Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
Status:
Recruiting
Trial end date:
2024-04-14
Target enrollment:
Participant gender:
Summary
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.