Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects

Authors

Georgia Colleluori
Rui Chen
Christie G Turin
Francesca Vigevano
Clifford Qualls
Biju Johnson
Sanjay Mediwala
Dennis T Villareal
Reina Armamento-Villareal

Publication Date

1-1-2020

Journal

Frontiers in Endocrinology

DOI

10.3389/fendo.2020.00277

PMID

32499757

PMCID

PMC7243137

PubMedCentral® Posted Date

5-15-2020

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Adult, Aged, Androgens, Aromatase Inhibitors, Biomarkers, Body Composition, Bone Density, Bone and Bones, Double-Blind Method, Estradiol, Follow-Up Studies, Hormone Replacement Therapy, Humans, Hypogonadism, Male, Metabolome, Middle Aged, Muscle Strength, Obesity, Pilot Projects, Prognosis, Testosterone, Weight Loss, hypogonadism, obesity, aromatase inhibitors, weight loss, sex hormones, bone density, bone microarchitecture, body composition

Abstract

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: Twenty-three obese men (BMI≥35 kg/m²), 35–65 years old, were randomized to weight loss (diet and exercise) plus either anastrozole (AI+WL, n = 12) at 1 mg daily or placebo (PBO+WL, n = 11) for 6 months. Inclusion criteria: total testosterone <300 ng/mL (average of 2 measurements), estradiol≥10.9 pg/ml, LH <9 IU/l. Symptoms of hypogonadism by questionnaires; muscle strength by Biodex dynamometer; body composition and bone mineral density by dual-energy X-ray absorptiometry; bone microarchitecture and finite element analysis by high resolution peripheral quantitative-computed tomography.

Results: After 6 months of therapy, AI+WL group had higher testosterone (p = 0.003) and lower estradiol (p = 0.001) compared to PBO+WL. Changes in symptoms and muscle strength did not differ between groups. AI+WL resulted in higher fat mass loss than PBO+WL (p = 0.04) without differences in changes in lean mass. Total and LDL cholesterol reduced more in the PBO+WL group compared to AI+WL (p = 0.03 for both), who experienced a minimal increase with unlikely meaningful clinical impact. Tibial trabecular bone area decreased more in PBO+WL than AI+WL group for which it remained stable (p = 0.03).

Conclusions: Although AI+WL is effective in reversing the hormonal profile of HHG in severely obese men without causing major side effects, it does not lead to greater improvements in muscle strength and symptoms of hypogonadism compared to WL alone.

Comments

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02959853.

Associated Data