Sexual Dysfunction

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Review Article
Sexual Dysfunction: An Overview and Medicinal Plant used for
treatment of Sexual dysfunction
Ramandeep Singh*
, Sarabjeet Singh, G. Jeyabalan
,
Ashraf Ali, Alok Semwal
1
Department of Pharmacy, Sunrise University, Alwar, Rajasthan, India.
1
Department of Pharmacy, Himachal Institute of Pharmacy, Paonta Sahib (H.P)
ABSTRACT
Sexual dysfunction (SD) or male impotence is defined as the inability to have or sustain an erection long
enough to have a meaningful sexual intercourse. SD 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 SD
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. In this
oral drugs sildenafil citrate, vardenfil, tadalafil, alprostadil, phenotolamine injections are mainly inhibiting
the PDE5 and enhancing the penile erection and non pharmacological therapies vaccum therapy, surgery
(penile prosthesis), counseling also shows role in SD treatment, currently herbal medicines are shows
prominent role in SD patients. 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.
Keywords: Aphrodisiac, Sexual dysfunction, Phosphodiesterease, herbal drugs.
INTRODUCTION
Sexual dysfunction (SD or ED; Erectile dysfunction; or impotence) and premature
ejaculation (PE) are the two most prevalent complaints in male sexual dysfunction. Male
sexual dysfunction can be caused by physical or psychological problems. Sexual
dysfunction is defined as a difficulty in initiating or maintaining penile erection adequate
for sexual relations. A cause of this type of impotency includes psychological,
neurological, hormonal, and vascular pathologies, or combinations of these factors and
also some diseases, disorders or their treatment means drug induction. There are many
treatment strategies of sexual dysfunction. One of the novel strategies is use of
aphrodisiac herbs. An aphrodisiac is defined as any substance or activity that arouses
sexual interest and desire, increases pleasure and performance. The word ‘Aphrodisiac’ is
derived from ‘Aphrodite’, the Greek goddess of love and most of these substances are
derived from plants. Two main types of aphrodisiacs are psycho physiological stimuli
(visual, tactile, olfactory and aural) preparations and internal preparations (food,
alcoholic drinks and love portions). Management options of Male Sexual Dysfunction
include psychological/behavioral therapy with a trained counselor aimed at helping
CRITICAL REVIEW IN PHARMACEUTICAL SCIENCES
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people to address feelings of anxiety, fear and guilt that may have an impact on sexual
function; drug therapy that is use of testosterone replacement therapy for cases of
androgen insufficiency and other pharmacological agents; non surgical devices which
include vacuum pump (expands the penis and reduces pressure within the cavernous
sinusoidal space) and constrictive rings [1]. Fig.1-3 indicates causes of Sexual/erectile
dysfunction and its pathogencity.
Fig.1 Probable mechanism of pathogenesis of ED
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Fig.2 Pie digram represents various anatomical sites involved in SD/ED
Fig.3. Probable biochemical mechanism of erectile/Sexual dysfunction
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Male Sexual Dysfunction
Sex disorders of the male are classified
into disorders of sexual function, sexual
orientation and sexual behavior. 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 [2].
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 difficult 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 [3].
Sexual dysfunction is more prevalent in
males than in females and thus, it is
conventional to focus more on male
sexual difficulties. It has been
discovered that men between 17 and 96
years could suffer 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 deficiencies
(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 inflow disorder),
neurological disorders (Parkinson's
disease, stroke, cerebral trauma,
Alzheimer's spinal cord or nerve injury),
drugs (side-effects) (anti-hypertensives,
central agents, psychiatric medications,
antiulcer, anti-depressants and anti-
androgens), life style (chronic alcohol
abuse, cigarette smoking), ageing
(decrease in hormonal level with age)
and systemic diseases (cardiac, hepatic,
renal pulmonary, cancer, metabolic,
post-organtransplant)[2].
CAUSES OF MALE SEXUAL
DYSFUNCTION
• Problems in the relationship with the
sexual partner can lead to sexual
dysfunction.
• Lowered levels of the male hormone
testosterone (a condition known as
hypogonadism) can cause low libido or
ED.
• Certain drugs, such as antidepressants
and blood pressure medications, can
cause sexual dysfunction.
• Erectile function can be impaired by a
stroke or by nerve damage from diabetes
or surgery.
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• Disorders affecting blood vessels, such
as atherosclerosis (hardening of the
arteries) and high blood pressure, are
risk factors for ED.
• Other possible causes of sexual
dysfunction include smoking, obesity,
kidney problems, depression, anxiety
disorders, and alcoholism.
