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European Society of Hypertension Scientific Newsletter:Update on Hypertension Management
HYPERTENSION AND SEXUAL DYSFUNCTION
Athanasios J. Manolis, Cardiology Department, Asklepeion Voula Hospital, Athens, Greece; Michael Doumas, Department of Internal Medici-
ne, University of Thrace, Alexandroupolis, Greece; Margus Viigimaa, Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia;
Krzysztof Narkiewicz, Department of Hypertension and Diabetology, Medical University of Gdańsk, Poland
Sexual dysfunction represents a common condition in the general pop-
ods used for erectile function assessment are not appropriate [1, 14–
ulation placing a major burden on patients’ and their sexual partners’
–16]. Thus, we believe that only a multinational study all over Eu-
quality of life. Sexual dysfunction has been traditionally attributed to
rope, with accurate blood pressure measurement, careful recording
psychogenic origins and managed by mental health professionals and
of all concomitant conditions, and use of a validated method (the
urologists. However, advances in pathophysiology research point to
International Index for Erectile Function, IIEF) could precisely evalu-
a vascular origin of the problem in the majority of patients, possibly
ate the prevalence of erectile dysfunction in hypertensive patients.
due to atherosclerotic lesions in the genital arteries that result in de-creased blood flow. In addition, the discovery of phosphodiesterase-5
Physiology and pathophysiology
inhibitors has produced an easily available effective treatment, and
Penile erection is the result of a complex interplay between psycho-
nowadays patients seek help from cardiologists, internists and general
logical, neurological, hormonal and vascular factors. Since the sym-
practitioners in increasing numbers. Physicians skilled in hypertension
pathetic nervous system, the intact endothelium and notably nitric
management often feel unqualified to deal with sexual problems since
oxide have a central role in a successful erection, it is no surprise
adequate training regarding sexuality has not been offered in under- or
that essential hypertension is related to erectile dysfunction.
in post-graduate training . In our point of view, several important
Hypertension induces structural changes in the penile vascu-
reasons exist to motivate hypertension specialists to become familiar
lature thus decreasing arterial blood inflow, as well as functional
with sexual dysfunction, including the following facts:
abnormalities like increased sympathetic activity, endothelial dys-
• sexual dysfunction can be detected in a significant percentage of
function, reduced nitric oxide bioavailability and activation of the
hypertensive patients, affecting their quality of life. Since most
renin-angiotensin system. All of the above abnormalities may lead
patients are reluctant to address this issue, they either remain
to impairment of penile vasodilatation, lack of relaxation and subse-
untreated or obtain drugs from unauthorized sources (Internet)
• sexual dysfunction may be an adverse event of antihypertensive
Relation to cardiovascular disease
medications. Since some drug categories may cause sexual dys-
Patients with erectile dysfunction have an increased risk of suffering
function, a change in drug category may alleviate the symptoms;
from asymptomatic severe coronary heart disease ; moreover,
• phosphodiesterase-5 inhibitors are vasodilators and reduce blood
erectile dysfunction correlates with the number of occluded coro-
pressure. Although blood pressure reduction is usually modest,
nary vessels as assessed by angiography . In addition, it seems
some susceptible patients (especially older and sodium-depleted)
that erectile dysfunction and coronary heart disease share common
risk factors, since erectile dysfunction is more prevalent in individu-
• sexual intercourse may be detrimental in high-risk patients, and
als with multiple cardiovascular risk factors .
patients with untreated, poorly-controlled, accelerated or malig-
Based on data demonstrating that the probability of undiag-
nant hypertension are considered as high-risk; thus, sexual activi-
nosed coronary artery disease is very high in patients with erectile
ty has to be deferred until patients’ stabilization and after appro-
dysfunction (up to 40%) , we believe that erectile dysfunction might
priate medical counselling has been obtained;
raise the possibility of underlying cardiovascular disease by being one
• many patients with hypertension suffer from coronary artery dis-
of the first signs thereof. Therefore, erectile dysfunction can be consid-
ease or heart failure and are on nitrate treatment. Since PDE-5
ered as an “early diagnostic window” of coronary heart disease.
