CHAPTER 69
SEXUAL DYSFUNCTION IN
HYPERTENSIVE PATIENTS
RAYMOND R. TOWNSEND, MD
Introduction
As pointed out by Nazereth and colleagues in their recent
survey of sexual problems encountered in general prac-
tice in the United Kingdom, sexual dysfunction is often
poorly defined, not well understood in terms of preva-
lence, and represents a difficult clinical area for providers
who may feel inadequately trained or informed in evalu-
ating and managing this problem. 1 Hypertension is
common, and it stands to reason that the sexual dysfunc-
tion is present in a significant number of patients,
whether or not it is related to their blood pressure status
and/or its medical therapy. Drug treatment for hyperten-
sion in the 1970s relied heavily upon diuretic and antia-
drenergic agents, which were often given in high doses
and contributed to impairment in sexual performance,
giving the public (and providers) the impression that
treating hypertension is linked to a reduction in sexual
function. Newer antihypertensive agents, improvements
in understanding the processes involved in sexual func-
tioning, and candid conversations with patients should
help us shed this image of expecting sexual dysfunction
in the course of antihypertensive treatment. The issue is
particularly important since the benefits of effective long
term antihypertensive drug therapy in reducing target
organ damage are predicated on taking the medication
and at least two thirds of adults with hypertension fail to
achieve adequate blood pressure control, which in some
cases may result from noncompliance because of fear of
loss of sexual function.2 Noncompliance with antihyper-
tensive drugs is clearly a factor in the failure to achieve
better control statistics.3,4 This is supported by the find-
ing that up to 70% of hypertensive patients experiencing
side effects are noncompliant with their antihypertensive
597
medication, and this negative impact on their quality of
life is associated with a 40 to 60% higher rate of medica-
tion discontinuation than seen in patients whose quality
of life is not affected.5,6
In this chapter we plan to review briefly the relevant
physiology and pathphysiology underlying sexual
responsiveness, cover relevant points in the evaluation of
sexual dysfunction in men and women, point out mecha-
nisms by which antihypertensive medications in particu-
lar may contribute to alterations in these responses,
conclude with some suggestions on communicating with
patients and a few recommendations for how to manage
this oft-neglected aspect of clinical care.
Physiology of Sexual Responses
MEN
Typical male sexual physiology is parsed into five phases.
The first of these is libido (sexual desire) and is ignited by
psychological factors and male hormone (testosterone).
It culminates in erection of the phallus, a neurovascular
event resulting from a complicated interplay of involun-
tary and somatic neural inputs into the penis. This neural
input also controls the smooth and striated musculatures
of the corpora cavernosa and the floor of the pelvis in
addition to the arterial circulation of the paired pudendal
arteries. The second phase is maintenance of the erection
resulting from increased arterial inflow to the corpora
cavernosa. Maintenance of erection is abetted by venous
constriction, which sequesters blood in the tissues.
Among the neurotransmitters thought to regulate this
process are nitric oxide, vasoactive polypeptide,
prostaglandins, and acetylcholine. An average erection
598 / Advanced Therapy in Hypertension and Vascular Disease

augments the penis storage capacity with at least 100 to

140 mL of blood and is predicated on minimal venous
outflow. When maximally turgid, the intracavernous
pressure can exceed the systolic blood pressure. If this
volume is not attained, a full erection is impossible.
Ejaculation marks the third phase of normal male
sexual function. This is under the control of the sympa-
thetic nervous system and has two parts: seminal emis-
sion and true ejaculation. The closely linked fourth phase
is orgasm. This is a cortical sensory pleasure phenome-
non. The fifth and final phase is detumescence. This
comes about through drainage of the venous sinuses,
resulting in penile flaccidity.

WOMEN
The male responses are much easier to delineate and to
recognize because the processes, particularly erection, are
directly observable. Female sexual responses have been Figure 69-1 Sex response cycle, showing responsive desire experi-
much more difficult to categorize, and the attempts to do enced during the sexual experience as well as variable initial (sponta-
so have, at times, resulted in more harm than good, as neous) desire. Printed with permission from Basson R.9
outlined in the recent editorial by Moynihan.7 Although
estimates are that as many as 2 of 5 women have some
degree of sexual dysfunction, this figure has been
contested, and studies in hypertensive women, in partic-
ular, show much lower figures. 7,8 It is apparent that
fulfillment of sexual desire is an uncommon
reason/incentive for sexual activity for many women,
and, in fact, sexual desire is frequently experienced only
after sexual stimuli have elicited subjective sexual arousal.
