Patient reported frequency and severity of urological symptoms

Presenting symptoms (described by patients and recorded by urologists) in 1074 patients with prostatitis.(1)

Symptom	N (%)
Frequency	689 (64.2)
Obstructive voiding	675 (62.8)
Perineal pain or discomfort	630 (58.7)
Suprapubic pain or discomfort	492 (45.8)
Penile pain or discomfort	360 (33.5)
Premature ejaculation	305 (28.4)
Malaise	229 (21.3)
Urethral discharge	220 (20.5)
Inguinal pain or discomfort	216 (20.1)
Erectile dysfunction	205 (19.1)
Haematospermia	169 (15.7)
Voiding difficulties	162 (15.1)
Fever	159 (14.8)
Purulent urine	150 (14.0)
Abnormal seminal fluid	97 (9.0)
Myalgia	64 (6.0)
Abnormal urine (mucus)	61 (5.7)
Haematuria	46 (4.3)

	Mean (sd) score
	frequency	severity
Penile pain or discomfort	55.2 (386/699)	1.3 (1.4)	3.1 (2.7)
Perineal pain or discomfort	81.6 (666/816)	2.2 (1.3)	4.5 (2.5)
Suprapubic pain or discomfort	74.6 (561/779)	2.0 (1.4)	4.3 (2.5)
Ejaculatory pain or discomfort	63.9 (461/721)	1.4 (1.3)	3.3 (2.4)
Testicular pain or discomfort	43.9 (302/688)	0.9 (1.2)	2.5 (2.5)
Lumbar/inguinal/thigh pain	35.4 (240/678)	0.8 (1.3)	2.3 (2.8)
or discomfort
Incomplete bladder emptying	72.8 (541/743)	1.8 (1.4)	3.7 (2.7)
Burning during micturition	81.7 (652/798)	2.0 (1.3)	4.2 (2.5)
Urgency	72.4 (514/710)	1.7 (1.4)	3.9 (2.8)
Urinary frequency	86.4 (717/830)	2.4 (1.4)	5.0 (2.7)

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(1) Rizzo M, Marchetti F, Travaglini F, Trinchieri A, Nickel JC. Prevalence, diagnosis and treatment of prostatitis in Italy: a prospective urology outpatient practice study. BJU Int 92(9):955-959, 2003.

Managment, evaluation and differential diagnosis

Below follows an overview of the current management recomendations (1-3) [and personal experience]. The obvious goal of the procedure is to exclude other possible conditions with similar presentation to CPPS.

The standard procedure is to:

• take an anamnesis (ambition varies, but used medications, previous surgery and treatment directed at the lower abdomen and pelvis should be checked for),
• do some tests (PSA, standard blood, urinalysis and presence of STD),
• palpate the prostate and testicles and
• give anti-biotics (e.g. ciprofloxacin), anti-inflammatories and alpha-blockers.

An ambitious urologist may also perform a urography, suprapubic and transrectal ultrasound scans, especially on NIH-I suspicion, and do the NIH-CPSI, IPSS or similar. A Meares-Stamey test is not likely to be performed. If further evaluation is warranted urine cytology and urography / flow rate is recommended.

Some optional procedures are also recommended. These are semen analysis (especially if the patient is young and can be expected to want children), urethral swab (to search for micro-organisms), flow-EMG, cystoscopy (e.g. if IC is suspected) and MRI / CAT-scan / X-rays (especially on suspiscion of cancer). If CPPS is assumed an in-depth evaluation of pain, sexual discomfort, dysuric discomfort, abdominal-pelvic status and muscular tone (“pelvic floor assessment”) should also be made (by palpation).

Conditions to differentiate from (the list is not to be regarded as a complete listing):

• Abdominal wall defects: inguinal or ventral wall hernias, myofascial trigger points.
• Gastrointestinal causes: appendicitis, diverticulitis, constipation, anal fissures, hemorrhoids. [Do notice that constipation may occur in CPPS!]
• Infection: sexually transmitted diseases, chronic bacterial prostatitis, fungal infection.
• Musculoskeletal causes: neoplasm (primary or metastatic), degenerative joint disease of the hips, sacroileitis.
• Neurologic causes: low thoracic or lumbar herniated nucleus pulposis, lumbar stenosis, Parkinson disease, diabetic cystopathy, demyelinating disease.
• Urologic causes: urinary retention, prostatic abcess, renal calculi, varicocele, epididymitis, testicular neoplasm, interstitial cystitis, bladder outlet obstruction, bladder neck hypertrophy, vesical sphincter dyssynergia, prostatic cysts, kidney disease.
• And of course prostate cancer and BPH.

