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Association Between Androgen Receptor Gene CAG Repeat Polymorphism and Plasma Testosterone Levels in Postmenopausal Women

Department of Physiology, Universidade Federal do Rio Grande do Sul; Gynecological Endocnnology Unit, Division of Endocrinology, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; Service D'Hormonologie du Development et de La Reproduction Hopital Lapeyronie et Unite INSERM U-540, Montpellier, France; Department of Physiology, UFRGS, Rua Sarmento Leite, 500, 90050-170 Porto Alegre, RS, Brazil;ilma{at}ufrgs.br

Poli Mara Spritzer, MD, PhD

Franyoise Paris, MD

Maria Augusta Maturana, MD, MSc

Franyoise Audran, PhD

Charles Sultan, MD, PhD

Department of Physiology, Universidade Federal do Rio Grande do Sul; Gynecological Endocnnology Unit, Division of Endocrinology, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; Service D'Hormonologie du Development et de La Reproduction Hopital Lapeyronie et Unite INSERM U-540, Montpellier, France

Objectives: The biologic action of androgens in target cells depends on plasma androgen levels and receptor transcriptional activity. We investigated the relationship between androgen receptor (AR) CAG repeat polymorphism, serum androgen levels, and anthropometric, metabolic, and hormonal variables in 39 postmenopausal women, taking into consideration the patterns of X-chromosome inactivation.

Methods: Genomic DNA was extracted from peripheral leukocytes. Polymerase chain reactions (PCRs) were performed to amplify the polymorphic (CAG)_n repeat of the human AR gene, which were analyzed with GeneScan software (Applied Biosystems, Foster City, CA). The X-chromosome inactivation analysis was based on the AR gene methylation patterns.

Results: The mean age of participants was 54.7 years; mean age at menopause was 48 years. The number of CAG repeats ranged from 15 to 30, with a median length of 23. Analysis of X-chromosome inactivation patterns showed 19 cases with a degree of skewing (DS) 70% and seven with a DS 90%. The X-weighted CAG repeat biallelic mean was significantly lower in individuals with total testosterone (TT)greater than 0.56 ng/mL (group mean) than in thegroup with TT0.56 (P=.018). No dfference was observed between the groups regarding dehydroepiandrosterone suffate (DHEA-S). Plasma TT was signfitcantly higher in the group with the smaller X-weighted CAG repeat biallelic mean (P=.01). Free androgen index (FAI) was also signficantly higher in this group (P=.033). Testosterone levels and FAI were inversely correlated to X-weighted CAG repeat biallelic mean.

Conclusion: Our data indicate an association between testosterone plasma levels and AR CAG repeats in postmenopausal women, and suggest that plasma levels of androgens in postmenopausal women may be related to variants of the AR gene.

Key Words: Androgen receptor • postmenopause • testosterone • polymorphism

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