The latter is often poorly correlated with genital vasocon-
gestion. Complaints of lack of subjective arousal despite
apparently normal genital vasocongestion are common
(see next section). Female sexual responses have been
assumed to progress in a linear fashion from an initial
awareness of sexual desire to one of arousal (with a focus
on genital swelling and lubrication), to orgasmic release Figure 69-2 Differential diagnosis of sexual dysfunction showing
the complex inter-relationships which can influence sexual dysfunc-
and resolution. The evidence to date shows that many
tion.
facets of women’s sexual function are at variance with
this model. 9 Women describe overlapping phases of
sexual response in a variable sequence that blends the ED of organic origin (eg, neurologic, vascular,
responses of mind and body (Figure 69-1). endocrine, or pharmacologic causes) is characterized by
the gradual onset of deteriorating function. Neurologic
Pathophysiology factors that interfere with normal sexual function in men
(eg, multiple sclerosis, tumors, peripheral neuropathies,
injuries, pernicious anemia, syphilis, spinal cord trauma)
MEN interrupt the transmission of nerve impulses. Vascular
Erectile dysfunction (ED) can result from a problem at diseases (eg, seen in the background of patients with
any phase of producing tumescence, including organic heart attack, arteriosclerosis, hypertension, stroke)
and/or psychogenic causes. Figure 69-2 places the spec- compromise the development of a proper erection
trum of factors involved in sexual dysfunction into some because of reduced blood supply to the penis. This was
perspective. shown in studies of the arterial bed of the penis that

demonstrated fibrous proliferation of the vascular
intima, medial fibrosis, and calcification and narrowing
of the lumen. 10 Reduction in the levels of certain
hormones characterize endocrine causes of erectile
dysfunction. Low testosterone levels combined with high
progesterone levels reduce libido and, thus, affect sexual
function. It is estimated that about a quarter of cases of
erectile dysfunction result from pharmacologic factors.
The disorder is a side effect of many medications, includ-
ing some antihypertensives (covered later), estrogens,
anticholinergics, disulfiram, and antihistamines. Nicotine
and substance use (ie, alcohol, stimulants, narcotics, all
psychotropic drugs) are also implicated in ED. Pelvic
trauma and surgical procedures, particularly those
involving the urogenital system, can cause ED if the
blood vessels or nerve pathways involved in sexual func-
tion are damaged.
ED of psychogenic origin is usually episodic and is
more likely to show a sudden onset especially when
preceded by times of heightened stress. Fatigue, depres-
sion, and anxiety also contribute commonly, and are
exacerbated by the patient’s frustration about erectile
dysfunction itself.
Hypertension and Erectile Dysfunction
The endothelium modulates vascular tone through various
vasoactive substances that include vasodilators (eg, prosta-
cyclin, nitric oxide) and vasoconstrictors (eg, endothelin-1,
prostaglandin).11 A constant trickle of nitric oxide from
endothelial cells maintains the vasculature in a dilated state,
and a reduction in nitric oxide production and release is
thought to contribute to hypertension. Nitric oxide defi-
ciency may contribute to erectile dysfunction, particularly
in patients with diabetes, as shown in a recent study.12
Further support for this is the finding that ED can be
treated with intercavernosal injection of nitrovasodilators;
thus, nitric oxide released from the cavernosal endothelium
and, possibly, from inhibitory nerves may be essential for
penile erection.13 These aspects make it clear that it is
unwise to immediately conclude that the drug therapy used
in treating the hypertension is the culprit without at least
considering that sexual function is an extremely compli-
cated process and simple answers, although satisfying, are
not always the right or the best ones.
