Clinical trial NCT02959853
Conditions: Hypogonadism Severe Obesity
Keywords: Hypogonadism Severe obesity
Sponsor: Baylor College of Medicine
Start date: 2016-06-01; Completion date: 2018-12-20
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
After the age of 40, there is a gradual decline in the production of testosterone. Among obese men, the decline in testosterone levels is exacerbated by the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. The high expression of aromatase enzyme in the adipose tissue enhances the conversion of androgens into estrogens which in turn exert a negative feedback on the hypothalamus and pituitary, leading to the inhibition of production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH), and as a consequence, of testosterone by the testis resulting in hypogonadotropic hypogonadism (HH). Though bone loss is a well recognized side effect of AI in certain populations, such as women with breast cancer, HH obese men present high levels of circulating estrogens that could potentially prevent them from bone loss, estradiol being the main regulator of the male skeleton. This study is designed to determine if aromatase inhibitors in combination with weight loss, compared to weight loss alone, will have a positive effect on muscle strength, symptoms of hypogonadism, and body composition without negatively impacting bone mineral density and bone quality. Results from this study will help determine if certain groups of obese patients would benefit from therapy with aromatase inhibitors.

Detailed description:
After the age of 40, testosterone (T) production in men gradually decreases at a rate of 1.6% per year for total and to 2-3% per year for bioavailable T. Because of the age-related increase in sex hormone binding globulin, the magnitude of the decrease in bioavailable T in men is even greater than the decline in total T levels. This reduction in T production in men parallels the age-associated loss of muscle mass that leads to sarcopenia and impairment of function and the age-associated loss of bone mass that leads to osteopenia and fracture risk. Hypogonadism is a condition associated with multiple symptom complex including fatigue, depressed mood, osteoporosis, increased fat mass, loss of libido and reduced muscle strength, all of which deeply affect patient's quality of life. The prevalence of hypogonadismamong obese men ranges between 29.3% to 78.8%, with levels of androgens decreasing proportionately to the degree of obesity. This decline in T levels is exacerbated among obese patients due the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. The high expression of aromatase enzyme in the adipose tissue enhances the conversion of androgens into estrogens (E) which in turn exerts a negative feedback on hypothalamus and pituitary, inhibiting the production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) and, as a consequence, of T by the testis resulting in hypogonadotropic hypogonadism (HH). Considering the high aromatase expression in the adipose tissue, the administration of T among obese men with HH could increase the conversion of the substrate T to estradiol (E2) and fuels the negative feedback on the hypothalamus and pituitary, producing a greater suppression of GnRH and gonadotropins.

Thus, men with obesity induced HH may benefit from other treatment strategies that target the pathophysiology of the disease. Weight loss intervention which improves hormonal and metabolic abnormalities related to obesity may also be considered a logical approach to improve obesity-induced HH.

One possible approach consists of the use of aromatase inhibitors (AI) to stop the conversion of T to E2 thereby interrupting the vicious cycle of E2 inhibition of the hypothalamic-pituitary-gonadal axis and restoring T production to normal levels. Increased T and reduced E2 levels have been reported in men with low levels of T after AI administration, even though very few studies investigated clinical outcomes.

We believe that AI use could promote positive changes on hypogonadal symptoms and body composition in HH severely obese patients, acting at the physiopathology of the disease without necessarily causing bone loss.

Arms: arm 1: Patients given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent arm 2: Patient placed on an aromatase inhibitor anastrazole 1 mg daily plus given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent
Interventions: intervention 1: Anastrazole intervention 2: weight loss
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
Institutional Review Board for Baylor College of Medicine and Affiliated Hospitals  
Protocol Number:    H-36912 
Status:                        Approved 
Initial Submit Date:  5/1/2015 
Approval Period:       9/24/2019 - 9/23/2020 
 Section Aa:  Title & PIA1.  Main Title 
     AROMATASE INHIBITORS IN SEVERELY OBESE HYPOGONADAL MALE VETERANS 
A2.  Principal Investigator 
  
     Name:   
REINA VILLAREAL 
Phone:   
713-794-7534 
     Id:   
184419 
Fax:   
713-794-7771 
     Department:   MEDICINE: ENDOCRINOLOGY 
Email:    
rvillare@bcm.tmc.edu
     Center:   
Mail Stn:   BCM185 
A3.  Administrative Contact 
  
     Name: 
DIANA NIETO 
Phone:   
713-7947920 
     Id:   
Non-Baylor 
Fax:   
     
Email:    
nieto.diana@va.gov
     
Mail Stn:   
A3a.  Financial Conflict of Interest 
Does any member of study personnel (Investigator (including investigator’s spouse and/or dependent children)) that 
are involved in the design, conduct, or reporting of the research have a Significant Financial Interest (SFI) that would 
reasonably appear to be affected by the research for which funding is sought and/or associated with an 
entity/business that would reasonably appear to be affected by the research? 
         No 
 Section Ab:  General Information     
A4.  Co-Investigators 
  
     Name:   
RUI CHEN 
Phone:   
713-798-0190 
Id:   
177323 
Fax:   
Department:   MEDICINE: ENDOCRINOLOGY 
Email:    
ruic@bcm.tmc.edu
Center:   
Mail Stn:   BCM620 
  
     Name:   
BRYAN JIANG 
Phone:   
713-798-0190 
Id:   
177335 
Fax:   
Department:   MEDICINE: ENDOCRINOLOGY 
Email:    
bjiang@bcm.tmc.edu
Center:   
Mail Stn:   BCM620 
  
     Name:   
DENNIS VILLAREAL 
Phone:   
713-794-7156 
Id:   
184416 
Fax:   
713-794-7771 
Department:   MEDICINE: ENDOCRINOLOGY 
Email:    
villarea@bcm.tmc.edu
Center:   
Mail Stn:   BCM185 
  
     Name:   
GEORGIA COLLELUORI 
Phone:   
713-794-7156 
Id:   
187403 
Fax:   
Department:   MEDICINE: ENDOCRINOLOGY 
Email:    
colleluo@bcm.tmc.edu
Center:   
Mail Stn:   BCM185 
  
     Name:   
FRANCESCA VIGEVANO 
Phone:   
713-578-4300 
Id:   
204819 
Fax:   
713-798-8764 
Department:   MEDICINE: ENDOCRINOLOGY 
Email:    
vigevano@bcm.tmc.edu
Center:   
Mail Stn:   BCM185 
  
     Name:   
SANJAY MEDIWALA 
Phone:   
713-791-1414 
Id:   
691884 
Fax:   
713-794-7714 
Department:   MEDICINE: ENDOCRINOLOGY 
Email:    
mediwala@bcm.tmc.edu
Center:   
Mail Stn:   BCM185 
  


