ORIGINAL RESEARCH & REVIEWS

ONCOLOGY

Effects of Preoperative Atorvastatin Treatment On Erectile Function

After Radical Prostatectomy: Results From a Subgroup of ESTO1, a
Randomized, Double-Blind, Placebo-Controlled Study
Aino Siltari, PhD,1 Jarno Riikonen, MD, PhD,2 Mikkel Fode, MD, PhD,3 and Teemu J. Murtola, MD1,2,4

ABSTRACT

Introduction: Erectile dysfunction is common after radical prostatectomy because of damage to the cavernous
nerves. Thus, it is important to identify new ways to avoid this problem. For example, statins have shown positive
effects on erectile function and may have anti-inflammatory effects that improve recovery after surgery.
Aim: The aim of this exploratory analysis of a subgroup from ESTO1, a randomized, double-blind, placebo-
controlled study, was to evaluate the preoperative use of atorvastatin on erectile function after radical prostatectomy.
Method: Patients were randomized to either 80 mg atorvastatin or placebo daily before undergoing radical
prostatectomy from study inclusion to the day of surgery. Altogether 118 men with prostate cancer and
scheduled for radical prostatectomy were asked to fill out the 5-item version of the International Index of Erectile
Function (IIEF-5) questionnaire before surgery and at 3, 6, 9, and 12 months after surgery.
Main Outcome Measurements: The study was exploratory, with the main outcome being the overall difference
between IIEF-5 scores in the 2 groups at 12 months. Several hypotheses generating sub-analyses were conducted.
Results: Overall, 85% filled out the IIEF-5 questionnaire before their operation and 85%, 81%, 78%, and 78%
completed it at 3, 6, 9, and 12 months follow-up, respectively. 52% of men had information available at all time
points. There were no statistically significant differences between the groups at baseline in either erectile function,
comorbidities, or tumor characteristics. The median duration of use of atorvastatin and placebo before surgery
was 27 and 25 days, respectively. Preoperative atorvastatin treatment had no statistically significant effect on
erectile function after prostatectomy as compared with placebo, although IIEF-5 scores were higher at all time
points in the statin arm. Furthermore, atorvastatin treatment compared with placebo improved IIEF-5 scores at
12 months after surgery when the cavernous nerves were at least partially intact bilaterally (P < .04, n ¼ 65);
however, after full bilateral or unilateral nerve-sparing, the difference was not statistically significant.
Clinical Implication: Short-term statin treatment did not improve recovery of erectile function after prosta-
tectomy; however, further studies are needed before final conclusions.
Strengths & Limitations: This was a randomized placebo-controlled study. Original ESTO1 study was
designed to detect a difference in prostate cancer biomarkers.
Conclusion: Short-term atorvastatin treatment before radical prostatectomy had no statistically significant effect
on the recovery of erectile functions in a non-selected cohort of patients undergoing radical prostatectomy.
Further studies will be needed to clarify the role of long-term atorvastatin use before and after prostatectomy.
Siltari A, Riikonen J, Fode M, et al. Effects of Preoperative Atorvastatin Treatment On Erectile Function
After Radical Prostatectomy: Results From a Subgroup of ESTO1, a Randomized, Double-Blind, Placebo-
Controlled Study. J Sex Med 2019;16:1597e1605.
Copyright
2019, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Key Words: Atorvastatin; Clinical Drug Study; Erectile Dysfunction; IIEF-5 Questionnaire; Radical Prosta-
tectomy; Cavernous Nerves

4
Received April 24, 2019. Accepted July 3, 2019. Seinäjoki Central Hospital, Department of Surgery, Seinäjoki, Finland
1
Tampere University, Faculty of Medicine and Life Sciences, Tampere, Copyright ª 2019, International Society for Sexual Medicine. Published by
Finland; Elsevier Inc. All rights reserved.
2
Tampere University Hospital, Department of Urology, Tampere, Finland; https://doi.org/10.1016/j.jsxm.2019.07.001
3
Herlev and Gentofte Hospital, Department of Urology, Herlev, Denmark;

