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Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase.

ABSTRACT: The effects of testosterone on early atherogenesis and the role of aromatase, an enzyme that converts testosterone to estrogens, were assessed in low density lipoprotein receptor-deficient male mice fed a Western diet. Castration of male mice increased the extent of fatty streak lesion formation in the aortic origin compared with testes-intact animals. Administration of anastrazole, a selective aromatase inhibitor, to testes-intact males increased lesion formation to the same extent as that observed with orchidectomized animals. Testosterone supplementation of orchidectomized animals reduced lesion formation when compared with orchidectomized animals receiving the placebo. This attenuating effect of testosterone was not observed when the animals were treated simultaneously with the aromatase inhibitor. The beneficial effects of testosterone on early atherogenesis were not explained by changes in lipid levels. Estradiol administration to orchidectomized males attenuated lesion formation to the same extent as testosterone administration. Aromatase was expressed in the aorta of these animals as assessed by reverse transcription-PCR and immunohistochemistry. These results indicate that testosterone attenuates early atherogenesis most likely by being converted to estrogens by the enzyme aromatase expressed in the vessel wall.

SUBMITTER: Nathan L

PROVIDER: S-EPMC30697 | biostudies-literature | 2001 Mar

REPOSITORIES: biostudies-literature

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Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase.

Nathan L L Shi W W Dinh H H Mukherjee T K TK Wang X X Lusis A J AJ Chaudhuri G G

Proceedings of the National Academy of Sciences of the United States of America 20010306 6

The effects of testosterone on early atherogenesis and the role of aromatase, an enzyme that converts testosterone to estrogens, were assessed in low density lipoprotein receptor-deficient male mice fed a Western diet. Castration of male mice increased the extent of fatty streak lesion formation in the aortic origin compared with testes-intact animals. Administration of anastrazole, a selective aromatase inhibitor, to testes-intact males increased lesion formation to the same extent as that obse ...[more]

PMID: 11248122

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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.

Dataset Information

Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase.

Publications

Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase.

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