Common Drug-Induced Alterations in Sexual Response
Drug Categories Clinical Considerations
Diuretic thiazides Temporal association with sexual dysfunction. Reported incidence varies
; however, impotence generally is not considered
common. Mechanism believed to be a “stealsyndrome” whereby blood is
routed from erectile tissues to skeletal muscle.
Spironolactone Associated with ↓ libido, impotence, and gynecomastia. Mechanism may be
hormone related. Incidence is dose related and reported to be 5%–67%165
and much more commonly encountered than with the thiazides. May be owing
to antiandrogen effects of drug.
Methyldopa Central action mediated causing vasodilation resulting in erectile dysfunction.
Clonidine Induces erectile dysfunction. Mechanism similar to methyldopa and other
-agonists. Incidence reported to be 4%–70% and dose
Guanabenz, guanfacine Incidence and mechanism believed to be similar to other central α2
Propranolol Associated with erectile dysfunction and ↓ libido. Mechanism believed to be
caused by ↓ vascular resistance and central effects. Erectile dysfunction
reported to begin at doses of 120 mg/day. Incidence may be as high as 100%
Atenolol, metoprolol, pindolol,
Incidence of erectile dysfunction is significantly less than nonselective βblockers.
Doxazosin, prazosin, terazosin Associated with erectile dysfunction and priapism.
-blockade resulting in vasodilation.
Erectile dysfunction and priapism appear to be unique to the nonspecific α1
Phenoxybenzamine Associated with priapism, retrograde ejaculation, and inhibited emissions
during erection. Effects are dose related.
Hydralazine Associated with erectile dysfunction. Mechanism is vascular smooth muscle
relaxation. Incidence not reported.
Nifedipine Associated with erectile dysfunction. Mechanism believed to be vasodilation
and possibly muscle relaxation. Reported incidence: <2%.
Diltiazem, verapamil Similar to nifedipine. Reported incidence: <1%.
Class 1A Disopyramide Associated with erectile dysfunction in patients treated for ventricular
arrhythmias. Incidence not reported. Mechanism believed to be caused by
strong anticholinergic effect.
Carbamazepine, phenytoin May be associated with sexual dysfunction through decreasing DHEA, which
is a precursor to testosterone, estrogen, and pheromones.
Drugs with prominent serotonin agonist effects commonly cause delayed
ejaculation and anorgasmia. The reported incidence for delayed ejaculation
among men is 2% to 12%; for anorgasmia among women users, the incidence
appears to be <3%. This adverse effect is directly dose related.
Associated with impairment of sexual performance in both male and female: ↓
libido, anorgasmia, retrograde ejaculation, erectile dysfunction. Mechanism
believed to be caused by anticholinergic and serotonergic effects. Incidence
not reported; several case studies in the literature.
Trazodone Associated with priapism in men and ↑ libido in women. Mechanism similar to
TCA. Incidence not reported but believed to be dose related.
literature reports that overall there is less sexual dysfunction with desipramine
than with other antidepressants.)
Phenothiazines Frequently associated with sexual dysfunction. Commonly, ↓ libido is reported.
Mechanism is owing to hyperprolactinemia secondary to central dopamine
antagonism. Thioridazine is the most often reported offender. Erectile and
ejaculatory pain are very common with this drug class; the α-antagonism and
anticholinergic effects are responsible. Priapism is common with this drug
group, owing to the peripheral α-blockade property. Incidence for allsexual
dysfunctions with this drug class: approximately 50% of users.
CNS depression causes ↓ libido and performance.
Benzodiazepines Biphasic effect. At low doses, ↑ libido, whereas at higher dosages, CNS
depression causes performance failure. Some reports of anorgasmia (men and
women) and ejaculatory failure.
Alcohol Alcohol is thought to impair sexual function through its chronic effects on the
nervous system. Short-term use of alcohol can induce erectile dysfunction
through its sedative effects. More than 600 mL/week of alcohol increases the
probability of erectile dysfunction.
At low doses, it actually may enhance libido. Sexual dysfunction is dose
related and caused by CNS depressant effects.
Cocaine Biphasic effect. At low doses, there is enhanced sexual desire (similar to
amphetamines) and possibly performance. At higher dosages, there may be
arousal dysfunction, ejaculatory dysfunction, and anorgasmia. Freebasing has
been associated with spontaneous orgasm. Continued use (on a run) causes
significant loss of sexual interest and performance ability. Chronic use
associated with hyperprolactinemia resulting in ↓ libido.