     Name:   
BIJU JOHNSON 
Phone:   
7137948850 
Id:   
Non-Baylor 
Fax:   
Institution:   
Michael DeBakey VAMC 
Email:    
Biju.Johnson@va.gov
Address:   
2002 Holcombe Blvd 
A5.  Funding Source: 
     Baylor College of Medicine (Internal Funding Only)
A6a.  Institution(s) where work will be performed: 
     BCM: Baylor College of Medicine 
Michael E. DeBakey Veterans Affairs Medical Center
A6b.  Research conducted outside of the United States: 
     
Country:   
Facility/Institution:   
Contact/Investigator:   
Phone Number:  8326592947 
If documentation of assurances has not been sent to the Office of Research, please explain:
A7.  Research Category: 
     
A8. Therapeutic Intent 
Does this trial have therapeutic intent? 
     Yes 
 Section B:  Exempt RequestB.  Exempt From IRB Review 
     Not Applicable 
 Section C:  Background Information 
     
BACKGROUND After age of 40, testosterone (T) production in men gradually decreases at a rate of 1.6% per 
year for total and to 2-3% per year for bioavailable T (5). Because of the age-related increase in sex hormone 
binding globulin, the magnitude of the decrease in bioavailable T in men is even greater than the decline in total T 
levels (6). This reduction in T production in men parallels the age-associated loss of muscle mass that leads to 
sarcopenia and impairment of function and the age-associated loss of bone mass that leads to osteopenia and 
fracture risk (7;8). Hypogonadism is a condition associated with multiple symptom complex including fatigue, 
depressed mood, osteoporosis, increased fat mass, loss of libido and reduced muscle strength, all of which 
deeply affect patient's quality of life (9). The prevalence of hypogonadismamong obese men ranges between 
29.3% to 78.8% (2;10), with levels of androgens decreasing proportionately to the degree of obesity (11), This 
decline in T levels is exacerbated among obese patients due the suppression of the hypothalamic-pituitary-
gonadal axis by hyperestrogenemia (12). The high expression of aromatase enzyme in the adipose tissue 
enhances the conversion of androgens into estrogens (E) which in turn exerts a negative feedback on 
hypothalamus and pituitary (1), inhibiting the production of gonadotropin-releasing hormone (GnRH), luteinizing 
hormone (LH) and follicle stimulating hormone (FSH) and, as a consequence, of T by the testis resulting in 
hypogonadotropic hypogonadism (HH). Considering the high aromatase expression in the adipose tissue, the 
administration of T among obese men with HH could increase the conversion of the substrate T to estradiol (E2) 
and fuels the negative feedback on the hypothalamus and pituitary, producing a greater suppression of GnRH and 
gonadotropins. Accordingly, preliminary data from our ongoing study (CYP19A1 Gene and Pharmacogenetics of 
Response to Testosterone Therapy) showed no improvement in hypogonadal symptoms and lean mass in 
severely obese men (BMI higher than 35 kg/m2) after treatment with T, compared to subjects with lower BMI. In 
addition, we also have data from our lifestyle intervention in obese men showing statistically significant 
improvement in T levels after 1 year among patients randomized to the weight loss groups relative to the weight 
maintenance groups. However, the increase in T levels is barely above the cut-off of 300 ng/dl set by the 
Endocrine Society as criteria for diagnosis of hypogonadism and far from the mid-eugonadal range. Unfortunately, 
as this was not a study on hypogonadism, no data on changes in symptoms related hypogonadism were 
collected. Thus, men with obesity induced HH may benefit from other treatment strategies that target the 
pathophysiology of the disease. Weight loss intervention which improves hormonal and metabolic abnormalities 
related to obesity may also be considered a logical approach to improve obesity-induced HH. A metaanalysis 
showed reduction in E2 and increase in LH, free and total T in men after both lifestyle and bariatric surgery 
interventions (2). However, increased T levels induced by weight loss are often lost due to weight regain (3), 
which is very frequent among patients undergoing massive weight loss (13). One possible approach consists of 
the use of aromatase inhibitors (AI) to stop the conversion of T to E2 thereby interrupting the vicious cycle of E2 
inhibition of the hypothalamic-pituitary-gonadal axis and restoring T production to normal levels. Increased T and 
reduced E2 levels have been reported in men with low levels of T after AI administration, even though very few 


studies investigated clinical outcomes (14).The only study that explored the effect of AI on clinical outcomes such 
as bone density, body composition, psychological function and exercise capacity in HH obese men was the one of 
Loves et al. (15). However, a definitive conclusion could not be darwn from this study due to study design, i.e. 
escalating doses of Letrozole starting at 2.5 mg/week were administrated until a serum total testosterone of 20 
nmol/l was reached. At the end of the 6-month study, research participants were on varied doses of AIs. In other 
studies using anastrozole 1 mg daily in elderly patients, an increase in testosterone to the mid-eugonadal range 
was observed but there were no improvement in symptoms, likely because these patients were not necessarily 
obese. However, there were also minimal side effects on bone health among men(15). Among the studies along 
looking at the effect of AIs in men with hypogonadism, only one reported a mild decrease in bone density which 
was not accompanied by deterioration in bone quality (21). In addition, there were no significant effects on the 
changes in body composition, metabolic risk factors, hematocrit, urinary symptoms and prostate-specific antigen 
(PSA) (14, 21). Bone loss is a recognized side effect of AIs in women with breast cancer (17;18;19;20;27;28;29), 
however, negative side effect on bone metabolism does not appear to be a major problem. In addition, in contrast 
to hypogonadal patients who have low E2 production from reduced T production, HH obese men present high 
levels of circulating estrogens that could potentially prevent them from bone loss, estradiol being the main 
regulator of the male skeleton. Our preliminary data showed significantly higher levels of estradiol, bone density at 
the lumbar spine total hip, trochanter and intertrochanter in men with a BMI greater than 35 kg/m2 (ongoing study: 
CYP19A1 Gene and Pharmacogenetics of Response to Testosterone Therapy). In HH obese men with baseline 
values of E2 more than 40 pmol/l, no bone loss was demonstrated after 6 month of AI administration compared to 
placebo (15). Our data (under review in the European Journal of Endocrinology) showed that hypogonadal men 
with high aromatase activity were able to maintain higher BMD despite low circulating T, but had lower lean and 
higher truncal fat mass compared to those with lower aromatase activity. We believe that AI use could promote 
positive changes on hypogonadal symptoms and body composition in HH severely obese patients, acting at the 
physiopathology of the disease without necessarily causing bone loss as reported by Loves et al (15). Given the 
difficulties among massively obese patients in losing weight to a BMI of less than 35 together with the difficulty 
related to weight loss maintenance, the effect of AI in conjunction with weight loss should be considered as an 
attractive alternative to increase and maintain T levels to normal. 
 Section D:  Purpose and Objectives 
     
