: deformity <60 , no complex deformity, Nesbit procedure predicted loss of erectile length <20%. Lue procedure loss of penile lengt h. : deformity >60 , hinge deformity, aim for minimal Patients with poor erectile function preoperatively (and/or poor response to pharmacotherap y) - : deformity >60 , complex deformity, cavernosal Penile prosthesis \201 brosis. 1 Ralph D, Gonzalez-Cadavid N, Mirone V, et al. (2010)The management of Peyronie \200\231s disease: evidence based 2010 guidelines. J Sex Med 7:2359 \200\22374. 2 Gelbard MK, Dorey F, James K, et al. (1990) The natural history of Peyronie \200\231s dis ease. J Urol 144:1376 \200\2239. 3 Levine LA, Goldman KE, Green \201 eld JM (2002) Experience with intraplaque injection of verapamil for Peyronie \200\231s disease. J Urol 168:621 \200\2235. 4 Riedl CR, Plas E, Engelhardt P, Daha K, P \202 ger H (2000) Iontophoresis for treatmen t of Peyronie \200\231s disease. J Urol 163:95 \200\2239. This page intentionally left blank CHAPTER 13 Sexual health 584 Priapism De \201 nition: prolonged, unwanted erection, in the absence of sexual desire or stimulus, lasting >4h. Epidemiology: incidence of 1.5 per 100 000,1 with peaks at ages 5 \200\22310 and 20 \200 \22350. Classi \201 cation - Low- \202 ow (ischaemic) priapism: (intracavernosal pressures of 80 \200\223120mmHg). Most common form which manifests as a painful, rigid erection, with absent or low cavernosal bl ood \202 ow. Ischaemic priapism >4h requires emergency intervention. Blood gas analysis s hows hypoxia and acidosis. High- \202 ow (non-ischaemic) priapism: blood \202 ow, presen ting with a semi-rigid, painless erection. Usually due to trauma and subsequent \201 stul a development and usually self-limiting. Blood gas analysis shows similar results to arteri al blood. Recurrent (or stuttering) priapism: disease. Usually high \202 ow, but may chan ge to low \202 ow with anoxia. due to veno-occlusion due to unregulated arterial most commonly seen in sickle cell Etiology (Tables 13.5, 13.6) Causes are primary (idiopathic) or secondary, including: - pap averine; PGE1. - Intracavernosal injection therapy: A-blockers; antidepressants; antipsychotics; psychotroph ics; Drugs: tranquilizers; anxiolytics; anticoagulants; recreational drugs; alcohol excess; total parenteral nutrition. Thromboembolic: emboli. Neurogenic: Trauma: laceration or arte riovenous \201 stula formation. Infection: Other: sickle cell disease; leukemia; thalassaemia; fat spinal cord lesion; autonomic neuropathy; anesthesia. penile or perineal injury, resulting in cavernosal artery malaria; rabies; scorpion sting, genitourinary sepsis. prostate or bladder cancer extending into penis; amyloidosis. Pathophysiology Priapism lasting for 12h causes trabecular interstitial oedema, followed by destruction of sinusoidal endothelium and exposure of the basement membrane at 24h and sin usoidal thrombi, smooth muscle cell necrosis, and \201 brosis at 48h. Evaluation - - - Serum testing: Cavernous blood samples: Color Doppler Reduced blood \202 ow in ischaemic priapism; ruptured artery with pooling of blood around injured area in non-ischaemic priapi sm. to exclude sickle cell, leukemia, and thalassaemia. to determine type of priapism. USS: of cavernosus artery and corpora cavernosa. Management in adults (Fig.13.4) Ice packs, cold showers, and exercise may be bene \201 cia l in early stages. PRIAPISM 585 Low- \202 ow priapism Decompress urgently with aspiration of blood from the corpora (5mL p ortions using a 18 \200\22320 gauge butter \202 y needle until oxygenated red blood is obt ained). If no change after 10min, proceed to intracavernosal injec- tion of A1-adrenergic a gonist (phenylephrine 100 \200\223200mcg (0.5 \200\2231mL of a 200mcg/mL solution to a maxi mum of 1mg)) every 5 \200\22310min until detu- mescence (loss of erection) occurs; see M ww w.bnf.org). Monitor BP and pulse during drug administration. Oral terbutaline may be effect ive treatment for intracavernosal injection-related cases. Sickle cell disease requires, in addition, aggressive rehydration, oxygenation, analgesia, and hematological input (conside r exchange transfusion). If aspiration and phenylephrine fails after 1h, surgical intervention is attempted with shu nt and biopsy. Following a penile block, the Winter technique places a Trucut biopsy needle through the glans into the corpora cavernosa to remove small pieces of tunica albuginea an d allow evacuation of hypoxic blood. Alternatively, a small blade stab incision is made via the glans into the corpora, avoiding the urethra. If there is no response, corpo- rosaphen ous shunting can be considered