Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)
Condition: Hypogonadism; Severe Obesity
MeSH terms: Obesity, Morbid; Hypogonadism; Weight Loss
Intervention: Anastrazole; weight loss
Intervention MeSH terms: Anastrozole
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 23.0
Sex: Male
Minimum age: 35 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hypogonadism; Severe obesity

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  severely obese (BMI >= 35) male veterans with hypogonadotropic hypogonadism defined as
             low total testosterone (lower than 300 ng/dl) between 35-65 years of age

          -  Luteinizing hormone (LH) lower than 9 U/L

          -  estradiol above 40 pmol/l

          -  normal Free T4 (FT4), Thyroid Stimulating Hormone (TSH), prolactin, cortisol,
             Adrenocorticotropic hormone (ACTH), and Insulin-like growth factor-1 (IGF-1) levels.

          -  Subjects must be ambulatory, willing and able to provide written informed consent

        Exclusion Criteria:

          -  clinical or biochemical evidence of pituitary or hypothalamic disease

          -  any ongoing illness that, in the opinion of the investigator, could prevent the
             subject from completing study

          -  any med known to affect gonadal hormones, steroid hormone-binding globulin or bone
             metabolism, e.g.,

               -  androgens

               -  estrogens

               -  glucocorticoids

               -  phenytoin

               -  bisphosphonates

               -  any medication known to interfere with anastrozole metabolism, e.g. tamoxifen or
                  estrogens

          -  diseases known to interfere with bone metabolism as

               -  osteoporosis

               -  hyperparathyroidism

               -  untreated hyperthyroidism

               -  osteomalacia

               -  chronic liver disease

               -  renal failure

               -  hypercortisolism

               -  malabsorption

               -  immobilization

               -  patients with a Total T score lower than -2.0 at Lumbar Spine or Left Femur.

          -  patients with symptomatic prostate disease, prostate carcinoma, or elevated serum
             Prostate-specific antigen (PSA) >4 ng/ml or >3 for subjects with a family history of
             prostate cancer among 1st degree relatives needs urologic evaluation before admission
             into study

          -  hematocrit greater than 50%

          -  untreated severe obstructive sleep apnea

          -  severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS)
             above 19

          -  documented heart failure

          -  cardiovascular disease

          -  liver disease

          -  excessive alcohol or substance abuse

          -  unstable weight (changes in weight more than ± 2 kg) during the last 3 months

          -  history of bariatric surgery

          -  subjects with elevated liver enzymes as alanine transaminase (ALT), aspartate
             aminotransferase (AST), Alkaline phosphatase (ALP), and bilirubin at greater than
             twice the upper limit of normal.