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Safety and Efficacy of the Herbal Drug Hypericum Perforatum for the Treatment of Premature Ejaculation

Authors:
  • Urology Research Center, Guilan University of Medical Sciences

Abstract

INTRODUCTION: Premature ejaculation (PE) is one of the most prevalent forms of male sexual dysfunction. The benefits of Hypericum perforatum for treatment of PE are unknown, although it is hypothesized that its effect on depression and neurotransmitter activity may be beneficial. The authors assessed the efficacy and safety of H. perforatum for the treatment of PE. METHODS: A prospective, double-blind, randomized, placebo-controlled design was used. Participants were 50 married men with PE. They were 18-50 years old and were evaluated between January 2007 and December 2008. Patients were randomly assigned to one of 2 equal groups. Group 1 received 3 daily tablets of hypericum extract (150 mg per tablet). Each tablet contained 160μg of hypericin. Group 2 received a placebo. All participants recorded intravaginal ejaculation latency time (IELT) and completed the International Index of Erectile Function (IIEF-5) questionnaire before and after treatment. Side effects were self-reported using a questionnaire. Results were compared using chi-square and paired t tests. RESULTS: Forty-two patients completed the study. Hypericum extract was discontinued due to anejaculation (n = 2) and erectile dysfunction (n = 1); 5 patients taking the placebo were lost to follow-up. There was a significant group difference in mean IELT (P < .001); IELT increased from 1.17 minutes to 5.8 minutes in the group taking hypericum extract. Patients taking hypericum extract also had significantly higher IIEF-5 ratings for the measures of intercourse satisfaction and overall satisfaction (P < .001). There were no significant group differences in mean IIEF-5 ratings of orgasmic function, erectile function, or sexual desire. Mild adverse events of headache, constipation, and photosensitivity were seen in 6 patients (27%) taking hypericum extract. CONCLUSION: H. perforatum (St. John's wort) may be an effective and safe treatment for PE, possibly because of its effect on neurotransmitters such as serotonin.
©2010 UroToday International Journal / Vol 3 / Iss 3 / June
doi:10.3834/uij.1944-5784.2010.06.21
http://www.urotodayinternationaljournal.com
ISSN 1944-5792 (print), ISSN 1944-5784 (online)
Seyyed Alaeddin Asgari, Siavash Falahatkar, Seyed Hosein Hoseini Sharifi, Ahmad Enshaei, Michael Fariad Jalili,
Aliakbar Allahkhah
Urology Research Center, Guilan University of Medical Sciences, Razi Hospital, Rasht, Iran
Submitted April 24, 2010 - Accepted for Publication May 4, 2010
www.urotodayinternationaljournal.com
Volume 3 - June 2010
Safety and Efficacy of the Herbal Drug Hypericum Perforatum
for the Treatment of Premature Ejaculation
Abbreviations and Acronyms
5HT = 5-hydroxytryptamine
IELT = intravaginal ejaculation latency time
IIEF-5 = International Index of Erectile
Function
PE = premature ejaculation
SJW = St. John’s wort
SSRI = selective serotonin reuptake
inhibitors
ABSTRACT
KEYWORDS: Hypericum perforatum; Premature ejaculation; IELT; IIEF-5; Drug
therapy.
CORRESPONDENCE: Siavash Falahatkar, MD, Urology Research Center, Guilan
University of Medical Sciences, Razi Hospital, Sardare Jangal Street, Rasht, Guilan
41448, Iran (falahatkar_s@yahoo.com).
CITATION: UroToday Int J. 2010 Jun;3(3). doi:10.3834/uij.1944-5784.2010.06.21
INTRODUCTION: Premature ejaculation (PE) is one of the most prevalent forms of male sexual dysfunction. The
benefits of Hypericum perforatum for treatment of PE are unknown, although it is hypothesized that its effect
on depression and neurotransmitter activity may be beneficial. The authors assessed the efficacy and safety of H.
perforatum for the treatment of PE.
METHODS: A prospective, double-blind, randomized, placebo-controlled design was used. Participants were 50
married men with PE. They were 18-50 years old and were evaluated between January 2007 and December 2008.