where the long saphenous vein is tunneled and anastomosed on to the corpora cavernosum. If this fails or patients present late (after 48 \200\22372h), discuss the insertion of a p enile prosthesis. This will treat both the priapism and inevitable ED and avoids the dif \201 culty and high complication rates of delayed insertion into a \201 brotic penis. High- \202 ow priapism Conservative treatment is recommended in most cases. Traumatic or d elayed presentations require arteriography and either selective or internal pudendal artery embolization with autologous blood clot or fat. Ligation of \201 stula may be required. Recurrent priapism Optimize hematological management of sickle cell disease to reduce fre- quency of attacks. Regular oral alpha agonists such as etylephrine can be helpful and/or an drogen suppression (i.e. cyproterone acetate). Complications: 90% of priapism lasting >24h develop complete ED. CHAPTER 13 Sexual health 586 Table 13.5 Causes of low- and high- \202 ow priapism Low- \202 ow priapism High- \202 ow priapism Intracavernosal drug injection Arteriovenous \201 stula (secondary to penile or perineal trauma or surgery) Oral medications Hematological disease: sickle cell disease, leukemia, thalassaemia Fat embolus Spinal cord lesion Autonomic neuropathy Malignancy Table 13.6 Examples of drugs which may cause priapism Class of drug Examples Antihypertensives/alpha blockers Prazosin, hydralazine Antidepressants Sertraline, \202 uoxetine, lithium Antipsychotics Clozapine Psychotrophics Chlorpromazine Tranquilizers Mesoridazine Anxiolytics Hydroxyzine Anticoagulants Warfarin, heparin Recreational drugs Cocaine 1 Eland IA, van der Lei, Strickler BH, et al. (2001) Incidence of priapism in the general p opulation. Urology 57:970 \200\2234. PRIAPISM 587 History, examination, hematological analysis \200 Ice packs, cold showers, exercise \200 Analgesia, consider oral drugs (terbutaline) \200 Resuscitate sickle cell crisis Initial management Corporal blood gas analysis \200 Doppler USS (if available) Aspiration Bright red blood/ non-ischaemic Black blood/ ischaemic Low - flow priapism High - flow priapism \200 Observation Aspiration irrigation Conservative management Intracavernosal phenylephrine Shunt and biopsy \200 Penile prosthesis Embolization Failed conservative management Fig. 13.4 Management of priapism. CHAPTER 13 Sexual health 588 Retrograde ejaculation De \201 nition Failure of adequate bladder neck contraction results in the propulsion of sperm back into the bladder on ejaculation. Etiology Acquired causes are due to damage or dysfunction of the bladder neck sphincter mec hanism. These include neurological disease (SCI; neuropa- thy associated with diabetes mell itus; nerve damage after retroperitoneal surgery) or anatomical disruption following transu rethral resection of ejaculatory ducts (for obstruction), bladder neck incision (BNI), TURP , or open prostatectomy. Drugs to treat BOO (A-blockers) causes reversible retrograde ejacu lation in 5% of men. Congenital causes include bladder exstrophy, ectopic ejaculatory ducts , and spina bi \201 da. Incidence Retrograde ejaculation following TURP or open prostatectomy occurs in 9 out of 10 men and after BNI, in 1 \200\2235 in 10. Presentation \200\230Dry \200\231 ejaculation (failure to expel ejaculate \202 uid from the urethral meatus) or low ejaculate volume (<1mL) and cloudy urine (containing sperm) in the \201 rst void after intercourse. Investigation The presence of >10 \200\22315 sperm per high powered \201 eld in post-orga smic urine specimens con \201 rms the diagnosis of retrograde ejaculation. Treatment Medical therapy: is initiated in men wishing to preserve fertility and is only ef fective in patients who have not had bladder neck surgery. Therapy is often given for 7 \200\22310 days prior to a planned ejaculation (coordinated with the partner \200\231s ovul ation). - A-adrenergic receptor agonist drugs (ephedrine sulfate, Oral pseudoephedrine) may be used t o increase the sympathetic tone of the bladder neck smooth muscle sphincter mechanism. Imip ramine, a tricyclic antidepressant drug with anticholinergic and sympathomimetic effect, ma y also be used (25mg bd to tds). Sperm retrieval from urine for assisted fertility techniques Oral sodium bicarbonate and ad justment of \202 uid intake is initiated to opti- mize urine osmolarity and pH and enhanc e sperm survival. Sperm are collected by gentle urine centrifuge and washed in insemination media in preparation for IUI or IVF treatments. This page intentionally left blank CHAPTER 13 Sexual health 590 Premature ejaculation De \201 nition Premature ejaculation (PE) is classi \201 ed as life long or acquired. The International Society for Sexual Medicine (ISSM) de \201 nes lifelon g PE as \200\230ejaculation which always or nearly always occurs prior to or within one mi nute of vaginal penetration and the inability to delay ejaculation on all or nearly all vag inal penetrations and negative consequences such as distress, bother, frustration, or avoid ance of sexual intimacy \200\231.1 Related conditions include natural variable PE and PE-li ke dysfunction. Etiology Psychological - - - Early sexual experience. Anxiety. Reduced frequency of sexual intercourse. Biological - - Penile hypersensitivity. 