Abstract
Context:Deficiency of aromatase, the enzyme that catalyzes the conversion of androgens to estrogens, is associated with insulin resistance in humans and mice.Objective:We hypothesized that pharmacological aromatase inhibition results in peripheral insulin resistance in humans.Design:This was a double-blind, randomized, controlled, crossover study.Setting:The study was conducted at a clinical research facility.Participants:Seventeen healthy male volunteers (18–50 y) participated in the study.Intervention:The intervention included oral anastrozole (1 mg daily) and placebo, each for 6 weeks with a 2-week washout period.Main Outcome Measure:Glucose disposal and rates of lipolysis were measured during a stepwise hyperinsulinemic euglycemic clamp. Data are mean (SEM).Results:Anastrozole therapy resulted in significant estradiol suppression (59.9 ± 3.6 vs 102.0 ± 5.7 pmol/L, P = < .001) and a more modest elevation of total T (25.8 ± 1.2 vs 21.4 ± 0.7 nmol/L, P = .003). Glucose infusion rate, during the low-dose insulin infusion, was lower after anastrozole administration (12.16 ± 1.33 vs 14.15 ± 1.55 μmol/kg·min, P = .024). No differences in hepatic glucose production or rate of lipolysis were observed.Conclusion:Aromatase inhibition reduces insulin sensitivity, with respect to peripheral glucose disposal, in healthy men. Local generation and action of estradiol, at the level of skeletal muscle, is likely to be an important determinant of insulin sensitivity.
Highlights
British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom
Local generation and action of estradiol, at the level of skeletal muscle, is likely to be an important determinant of insulin sensitivity
Testosterone deficiency is associated with an increased risk of type 2 diabetes mellitus (T2DM) [2] and pharmacological androgen deprivation, employed in the treatment of prostate cancer, is associated with deteriorating insulin sensitivity [3]
Summary
We hypothesized that pharmacological aromatase inhibition results in peripheral insulin resistance in humans. Participants: 17 healthy male volunteers (18 – 50 years). Intervention: Oral anastrozole (1mg daily) and placebo, each for 6 weeks with 2 week ‘washout’ period. Main outcome measure: Glucose disposal and rates of lipolysis were measured during a stepwise hyperinsulinemic euglycemic clamp.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: The Journal of Clinical Endocrinology & Metabolism
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.