WOMEN
Prior concepts of female sexual dysfunction assumed that
a woman’s sexual response begins with sexual desire, with
sexual thoughts and fantasies, arguing that their absence
was evidence of dysfunction or disease. A survey of
American women showed that the most common sexual
complaint among women (18–59 years of age) was a low
Sexual Dysfunction in Hypertensive Patients / 599
desire for sex, reported by about 30% of those surveyed,
with little alteration in the percentage with advancing
age.14 Although these women report low or absent spon-
taneous desire, they may still experience triggered desire
during sex. Importantly, unlike in men, the robust corre-
lation between subjective arousal and genital congestion
(erection) is not seen in women. 15 Devices which
measure vaginal vasocongestion (reflecting physiological
arousal) show that while women may respond physiolog-
ically to erotic (often visual) stimuli, their subjective
responses (like sexual arousal and positive and negative
emotions) are flat. For example, in psychologic evalua-
tions of women with arousal disorders (as defined by
Diagnostic & Statistical Manual of Mental
Disorders–Fourth Edition-Text Revision (DSM-IV-TR),
despite a subjective lack of reported arousal or lubrica-
tion/swelling responses while watching erotic videos,
increases in vasocongestion were very similar to those in
the control participants without arousal disorders who
did report subjective arousal while watching the same
videos.16 Since the definitions of arousal disorder (one of
the female sexual dysfunction disorders) focus only on
the genital lubrication or swelling responses, studies like
those of Morokoff and Heiman confirm the poor correla-
tion of genital engorgement with the woman’s subjective
arousal and excitement in response to sexual stimulation
and emphasize the difficulty pursuing both the defini-
tions and the pathophysiology of female sexual responses
and female sexual dysfunction.16
Evaluation
For both men and women, a good history and, to a lesser
extent, a physical exam pursue common causes of sexual
dysfunction such as cardiovascular, endocrine, neurologi-
cal, and urogenital disorders along with medication
usage. Considerations for how to approach the evalua-
tion and things to avoid are outlined in Tables 69-1 and
69-2. Identifying cause(s) of sexual dysfunction may help
direct your choice of treatment.
MEN
An ED diagnosis is made when men have a consistent
inability over the course of 3 months to attain and main-
tain an erection sufficient for sexual intercourse. The
International Index of Erectile Function 5 questionnaire
may help you determine the severity (mild, moderate, or
severe) of ED (found at < http://www.jr2.ox.ac.uk/
bandolier/band90/b90-6.html > accessed August 15,
2005). Classifying the cause of ED as psychogenic (result-
ing from or in association with psychological or interper-
sonal factors), organic (resulting from endocrinological,
neurological, or vascular disorders), or a combination of
600 / Advanced Therapy in Hypertension and Vascular Disease
Table 69-1 Considerations for the Evaluation of Sexual
Dysfunction in the Hypertensive
Recommendation Rationale
Initiate the discussion Patients may be waiting for you to bring up the topic.
Maintain self-reflection Your attitudes/beliefs/prejudices about sexuality
may dampen communication through poor
presentation either in manner or speech.
Tasteful decorum Consider a small display in the waiting area or in the
exam rooms; if the patient has a brochure with
them when you see them it may help both/all of
you to open the discussion.
Reassure These are common problems, with a lot of causes
and treatment opportunities; sometimes patients
are not so much seeking relief as seeking
sympathy from someone who cares for them and
with whom they can discuss this.
Avoid jargon Use similar terms to what the patient says or define
your language clearly when discussing this topic.
Refer Many times the problems can be managed or
resolved by the primary provider, but some cases
will benefit from the opinion of a specialist when
usual measures seem to be inadequate for their
needs.
Table 69-2 Pitfalls in Sexual Dysfunction Evaluation
Recommendation Rationale
Do not ask for a “yes or no Inquire in a fashion that allows a discussion
answer so that the patient has a chance to express
themselves, perhaps by telling about what
actually happens to them.
Older age  inactivity In either gender, this has been one of the
most eye-opening aspects for the author.
Cultural insensitivity Those of the other gender, those who feel a
huge gulf between them and the doctor,
those with statistically less likely sexual
preference, and those from a different
ethnic background may be very reluctant to
discuss this sensitive problem.
Use appropriate language/tone Avoid the temptation to try and relieve
tension by a joke or trivializing the patients
complaint; the direct advertising to
consumer has raised expectation and
patients may have high hopes for relief.