5-Hydroxytryptamine (5- central control of ejaculation). Hyperexci table ejaculatory re \202 ex. HT) receptor sensitivity (involved in the Evaluation Detailed medical, sexual, and psychosocial history and physical examina- tion. E stablish perceived degree of ejaculatory control, onset, and duration of the problem. Quant itative measures of sexual intercourse include: - Intravaginal ejaculatory latency time ( IELT) \200\224the time between vaginal penetration and ejaculation averaged over several performances. IELT <1 \200\2232min suggests a diagnos is of PE.* Score of partner \200\231s sexual satisfaction. Patient \200\231s assessment of his voluntary control over ejaculation. Treatment Behavioral - - Counseling. Seman \200\231s stop \200\223start maneuver (inhibiting the urge to ejaculate b y repeatedly stopping sexual stimulation). Masters \200\231s and Johnson \200\231s squeeze technique (inhibiting the urge to ejaculate by squeezing the glans penis). Sensate focus. Pharmacological - SSRIs). Paroxetine 20mg daily Selective serotonin reuptake inhibitors ( (unlicensed) is the most effective and can also b e used on demand 4 \200\2236h before intercourse. Dapoxetine is licensed for on demand use and has a more rapid onset of action and shorter half-life. Alternatives taken daily are se rtraline, \202 uoxetine, and citalopram (not licensed). Side effects include gastrointest inal effects, anorexia, and rash. PREMATURE EJACULATION 591 Clomipramine (tricyclic antidepressant) given daily or as required 4 \200\2236h before inte rcourse. Side effects include dry mouth, sedation, blurred vision, dif \201 culty voiding. Topical local anesthetics such as lidocaine and/or prilocaine cream, gel, or spray (with c ondom to prevent transvaginal absorption with resultant vaginal numbness). PDE5 ejaculation associated with ED. inhibitors (sildena \201 l): limited role for acquired premature Gradual withdrawal of drug therapy can be attempted after 6 \200\2238 weeks. 3 \200\22330min. Both conditions respond to reassurance, education, and behavioral therapy. In comparison, natural variable PE has an IELT of 3 \200\2238min; PE-like dysfunction has a n IELT of 1 Montorsi F, Adaikan G, Becher E, et al. (2010) Summary of the recommendations on sexual d ysfunction in men. J Sex Med 7:3572 \200\22388. CHAPTER 13 Sexual health 592 Other disorders of ejaculation and orgasm De \201 nition The ISSM de \201 nes orgasmic dy sfunction as: \200\230inability to achieve an orgasm or markedly diminished intensity of o rgasmic sensation \200\231 or \200\230marked delay of orgasm during any kind of sexual sti mulation \200\231.1 Under this category, they include delayed ejaculation, inhibited ejacul ation, retarded (and partially retarded) ejaculation, anejaculation, and anorgasmia.1 Delayed ejaculation (DE): is \200\230the persistent or recurrent dif \201 culty, delay in , or absence of attaining orgasm after sexual suf \201 cient stimulation, which causes per sonal distress \200\231.2 It may be lifelong or acquired, global or situ- ational, and the prevalence increases with age (Table 13.7).3 Anejaculation: is the complete absence of an antegrade or retrograde ejaculation. There is failure of emission from the seminal vesicles, prostate, and ejaculatory ducts into the ure thra. True anejaculation is associated with normal orgasm and is most often due to drug-rel ated causes or cen- tral or peripheral nervous system dysfunction (Table 13.7). Anorgasmia: is the inability to reach orgasm (which may give rise to ane- jaculation in men ). This is rare. Primary conditions are usually attributed to psychological causes. Seconda ry causes may be related to drugs or decreased penile sensation (secondary to pudendal nerv e dysfunction, seen in peripheral neuropathy associated with diabetes mellitus) (Table 13.7 ). Evaluation A detailed sexual history, including the exact symptoms, duration, related arous al or desire problems, and precipitating factors should be taken. A