Erectile dysfunction: A review and herbs used for its treatment

Abstract

Erectile dysfunction (ED) or male impotence is defined as the inability to have or sustain an erection long enough to have a meaningful sexual intercourse. ED tends to occur gradually until the night time or early morning erections cease altogether or are so flaccid that successful intercourse does not occur. Sexual health is an important determinant of quality of life. Today, millions of men, young and old, suffer from ED due to high levels of synthetic hormones (known as Xenoestrogens) in our diet/environment; nutritionally imbalanced diet resulting from poor quality of produces; and extremely low levels of testosterone. To overcome the problem of sexual (or) ED various natural aphrodisiac potentials are preferred. The present review discusses about aphrodisiac potential of plants, its biological source, common name, part used and references, which are helpful for researchers to develop new aphrodisiac formulations.

Full text

International Journal of Green Pharmacy | April-June 2012 |
109
Review ARticle
Erectile dysfunction: A review and herbs used for
its treatment
Ashwin Saxena, Pawan Prakash, Mayur Porwal, Neeraj Sissodia, Pravesh Sharma1
Department of Pharmaceutics, Vivek College of Technical Education, Bijnor, Uttar Pradesh, 1Department of Pharmacology, Sanjeevan College
of Pharmacy, Dausa, Rajasthan, India
Erectile dysfunction (ED) or male impotence is defined as the inability to have or sustain an erection long enough to have a
meaningful sexual intercourse. ED tends to occur gradually until the night time or early morning erections cease altogether or are
so flaccid that successful intercourse does not occur. Sexual health is an important determinant of quality of life. Today, millions of
men, young and old, suffer from ED due to high levels of synthetic hormones (known as Xenoestrogens) in our diet/environment;
nutritionally imbalanced diet resulting from poor quality of produces; and extremely low levels of testosterone. To overcome the
problem of sexual (or) ED various natural aphrodisiac potentials are preferred. e present review discusses about aphrodisiac
potential of plants, its biological source, common name, part used and references, which are helpful for researchers to develop new
aphrodisiac formulations.
Key words: Aphrodisiac, erectile dysfunction, Phosphodiesterease
Address for correspondence: Prof. Ashwin Saxena, Department of Pharmaceutics, Vivek College of Technical Education, Bijnor, Uttar Pradesh,
India. E-mail: ashwinpharma04@gmail.com
Received: 18-11-2011; Accepted: 21-02-2012
Access this article online
Quick Response Code: Website:
www.greenpharmacy.info
DOI:
10.4103/0973-8258.102825
INTRODUCTION
Erectile dysfunction (ED), otherwise known as
impotency, aects more than 30 million men each year;
yet only about 200,000 seek help from a physician.
Impotency remains largely unrecognized simply
because most men do not discuss sexual problems
with their doctors. In addition, many physicians do
not ask or are uncomfortable dealing with the subject.
ED is dened as the inability to sustain an erection
well enough to perform intercourse and ejaculation.[1]
While almost all men will experience some degree of
sexual diculty at one time or another, only those who
are unable to have successful intercourse 75 percent of
the time are considered impotent. Contrary to popular
belief, ageing is not an inevitable cause of impotency.
It does, however, take elderly men longer to develop
erection and the force of ejaculation is diminished.[2]
Conventional medicine usually addresses ED issues
by prescribing a drug regimen or surgery. Oral
medications such as Erecaid or testosterone are
rarely eective unless the condition is due to low
testosterone levels. Viagra, Cialis and Levitra, which
act to relax corpus cavernosal smooth muscle and
facilitate erections, are not without their side‑eects.
Penile injections of Papaverine or Prostaglandin
E1, which affect penile blood flow, can result in
prolonged erections necessitating other drug therapy
to counter act its eects. Additionally, the therapy
can cause burning and eventual brosis of the penis.
Lastly, malleable or inatable prosthesis are used in
severe cases, requiring surgical implantation. Such
prosthesis oen need to be surgically re‑implanted,
are uncomfortable and are subject to periodic failure.
ED can be broken down into primary and secondary
impotency. Primary causes are rare and may be
associated with low androgen levels, genetic defects
and severe psycho-pathology. Secondary impotency is
much more common and, as the name implies, results
from something else such as diabetes, arteriosclerosis,
neurological disorders, psychological issues,
prolonged stress or previous surgery to the genitalia.
Blood pressure medications and antidepressants may
also lead to impotency, especially in the elderly.
Dietary factors largely ignored by conventional
medicine, also fuel the problem as men with diets high
in caeine, sugar and alcohol experience more ED,
as do men who smoke and use recreational drugs.
[3]
Psychological causes account for the majority of
impotency complaints. A skilled and sensitive physician
may oen uncover this during an interview and suggest
corrective measures.
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy
| April-June 2012 | 110
Men experience three types of erections:
• Reexogenic erections are induced by tactile stimulation
of the genitals. Men with lesions of the cervical or
thoracic spinal cord (paraplegics) are still able to have
this type of erection. A small number of men with
complete transection of the spinal cord can also have
erections, which are psychogenically induced.
• Psychogenic erections are induced by visual or memory
associations.
• Nocturnal erections occur during rapid eye movement
sleep and may take place anywhere from three to six
times a night, lasting from 20 to 40 minutes. Generally,
nocturnal erections begin with the onset of puberty
and diminish in intensity, duration and frequency later
in life. Erections during arousal and intercourse are
oen achieved as a combination of reexogenic and
psychogenic and a decit in one or both areas can lead
to impotency.
male sexUal DysfUNCTION
Sex disorders of the male are classied into disorders of
sexual function, sexual orientation and sexual behaviour.
In general, several factors must work in harmony to
maintain normal sexual function. Such factors include
neural activity, vascular events, intracavernosal nitric oxide
system and androgens.[4] Thus, malfunctioning of at least
one of these could lead to sexual dysfunction of any kind.
