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patients with platinum-treated advanced urothelial carcinoma.
Clin Cancer Res. In press.
.
Kerstin Junker*, Carsten-Henning Ohlmann
Clinic of Urology and Pediatric Urology, Saarland University,
Homburg, Germany
*Corresponding author. Clinic of Urology and Pediatric Urology, Saarland
University, Kirrberger Strasse 1, 66424 Homburg, Germany.
E-mail address: (K. Junker).
# 2017 European Association of Urology.
Published by Elsevier B.V. All rights reserved.
Re: Risk of Erectile Dysfunction Associated with
Use of 5a-Reductase Inhibitors for Benign Prostatic
Hyperplasia or Alopecia: Population Based Studies Using
the Clinical Practice Research Datalink
Hagberg KW, Divan HA, Persson R, Nickel JC, Jick SS
BMJ 2016;354:i4823,
Experts’ summary:
Hagberg et al investigated the risk of erectile dysfunction (ED)
or sexual dysfunction (SD) caused by 5a-reductase inhibitors
(5-ARIs) prescribed for androgenetic alopecia (AGA) and lower
urinary tract symptoms due to benign prostatic hyperplasia
(LUTS/BPH). The authors used the Clinical Practice Research
Datalink, a validated, longitudinal database from the UK, to
identify male cases and controls diagnosed with AGA and
LUTS/BPH. The authors found no significant increase in ED
or SD in men taking 5-ARIs when compared to matched
controls.
Experts’ comments:
As the population grows older, maintaining vitality, including
a younger appearance, has become more of a focus. Thus, men
often turn to 5-ARIs such as finasteride to alleviate the ills of
aging, specifically with regard to AGA and LUTS/BPH. Howev-
er, anecdotal reports and poorly designed studies have re-
ceived increased media coverage concerning the persistence
of ED and SD following cessation of even a small dose of
finasteride, putatively termed the post-finasteride syndrome
(PFS) [1]. It is not surprising that men on finasteride report low
levels of sexual dysfunction. Interestingly, in the MTOPS trial,
in which baseline erection, ejaculation, and libido were quan-
titatively measured using validated scales, ejaculation, but not
erection or libido, worsened in men on finasteride when
compared to controls [2].
A critical lesson was learned from the MTOPS cohort: one
must control for baseline demographic and clinical char-
acteristics that drive sexual dysfunction, including age,
lower education level, obesity, and severe LUTS, as these are
significantly associated with poorer sexual drive, erectile
function, ejaculatory function, sexual problem assessment,
and overall satisfaction [3]. Most of the above-mentioned
flawed studies did not control for these risk factors driving
nascent sexual dysfunction, which must be accounted for to
prevent erroneous attribution of future ED and ejaculatory
dysfunction. Hagberg et al used a cohort study with nested
case-control analyses in both a BPH group and an alopecia
group that included baseline measures of sexual function.
For the alopecia population of >12 000 men, the risk of ED
was not higher for users of finasteride 1 mg (incidence
rate ratio [IRR] 1.03, 95% confidence interval [CI] 0.73–1.44)
than for unexposed men with alopecia (IRR 0.95, 95% CI
0.64–1.41). They concluded that finasteride does not
significantly increase the risk of incident ED, regardless of
indication for use. Similarly, Unger at el reviewed the risk
of developing long-termadverse consequences of finasteride
using Prostate Cancer Prevention Trial data. Using baseline
measurements of sexual function, over a follow-up assess-
ment time of 16 yr there was no increase in SD. Use of a
control population and baseline assessment are critical in
assessing the risk of SD. In these, like other well-designed
and controlled epidemiological studies, there is no evidence
of a link between ED and previous finasteride exposure.
Biologically, the mechanism of action in PFS is question-
able. While the biology of loss of libido with finasteride can
be explained by a resultant dearth of dihydrotestosterone
(DHT), the lack of DHT does not explain why this effect is not
reversible when finasteride is stopped, 5a-reductase is no
longer inhibited, and DHT returns to baseline levels. ED is
less directly related to androgen levels and is more
indicative of vascular health. Vascular integrity requires a
significant time to deteriorate and almost certainly would
not occur within 1 yr of starting treatment, as is the case
with most reports of PFS [5], without some pre-existing
vascular disease.
The possibility that a medication as prevalent as
finasteride causes irreversible SD is alarming, especially
when the treatment population includes younger, other-
wise healthy men. However, good science with appropriate
controls and follow up is necessary to elucidate whether the
effect is real and to ensure we do not shun effective therapy
because of confirmation and selection bias.
Conflicts of interest: Kevin T. McVary is retained as an expert for Merck in
a law suit concerning persistence of sexual problems following cessation
of finasteride (Propecia). Nikhil K. Gupta has nothing to disclose.
References
[1]
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[2]
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[3]
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[4] Unger JM, Till C, Thompson Jr IM, et al. Long-term consequences of
finasteride vs placebo in the Prostate Cancer Prevention Trial. J Natl
Cancer Inst 2016;108 .
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