full medical and drug h istory identi \201 es any underlying or reversible causes. A focused physical (including e xternal genitalia and palpation for bilateral vasa) and neurological examination (including bulbocavernosus re \202 ex, anal sphincter tone, and perineal sensitivity where appropria te) should be performed. Urine microscopy and culture may identify infection. Post- ejacula tory urinalysis can be performed to exclude retrograde ejacula- tion. If there is clinical suspicion of possible ejaculatory duct obstruction, consider transrectal USS, vasography, o r percutaneous puncture of the seminal vesicles. Cystourethroscopy can be used to assess th e ejaculatory ducts and exclude urethral obstruction (urethral stensosis). Management General: aim to identify and treat the underlying etiology and address any infer tility issues in men of reproductive age. Patient education and coun- selling on lifestyle change (i.e. reducing alcohol consumption, attempting sexual intercourse when not tired) ar e helpful adjuvants. If an organic cause has been excluded, psychosexual therapy is recomme nded. Drugs: that facilitate ejaculation by central dopaminergic or antiseroton- ergic acti on have been tried, especially in drug-induced anejaculation, OTHER DISORDERS OF EJACULATION AND ORGASM 593 Table 13.7 Causes of delayed ejaculation, anejaculation, and anorgasmia3 Drugs Antihypertensive drugs (thiazides) Antidepressants (tricyclics, SSRIs) Antipsychotic drugs (phenothiazines) Alcohol excess Neurological Diabetic autonomic neuropathy Spinal cord injury Multiple sclerosis Parkinson \200\231s disease Pelvic surgery (2 to proctocolectomy) Para-aortic lymphadenectomy Psychological Surgical Prostate surgery (TURP, BNI) Congenital Mullerian duct obstruction Infection Urethritis Endocrine Hypogonadism, hypothyroidism although no randomized trials have been carried out for this condition. Examples include: 5 -HT receptor antagonists (cyproheptadine); dop- aminergic drugs (amantadine, yohimbine); do pamine reuptake inhibitors (bupropion); 5-HT1A receptor agonists (buspirone). The treatment of delayed ejaculation is similar to anejaculation. Anejaculation: where the aim is to ret rieve sperm for ART methods include: - Vibrostimulation evoking the ejaculation re \202 ex. It requires an intact lumbosacral spi nal cord segment. Electroejaculation: nerves via a rectal probe, usually under anesthesia. Can also be used for anorgasmia. ( \201 rst-line therapy): a vibrator is applied to the penis, involves the electrical stimulation of periprostatic 1 Montorsi F, Adaikan G, Becher E, et al. (2010) Summary of the recommendations on sexual d ysfunction in men. J Sex Med 7:3572 \200\22388. 2 McMahon CG, Althof SE, Waldinger MD, et al. (2008) An evidence-based de \201 nition of l ifelong premature ejaculation: Report of the International Society of Sexual Medicine (ISSM ) ad hoc com- mittee for the de \201 nition of premature ejaculation. J Sex Med 5:1590 \200\223606. 3 Rowland D, McMahon CG, Abdo C, et al. (2010) Disorders of ejaculation and orgasm in men. J Sex Med 7:1668 \200\22386. CHAPTER 13 Sexual health 594 Late-onset hypogonadism (LOH) Late-onset hypogonadism (LOH): is de \201 ned as \200\230a clinical and biochemical syndrome associated with advancing age and characterized by sympto ms and a de \201 ciency in serum testosterone levels (below the young healthy adult male r eference range). This condition may result in signi \201 cant det- riment in the quality o f life and adversely affect the function of multiple organ systems \200\231.1 It is also kn own as age-associated testosterone de \201 ciency (TDS).1 Pathophysiology LOH involves components of both primary and secondary hypogonadism (see b p . 596) and a degree of reduced responsiveness of target organs to testosterone and its adro genic mediators. Ageing decreases the pro- duction of LHRH and LH due to effects on the hyp othalamus and pitui- tary. This causes a decline in the both the number of Leydig cells in the testes and their sensitivity to LH so reducing testosterone levels. SHBG binds testoste rone and renders it unavailable to most tissues and levels of SHBG increase with age. Along with age-related changes in androgen receptors and altered androgen metabolism, the result is less bioavailable testosterone. Presentation ED- - - - - - - - - - - . Reduced libido. Reduced concentration. Hot \202 ushes. Changes in mood (depression). Leth argy/fatigue. Sleep disturbance. Hair/skin changes. Osteoporosis. Decreased muscle mass and strength. Infertility. Evaluation (see Fig. 13.5) - - History to elicit symptoms related to low testosterone