J Sex Med 2019;16:1597e1605 1597

1598
INTRODUCTION
Erectile dysfunction (ED) is common after radical prosta-
tectomy because of damage to the cavernous nerves.1 Despite
increasing experience with the procedure and the introduction
of new surgical methods, the incidence of ED after radical
prostatectomy has not declined in recent years.2 In addition,
attempts at penile rehabilitation through treatment with erec-
togenic aids and neuromodulatory compounds after surgery
have not achieved any clear benefits on long-term spontaneous
erections.3e5 Therefore, there is an unmet clinical need for new
methods of preserving post-prostatectomy erectile function.
Statins decrease cholesterol levels by inhibiting the rate-
limiting enzyme, HMG-CoA. Decreased cholesterol levels also
affect the mevalonate pathway, which generates other sterols such
as testosterone. Accordingly, statin treatment seems to slightly
decrease testosterone levels in men.6 Thus, in theory, statins
could increase ED by reducing testosterone levels. However, this
does not seem to be the case, because, in practice, statins have
actually been shown to improve erectile function.7 This is
possibly due to increased nitric oxide generation and a subse-
quent improvement in endothelial function.8 Increased nitric
oxide production in the vasculature9e11 may also enhance the
effects of phosphodiesterase type 5 inhibitors, such as sildenafil.
Finally, statins are known to possess anti-inflammatory proper-
ties12 and may reduce the neuronal inflammatory response and,
thus, hasten recovery after nerve damage.13 Thus, statin therapy
might be one feasible way to promote the recovery of the nerves
responsible for erectile function after radical prostatectomy. A
recent study investigated the effects of statins on neuronal
damage in a microglia cell model.14 It was concluded that statin
treatment seemed to attenuate the extent of the damage by
inhibiting the nuclear factor-k B-pathway, which triggers the
production of inflammatory cytokines.
Nonetheless, the administration of a statin to improve erectile
function after nerve-sparing radical prostatectomy has been
investigated in only 1 clinical study.15 In that study, 50 men
without hypercholesterolemia were randomized to receive either
sildenafil on demand or 10 mg of atorvastatin daily plus sildenafil
on demand for 90 days after surgery. Although not statistically
significant, there was a tendency toward a better postoperative
recovery of potency in the atorvastatin group (26.1% vs 55%,
P ¼ .068). However, the study was hampered by a lack of
blinding and uncertainty about the use of sildenafil in the 2
groups. Even more importantly, the postoperative dosing of
atorvastatin meant that its putative anti-inflammatory effects in
conjunction with surgery could not be evaluated, which may well
have missed most of the theoretical benefits. In this subgroup
study of the ESTO1 trial, a randomized placebo-controlled
study, we investigated the effects of preoperative statin treat-
ment on erectile function after radical prostatectomy in Finnish
men.
Siltari et al
MATERIAL AND METHODS
Study Cohort
This study presents the results of the planned exploratory sub-
group analyses from the ESTO1-study population. Full informa-
tion and results of the main endpoints of the ESTO1-study can be
found in our previous publication.16 Briefly, the original study
included 158 statin-naïve patients who were randomized to either
80 mg atorvastatin or placebo daily before undergoing radical
prostatectomy from study inclusion to the day of surgery. From that
population, 118 men were asked to complete the abridged, 5-item
version of the International Index of Erectile Dysfunction (IIEF-5)
questionnaire.17 Blinding was maintained throughout the trial.
Clinical information of prostate cancer included details of the
Gleason score from both biopsies and tumors, tumor T-stage,
tumor volume, and the prostate-specific antigen value at the time of
diagnosis. Data were supplemented with information of comor-
bidities at recruitment (categorized as yes or no), such as diabetes
and hypertension, and some background information, such as
smoking habits (categorized as current, previous, never). We also
had information on nerve-sparing at prostatectomy (categorized as
non-nerve sparing, partial/full on 1 side, at least partial on both
sides, or full nerve-sparing on both sides) and prostate intra-
inflammation score, which was evaluated using histopathologic
classification.18 Study protocol was approved by the Ethics Com-
mittee of the Pirkanmaa Hospital District (ETL R03230), and all
subjects signed an informed consent form before enrollment into
the study. The study was also registered by EudraCT (2011-
005438-20) and clinicaltrials.gov (NCT01821404) and was con-
ducted by adhering to the principles of Good Clinical Practice and
Declaration of Helsinki.
Information of Erectile Function
The IIEF-5 questionnaire was collected at baseline and at 3, 6,
9, and 12 months after surgery. The severity of ED was divided
into the following groups based on the IIEF-5 scores: score 1e7
severe, 8e11 moderate, 12e16 mild-moderate, 17e21 mild,
and 22 no ED.
Statistical Analysis
Non-parametric Mann-Whitney tests were used to compare
IIEF-5 scores in the atorvastatin arm to placebo arm at different
time points. Linear regression was used to test for trends in
IIEF-5 scores over time after prostatectomy. Friedman test was
used to evaluate statistical significance of differences in IIEF-5
trends between the study arms. Separate analyses for the sub-
groups of hypertensive and diabetic subjects, and based on the
severity of baseline ED, smoking habits, duration of study drug
use, and the degree of nerve-sparing at prostatectomy were
conducted. Differences were assumed as statistically significant
if P < .05.
J Sex Med 2019;16:1597e1605
Atorvastatin and Erectile Function 1599