OBJECTIVES: 1. To evaluate the effect of AIs in combination with weight loss compared to weight loss alone on 
the changes in muscle strength, and symptoms of hypogonadism in massively obese men with hypogonadotropic 
hypogonadism 2. To evaluate the effect of AIs in combination with weight loss compared to weight loss alone on 
the changes in body composition and visceral adipose tissue in massively obese men with hypogonadotropic 
hypogonadism. 3. To evaluate the effect of AIs in combination with weight loss compared to weight loss alone on 
bone mineral density and bone quality in massively obese men with hypogonadotropic hypogonadism. We 
hypothesize that in severely obese men with HH, the combination of AI therapy and weight loss intervention would 
be an effective alternative treatment strategy in improving HH related signs and symptoms without the adverse 
effect on bone metabolism. 
 Section E:  Protocol Risks/SubjectsE1.  Risk Category 
     Category 2: Research involving greater than minimal risk, but presenting the prospect of direct benefit to the 
individual subjects. 
E2.  Subjects 
Gender: 
     Male 
Age: 
     Adult (18-64 yrs), Geriatric (65+ yrs)
Ethnicity: 
     All Ethnicities 
Primary Language: 
     English 
Groups to be recruited will include: 
     Patients 
Which if any of the following vulnerable populations will be recruited as subjects? 
     
Vulnerable populations require special protections.  How will you obtain informed consent, protect subject 
confidentiality, and prevent undue coercion? 
     
E3.  Pregnant woman/fetus 


Will pregnant women and/or fetuses (as described in 45 CFR 46 Subpart B) be enrolled in the research? 
     No
E4.  Neonates 
Will neonates of uncertain viability or nonviable neonates (as described in 45 CFR 46 Subpart B) be enrolled in the 
research? 
     No
E5.  Children 
Will children be enrolled in the research? 
     No
 Section F:  Design/ProcedureF1.  Design 
Select one category that most adequately describes your research: 
     c) Pilot 
Discuss the research design including but not limited to such issues as: probability of group assignment, potential for 
subject to be randomized to placebo group, use of control subjects, etc. 
     See attachment entitled " F1 Design IRB 7.29"
Inclusion Criteria: 
     
Inclusion criteria: we will enroll 35-65 years old severely obese (BM I= or above 35 kg/m2 ) male veterans with 
hypogonadotropic hypogonadism defined as low total testosterone (lower than 300 ng/dl) taken from the average 
of two morning blood samples obtained between 8:00 and 11:00 AM in different days, at least 2-3 days apart, with 
LH lower than 9 U/L, estradiol above 40 pmol/l, and normal FT4,TSH, prolactin, cortisol, ACTH and IGF1 levels. 
Subjects must be ambulatory, willing and able to provide written informed consent. 
Exclusion Criteria: 
     
Exclusion criteria: 
1) clinical or biochemical evidence of pituitary or hypothalamic disease; 2) any ongoing illness that, in the opinion 
of the investigator, could prevent the subject from completing the study; 3) any medication known to affect 
gonadal hormone levels, steroid hormone-binding globulin levels or bone metabolism (e.g., androgens, estrogens, 
glucocorticoids, phenytoin, or bisphosphonates); any medication known to interfere with anastrozole metabolism 
(tamoxifen and estrogens). 4) diseases known to interfere with bone metabolism as osteoporosis, 
hyperparathyroidism, untreated hyperthyroidism, osteomalacia, chronic liver disease, renal failure, 
hypercortisolism, malabsorption and immobilization; patients with a Total T score lower than -2.0 at Lumbar Spine 
or Left Femur. 5) symptomatic prostate disease, prostate carcinoma or elevated serum PSA more than 4 ng/ml or 
>3 for subject with family history of prostate cancer among first degree relatives (needs urologic evaluation before 
admission into study); 6) hematocrit greater than 50%, untreated severe obstructive sleep apnea, severe lower 
urinary tract symptoms with International Prostate Symptom Score above 19; 7) documented heart failure, 
cardiovascular disease, liver disease; 8) excessive alcohol or substance abuse; 9) unstable weight (changes in 
weight more than ± 2 kg) during the last 3 months; 10) history of bariatric surgery 11) subjects with elevated liver 
enzymes as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and bilirubin 
at more than twice the upper limit of normal. 
F2.  Procedure 
     
Screening and baseline tests: 
1. Medical, social and medication history, body weight and height data will be collected and a physical 
examination with a digital rectal examination (DRE) will be done (all are standard of care). 2. Blood testing will be 
obtained for fasting testosterone from two samples taken between 8-11 AM at 2 separate days and at least 2-3 
days apart (standard of care). 3. Blood tests for comprehensive metabolic panel (CMP), fasting lipid panel, 
aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubine, 
HbA1c, complete blood count (CBC), prostate specific antigen (PSA), luteinizing hormone (LH), follicle stimulating 
hormone (FSH), prolactin, thyroid stimulating hormone (TSH), insulin growth factor-1 (IGF1), free thyroxine (FT4), 
cortisol , adrenocorticotropic hormone (ACTH), 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), 
estradiol, bone markers osteocalcin, and N-terminal telopeptide (NTx), and sex hormone binding globulin (SHBG). 
Blood obtained from an antecubital vein, will be processed immediately, and be stored in aliquots at -80C 
(standard of care). 4. Quantitative Androgen Deficiency in Aging Male (ADAM) questionnaire to assess for 
symptoms of hypogonadism and severity (25), International Index of Erectile Function (IIEF) questionnaire, 
Stanford physical activity 7 days recall questionnaire, SF-36 questionnaire to assess patient¿s quality of life, and 
the Impact of Weight on Quality of Life Questionnaire- Lite (IWQOL ) to evaluate the effect of excess weight on 
quality of life will be all administered These questionnaires are mostly research although most of the questions in 
the questionnaires are part of the review of systems which is standard of care. 5. Muscle strength will be 