levels. Examination, including prior to giving testosterone and to assess prostate size). Flow rate and post-void residual volu me to assess for Serum bloods: early morning total testosterone, and fasting lipid pro \201 le. Further blood tests: prolactin (if total testosterone <5.2nmol/L); SHBG (if border line testosterone or if suspect secondary hypogonadism). DEXA DRE (with PSA to exclude prostate cancer BOO. LH, PSA, FBC, LFT, scan to check bone mineral density. LATE-ONSET HYPOGONADISM (LOH) 595 Testosterone assessment In a normal adult male, the serum testosterone reference range is a round 10.4 \200\22334.7nmol/L. Testosterone levels show diurnal variation, peaking in early morning and recommendations for testing are: - - Early morning serum total testosterone (taken 8:00 \200\22311:00 a.m.). If low or borderlin e total testosterone level, perform repeat testosterone level with LH, FSH, and prolactin. Treatment of LOH Symptoms and biochemical evidence of testosterone de \201 ciency indicate the need for testosterone replacement therapy (Fig. 13.5). Where testo- sterone levels are borderline/normal, but symptoms are present, consider an initial 3-month trial of testoste rone and then review (see b p. 597). Residual symptoms may need speci \201 c treatment suc h as PDE5 inhibitors for ED. For normal testosterone physiology, refer to b p. 552; for normal androgen metabolic pathways, see b p. 684. Symptomatic LOH History Examination (DRE) Serum PSA, FBC, LFT, lipids Early morning serum total testosterone Normal testosterone Low testosterone Borderline low Repeat testosterone with LH/FSH prolactin Reassess Repeat testosterone with LH/FSH and prolactin Low testosterone Borderline low and symptoms Testosterone replacement therapy 3 month trial testosterone therapy Clinical symptom improvement DRE + PSA 3 monthly 1st year then annually Recheck FBC, lipids Yes No Fig. 13.5 Management pathway for symptomatic LOH. 1 Wang C, Nieschlag E, Swerdloff R, et al. (2009) Investigation, treatment and monitoring o f late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 55:121 \200\22330. CHAPTER 13 Sexual health 596 Hypogonadism and male hormone replacement therapy Male hypogonadism has been de \201 ned a s inadequate gonadal function due to de \201 ciencies in gametogenesis and/or the secretio n of gonadal hormones. Hypogonadism may be primary (due to abnormal testicular function or testicular response to gonadotrophins) or secondary (due to failure of the hypothalamic \200\223pituitary axis, leading to inadequate gona- dotrophic stimulation and reduced testi cular testosterone production (Table 13.8). The result is testosterone de \201 ciency. Indications for testosterone treatment Hypogonadism and related symptoms caused by low test osterone levels. Symptomatic LOH and primary hypogonadism should be treated with androgens. Patients with secondary hypogonadism may be given LH and FSH or pulsatile LHRH if fertilit y is required, otherwise they should receive androgen replacement (see b p. 598). The aim i s to achieve nor- mal serum testosterone levels. Contraindications to testosterone treatment - - - - - - - - Male breast cancer. Prostate cancer (current recommendation, but is controversial). History of primary liver tumor. Hypercalcaemia. Clinically signi \201 cant obstructive benign pro static enlargement. Pre-existing polycythaemia. Avoid if untreated severe liver, renal, or heart failure. Untreated sleep apnoea. Assessment prior to testosterone treatment - In men >45y, prostate health. Fasting lipid pro \201 le LFT FBC . Flow rate, residual v olume, IPSS to assess for BOO. Assess bone density prior to and during treatment ( DRE and serum PSA are mandatory to assess - - - DEXA scan). Assessment during testosterone treatment - DRE (for prostate cancer). FBC new onset polycythaemia). Fasting lipid pro \201 le (testos terone can alter total and low-density lipoprotein cholesterol). and PSA every 3 \200\2236 months for the \201 rst 12 months, then yearly every 3 \200\2236 months for the \201 rst year and then yearly (to assess for HYPOGONADISM AND MALE HORMONE REPLACEMENT THERAPY 597 Side effects of testosterone treatment - - - - - - - - - - Headache. Oedema due to sodium retention. Depression. Gastrointestinal bleeding. Nausea. Ch olestatic jaundice. Liver toxicity. Gynaecomastia. Androgenic effects (hirsutism, male patt ern baldness). Polycythaemia. Testosterone treatment Testosterone replacement can be given by transdermal patch or gel, i ntramuscular injection, subdermal implant, buccal, and oral administra- tions (Table 13.9). Transdermal preparations produce a normal testoster- one