Table 1. Population characteristics Table 1. Continued

Trial arm Trial arm
Atorvastatin Placebo Atorvastatin Placebo
(n ¼ 60) (n ¼ 58) (n ¼ 60) (n ¼ 58)
Age, median (IQR) 64 (58.5e68) 64 (58e69) High-grade PCa 11 (18) 10 (17)
Preoperative statin 27 (17e33) 25 (17e36) (T-stage T2c or more)
use, median days (%)
(IQR) Prostate volume, median 34 (29.5-47.5) 34 (25-45)
Compliance 100 (82e102) 97 (89e102) (IQR) (mL)
(used study drugs Intra-prostate
from the goal), inflammation score*
median (IQR) (%) 9 (%) 23 (38) 23 (40)
Compliance (IIEF-5 9> (%) 36 (60) 33 (57)
questionnaire
Testosterone levels†
available), n (%)
Preoperative, median 14.5 (11.1-19) 14.6 (13-20.2)
Baseline 51 (85) 49 (84)
(IQR) (nmol/L)
3 months after 51 (85) 49 (84)
Postoperative, 13.4 (11.2-17.5) 16 (11.6-23.2)
operation
median (IQR)
6 months after 48 (80) 47 (81) (nmol/L)
operation
Nerve-sparing
9 months after 51 (85) 41 (71)
Bilateral, n (%) 20 (33) 17 (29)
operation
Unilateral, n (%) 17 (28) 14 (24)
12 months after 46 (77) 46 (79)
Partial, n (%) 14 (23) 22 (38)
operation
None, n (%) 9 (15) 4 (7)
BMI (kg/m2), median 26.5 (24.1e29.3) 26.4 (24.7e28.9)
(IQR) BMI ¼ body mass index; IIEF-5 ¼ 5-item version of the International Index
Smoking of Erectile Function; IQR ¼ interquartile range; PCa ¼ prostate cancer;
Current regular (%) 10 (16) 6 (10) PSA ¼ prostate-specific antigen.
A randomized placebo-controlled study on preoperative statin treatment on
Current irregular (%) 2 (3) 1 (2)
erectile function after radical prostatectomy.
Previous smoker (%) 1 (3) 0 (0) *Scores were created based on international consensus criteria.18
Never smoked (%) 46 (75) 51 (86) †
Data were available in only part of the study population; normal limit values
Comorbidities in Finland 10e38 nmol/L.
Hypertension (%) 24 (39) 21 (36)
Diabetes mellitus (%) 6 (10) 7 (12) To determine the detectable between-group difference in IIEF-5
Gleason score from scores in the study, a power analysis was performed based on the size
biopsy of our study population and the observed IIEF-5 SD (5.7). This
6 (%) 25 (41) 23 (39) showed that, with 46 subjects in each arm, the median difference
7 (%) 27 (44) 28 (48) between the groups would need to be 3.6 points or more to achieve a
8e10 (%) 9 (15) 8 (14) power of 80% with the a ¼ 0.05. Accordingly, this difference should
Clinical T-stage be considered the primary end point of the study. All statistical tests
T1 (%) (not specified) 1 (2)
were done using IBM SPSS statistics (version 24; Chicago, IL, USA).
T1a (%) - 1 (2)
T1b (%) - 1 (2)
T1c (%) 36 (59) 36 (61)
RESULTS
T2 (%) (not 8 (13) 7 (12)
specified) Population Characteristics
T2a (%) 3 (5) 2 (3) There were no differences in population characteristics be-
T2b (%) 1 (2) 2 (3) tween the study arms (Table 1). The median age of the study
T2c (%) 8 (13) 8 (14) subjects was 64 years old, and the median body mass index
T3 (%) 3 (5) 2 (3) was 26.5 in the statin group and 26.4 in the placebo group.
Preoperative PSA value Most of the study participants were non-smokers (82%). In
<5 ng/mL (%) 6 (10) 4 (7)
both arms, about every third participant had hypertension,
5e10 ng/mL (%) 27 (44) 23 (39)
and about 1 in 10 had diabetes. The median duration of
>10 ng/mL (%) 7 (11) 12 (20)
preoperative study drug use was 27 days in the statin arm and
(continued) 25 days in the placebo arm. Median compliance with the drug