Main Type of male Sexual
Dysfunction
• Low libido (sexual interest)
• Erectile dysfunction (ED, difficulty
achieving or maintaining an erection)
• Premature ejaculation (reaching
orgasm [sexual climax] too quickly)
• Delayed or inhibited orgasm
• Physical abnormalities of the penis
Treating male Sexual
DysfunctionTING MALE SEXUAL
DYSFUNCTION
• For psychological causes of sexual
dysfunction, such as relationship
problems, counseling, either individually
or as a couple, may be beneficial. Sexual
therapy with a therapist who specializes
in sexual dysfunction may also help.
• Depression or anxiety disorders may
need treatment.
• Any physical problems that may be
affecting sexual function should be
addressed.
• If a medication is interfering with
sexual function, it may be possible to
change or discontinue the medication.
• Prescription medications that treat
erectile dysfunction may help a man
achieve and maintain erections.
• Hormonal treatment, such as
testosterone replacement therapy, may
help with hormone imbalances that are
contributing to sexual dysfunction [4].
EPIDEMIOLOGY
Erectile dysfunction is a common and
widespread health problem that affects
approximately 30
million men in US and in 1995 there
was an estimated projection of 152
million men world wide who
experienced ED [5]. If will rise to about
322 million men by the year 2025. The
ED increases with age and other
concomitant conditions like causes and
psychological parameters. The executive
committee of this conference believes
that the current prevalence data
regarding ED are strong, they see a need
for strengthening the incidence data [6].
The Massachusetts male aging study is
one of the pivotal studies on the
prevalence of ED or SD between 1987
and 1989, men between the ages of 40
and 70 years were asked to categorize
their sexual health [5].
ETIOLOGY
There are various and often multiple
underlying causes. Some of which are
treatable medical conditions. The most
important organic causes are
cardiovascular disease and diabetis,
neurological problems (for example,
trauma from prostatectomy surgery),
hormonal insufficiencies
(hypogonadism) and drug side effects.
ED mainly based on various causes as
psychogenic, organic (hormonal,
vascular, drug induced, or neurogenic)
or mixed psychogenic and organic [7].
Up to 80% of ED cases have an organic
origin. The most common cause of ED is
vascular disease in this coronary artery
disease, peripheral vascular disease,
hypertension, diabetis mellitus and
psychogenic, neurogenic and
multifactorial factors like aging, end-
stage renal disease pelvic trauma. Some
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drugs induced the ED mainly β-
blockers, calcium channel blockers,
alcohol, antidepressant, anti psychotic,
antiandrogens etc. Artherosclerosis is the
most common cause of vasculogenic
ED. Chronic tobacco use is a major risk
factor for the development of
vasculogenic ED because of its effects
on the vascular endothelium [8].
Additionally chronic illness, depression,
and lack of a sexual partners are all
prevalent in this age population. Some
sorts of surgery like radiation therapy,
surgery of the colon, prostate, bladder,
or rectum may damage the nerves and
blood vessels involved in erection.
Prostate and bladder cancer surgery
often require removing tissue and nerves
surrounding a tumor which increases the
risk for impotence convernosal disorders
like peyronie’s diseases and ED causes
mainly hormonal deficiency pituitary
gland tumor, abnormally high levels of
the penis. Neurogenic disorders like
spinal cord and brain injuries, nerve
disorders such as parkinson’s disease,
alzheimer’s diseases, multiple sclerosis,
and stroke some evidence suggests that
smaller penis size is associated with
erectile dysfunction [9].
PATHOPHYSIOLOGY
Most basic and clinical studies of ED
have shown the condition to be caused
by a variety of
psychological and organic factors. Many
of these factors have a direct effect on
the central and peripheral mechanism of
action of erectile function. In this five
synergistic systems of penile erection are
cyclic guanosine monophosphate, cyclic
adenosine monophosphate, protein
kinases and potassium
channels,Generally penile erection is
managed by two different mechanisms
[6]. The first are is the reflex erection, it
is achieved by directly touching the
pencil shaft. The second is the
phychogenic erection, it is achieved by
erotic or emotional stimuli. Atrophy
owning to loss of Bd- 1 expression in
smooth muscle, and increased
connective tissue synthesis, due to TGF
beta, result in decreased compliance of
cavernosal tissue [10]. Both there
changes reduce with the gap junctions
and K+ channels in cavernosal smooth
muscle that are necessary for
coordinated relaxation of cavernosal
tissue [11]. In Peripheral mechanisms of
the penis mainly the signals from the
central nervous system influence the
balance between the contract and
relaxant factors that leads to stimulation
of penile shat [12]. and secretion of
nitric oxide (No), which causes the
relaxation of smooth muscles of corpora
cavernosa and subsequently penile
erection will occurs and additionally
adequate levels of testosterone and an
intact pituitary gland are require for the
development of a healthy erectile
system. α, me lanocyte, melanocortin
receptor, serotonin 5 HT
2
c receptors
stimulation are good therapeutic
alternations in the treatment of ED
[6,13]. In the normal erection impotence
may develop due to hormonal
deficiency, disorders of the neural
system, lack of adequate penile blood
supply or psychological problems. And
some diabetic patients apoptosis owing
to loss of BCT-2 expression in smooth
muscle, and increase connective tissue
synthesis, due to TGF beta, result is
decreased compliance of cavernosal
tissue [10, 14]. These changes reduce or
interfere with the gap junctions and K
channels in cavernosal smooth muscle
that are necessary for coordinated
relaxation of cavernosal tissue [13].