Pituitary disorders were not mentioned in the references.

Do also see discussion on co-morbidities that will follow later.

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(1) Potts J, Payne RE. Prostatitis: Infection, neuromuscular disorder, or pain syndrome? Proper patient classification is key. Cleveland Clinic Journal of Medicine, vol. 74, suppl 3, May 2007.
(2) Nickel JC. Recommendations for the evaluation of patients with prostatitis. World J Urol 21:75-81, 2003.
(3) Nickel JC, Baranowski AP, Pontari M, Berger RE, Tripp DA. Managment of men diagnosed with CP/CPPS who have failed traditional management. Reviews in Urology 9(2):63-72, 2007.

Seasonality, cyclicity and circadian rhythm

There seems to be a distinct seasonality in CP/CPPS. Overall symptoms worsen the more northerly you live. Over the year symptoms improve from about may to august and worsen from october to april. Overlying this longer cycle there is anecdotal evidence of a shorter cycle of about 3-6 weeks for dysuria and of a diurnal cycle were symptoms, especially dysuria and muscle pain, are worse in the morning and improve during the day.

I'll revisit this topic later.

Disease progression

N.B. there is very little scientific data and tons of anecdotal. The following is mainly based on personal recollection and anecdotal data from websites. It is very sketchy. There is notable personal variation in pain experience and symptom intensity.

The disease/condition develops over many years. Initial symptoms are diffuse and mainly concern dripping progressing to obviously split stream (but most likely muscular pain has preceded that). At some point back pain and occasional perineal spasms start occurring. Unclear if the back pain and spasms precede dripping or developes during or even after.

In addition to the above vague problems with “penile sensitivity” start occurring and slowly semen/ejaculate start changing appearance. Parallel to this bouts of fatigue and malaise occur with increasing frequency and usually during winter with possibly a late winter early spring peak. Spring does also see an increase in depression-like symptoms. Palpitations do also occur but have no obvious pattern. Painful and/or uncoordinated (early and/or unexpected) ejaculation and “discoloring” of glans seems to be some sort of “end stage” problem.

Cold and freezing seems to precipitate spells of dysuria, but initiation of really bothersome dysuria and frequency seem to need a precipitating event. It seems that many sufferers seek medical attention at this point. Thus explaining the focus on urological causes.

Full blown CPPS tends to persist “unabated” for years, while milder forms tend to resolve with a few years. (In small study by Nickel symptoms resolved within a year in 38% of the subjects.) Or at least get manageable.

There may be a hereditary component!

A flare may look like this: dripping and nocturia begins, then back pain and some events of short inexplicable bursts of irritation and anger occur (hours), after these longer periods (days) of listlessness follow and finally palpitations occasionally occur. During the flare intestinal motility and libido diminishes and a progressive feeling of tiredness and fatigue develops. Micturition intervals decrease. Pain may occur during micturition and intercourse. Back pain is relieved by micturition. Flare ends pretty abruptly. Duration may be 3-4 weeks.

There is a collection of patient stories on this page: http://home.swipnet.se/isop/fallbeskrivningar.htm. The numbered links lead to english text.

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Do all these symptom clusters mean anything

What conclusions or inferences can be drawn from the symptom clusters?

If only there were the Sickness behaviour, Ejaculatory-genital and Micturition problems symptom clusters it would reasonable to assume some urinary or kidney infection, but some signs, like e.g. fever and hematouria are missing.

What may the Seasonal cluster indicate? Seasonality and a cyclical pattern of excacerbations and remissions is a common finding in auto-immune disease. Could there be an auto-immune component to CPPS? Research is unfortunately not too helpful here. Most studies are small and preliminary.