Avoid a review of your own This is about their concerns so staying on
experiences target in the discussion is important.
both will help direct laboratory testing; however, test-
ing—particularly endocrine assessment—is not
performed routinely.
When men have a history of heart disease, they are
usually assigned to a low, intermediate, or high risk cate-
gory. It is recommended that you manage that risk before
recommending particular sexual dysfunction therapy or
the resumption of sexual activity. Those with low risk
have, among other issues, conditions such as hyperten-
sion, mild stable angina, and fewer than three cardiovas-
cular risk factors. Those in the intermediate category
have, among other factors, angina of more moderate
occurrence, class II congestive heart failure, or have expe-
rienced a heart attack within the last 6 weeks. The highest
risk category includes patients with unstable or refrac-
tory angina, class II to IV heart failure, obstructive
cardiomyopathies, and more severe valvular disease.
Categorization of men into risk categories as outlined
above is important in light of the increasing use of some
phosphodietserase (PDE) inhibitors, which can, in
circumstances where nitrates or 1 blockers are used,
conspire to lower blood pressure to levels that precipitate
coronary ischemia and risk myocardial infarction.
WOMEN
As part of the history, inquire about desire, arousal,
orgasm, and pain. Sometimes it may be helpful to
employ a diagnostic questionnaire—such as the Female
Sexual Function Index (<http://www.fsfi-questionnaire.
com/>) or the Brief Index of Sexual Functioning for
Women (BIS-F). 17 Inquiry into the nature of female
patients’ key emotional relationships is important since
women often are looking for romance, pleasure, and
desire intimacy. Although women acknowledge that
orgasm is important, it is not as critical to their sexuality
as it is with men so that the goal in understanding a
woman’s concerns may be different than in men.
However, as with male patients, lab testing may be useful,
particularly using studies which pursue specific compli-
cating factors such as hypothyroidism (TSH), markers of
ovarian failure such as FSH and low testosterone levels,
elevated prolactin (which may be important in decreased
desire), and tests for diabetes, renal failure, and athero-
sclerosis markers such as a lipid profile. In some cases,
estradiol level, when low, helps explain vaginal dryness,
painful intercourse (dyspareunia), and decreased libido.
Effects of Specific Classes of
Antihypertensive Medications
OVERVIEW
Providers frequently attribute sexual problems to the
antihypertensive medications and modify or discontinue
medication regimens to address this concern. Yet the
scientific evidence that links antihypertensive drugs to
sexual dysfunction in placebo-controlled trials is limited
both in the number of publications and in duration of
drug exposure in trials (which is often in the order of
weeks to months). The Treatment of Mild Hypertension

Study (TOMHS) specifically addressed the role of long
term (4 years) blinded antihypertensive therapy (includ-
ing a placebo group).8 In TOMHS, participants received
nutritional-hygienic interventions and were randomized
to receive either placebo or one of five drugs representing
commonly used classes of antihypertensive agents includ-
ing a  blocker (acebutolol), a calcium antagonist
(amlodipine), a diuretic (chlorthalidone), an 1 antago-
nist (doxazosin), or an angiotensin-converting enzyme
inhibitor (enalapril). Sexual problems, assessed by inter-
view, were reported in 14.4% of men and 4.9% of women
at baseline. In the men, it was predominantly ED. In the
women, 2% reported a problem with having orgasm and
about 11% noted a decrease in sexual activity in the year
preceding enrollment in the study. At 24 months, men in
the chlorthalidone group experienced the highest inci-
dence of problems obtaining an erection (15.7%), which
was significantly higher than placebo (4.9%, p < .01).
Interestingly, only doxazosin had a lower rate (2.8%)
than placebo at 24 months, but this percentage did not
differ significantly from that of the placebo. The acebu-
tolol, amlodipine, and enalapril groups had incidence
rates only slightly higher than the placebo group (p = .25,
p = .68, p = .73 for acebutalol, amlodipine and enalapril,
respectively). The overall rate of sexual dysfunction for
both men and women in TOMHS likely underestimates
that of the general hypertension population since
TOMHS excluded diabetics, those with a relatively high
alcohol intake, and those with clinical cardiovascular
disease. A few key lessons from this study are worth
emphasizing before going on to individual classes of anti-
hypertensive agents. In TOMHS, the rate of ED was rela-
tively constant until 60 years of age, after which it rose
substantially. For systolic blood pressure (SBP), the ED
rate was higher when SBP was
140 mm Hg, at which
level men had more than twice the rate of erectile prob-
lems compared with men whose SBP was < 140 mm Hg.