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CLINICAL MANIFESTATIONS
AND DIAGNOSIS
Physical Examination
The physical examination should include
a careful testicular examination to assess
testicular size,
asymmetries, presence of hernias, or
varicoceles. Additionally, a digital rectal
examination to assess the prostatic size,
consistency and presence of reduces in
warranted. Penile inspection and
palpation should be performed, with
special attention to possible fibrotic
plaques. Palpation and auscultation of
femoral arteries for possible bruits is
another important part of the
examination [15].
Medical Diagnosis
Erectile dysfunction diagnosis mainly
some blood tests are generally done to
exclude underlying
disease, such as diabetis, hypogonadism
and prolactinoma. Impotence is also
related to generally poor physical health,
poor dietary habits, obesity, and most
specially cardiovascular disease such as
coronary artery disease and peripheral
vascular disease.
Specific examinations and tests
Although most patients with SD can be
managed within the primary care setting,
some circumstances, presented in Table
1, require specific diagnostic testing [1].
Specific diagnostic tests are presented in
Table 2. [16]
Table 1 – Indications for specific
diagnostic tests
Patients with primary erectile
disorder (not caused by organic
disease or psychogenic disorder)
Young patients with a history of
pelvic or perineal trauma who
could benefit from potentially
curative vascular surgery.
Patients with penile deformities
(eg, Peyronie’s disease,
congenital curvature) that might
require surgical correction.
Patients with complex
psychiatric or psychosexual
disorders
Patients with complex endocrine
disorders
Specific tests may also be
indicated at the request of the
patient or his partner
For medicolegal reasons (eg,
penile prosthesis implant, sexual
abuse)
Table 2 – Specific diagnostic tests
Nocturnal penile tumescence and
rigidity using Rigiscan
Vascular studies
Intracavernous vasoactive drug
injection
Duplex ultrasound of the
cavernous arteries
Dynamic infusion
cavernosometry and
cavernosography
Internal pudendal arteriography
Neurologic studies (eg,
bulbocavernosus reflex latency,
nerve-conduction studies)
Endocrinologic studies
Specialised psychodiagnostic
evaluation
Clinical Management
Today there are many effective therapies
for the treatment of SD. First-line
therapies include oral
pharmacotherapy and psychosexual
therapy-second line therapies include
intra urethral and intracavernosal
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administration of vasoactive drugs,
vacuum devices and penile prostheses.
Vacuum devices can be used as first line
therapy for sexual dysfunction.
Pharmacological therapy
SD or ED can in many cases be treated
by drugs taken orally, injected or as
penile suppositories. There drugs
increase the efficacy of NO, which
dilates the blood vessels of corpora
cavernosa. Oral drugs or suppositories
less effective compare to injections into
the erectile tissue of the penile shaft are
extremely effective but occasionally
cause privapism. The first oral
medication for the treatment of ED was
sildenafil citrate (Viagra). Since then,
oral agents have become the preferred
mode of treatments by patients in
surveys world wide. There are three oral
agents that inhibit PDE5 currently on the
market. Those are sildenafil citrates
(Viagra), vardenfil (levitra), Tadalafil
(Cialis). These drugs inhibiting PDE5,
which maintains intracavernosal levels
of cGMP, subsequently producing
vasodilation and penile erection.
Sildenafil Citrate (Viagra)
Sildenafil citrate is a selective and potent
inhibitor of cyclic guanosine
monophosphate
(PDE5) that enhances penile erection to
sexual stimulation by the predominent
enzyme that metabolized cGMP in the
corpus cavernosum [17]. Since its
introduction in 1998, sildenafil has
gained worldwide acceptance as the
first-line treatment of erectile
dysfunction/Sexual dysfunction of
organic, psychogenic or mixed etiology
[7]. After oral administration the drug is
rapidly absorbed, with an appropriate
duration of therapeutic activity that is
convenient for most couples [18, 19].