What can the Pituitary cluster indicate? Yes the name of the cluster is very leading. I choose it to point out that the pituitary may be implicated in many odd symptoms reported by CPPS sufferers. What is interesting is that the Micturition, Cardio-vascular and, maybe, the Seasonal clusters also fit in. Sickness behaviour may fit in as indicative of a condition that cause the release of pro-inflammatory cytokines that activates the HPA axis. Could that cause be infectious, auto-immune, dietary or environmental?

What about the remaining clusters? These are more difficult to fit in. Some, like mouth dryness, may be related to the pituitary (diabetes insipidus), abdominal pains may be caused by referred pain from the scrotum. Abdominal distension may be caused by pituitary dysfunction.

You may wonder if there are there any studies on the HPA axis and CPPS, or if these are only my personal musings? Yes, the pituitary angle is my personal idea, but when I perused PubMed to see if there were any studies made I did actually find a couple (see below for references).

A distinctive problem with the pituitary/HPA axis idea is that it may be related with dental amalgam fillings and mercury accumulation in the pituitary and not adrenal dysfunction as suggested by some. The association of amalgam and CPPS seems to never have been researched and the pretty infected debate re. mercury toxicity makes it doubtful if any researcher would be eager to endure the, possibly, years of controversy such a study would cause.

In the following I will review general information about CP/CPPS, current treatment and research into various etiologies, before returning to the symptom subject.

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Anderson RU, Orenberg EK, Chan CA, Morey A, Flores V. Psychometric Profiles and Hypothalamic-Pituitary-Adrenal Axis Function in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome. J Urol. 179(3):956-960, 2008.
Dimitrakov J, Joffe HV, Soldin SJ, Bolus R, Buffington CA, Nickel JC. Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome. Urology 71(2):261-6, 2008.
Dimitrakov J, Guthrie D. Genetics and Phenotyping of Urological Chronic Pelvic Pain Syndrome. J Urol. 2009 Feb 19.
Björkman L, Lundekvam BF, Laegreid T, Bertelsen BI, Morild I, Lilleng P, Lind B, Palm B, Vahter M. Mercury in human brain, blood, muscle and toenails in relation to exposure: an autopsy study. Environ Health. 6:30, 2007.

Remaining symptoms and signs

Below follow some anecdotal symptoms and signs that do not fit any cluster and that may or may not be related to CPPS.

• Improvement of symptoms during other infection: e.g. influenza and cold.

• Decrease lung capacity (by decreased bronchodilation)?

• Sudden feeling of mouth dryness (no noticeable concomitant thirst -- disruption of water balance?)

• Lower back pain / burning sensation.

• Inter-scapular (thoracic) back pain / burning sensation.

• Axel pain and weakness and arm paresthesias especially with carrying and physical exercise.

• Sinusitis.

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Cardio-vascular symptom cluster

The part about blood clotting is tentative and inferred from the fact that many of the of treatments (incl. phytotherapies) have an anti-thrombotic component.

• Increased propensity för blood-clotting due to cold. Increased fibrinogen production?

• Platelet disruption?

• Palpitations (i.e. different heart rhythm) occuring e.g. at bedtime or at wakening.

• Tachycardia, i.e. a faster than normal heart rhythm occuring despite an absence of physical effort.

(There are many causes of heart arrythmias. In our case it could e.g. be caused by disruptions of water and electrolyte balance or acid-base imbalance.)

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Pituitary symptom cluster

This is a tentative cluster. It is based on anecdotal evidence, facets of urinary and sickness behaviour symptoms, and foods reported to exacerbate symptoms. (The pituitary is also called hypophysis.)

Possibly pituitary / HPA-axis related problems
• Problems with vasopressin regulation. This is indicated by increased susceptibility to vasopressin antagonists. E.g. worsening of nocturia, diuresis and urgency after alcohol and caffeine intake. (I.e. symptoms showing a similarity with diabetes insipidus.)

• Sleep disruption (nocturia-caused or not?)

• Abrupt mood fluctuations (irritability, aggression and anger).

• Sudden feelings axiety with no obvious cause.

• Cold sweats. Similar to night sweats. Body temperature regulation. Anecdotal.

• Depression.

• Fatigue.