assessed through Biodex System 4 isokinetic dynamometer (Shirley, NY); peak torque for isokinetic and isometric 
knee extensor and flexor will be measured. During the testing, the participants will seat with their backs supported 
and hips positioned at 120° of flexion and secured to the seat of the dynamometer with thigh and pelvic straps. All 
tests will be performed on the right leg. Testing will be performed at an angular velocity of 60° per second. The 
best of the 3 maximal voluntary efforts for each of the knee flexion and extension will be used as the measure of 
absolute strength and report as peak torque at 60° in Newton-meter (N.m) units. This is research. 6. Areal Bone 
mineral density (BMD) will be assessed by dual energy x-ray absorptiometry (DXA), of the spine, hip, wrist and 
whole body, bone volumetric BMD and bone quality of the spine and hip will be measured by central quantitative 
computed tomography (QCT), bone volumetric BMD and bone quality of the peripheral skeleton will be measured 
by high-resolution peripheral quantitative computed tomography (HR-pQCT) on the left tibia, and body 
composition and visceral adipose tissue volume by DXA. Trabecular bone score (TBS) will be calculated from the 
spine BMD obtained by DXA. BMD by DXA is standard of care while the rest is research. 
Follow-up testing (please see Table and Schedule of tests): 
1. Medical, social and medication history, and physical examination, body weight and height will be repeated at 3 
and 6 months. DRE will be repeated at 6 months. An additional physical examination (except for digital rectal 
exam) will be done after 2 weeks from the start of the intervention for safety monitoring. 2. The ADAM quantitative 
questionnaire, IIEF questionnaire, Stanford physical activity 7 days recall questionnaire, SF-36 questionnaire and 
the IWQOL will be administered at baseline, 3 and 6 months. 3. Muscle strength by Biodex will be assessed at 
baseline, 3 and 6 months (not standard of care). 4. Participants will be given instructions for keeping 7-day food 
intake records and provided with recording forms to estimate energy intake and nutrient composition. The food 
intake records will be analyzed using the Nutritionist IV computer program (N2 Computing, San Bruno, CA). The 
Stanford 7-Day Physical Activity Questionnaire will be used to quantify the time spent in different categories of 
activity during the previous 7 day period. Participants will also be asked to wear accelerometers for the whole 
intervention and to report daily data concerning the instrument usage. 5. Blood will be collected at 2 weeks a for 
testosterone, estradiol, LH and FSH, AST, ALT,ALP and bilirubin and at 3 and 6 months for repeat PSA, total 
testosterone, CBC, CMP, lipid panel, HbA1C, ALP, AST, ALT and bilirubin, markers of bone turnover, estradiol, 
SHBG, LH, FSH, 25-hydroxy vitamin D and PTH (all test are standard of care except for estradiol and SHBG). 6. 
Bone mineral density will be measured using DXA, QCT, and HR-pQCT at baseline and 6 months. TBS will be 
calculated at baseline and 6 months, whereas body composition and visceral adipose tissue volume will be 
measured at baseline, 3 and 6 months, both will be assessed using DXA. 7. At baseline, 3 and 6 month, blood will 
be drawn for extraction of DNA, which is part of the cell and os responsible for providing hereditary 
characteristics. The purpose of analyzing DNA is to determine whether hereditary characteristics are associated 
with obesity induced HHG and whether the response to weight loss and AI administration is affected by them 
 Section G:  Sample Size/Data AnalysisG1.  Sample Size 
How many subjects (or specimens, or charts) will be used in this study? 
     Local: 23              Worldwide: 30 
Please indicate why you chose the sample size proposed: 
     
This is a pilot study with the primary objective of gathering preliminary feasibility and effectiveness data for the 
development of a bigger study. We plan to enroll 30 subjects for this study. In prior studies of patients with HH 
using sample sizes of 20-40, a significant increase in T levels was observed for those on AIs compared to those 
without AIs. In our proposed study, we anticipate a greater increase in T in our patient's randomized to AI over 
and above the increase resulting from weight loss alone by the same magnitude of increase in above studies 
which compared the effect of AI alone to those not on AI. Thus, a sample of 30 was chosen for this pilot study. 
Although the above studies did not include changes in hypogonadal symptoms as outcomes, we aniticipate 
greater improvement in symptoms of hypogonadism among patients on AIs plus weight loss. It is highly likely that 
we may not be able to find a statisitcally significant difference between the AIs plus weight loss vs. weight loss 
alone group in our primary outcomes given this limited sample size, but our results would still provide important 
information for a bigger study if a trend is observed. 
G2.  Data Analysis 
Provide a description of your plan for data analysis. State the types of comparisons you plan (e.g. comparison of 
means, comparison of proportions, regressions, analysis of variance). Which is the PRIMARY comparison/analysis? 
How will the analyses proposed relate to the primary purposes of your study? 
     
Baseline characteristics between groups will be compared using independent t-test or Fisher¿s exact test. 
Percent changes in outcomes at 3 and 6-month time points will be compared between the 2 groups using 
repeated measures analysis of covariance adjusting for covariates such as age, ethnicity and medication use as 
appropriate. A p value of <0.05 will be considered significant. Simple correlations will be analyzed using Pearson 
correlation coefficient. 


Given the limited sample size, it is possible that we many not find a significant difference in outcomes between the 
anastrozole+weight loss vs. weight loss alone but the information generated from this pilot study will still be useful 
if a trend is observed for future proposals or plan for additional recruitment to enhance the sample size. 
 Section H:  Potential Risks/DiscomfortsH1.  Potential Risks/Discomforts 
Describe and assess any potential risks/discomforts; (physical, psychological, social, legal, or other) and assess the 
likelihood and seriousness of such risks: 
     
POTENTIAL RISKS AND DISCOMFORT We anticipate no psychological, social or legal risks beyond those of 
participation in health-related research in general. The potential risks of this study are small and primarily 
associated with the testing measures and anastrozole therapy as described in the next paragraphs: Risk related 
to aromatase inhibitors administration: available data regarding potential risks and discomfort due to the use of 
aromatase inhibitors refer to women (18;27-29). Furthermore, the lower levels of estradiol in postmenopausal 
women compared to men have to be taken into account. Bone loss was also reported primarily in women taking 
the medication for breast cancer(28;30). A report of bone loss was also reported in elderly men, not the population 
we are proposing in our study(19). A prior report showed no bone loss if patients are severely obese with estradiol 
levels over 40 pmol/L (10.9 pg/ml) which is the target population for this proposed project (15). Subject will be 
informed about the possible risks and discomfort and instructed to report all of them to the research team. The 
following are the side effect reported for women after AI treatment. a) Non severe side effect: weakness, 
headache; hot flashes; sweating; stomach pain; nausea; vomiting; loss of appetite; constipation; diarrhea; 
heartburn; joint; bone or muscle pain; breast pain; mood changes; depression; difficulty falling asleep or staying 
asleep; nervousness; dizziness; pain, burning, or tingling in the hands or feet; dry mouth; hair thinning. b) Severe 
side effects: chest pain; sore throat, cough, fever, chills, swollen glands, or other signs of infection; swelling, 
redness, or warmth in hand or arm; difficult, painful, or urgent urination; blurred vision or vision changes; yellowing 
of the skin or eyes; pain in the upper right part of the stomach; skin lesions, ulcers, or blisters; rash; hives; itching; 
shortness of breath; difficulty swallowing or breathing; swelling of the eyes, face, lips, tongue, throat, arms, hands, 
feet, ankles, or lower legs. Allergic reaction: Symptoms may include but not be limited to trouble breathing, fast 
heart rate, rash, dizziness, and swelling. Risks related to blood drawing: possible temporary pain and discomfort 
from the needle stick, occasional bruising and or bleeding at the site of needle insertion, sweating, feeling faint or 
lightheaded and in rare cases infection. There have been reported serious skin reactions (such as Stevens-
Johnson Syndrome). Risk related to radiation (x-ray) risks: This research involves exposure to radiation from the 
dual energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-
pQCT) for bone mineral density and body composition measurements, as well as from spine X-rays. The amount 
of radiation from these tests when averaged over our entire body is less than 3% of the allowable annual dose to 
a radiation worker (for example, X-ray technicians). The risk from the radiation exposure in this study is too small 
to be measured and not more than the usual daily exposure. Risk related to lifestyle intervention: A modest 
muscle and bone density loss associated with weight loss can occur. However, this is prevented by exercise 
(26;31) (32) which we propose to combine with weight loss. A rare risk of weight loss is the formation of gallstone. 
There are risks related to the loss of confidentiality. The health information that we may use, disclose or release 
for this research is past and present medical and mental health information, alcoholism or alcohol abuse 
information, medications, tests including diagnostic laboratory, pathology results, imaging such as x-rays, MRIs 
CT scans, dates of tests, demographic information such as name, date of birth, age, home address, phone 
number, last four SSN, race, dates of tests and test results, completed research questionnaires and records of 
study drug received. These information may be disclosed unintentionally in the course of the study. 
Genetic research risk: There are risks of loss of privacy, getting insured, becoming employed, and stigmatization 
from results of genetic testing. There are some protections afforded by the Genetic Information Nondiscrimination 
Act (GINA). Participation in research may involve a loss of privacy or confidentiality, but personal information will 
be kept as confidential as possible. Representatives from the Baylor College of Medicine Human Research 
Protection Office, Michael DeBakey VA Medical Center and National Institute of Health will be permitted to access 
patient records. 
There are risks of stress, emotional distress, and inconvenience associated with participating in aresearch study. 
Participants may experience emotional discomfortwhen answering some questions in the questionnaires. 
Participants will be encouraged to discuss the importance and the need to answer these questions with a member 
of the research team. If they remain uncomfortable in answering these questions despite the above efforts, 
participants will be given the option not to answer them. 
Unknown risks: The experimental treatments may have side effects that no one knows about yet including 
potential death. They may also have unknown risks to a fetus or embryo. 
H2.  Data and safety monitoring plan 