Sildenafil significantly improves the
ability to achieve and maintain erections
and successfully engage in sexual
intercourse [20]. Sildenatil is safe and
efficacy in special subsets of patients,
including those with concomitant type-1
or type-2 diabetes treated hypertension
depression, end-stage renal disease
maintained with heamodialysis [21].
Vardenafil (Levitra)
Verdenafil is a highly potent inhibitor of
PDE5 [6]. It was approved for use in the
United States in late 2003. It is a more
selective PDE5 inhibitor than sildenafil
citrate (Viagra). The absorption of
vardenefil is delayed by a fatty content
of more than 30% in a male [15]. The
half life of vardenafil is 4.4 to 4.8 hours,
the first trial using the agent included
580 patients, excluding patients with
spinal cord injury, radical prostatectomy,
hypogonadism, thyrotoxicosis [13].
Tadalafil (Cialis)
Tadalafit is a selective inhibitor of
PDE5 with a long half-life [22]. It has
half life of 17.5 hours. The clinical onset
of action occurs in less than 1 hour.
There is no interaction between food and
alcohol on the absorption of the drug
[15]. Tadalafil associated with an
improvement in depressive symptoms
and quality of life is men with a
diagnosis of mild to moderate depression
according to a structured rating
interview for DSM-IV [23].
Apomorphine (Uprima)
Apomorphine (Uprima) is a potent
emetic that acts on central dopaminergic
receptors. The stimulation of central
dopeminergic receptors transmits
excitatory signals down the spinal cord
to the sacral parasympathetic nucleus,
stimulating activity of the sacral nerves
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supplying the penis. It was been used
successfully in up to 67% of patients
when administered through a sublingual
preparation. Subcutaneous injections of
apomorphine produce almost a 100%
erectile response, but nausea and
vomiting are limiting factors to this
mode of administration.
Alprostadil (Prostaglandin E1)
Alprostadil can be injected the penis or
inserted using a special application
usually just before sexual intercourse. It
has an onset of action of 10-15 minutes
and its effects can last over 4 hours.
Alprostadil (Prostaglandin E1)
mechanism mainly PGE1 binds to PGE
receptors and causes a relaxation
response medicated by cyclic adenosine
monophosphate (cAMP).
Trazodone (Desyrel)
Trazodone (Desyrel) is a serotonin
reuptake inhibiting agent. Its action in
ED is believed to be the result of central
serotonergic and peripheral α-
adrenolytic activity. Side effects include
drowsiness, insomnia, headaches, and
weight loss.
Phentolamine (Regitine)
Phentolemine is a injection is used to the
dysfunction. It is an α
1
-and α
2
adrenergic
receptor antagonist. The mechanism of
phentolamine is dearly corporal smooth
muscle relaxation, noradrenaline is the
primary determinant of cavernosal
smooth muscle contraction and it is
released of NA induced contraction over
NO-induced smooth muscle relaxation
may contribute to ED. It having some
adverse effects nasal congestion,
headaches, dizziness and tachycardia
[15, 24].
Non Pharmacological Therapy
Non pharmacological therapy mainly
who do not want pharmacological
intervention and they need vaccum
therapy, surgery and counseling. These
current therapies shows prominent role
in the treatment of sexual dysfunction.
Vacuum therapy
Vacuum therapy is second line therapy.
In this vacuum devices can be used as
first-line therapy is couples who do not
need pharmacological intervention and
are not appropriate for counseling. It is
working by placing the penis in a
vacuum cylinder device. The device
helps draw blood into the penis by
applying negative pressure. A tension
ring is applied at the base of the penis to
help maintain the erection. This type of
device is some lines referred to as penis
pump and may be used just prior to
sexual inter course.
Surgery (Penile prosthesis)
This surgical therapy used to be quite
common before the advent of oral
agents. The use of prostheses is still a
suitable alternative for those who are
unresponsive to less invasive treatments.
Prostheses can be classified as rod, one-
piece inflatable, two-piece inflatable,
and three piece inflatable which involves
the insertion of artificial rods in to the
pen’s (ED). Patients are usually satisfied
with the results of prosthetic placement.
Counseling
Counseling is often a consideration, both
where a psychological cause is suspected
or must be ruled out of to assist in
management of any distress.
Testosterone
Testosterone provides intra penile
nitrous oxide synthase (Nos), which has
an important role in enhancing the
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production of NO’ subsequent local
vasodilation, and penile erection. Oral
testosterone can reduce ED in some men
with low levels of natural testosterone,
but it is often, ineffective and may cause
liver damage [25].