• Leg weakness.

• Lower than average bone density.

• Decreased / low libido. (Added march 4th 2009)

Possibly thyroid related problems
These symptoms may be caused by hypothyroidism. And yes there is a point in mentioning those with pituitary/HPA problems as pituitary regulation problems may cause secondary hypothyroidism.

• “Uncontrollable” nightly sweating / hot flashes. Indicates problems with body temperature regulation. Anecdotal.

• Cold sweats. Similar to night sweats. Body temperature regulation. Anecdotal.

• Feeling unfocused / not alert.

• Fatigue.

• Constipation.

• Feeling cold.

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Further reading
Sievers C, Ising M, Pfister H, Dimopoulou C, Schneider H, Roemmler J, Schopohl J, Stalla G. Personality in patients with pituitary adenomas is characterized by increased anxiety related traits: comparison of 70 acromegalic patients to patients with non-functioning pituitary adenomas and age- and gender matched controls. Europ J Endocrin 160:367, 2009.

Seasonal symptom cluster

This is an intriguing aspect of CP/CPPS symptoms. Question is what it means? Many auto-immune diseases show seasonal patterns superimposed on shorter term flare-remission patterns.

• General seasonal variation with all symptoms worsening during winter and improving during summer.

• Cold/winter exacerbated micturition problems (cold induced diuresis?). Caused by cold seat, cold feets, immersion in cold water and shivering etc.

• Cold/winter tension-induced muscular pains and aches (myalgia)?

• Cold/winter induced arthralgia (joint aches, but joints are not swollen or reddish)?

• Cold/winter induced fibrinogen production? This is inferred from the fact that a majority of treatments have an anti-thrombotic component and research (e.g. 1-2).

• Winter related dryness of eyes and nose? (Note that winter air is drier than summer air due to lower absolute humidity. Average water content below zero degress Celsius is below 5 grams water per kg air.)

• The micturition problems do also seem to follow a cyclical pattern (duration of about three weeks?) of exacerbations and improvement.

• There may also be a weak circadian rhythm.

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(1) Rudnicka AR, Rumley A, Lowe, GDO, Strachan DP. Diurnal, Seasonal, and Blood-Processing Patterns in Levels of Circulating Fibrinogen, Fibrin D-Dimer, C-Reactive Protein, Tissue Plasminogen Activator, and von Willebrand Factor in a 45-Year-Old Population. Circulation 115:996-1003, 2007.
(2) Crawford VLS, McNerlan SE, Stout RW. Seasonal changes in platelets, fibrinogen and factor VII in elderly people. Age and Ageing 32:661-665, 2003.

Some examples of human chronobiology:
One study showed e.g. that cortisol peaked in december, FT3 (thyroid hormone) and growth hormone in april, insulin in february, while prolactin and parathyroid hormone showed no variation. (Del Ponte A, Guagnano MT, Sensi S. Time-Related Behaviour of Endocrine Secretion: Circannual Variations of FT3, Cortisol, Hgh and Serum Basal Insulin in Healthy Subjects. Chronobiol Int 1(4):297-300, 1984.)

(Minor update/edit march 4th 2009)

Abdominal symptom cluster

Notice that this is not a "mixed" symptom cluster as I have bunched together problems that do likely have no gastro-intestinal origin whith those that most likely have.

1) One group of symptoms do most likely originate from the scrotum, but cause pain felt from the "upper" abdomen or elsewhere. These are:

• Flank pain (between iliac crest, hip, and lowest rib) from mild to appendicitis-like. A common cause is a focal source in the scrotum that is referred to one or both flanks. If this focal source, ususally sized 2-3 millimiters across, is palpated it should cause both localized pain to this little spot as well as pain in the flanks, and maybe nausea. INDICATIVE

• Appendicitis-like pain (see flank pain above for comments)

• Nausea (a common cause is scrotal pain)

2) The second group of problems is more clearly gastro-intestinal. These are:

• Constipation (may be related to flares)

• Abdominal distension (“swollen belly”)

• “Golf-ball in the rectum” feeling (this is similar to chronic proctalgia)

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Sickness behaviour symptom cluster

A combination of symptoms generally found after immune activation regardless of source (viral, bacterial, fungal, protozoal, pain, tissue damage etc). Clinically often noticed. Has been studied in cancer treatment. All these symptoms/signs can be regarded as indicative for CPPS-sufferers as they often wax and wane during the course of the illness, while no other obvious source can be found. Actually CPPS has been reported to occasionally go in remission when a CPPS sufferer falls ill in the flu, or catches a cold etc.

