© 2007 International Society for Sexual Medicine
Classic Citations
Priapism: Reasons for Failure by Frank Hinman Jr
Sidney Glina, MD,* Arthur L. Burnett, MD,† Edgardo Becher, MD,‡ Gerald Brock,§ and
Wayne Hellstrom, MD¶
*Department of Urology, Instituto H. Ellis, São Paulo, Brazil; †Department of Urology, The James Buchanan Brady
Urological Institute, The Johns Hopkins Hospital and The Johns Hopkins University School of Medicine, Baltimore, MD,
USA; ‡Division of Urology, University of Buenos Aires, Argentina; §Division of Urology, University of Western Ontario,
Canada; ¶Department of Urology, Tulane University, New Orleans, LA, USA
I
n his article from 1960, Frank Hinman Jr [1]
through the description of seven cases of idiopathic priapism gave the features of this disease.
All seven patients had had previous transient episodes of priapism and prolonged sexual excitement
before the final episode; erection of the corpora
cavernosa sparing of corpus spongiosum; presence
of dark thick blood, without clots, inside the
corpora and refilling with bright blood after aspiration; limited subsidence after aspiration and
eventual nonrefilling after it; and partial or complete erectile dysfunction after the episode.
Patients’ ages were between 31 and 53 years,
and six of seven had been treated with repeated
aspirations or incisions until the erection went
away. One patient had received a ganglionic blocking agent on the ninth day of priapism.
The author suggested that priapism was caused
by an overfunction of the normal erectile mechanism, sometimes reversible. For him, the disorder
was related to vascular stasis, increase of carbon
dioxide of the blood, and blood viscosity. He also
found on biopsies that cavernous spaces had
become edematous and thickened after days of
erection that progressed to fibrosis. This would be
one of the reasons why none of seven patients
regained a normal erection; although four had a
partial proximal erection.
After discussing the current theories of erection
mechanism in the 1950s, the author defined priapism “as persistent erection without sexual excitation.” He also proposed a classification of the
disorder: neurogenic, mechanical, and idiopathic.
Finally, he proposed a “working hypothesis” for
the physiopathology of priapism: erection was
prolonged by psychic or local excitatory factors,
resulting in venous stasis, rise in blood viscosity,
which produced relative venous occlusion at the
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site of the junction of cavernous spaces and collecting veins, edema of the trabeculae, which
reduced further venous outflow, eventually occlusion of the arterioles, and finally fibrosis and disruption of the arteriovenous supply mechanism
preventing normal erections.
Hinman evaluated available treatment options,
and declared that none was really effective because
they could neither restore venous drainage nor
eliminate the progressive damage to the erectile
tissue. He suggested sedation, analgesia, local
hypothermia, and aspiration as treatment. The last
suggestion did not promise a perfect result for the
patient.
Sidney Glina, MD
Editor, Classic Citations
The article by Frank Hinman Jr, on the subject
of priapism, is a classic article in the discipline of
sexual medicine [1]. In it, Hinman undertook an
illuminative, critical analysis of the clinicopathological features of priapism, a historically misconceived and mysterious clinical disorder, laying the
groundwork for its improved treatment. His main
interest was idiopathic priapism, an attribution
applied still today to more than half of documented clinical cases [2], which he distinguished
from forms of the disorder associated with neurogenic, vascular, neoplastic, and traumatic conditions. This inference itself, which the causation of
priapism is multifaceted, is an important contribution. The disorder should be correctly viewed
as originating from different causes and relating to
multiple conditions, much as we today acknowledge that the more commonplace erectile disorder—erectile dysfunction—arises in association
with different disease states and involves diverse
pathophysiologic underpinnings. Contemporary
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scientists and practitioners in this field may do
well to continue to demystify priapism and next
reduce the notion that idiopathic priapism refers
to a clinical disorder without an etiology but
rather one that has an etiology awaiting scientific
clarification.
Hinman elucidated the natural history of priapism and its stages of progression common to
erectile inability. He recorded that the disorder
may also have a recurrent nature, sometimes
allowing a return to normal erectile function.
This suggested to him that the disorder in some
situations could be typified as a “reversible
over-function rather than a gross, pathologic
derangement.” This insight, along with his additional observation that the recurrences frequently
followed the conditional stimulus of excessive
sexual activity, contributed to viewing priapism as
a problem in the control of penile erection. This
evolutionary view has now been supported by
several investigators, who have postulated more
concretely that upsetting or resetting the control
mechanisms associated with corporal smooth
muscle tone may account for some forms of priapism [2–5]. Accordingly, a contemporary thesis is
that such forms of priapism involve dysregulatory
mechanisms resulting in an unbalanced state
of enhanced corporal smooth muscle relaxation
and/or its impaired contraction. Very recently, the
new science of priapism upholds that dysregulations of the activity level of phosphodiesterase type
5 (PDE5), a crucial molecular regulator of the
nitric oxide-mediated erectile response [6], as well
as signaling of RhoA/Rho-kinase, the main mediator of tonic vasoconstriction in the penis [7], are
key factors in the molecular basis of priapism at the
local penile tissue level.
