Day 28 | 0.38 QUICKI index | Standard Deviation 0.02 |
Secondary
Sex Hormone Binding Globulin (SHBG)
Time frame: Baseline, Day 28
Population: Per protocol, the first 8 subjects were assigned to Group I. Subsequent subjects were randomly assigned to Group 2 or Group 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Sex Hormone Binding Globulin (SHBG) | Baseline | 34.9 nmol/L | Standard Deviation 17.1 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Sex Hormone Binding Globulin (SHBG) | Day 28 | 37.5 nmol/L | Standard Deviation 16.4 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Sex Hormone Binding Globulin (SHBG) | Baseline | 23.0 nmol/L | Standard Deviation 10.9 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Sex Hormone Binding Globulin (SHBG) | Day 28 | 22.1 nmol/L | Standard Deviation 10.1 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Sex Hormone Binding Globulin (SHBG) | Baseline | 27.6 nmol/L | Standard Deviation 6.3 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Sex Hormone Binding Globulin (SHBG) | Day 28 | 25.1 nmol/L | Standard Deviation 4.7 |
Secondary
Testosterone Concentration
Time frame: Baseline, Day 28
Population: Per protocol, the first 8 subjects were assigned to group I. Subsequent subjects were randomized to group 2 or group 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Acyline + Placebo Gel + Placebo Pill | Testosterone Concentration | Baseline testosterone concentration | 15.4 nmol/L | Standard Deviation 3.4 |
| Group 1: Acyline + Placebo Gel + Placebo Pill | Testosterone Concentration | Day 28 testosterone concentration | 0.8 nmol/L | Standard Deviation 0.8 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Testosterone Concentration | Baseline testosterone concentration | 16.3 nmol/L | Standard Deviation 3.3 |
| Group 2: Acyline + T-gel 10g/Day + Placebo Pill | Testosterone Concentration | Day 28 testosterone concentration | 17.8 nmol/L | Standard Deviation 5.5 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Testosterone Concentration | Baseline testosterone concentration | 16.5 nmol/L | Standard Deviation 2.6 |
| Group 3: Acyline + T-gel + Oral Anastrozole 1mg | Testosterone Concentration | Day 28 testosterone concentration | 19.0 nmol/L | Standard Deviation 7.3 |