This relationship with SBP persisted despite controlling
for age and previous use of antihypertensive medication.
Thus, it is important to keep in mind that sometimes
sexual dysfunction is just part of the hypertension spec-
trum and not always the consequence of medication(s).
DIURETIC THERAPY
Thiazide diuretics are occasionally associated with male
sexual dysfunction, including decreased libido, erectile
dysfunction, and difficult ejaculation.18 As is often the
case with antihypertensive therapy, the mechanism by
which thiazides affect erectile function or libido is
unclear. They may have a direct effect on vascular
smooth muscles or decrease the response to cate-
cholamines. Thiazides are inexpensive and provide effec-
Sexual Dysfunction in Hypertensive Patients / 601
tive control of hypertension in men who do not experi-
ence sexual dysfunction.
Spironolactone is structurally related to the sex
hormones and interferes with the binding of dihydrotestos-
terone to androgen receptors, resulting in an increased
clearance of testosterone.19 Younger cycling women often
have irregular menses when receiving spironolactone.
 BLOCKADE
 blockade reduces the outflow from the central sympa-
thetic nervous system, impairs vasodilatation of the
corpora cavernosa, and increases the tendency toward
sedation or depression, which may result in a loss of libido.
Occasionally serum testosterone levels are modestly
reduced during long term  blocking treatment.20
ANGIOTENSIN-CONVERTING ENZYME
INHIBITION/ANGIOTENSIN RECEPTOR
BLOCKADE
It is uncommon for angiotensin-converting enzyme (ACE)
inhibitors or angiotensin receptor blockers to cause sexual
dysfunction. Because they reverse endothelial dysfunction
by preventing the effects of angiotensin II, prolonging the
half life of nitric oxide, and decreasing the degradation of
bradykinin, they are actually beneficial in treating hyper-
tensive patients who may have experienced a problem with
other agents. Bradykinin is a potent stimulator of nitric
oxide and prostacyclin release and, therefore, would not be
expected to cause erectile dysfunction.21
CALCIUM CHANNEL BLOCKADE
Little evidence implicates calcium channel blockade in
sexual dysfunction. Since they promote vasodilation and
improve endothelial function, there isn’t much basis to
implicate them in erectile dysfunction. Nonetheless, older
reports note the occurrence of gynecomastia.22
ANTI-ADRENERGIC DRUGS AND
VASODILATORS
Centrally acting antihypertensive medications such as
methyldopa and clonidine have been associated with
sexual dysfunction in men. Methyldopa acts as a false
neurotransmitter. It decreases sympathetic nervous
outflow and can result in a reduction in libido, emission
volume, and ejaculation.23 Clonidine has a mechanism
similar to that of methyldopa; however, sexual impair-
ment is reported less often in patients given clonidine.24
ED and decreased libido are relatively rare complica-
tions of peripherally acting antiadrenergics. Although
priapism secondary to blockage of  receptors occurs
very rarely, it is the most significant sexual dysfunction
602 / Advanced Therapy in Hypertension and Vascular Disease
related to peripherally acting  blockers.24  Blockers
may also promote the secretion of prolactin, which
contributes to decreased libido and ED.24 Priapism and
ED are uncommon side effects of vasodilators such as
hydralazine and minoxidil.
Treatment
MEN
Using common sense, it is rational to change or discon-
tinue medications that adversely affect erectile function
when possible and to treat underlying medical conditions
like obesity through lifestyle changes. One study found
that about one third of obese men who lost weight and
exercised regained their ability to have an erection,
compared with only 5% in the control group.25
Therapy for ED utilizes oral agents such as sildenafil,
vardenafil, or tadalafil. All three drugs are contraindi-
cated in patients taking nitrates. Although sildenafil does
not have a contraindication with  blockers, tadalafil is
contraindicated in patients taking terazosin-like drugs
(except tamsulosin hydrochloride), and vardenafil is
contraindicated in patients taking all forms of  blockers.