Hinman characterized the pathologic changes
of the penis during episodes of priapism. This
description included the features of dark, viscous
blood in the corpora cavernosa, erectile tissue
ischemia, and its edematous changes that progress
to fibrosis. His “working hypothesis” about the
pathophysiology of priapism was that vascular
stasis and decreased venous outflow were the
primary determinants operating mechanically to
interfere with detumescence. He further proposed “changes in carbon dioxide tension” and
“decreased oxygen tension” as pathophysiologic
elements, which he contended caused erythrocytes
to become increasingly deformed in the penis in
patients, prominently in those with sickle cell
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disease, predisposing them to acquire priapism.
While plausible at the time of Hinman’s review,
we now appreciate that a more complex pathophysiology underlies many forms of the disorder.
The priapism associated with sickle cell disease
probably represents a penile vascular biologic
process and pertains to disturbances in the regulatory mechanisms of penile erection. Additionally,
for recurrent priapism, mechanisms of oxidative
and nitrosative stress acting at a molecular level in
the penile tissue are believed to be in play after
repeated ischemic insults to the penis, and also
condition the organ toward defective erection
regulatory responses.
Hinman also recognized that treatments for
ischemic priapism in his day were woefully inadequate, an assessment that unfortunately still
applies today. To improve outcomes when managing the disorder, he charged that “to be effective,
measures aimed at increasing venous drainage
must be applied early.” The recommendation is
consistent with demonstrations that relief of pain
and preservation of the health of the penis resulted
from maneuvers to address its failed venous
outflow. Over time, sundry descriptions of earlyadministered penile drainage procedures and
shunts emerged in the literature, and have taken
center stage in clinical practice. These interventions remain reactive in principle, however, and
they fail to prevent the disorder from recurring or
progressing in some individuals to an end stage
presentation. For the future, it would seem appropriate to pursue at least a secondary preventative
action as a definite management goal, and develop
effective treatment aimed at correcting the underlying pathophysiology. Active research in the field
should hopefully meet this new charge, thereby
preserving the sexual health and psychological
well-being of many individuals afflicted by the disorder.
Arthur L. Burnett, MD
In this landmark article [1], Hinman presented
the study of seven patients with idiopathic priapism showing seven common features: (i) previous episodes of priapism or intense sexual activity,
(ii) erection limited to the corpora, (iii) presence of
dark, thick blood on aspiration, (iv) refilling of
corpora with bright red blood after early aspiration, (v) limited subsidence after aspiration, (vi)
eventual nonrefilling if treated late, and (vii) partial
or complete impotency.
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Classic Citations
This is the first systematic observation of
idiopathic priapism events with an explanation of
a possible pathophysiology. The author clearly
expressed that the venous outflow is less than the
arterial inflow, and in this case of stasis, carbon
dioxide content rises, augmenting the blood viscosity. The author also supported Conti’s [8]
observation of the vascular “polsters” as vascular
inflow and outflow regulator. He suggested that
another mechanism described by Kiss [9], being
the compression of the veins against Buck’s fascia,
could play a role. The latter is a closer approach
to the current knowledge of corporeal venoocclusion. By that time, the tunica albuginea was
not differentiated from Buck’s fascia. The fibrotic
consequences of priapism were clearly stated,
leading to irreversible erectile dysfunction.
The author also presented a postulate for
normal erectile mechanism, where the erection is
mostly a consequence of an increased arterial
inflow with a fixed venous outflow regulated by
Conti’s “polsters.” At that time, the role of smooth
muscle relaxation, endothelium, and corporal
veno-occlusion were not known.
The available treatments at that time were
neural block, corporeal blood aspiration, pressure
dressings to prevent refilling, anticoagulants, estrogens, and sedatives. The author recognized the
poor results explaining that the reasons are that
those treatments do not restore the venous drainage and do not eliminate the progressive tissue
damage, stressing the need of early management.
Current knowledge has allowed us to differentiate between low-flow (ischemic) and high-flow
(arterial) priapism [10], and appropriate management of low-flow priapism with early aspiration
and eventual use of a-adrenergic drugs and the
rare need of percutaneous or surgical shunts.
Edgardo Becher, MD
Reflecting back over classic articles can be an
incredibly enriching experience. As in the world
of fashion, where not everything new is original,
in the discipline of scientific research and investigation, ideas in various forms of development
may have very humble beginnings. While researchers today are armed with powerful computers, microchip arrays, and molecular techniques,
the knowledge, important observations, and hypotheses passed down from our mentors can be
more powerful than any equipment available
today.
J Sex Med 2007;4:1539–1543
The classic article authored by Frank Hinman
Jr in 1960 [1] remains an often-cited reference
that has served as an essential thought-provoking
manuscript leading to our contemporary view of
priapism, but has also served as the nidus for future
work on the physiology of erection [11–13].
While the article reports on seven cases of idiopathic priapism and provides the readership with
Hinman’s theories of why therapy was not successful, his concepts of etiology of the condition and
the impact of therapy on the end organ are the
most valuable components of this landmark article.
In my opinion, his thoughts and theories remain
viable today as we continue to search for novel
neurophysiologic pathways and pharmacological
approaches to this common problem [14–16].
