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Aromatase inhibition decreases insulin resistance in healthy men
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Healthy men randomly assigned the aromatase-inhibiting drug Arimidex saw reduced insulin resistance at 6 weeks vs. men assigned placebo, according to recent findings.
In a double blind, randomized, crossover study, Fraser W. Gibb, PhD, consultant physician and honorary clinical senior lecturer at the University of Edinburgh, and colleagues analyzed data from 17 healthy men assigned 1 mg daily Arimidex (anastrozole, AstraZeneca) for 6 weeks and an additional 6 weeks of placebo, administered in random order with a 2-week washout period (mean age, 28 years). Researchers measured glucose disposal assessed by a three-phase hyperinsulinemic-euglycemic clamp, as well as height, weight, blood pressure and body fat.
When assigned anastrozole, participants experienced a 41% decline in estradiol (59.9 pmol/L vs. 102 pmol/L; P < .001) and a 21% increase in total testosterone (25.8 nmol/L vs. 21.4 nmol/L; P = .003); the changes did not correlate with insulin sensitivity.
During low-dose insulin infusion, participants assigned anastrozole required a lower glucose infusion rate to maintain euglycemia (12.16 µmol/kg/min vs. 14.15 µmol/kg/min; P = .024); glucose disposal rates tended to decrease with anastrozole (15.04 µmol/kg/min vs. 16.46 µmol/kg/min; P = .044). When assigned anastrozole, participants experienced a mean 4 mm Hg increase in systolic BP vs. placebo and lower heart rate (66 bpm vs. 71 bpm; P < .05). Anastrozole did not influence lipolysis rate or hepatic glucose production, and there were no significant between-treatment differences observed in weight, BMI or percentage of body fat, according to researchers.
“These results suggest suppression of estrogen action in skeletal muscle is the principal mechanism through which aromatase inhibitors exert a deleterious effect on glucose metabolism,” the researchers wrote. “This lends support to the hypothesis that, in male androgen deficiency, insulin resistance is largely a consequence of reduced aromatase substrate availability and consequent local estrogen deficiency in target tissue. The metabolic consequences for patients treated with aromatase inhibitors for breast cancer deserve closer investigation.” – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
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