Dataset Information

An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men.

ABSTRACT:

Objective

To describe the influence of the TTTA aromatase polymorphism (TTTAn) on the relation between obesity and plasma estradiol (E(2)) in obese men.

Design

A 2-year cohort study.

Setting

Clinical research center.

Patient(s)

Severely obese men (31 who had had gastric bypass surgery and 118 controls).

Intervention(s)

Men were genotyped for the TTTAn CYP19A1 polymorphism. Anthropomorphic measures, plasma E(2), and other hormonal levels were determined at baseline and 2-year follow-up.

Main outcomes measure(s)

Relationships between weight and changes in weight and plasma E(2) were examined in relation to the TTTAn polymorphism.

Result(s)

The mean age was 46.5 ± 10.82 years, and mean body mass index was 47.1 ± 8.46 kg/m(2). The most common repeats were 7 and 11. TTTAn number did not correlate with plasma E(2) in the univariate analysis. When patients were stratified per weight group, the correlation between plasma E(2) and weight was seen only among men with a higher TTTA repeat at baseline and 2 years. Similarly, only men with higher TTTA exhibited reduced E(2) levels after weight loss.

Conclusion(s)

A higher TTTA repeat is associated with a strengthened relationship between obesity and E(2). The well-established effect of increased weight on plasma E(2) appears to be absent in men with low TTTA numbers.

SUBMITTER: Hammoud A

PROVIDER: S-EPMC3719845 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men.

Hammoud Ahmad A Carrell Douglas T DT Meikle A Wayne AW Xin Yuanpei Y Hunt Steven C SC Adams Ted D TD Gibson Mark M

Fertility and sterility 20091211 5

<h4>Objective</h4>To describe the influence of the TTTA aromatase polymorphism (TTTAn) on the relation between obesity and plasma estradiol (E(2)) in obese men.<h4>Design</h4>A 2-year cohort study.<h4>Setting</h4>Clinical research center.<h4>Patient(s)</h4>Severely obese men (31 who had had gastric bypass surgery and 118 controls).<h4>Intervention(s)</h4>Men were genotyped for the TTTAn CYP19A1 polymorphism. Anthropomorphic measures, plasma E(2), and other hormonal levels were determined at base ...[more]

PMID: 20004389

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Project description:IntroductionTestosterone therapy (TTH) for testosterone deficiency (TD) may lead to elevated estradiol (E2) levels requiring management to avoid unnecessary adverse effects.AimTo examine the impact of aromatase inhibitors, specifically anastrozole (AZ), in men with elevated E2 on TTH.MethodsAll patients on TTH at a high volume sexual medicine practice between 2005 and 2019 were reviewed. Men with E2 levels >60 pg/mL regardless of symptoms or 40-60 pg/mL with subjective symptoms were started on AZ 0.5 mg 3x/week. Routine hormone profile and symptom assessment were completed to ensure symptom resolution, reduction of E2 levels and maintenance of testosterone levels. Multivariable logistic regression was completed to determine predictors of men more likely to respond to therapy.Main outcome measureDemographic and hormonal profiles of men on AZ and predictors of response to therapy.Results1708 men with TD were placed on TTH. Of these, 51 (3%) were treated with AZ (AZ+). After exclusions, 44 (2.6%) had elevated estradiol levels >60 pg/mL or >40 pg/mL with symptoms. Demographics were similar between groups. TTH distribution between groups was different with greater rates of topical TTH in the AZ- groups (AZ+:34.1% vs AZ-:53.5%) and greater rates of intramuscular TTH in the AZ+ group (AZ+:38.6% vs AZ-:18.5%) (P = .017 overall). Of the 44 men treated with AZ, 68.0% had pre-AZ E2 levels ≥60 pg/mL and 32.0% had levels between 40 and 60 pg/mL. Median pre-AZ E2 levels were 65 (interquartile range [IQR], 55-94) pg/mL in comparison to 22 (IQR 15-38) pg/mL post-AZ E2 levels (P < .001). Total testosterone levels were similar before and after AZ use (616 (IQR 548-846) ng/dL and 596 (IQR 419-798) ng/dL, respectively, P = .926). No statistically significant predictive factors of E2 reduction using AZ were found.ConclusionWhile no statistically significant predictors for E2 recovery in men on AZ were found, AZ remains a reasonable option for E2 reduction in men with elevated levels on TTH. Punjani N, Bernie H, Salter C, et al. The Utilization and Impact of Aromatase Inhibitor Therapy in Men With Elevated Estradiol Levels on Testosterone Therapy. Sex Med 2021;9:100378.

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

Dataset Information

An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men.

Objective

Design

Setting

Patient(s)

Intervention(s)

Main outcomes measure(s)

Result(s)

Conclusion(s)

Publications

An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men.

Similar Datasets

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