J Sex Med 2019;16:1597e1605

1600 Siltari et al

use was 97e100%, and compliance in filling out of the IIEF-5
questionnaire varied from 71e85% (Table 1). Full data in the
form of IIEF-5 questionnaire at all time points was available in
61 men (52%), and 77 patients (65%) filled out the ques-
tionnaire at baseline and 12 months after the surgery. Only
15% in the atorvastatin arm and 7% in the placebo arm had
undergone non-nerve-sparing surgery, whereas full nerve-
sparing was performed in 33% and 29% of patients, respec-
tively. All others had at least partial nerve-sparing at prosta-
tectomy (Table 1). Furthermore, intra-prostate inflammation
scores were similar between the study arms (Table 1).
Effects of Preoperative Use Of Atorvastatin On
Erectile Functions After Prostatectomy
At baseline, 43% of men in the statin arm and 45% in the
placebo arm had normal erectile function (IIEF-5 score of 22 or
more) (Table 2). The proportion declined 3 months after surgery
to 4% in the statin arm and 2% in placebo arm; at 12 months
from surgery, the proportions recovered to 9% in the statin arm
and 4% in the placebo arm (Table 2). Only 8% and 4% from
statin and placebo arms, respectively, had severe ED (IIEF-5
score 7 or less) at the baseline. 3 months after surgery, the
prevalence of severe ED was 78% in the statin and 90% in the
placebo groups; at 12 months after surgery, the values were still
high, that is, 65% in the statin arm and 78% in the placebo arms
(Table 2).
There were no significant differences in IIEF-5 scores between
the study arms at any time point after prostatectomy or at the
baseline (Table 3). Figure 1 illustrates the distribution of IIEF-5
scores at different time points in both arms. P values for the
Friedman test, which take into account all time points, were .098
for atorvastatin arm and .513 for the placebo arm. Furthermore,
regression coefficients did not statistically differ between the 2
arms (P ¼ .174). When taking into account the severity of ED
(Table 3), no differences were evident between the study arms for
ED of any grade. Noteworthy, IIEF-5 scores were higher in the
statin arm compared with the placebo arm at 12 months after
surgery in almost all analyses; however, the difference was not
statistically significant. Taking into account baseline diabetes,
hypertension, smoking, or duration of atorvastatin use did not
modify the result (Table 4). The median difference in IIEF-5
scores between the arms 12 months after surgery was 1.6.
When nerve sparing at prostatectomy was taken into account,
atorvastatin treatment compared with placebo seemed to
improve IIEF-5 scores at 12 months after surgery, when the
nerves were at least partially intact bilaterally (P < .04) (Table 5).
The trend was similar at other time points after surgery
(Table 5). However, in patients in the statin arm with full
bilateral or unilateral nerve-sparing surgery displayed no statis-
tically significant beneficial effect in their IIEF-5 scores
(Table 5). When the analysis was limited to men who had
normal erectile function (IEEF-5 score more than 21) at the
baseline and had full nerve-sparing at surgery, no significant
difference was evident in postoperative erectile function between
the arms (9.7 ± 2.2 vs 11.1 ± 2.3 atorvastatin vs placebo for 12
months after surgery). However, when subjects with nerve-
sparing surgery and high intra-prostate inflammation were
analyzed, atorvastatin use improved IIEF-5 scores (P ¼ .023)
(Table 5).
Effects of Diabetes, Hypertension, and Smoking on
Erectile Function
At baseline, diabetic subjects’ median IIEF-5 scores were lower in
comparison to their non-diabetic counterparts (15.9 ± 2 vs 19.7 ±
0.6; P ¼ .056). Hypertensive and non-hypertensive participants did
not differ at the baseline, but unexpectedly, at 3 months after