     Do the study activities impart greater than minimal risk to subjects? 
     
    Yes 
NOTE:  The answer to the questions in H2 requires the completion of the form: 'Section H – Data and Safety 
Monitoring Plan' as an attachment in Section S. 
H3.  Coordination of information among sites for multi-site research 
Is the BCM Principal Investigator acting as the SPONSOR-INVESTIGATOR for this multi-site research? 
         No or Not Applicable 
Is BCM the COORDINATING CENTER for this multi-site research? 
         No or Not Applicable 
 Section I:  Potential Benefits 
Describe potential benefit(s) to be gained by the individual subject as a result of participating in the planned work. 
     
POTENTIAL BENEFITS: Patients may or may not benefit from participating in this study. Improvement in quality 
of life and hypogonadal symptoms including muscle strength, sexual function, mood, and body composition, may 
be experienced by subjects participating in this study. Weight loss and related metabolic improvement may also 
occur. 
Describe potential benefit(s) to society of the planned work. 
     
The information gained from this study may help identifying the best way of treatment for the obesity-related 
hypogonadotropic hypogonadism : its different physiopathology necessitates an effective therapy able to act the 
the root of the disease and thus improve hypogonadal symptoms and muscle strength. According to our 
preliminary data, this subgroup of hypogonadal obese subject do not benefit from testosterone therapy. 
Do anticipated benefits outweigh potential risks? Discuss the risk-to-benefit ratio. 
     
The benefits to the subjects studied in this research protocol, and to society at large, far surpass the risks. In 
addition to having weight loss, improvement of symptoms related to hypogonadism may result from a combination 
of weight loss and anastrozole in severely obese subjects who are likely not to respond to testosterone treatment. 
On the other hand among the side effects, erythrocytosis, increase in PSA and prostatic enlargement are well-
recognized side effect of increase levels from testosterone administration. Furthermore, recent studies reported 
increase in the risks of myocardial infarction, stoke associated with testosterone treatment. Although we plan to 
monitor our subjects closely, these events have not been reported in studies using AIs. Bone loss has been 
reported in postmenopausal women with breast cancer and in elderly men hypothesized to be due to profound 
estrogen deficiency resulting from AI use. However, we do not foresee this as a problem for severely obese men 
who have elevated levels of estrogens at baseline. Thus, we believe that the benefits outweigh the risk with this 
treatment regimen which if found to be effective, may potentially become the standard of care for severely obese 
patients. 
 Section J:  Consent ProceduresJ1.  Waiver of Consent 
Will any portion of this research require a waiver of consent and authorization? 
     Yes 
Please describe the portion of the research for which a waiver is required. (Example: chart review to determine 
subject eligibility) 
     Chart review to determine subject eligibility (for screening purposes only). 
Explain why the research and the use or disclosure of protected health information involves no more than minimal 
risk (including privacy risks) to the individuals. 
     No 38 U.S.C. 7332 information (drug abuse, alcohol abuse, HIV infection and sickle cell anemia) will be used in 
this research study 
Explain why the waiver will not adversely affect the privacy rights and the welfare of the research subjects. 
     
We will review the patients charts in the electronic medical record system in the VA known as Computerized 
Patient Record System (CPRS) in the same way as we review records of our clinical patients, the access to which 
is password protected. All members of the research team will be issued an individual password. We plan to 
protect identifiers from improper use or disclosure. Records that are queried will be stored in folders on VA 
computer space to which acess is restricted to personnel authorized by the VA Research and Development 
Committee, specifically the PI and study coordinator. Data will not be shared on hard drives of any workstation, or 
transmitted to any other facilty. All printing will be directed to a printer in a private office, not to common work 
areas. Once permission has been obtained from their providers to contact patients, files containing identifiers will 
be maintained for as long as it takes to mail out solicitation letters and fully recruit for the study. 
Any information that is collected as part of the research including PHI will not be used or disclosed to a third party 
except as required by law or permitted by a HIPAA authorization. The identifiers will be destroyed at the earliest 
opportunity according to VA guidelines 


Explain why the research could not practicably be conducted without the waiver and could not practicably be 
conducted without access to and use of the protected health information. 
     
There are a large number of patients in the database and it is not possible to identify whether they might meet 
basic eligibility criteria without first accessing PHI and we would not be able to obtain HIPAA authorization from all 
of these patients prior to enrollment. 
Describe how an adequate plan exists in order to protect identifiers from improper use and disclosure. 
     
Access to the CPRS at the MEDVAMC is limited to individuals who are involved in patient care or human 
research and is password protected. Paper documents will be placed in double locked doors with only members 
of research team are allowed access. In addition, no names will be used in any communication or publication 
resulting from the study. Please also see our response to (a) above. 
Describe how an adequate plan exists in order to destroy identifiers at the earliest opportunity consistent with 
conduct of the research, unless there is a health or research justification for retaining the identifiers or such retention 
is otherwise required by law. 
     