inhibitors are contraindicated in patients receiving nitrates, andspecial precautions have to be taken, patients must be under
Safety of sexual activity in hypertension
According to the Second Princeton Consensus Conference , pa-
• sexual dysfunction can be considered as an early sign of wide-
tients with controlled hypertension are considered low-risk patients
spread atherosclerotic disease in other vascular beds as well.
and may safely proceed with sexual intercourse, since sexual activity
Thus, its detection offers an opportunity for early recognition of
in such patients doubles the extremely low risk of a cardiac event.
atherosclerotic lesions in other sites (coronary vessels, brain, kid-
On the contrary, high-risk patients have a 10-fold increased risk of
ney, peripheral arteries) through thorough investigation.
cardiac event during sexual intercourse as well as in the followingtwo hours. Since patients with untreated, poorly controlled, acceler-
Definition and prevalence
ated, or malignant hypertension are considered high-risk patients,
Erectile dysfunction is defined as the persistent inability to attain and/
sexual activity should be deferred until their condition has been
/or maintain penile erection sufficient for sexual intercourse. It has
stabilized or a decision has been made by a cardiologist that sexual
been recently estimated that over 150 million men all over the world
activity may be safely resumed .
have some degree of erectile dysfunction, while the projection for thepatient population in 2025 is 322 million men worldwide. The preva-
Quality of life
lence of erectile dysfunction in the general population varies markedly
Erectile dysfunction compromises overall quality of life, exerting
among different countries, ranging from 15% in Brazil to 74% in
a major impact on patients’ social and psychological well-being .
Finland, probably reflecting different sample populations and assess-
Moreover, it adversely affects patients’ sexual partners’ interest in sex
ment methods, as well as cultural and religious differences in discuss-
and their quality of life , thus resulting in the loss of emotional and
ing and accepting such a social stigma [2–12].
physical intimacy for both of them (sometimes even leading to divorce).
The vast majority of available data indicates that erectile dys-
function is more frequent in patients with essential hypertension
Effects of antihypertensive drug therapy
when compared to normotensive subjects, irrespective of the meth-
Although essential hypertension is related to erectile dysfunction, an
od used for erectile dysfunction evaluation. Severity and duration of
important issue has been raised as to whether this represents
hypertension, age and antihypertensive treatment seem to be major
a result of hypertension per se
, of antihypertensive treatment, or
determinants of erectile dysfunction in hypertensive patients .
However, available data on hypertension is not of the highest
Erectile dysfunction is considered an adverse drug event in
quality, showing pronounced prevalence variation (26–79%) and
one out of five cases . Antihypertensive agents represent one of
sometimes relying on self-reporting of hypertension without valida-
the most implicated drug classes , and hypertensives who expe-
tion of medical records; furthermore, the cohorts seem highly-select-
rience erectile dysfunction (real or perceived) become non-adherent
ed in some studies without reporting co-morbidities, and the meth-
to treatment and usually discontinue drugs.
Available data clearly demonstrate that older antihypertensive
inability to achieve an orgasm and/or the feeling of pain during
drugs exert negative effects on erectile function. In detail, centrally-
sexual intercourse (dyspareunia) . Most women exhibit a combi-
acting antihypertensives, diuretics and beta-blockers have been re-
nation of abnormalities in these four aspects of female sexuality
lated to erectile dysfunction, and many patients experience erectile
dysfunction as a consequence of treatment with these drugs [26–
Female sexuality is markedly under-investigated compared
–28]. Although data regarding ACE-inhibitors and calcium antago-
to its male counterpart for several reasons: a) female perceptions
nists are not quantitatively and qualitatively adequate, they point
about sex are much more complicated; b) the physiology and patho-
towards a neutral effect of these drugs on erectile function . On
physiology of female sexual function remain largely unclarified; c)
the contrary, available data for alpha-blockers and especially for
no firm, objective measures of female sexual dysfunction exist; and
angiotensin receptor antagonists suggest that these drugs may have
d) so far, no effective therapy is available.