Second- and third-line therapies are reserved for patients
who do not respond to one or more first-line treatments,
or for whom first-line therapies are contraindicated.
Second-line therapy consists of intraurethral supposito-
ries (alprostadil) and intracavernous injections
(alprostadil). Third-line therapy consists of surgical pros-
theses. Attempts to treat ED with hormones are not very
successful. Testosterone, important as it is to desire and
sperm production, has little effect on ED.
WOMEN
Aside from correcting the occasional reversible causes of
sexual dysfunction by making lifestyle or medication
changes, there are several other steps that can be taken
(Table 69-3). Keep in mind the advice of Kathleen Walsh,
MD, in an ACP Observer interview in March 2005 where
she stated, “Many physicians are frightened to talk about
sexual dysfunction with their female patients because
they don’t know how to treat it. But they don’t always
have to treat it—just acknowledging the problem can
make a huge difference.” Non-drug therapies such as
stimulation devices, psychotherapy, and biofeedback may
be of help in select patients but often require specialized
help and guidance. When pain is the issue, varying sexual
positions, the use of lubricants, and pursuit of pelvic
floor physical therapy may benefit. Drug treatment can
sometimes play a role in treating women’s low desire,
decreased arousal, anorgasmia, and pain disorder.
Table 69-3 Treatment Considerations
Problem Consideration
Relationship problems Counseling referral
Concurrent depression or anxiety Antidepressant, anxiolytic, psychologist
disorder
Potential antihypertensive Reconsider indication, adjust dose, try
medication effect another agent in class, switch to
different class of agent
Libido (desire) issues Low dose testosterone; gynecology or
urology referral
ED Review medications, comorbidities;
consider psychologic factors; PDE
inhibitor (some insurers require a
testosterone level)
Consider estrogen therapy (ring, tablet, patch, or cream)
when the complaint is that of vaginal dryness, burning,
and urinary frequency and urgency. One potential draw-
back is that oral estrogen replacement may increase
blood levels of sex hormone-binding globulin, reducing
bioavailable testosterone, and impairing sexual desire,
further compounding the initial problem.
Testosterone therapy in women remains controversial.
You might consider it (alone or in combination with
estrogen in perimenopausal and postmenopausal women)
with a complaint of decreased desire, dyspareunia, or lack
of vaginal lubrication. Testosterone therapy can affect
liver function tests and lipid levels, so it is important to
monitor these if testosterone therapy is used.
In both sexes it is important to keep in mind that
drugs won’t change the relationship with a partner; thus,
the need is always to keep in mind the big picture where
it concerns sexual difficulties.
Other Sources of Information
Several places offer information on sexual dysfunction.
The PIER modules by Arthur L. Burnett, MD on ED,
available at <http://pier.acponline.org/physicians/
diseases/d242/d242.html> and Kathleen Walsh, MD, and
colleagues on female sexual dysfunction <http://pier.
acponline.org/physicians/diseases/d664/d664.html> are
good starting places.
Additional resources include the “Patient-Page”
feature in JAMA and the websites of the American
Association of Clinical Endocrinologists at <http://www.
aace.com> and the American Urologic Society at
<www.urologyhealth.com>. 26
The on-line female sexual function index (FSFI),
although not directly applicable to clinical practice,
provides the kernels of the questions regarding sexual
function in women and is available at <http://www.fsfi-
questionnaire.com/> along with validation documenta-
tion, scoring instructions, and text that explains the test.

Summary
The widespread promotion of ED medications has likely
made it easier for patients to bring up the subject of
sexual dysfunction during health care visits. Yet for most
patients, it’s still up to providers to broach the topic and
screen for sexual dysfunction. A few key open-ended
questions to initialize the discussion and a brief review of
comorbidities and medications with attention to other
physical/psychologic factors can make a huge difference
in the sexual function of patients. In some cases referral
to urology, gynecology, psychology/psychiatry or practi-
tioners such as sex therapists is reasonable when treat-
ment measures are inadvisable, poorly tolerated, or
ineffective.
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