Effects of Aromatase Inhibition in Hypogonadal Older Men: A Randomized, Double-Blind, Placebo-controlled Trial

Sherri-Ann M. Burnett-Bowie; Kristen C. Roupenian; Melissa E. Dere; Hang Lee; Benjamin Z. Leder


Clin Endocrinol. 2009;70(1):116-123. 

In This Article

Abstract and Introduction


Objective: To assess the effects of sustained aromatase inhibition in older hypogonadal men.
Design and Patients: In a 1-year randomized, double-blind, placebo-controlled trial, 88 men, aged 60 years and older with testosterone levels between 5·2 and 10·4 nmol/l on a single measure or between 10·4 and 12·1 nmol/l on two consecutive measures, and with symptoms of hypogonadism were recruited. Subjects received either anastrozole 1 mg daily or placebo.
Measurements: Changes in gonadal steroid hormone levels, body composition [by computerized tomography (CT) and dual X-ray absorptiometry (DXA)], strength, prostate specific antigen (PSA), symptoms of benign prostatic hypertrophy (BPH), haematocrit and lipid levels were assessed.
Results: Testosterone levels increased from 11·2 ± 3·3 nmol/l at baseline to 18·2 ± 4·8 nmol/l at month 3 (P < 0·0001 vs. placebo) while bioavailable testosterone levels increased from 2·7 ± 0·8 nmol/l at baseline to 5·4 ± 1·7 nmol/l at month 3 (P < 0·0001 vs. placebo). Testosterone and biotestosterone levels peaked at month 3 and then declined by month 12 (though they remained significantly higher than baseline and greater than placebo). E2 levels decreased from 55·8 ± 15·4 pmol/l at baseline to 42·2 ± 13·6 pmol/l at month 3 and then remained stable (P < 0·0001). Body composition and strength did not change, nor did PSA, BPH symptoms, haematocrit or lipid levels.
Conclusions: Anastrozole administration normalized androgen production in older hypogonadal men and decreased E2 production modestly. These alterations did not improve body composition or strength.


Male ageing is associated with declining androgen production and a myriad of physiologic changes including increased fat, decreased muscle, and diminished strength that are also associated with hypogonadism in younger men.[1] Testosterone administration is potentially beneficial in ageing hypogonadal men, but its use remains controversial due to efficacy and safety concerns.[2] Several larger-scale, randomized clinical studies have assessed the effects of testosterone replacement on physiological end-points in older men with mixed results.[3,4,5] Furthermore, adherence to testosterone therapy can be challenging given its topical or parenteral administration. Additionally, because testosterone therapy increases E2 (via peripheral aromatization), its administration may expose men to oestrogen-related effects. In a 12-week pilot study, we demonstrated that anastrozole (Arimidex®, AstraZeneca Pharmaceuticals), a potent orally administered aromatase inhibitor used in breast cancer treatment, increases testosterone production and normalizes serum testosterone in older men with mild hypogonadism.[6] We thus hypothesized that sustained anastrozole therapy may improve body composition and strength in older men with decreased androgen production and hypogonadal symptoms. To test this hypothesis, we assessed the effects of daily anastrozole administration on gonadal steroid hormone levels, body composition, strength, and prostate-related and other safety parameters in men aged 60 years or older with mild-to-moderate hypogonadism in a 1-year, double-blind, randomized, placebo-controlled trial.


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