Table 2. Amount of participants in different groups of erectile dysfunction based on the IIEF-5 scores
Baseline 3 months 6 months 9 months 12 months
IIEF-5 score 7 or less (severe erectile dysfunction)
Statin, n (%) 4 (8) 40 (78) 33 (69) 33 (65) 30 (65)
Placebo, n (%) 2 (4) 44 (90) 37 (79) 36 (88) 36 (78)
IIEF-5 score 8e11 (moderate erectile dysfunction)
Statin, n (%) 4 (8) 2 (4) 4 (8) 6 (12) 3 (7)
Placebo, n (%) 3 (6) 2 (4) 3 (6) 1 (2) 3 (7)
IIEF-5 score 12e16 (mild-moderate erectile dysfunction)
Statin, n (%) 6 (12) 4 (8) 5 (10) 3 (6) 6 (13)
Placebo, n (%) 7 (14) 2 (4) 4 (9) 5 (12) 2 (4)
IIEF-5 score 17e21 (mild erectile dysfunction)
Statin, n (%) 15 (29) 3 (6) 5 (10) 3 (6) 3 (7)
Placebo, n (%) 15 (31) 2 (4) 3 (6) 2 (5) 3 (7)
IIEF-5 score 22 (normal erectile function)
Statin, n (%) 22 (43) 2 (4) 1 (2) 3 (6) 4 (9)
Placebo, n (%) 22 (45) 1 (2) 0 0 2 (4)
IIEF-5 ¼ 5-item version of the International Index of Erectile Function.

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J Sex Med 2019;16:1597e1605

Atorvastatin and Erectile Function

Table 3. Effects of statin treatment on erectile functions measured using IIEF-5 questionnaire 3, 6, 9, and 12 months after radical prostatectomy in Finnish men
Baseline 3 months 6 months 9 months 12 months

Baseline IIEF-5 N IIEF-5 score P N IIEF-5 score P N IIEF-5 score P N IIEF-5 score P N IIEF-5 score P
score value (mean ± SEM) value value (mean ± SEM) value value (mean ± SEM) value value (mean ± SEM) value value (mean ± SEM) value
All cases .78 .63 .96 .55 .18
Statin 51 18.8 ± 0.9 51 7.7 ± 0.7 48 8.2 ± 0.8 51 8.2 ± 0.8 46 9.3 ± 0.9
Control 49 19.6 ± 0.7 49 6.6 ± 0.6 47 7.1 ± 0.5 41 7.2 ± 0.6 46 7.7 ± 0.8
>7 .93 .71 .49 .77 .55
Statin 47 20 ± 0.7 41 8 ± 0.9 36 7.7 ± 0.8 39 7.4 ± 0.7 35 8.2 ± 0.9
Control 47 20.1 ± 0.6 38 7 ± 0.7 38 7.2 ± 0.6 33 7.3 ± 0.7 37 7.9 ± 0.9
>11 .77 .7 .34 .74 .84
Statin 43 20.9 ± 0.6 39 8.2 ± 0.9 34 7.5 ± 0.8 36 7.6 ± 0.8 33 7.9 ± 0.8
Control 44 20.8 ± 0.5 36 7.1 ± 0.8 35 7.4 ± 0.6 30 7.5 ± 0.8 34 8.2 ± 0.9
>16 .84 .41 .97 .75 .49
Statin 37 22 ± 0.4 33 8.8 ± 1 28 8.1 ± 0.9 31 8 ± 0.9 28 8.5 ± 1
Control 37 22 ± 0.4 30 7.4 ± 0.6 29 7.1 ± 0.7 25 7.3 ± 0.7 30 8.1 ± 1
>21 .29 .61 .94 .86 .61
Statin 22 24 ± 0.2 20 8.3 ± 1.4 16 8.3 ± 1.3 18 8.8 ± 1.4 16 9 ± 1.5
Control 22 23.6 ± 0.3 17 7.1 ± 1.1 19 7.4 ± 0.9 16 7.9 ± 1 17 8.4 ± 1.5
IIEF-5 ¼ 5-item version of the International Index of Erectile Function; SEM ¼ standard error of the mean.