beneficial effects on erectile function [24, 29–32]. However, we be-
It came as a big surprise when the US National Health and Social
lieve that large, randomized trials, examining specifically erectile
Life Survey reported that female rather than male sexual dysfunction is
function, are needed to demonstrate clearly the effect of the differ-
more frequent ; several subsequent reports have confirmed this find-
ing and attracted scientific interest in this topic [39–41]. However,
Although the Second Princeton Consensus  states that
available data regarding the relation between essential hypertension
a change in class of antihypertensive drugs rarely results in the
and female sexual dysfunction are far from conclusive [14, 41, 42];
restoration of sexual function, data from open studies challenge this
nevertheless, most evidence points to a higher prevalence of sexual
statement indicating that a switch to angiotensin receptor blockers
dysfunction in hypertensive women when compared to normotensive
[29–31] or specific beta-blockers (nebivolol)  may reverse erectile
women. In a study of 417 hypertensive and normotensive women,
dysfunction in hypertensive patients taking drugs from other class-
increasing systolic blood pressure, increasing age and beta-blocker ad-
es. Thus, it seems that a switch to angiotensin receptor blockers
ministration were significant predictors of female sexual dysfunction,
might prove to be an effective approach for hypertensive men with
while success in controlling blood pressure was related to a lower
erectile dysfunction while on other antihypertensive agents, before
prevalence of sexual dysfunction in hypertensive women .
administrating a phosphodiesterase-5 (PDE-5) inhibitor .
The relative lack of data in this field implies that specific studies
with appropriate methods (Female Sexual Function Index, FSFI) have
PDE-5 inhibitors in hypertensive patients
not been performed, rather than suggesting that hypertensive wom-
Although all available PDE-5 inhibitors (sildenafil, tadalafil, vardena-
en do not experience sexual problems. We believe that despite the lag
fil) may cause hypotension through increased nitric oxide bioavail-
in female sexual dysfunction research, intense efforts to clarify the
ability, and despite the statement of the American Heart Association
pathophysiology of female sexual dysfunction will lead to the devel-
(in 1999) indicating that sildenafil could be “potentially hazardous”
opment of effective treatment modalities; moreover, its relationship
in hypertensive patients taking complicated, multi-drug regimens
to essential hypertension needs further verification, along with the
, recent clinical data nonetheless clearly demonstrate that PDE-5
effect of antihypertensive treatment upon its appearance.
inhibitors may be safely co-administered with all classes of antihy-pertensive drugs, even in patients receiving multiple antihyperten-
In conclusion, sexual dysfunction is more prevalent in hypertensive
The only class that need special precautionary measures are
than in normotensive individuals. Erectile dysfunction may be the
alpha-blockers; although, even these drugs are not absolutely con-
first sign of asymptomatic coronary heart disease and contribute to
traindicated in hypertensive men taking PDE-5 inhibitors . Since
its diagnosis. Older antihypertensive drugs exhibit detrimental ef-
some beta-blockers possess simultaneous alpha-blocker properties,
fects on sexual function, while the newer drugs have either neutral
these drugs should also be used with caution.
or beneficial effects. All classes can be safely co-administered withPDE-5 inhibitors, while special precautions should be taken for
Female sexual dysfunction
a-blockers. Finally, in our point of view, hypertension guidelines should
Female sexual dysfunction can be defined as the persistent or recur-
neither ignore nor superficially address this rather important issue
rent decrease in sexual desire or arousal, the difficulty or even the
that greatly affects patients’ and their sexual partners’ quality of life.
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