Any files that contain identifiers for the specific purpose of screening and determining eligibility (as part of this 
waiver of consent) will be destroyed at the earliest opportunity (i.e. when no longer used to determine eligibility 
and recruit for the study) according to VA guidelines. 
Describe how adequate written assurances exist in order to ensure that the PHI will not be reused or disclosed to 
(shared with) any other person or entity, except as required by law, for authorized oversight of the research study, or 
for other research for which the use or disclosure of the PHI would be permitted under the Privacy Rule. 
     
Names will not be used in any communication or published reports about this study. In the event that samples had 
to be shared with other laboratories, coded samples will be transferred without identifiers. 
Information from health records such as diagnoses, progress notes, medications, lab or radiology findings, etc. 
     Yes 
Specific information concerning alcohol abuse: 
     No
Specific information concerning drug abuse: 
     No
Specific information concerning sickle cell anemia: 
     No
Specific information concerning HIV: 
     No
Specific information concerning psychiatry notes: 
     No
Demographic information (name, D.O.B., age, gender, race, etc.): 
     Yes 
Full Social Security #: 
     No
Partial Social Security # (Last four digits): 
     Yes 
Billing or financial records: 
     No
Photographs, videotapes, and/or audiotapes of you: 
     No
Other: 
     No
Will additional pertinent information be provided to subjects after participation? 
     No
If No, explain why providing subjects additional pertinent information after participation is not appropriate. 
     No 38 U.S.C. 7332 information (drug abuse, alcohol abuse, HIV infection and sickle cell anemia) will be used in 
this research study 
 J1a.  Waiver of requirement for written documentation of Consent 
Will this research require a waiver of the requirement for written documentation of informed consent? 
     No
J2.  Consent Procedures 
Who will recruit subjects for this study? 


     PI 
PI's staff 
Describe how research population will be identified, recruitment procedures, any waiting period between informing 
the prospective participant and obtaining consent, steps taken to minimize the possibility of coercion or undue 
influence and consent procedures in detail. 
     
We will recruit primarily male veterans attending the Endocrine, Primary Care and Urology Clinics at the Michael 
DeBakey VA Medical Center, Houston, TX. Active advertisement through posters and flyers, and direct mailings 
of printed materials to potential subjects will be done. Potential subjects will be identified from direct referral by the 
attending physicians of patients who have testosterone levels of lower than 300 ng/ml and a BMI= or higher than 
35 kg/m2 under the inclusion criteria. The records will be reviewed for exclusion criteria. A member of the staff will 
then send a letter asking each primary care physician (PCP) for permission to contact his or her eligible patients. 
The PCP will respond by checking the names of those appropriate for this study. Once the provider¿s permission 
is obtained, a letter from the PCP will be sent to the patient describing the study and introducing the investigators. 
Interested patients will be asked to return a postcard. 
Individuals who express an interest in participation will undergo a brief (~10 min) telephone interview by a 
member of the research team. All individuals who express an interest in participating and meet the preliminary 
inclusion criteria will be invited to visit our facility and discuss their potential participation in greater detail. During a 
60 min long orientation session with members of the research team, detailed information will be provided 
regarding the aims of the study, and all of the tests and measurements that they will undergo if they participate in 
the study. Verbal and written information about the potential benefits and risks of the study will be provided; their 
questions will be answered and any concerns that they have will be addressed. If the individual is interested in 
participating, a screening evaluation will be scheduled. Prior to enrollment and randomization, the volunteers will 
undergo a detailed medical history and physical examination, and a clinical laboratory testing after a proper 
consent has been obtained in writing. During this session they will have the nature and purpose of the study 
explained to them again, discuss their reasons and motivation for participation in the research to determine 
whether they are realistic and discuss any potential problems, that might interfere with participation and have their 
questions answered. Informed consent to participate in the study will be obtained in writing by one of the 
investigators before any tests or measurements are performed. Data which include HIPAA identifiers such as 
names, date of birth or age, dates of tests and medical record number (first letter of last name plus last 4 digits of 
social security number) will be collected. 
Each subject will be informed that their participation in the study is completely voluntary and they may withdraw by 
telling the study team that they are no longer interested in participating in the study or they may send in a 
withdrawal letter. They will also be informed that their choice will not at any time affect the commitment of their 
health care providers to administer care and that there will be no penalty or loss of benefits to which they are 
otherwise entitled. 
For the Waiver of Consent for Subject Identification, please see the attached document entitled "J2- Waiver for 
Identification". 
Are foreign language consent forms required for this protocol? 
     No
J3.  Privacy and Intrusiveness 
Will the research involve observation or intrusion in situations where the subjects would normally have an 
expectation of privacy? 
     No
J4.  Children 
Will children be enrolled in the research? 
     No
J5.  Neonates 
Will non-viable neonates or neonates of uncertain viability be involved in research? 
     No
J6.  Consent Capacity - Adults who lack capacity 
Will Adult subjects who lack the capacity to give informed consent be enrolled in the research? 
     No
J7.  Prisoners 
Will Prisoners be enrolled in the research? 
     No


 Section K:  Research Related Health Information and Confidentiality 
Will research data include identifiable subject information? 
     Yes 
Information from health records such as diagnoses, progress notes, medications, lab or radiology findings, etc. 
     Yes 
Specific information concerning alcohol abuse: 
     Yes 
Specific information concerning drug abuse: 
     Yes 
Specific information concerning sickle cell anemia: 
     No
Specific information concerning HIV: 
     No
Specific information concerning psychiatry notes: 
     No
Demographic information (name, D.O.B., age, gender, race, etc.): 
     Yes 
Full Social Security #: 
     No
Partial Social Security # (Last four digits): 
     Yes 
Billing or financial records: 
     No
Photographs, videotapes, and/or audiotapes of you: 
     No
Other: 
     No
At what institution will the physical research data be kept? 
     Hard copies of the research data will be maintained at the MEDVAMC building 110, and will be stored in a locked 
office (room 240) inside a locked file cabinet, located in a restricted area. 
How will such physical research data be secured? 
     Only the PI and research staff will have access to the room and cabinet where the information will be stored and 
they will take care of locking both at all time of usage. 
At what institution will the electronic research data be kept? 
     
Electronic data will be stored on the secure MEDVAMC S drive (restricted shared drive permission) in a subfolder 
of the main research folder. 
The exact location of the electronic data is S:\Research-Data\Villareal, Reina\H-36912 
Database location will be on a VA server 
Such electronic research data will be secured via BCM IT Services- provided secured network storage of electronic 
research data (Non-Portable devices only): 
     No
Such electronic research data will be secured via Other: 
     
Yes, (describe below): 
Electronic data will be stored on the secure MEDVAMC S drive (restricted shared drive permission) in a subfolder 
of the main research folder . 
The exact location of the electronic data is S:\Research\Villareal, Reina\H-36912 
Database location will be on a VA server 
Will there be anyone besides the PI, the study staff, the IRB and the sponsor, who will have access to identifiable 
research data? 
     
