Download A review of medicines that affect sexual performance

Review
A review of medicines that affect
sexual performance
Gail Mkele, BPharm, MSc(Med)Pharm
Correspondence to: Gail Mkele, e-mail: [email protected]
Keywords: sexual dysfunction, medicine-induced, antidepressants
Abstract
Medicine-induced sexual dysfunction is an adverse effect that is relatively common, and yet is poorly understood. Several classes of
medicine cause or contribute to sexual dysfunction in both men and women. Sexual dysfunction attributed to the use of medicine
can be a major cause of nonadherence to treatment. Healthcare professionals often find it difficult to discuss sexual function with their
patients, and patients may also find this to be an awkward topic to raise. However, it is an important issue that needs to be understood
and managed accordingly.
© Medpharm
S Afr Pharm J 2014;81(4):34-37
Introduction
These phases are controlled by a multifaceted interplay between
circulating sex hormones, i.e. testosterone, oestrogen and
progesterone, the autonomic nervous system, neurotransmitters,
e.g. dopamine, noradrenaline, serotonin and gamma-aminobutyric
acid, and vasoactive peptides, such as nitric oxide.1,2,6
Although many classes of medicine are known to negatively
impact on sexual function, antidepressants, and in particular,
serotonergic agents and tricyclic antidepressants, antipsychotic
agents, anticonvulsants, histamine-receptor blockers and
antihypertensive agents, are frequently implicated.1-5 If not
managed appropriately, medicine-induced sexual dysfunction can
compromise adherence to treatment, as well as the individual’s
quality of life and relationship with his or her partner.
Sexual dysfunction
The sexual response cycle
Sexual dysfunction can be defined as a disturbance in sexual
functioning that may either be psychogenic or organic, and which
involves one or more of the phases of the sexual response cycle.
Sexual dysfunction generally occurs when the normal pattern of
sexual interaction between partners is interrupted. Symptoms
that are typically associated with sexual dysfunction are detailed
in Table I.
The sexual response cycle consists of four phases, namely desire,
arousal, orgasm and resolution, which occur in both men and
women.1,2,6 Each of the phases in this sexual response cycle model
are regarded as distinct and sequential (Figure 1).
The proposed pharmacological mechanisms that account for
these adverse effects include adrenergic inhibition, adrenergicreceptor blockade, anticholinergic effects, dopamine inhibition
and endocrine effects, as well as sedative effects. This article explores the topic of medicine-induced sexual
dysfunction, and some of the medicines which are implicated.
First the sexual response cycle will be discussed.
Men
Libido
Erection
Ejaculation
Refractory
period
Desire
(also known as excitement)
Arousal
Orgasm
Resolution
Libido
Swelling and
lubrication
Orgasm or
climax
Sense of
well-being
Women
Figure 1: Sexual response cycle
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Review
• Psychological causes, e.g. depression, anxiety and stress
Table I: Symptoms associated with sexual dysfunction
• Co-morbid disease conditions, e.g. diabetes, cardiovascular
diseases and urological disorders
Sexual phase Typical symptoms in males and females
or area of
dysfunction
Desire
• Nerve damage, e.g. neurological diseases, spinal cord injuries,
pelvic surgery, prostate surgery and radiation treatment. Nerve
damage can impair autonomic nervous function, resulting in
disorders of arousal and orgasm
Males: Low sexual desire or lack of sexual desire or interest
in sex (loss of libido), decreased interest in sexual activity
and lack of spontaneous sexual thoughts.
Females: Recurrent lack of sexual thoughts and receptivity
to sexual activity.
Arousal
• Hormonal imbalances, e.g. observed during menopause
Males: The inability to become physically aroused during
sexual activity. This can manifest as erectile dysfunction
in males, i.e. failure to gain or maintain an erection that is
adequate for satisfactory sexual activity.
• Psychosocial factors
• Relationship challenges.
Males: This can include premature, retrograde or absent
ejaculation.
In addition to these, increasing age, poor physical health, heavy
smoking, and alcohol and drug abuse are also factors that play
a major role in sexual dysfunction. Therefore, all of these factors
need be considered during an assessment of a patient who reports
medicine-induced sexual dysfunction.
Females: The delay or absence of orgasm (anorgasmia) or
the inability to climax.
Medicine-induced sexual dysfunction
Females: The inability to become physically aroused during
sexual activity. This can manifest as lack of swelling and
lubrication in women.
Orgasm
Pain
Males: Pain during intercourse.