Patients were randomly assigned to one of 2 equal groups. Group 1 received 3 daily tablets of hypericum extract
(150 mg per tablet). Each tablet contained 160μg of hypericin. Group 2 received a placebo. All participants
recorded intravaginal ejaculation latency time (IELT) and completed the International Index of Erectile Function
(IIEF-5) questionnaire before and after treatment. Side effects were self-reported using a questionnaire. Results
were compared using chi-square and paired t tests.
RESULTS: Forty-two patients completed the study. Hypericum extract was discontinued due to anejaculation (n =
2) and erectile dysfunction (n = 1); 5 patients taking the placebo were lost to follow-up. There was a significant
group difference in mean IELT (P < .001); IELT increased from 1.17 minutes to 5.8 minutes in the group taking
hypericum extract. Patients taking hypericum extract also had significantly higher IIEF-5 ratings for the measures
of intercourse satisfaction and overall satisfaction (P < .001). There were no significant group differences in
mean IIEF-5 ratings of orgasmic function, erectile function, or sexual desire. Mild adverse events of headache,
constipation, and photosensitivity were seen in 6 patients (27%) taking hypericum extract.
CONCLUSION: H. perforatum (St. John’s wort) may be an effective and safe treatment for PE, possibly because of
its effect on neurotransmitters such as serotonin.
UroToday International Journal®
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J
©2010 UroToday International Journal / Vol 3 / Iss 3 / June
doi:10.3834/uij.1944-5784.2010.06.21
http://www.urotodayinternationaljournal.com
ISSN 1944-5792 (print), ISSN 1944-5784 (online)
UroToday International Journal®
original study
Safety and Efficacy of the Herbal Drug Hypericum Perforatum for the Treatment of Premature Ejaculation
INTRODUCTION
Premature ejaculation (PE) is one of the most frequent male
sexual complaints. It is estimated that 20% to 30% of men
experience PE at some point in their lifetime; however, the
prevalence depends on the definition employed [1,2]. A
universally accepted definition of PE has yet to be established,
but the Diagnostic and Statistical Manual of Mental Disorders [3]
defines it as, “persistant or recurrent ejaculation with minimal
sexual stimulation before, on, or shortly after penetration and
before the person wishes it.” PE frequently leads to marked
distress or interpersonal difficulty.
Intravaginal ejaculation latency time (IELT) is the numerical
indicator most frequently used to assess PE treatments during
clinical trials [4-6]. An IELT of < 2 minutes has been considered
consistent with the diagnosis of PE [7].
Pharmacological treatment of PE includes selective serotonin
reuptake inhibitors (SSRIs), tricyclic antidepressants,
phosphodiesterase (PDE) inhibitors, and topical anesthetics [8-
10]. Hypericum perforatum (H. perforatum), also known as St.
John’s wort (SJW), is a widely used over-the-counter drug for
treatment of depression. Its increase in popularity seems to
indicate a growing need for an alternative drug that may be able
to avoid the undesirable adverse effects associated with some
of the most commonly prescribed synthetic antidepressants.
SJW is widely prescribed in the United States and Europe,
and its use in other countries is increasing [11]. It is by far the
most commonly prescribed antidepressant in Germany, where
physicians prescribe it 4 times more often than fluoxetine.
A meta-analysis published in 2001 [12] analyzed 22 randomized
controlled trials and concluded that SJW is significantly
more effective than placebo and as effective as standard
antidepressants in the treatment of depression. Two double-
blind randomized controlled studies compared SJW with 2
SSRIs (fluoxetine and sertraline). Both studies found similar
clinical improvements in depressive symptoms as evidenced by
significantly reduced scores on the Hamilton Rating Scale for
depression [13,14]. Several randomized-sample studies [13,15]
have shown that H. perforatum was more effective than a
placebo and at least as effective as imipramine and fluoxetine
in the treatment of mild to moderate depression. The studies
further showed that H. perforatum had more benefits than the
other drugs, including decreased side effects and an increased
ability of patients to tolerate the medication. However, some
limitations to the studies using H. perforatum have been
noted, and studies measuring the effect of Hypericum in major
depression have reported conflicting results [16].
