title: Testosterone vs. aromatase inhibitor in older men with low testosterone: effects on cardiometabolic parameters.
abstract: Testosterone (T) replacement is being increasingly offered to older men with age-related decline in testosterone levels. The effects of long-term testosterone replacement and aromatase inhibition (AI) on glucose homeostasis and cardiometabolic markers were determine in older non-diabetic men with low testosterone levels. Men ≥65 years, mean age 71 ± 3 years with serum total T < 350 ng/dL were randomized in a double-blind, placebo-controlled, parallel-group, proof-of-concept trial evaluating the effects of 5 g transdermal testosterone gel (TT) (n = 10), 1 mg anastrozole (n = 10) or placebo (n = 9) daily for 12 months. Homeostatic Model Assessment of insulin resistance (HOMAIR) was the primary outcome. Secondary outcomes included OGIS in response to OGTT, fasting lipids, C-reactive protein (CRP), adipokines, and abdominal and mid-thigh fat by computed tomography. All outcomes were assessed at baseline and 12 months. After 12 months, absolute changes in HOMAIRin both treatment arms (TT group: -0.05 ± 0.21); (AI group: 0.15 ± 0.10) were similar to placebo (-0.11 ± 0.26), as were CRP and fasting lipid levels. Adiponectin levels significantly decreased in the TT group (-1.8 ± 0.9 mg/L, p = 0.02) and abdominal subcutaneous fat (-60.34 ± 3.19 cm2, p = 0.003) and leptin levels (-1.5 ± 1.2 ng/mL, p = 0.04) were significantly lower with AI. Mid-thigh subcutaneous fat was reduced in both treatment arms (TT group: -4.88 ± 1.24 cm2, p = 0.008); (AI group: -6.05 ± 0.87 cm2, p = 0.0002). In summary, in this proof-of-concept trial, changes in HOMAIRAI were similar in all three groups while the effects of intervention on subcutaneous fat distribution and adipokines were variable. Larger efficacy and safety trials are needed before AI pharmacotherapy can be considered as a treatment option for low T levels in older men.
authors: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA.
authors: J P
authors: JP
authors: Dias
authors: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors: M D
authors: MD
authors: Shardell
authors: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA.
authors: O D
authors: OD
authors: Carlson
authors: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA.
authors: D
authors: D
authors: Melvin
authors: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors: G
authors: G
authors: Caturegli
authors: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors: L
authors: L
authors: Ferrucci
authors: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors: C W
authors: CW
authors: Chia
authors: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA.
authors: J M
authors: JM
authors: Egan
authors: Section on Men's Health, Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: S
authors: S
authors: Basaria
mesh_terms: D050153:Abdominal Fat / Q000000981:diagnostic imaging; D054392:Adipokines / Q000097:blood; D000368:Aged; D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D013739:Testosterone / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; D047072:Aromatase Inhibitors; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D013739:Testosterone; D002097:C-Reactive Protein
keywords: aromatase inhibition; inflammation; insulin sensitivity; lipids; testosterone