Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism

Completed · Phase 4 · Has a placebo group

Conditions studied: Hypogonadism, Hypogonadotropic, Obesity

In brief

The investigators have preliminary data suggesting that obese patients with hypogonadotropic hypogonadism (HHG) have minimal benefit from testosterone therapy likely because of its conversion to estradiol by the abundant aromatase enzyme in the adipocytes. The increased conversion of androgens into estrogens in obese men results in a negative feedback of high estradiol levels 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 testosterone by the testis. Testosterone administration could increase estradiol production, further promoting the inhibitory feedback to the hypothalamic-pituitary-gonadal axis. Although weight loss from lifestyle modification has been shown to reduce estradiol and increase testosterone levels, the effect is at best modest and weight regain results in recurrence of hypogonadism. The use of aromatase inhibitors, in combination with weight loss, could be an effective alternative strategy due to its action at the pathophysiology of the disease. Intervention Subjects (body mass index of ≥35, testosterone \<300 ng/dl) will be randomized to the active (anastrozole) or control (placebo) group. Anastrozole 1 mg tablet / day will be self-administered with or without food, at around the same time every day (active group); placebo 1 tablet/day with or without food to take at around the same time every day (control group). The study duration will be 12 months. Both groups will undergo lifestyle intervention consisting of diet and supervised exercise program. Target weight loss will be at least 10% of baseline body weight during the intervention. Subjects will attend weekly group behavior modification sessions which will last \~75-90 min for the first 3 months and decreased to every two weeks from 3 to 12 months. Subjects will attend supervised research center-based exercise sessions during the first 6 months followed by community fitness center-based sessions during the next 6 months for at least 2 d/wk, with recording of home-based exercises for the other 2-4 days/week. Although the above original protocol requires the participants to come to our center for dietary and exercise training, since the Covid19 pandemic, study participants were given the following options for lifestyle intervention: 1) in-person visits at our facility for dietary classes and exercise training, 2) to enlist in the gym of their choice with membership paid for by the study, or 3) virtual method of lifestyle intervention. These amendments were put in place due to Covid 19 restrictions; however, we decided to keep these methods because most of our subjects prefer them over coming for in-person visits at our lab even after COVID restrictions were lifted. Since the study had just the first 25 subjects enrolled prior to COVID outbreak, majority of the subject's lifestyle interventions were done by virtual dietary classes every week for the first 3 months and then every 2 weeks thereafter either as a group or by one-on-one sessions. Exercise program was also supervised by exercise physiologist virtually or by phone for subjects who want to exercise at a community gym

Key facts

Study ID: NCT03490513
Run by: Baylor College of Medicine
People needed: 121
Starts: 2018-04-15
Expected to finish: 2025-05-31
Last updated by the study team: 2025-08-07

Who can join

Age: 40 and older, up to 65. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

obese men with body mass index (BMI) of ≥35 kg/m2
age between 40 to 65 years old
average fasting testosterone level from 2 measurements taken between 8 to 10 AM on 2 separate days of <300 ng/dl
Luteinizing Hormone (LH) of <9.0 mIU/L
Estradiol of ≥17 pg/ml
Symptoms consistent with androgen deficiency as assessed by Androgen Deficiency in Aging Male (ADAM) questionnaire

You may not qualify if…

pituitary or hypothalamic disease,
drugs affecting gonadal hormone levels, production and action or bone metabolism (bisphosphonates, teriparatide, denosumab, glucocorticoids, phenytoin)
diseases affecting bone metabolism (e.g. hyperparathyroidism, untreated hyperthyroidism, osteomalacia, chronic liver disease, significant renal failure, hypercortisolism, malabsorption, immobilization, Paget's disease),
prostate carcinoma or elevated serum prostate specific antigen (PSA)> 4 ng/ml,
Hematocrit > 50%,
untreated severe obstructive sleep apnea,
Cardiopulmonary disease (e.g. recent myocardial infarction, unstable angina, stroke) or unstable disease (e.g., New York Heart Association Class III or IV congestive heart failure
severe pulmonary disease requiring steroid pills or the use of supplemental oxygen (that would contraindicate exercise or dietary restriction)
History of deep vein thrombosis or pulmonary embolism
severe lower urinary tract or prostate symptoms with International Prostate Symptom Score (IPSS) above 19
excessive alcohol or substance abuse
unstable weight (i.e. >±2 kg) in the last 3 months
condition that could prevent from completing the study
screening bone mineral density (BMD) T-score of <-2.0 at the spine, femoral neck or total femur
history of osteoporosis or fragility fracture
Diabetes mellitus with a fasting blood glucose of >140 mg/dl, and/or Hemoglobin A1C (A1C) >8.5%.

Where it is running

Michael E. DeBakey VAMC — Houston, Texas, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.