Sexual dysfunction in men refers to repeated inability to
achieve normal sexual intercourse. It can also be viewed
as disorders that interfere with a full sexual response cycle.
These disorders make it dicult for a person to enjoy or to
have sexual intercourse. While sexual dysfunction rarely
threatens physical health, it can take a heavy psychological
toll, bringing on depression, anxiety and debilitating
feelings of inadequacy. Unfortunately, it is a problem oen
neglected by the healthcare team who strive more with the
technical and more medically manageable aspects of the
patient’s illness.[5]
Sexual dysfunction is more prevalent in males than in
females and thus, it is conventional to focus more on male
sexual diculties. It has been discovered that men between
17 and 96 years could suer sexual dysfunction as a result
of psychological or physical health problems. Generally,
a prevalence of about 10% occurs across all ages. Because
sexual dysfunction is an inevitable process of aging, the
prevalence is over 50% in men between 50 and 70 years of age.
As men age, the absolute number of Leydig cells decreases
by about 40%, and the vigour of pulsatile lutenizing hormone
release is dampened. In association with these events, free
testosterone level also declines by approximately 1.2%
per year. These have contributed in no small measure to
prevalence of sexual dysfunction in the aged.
Male sexual dysfunction (MSD) could be caused by
various factors. These include: Psychological disorders
(performance anxiety, strained relationship, depression,
stress, guilt and fear of sexual failure), androgen deciencies
(testosterone deficiency, hyperprolactinemia), chronic
medical conditions (diabetes, hypertension, vascular
insufficiency (atherosclerosis, venous leakage), penile
disease (Peyronie’s, priapism, phinosis, smooth muscle
dysfunction), pelvic surgery (to correct arterial or inow
disorder), neurological disorders (Parkinson’s disease,
stroke, cerebral trauma, Alzheimer’s spinal cord or nerve
injury), drugs (side‑eects) (anti‑hypertensives, central
agents, psychiatric medications, antiulcer, anti-depressants
and anti-androgens), life style (chronic alcohol abuse,
cigaree smoking), ageing (decrease in hormonal level
with age) and systemic diseases (cardiac, hepatic, renal
pulmonary, cancer, metabolic, post-organ transplant).[4]
Sexual dysfunction takes different forms in men.
A dysfunction can be life-long and always present, acquired,
situational, or generalized, occurring despite the situation.
A man may have a sexual problem if he:
• Ejaculates before he or his partner desires
• Does not ejaculate, or experiences delayed ejaculation
• Is unable to have an erection sucient for pleasurable
intercourse
• Feels pains during intercourse
• Lacks or loses sexual desire.
MSD can be categorized as disorders of desire, disorders
of orgasm, ED and disorders of ejaculation and failure of
detumescence.
Disorders of Desire
Disorders of desire can involve either a deficient or
compulsive desire for sexual activity. Dysfunctions that can
occur during the desire phase include:
i. Hypoactive sexual desire (HSD) dened as persistently
or recurrently decient (or absent) sexual fantasy and
desire for sexual activity leading to marked distress
or interpersonal diculty. It results in a complete or
almost complete lack of desire to have any type of sexual
relation.
ii. Compulsive sexual behaviours (CSBs) constitute a
wide range of complex sexual behaviours that have
strikingly repetitive, compelling or driven qualities.
They usually manifest as obsessive‑compulsive sexuality
(e.g., excessive masturbation and promiscuity), excessive
sex-seeking in association with affective disorders
(e.g., major depression or mood disorders), addictive
sexuality (e.g., aachment to another person, object,
or sensation for sexual gratication to the exclusion of
everything else) and sexual impulsivity (failure to resist
an impulse or temptation for sexual behaviour that is
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy | April-June 2012 |
111
harmful to self or others such as exhibitionism, rape or
child molestation).[6]
Erectile Dysfunction
This is a problem with sexual arousal. ED can be dened
as the diculty in achieving or maintaining an erection
sufficient for sexual activity or penetration, at least
50% of the time, for a period of six months. It results in
signicant psychological, social and physical morbidity,
and annihilates his essence of masculinity.[7]
Disorders of Ejaculation
There exists a spectrum of disorders of ejaculation ranging
from mild premature to severely retard or absent ejaculation.
DIagNOsIs
Epidemiology and Risk Factors
Erection is a neurovascular phenomenon under hormonal
control. It includes arterial dilatation, trabecular smooth
muscle relaxation and activation of the corporeal veno-
occlusive mechanism.
ED has been dened as the persistent inability to aain and
maintain an erection sucient to permit satisfactory sexual
performance. Although ED is a benign disorder, it aects
physical and psychosocial health and has a signicant
impact on the quality of life (QoL) of suerers and their
partners and families.[8]
Epidemiology
Recent epidemiological data have shown a high prevalence
and incidence of ED worldwide. The first large scale,
community‑based study of ED was the Massachusetts
Male Aging Study (MMAS). The study reported an overall
prevalence of 52% ED in non‑institutionalized 40‑ to 70‑year‑
old men in the Boston area in the USA; specic prevalences
for minimal, moderate and complete ED were 17.2%, 25.2%
and 9.6%, respectively. In the Cologne study of men aged
30‑80 years old, the prevalence of ED was 19.2%, with a steep
age-related increase from 2.3% to 53.4%.[9] In the National
Health and Social Life Survey (NHSLS), the prevalence
of sexual dysfunctions (not specic ED) was 31%. The
incidence rate of ED (new cases per 1000 men annually)
was 26 in the MMAS study, 65.6 (mean follow‑up of 2 years)
in a Brazilian study and 19.2 (mean follow-up of 4.2 years)
in a Dutch study. Dierences between these studies can be
explained by dierences in methodology and in the ages
and socio-economic status of the populations studied.