Yes, identify the classes of the persons: 
People who ensure quality from the institutions where the research is being done, federal and other regulatory 
agencies will have access to all of the research data such as Food and Drug Administration (FDA) and Data 


Monitoring Committee (DMC). The purpose of collecting information covered under 38 U.S.C. 7332 is to conduct 
scientific research and no personnel involved in this study will identify, directly or indirectly, any individual patient 
or subject in any report of such research. 
Please describe the methods of transmission of any research data (including PHI, sensitive, and non-sensitive data) 
to sponsors and/or collaborators. 
     Data will not leave the MEDVA.
  
Will you obtain a Certificate of Confidentiality for this study? 
     No
Please further discuss any potential confidentiality issues related to this study. 
     
Research records, including identifiers will be destroyed 6 years after cutoff (at the end of the fiscal year) after 
completion of the research project, but may be retained longer if required by other federal regulations or sponsor 
archive requirement. 
 Section L:  Cost/Payment 
Delineate clinical procedures from research procedures. Will subject's insurance (or subject) be responsible for 
research related costs? If so state for which items subject's insurance (or subject) will be responsible (surgery, 
device, drugs, etc). If appropriate, discuss the availability of financial counseling. 
     Subjects are not responsible for any costs related to participation in the research. 
If subjects will be paid (money, gift certificates, coupons, etc.) to participate in this research project, please note the 
total dollar amount (or dollar value amount) and distribution plan (one payment, pro-rated payment, paid upon 
completion, etc) of the payment. 
Dollar Amount: 
     60 
Distribution Plan: 
     Subjects will be paid 20$ at baseline, 3 and 6 months. Total payment for completing the study will be 60$ per 
patient. 
 Section M:  Genetics 
How would you classify your genetic study? 
     DNA diagnostic study 
Discuss the potential for psychological, social, and/or physical harm subsequent to participation in this research. 
Please discuss, considering the following areas: risks to privacy, confidentiality, insurability, employability, 
immigration status, paternity status, educational opportunities, or social stigma. 
     
There is an associated genetic risk if the genetic information is leaked which may affect a subjects insurability. 
However, all of the patients are veterans getting medical care at the Michael DeBakey VA Medical Center whose 
benefits will not terminate with any breach of genetic information. In addition, since the type of genetic variations 
that this study is investigating are common genetic variations in the population, we foresee no consequences on 
the patients employablity, immigration status, educational opportunities or social stigma and not useful in 
establishing paternity. 
Will subjects be offered any type of genetic education or counseling, and if so, who will provide the education or 
counseling and under what conditions will it be provided? If there is the possibility that a family's pedigree will be 
presented or published, please describe how you will protect family member's confidentiality? 
     
No, subjects will not be offered any type of genetic education or counseling. There is not the possibility that a 
family's pedigree will be presented or published. The results of the genetic testing will not be given to the subjects. 
As the patients blood sample will not be linked to the patients identity, we plan to match the subjects identity with 
their DNA results with a study code assigned to each subjects DNA results which can only be interpreted with a 
special decrypting file. 
 Section N:  Sample CollectionSAMPLE:   Other: blood 
What is the purpose of the sample collection? 
     
Blood samples will be collected for 1) medical screening to determine eligibility for the study (see 
inclusion/exclusion criteria, 2) to monitor blood levels of testosterone, estradiol, LH, FSH and side effects on blood 
count and PSA, 3) overall safety monitoring while in the study 
For blood draws, specify the amount drawn, in teaspoons, at each visit and across the course of the subjects entire 
participation time. 
     A total of 4 tablespoons of blood at baseline and 6 months, and 3 tablespoons at 2 weeks and at 3 months. Total 
amount of blood collected for participating in the study 14 tablespoons. 
Is there the possibility that cell lines will be developed with this sample?No 
Sample will be obtained from: 


     Clinical Labs, Research Labs 
Will the sample be stripped of identifiers? 
     No
If sample will be released outside the hospital: 
Will sample be released to anyone not listed as an investigator on the protocol? Will the information be identifiable, 
coded or de-identified? 
     Yes, to BCM collaborators. All samples will be coded using random numbers not linked to SSN. 
Will sample material be sold or transferred to any third parties? Will the information be de-identified? 
     No.
If sample will be banked for future use: 
Where will the sample be banked and for how long? 
     At the Michael DeBakey VA Medical Center for 10 years
Does the banking institution have an approved policy for the distribution of samples? 
     Yes. 
If the entire sample will NOT be used during the course of this research study: 
Will the remaining tissue be discarded? If not what will be done with the remaining sample after study completion and 
how long will the sample be kept? 
     We will keep the samples for 10 years after study completion after which they will be discarded. 
Will samples be made available to the research subject (or his/her medical doctor) for other testing? 
     No
If a subject withdraws from the study: 
Will subject have the option to get the remaining portion of their sample back? 
     No
Will samples be destroyed? If not, will they be kept anonymously? What will happen to the sample if the subject 
revokes authorization? 
     If the patient withdraws from the study, samples will not be destroyed and will be stored anonymously. If the 
subject revokes authorization, the samples will be destroyed or discarded. 
Will data obtained from their sample be deleted? What will happen to the sample if the subject revokes 
authorization? 
     For those who withdraw from the study, we will use the data generated from the samples. However, for subjects 
who revoked authorization, their data will be deleted and samples destroyed or discarded. 
Will study data or test results be recorded in the subject's medical records? 
     Yes 
Will results of specific tests and/or results of the overall study be revealed to the research subject and or his/her 
doctor? 
     
Standard test results that are done at VA lab and have clinical use are reported in CPRS, or Computerized Patient 
Record System, and thus they are automatically included in the subjects medical records (i.e. in CPRS, which is 
accessible to the vets primary provider). Any abnormal findings will be shared with the subject¿s primary care 
physicians for further evaluation and appropriate treatment through the CPRS which are shared with their VA 
primary care physicians. Depending on the urgency of the abnormal findings, the PI may directly contact the 
primary care provider by phone to discuss the abnormal findings 
Please identify all third parties, including the subject's physician, to receive the test results. 
     Participants treating physicians. 
 SAMPLE:  Blood 
What is the purpose of the sample collection? 
     1) DNA collection to investigate the impact of the genetic profile on the response to anastrazole and/or weight loss 
intervention. 
For blood draws, specify the amount drawn, in teaspoons, at each visit and across the course of the subjects entire 
participation time. 
     A total of 1 tablespoons of blood at baseline, 3 months and 6 months. Total amount of blood collected for genetic 
testing for participating in the study is 3 tablespoons. 
Is there the possibility that cell lines will be developed with this sample?No 
Sample will be obtained from: 
     Research Labs 
Will the sample be stripped of identifiers? 
     No