Exercise: Particularly aerobic exercise is
an effective cheap treatment for erectile
dysfunction [26].
Herbal therapy
Despite of all the advances in modern
medicine, traditional medicine still plays
a significant role in the lives of many
people Sexual dysfunction, known
clinically as an inability to obtain or
maintain an erection. It is a medical
problem affecting young as well as old
men. Although a number of therapies
become available in the last two
decades, problems with costs, efficacy,
safety and case to administer were
experienced. The therapies ranged from
herbal remedies used by native healers,
these drugs based on physiological
mechanisms of erection Several
medicinal plants have always been
available and used to treat many
ailments including impotence. The
medicinal Plants having aphrodisiac
activity is given in Table 3.
Table.3 Aphrodisiac Plants
S. No. Plant Name Family Part Used Reference
1.
Asteracanta
longifolia
Acanthaceae Seeds 27
2.
Anacyclus
pyrethrum DC.
Compositae Roots 28
3.
Piper
guineense
Piperaceae Fruit 29
4.
Curculigo
orchioides
Gaertn.
Amaryllidaceae Rhizomes 30, 46
5.
Nymphaea
stellata
Nymphaeceae Leaves 31
6.
Passiflora
incarnate
Linn.
Passifloraceae Leaves 32
7.
Turnera
aphrodisiaca
Turneraceae Aerial parts 33
8.
Pedalium
murex (L.)
Pedaliaceae Roots 34
9.
Mimosa
Pudica Linn.
Mimosae Roots 35
10.
Blepharis
edulis Linn.
Acanthaceae Seeds 36
11.
Butea frondosa
Papilionaceae Bark 37
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Koen.ex Roxb.
12.
Myrisita
fragrans
Houtt.
Myristicaceae Kernel 38
13.
Chlorophytum
borivilianum
Liliaceae Root 39
14.
Ocimum
gratissimum
Lamiaceae Leaves 40
15.
Crocussativus
Iridaceae Stigma 41
16.
Tynanthus
panurensis
(Bur.) Sandw.
Bignoniaceae Bark, wood 42
17.
Vanda
tessellata
(Roxb.) Hook.
ex Don.
Orchidaceae Flower, Root 42
18.
Valeriana
jatamansi
Wall.
Valerianaceae Root 42
19.
Vanda
tessellata
Orchidaceae Flower 42
20.
Withania
somnifera
Linn.
Solanaceae Leaf, Root 42
21.
Bryonia
laciniosa
Cucurbitaceae Seeds 43
22.
Spilanthes
acmella (L.)
Murr.
Asteraceae Flower 44
23. Arctium lappa
L.
Compositae Roots 45
24.
Durio
zibenthinus
Linn.
Bombacaceae Fruit 47
25.
Abelmoschus
manihot (L.)
Malvaceae Seeds 48
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CONCLUSION
The review article focused on current
therapy on Sexual dysfunction. SD is the
inability to attain an erection sufficient
for satisfactory sexual performance.
Today there are many effective therapies
for treatment of SD. Sexual dysfunction
is also indicative of underlying
vasculopathy and represents a predictor
of more serious cardiovascular,
psychoactive disorders. In this first line
therapies include oral pharmacotherapy
and psycho sexual therapy. Second line
therapies include intraurethral and
intracavernosal administration of
vasoactive drugs, vaccum devices and
surgery (Penile prostheses). In the oral
therapy sildenafil citrate (Viagra) and
other PDE-5 inhibitor drugs vardenefil,
Tadalfil, Alprostadil shows major role in
treating SD/ED and vaccum device
therapy, surgery and following
counseling also useful to treatment the
SD. Now days the patients shows
interest in the herbal therapy. These
traditional herbal remedies are accepted
among men and they provide them with
an easy alternative to legitimize medical
treatment for their sexual problem. In the
Males study, about 50% of the
respondents claimed that the reasons for
not using phosphodiesterase type 5
(PDE-5) were because it was risky and
they were looking for natural therapies.
Other important characteristics of the SD
therapies that are sought by sufferers
include safety, containing natural
aphrodisiac agent. One has to be
extremely cautious about the use of
traditional herbal medicines due to the
fact that in India, quality control
regulations are non-existent or they are
too flexible. Further investigation on the
plants can increase the isolation of the
newer molecules which will be helpful
for the treatment of Sexual dysfunction.
Acknowledgment
Authors wish to express humble and
sincere thanks to Honrable Vice
Chancellor, Sunrise University, Alwar
(Rajasthan) for his intense support and
providing necessary facilities to prepare
this review.
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