Risk factors
ED shares common risk factors with cardiovascular
disease (e.g., lack of exercise, obesity, smoking,
hypercholesterolaemia, metabolic syndrome), some of
which can be modied. In the MMAS, men who began
exercising in midlife had a 70% reduced risk for ED
compared to sedentary men and a significantly lower
incidence of ED over an 8‑year follow‑up period of regular
exercise. A multicentre, randomised, open label study in
obese men with moderate ED compared 2 years of intensive
exercise and weight loss with a control group given general
information about healthy food choices and exercise.[10]
Signicant improvements in body mass index (BMI) and
physical activity scores, as well as in erectile function, were
observed in the lifestyle intervention group. These changes
were highly correlated with both weight loss and activity
levels. However, it should be emphasized that controlled
prospective studies are necessary to determine the eects
of exercise or other lifestyle changes in prevention or
treatment of ED.
Post‑radical Prostatectomy Erectile Dysfunction
Radical prostatectomy (RP) in any form (open, laparoscopic
or robotic) is a widely performed procedure for patients
with clinically localized prostate cancer (PCa) and a life
expectancy of at least 10 years. This procedure may lead to
treatment‑specic sequelae aecting health‑related QoL.
This outcome has become increasingly important with
the more frequent diagnosis of PCa in younger patients.
Research has shown that about 25-75% of men experience
post‑operative ED. Post‑RP ED is multifactorial. Cavernosal
nerve injury induces pro-apoptotic (loss of smooth muscle)
and pro‑brotic (increase in collagen) factors within the
corpora cavernosa. These changes may also be caused by
poor oxygenation due to changes in the blood supply to
the cavernosa. Because pre-operative potency is a major
factor associated with the recovery of erectile function
aer surgery, patients being considered for a nerve‑sparing
radical prostatectomy (NSRP) should ideally be potent. It
is also clear that cavernosal nerves must be preserved to
ensure erectile function recovers aer RP. In addition, the
role of vascular insuciency is of increasing interest in
post‑operative ED.[11]
Advances in basic and clinical research in ED during the
past 15 years have led to the development of several new
treatment options for ED, including new pharmacological
agents for intracavernous, intraurethral, and, more
recently, oral use. Treatment strategies have also changed
following the poor outcomes seen in long-term follow-up of
reconstructive vascular surgery.[12] An increasing number of
men are seeking help for ED due to the great media interest
in ED and the availability of eective and safe oral drug
therapy. However, there are many physicians evaluating
and treating ED without appropriate background
knowledge and clinical experience. Thus, some men with
ED may receive lile or no evaluation before treatment
and will therefore not receive treatment for any underlying
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy
| April-June 2012 | 112
disease that may be causing their ED. Other men without
ED may be requesting treatment simply to enhance their
sexual performance. Given this situation, these European
Association of Urology guidelines for the diagnosis and
treatment of ED are a necessity [Figure 1].
Treatment of Erectile Dysfunction
The primary goal in the management strategy of a patient
with ED is to determine the aetiology of the disease and
treat it when possible, and not to treat the symptom alone.
ED may be associated with modiable or reversible factors,
including lifestyle or drug‑related factors. These factors may
be modied either before, or at the same time as, specic
therapies are used.
As a rule, ED can be treated successfully with current
treatment options, but cannot be cured. The only exceptions
are psychogenic ED, post‑traumatic arteriogenic ED in
young patients and hormonal causes (e.g., hypogonadism,
hyperprolactinaemia), which can be potentially cured with
specic treatment. Most men with ED will be treated with
treatment options that are not cause‑specic. This results
in a structured treatment strategy that depends on ecacy,
safety, invasiveness and cost, as well as patient preference.
[13]
To counsel patients properly with ED, physicians must be
fully informed of all treatment options. The assessment
of treatment options must consider the eects on patient
and partner satisfaction and other QoL factors as well as
ecacy and safety.
Lifestyle Management in Erectile Dysfunction with
Concomitant Risk Factors
The basic work‑up of the patient must identify reversible
risk factors for ED. Lifestyle changes and risk factor
modication must precede or accompany ED treatment. The
potential benets of lifestyle changes may be particularly
important in individuals with ED and specic comorbid
cardiovascular or metabolic diseases, such as diabetes
or hypertension.[14] Besides improving erectile function,
aggressive lifestyle changes may also benefit overall
cardiovascular and metabolic health, with recent studies
supporting the potential of lifestyle intervention to benet
both ED and overall health. Although further studies are
needed to make clear the role of lifestyle changes in the
management of ED and related cardiovascular disease,
lifestyle changes can be recommended alone or combined
with Phosphodiesterease (PDE5) therapy. Some studies have
suggested that the therapeutic eects of PDE5 inhibitors
Figure 1: Managing ED: Implications for everyday clinical practice
Patient with Erectile Dysfunction (self-reported)
Medical and psychosexual history (use of validated instruments e.g. IIEF)
Focused Physical Examination
Laboratory tests
Identity other than
ED sexual products
Identity common
causes of ED
Identity reversible
risk factors for ED
Assess psychological
status
Penile deformitiesProstatic disease Signs of
hypogonadism
Cardiovascular and
neurological status
Glucose lipid profile
(if not assessed in the last 12 months)
Total testosterone (morning sample)
If available: Bio-available or free
testosterone
(instead of total)
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy | April-June 2012 |
113
may be enhanced when other comorbidities or risk factors
are aggressively managed. However, these results have
yet to be conrmed in well‑controlled, long‑term studies.
Because of the success of pharmacological therapy for ED,
clinicians need to provide specic evidence for the benets
of lifestyle change and hopefully future research will show
this.