level with physiological diurnal pro \201 le, but they can produce local skin reaction. Intramuscular injections are long-a cting, but do not pro- vide normal hormonal circadian rhythm. Oral preparations tend to be less used due to variable pharmacokinetics. Buccal mucoadhesive tablets (Striant ) produce more reliable testosterone levels, but require twice daily application. Metabolic syndrome This is characterized by central obesity, insulin resistance, dyslipidae mia, and hypertension, resulting in increased risk of cardiovascular disease and progressio n to diabetes mellitus. Hypogonadism is frequently associated with metabolic syndrome. Ther e is evidence that testosterone treatment may help some conditions associated with the synd rome and reduce the risk of cardiovascular complications. Table 13.8 Causes of primary and secondary hypogonadism Primary hypogonadism (hypergonadotrophic hypogonadism) Secondary hypogonadism (hypogonadotrophic hypogonadism) Congenital Chromosomal (Klinefelter \200\231s syndrome) Undescended testes Congenital Kallmann \200\231s syndrome* Acquired Acquired Surgery (bilateral orchidectomy) Hypopituitarism (pituitary lesion; surgery or radiation to the cranium) Bilateral testicular torsion Radiotherapy/chemotherapy Infection (bilateral orchitis) Cirrhosis Kallman \200\231s syndrome is an isolated gonadotrophin (GnRH) de \201 ciency which leads to hypogonadism. CHAPTER 13 Sexual health 598 Table 13.9 Testosterone preparations Route of administration Examples of preparations Dosing regimen Intramuscular injection Testosterone enantate Initial: 250mg every 2 \200\2233 weeks Maintenance: 250mg every 3 \200\2236 weeks Sustanon 250 1mL every 3 weeks Nebido 1g every 6 weeks for 12 weeks Maintenance: 1g every 3 months Implant Testosterone 100 \200\223600mg; 600mg maintains plasma testosterone in normal range for 4 \200\2235 mont hs Andropatch Transdermal patch 2.5 \200\2237.5mg/24h: dose according to plasma testosterone concentration Testim Transdermal gel 5g gel (50mg testosterone) apply daily; adjust according to response (max 10g gel/24h) Testogel 5g gel (50mg testosterone), apply daily Can be increased to 10g daily Striant Buccal 30mg 12-hourly Restandol (testosterone undecanoate) Oral 40mg 3 \200\2234 times per day (120 \200\223160mg daily) for 2 \200\2233 weeks Maintenance: 40 \200\223120mg daily This page intentionally left blank CHAPTER 13 Sexual health 600 Urethritis Urethritis is in \202 ammation of the urethra. Infective urethritis may present with clear, mucopurulent, or purulent urethral discharge, colored white, yellow, green, or brown. It can be associated with dysuria and pain at the external urethral meatus or in th e penile shaft, which persist between voiding. There may be urinary frequency and urgency. Some infections are asymptomatic. Infective causes - - - - - - Chlamydia (C.) trachomatis. Neisseria (N.) gonorrhoeae. Trichomonas vaginalis. Ureaplasma u realyticum. Mycoplasma genitalium. Herpes simplex virus. Evaluation Assess symptoms, sexual history, and sexual contacts. Examine external genitalia for testicular or epididymal tenderness, discharge at the mea- tus, lymphadenopathy, or sk in lesions. Refer to genitourinary medicine for management and to trace and treat contacts. Investigation The diagnosis of urethritis on urethral smear is de \201 ned as \211 5 poly morpho- nuclear leucocytes (PMNL) per high powered \201 eld (1000 magni \201 cation) or \211 10 PMNL per high powered \201 eld (400 times magni \201 cation) in the \201 rst voiding urine specimen. Speci \201 c tests - Urethral swabs (with endocervical swabs in women) transported in charcoal transportation me dium. Used for culture and Gram stain to identify N. gonorrhoeae. Also used for nucleic aci d ampli \201 cation test (NAAT) or enzyme immunoassay (EIA) to detect N. gonorrhoeae and C . trachomatis. First 20mL void of urine (after holding urine identify C. trachomatis. MSU I n selected cases, consider plasma regain (RPR) test. \211 1h). Used for EIA to : dipstick testing 9 microscopy to investigate UTI. HIV and syphilis testing with serum rapid Gonococcal urethritis (GU): is caused by the Gram-negative dipplococ- cus N. gonorrhea. Com plications include genitourinary tract involvement causing epididymitis. Haematogenous spre ad of infection to other sites (71%) can cause disseminated gonococcal infection (DGI), man ifest initially as tendon or joint pain (see Table 13.10). Non-gonococcal urethritis (NGU): is mainly caused by C. tracho- matis infection and may be asymptomatic (particularly in women). include oculogenital syndrome (NGU and Speci \201 c complications