Hypricin and hyperforin, 2 isolates of H. perforatum, are
among the most researched active components of SJW. They
have been found to inhibit synaptosomal uptake of several
neurotransmitters, including serotonin, norepinephrine, and
gamma-aminobutyric acid (GABA) [15,17,18].
Treatment of PE in the field of urology is challenging, but
antidepressive medications have been part of the standard
management protocol. The benefits of H. perforatum for
treatment of PE are unknown, although it is hypothesized that
its effect on depression and neurotransmitter activity may be
beneficial. Therefore, the purpose of the present investigation
was to assess the efficacy and safety of H. perforatum for the
treatment of PE.
METHODS
Participants
A total of 50 married men with PE presented to the authors’
urology clinic between January 2007 and December 2008. The
patients ranged in age from 18-50 years.
PE was defined as IELT of < 2 minutes, occurring more than 50%
of the time while attempting sexual intercourse, and causing
significant distress for the patient and his partner. The diagnosis
was made by a physician. Patients were included if they had a
stable sexual relationship with a female sexual partner for at
least 1 year and had sexual intercourse more than once a week.
Exclusion criteria included: (1) patients with psychiatric
disorders or concurrent erectile dysfunction; (2) patients taking
medication known to impair sexual function; (3) patients with
a history of previous pelvic or spinal surgery, chronic prostatitis,
or urethritis; (4) patients with other sexual disorders such as
decreased libido; (5) patients receiving other treatments for PE.
Procedures
The study was approved by the ethics committee of the authors’
institution. A prospective, randomized, double-blind, placebo-
controlled design was used.
Patients were randomly assigned to one of 2 equal groups by
blocked random allocation sequence. The mean age of the
patients in group 1 and group 2 was 30.68 years and 31.7 years,
respectively.
Patients in group 1 were treated with 3 daily tablets of
Hypericum extract (Goldarou Comp. Isfahan), given at a dose of
150 mg per tablet. Each tablet contained 160μg of hypericin.
Patients in group 2 received identical placebo pills that did not
appear to be factitious. Participants in both groups received
UI
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UroToday International Journal®
©2010 UroToday International Journal / Vol 3 / Iss 3 / June
doi:10.3834/uij.1944-5784.2010.06.21
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ISSN 1944-5792 (print), ISSN 1944-5784 (online)
www.urotodayinternationaljournal.com
original study
Seyyed Alaeddin Asgari, Siavash Falahatkar, Seyed Hosein
Hoseini Sharifi, Ahmad Enshaei, Michael Fariad Jalili, Aliakbar Allahkhah
identical instructions. The medications were dispensed by a
pharmacologist who did not know the purpose of the research.
The investigators did not know which individual patients were
receiving the placebo or the Hypericum extract.
Before beginning treatment, all patients were asked to measure
IELT by using a stopwatch. They recorded the average IELT in
seconds from 3 consecutive separate occasions of intercourse.
All participants also completed the International Index of
Erectile Function (IIEF-5) questionnaire [19]. Thirty days after
completing the study, patients were asked to measure their
IELT and complete the IIEF-5 questionnaire a second time. Side
effects were self-reported using a questionnaire.
Data before and after treatment were compared using the
paired t test for continuous data and chi-square test for
categorical data. Because of the large number of paired
comparisons, a conservative probability level of P < .001 was
considered statistically significant. A power analysis was not
conducted. Therefore, the possibility of type II error exists with
this sample size.
RESULTS
Of the 50 original participants, 42 (84%) completed the
study (22 in group 1; 20 in group 2). In group 1, therapy was
discontinued due to anejaculation in 2 patients and erectile
dysfunction in 1 patient. In group 2, 5 patients did not return
to complete the study.
The mean age for patients in group 1 and group 2 was 30.7
years and 31.7 years, respectively, with no significant group
difference (P = .57). The mean duration of marriage for patients
in group 1 and group 2 was 3.7 years and 4.1 years, respectively,
with no significant group difference (P = .82).