Whereas the article refers to cases of idiopathic
priapism, we would likely classify them as ischemic
or veno-occlusive priapism. In several parts of
this report, Hinman described the development
of increased viscosity of the blood leading to
impaired drainage. He identified sickle cell disease
as a prototypical example of this disordered state of
normal physiology, and reflected on the potential
of conservative management to be effective at
times.
In our own publication, more than three decades subsequently, we reported on the potential
for conservative management approaches in cases
of high-flow priapism [17]. Hinman’s article puts
forth the hypothesis that normal erection is mediated primarily by arterial inflow, and that polsters
or valves cannot be supported by histological
studies performed at that time. This assessment
and interpretation would be confirmed within two
decades by a number of investigators using dog,
monkey, and cadaveric models.
Within the past decade, there has been a renaissance in the field of priapism research. Novel
animal models and innovative therapeutic approaches have been reported in an attempt to
reduce the morbidity that results from this condition. In contrast to Hinman’s article, a clear classification system based on physiologic findings
within the penis now exists and serves as a foundation of management. Our genuine understanding of the cellular basis of this problem among
many of those affected remains lacking.
Finally, in his conclusions, he stated that therapy for priapism often fails owing to (i) failure to
restore venous drainage and (ii) treatment does
not eliminate the progressive damage to the local
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erectile mechanisms. These causes for treatment
failure are as true today as they were more than 45
years ago. His summary states that prolonged
erection leads to venous stasis, increased viscosity
with venous outflow occlusion, and ultimately
fibrosis. That impotency is the usual end result, is
his final comment, a statement that remains as
accurate today as it was then, disappointing as that
is.
Gerald Brock, MD
“Those who do not read history are condemned to repeat it.”
George Santayana
As a fledgling urology resident keen on doing
novel urologic research, Frank Hinman Jr impressed upon me that new ideas in science were
rare; all one had to do was search the literature to
find that most things had already been done. He
was particularly fond of German researchers from
the 19th century.
Priapism (persistent penile erection without
pleasure) and its treatments have been known since
antiquity, as portrayed in Egyptian papyrus drawings. It was first recorded in modern literature by
Petraeus in 1616, and successfully treated with
leeches by Trife in 1845. In 1914, Frank Hinman
Sr published his 27-page seminal treatise on the
pathophysiology of priapism [18].
While Hinman Sr classified priapism into neurogenic, vascular, neoplastic, and traumatic as recognized etiologies, Frank Hinman Jr decided to
focus on the idiopathic or unknown category in his
1959 and 1960 articles [1]. It must be appreciated
that half a century ago, most urologists advocated delayed intervention for priapism, as many
viewed treatment as the major cause of erectile
dysfunction.
Simple as it may seem, Hinman Jr tabulated
features from seven men with idiopathic priapism,
reviewed the pertinent literature on the subject,
obtained conventional microscopy of cavernosal
tissues, and deduced a workable hypothesis on the
pathophysiology of idiopathic priapism.
The cornerstone of his contribution was noting
the progression of changes with time using light
microscopy of sections from the afflicted cavernosal tissues. Initially, there was “edema of the
myriad trabeculae in the corpora.” With time,
fibrosis of the smooth muscle cells takes place,
making recovery of erection impossible. Further
corroboration of these findings was confirmed by
Spycher and Hauri in 1986 [19]. Using electron
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microscopic analysis, they clearly showed trabecular smooth muscle being transformed into
fibroblast-like cells or areas of necrosis after a
24-hour hypoxia.
Hinman invoked many early scientific writings
to unify his pathophysiologic concepts. He mentioned Conti’s polster theory [8] but more importantly referenced Kiss’ impedance of venous
outflow by compression of the veins against
the fibrous coats of Buck’s fascia [19]. He, in effect,
described an overfunctioning veno-occlusive mechanism as being the major factor causing idiopathic priapism.
Finally, Hinman identified fibrosis as causing
permanent impotency, and identified the two basic
reasons for its occurrence:
1. not restoring venous drainage
2. not eliminating the progressive damage to the
erectile mechanism.
He suggested that venous drainage must be
applied early, irrespective of the arterial supply,
and that prevention of fibrosis is paramount in
preserving erectile function.
Currently, research has moved to molecularbased concepts. Researchers have new molecules
(e.g., nitric oxide), pathways (e.g., Rho-kinase),
and treatment options (e.g., PDE5 inhibitors) to
study priapism and similar idiopathic diseases.
Young researchers will soon investigate conditions
that have plagued urologists and patients for centuries, specifically the concept of “fibrosis” as
noted by Frank Hinman Jr. As we deal with
common conditions, such as Peyronie’s disease,
cavernosal fibrosis, and urethral strictures, it will
be important to study the past in order to move
forward.
Wayne Hellstrom, MD
Corresponding Author: Sidney Glina, MD, Department of Urology, Instituto H. Ellis, Rua Almirante
Pereira Guimarães 360, São Paulo, São Paulo-SP,
01250-000, Brazil. Tel: 55 11 387 12466; Fax: 55 11 387
12466; E-mail: glinas@terra.com.br
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