1601
1602
Figure 1. Distribution of IIEF-5 values at baseline and after pros-
tatectomy in the atorvastatin arm and the placebo arm. P ¼ .513 in
the placebo arm and P ¼ .098 in the atorvastatin arm. P ¼ .174 for
regression comparison between the arms. Collums from left:
baseline, 3, 6, 9, and 12 months' time points, respectively; IIEF-5 ¼
5-item version of the International Index of Erectile Function.
surgery, the hypertensive patients had higher IIEF-5 scores than
their non-hypertensive counterparts (7.9 ± 0.8 vs 6.7 ± 0.6;
P ¼ .015). Smokers and non-smokers had similar IIEF-5 scores at
the baseline; however, at 3 months after surgery, non-smokers had a
better recovery in their IIEF-5 scores (5.1 ± 0.1 vs. 7.5 ± 0.6,
P ¼ .01). Similar trends with smoking were also seen at other time
points, although differences were not statistically significant
(5.4 ± 0.3 vs 8.0 ± 0.5 for 6 months, 6.2 ± 0.6 vs 8.1 ± 0.6 for 9
months, and 5.8 ± 0.4 vs 9.0 ± 0.7 for 12 months after the
operation).
DISCUSSION
ED is one of the main side effects encountered after radical
prostatectomy; thus, it is important to devise new ways to avoid
this problem. This study is the first that has evaluated the pre-
operative use of atorvastatin on erectile function after radical
prostatectomy in a randomized setting.
According to some publications10,19-21 but not all clinical
studies,22,23 statin treatment may improve ED in men in general.
In these studies, the daily doses of the statin have varied from 10
mg to 80 mg and the duration of the treatment from 6 weeks to
6 months. Some of the studies investigated the effects of statin
treatment on erectile function among sildenafil non-
responders.10,19,21,24 In all of these studies, patients had ED,
but none that was due to cavernous nerve damage after radical
prostatectomy. Rather, the main pathophysiology has been car-
diovascular disease, although in only 2 studies was either hy-
percholesterolemia specifically described19or endothelial
dysfunction22 applied as an inclusion criterion. Thus, the pa-
tients in our study are not directly comparable to those in the
above-mentioned publications. However, as described, there are
Siltari et al
theoretical considerations to indicate that statins could be of
value in conjunction with radical prostatectomies.
In this study, we were unable to find evidence that preoper-
ative statins can achieve overall significant improvements of
postoperative erectile function. According to the power analysis,
our sample size was sufficient to demonstrate an IIEF-5 score
difference 3.6. Therefore, we cannot rule out smaller IIEF-5
differences. Notably, the median IIEF-5 score at 12 months
was 1.6 points better in the atorvastatin arm compared with the
placebo arm, suggesting a benefit by statin use that is too small to
detect in this sample size. Therefore, larger studies are needed to
confirm our findings.
In the subgroup of patients with at least partially spared nerves
bilaterally, the atorvastatin group did show better IIEF-5 scores
at 12 months after surgery. Considering the size of the subgroup
and the exploratory nature of our analyses, this cannot be taken
as evidence of an actual effect. Nonetheless, it does indicate that
an anti-inflammatory effect of statins may be of specific benefit
in partially intact nerves. This seems intuitive because statins
cannot be expected to restore the function of resected nerves,
and, thus, further studies in this subgroup are justified.
Furthermore, it is not known how long statins need to be
administered to exhibit a significant anti-inflammatory response.
In our study, the statin treatment was short term, that is, the
median duration of use was 27 days. It may be that, to achieve
anti-inflammatory response, which would protect nerves during
surgery and improve the subsequent recovery, longer-term statin
use may be needed. This hypothesis is supported by the finding
that intraprostatic inflammation was quantified in our study
population and found to be similar in both study arms.16
In a cell model involving microglial cells, statin use protected
cells from nerve damage by decreasing the inflammatory
response.14 However, we did not measure the inflammatory
status of nervous tissue in this study; thus, the putative anti-
inflammatory effect of statin treatment on cavernous nerves
will need to be confirmed. In addition, additional benefits of
statin use could become evident by extending the dosing into the
post-operative period, a hypothesis that could be evaluated in
further clinical studies. Meanwhile, the statin dose in our study
(80 mg daily) was high when compared with the average defined
daily dose (20 mg daily) as listed by the World Health Orga-
nization25 for treatment of hypercholesterolemia or atheroscle-
rosis, diseases for which they are usually prescribed. Thus, it is
unclear whether average doses of statin could impact on the re-
covery of erectile function after prostatectomy.
Diabetes is a known risk factor for ED in men.26 This can be
seen also in our study: baseline IIEF-5 scores were lower among
diabetic subjects than in non-diabetics. A similar phenomenon
was not seen among smokers and non-smokers or between hy-
pertensive and normotensive subjects at baseline. However, our
study did not point to any specific benefits in these subgroups.
Hypertensive subjects had higher IIEF-5 scores at 3 months from
J Sex Med 2019;16:1597e1605
Atorvastatin and Erectile Function 1603