If sample will be released outside the hospital: 
Will sample be released to anyone not listed as an investigator on the protocol? Will the information be identifiable, 
coded or de-identified? 
     Yes, to BCM collaborators. All samples will be coded using random numbers not linked to SSN. 
Will sample material be sold or transferred to any third parties? Will the information be de-identified? 
     No
If sample will be banked for future use: 
Where will the sample be banked and for how long? 
     At the Michael DeBakey VA Medical Center for 10 years
Does the banking institution have an approved policy for the distribution of samples? 
     Yes 
If the entire sample will NOT be used during the course of this research study: 
Will the remaining tissue be discarded? If not what will be done with the remaining sample after study completion and 
how long will the sample be kept? 
     We will keep the samples for 10 years after study completion after which they will be discarded. 
Will samples be made available to the research subject (or his/her medical doctor) for other testing? 
     No
If a subject withdraws from the study: 
Will subject have the option to get the remaining portion of their sample back? 
     No
Will samples be destroyed? If not, will they be kept anonymously? What will happen to the sample if the subject 
revokes authorization? 
     If the patient withdraws from the study, samples will not be destroyed and will be stored anonymously. If the 
subject revokes authorization, the samples will be destroyed or discarded. 
Will data obtained from their sample be deleted? What will happen to the sample if the subject revokes 
authorization? 
     For those who withdraw from the study, we will use the data generated from the samples. However, for subjects 
who revoked authorization, their data will be deleted and samples destroyed or discarded. 
Will study data or test results be recorded in the subject's medical records? 
     Yes 
Will results of specific tests and/or results of the overall study be revealed to the research subject and or his/her 
doctor? 
     
Standard test results that are done at VA lab and have clinical use are reported in CPRS, or Computerized Patient 
Record System, and thus they are automatically included in the subjects medical records (i.e. in CPRS, which is 
accessible to the vets primary provider). Any abnormal findings will be shared with the subject¿s primary care 
physicians for further evaluation and appropriate treatment through the CPRS which are shared with their VA 
primary care physicians. Depending on the urgency of the abnormal findings, the PI may directly contact the 
primary care provider by phone to discuss the abnormal findings. 
Please identify all third parties, including the subject's physician, to receive the test results. 
     Participants treating physicians. 
 Section O:  Drug Studies 
Does the research involve the use of ANY drug* or biologic? (*A drug is defined as any substance that is used to 
elicit a pharmacologic or physiologic response whether it is for treatment or diagnostic purposes) 
     Yes 
Does the research involve the use of ANY gene transfer agent for human gene transfer research? 
     No
O1.  Current DrugsDrug :  Arimidex 1 mg (anastrazole 1 mg tablet for oral use)  
Is this study placebo-controlled? 
     Yes 
If yes, be sure that you justify the use of the placebo for this research in the space below. 
     
The placebo controlled trial is required to evaluate which is the best approach for the treatment of 
hypogonadotropic hypogonadism in severely obese men: life style intervention induced weight loss alone 
(placebo group) or life style intervention induced weight loss combined with anastrazole therapy (active group). 
IND # 126696 
Will the research involve a radioactive drug that is not approved by the FDA? 
     No


 Section P:  Device Studies 
     Does this research study involve the use of ANY device? 
         No 
 Section Q.  Consent Form(s) 
None 
 Section R:  AdvertisementsMode of Advertising:  Bulletin Board 
Exact language of Advertisement: 
     
Below is the exact language of the advertisement for the study: This study is looking at the effect of weight loss 
alone or in combination with anastrozole, a medication which may increase testosterone levels, on muscle 
strength and symptoms related to low circulating testosterone. VOLUNTEERS MUST: - Be a male veteran - Be 
age 35-65 - Be obese - Not have prostate cancer - Not have a history of bariatric surgery - Not be on testosterone 
DURATION and LOCATION- Participation in the study will be 6 months. The study is conducted by Baylor 
College of Medicine and the Michael E. DeBakey VA Medical Center. The study will take place at the Michael E. 
DeBakey, Houston VA. INTERVENTION- Participants will take either the active drug (anastrozole) or placebo in 
addition to participation in a weight loss program (diet+exercise) TEST/PROCEDURES - Include phone 
screening, orientation session, medical examination, strength testing, bone mineral density and body composition 
testing and simple blood testing. COMPENSATION- Volunteers may receive up to $60.00. PI: Dr. Reina Villareal, 
M.D. 713-7947534 or 713-7911414 extension #24084 
Mode of Advertising:  Other: Flyers 
Exact language of Advertisement: 
     
Below is the exact language of the advertisement for the study: Testosterone study 
This study is looking at the effect of weight loss alone or in combination with anastrozole, a medication which may 
increase testosterone levels, on muscle strength and symptoms related to low circulating testosterone. 
VOLUNTEERS MUST: - Be a male veteran - Be age 35-65 - Be obese (BMI >35) - Not have prostate cancer - Not 
have a history of bariatric surgery - Not be on testosterone 
DURATION - Participation in the study will be 6 months. The study is conducted by Baylor College of Medicine 
and the Michael E. DeBakey VA Medical Center. The study will take place at the Michael E. DeBakey, Houston 
VA. 
INTERVENTION- Participants will take either the active drug (anastrozole) or placebo in addition to participation 
in a weight loss program (diet+exercise) 
TEST/PROCEDURES - Include phone screening, orientation session, medical examination, strength testing, bone 
mineral density and body composition testing and simple blood testing. 
COMPENSATION- Volunteers may receive up to $60.00. 
PI: Dr. Reina Villareal, M.D. 713-7947534 or 713-7911414 extension #24084 
Mode of Advertising:  BCM Clinical Trials Website 
Exact language of Advertisement: 
     
Below is the exact language of the advertisement for the study: This study is looking at the effect of weight loss 
alone or in combination with anastrozole, a medication which may increase testosterone levels, on muscle 
strength and symptoms related to low circulating testosterone. VOLUNTEERS MUST: - Be a male veteran - Be 
age 35-65 - Be obese - Not have prostate cancer - Not have a history of bariatric surgery - Not be on testosterone 
DURATION and LOCATION- Participation in the study will be 6 months. The study is conducted by Baylor 
College of Medicine and the Michael E. DeBakey VA Medical Center. The study will take place at the Michael E. 
DeBakey, Houston VA. INTERVENTION- Participants will take either the active drug (anastrozole) or placebo in 
addition to participation in a weight loss program (diet+exercise) TEST/PROCEDURES - Include phone 
screening, orientation session, medical examination, strength testing, bone mineral density and body composition 
testing and simple blood testing. COMPENSATION- Volunteers may receive up to $60.00. PI: Dr. Reina Villareal, 
M.D. 713-7947534 or 713-7911414 extension #24084