Treatment Effects
Pretreatment Group Differences. Table 1 contains the
pretreatment means and standard deviations for the measures
of IELT and the 5 categories of the IIEF-5 (intercourse satisfaction,
overall satisfaction, orgasmic function, erectile function, sexual
desire) and the probability of significant group differences. The
mean IELTs were 70.23 seconds and 67.50 seconds for patients
in groups 1 and 2, respectively. These times are indicative of
PE. There were no significant pretreatment group differences
in any variable (P > .001).
Intragroup Effect of Drug Treatment. Table 2 contains the
means and standard deviations of the outcome measures before
and after receiving Hypericum extract and the probability of
significant differences due to treatment. After 4 weeks of
treatment, the mean IELT had significantly increased from
70.23 seconds (1.17 minutes) to 349.09 seconds (5.8 minutes)
(P < .001). There was also a significant increase in mean
ratings of intercourse satisfaction and overall satisfaction, and
a significant decrease in the mean rating of erectile function
(P < .001). There were no significant differences in orgasmic
function or sexual desire.
Intragroup Effect of Placebo Treatment. Table 3 contains
the means and standard deviations of the outcome measures
before and after receiving the placebo and the probability
of significant differences due to treatment. After 4 weeks of
placebo treatment, the mean IELT had significantly increased
from 67.5 seconds to 99 seconds (P < .001). There was also a
significant decrease in the IIEF-5 variable of erectile function
(P < .001). There were no placebo treatment effects for the
remaining IIEF-5 variables.
Group Differences in Treatment. Table 4 contains the means
and standard deviations of the outcome measures following
treatment with Hypericum extract or the placebo, and the
probability of significant group differences. There were
significant group differences in mean IELT (P < .001); patients
taking the Hypericum extract had a significantly longer
IELT than the patients taking the placebo. Patients taking
Hypericum extract also had significantly higher IIEF-5 ratings for
the measures of intercourse satisfaction and overall satisfaction
Measure Group Mean SD P
Intravaginal ejaculation
latency time (s)
Drug 70.23 21.07 .68
Placebo 67.50 21.18
Intercourse satisfaction (score) Drug 3.59 1.01 .34
Placebo 3.25 1.25
Overall satisfaction (score) Drug 9.59 1.26 .91
Placebo 9.55 1.00
Orgasmic function (score) Drug 9.41 0.50 .06
Placebo 9.15 0.37
Erectile function (score) Drug 27.14 1.61 .71
Placebo 26.95 1.57
Sexual desire (score) Drug 9.82 0.39 .88
Placebo 9.80 0.41
Table 1. Pretreatment Means and Standard Deviations
(SD) of Outcome Measures for Patients Receiving
Hypericum Extract (n = 22) and a Placebo (n = 20);
Probability of Significant Group Differences.
doi: 10.3834/uij.1944-5784.2010.06.21t1
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©2010 UroToday International Journal / Vol 3 / Iss 3 / June
doi:10.3834/uij.1944-5784.2010.06.21
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ISSN 1944-5792 (print), ISSN 1944-5784 (online)
UroToday International Journal®
original study
Safety and Efficacy of the Herbal Drug Hypericum Perforatum for the Treatment of Premature Ejaculation
(P < .001). There were no significant group differences in mean
orgasmic function, erectile function, or sexual desire.
Adverse Events
Adverse events were seen in 6 patients (27%) taking
Hypericum extract: headache (n = 3), constipation (n = 2), and
photosensitivity (n = 1). None of these 6 patients discontinued
treatment. There was 1 report of nausea in the patients taking
the placebo.
DISCUSSION
PE is ejaculation occurring without the control or desire of the
Table 2. Means and Standard Deviations (SD) of Outcome
Measures Before and After Treatment for Patients
Receiving Hypericum Extract (n = 22); Probability of
Significant Differences.
doi: 10.3834/uij.1944-5784.2010.06.21t2
Measure Time Mean SD P
Intravaginal ejaculation
latency time (s)
Before 70.23 21.07 <.001
After 349.09 119.16
Intercourse satisfaction
(score)
Before 3.59 1.01 <.001
After 7.32 1.32
Overall satisfaction (score) Before 9.59 1.26 <.001
After 12.68 1.13
Orgasmic function (score) Before 9.41 0.50 .042
After 9.23 0.43
Erectile function (score) Before 27.14 1.61 <.001
After 25.18 1.44
Sexual desire (score) Before 9.82 0.39 .083
After 9.95 0.21
Table 3. Means and Standard Deviations (SD) of Outcome
Measures Before and After Treatment for Patients
Receiving the Placebo (n = 20); Probability of Significant
Group Differences.
