Cardiovascular risks and elevation of serum DHT vary by route of testosterone
administration: a systematic review and meta-analysis.
Author(s): Borst SE(1), Shuster JJ, Zou B, Ye F, Jia H, Wokhlu A, Yarrow JF.
Affiliation(s): Author information:
(1)Geriatric Research, Education and Clinical Center, Malcom Randall VA Medical
Center, 1601 SW Archer RD, Gainesville 32605-1197, FL, USA. Stephen.borst@va.gov.
Publication date & source: 2014, BMC Med. , 12:211
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.
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