Notice that some of the symptoms below are more or less synonyms (anhedonia and depression; fatigue, asthenia, sleepiness and tiredness).

• Malaise: “A feeling of general discomfort or uneasiness, an 'out-of-sorts' feeling...” (From Stedman’s.)

• Fatigue: “…a lessened capacity for work and reduced efficiency of accomplishment, usually accompanied by a feeling of weariness, sleepiness, or irritability; may also supervene when, from any cause, energy expenditure outstrips restorative processes…” (From Stedman’s.)

• Asthenia: weakness, “lack of motor activity or strength”.

• Tiredness / sleepiness.

• Depression / dejection (lessened interest in other people, withdrawal etc). It may be noted that a subgroup of clinically depressed people have excess levels of (pro-) inflammatory mediators (substances).

• Anhedonia / listlessness (“…sensation of boredom and lassitude due to absence of stimulation, monotony, or lack of interest in one's surroundings.” From Stedman’s.)

• Lessened hunger / difficulty putting on weight (“anorexia”).

• Anxiety (withdrawal, feeling uncomfortable / nervous in public places or social situations, “paranoia”) etc..

• Irritability normally co-occuring with fatigue / tiredness etc, but may also occur for no obvious reason.

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Ejaculatory-genital symptom cluster

These are all anecdotal (meaning patient or practitioner observations). Notice that if you have pain in the left scrotum/testicle, then you should have left sided penile and flank pain (may be bilateral though). Focal thigh pain should also be leftsided. Most of these symptoms are indicative. If it is not sure if indicative a (Ind?) has been added at the end of the symptom/sign description.

Penile paresthesia-like symptoms:
• Penis / glans pain / discomfort (not necessarily at urination).

• Penile numbness / insensitivity to “friction” and maybe also diminished feeling of orgasm (diminished “sexual excitability”). Less noticeable in circumcised men? (Ind?).

• “Ejaculatory dyssynergia”: uncoordinated (early, unexpected, partially “failed”, “incomplete”) ejaculation.

Pain phenomena:
• Painful ejaculation (epidydimitis?).

• Groin pain / discomfort.

• Pain / discomfort from the scrotum (often referred to as testicular pain, orchialgia, or “tight trousers feeling” or “uncomfortable chair feeling”).

• Perineal spasms and pain / discomfort (lasting seconds to minutes and then disappearing completely -- this is similar to proctalgia fugax that is centerad around the anus).

• Focal thigh pain or pain down one leg associated with scrotal pain (many other possible causes though: knee problems, leg length, sciatica etc).

Other:
• Receding foreskin during flares (Ind?).

• Discoloration (bluish-whitish-pinkish mottled hue) of glans (Ind?).

• Semen abnormalities (yellowish, “watery”, non-homogenous look) (Ind?).

• Decreased / low libido. (Added march 4th 2009)

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Micturition problems symptom cluster

All of the below items are regarded as indicative for CP/CPPS, but also for infection, and in part for dyssynergia (detrusor (sphincter) dyssynergia) or obstruction.

• Diuresis/Pollakiuria: frequent urination/micturition of varying amounts (normal is about 3-6 times tops during the day and none during sleep).

• Nocturia (nycturia): micturition urge that is causing the interruption or shortening of normal sleep. Especially if often and repeatedly recurring.

• Urinary urgency: a sudden and pressing urge to urinate (normally this feeling should slowly start to grow as the bladder is distended, ie filled, beyond a certain cut-off).

Dysuria and stranguria like problems:
• Difficulty and/or painful urination in general.

• Dribbling, weak (slow) and split stream without burning sensation or pain.

• Start-stop micturition (especially at the end of micturition). A feeling of having to “squirt out” the last drops.

• A feeling of not having completely emptied the bladder.