doi: 10.3834/uij.1944-5784.2010.06.21t3
Measure Time Mean SD P
Intravaginal ejaculation
latency time (s)
Before 67.5 21.18 <.001
After 99 37.26
Intercourse satisfaction (score) Before 3.25 1.25 .008
After 3.75 1.37
Overall satisfaction (score) Before 9.55 1.00 .014
After 10.05 0.89
Orgasmic function (score) Before 9.15 0.37 .01
After 9.45 0.51
Erectile function (score) Before 26.95 1.57 <.001
After 25.8 1.61
Sexual desire (score) Before 9.8 0.41 .163
After 9.7 0.57
Measure Group Mean SD P
Intravaginal ejaculation
latency time (s)
Drug 349.09 119.16 <.001
Placebo 99 37.26
Intercourse satisfaction (score) Drug 7.32 1.32 <.001
Placebo 3.75 1.37
Overall satisfaction (score) Drug 12.68 1.13 <.001
Placebo 10.05 0.89
Orgasmic function (score) Drug 9.23 0.43 .136
Placebo 9.45 0.51
Erectile function (score) Drug 25.18 1.44 .196
Placebo 25.8 1.61
Sexual desire (score) Drug 9.95 0.21 .073
Placebo 9.7 0.57
Table 4. Posttreatment Means and Standard Deviations (SD) of Outcome Measures
for Patients Receiving Hypericum Extract (n = 22) and a Placebo (n = 20); Probability
of Significant Group Differences. doi: 10.3834/uij.1944-5784.2010.06.21t4
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UroToday International Journal®
©2010 UroToday International Journal / Vol 3 / Iss 3 / June
doi:10.3834/uij.1944-5784.2010.06.21
http://www.urotodayinternationaljournal.com
ISSN 1944-5792 (print), ISSN 1944-5784 (online)
www.urotodayinternationaljournal.com
original study
Seyyed Alaeddin Asgari, Siavash Falahatkar, Seyed Hosein
Hoseini Sharifi, Ahmad Enshaei, Michael Fariad Jalili, Aliakbar Allahkhah
patient, and the diagnosis should only be made when there is
marked distress [20]. PE is one of the most prevalent sexual
dysfunctions in males and is reported to be more prevalent
than erectile dysfunction [21]. Although some biological and
psychological conditions have been proposed as contributing
to PE, the exact pathogenesis remains to be clarified [22].
Pharmacologic treatment for certain ejaculatory disorders
exists, such as the off-label use of SSRIs for PE. Recent research
has elucidated more about the role of serotonin and dopamine
at the central level in the physiology of both arousal and
orgasm [23]. There has been emphasis on identifying the
biological basis of ejaculation and its dysfunction. At present,
the most studied neurotransmitter in the neurophysiology of
ejaculation seems to be 5-hydroxytryptamine (serotonin) [23].
In contrast to the presynaptic 5-HT1a autoreceptors, the 5-HT1b
and 5-HT2c receptors have been shown to prolong ejaculatory
latency [24].
The exact physiological mechanisms contributing to the
positive results of Hypericum extract on PE in the present
study are not known and require further study. However,
the authors hypothesize that its effect on neurotransmitters
may have been involved. Preclinical studies have found that
SJW inhibits the synaptic reuptake system of serotonin and
norepinephrine [25-27]. Most of this herb’s pharmacological
activities are attributable to hypericin and hyperforin [26].
SJW up-regulates serotonin receptors and also has a significant
affinity for opiate sigma receptors, which may contribute to its
antidepressant effect [27]. The antidepressant effect of SJW
may also be mediated via reduction of corticotropin-releasing
hormone (CRH) secretion, through suppression of interleukin-6
(IL-6) release [28].
There exists some controversy about whether or not SJW
interferes with the action of other prescribed medications.
