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CONTEXT: Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. OBJECTIVE: We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. DESIGN AND SETTING: Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. PARTICIPANTS: A total of 2748 men, aged 40-79 (mean +/- sd, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). MAIN OUTCOME MEASURES: We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. RESULTS: Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). CONCLUSION: In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.

Original publication

DOI

10.1210/jc.2009-2071

Type

Journal article

Journal

The Journal of clinical endocrinology and metabolism

Publication Date

04/2010

Volume

95

Pages

1898 - 1908

Addresses

Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom. ilpo.huhtaniemi@imperial.ac.uk

Keywords

European Male Aging Study Group, Testis, Pituitary Gland, Humans, Gonadal Steroid Hormones, Sex Hormone-Binding Globulin, DNA, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cohort Studies, Prospective Studies, Cross-Sectional Studies, Health Status, Aging, Gene Frequency, Genotype, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Databases, Genetic, Adult, Aged, Middle Aged, Europe, Male