Table 4. Effects of statin treatment on erectile function

Baseline 3 months 12 months

IIEF-5 score P IIEF-5 score IIEF-5 score

n-value (mean ± SEM) value n-value (mean ± SEM) P value n-value (mean ± SEM) P value
Diabetic .63 1 .32
Statin 6 14.2 ± 3.5 5 6.2 ± 0.8 4 6.3 ± 0.8
Control 6 17.7 ± 2 6 5.8 ± 0.5 6 9±2
Non-diabetic .73 .6 .1
Statin 45 19.4 ± 0.8 45 7.9 ± 0.8 42 9.6 ± 1
Control 42 20 ± 0.8 44 6.7 ± 0.6 40 7.5 ± 0.8
Hypertensive .77 .19 .44
Statin 21 18.8 ± 1.1 22 9.2 ± 1.3 19 9 ± 1.3
Control 17 18.4 ± 1.3 18 6.2 ± 0.7 19 8.4 ± 1.4
Non-hypertensive .54 .55 .29
Statin 29 18.6 ± 1.3 28 8.9 ± 1.2 26 9.7 ± 1.4
Control 31 20.4 ± 0.9 31 6.8 ± 0.8 27 7.2 ± 0.8
Smokers .32 .64 .53
Statin 12 20.1 ± 1.6 10 5 ± 0.1 7 6.1 ± 0.7
Control 4 17.8 ± 3 6 5.2 ± 0.2 5 5.4 ± 0.4
Non-smokers .35 .41 .2
Statin 37 18.2 ± 1.1 39 8.4 ± 0.9 37 10.2 ± 1.1
Control 44 19.9 ± 0.8 43 6.8 ± 0.7 41 8 ± 0.8
Preoperative statin .56 .52 .43
use 28 days
Statin 22 19.7 ± 1.3 23 7.1 ± 1.1 19 10.2 ± 1.6
Control 20 10 ± 1 16 7.5 ± 1.2 21 7.5 ± 1.1
Preoperative statin .39 .25 .27
use 27 days
Statin 29 18.1 ± 1.1 28 8.1 ± 1 27 8.8 ± 1.1
Control 28 19.5 ± 1 33 6.2 ± 0.6 25 7.9 ± 1.1
Intra-prostate .92 .52 .19
inflammation score >9
Statin 18 18.6 ± 1.6 19 8.2 ± 1.4 15 10.2 ± 1.9
Control 19 19.9 ± 1.1 18 7.6 ± 1.4 17 6.8 ± 1
IIEF-5 ¼ 5-item version of the International Index of Erectile Function; SEM ¼ standard error of the mean.
Participants stratified by comorbidities, by smoking, or by preoperative duration of study drug use or by intra-prostate inflammation score.