Erectile Dysfunction aer Radical Prostatectomy
Use of pro-erectile drugs following RP is very important in
achieving erectile function following surgery. Several trials
have shown higher rates of erectile function recovery aer RP
in patients receiving any drug (therapeutic or prophylactic)
for ED. Historically, the treatment options for post‑
operative ED included intracavernous injections, urethral
microsuppository, vacuum device therapy and penile
implants. Intracavernous injections and penile implants
are still suggested as second- and third-line treatments,
respectively, when oral compounds are not adequately
eective or contraindicated for post‑operative patients.
The management of post‑RP ED has been revolutionized
by the advent of PDE5 inhibitors, with their demonstrated
ecacy, ease of use, good tolerability, excellent safety,
and positive impact on QoL. At present, PDE5 inhibitors
are the rst‑line choice of oral pharmacotherapy for post‑
RP ED in patients who have undergone a nerve‑sparing
(NS) surgical approach. The choice of PDE5 inhibitors as
rst‑line treatment is controversial because the experience
(surgical volume) of the surgeon is a key factor in preserving
postoperative erectile function in addition to patient age and
NS technique.[15] In fact, PDE5 inhibitors are most eective
in patients who have undergone a rigorous NS procedure,
which is more commonly performed by the largest-volume
surgeons. The early use of a high dose of sildenal aer RP
is associated with the preservation of smooth muscle within
the human corpora cavernosa. Daily sildenal also resulted
in a greater return of spontaneous normal erectile function
post RP compared to placebo following bilateral nerve-
sparing RP (NSRP) in patients who were fully potent before
surgery. The response rate to sildenal treatment for ED
aer RP in dierent trials ranged from 35% to 75% among
those who underwent NSRP and from 0% to 15% among
those who underwent non-NSRP.[16] The eectiveness of
both tadalal and vardenal as on‑demand treatment has
also been evaluated in post‑RP ED:
• A large multicentre trial in Europe and USA studied
tadalal in patients with ED following a bilateral NS
procedure. Erectile function was improved in 71% of
patients treated with tadalal 20 mg versus 24% treated
with placebo, while the rate of successful intercourse
aempts was 52% with tadalal 20 mg versus 26% with
placebo
• Similarly, vardenal has been tested in patients treated
with ED following either an unilateral or bilateral
NS procedure in a multicentre, prospective, placebo-
controlled, randomised North American study.[17]
Following bilateral NSRP, erectile function improved
by 71% and 60% with vardenal, 20 mg and 10 mg,
respectively. An extended analysis of the same patients
undergoing NSRP has underlined the benet of vardenal
compared to placebo regarding intercourse satisfaction,
hardness of erection, orgasmic function and overall
satisfaction with sexual experience. A randomized,
double-blind, double-dummy, multicentre, parallel-
group study in 87 centres across Europe, Canada, South
Africa and the USA, compared on- demand and nightly
dosing of vardenal in men with ED following bilateral
NSRP. In patients whose IIEF erectile function domain
(IIEF‑EF) score was ≥26 before surgery, vardenafil
was ecacious when used on demand, supporting a
paradigm shi towards on‑demand dosing with PDE5
inhibitors in post‑RP ED. Patients who do not respond
to oral PDE5 inhibitors aer NSRP should be treated
with prophylactic intracorporeal alprostadil. A penile
prosthesis remains a satisfactory approach for patients
who do not respond to either oral or intracavernous
pharmacotherapy or to a vacuum device.[18]
Curable Causes of Erectile Dysfunction
Hormonal causes
An endocrinologist’s advice is essential for managing
patients with hormonal abnormalities. Testosterone
deficiency is either a result of primary testicular
failure or secondary to pituitary/hypothalamic causes,
including a functional pituitary tumour resulting in
hyperprolactinaemia. Testosterone replacement therapy
(intramuscular, oral or transdermal) is effective, but
should only be used aer other endocrinological causes
for testicular failure have been excluded. Testosterone
replacement is contraindicated in men with a history
of prostate carcinoma or with symptoms of prostatism.
Before initiating testosterone replacement, a digital rectal
examination (DRE) and serum Prostate‑specic antigen
test should be performed. Patients given androgen
therapy should be monitored for clinical response and
the development of hepatic or prostatic disease. There is
no contraindication for testosterone therapy in men with
coronary artery disease who have been properly diagnosed
with hypogonadism and/or ED. However, the haematocrit
level should be monitored and a dose adjustment of
testosterone may be necessary, especially in congestive
heart failure. Hormonal treatment is not always eective in
the management of ED associated with hypogonadism.[19]
Post‑traumatic arteriogenic ED in young patients
In young patients with pelvic or perineal trauma, surgical
penile revascularization has a 60‑70% long‑term success rate.
The lesion must be demonstrated by Duplex ultrasound and
conrmed by penile pharmacoarteriography. Corporeal
veno-occlusive dysfunction is a contraindication to
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy
| April-June 2012 | 114
revascularization and must be excluded by dynamic
infusion cavernosometry or cavernosography. Vascular
surgery for veno-occlusive dysfunction is no longer
recommended because of poor long-term results.[20]
Psychosexual counselling and therapy
For patients with a significant psychological problem,
psychosexual therapy may be given either alone or with
another therapeutic approach. Psychosexual therapy takes
time and has had variable results.
First‑line Therapy
Oral pharmacotherapy
The PDE5 enzyme hydrolyzes cyclic guanosine
monophosphate (cGMP) in the cavernosum tissue
of the penis. Inhibition of PDE5 results in increased
arterial blood ow leading to smooth muscle relaxation,
vasodilatation and penile erection. Three potent selective
PDE5 inhibitors have been approved by the European
Medicines Agency (EMEA) and the US Food and Drug
Administration (FDA) for treatment of ED. They are not
initiators of erection and require sexual stimulation to
facilitate an erection.
