@article {6277, title = {Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.}, journal = {Clin Endocrinol (Oxf)}, volume = {81}, year = {2014}, month = {2014 Nov}, pages = {746-53}, abstract = {

OBJECTIVE: Ischaemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine whether testosterone (T) or dihydrotestosterone (DHT) was associated with incident ischaemic stroke in elderly men.

DESIGN: Cohort study.

PARTICIPANTS: Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease or prostate cancer as of 1994 and were followed until December 2010.

MEASUREMENTS: Adjudicated ischaemic stroke.

RESULTS: Among 1032 men (mean age 76, range 66-97), followed for a median of 10~years, 114 had an incident ischaemic stroke. Total T and free T were not significantly associated with stroke risk, while DHT had a nonlinear association with incident stroke (P~=~0{\textperiodcentered}006) in analyses adjusted for stroke risk factors. The lowest risk of stroke was at DHT levels of 50-75~ng/dl, with greater risk of stroke at DHT levels above 75~ng/dl or below 50~ng/dl. Results were unchanged when SHBG was added to the model. Calculated free DHT had an inverse linear association with incident ischaemic stroke with HR 0{\textperiodcentered}77 (95\% CI, 0{\textperiodcentered}61, 0{\textperiodcentered}98) per standard deviation in analyses adjusted for stroke risk factors.

CONCLUSIONS: Dihydrotestosterone had a nonlinear association with stroke risk in which there was an optimal DHT level associated with the lowest stroke risk. Further studies are needed to confirm these results and to clarify whether there is an optimal androgen range associated with the least risk of adverse outcomes in elderly men.

}, keywords = {Aged, Aged, 80 and over, Brain Ischemia, Cardiovascular Physiological Phenomena, Dihydrotestosterone, Health, Humans, Incidence, Longitudinal Studies, Male, Stroke, Testosterone}, issn = {1365-2265}, doi = {10.1111/cen.12452}, author = {Shores, Molly M and Arnold, Alice M and Biggs, Mary L and Longstreth, W T and Smith, Nicholas L and Kizer, Jorge R and Cappola, Anne R and Hirsch, Calvin H and Marck, Brett T and Matsumoto, Alvin M} } @article {6278, title = {Testosterone, dihydrotestosterone, and incident cardiovascular disease and mortality in the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {99}, year = {2014}, month = {2014 Jun}, pages = {2061-8}, abstract = {

CONTEXT: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this.

OBJECTIVE: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality.

DESIGN: In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection.

MAIN OUTCOME: The main outcomes were incident CVD and all-cause mortality.

RESULTS: Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P < .002 and P = .04, respectively) and all-cause mortality (P < .001 for both).

CONCLUSIONS: In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Dihydrotestosterone, Humans, Incidence, Longitudinal Studies, Male, Mortality, Residence Characteristics, Risk Factors, Testosterone}, issn = {1945-7197}, doi = {10.1210/jc.2013-3576}, author = {Shores, Molly M and Biggs, Mary L and Arnold, Alice M and Smith, Nicholas L and Longstreth, W T and Kizer, Jorge R and Hirsch, Calvin H and Cappola, Anne R and Matsumoto, Alvin M} } @article {9804, title = {Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.}, journal = {Eur J Endocrinol}, volume = {191}, year = {2024}, month = {2024 Oct 29}, pages = {523-534}, abstract = {

OBJECTIVE: Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages.

DESIGN: This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study.

METHODS: Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses.

RESULTS: Cohort median ages ranged from 40 to 76 years and median cFT concentrations from 174.3 to 422.8 pmol/L. In men aged 17-99 years, there was a linear inverse association of cFT with age (-57.2 pmol/L [95\% confidence interval, -69.4, -44.9] per 1 SD increase in age). Calculated free T increased with increasing baseline body mass index (BMI) among men with BMI < 23.6 kg/m2, but decreased among men with BMI > 23.6 kg/m2 (-24.7 pmol/L [-29.1, -20.3] per 1 SD increase in the 25.4-29.6 kg/m2 BMI range). Calculated free T was lower in younger men, who were married or in a de facto relationship (-18.4 pmol/L [-27.6, -9.3]) and in men who formerly smoked (-5.7 pmol/L [-8.9, -2.6]), were in poor general health (-14.0 pmol/L [-20.1, -7.8]), and had diabetes (-19.6 pmol/L [-23.0, -16.3]), cardiovascular disease (-5.8 pmol/L [-8.3, -3.2]), or cancer (-19.2 pmol/L [-24.4, -14.1]).

CONCLUSIONS: Calculated free T was most prominently associated with age and BMI. The linear, inverse association with age, nonlinear association with BMI, and presence of diabetes, cancer, and sociodemographic factors should be considered when interpreting cFT values.

}, keywords = {Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Cross-Sectional Studies, Humans, Life Style, Male, Middle Aged, Sex Hormone-Binding Globulin, Sociodemographic Factors, Socioeconomic Factors, Testosterone, Young Adult}, issn = {1479-683X}, doi = {10.1093/ejendo/lvae133}, author = {Narinx, Nick and Marriott, Ross J and Murray, Kevin and Adams, Robert J and Ballantyne, Christie M and Bauer, Douglas C and Bhasin, Shalender and Biggs, Mary L and Cawthon, Peggy M and Couper, David J and Dobs, Adrian S and Flicker, Leon and Hankey, Graeme J and Hannemann, Anke and Wilkening, Robin and Martin, Sean A and Matsumoto, Alvin M and Ohlsson, Claes and O{\textquoteright}Neill, Terence W and Orwoll, Eric S and Shores, Molly M and Steveling, Antje and Travison, Thomas G and Wittert, Gary A and Wu, Frederick C W and Antonio, Leen and Vanderschueren, Dirk and Yeap, Bu B} }