Other:
• Urine smell (despite no obvious alimentary source like asparagus, white wine or selenium yeast supplements).

• “Foaming urine”, i.e. when stream hits enclosed water surface, without any proteinuria.

• Sporadic dark urine?, despite adequate water intake and no no obvious alimentary source.

• Penile paresthesia-like problems: burning sensation or pain in urether or tip of penis when urinating and not.

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The concept of symptom clusters

The concept of symptom clusters -- "a stable group of two or more concurrent symptoms that are related to one another and independent of other symptoms” was advanced some years ago as a viable way of systematically improve the treatment of primarily cancer patients.(1,2) Clusters, even if the concept is not used, are also the common way of describing diseases of unknown etiology: aka “syndromes”.

Ideally clustering should help identify patient subgroups and indicate possible underlying causes.

A couple of CPPS clusters are tentatively singled out below. The "micturition" and "ejaculatory-genital" clusters are the common reason that advice is sought from a urologist, as these, especially frequency and dribbling and sexual disturbances, conspicuously affect daily life.

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(1) Dodd M, Janson S, Facione N, Faucett J, Froelicher ES, Humphreys J, Lee K, Miaskowski C, Puntillo K, Rankin S, Taylor D. Advancing the science of symptom management. J Adv Nurs 33(5):668-676, 2001.
(2) Barsevick AM. The elusive concept of the symptom cluster. Oncol Nurs Forum 34(5):971-980, 2007.

Symptoms and signs

CPPS is a slow disease evolving usually over many years. The patient commonly begins feeling weak with influenza like symptoms(fatigue/malaise) and having occasional discomfort with diffuse urinary problems like dribbling and penile "insensitivity" (paresthesia) that progresses in the worst case to severely debilitating pain and urgency. Progress can be sudden and rapid (within a few weeks), and an assumed triggering event is sometimes mentioned. Help is usually sought when pain and/or urinary and sexual problems begin to interfere with everyday life or there is a sudden obvious increase in symptoms. Sudden onset of urgency seems btw to be an important cause to seek medical advice. Stabilization and even permanent remission may occur after many years.

The common denominators for prostatitis/CPPS are symptoms emanating especially from the pelvis, groin and uro-genital apparatus.(1) The disease has a distinct periodicity / cyclicity with recurring flares (exacerbations) and improvements (remissions). Anecdotal evidence and studies also indicate that winter and spring see more flares and pain (discomfort, pressure-like sensations), while symptoms tend to vane or disappear during the summer (cold seems to worsen problems, while sun and heat ameliorates them).

Many patients indicate that flares are triggered by cold (freezing in general, just the feet, sitting on cold surfaces and swims in cold water). Also bicycling and vibrations from motorcycles and similar have been mentioned as problematical. Symptoms that may indicate a myofascial/tension disorder.

A small study noted that: "The informants also reported that cold exposure caused aggravation of symptoms and provoked their relapse. Sitting on cold objects, spending time in cold, damp or windy surroundings and walking on a cold floor were provocative and thus were avoided."(2)

A detailed review of symptom frequency can be found in "Symptoms correlated with prostatitis".(3) "A summary report on the impact of Prostatitis and Benign Prostatic Hyperplasia on men's lives and those of their families"(4) is also available.

In my next posts I will discuss symptom clusters and suggest clusters in CPPS (I have grouped symptoms, documented and anecdotal--I will also add INDICATIVE after the symptoms/signs that are most likely indicative of CPPS).

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(1) Moon TD et al., Urinary symptomatology in younger men, J Urol 50:700-703, 1997
(2) Hedelin H, Jonsson K. Chronic abacterial prostatitis and cold exposure. Scand J Urol Nephrol. 2007 May 9;1-6 [Epub ahead of print].
(3) Guercini F, Pajoncini C, Bini V, Porena M. Symptoms correlated with prostatitis. International Continence Society 2002:237.
(4) Bernardes J, Cameron E, Dunn P.“A summary report on the impact of Prostatitis and Benign Prostatic Hyperplasia on men's lives and those of their families” (“http://uk.groups.yahoo.com/group/bps-assoc/files/ Kings Fund Full Report (pdf)”)