surgery, which was not seen at other time points. This may also
be a random finding and will need to be confirmed in the future.
Unfortunately, we did not have access to the blood pressure
levels of the subjects, nor did we have information on which
specific antihypertensive medications had been prescribed for the
patients, meaning that no specific hypothesis can be constructed
in this regard.
Our study has some important strengths. First, it is a ran-
domized, placebo-controlled double-blind study; thus, influ-
ence of background confounding factors was controlled in the
study design. Compliance with the study intervention was
documented to be high: 100% in the statin group and 97% in
the placebo group. In addition, the compliance rate for
completing the IIEF-5 questionnaire was high: 85% at baseline
and 78% at 12 months after surgery. 65% of men filled out the
IIEF-5 questionnaire both at baseline and at the 12-month
time point.
As a limitation, erectile function was not the primary
endpoint for the trial, which was designed to detect a difference
in prostate cancer biomarkers. This means that there was
considerable variation in baseline erectile function and nerve-
sparing. In addition, our study may be affected by a type 2
error, and especially in the subgroup analysis, the statistical
power is low. Also, we only evaluated erectile function. Overall
sexual function is impacted also by other aspects of sexuality,
such as confidence and orgasmic function. Future studies
should preferably use more sophisticated surveys measuring
other aspects of sexuality to obtain a more comprehensive view
on statins’ effects on sexuality preservation after radical
prostatectomy.

J Sex Med 2019;16:1597e1605

1604 Siltari et al

Table 5. Effects of statin treatment on erectile functions. Participants stratified by nerve-sparing after prostatectomy
Baseline 3 months 12 months

IIEF-5 score P IIEF-5 score P IIEF-5 score P

n-value (mean ± SEM) value n-value (mean ± SEM) value n-value (mean ± SEM) value

Intact nerves both side .74 .13 .45

Statin 18 20.1 ± 1.1 17 9.5 ± 1.4 16 10.4 ± 1.7
Control 15 20.8 ± 1 17 6.9 ± 1.2 16 9.9 ± 1.8
At least partial nerves on both side .49 .17 .04
Statin 34 20.4 ± 0.8 34 8.9 ± 1 31 10.8 ± 1.2
Control 37 19.5 ± 0.9 35 6.8 ± 0.7 34 8.2 ± 1
At least partial nerves on 1 side .66 .48 .67
Statin 9 19.9 ± 1.9 10 5.2 ± 0.1 8 5.5 ± 0.2
Control 10 19.9 ± 1.4 10 6.5 ± 1.2 9 6.7 ± 1.1
No intact nerves after surgery .18 .53 .83
Statin 8 10.8 ± 1.9 7 5 7 7.1 ± 2.1
Control 2 18.5 ± 3.5 4 5.3 ± 0.3 3 5.3 ± 0.3
At least partial nerves on both .61 .29 .023
side and intra-prostate
inflammation score >9
Statin 11 20.7 ± 1.6 11 10.4 ± 2.1 9 13.6 ± 3
Control 14 20.4 ± 1.2 12 8.8 ± 2 12 7.3 ± 1.4
IIEF-5 ¼ 5-item version of the International Index of Erectile Function; SEM ¼ standard error of the mean.

CONCLUSION STATEMENT OF AUTHORSHIP

Overall, we conclude that short-term atorvastatin treatment Category 1
before radical prostatectomy conferred no significant benefit on (a) Conception and Design
the recovery of the erectile function in this unselected group of Mikkel Fode; Teemu J. Murtola
men. However, because the IIEF-5 scores were consistently (b) Acquisition of Data
higher, but not statistically significantly, in the statin arm, there Jarno Riikonen; Teemu J. Murtola
may be effects in specific subgroups. Our results will need (c) Analysis and Interpretation of Data
Aino Siltari; Teemu J. Murtola
confirmation from larger trials, with postoperative erectile
function as a main outcome, and the effects of extended Category 2
postoperative statin use will need to be evaluated in other (a) Drafting the Article
clinical studies. Aino Siltari; Teemu J. Murtola
(b) Revising It for Intellectual Content
Corresponding Author: Aino Siltari, Tampere University, Jarno Riikonen; Mikkel Fode
Faculty of Medicine and Health Technology, Arvo Ylpön katu
34, 33520 Tampere, Finland. Tel: þ358 29 412 5347; Fax: Category 3
þ358 191 25364; E-mail: aino.siltari@helsinki.fi (a) Final Approval of the Completed Article
Aino Siltari; Jarno Riikonen; Mikkel Fode; Teemu J. Murtola
Conflicts of Interest: Dr. Siltari reports no conflicts of interest;
Dr. Riikonen receives reimbursements for travel and confer-
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