Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats.
BACKGROUND
The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive.


OBJECTIVE
The aim was to investigate the relationships between health status, various reproductive hormones, and the AR CAG repeat length.


METHODS
We conducted a multinational prospective cohort observational study with cross-sectional baseline data.


METHODS
This was a population survey of community-dwelling men.


METHODS
Men (40-79 yr old; n = 3369) were randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2878 men.


METHODS
We measured the correlations of the CAG repeat length with selected endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action.


RESULTS
Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free, and bioavailable levels of testosterone (T) and estradiol. FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions.


CONCLUSIONS
The AR CAG repeat length correlates significantly with serum T and estradiol of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or nearly totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions after aromatization of the higher T levels.
Huhtaniemi
Ilpo T
IT
Department of Reproductive Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom. ilpo.huhtaniemi@imperial.ac.uk
Pye
Stephen R
SR
Limer
Kate L
KL
Thomson
Wendy
W
O'Neill
Terence W
TW
Platt
Hazel
H
Payne
Debbie
D
John
Sally L
SL
Jiang
Min
M
Boonen
Steven
S
Borghs
Herman
H
Vanderschueren
Dirk
D
Adams
Judith E
JE
Ward
Kate A
KA
Bartfai
György
G
Casanueva
Felipe
F
Finn
Joseph D
JD
Forti
Gianni
G
Giwercman
Aleksander
A
Han
Thang S
TS
Kula
Krzysztof
K
Lean
Michael E J
ME
Pendleton
Neil
N
Punab
Margus
M
Silman
Alan J
AJ
Wu
Frederick C W
FC
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011944:Receptors, Androgen / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood*; D018911:Trinucleotide Repeats
C410798:AR protein, human; D011944:Receptors, Androgen; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone