PMID- 25428524
OWN - NLM
STAT- MEDLINE
DCOM- 20150528
LR  - 20181202
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 12
DP  - 2014 Nov 27
TI  - Cardiovascular risks and elevation of serum DHT vary by route of testosterone 
      administration: a systematic review and meta-analysis.
PG  - 211
LID - 10.1186/s12916-014-0211-5 [doi]
LID - 211
AB  - BACKGROUND: Potential cardiovascular (CV) risks of testosterone replacement 
      therapy (TRT) are currently a topic of intense interest. However, no studies have 
      addressed CV risk as a function of the route of administration of TRT. METHODS: 
      Two meta-analyses were conducted, one of CV adverse events (AEs) in 35 randomized 
      controlled trials (RCTs) of TRT lasting 12 weeks or more, and one of 32 studies 
      reporting the effect of TRT on serum testosterone and dihydrotestosterone (DHT). 
      RESULTS: CV risks of TRT: Of 2,313 studies identified, 35 were eligible and 
      included 3,703 mostly older men who experienced 218 CV-related AEs. No 
      significant risk for CV AEs was present when all TRT administration routes were 
      grouped (relative risk (RR) = 1.28, 95% confidence interval (CI): 0.76 to 2.13, P 
      = 0.34). When analyzed separately, oral TRT produced significant CV risk (RR = 
      2.20, 95% CI: 1.45 to 3.55, P = 0.015), while neither intramuscular (RR = 0.66, 
      95% CI: 0.28 to 1.56, P = 0.32) nor transdermal (gel or patch) TRT (RR = 1.27, 
      95% CI: 0.62 to 2.62, P = 0.48) significantly altered CV risk. Serum 
      testosterone/DHT following TRT: Of 419 studies identified, 32 were eligible which 
      included 1,152 men receiving TRT. No significant difference in the elevation of 
      serum testosterone was present between intramuscular or transdermal TRT. However, 
      transdermal TRT elevated serum DHT (5.46-fold, 95% CI: 4.51 to 6.60) to a greater 
      magnitude than intramuscular TRT (2.20-fold, 95% CI: 1.74 to 2.77). CONCLUSIONS: 
      Oral TRT produces significant CV risk. While no significant effects on CV risk 
      were observed with either injected or transdermal TRT, the point estimates 
      suggest that further research is needed to establish whether administration by 
      these routes is protective or detrimental, respectively. Differences in the 
      degree to which serum DHT is elevated may underlie the varying CV risk by TRT 
      administration route, as elevated serum dihydrotestosterone has been shown to be 
      associated with CV risk in observational studies.
FAU - Borst, Stephen E
AU  - Borst SE
AD  - Geriatric Research, Education and Clinical Center, Malcom Randall VA Medical 
      Center, 1601 SW Archer RD, Gainesville 32605-1197, FL, USA. Stephen.borst@va.gov.
FAU - Shuster, Jonathan J
AU  - Shuster JJ
FAU - Zou, Baiming
AU  - Zou B
FAU - Ye, Fan
AU  - Ye F
FAU - Jia, Huanguang
AU  - Jia H
FAU - Wokhlu, Anita
AU  - Wokhlu A
FAU - Yarrow, Joshua F
AU  - Yarrow JF
LA  - eng
GR  - P30 AG028740/AG/NIA NIH HHS/United States
GR  - UL1 TR000064/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20141127
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Administration, Cutaneous
MH  - Adult
MH  - Cardiovascular Diseases/blood/*etiology
MH  - Dihydrotestosterone/*blood
MH  - Hormone Replacement Therapy
MH  - Humans
MH  - Injections, Intramuscular
MH  - Male
MH  - Randomized Controlled Trials as Topic
MH  - Risk Factors
MH  - Testosterone/*administration & dosage
PMC - PMC4245724
EDAT- 2014/11/28 06:00
MHDA- 2015/05/29 06:00
PMCR- 2014/11/27
CRDT- 2014/11/28 06:00
PHST- 2014/09/09 00:00 [received]
PHST- 2014/10/14 00:00 [accepted]
PHST- 2014/11/28 06:00 [entrez]
PHST- 2014/11/28 06:00 [pubmed]
PHST- 2015/05/29 06:00 [medline]
PHST- 2014/11/27 00:00 [pmc-release]
AID - s12916-014-0211-5 [pii]
AID - 211 [pii]
AID - 10.1186/s12916-014-0211-5 [doi]
PST - epublish
SO  - BMC Med. 2014 Nov 27;12:211. doi: 10.1186/s12916-014-0211-5.