Medicine plays a major role in sexual dysfunction in both males
and females. Medicines that are frequently associated with sexual
dysfunction are listed in Table II.
Females: Pain during intercourse (dyspareunia). This is
commonly experienced by women.
The dopamine system, for example, is said to be directly and
indirectly (through prolactin) involved in sexual functioning.
Dopamine is involved in most phases of sexual behaviour, such as
desire and orgasm, and possibly arousal, i.e. erection and vaginal
lubrication.2,7,8 A decrease in dopaminergic activity has been
associated with sexual dysfunction in both males and females.6
The elevation of prolactin is associated with sexual dysfunction,
although its mechanism is not well understood.2,6,9 Research
suggests that a secondary effect of elevated prolactin levels may
be a decrease in oestrogen and testosterone levels, and that this
may contribute to symptoms of sexual dysfunction.7,8
A significant amount of serotonin is localised in the periphery,
where, when elevated, it directly reduces sensation in the
anatomical structures of the reproductive system, as well as
diminishing erection, vaginal lubrication, ejaculation and orgasm.
In addition, serotonin inhibits the production of nitric oxide
production.2,4 Nitric oxide is known to be an essential component
in the production of penile and possibly clitoral vasocongestion,
and thus the promotion of arousal of the genitalia (erection in
men and lubrication in women).6,9
A number of studies have reported that noradrenaline levels
increase during sexual activity, and that medicines that act by
enhancing noradrenergic neurotransmission have fewer sexual
adverse effects.2,6
Causes
Sexual dysfunction has a number of causes, both emotional and
physical. Factors that may impact normal sexual function include:
• Medicines
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Management strategies
It is common for people to experience variations in sexual interest
and sexual functioning at various stages of their lives. As a result,
many individuals may not realise that a medicine is responsible
for inducing or aggravating sexual dysfunction. Therefore, the first
stage in the management of sexual dysfunction is to ensure that
the dysfunction relates to the medicine, and to exclude any other
confounding factors. Strategies to manage medicine-induced sexual adverse effects
include:2,3,5,7,11
• Selecting a medicine with a lower incidence of sexual
dysfunction
• Switching to an alternative medicine which does not cause
sexual dysfunction, or which has a lower risk of causing sexual
dysfunction
• Reducing the dose of the medicine, while still maintaining the
therapeutic benefit. Clinical experience suggests that adverse
effects are generally dose related. Thus, effecting a dose
reduction is a reasonable strategy to consider
• A drug holiday: The issue of a drug holiday is controversial
because of its effect on adherence to treatment, and possible
withdrawal symptoms, depending on the medicine in question.
Tolerance to reported sexual adverse effects of medicines does
not appear to develop. Thus, it may not be helpful to ask patients
to wait for spontaneous recovery. Having said this, patients should
be informed that adverse effects in respect of sexual function are
reversible upon stopping treatment.8
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Table II: A summary of medicines that cause sexual dysfunction
Class
Example
Reported sexual dysfunction
Proposed mechanism
for sexual dysfunction
Antidepressants
SSRIs
Inhibited desire, erectile
• These effects relate to the
dysfunction, delayed ejaculation,
serotonin-induced inhibitory
decreased vaginal lubrication and
action on orgasm and
decreased or delayed orgasms
ejaculation
SNRIs
Delayed or absent orgasms,
erectile dysfunction and
abnormal ejaculation
• These medicines also decrease
dopamine and increase
prolactin levels
Selective noradrenaline reuptake
inhibitors, e.g. duloxetine,
venlafaxine, have been shown to
cause less sexual dysfunction than
SSRIs9
TCAs
Inhibited sexual desire, erectile
dysfunction, delayed ejaculation
and decreased orgasms
The anticholinergic properties
of the TCAs, with the possible
exception of decreased sexual
desire, which may relate to
dopamine antagonist properties
An approximate 30% prevalence of
sexual dysfunction has been reported
with the use of TCAs3,4
MAOIs
Decreased libido and delayed
orgasms
MAOIs cause a decrease in
dopamine levels, and an increase
in prolactin levels
• Approximately 40% of patients
taking nonselective MAOIs, e.g.
tranylcypromine, experience some
form of sexual dysfunction4
Comments
A prevalence of 58-73% of sexual
dysfunction has been reported with
the use of SSRIs4
• The selective MAOIs, e.g.