Sildenal
Sildenal, launched in 1998, was the rst PDE5 inhibitor
available on the market. Ecacy is dened as an erection
with rigidity sucient for vaginal penetration. Sildenal is
eective from 30 to 60 min aer administration. Its ecacy
is reduced after a heavy fatty meal due to prolonged
absorption. It is administered in 25, 50 and 100 mg doses.
The recommended starting dose is 50 mg and should be
adapted according to the patient’s response and side‑eects.
Ecacy may be maintained for up to 12 h. Adverse events
are generally mild in nature and self-limited by continuous
use. The drop‑out rate due to adverse events is similar to
placebo. Aer 24 weeks in a dose‑response study, improved
erections were reported by 56%, 77% and 84% of men taking
25, 50 and 100 mg of sildenal, respectively, compared
to 25% of men taking placebo. Sildenafil statistically
improved patient scores in IIEF, sexual encounter prole 2
(SEP2), SEP3 and general assessment question (GAQ) and
treatment satisfaction. The ecacy of sildenal in almost
every subgroup of patients with ED has been successfully
established. In diabetic patients, 66.6% reported improved
erections (GAQ) and 63% successful intercourse aempts
compared to 28.6% and 33% of men taking placebo,
respectively.[21]
Tadalal
Tadalal, licenced for the treatment of ED as of February
2003, is eective from 30 min aer administration, with
peak ecacy aer about 2 h. Ecacy is maintained for up to
36 h and is not aected by food. It is administered in 10 and
20 mg doses. The recommended starting dose is 10 mg and
should be adapted according to the patient’s response and
side‑eects. Adverse events are generally mild in nature,
self‑limited by continuous use. The drop‑out rate due to
adverse events is similar to placebo.[22]
Vardenal
Vardenal, commercially available as of March 2003, is
effective from 30 min after administration. Its effect is
reduced by a heavy fay meal (>57% fat). It is administered
in 5, 10 and 20 mg doses. The recommended starting dose
is 10 mg and should be adapted according to the patient’s
response and side‑eects. In vitro, it is 10-fold more potent
than sildenal, though this does not necessarily mean
greater clinical ecacy. Adverse events are generally mild in
nature and self-limited by continuous use, with a drop-out
rate similar to placebo. Aer 12 weeks in a dose‑response
study, improved erections were reported by 66%, 76% and
80% of men taking 5 mg, 10 mg and 20 mg of vardenal,
respectively, compared with 30% of men taking placebo.
Vardenal statistically improved patient scores for IIEF,
SEP2, SEP3 and GAQ and treatment satisfaction. Ecacy
was confirmed in post-marketing studies. Vardenafil
improved erections in difficult‑to‑treat subgroups. In
diabetic patients, 72% reported improved erections (i.e.,
improved GAQ) compared to 13% of patients taking placebo
and the nal IIEF‑EF score was 19 compared to 12.6 for
placebo.[23]
Choice or Preference between the Different PDE5
Inhibitors
To date, no data are available from double‑ or triple‑blind
multicentre studies comparing the ecacy and/or patient
preference for sildenal, tadalal and vardenal. Choice of
drug will depend on the frequency of intercourse (occasional
use or regular therapy, 3-4 times weekly) and the patient’s
personal experience. Patients need to know whether a drug
is short- or long-acting, possible disadvantages and how
to use it.
On‑demand or Chronic Use of PDE5 Inhibitors
Animal studies have shown that chronic use of PDE5
inhibitors improves or prevents significantly the
intracavernous structure alterations due to age, diabetes
or surgical damage. In humans, a randomised study
(n=145) showed that daily tadalal led to a signicantly
higher IIEFEF score and higher completion of successful
intercourse aempts compared to on‑demand tadalal.
Two major double‑blind randomised studies, using daily
5 and 10 mg tadalal for 12 weeks (n=268)[24] and daily
2.5 and 5 mg tadalal for 24 weeks (n=286), showed that
daily dosing was well tolerated and signicantly improved
erectile function. However, these studies lacked an on-
demand treatment arm. An open-label extension was
carried out of both studies in 234 patients for 1 year and
238 patients for 2 years. Tadalal, 5 mg once daily, was
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy | April-June 2012 |
115
shown to be well tolerated and eective. Tadal, 5 mg
once daily, therefore provides an alternative to on-demand
dosing of tadalal for couples who prefer spontaneous
rather than scheduled sexual activities or who anticipate
frequent sexual activity, with the advantage that dosing
and sexual activity no longer need to be temporally linked.
Nevertheless, in the 1-year open-label 5 mg tadalafil
extension study followed by 4 weeks of wash-out, erectile
function was not maintained after discontinuation of
therapy in most patients (about 75%). A double-blind,
placebo-controlled, multicentre, parallel-group study
was conducted in 236 men with mild‑to‑moderate ED
randomised to receive once‑daily vardenal 10 mg plus
on-demand placebo for 12 or 24 weeks, or once-daily
placebo plus on‑demand vardenal 10 mg for 24 weeks,
followed by 4 weeks of wash-out. Despite preclinical
evidence, the results suggested that once-daily dosing
of vardenal 10 mg does not oer any sustainable eect
after cessation of treatment compared to on-demand
administration in patients with mild‑to‑moderate ED.