Hallucinogens Biphasic effect for most drugs in this category. At low doses, libido is
enhanced; at higher doses, libido is severely ↓. No reports on chronic use.
Marijuana Biphasic effect similar to ethanol. With chronic use there is a ↓ in libido.
Mechanism may be owing to ↓ testosterone. Incidence not reported.
Opioids Associated with sexual dysfunction: erection lubrication, orgasm, and
ejaculation. Chronic use associated with ↓ libido. Mechanism may be owing to
α-antagonism, alterations in testosterone, and the intoxicating effects.
Amyl nitrate Associated with intense and prolonged orgasms in both men and women.
Impotence has been reported in some cases owing to vasodilation.
Cimetidine, ranitidine Associated with ↓ libido and erectile dysfunction. Mechanism owing to
antiandrogen qualities and drug-induced elevation of prolactin. May be dose
Metoclopramide Associated with
libido and erectile dysfunction. Mechanism is through CNS
dopamine antagonism, resulting in hyperprolactinemia. Incidence not
CNS, central nervous system; DHEA, dehydroepiandrosterone; TCA, tricyclic antidepressants.
Ideally, assessment of ED should include urologic, endocrinologic, psychiatric,
and neurologic evaluations as close together as possible. The chief complaint of ED
must be identified carefully and described because medical intervention is indicated
if it occurs for a 6-month period and in greater than 50% of attempts.
history should determine whether ED varies with partners, sexual settings, position,
and masturbation, and whether morning and nocturnal erections are impaired.
RELATIONSHIP OF MEDICAL HISTORY AND ERECTILE DYSFUNCTION
CASE 109-4, QUESTION 3: What is the relationship among hypertension, cigarette smoking, diabetes
In the Massachusetts Male Aging Study (MMAS), heart disease with hypertension
and low serum high-density lipoprotein correlated with ED.
erection can be impaired in patients with myocardial infarction, coronary artery
bypass surgery, cerebrovascular accidents, and peripheral vascular disease.
several studies of impotent men, the number of abnormal penile vascular findings
significantly increased when the history included hypertension and cigarette smoking.
Control of blood pressure among hypertensive male patients does not necessarily
erectile function, and antihypertensive medications can have a significant effect on
ED and sexual performances (Table 109-6).
The prevalence of cigarette smoking among men with ED is higher than in the general
189–191 When the relation between cigarette smoking and erectile
physiology was studied in 314 men with ED,
192 smoking was noted to further
compromise penile physiology in men experiencing difficulty maintaining erections
long enough for satisfactory intercourse. Several investigators report lower penile
blood pressure indices, penile arterial insufficiency, and abnormal blood perfusion
associated with cigarette smoking.
189,193 Clearly, smoking cessation may benefit men
Diabetes mellitus has been associated with ED. In the MMAS, male patients with
diabetes mellitus were 3 times more likely to have ED than patients without
136 Other investigators using exclusively diabetic populations have found a
prevalence of ED as high as 75% among subjects.
194,195 The onset of ED in the
diabetic patient occurs at an earlier age when compared with the general population.
In a few cases, it may be the presenting symptom of diabetes mellitus, and in most
cases, ED follows within 10 years of the diagnosis, regardless of insulin dependence
196,197 Researchers disagree as to the exact contribution of diabetes mellitus to
ED, but most of the literature supports an atherosclerotic etiology.
possible causes also include autonomic neuropathy and gonadal dysfunction.
GONADAL FUNCTION IN ERECTILE DYSFUNCTION
CASE 109-4, QUESTION 4: What is the significance of the gonadal function results for F.M.?
Abnormalities of primary or secondary hypogonadism must be ruled out, particularly
in patients with a decreased libido with or without ED. The results of F.M.’s gonadal
function tests are relatively normal for an aged male. Testosterone serum levels
decline with aging as a result of hypothalamic–pituitary changes or Leydig cell
dysfunction. The understanding of changes that take place in the hypothalamic–
pituitary level with advancing age is in a state of flux. For some time, most
investigators focused on the increased serum concentration of male gonadotropins
(LH, FSH), believing that all elderly men had some degree of primary
200 Other studies have shown, however, that LH levels in elderly men
are lower than the median of those in younger patients.
LH levels do not increase in response to the decrease in testosterone serum
concentrations in the aged male, indicating a defect in the hypothalamic–pituitary
axis, leading to secondary hypogonadism.
201 Secondary hypogonadism results when
there is a dysregulation of pituitary LH release, resulting in low serum testosterone
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