moclobemide, appear to be less
likely to cause sexual dysfunction4
Antipsychotic
medicines
First-generation
Decreased libido, erectile
antipsychotics,
dysfunction, decreased orgasmic
e.g. phenothiazines quality with delayed, inhibited
ejaculation and diminished
interest in sex
Antihypertensive β blockers
medicines
Erectile dysfunction, decreased
libido and difficulty in reaching
orgasm
The mechanism of sexual
dysfunction reported with
antipsychotics is complex,
and is thought to relate to
dopamine blockade, increased
prolactin levels and the ability
to antagonise the effects of
testosterone7,8,10
• First-generation antipsychotics
may induce sexual adverse effects
in 30-60% of patients8
β blockers cause a change in
vascular tone, thus resulting in
peripheral vasoconstriction and
decreased genital blood flow
• β blockers, such as atenolol,
bisoprolol and acebutolol, have a
lower incidence of sexual adverse
effects than propranolol
• Quetiapine, an atypical or secondgeneration antipsychotic, is a
reasonable alternative to typical
antipsychotics9
• Other antihypertensive agents
which may be considered as
alternatives include angiotensinconverting enzyme inhibitors,
angiotensin-receptor blockers or
calcium-channel blockers
Thiazide diuretics
Erectile dysfunction, decreased
libido, difficulty in reaching
orgasm and impaired sexual
function
Thiazides decrease dopamine
response and impair smooth
muscle relaxation
Loop diuretics, e.g. furosemide, are
less likely to cause sexual dysfunction
than the thiazides or spironolactone9
Centrally acting
α agonists, e.g.
clonidine and
methyldopa
Loss of libido, erectile
dysfunction, ejaculatory failure
and anorgasmia
These agents decrease
sympathetic outflow and inhibit
penile smooth muscle relaxation
Little information is available
documenting the frequency of these
effects
Aldosterone
receptor blockers,
e.g. spironolactone
Blocks the androgen receptor,
resulting in erectile dysfunction
Antiandrogenic effects
MAOIs: monoamine oxidase inhibitors, SNRIs: serotonin and noradrenaline reuptake inhibitors, SSRIs: serotonin reuptake inhibitors, TCAs: tricyclic antidepressants
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Issues that should not be neglected when managing medicinerelated sexual dysfunction include psychological factors that
relate to sexual response, sexual problems associated with
economic factors, the relationship or partner issues, and issues
around lifestyle.
The role of the pharmacist
Pharmacists need to be aware of disease conditions that are likely
to cause or contribute to sexual dysfunction, as well as medication
that can cause or aggravate sexual dysfunction. It is important
to open the lines of communication, ask the correct questions
and create an environment that will encourage patients to ask
questions and report adverse effects. Patients often discontinue
taking their medication because of sexually related adverse
effects. Understanding the potential for medicine-induced sexual
dysfunction and its impact on adherence to treatment will enable
pharmacists to provide the necessary counselling.
References
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2.
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Higgins A, Nash M, Lynch AM. Antidepressant-associated sexual dysfunction: impact,
effects and treatment. Drug, Health Patient Saf. 2010:2:141-150.
3. Conaglen HM, Conaglen JV. Drug-induced sexual dysfunction in men and women.
Australian Prescriber. 2013;36(2):42-45.
4. Jerspesen S. Antidepressant induced sexual dysfunction Part 1: epidemiology and clinical
presentation. S Afr Psychiatry Rev. 2006;9:24-27.
5. Knegtering H, Bruggeman R. What are the effects of antipsychotics on sexual functioning?
Primary Psychiatry. 2007;14(2):51-56.
6. Meston CM, Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry.
2000;57(11):1012-1030.
7. Balon R. Medications and sexual function and dysfunction. In: Balon R, Segraves RT, editors.
Clinical manual of sexual disorders. Arlington: American Psychiatric Publishing, 2009;
p. 95-115.
8. Khan M. Erectile dysfunction. US Pharmacist [homepage on the Internet]. 2012. Available
from: www.uspharmacist.com
9. Viana L. Sexual dysfunction: pharmacy practice. Canadian Health Care Network [homepage
on the Internet]. 2010. Available from: www.canadianhealthcarenetwork.ca
10. Montgomery KA. Sexual desire disorders. Psychiatry (Edgmont). 2008;5(6):50-55.
11. Sachs GS, Chan C. Medication-induced sexual dysfunction. Medscape [homepage
on the Internet]. Available from: www.medscape.com. http://www.medscape.com/
viewarticle/420273_print
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