The decline of serum testosterone levels in community-dwelling men over 70 years of age: descriptive data and predictors of longitudinal changes.
OBJECTIVE
This study was designed to assess longitudinal changes in serum testosterone levels, explore relationships with aging, genetic-, health-, and lifestyle-related factors, and investigate predictors of changes in healthy elderly men.


METHODS
Population-based, longitudinal, 4-year observational study in 221 community-dwelling men aged 71-86 years at baseline.


METHODS
Hormone levels assessed by immunoassay, anthropometry, questionnaires on general health, and genetic polymorphisms. Predictors of changes in testosterone levels explored using linear mixed-effects modeling for longitudinal analyses.


RESULTS
Total testosterone (TT), free testosterone, and bioavailable testosterone (BioT) levels decreased with aging, decreases in BioT being most marked. No changes in sex hormone-binding globulin (SHBG) or estradiol (E(2)), while LH and FSH levels increased during follow-up. Subjects who gained weight displayed a greater decline in TT levels, mainly due to decreasing SHBG levels. However, baseline body composition was not predictive of subsequent changes in testosterone levels. Baseline E(2) (P=0.023 to 0.004), LH (P=0.046 to 0.005), and FSH (P<0.002) levels were independently positively associated with a faster decline in testosterone fractions, although only FSH remained significant when adjusting for baseline testosterone (P=0.041-0.035). Carriers of a 'TA' haplotype of the estrogen receptor alpha gene (ER alpha) PvuII and XbaI polymorphisms displayed a slower decline of TT and BioT (P=0.041-0.007).


CONCLUSIONS
In elderly men with already low serum testosterone levels, a further decline was observed, independent of baseline age. The identification of FSH levels as a predictor of this decline appears to reflect the testicular mechanisms of aging-related changes in testosterone production, whereas associations with E(2) and ER alpha polymorphisms are suggestive of estrogen-related processes, possibly related to changes in the neuroendocrine regulation of testosterone production.
Lapauw
B
B
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium. bruno.lapauw@ugent.be
Goemaere
S
S
Zmierczak
H
H
Van Pottelbergh
I
I
Mahmoud
A
A
Taes
Y
Y
De Bacquer
D
D
Vansteelandt
S
S
Kaufman
J M
JM
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D001141:Aromatase / Q000235:genetics; D001823:Body Composition; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008019:Life Style; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D054526:Men's Health; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012111:Residence Characteristics; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood* / Q000172:deficiency*
D047628:Estrogen Receptor alpha; D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001141:Aromatase