Will-Shahab et al [19] reported that reduced-hyperforin SJW
preparations are less likely to interact with drugs and may
substantially lower the risk of serious herb-drug interactions.
Studies have been designed to investigate the effects of a
specific SJW extract (Ze 117) on the pharmacokinetics of
ethinylestradiol and 3-ketodesogestrel, which are the 2
pharmacologically effective components of the low-dose
contraceptive Lovelle [19,29,30]. The authors reported that
the intake of reduced-hyperforin SJW preparations is less
likely to interact with drugs and may substantially lower the
risk of serious herb-drug interactions. However, another study
showed the risk of interactions of SJW with other drugs and the
possible mechanisms of these interactions [31]. For example,
SJW extracts may interact with the hormonal components of
oral contraceptives, thus causing spotting or break-through
bleeding. Additional studies are needed to show whether or
not SJW is a benign treatment.
In an observational study undertaken in 2007, Schulz [32]
reported an incidence of adverse events between 1-3% for
SJW, which was 10 times less frequent than those commonly
associated with synthetic antidepressants. The adverse effects
of SJW were found to include headache, itching, dizziness,
constipation, and fatigue [33]. In the present study, SJW
was effective on PE and had minor side effects of headache,
constipation, and photosensitivity. Reported complications
were fewer than those reported elsewhere from SSRIs such as
fluoxetine and sertraline.
CONCLUSION
Hypericum extract significantly increased IELT and significantly
improved some subjective scores on the IIEF-5 questionnaire,
possibly due to its effect on neurotransmitters such as serotonin.
It had few associated side effects when compared with
classically used antidepressants. These results suggest that H.
perforatum might be an effective and safe treatment modality
for PE. Additional studies with larger numbers of patients and
longer follow-up are needed to confirm this conclusion.
Conflict of Interest: none declared
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©2010 UroToday International Journal / Vol 3 / Iss 3 / June
doi:10.3834/uij.1944-5784.2010.06.21
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ISSN 1944-5792 (print), ISSN 1944-5784 (online)
UroToday International Journal®
original study
Safety and Efficacy of the Herbal Drug Hypericum Perforatum for the Treatment of Premature Ejaculation
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©2010 UroToday International Journal / Vol 3 / Iss 3 / June
doi:10.3834/uij.1944-5784.2010.06.21
http://www.urotodayinternationaljournal.com
ISSN 1944-5792 (print), ISSN 1944-5784 (online)
www.urotodayinternationaljournal.com
original study
Seyyed Alaeddin Asgari, Siavash Falahatkar, Seyed Hosein
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Article
Full-text available
Purpose: St John's wort (Hypericum perforatum) is an herbal remedy that is widely used in the treatment of depression. Recent clinical data have demonstrated that St John's wort extracts interfere with the action of various drugs and possibly also with combined oral contraceptives. Therefore, we investigated the effects of a St John's wort extract (Ze 117) with low hyperforin content on the pharmacokinetics of ethinylestradiol and 3-ketodesogestrel. Method: Sixteen healthy female volunteers, who had taken a low-dose oral contraceptive (Lovelle contains 0.02 mg ethinylestradiol + 0.15 mg desogestrel) for at least 3 months, participated in the study. Pharmacokinetic data (AUC, C(max), t(max)) were determined the day before (reference) and after (test) a 14-day period of Ze 117 intake (250 mg twice daily). Results: Before the co-administration of Ze 117 on day 7, the geometric mean (geometric coefficient of variation) for the AUC(0-24) of ethinylestradiol was 152.53 pg.h/ml (87.39%) and after co-administration on day 21 it was 196.57 pg.h/ml (78.14%). The respective values for ketodesogestrel were 36.37 pg.h/ml (34.18%) and 41.12 pg.h/ml (34.36%). The mean of individual ratios (reference-to-test) of log-transformed AUC values (90% confidence interval) were 0.951 (0.915-0.986) for ethinylestradiol and 0.968 (0.944-0.992) for ketodesogestrel indicating a small gain [corrected] in bioavilability, but bioequivalence nevertheless. Conclusion: These results indicate that the recommended dose of the hypericum extract Ze117, which has a low hyperforin content, does not interact with the pharmacokinetics of the hormonal components of the low-dose oral contraceptive.