Other studies (open-label, randomised, cross-over studies
with limited patient numbers) showed that chronic, but
not on‑demand, tadalal treatment improved endothelial
function with sustained eect aer its discontinuation. This
was conrmed in another study of chronic sildenal in men
with type 2 diabetes. Recently, in the rst double‑blind
placebo-controlled study, enrolling 298 men with diabetes
and ED for 12 weeks, once‑daily tadalal 2.5 mg and 5 mg
was ecacious and well tolerated. This regimen provides
an alternative to on-demand treatment for some diabetic
men. However, when patients have the choice, it seems that
they prefer on-demand rather than continuous therapy.[25]
Nitric Oxide Donors
Nitric oxide (NO) is a physiologic signal essential to penile
erection, and disorders that reduce NO synthesis or release
in the erectile tissue are commonly associated with erectile
dysfunction. NO synthase (NOS) catalyzes production
of NO from L-arginine.[26] While both constitutively
expressed neuronal NOS (nNOS) and endothelial NOS
(eNOS) isoforms mediate penile erection, nNOS is widely
perceived to predominate in this role. Demonstration
that blood‑ow‑dependent generation of NO involves
phosphorylative activation of penile eNOS challenges
conventional understanding of NO-dependent erectile
mechanisms. Regulation of erectile function may not be
mediated exclusively by neurally derived NO. Blood-
ow‑induced uid shear stress in the penile vasculature
stimulates phosphatidyl-inositol 3-kinase to phosphorylate
protein kinase B, which in turn phosphorylates eNOS
to generate NO. There are many herbal drugs that have
been used by men for ED with varying degrees of success.
Most potent herbal aphrodisiacs are available and have
lile or very lile side eects [Table 1]. Thus, nNOS may
initiate cavernosal tissue relaxation, while activated
eNOS may facilitate attainment and maintenance of
full erection.
1. L-arginine
2. Nitroglycerin paste
3. Paroxetine (NOS inhibitor)
Other Oral Agents
Several other drugs have been used in the treatment of ED
with various mechanisms of action,[27] but today there is no
place for these drugs in the treatment of ED.
Table 1: Herbal approaches in the treatment of erectile dysfunction
Name of plant Common name Family Part used Reference
Allium sativum L. Garlic Liliaceae Bulb [30]
Asparagus racemosus Willd. Asparagus Liliaceae Root [31]
Boerhavia diffusa L. Punarnava Nyctaginaceae Root [32]
Chlorophytum tuberosum Baker. Safed musli Liliaceae Whole plant [33]
Cocculs cardifolia Linn. Guduchi Menispermaceae Stem, leaf, root [34]
Fadogia agrestis Schweinf. Ex Heim Black aphrodisiac Rubiaceae Stem [35]
Myristica fragrans Houtt Nutmeg Myristicaceae Seed [36]
Panax ginseng Ginseng Araliaceae Root [37]
Turnera aphrodisiaca Damiana Trneraceae Areal part [38]
Withania somnifera Linn. Ashwagandha Solanaceae Leaf, root [39]
Pausinystalia yohimbe Yohimbine Rubiaceae Bark [40]
Ginkgo biloba Ginkgo Ginkgoaceae Leaves, seeds [41]
Tribulus terristeris Caltrop Zygophyllaceae Seeds [42‑44]
Asphaltum bitumen Shilajit – Pitch [45]
Mucuna pruriens Kapi kacchu Fabaceae Seed [46]
Asparagus racemosus Shatawari Liliaceae Root [47]
Erythroxylem catuaba Catuaba Erythroxylaceae Bark [48]
Ipomoea digitata Vidari kandha Convolvulaceae Root [49]
Anacyclus pyrethrum Akarakarabha Compositae Root [50,51]
Allium tuberosum Chienese chive Zingiberaceae Seed [52,53]
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy
| April-June 2012 | 116
• Yohimbine is a centrally and peripherally active alpha‑2
adrenergic antagonist used as an aphrodisiac for almost
a century.
• Delequamine is a more specic and selective alpha‑2
adrenergic antagonist than yohimbine.
• Trazodone is a serotonin reuptake inhibitor (anti‑
depressant) associated with prolonged erections and
priapism. It is also a non‑selective alpha‑adrenergic
antagonist in the corporal smooth muscle cells.
• L‑arginine is a nitric oxide donor and nalmefene/
naltrexone is an opioid-receptor antagonist.
• Red Korea ginseng is a formulation with an unknown
mechanism of action (though it may possibly act as a
nitric oxide donor).[28]
• Limaprost is an alprostadil derivative for oral use.
• An oral formulation of phentolamine (non‑selective
alpha‑adrenergic antagonist) has undergone phase III
clinical trials. Randomised trials have shown that
yohimbine and trazodone have a similar ecacy to
placebo in patients with organic causes of ED (99). Oral
phentolamine had ecacy rates (erections sucient for
intercourse) of about 50%, but possible carcinogenesis in
animal models stopped further development. Ecacy
data on Red Korea ginseng suggested it might have a
role in treatment of ED.[29] There are no ecacy data on
the other drugs listed above.
CONClUsION
Sexual function is an important component of quality of life
and essential for subjective well being in humans. Sexual
problems are widespread and adversely aect mood, well
being and interpersonal functioning. Sexual problems are
related to sexual desire and male erectile dysfunction.
Successful treatment of sexual dysfunction may improve
not only sexual relationships, but also the overall quality
of life. Thus, this review has dealt with various approaches
by which the screening of medicinal plants can be achieved.
This is very important because of the side‑eects associated
with other treatment options and the readily availability of
medicinal plants; now that the world is fast turning into the
use of medicinal plants for managing sexual dysfunctions.
Moreover, the side-effects occur through the use of
allopathic drugs may limit the use of such drugs; therefore,
the use of herbal drugs can be used as an alternative as there
are less side eects in herbal medications.
RefeReNCes
1. Ackerman M, Rajiah K, Veettil SK, Kumar S, Mathew EM.
Impotence: Help for Erectile Dysfunction Patient Care. Victoria
Island, Lagos: Scientic Research and Essays; 1994. p.22‑56.
2. Mulligan T. Geriatric Sexual Dysfunction: A Rational Approach to
a Sensitive Topic. 730 East Broad Street P.O. Box 980229 Richmond,
VA 23298‑0229: Virginia Geriatric Education Center; 1990.