Article
Full-text available
St John's wort (Hypericum perforatum) is an herbal remedy that is widely used in the treatment of depression. Recent clinical data have demonstrated that St John's wort extracts interfere with the action of various drugs and possibly also with combined oral contraceptives. Therefore, we investigated the effects of a St John's wort extract (Ze 117) with low hyperforin content on the pharmacokinetics of ethinylestradiol and 3-ketodesogestrel. Sixteen healthy female volunteers, who had taken a low-dose oral contraceptive (Lovelle contains 0.02 mg ethinylestradiol + 0.15 mg desogestrel) for at least 3 months, participated in the study. Pharmacokinetic data (AUC, C(max), t(max)) were determined the day before (reference) and after (test) a 14-day period of Ze 117 intake (250 mg twice daily). Before the co-administration of Ze 117 on day 7, the geometric mean (geometric coefficient of variation) for the AUC(0-24) of ethinylestradiol was 152.53 pg.h/ml (87.39%) and after co-administration on day 21 it was 196.57 pg.h/ml (78.14%). The respective values for ketodesogestrel were 36.37 pg.h/ml (34.18%) and 41.12 pg.h/ml (34.36%). The mean of individual ratios (reference-to-test) of log-transformed AUC values (90% confidence interval) were 0.951 (0.915-0.986) for ethinylestradiol and 0.968 (0.944-0.992) for ketodesogestrel indicating a small gain [corrected] in bioavilability, but bioequivalence nevertheless. These results indicate that the recommended dose of the hypericum extract Ze117, which has a low hyperforin content, does not interact with the pharmacokinetics of the hormonal components of the low-dose oral contraceptive.
Article
The effect of hypericum extract LI 160 on the stimulated cytokine expression was investigated in vitro in a whole blood culture system. Blood samples were taken from five healthy volunteers and four depressive patients. The release of interleukin-6 (IL-6), interleukin-lβ (IL-lβ) and tumor necrosis factor-α (TNF-α) was measured quantitatively after an incubation time of 24 hours on microtiter plates. A massive suppression of the interleukin-6 release was found for PHA-stimulated hypericum extract. Possible relations to the antidepressive effects of hypericum extract are discussed.
Article
Objective: To review and assess the update studies regarding selective serotonin reuptake inhibitors (SSRIs) in the treatment of premature ejaculation (PE) and then provide practical recommendations and possible mechanisms concerning state of the art knowledge for the use of SSRIs in alleviating PE. Data sources: Using the Medline, 48 articles published from January 1st, 1996 to August 1st, 2006 concerning the use of SSRIs and their possible mechanisms in alleviating PE were found and reviewed. Study selection: PE, rapid ejaculation, early ejaculation and SSRIs were employed as the keywords, and relevant articles about the use of SSRIs and their possible mechanisms in the treatment of PE were selected. Results: Many kinds of SSRIs, such as fluoxetine, sertraline, paroxetine and citalopram, have widely been employed to treat PE. However, their effects are moderate and there is no a universal agreement about the kind, dose, protocol and duration. Dapoxetine, as the first prescription treatment of PE, may change this bottle-neck situation. SSRIs are suggested to be used in young men with lifelong PE, and acquired PE when etiological factors are removed but PE still exists. Phosphodiesterase 5 inhibitors (PDE(5)-Is) are suggested to be employed alone or combined with SSRIs when SSRIs fail to treat PE or sexual dysfunction associated with SSRIs occurs. The protocol of taking drugs on demand based on taking them daily for a suitable period is proposed to be chosen firstly. The possible mechanisms include increasing serotonergic neurotransmission and activating 5-hydroxytryptamine 2C (5-HT(2C)) receptors, then switching the ejaculatory threshold to a higher level, decreasing the penile sensitivity and their own effect of antidepression. Conclusion: The efficacies of the current SSRIs are moderate in the treatment of PE and they have not been approved by the FDA, therefore new SSRI like dapoxetine needs to be further evaluated.