3. Kahn J. Smoking May Increase Risk of Impotence Medical Tribune.
Am J Epidemiol 1995;5:19.
4. Guay AT, Spark RF, Bansal S, Cunningham GR, Goodman NF,
Nankin HR, et al. American Association of Clinical Endocrinologists
medical guidelines for clinical practice for the evaluation and
treatment of male sexual dysfunction: A couple’s problem–2003
update. Endocr Pract 2003;9:77‑95.
5. Salmon PH. Psychosexual dysfunction in chronic renal failure: An
overview. Proc EDTNA. Pharmacogn Rev 1983;12:209‑12.
6. Kaplan HS. Erotic obsession: Relationship to hypoactive sexual desire
disorder and paraphilia. Am J Psychiatry 1996;153(7 Suppl):30‑41.
7. Bosch RJ, Benard F, Aboseif SR, Stief CG, Lue TF, Tanagho EA.
Penile detumescence: Characterization of three phases. J Urol
1991;146:867‑71.
8. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ,
McKinlay JB. Impotence and its medical and psychosocial
correlates: Results of the Massachuses Male Aging Study. J Urol
1994;151:54‑61.
9. Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M,
Engelmann U. Epidemiology of erectile dysfunction: Results of
the ‘Cologne Male Survey’. Int J Impot Res 2000;12:305‑11.
10. Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB,
McKinlay JB. Modiable risk factors and erectile dysfunction: Can
lifestyle changes modify risk. Urology 2000;56:302‑6.
11. Mulhall JP, Slovick R, Hotaling J, Aviv N, Valenzuela R,
Waters WB, et al. Erectile dysfunction aer radical prostatectomy:
Hemodynamic proles and their correlation with the recovery of
erectile function. J Urol 2002;167:1371‑5.
12. Wespes E, Schulman C. Venous impotence: Pathophysiology,
diagnosis and treatment. J Urol 1993;149:1238-45.
13. Hatzichristou D, Rosen RC, Broderick G, Clayton A, Cuzin B,
Derogatis L, et al. Clinical evaluation and management strategy
for sexual dysfunction in men and women. J Sex Med 2004;1:49-57.
14. Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB,
McKinlay JB. Modiable risk factors and erectile dysfunction: Can
lifestyle changes modify risk. Urology 2000;56:302‑6.
15. Bianco F, Kaan M, Eastham J, Scardino PT, Mulhall JP. Surgeon
and surgical volume as predictors of erectile function outcomes
following radical prostatectomy. J Sex Med 2004;1:34.
16. Padma‑Nathan H, McCullough AR, Levine LA, Lipschultz LI,
Siegel R, Montorsi F, et al. Randomized, double-blind, placebo-
controlled study of postoperative nightly sildenal citrate for the
prevention of erectile dysfunction aer bilateral nerve‑sparing
radical prostatectomy. Int J Impot Res 2008;20:479‑86.
17. Brock G, Nehra A, Lipshultz LI, Karlin GS, Gleave M, Seger M,
et al. Safety and ecacy of vardenal for the treatment of men
with erectile dysfunction aer radical retropubic prostatectomy.
J Urol 2003;170:1278-83.
18. Montague DK. Penile prosthesis implantation for end-stage erectile
dysfunction aer radical prostatectomy. Rev Urol 2005;7 Suppl
2:S51-7.
19. Morales A, Heaton JP. Hormonal erectile dysfunction. Evaluation
and management. Urol Clin North Am 2001;28:279-88.
20. Wespes E, Wildschutz T, Roumeguere T, Schulman CC. The place
of surgery for vascular impotence in the third millennium. J Urol
2003;170:1284‑6.
21. Stuckey BG, Jadzinsky MN, Murphy LJ, Montorsi F, Kadioglu A,
Fraige F, et al., Deerochanawong C. Sildenal citrate for treatment
of erectile dysfunction in men with type 1 diabetes: Results of a
randomized controlled trial. Diabetes Care 2003;26:279‑84.
22. Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins V,
et al. Ecacy and safety of tadalal for the treatment of erectile
dysfunction: Results of integrated analyses. J Urol 2002;168:1332‑6.
23. Goldstein I, Young JM, Fischer J, Bangerter K, Segerson T,
Taylor T. Vardenal, a new phosphodiesterase type 5 inhibitor,
in the treatment of erectile dysfunction in men with diabetes:
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal

Saxena, et al.: Erectile dysfunction
International Journal of Green Pharmacy | April-June 2012 |
117
A multicenter double‑blind placebo‑controlled xed‑dose study.
Diabetes Care 2003;26:777‑83.
24. Porst H, Giuliano F, Glina S, Ralph D, Casabé AR, Elion‑
Mboussa A, et al. Evaluation of the ecacy and safety of once‑a‑
day dosing of tadalal 5 mg and 10 mg in the treatment of erectile
dysfunction: Results of a multicenter, randomized, double-blind,
placebo‑controlled trial. Eur Urol 2006;50:351‑9.
25. Mirone V, Costa P, Damber JE, Holmes S, Moncada I, Van
Ahlen H, et al. An evaluation of an alternative dosing regimen
with tadalal, 3 times/week, for men with erectile dysfunction:
SURE study in 14 European countries. Eur Urol 2005;47:846‑54;
discussion 854.
26. Burne AL. Novel nitric oxide signaling mechanisms regulate the
erectile response. Int J Impot Res 2004;16 Suppl 1:S15‑9.
27. Padma‑Nathan H, Christ G, Adaikan G, Becher E, Brock G,
Carrier S, et al. Pharmacotherapy for erectile dysfunction. J Sex
Med 2004;1:128-40.
28. Hong B, Ji YH, Hong JH, Nam KY, Ahn TY. A double‑blind
crossover study evaluating the ecacy of korean red ginseng in
patients with erectile dysfunction: A preliminary report. J Urol
2002;168:2070‑3.
29. Hong B, Ji YH, Hong JH, Nam KY, Ahn TY. A double‑blind
crossover study evaluating the ecacy of korean red ginseng in
patients with erectile dysfunction: A preliminary report. J Urol
2002;168:2070‑3.
30. Joy PP, Thomas J, Mathew S, Skaria PB, Medicinal Plants. Thrissur,
Kerala: Kerala Agricultural University, Aromatic and Medicinal
Plants Research Station; 1998.
31. Satyavati GV, Raina MK, Sharma M, Medicinal Plants of India.
Vol. 1. New Delhi: Ind. Council on Med. Res; 1976.
32. Jahan S, Rasool S, Khan MA, Ahmad M, Zafar M, Abbasi AM.
Antifertility eects of ethanolic seed extract of Abrus precatorius
L. on sperm production and DNA integrity in adult male mice.
Indian J Tradit Knowl 2005;4:317‑24.
33. Maiti S, Geetha KA. Horticulture Floriculture Medicinal and
Aromatic Plants in India; 2007.
34. Prasanth PR, Kumar A. Ethno‑medico botany of medicinal plants
for the treatment of diabetic activity in Krishna district, Andhra
Pradesh. Int J Pharm Res Dev 2008;9:1‑9.
35. Yakubu MT, Adewmi MA, Oladi TA. Male sexual dysfunction
and methods used in assessing medicinal plants with aphrodisiac
potentials. Res J Med Plants 2008;2:66‑73.
36. Sumalatha K, Kumar SA, Lakshmi SM. Review on Natural
Aphrodisiac potentials to treat Sexual dysfunction. Int J Pharm
Ther 2010;1:10‑8.
37. Nocerino E, Amato M, Izzo AA. The aphrodisiac and adaptogenic
properties of ginseng. Fitoterapia 2000;71 Suppl 1:S1‑5.
38. Kumar S, Madaan R, Sharma A. Evaluation of Aphrodisiac Activity
of Turnera aphrodisiaca, Int J Pharmacognosy Phytochem Res
2009;1:1-4.
39. Singh KP, Kumar V, Tiwari KR, Sharma A, Rao CV, Singh RH.
Medico‑Ethnobotany of 'Chatara' Block of District Sonebhadra,
Uar Pradesh, India. Adv Biol Res 2010;4:65‑80.
40. Fabricant SD, Farnsworth RN. The value of Plants Used in
Traditional Medicine for Drug Discovery. Environ Health Perspect
2001;109 Suppl 1:69‑75.
41. Welt K, Weiss J, Koch S, Fitzl G. Protective eects of Ginkgo
biloba extract EGb 761 on the myocardium of experimentally
diabetic rats. II. Ultrastructural and immunohistochemical
investigation on microvessels and interstitium. Exp Toxicol
Pathol 1999;51:213-22.
42. Available from: http://www.ayurhelp.com/plants/tribulus-
terrestris.htm. [Last accessed on 2011 Nov 4].
43. Gauthaman K, Adaikan PG, Prasad RN. Aphrodisiac properties of
Tribulus Terrestris extract (Protodioscin) in normal and castrated
rats. Life Sci 2002;71:1385‑96.
44. Tomova M, Gyulemetova R. Steroidsapogenine, Tribulus terrestris
Linn: A review article. Planta Med 1978;34:188-91.
45. Frotan MH, Acharya SB. Pharmacological studies of shilajit. Indian
J Pharmacol 1984;16:45.
46. Parekar S. Estrogenic activity of Mucuna pruriens in swiss albino
mice. Int Res J Pharm 2011;2:191‑3.
47. Available from: hp://www.science20.com/humboldt_fellow_
and_science/blog/asparagus_racemosus_willd_has_medicinal_
properties. [Last accessed on 2011 Nov 4].
48. Available from: hp://thamilar‑nalasevai.info/Media/healthcare/
Male‑Support_eng.pdf. [Last accessed on 2011 Nov 4].
49. Available from: hp://www.himalayahealthcare.com/herbnder/h_
ipomoea.htm. [last accessed on 2011 Nov 4].
50. Available from: hp://enchantingkerala.org/ayurveda/ayurvedic‑
medicinal plants/akkikaruka.php. [Last accessed on 2011 Nov 4].
51. Available from: hp://users.skynet.be/bertram.zambiafoundation/
Afbeeldingen/Literature_revue_Pyrethrum_root.pdf. [Last
accessed on 2011 Nov 4].
52. Guohua H, Yanhua L, Rengang M, Dongzhi W, Zhengzhi M,
Hua Z. Aphrodisiac properties of Allium tuberosum seeds extract.
J Ethnopharmacol 2009;122:579‑82.
53. Available from: http://www.inharmonyherbs.com/articles/95-
herbal-aphrodisiacs.html. [Last accessed on 2011 Nov 4].
How to cite this article: Saxena A, Prakash P, Porwal M, Sissodia N, Sharma
P. Erectile dysfunction: A review and herbs used for its treatment. Int J Green
Pharm 2012;6:109-17.
Source of Support: Nil, Conict of Interest: None declared.
Announcement
Android App
A free application to browse and search the journal’s content is now available for Android based
mobiles and devices. The application provides “Table of Contents” of the latest issues, which
are stored on the device for future offline browsing. Internet connection is required to access the
back issues and search facility. The application is compatible with all the versions of Android. The
application can be downloaded from https://market.android.com/details?id=comm.app.medknow.
For suggestions and comments do write back to us.
[Downloadedfreefromhttp://www.greenpharmacy.infoonMonday,October22,2012,IP:117.201.71.130]||ClickheretodownloadfreeAndroidapplicationforthis
journal