Article
Observational studies with preparations of St. John's wort have recorded an incidence of adverse events (AE) among those treated of between 1 and 3%. This is some ten times less than with synthetic antidepressants. The most common adverse events (1 per 300000 treated cases) among the spontaneous reports in the official register concern reactions of the skin exposed to light. Investigations in volunteers have shown that the threshold dose for an increased risk of photosensitisation is about 2-4 g/day of a usual commercial extract (equivalent to approximately 5-10 mg of the hypericin that causes the phenomenon). In view of the newly observed side effects and interactions, the following additional restrictions on use appear justified: as with all preparations in this group of indications, hypericum preparations must not be taken at the same time as other antidepressants. If co-medication with coumarin-type anticoagulants is unavoidable, it must only be undertaken provided the physician closely monitors clotting parameters. Co-medication with ciclosporin and indinavir, and for the time being, other protease inhibitors used in anti-HIV treatment, is absolutely contraindicated. Without exception, all preparations of St. John's wort must only be available through pharmacies.
Article
Conflict of Interest. Dr. Rowland is a part-time consultant for ALZA Corporation. Drs. Bull, Jamieson and Ho are employees of the ALZA Corporation. Background. Although premature ejaculation (PE) is a common male sexual dysfunction, its relevant parameters have not been adequately studied in large community-based samples. Objective. To examine the diagnostic utility of two self-report questions based on the DSM-IV-TR definition of PE and to investigate the relationship between self-identified PE, sexual functioning, and sexual satisfaction in men. Methods. An Internet survey of general health and aspects of sexual functioning and satisfaction was conducted in 2056 males. Subjects were classified as having “probable” or “possible” PE, or as “non-PE” by survey responses. Results. A total of 1158 men met the selection criteria (sexually active in a stable heterosexual relationship), and 189 (16.3%) were classified as having probable PE by reporting they ejaculated before they wished and indicating it was “very much” or “somewhat” a problem. Another 188 (16.2%) men reported ejaculating before they wished but rated their distress lower and were classified as having possible PE. Compared to non-PE men, those with probable and possible PE reported significantly worse sexual functioning in 6 of 8 study measures. Concern about partner satisfaction was high in all groups. The importance of ejaculatory control and the ability to have intercourse for the desired time was significantly higher in men with PE as compared to non-PE men (P < 0.01). Conclusions. PE was a common problem, was characterized by a lack of ejaculatory control, and was associated with significant effects on sexual functioning and satisfaction. Additional research on the sensitivity and specificity of these self-report questions should be pursued.
Article
Introduction: There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease. Aim: To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions. Methods: An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area. Main outcome measure: New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations. Results: Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided. Conclusions: Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28-July 1, 2003.
Article
This paper summarizes the measurement problems inherent to the assessment of rapid ejaculation, focusing on the inadequacy and lack of universally accepted specific criterion sets defining the dysfunction. Six methodologies are examined, including self-report, clinician judgment, omnibus sexuality inventories, self-administered rapid ejaculation questionnaires, and stopwatch assessment. The clinical and scientific methods used to assess this dysfunction are critically reviewed and discussed. This paper also provides suggestions for broadening the focus of future research in rapid ejaculation from primarily ejaculatory latency, control, and distress to relevant quality-of-life parameters.
Article
The herb St John's wort (Hypericum perforatum) has been used for centuries to treat a variety of medical illnesses. In certain areas of Europe, St John's wort has been a commonly prescribed treatment for depression, but, in the United States, it is available for purchase over the counter as an herbal supplement. Some researchers believe that specific chemical constituents of St John's wort produce change in depression in a way similar to that of antidepressant medications, yet this hypothesis is problematic. In addition, studies that support the efficacy of St John's wort in patients with mild-to-moderate depression have limitations that may affect the accuracy of their conclusions. Studies measuring the effect of St John's wort in major depression have reported conflicting results and need to be reexamined. Because St John's wort is considered by some to be an alternative to conventional therapies, clinicians need to know whether it is an effective and safe treatment for different levels of severity of depression. Current evidence does not support its use, and, because of potential drug interactions, St John's wort is not a benign treatment.
Article
Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures.  New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men's and women's individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie's disease; and priapism. Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.