conjunctivitis). Transmission to females results in increased risk of pelvic URETHRITIS 601 in \202 ammatory disease, abdominal pain, ectopic pregnancy, infertility, and perinatal in fection (see Table 13.10). Genitourinary tract complications - - - Epididymitis. Prostatitis. Urethral stricture. Post-gonococcal urethritits Recurrence of symptoms and signs 4 \200\2237 days after success ful single-dose therapy for GU, caused by a dual urethral infection for which the NGU eleme nt was untreated. The most common cause is C. trachomatis. It is recommended an active anti chlamydial treatment should be added in to the original gonorrhea treatment because of this . Table 13.10 Comparison and treatment of non-gonococcal and gonoccocal urethritis Non-gonococcal urethritis Gonococcal urethritis Main causative organism C. trachomatis N. gonorrhea Incubation time (days) 7 \200\22321 2 \200\2237 Onset Gradual Sudden Discharge Watery and clear Larger volume and yellow Dysuria Mild Moderate Treatment Azithromycin 1g single oral dose or Ce \201 xime 400mg single oral dose or Doxycycline 100mg bd oral for 7 days Ceftriaxone 250mg single deep intramuscular dose or Cipro \202 oxacin 500mg single oral dose CHAPTER 13 Sexual health 602 Non-speci \201 c urethritis and urethral syndrome Non-speci \201 c urethritis (NSU): is d escribed as the presence of PMNL ( \211 5 per high powered \201 eld at 1000 magni \201 c ation) in a male urethral smear, in the absence of any proven speci \201 c infection. Causes of NSU Infective causes of urethritis with false-negative laboratory results (i.e. m issed sexually transmitted infection (STI)). Non-infective causes of urethritis - Urethral trauma/foreign object. - Contact urethritis ( spermicides, shower gel). - Reiter \200\231s syndrome (urethritis, seronegative arthritis, and conjunctivitis). - Wegener \200\231s granulomatosis (vasculitis of unknown etiology). Management Urethral swab: culture, Gram stain, and NAAT to exclude STI. Bearing in mind tha t some cases of NSU may be due to STI with false-negative results, sexual contacts should b e traced and antibiotics can often alleviate symptoms. Standard C. trachomatis treatments a re usually recommended (azithromycin 1g single oral dose or oral doxycycline 100mg bd 7 day s) and are often effective. Urethral syndrome This is a condition of uncertain etiology that only affects women. It man i- fests as dysuria, frequency, urgency, and suprapubic discomfort without any evidence of infection or urological abnormality to account for the symptoms. Differential diagnosis Infection, painful bladder syndrome/interstitial cystitis, urethral diverticulum. Management It is a diagnosis of exclusion. Urethral and endocervical swabs should be taken for culture, Gram stain, and NAAT to exclude an STI cause and MSU specimen to examine for U TI. Where indicated, consider cystos- copy to exclude BPS/IC or MRI to investigate for uret hral diverticulum. Treatment A course of antibiotics (covering C. trachomatis and anaerobes) can provide sympt om relief in some cases, even in the absence of positive cul- tures. Alkalinization of the urine (potassium citrate, sodium bicarbonate) may help alleviate symptoms. 603 Chapter 14 Neuropathic bladder Innervation of the lower urinary tract (LUT) 604 The physiology of urine storage and mictur ition 608 Bladder and sphincter behavior in the patient with neurological disease 610 The neuropathic lower urinary tract: clinical consequences of storage and emptying problems 612 Bladder management techniques for the neuropathic patient 614 Catheters and sheaths and the neuropathic patient 622 Management of incontinence in the neu ropathic patient 624 Management of recurrent urinary tract infections (UTIs) in the neuropathic patient 628 Management of hydronephrosis in the neuropathic patient 630 Bladder dysfunction in multiple sclerosis, Parkinson \200\231s disease, spina bi \201 da, after stroke, and in other neurological disease 632 Neuromodulation in neuropathic and non-neuropathic lower urinary tract dysfunction 636 CHAPTER 14 Neuropathic bladder 604 Innervation of the lower urinary tract (LUT) Motor innervation of the bladder Parasympathet ic motor innervation of the bladder Preganglionic, parasympathetic nerve cell bodies are lo cated in the intermediolateral column of spinal segments S2 \200\2234. These preganglionic, parasympathetic \201 bres pass out of the spinal cord through the anterior primary rami of S2, S3, and S4 and contained within nerves called the nervi erigentes, they head towards the pelvic plexus. In the pelvic plexus (in front of the piriformis muscle), the pregangli onic, parasympathetic \201 bres synapse within ganglia with the cell bodies of the post-g anglionic parasym- pathetic nerves which then run to the bladder and urethra. Fifty percent of the ganglia of the pelvic plexus lie in the adventitia of the bladder and bladder base (the connective tissue surrounding the bladder) and 50% are within the bladder wall. The po st-ganglionic axons provide cholinergic excitatory input to the smooth muscle of the bladde r. Sympathetic motor innervation of the bladder In the male, preganglionic sympathetic nerve \201 bres arise from the interme- diolateral column of T10 \200\22312 and L1 \200\2232. Th ese preganglionic neurons syn- apse in the sympathetic chain and post-ganglionic sympatheti c nerve \201 bres travel as the hypogastric nerves to innervate the trigone, blood vessel s of the bladder, and the smooth muscle of the prostate and preprostatic sphincter (i.e. th e bladder neck). In the female, there is sparse sympathetic innervation of the bladder neck and urethra. In both sexes, some post-ganglionic sympathetic nerves also terminate in parasympathetic ga nglia (in the adventitia surrounding the bladder and within the bladder wall) and exert an inhibitory effect on bladder smooth muscle contraction. Afferent innervation of the bladder Afferent nerves from receptors throughout the bladder a scend with para- sympathetic neurons back to the cord and from there, up to the pontine sto rage and micturition centers or to the cerebral cortex. They sense bladder \201 lling. Other receptors are located in the trigone and afferent neurons from these neurons ascend w ith sympathetic neurons up to the thoracolumbar cord and thence to the pons and cerebral co rtex. Other receptors are located in the urethra. The afferent neurons pass through the pudendal nerve and again ascend to the pons and cerebral cortex. All these neurons have local relays in the cord. Somatic motor innervation of the urethral sphincter: the distal urethral sphincter mechanis m Anatomically, this is located slightly distal to the apex of the prostate in the male (be tween the verumontanum and proximal bulbar urethra) and in the mid-urethra in the female. I t has three components: - Extrinsic skeletal muscle: urethral sling (part of levator ani). Composed of striated muscl e and this is the outermost layer, the pubo- INNERVATION OF THE LOWER URINARY TRACT (LUT) 605 innervated by the pudendal nerve (spinal segments S2 \200\2234, somatic nerve \201 bres). It is activated under conditions of stress and augments urethral occlusion pressure. Smoot h muscle within the wall of the urethra: innervation. Tonically active. Relaxed by nitric o xide (NO). Intrinsic striated muscle urethra, hence known as the \200\230intrinsic rhabdos phincter \200\231): it forms a \200\230U \200\231 shape around the urethra and around the anterior and lateral aspects of the membranous urethra and is absent posteriorly (i.e. it d oes not completely encircle the membranous urethra). It may produce urethral occlusion by k inking the urethra rather than by circumferential compression. cholinergic (i.e. skeletal muscle within the wall of the Preganglionic somatic nerve \201 bres (i.e. neurons which innervate striated muscle) are, along with parasympathetic nerve \201 bres (which innervate the bladder), derived from s pinal segments S2 \200\2234, speci \201 cally from Onuf \200\231s nucleus (also known as s pinal nucleus X) which lies in the medial part of the anterior horn of the spinal cord. (On uf \200\231s nucleus is the location of the cell bodies of somatic motoneurons that provide motor input to the striated muscle of the pelvic \202 oor \200\224the external urethral and anal sphinc- ters.) These somatomotor nerves travel to the rhabdosphincter via the peri neal branch of the pudendal nerve (documented by direct stimulation studies and horseradish peroxidase (HRP) tracing \200\224accumulates in Onuf \200\231s nucleus following injection into either the pudendal or pelvic nerves). There also seems to be some innervation to the rhabdosphincter from branches of the pelvic plexus (speci \201 cally the inferior hypogas tric plexus) via pelvic nerves. In dogs, complete silence of the rhabdosphincter is seen on ly if both the pudendal and pelvic efferents are sectioned. Thus, puden- dal nerve block or pudendal neurectomy does not cause incontinence. The nerve \201 bres that pass distally to the distal sphincter mechanism are located in a dorsolateral position (5 and 7 o \200\231clock). More distally, they adopt a more lateral position. Sensory innervation of the urethra Afferent neurons from the urethra travel in the pudendal nerve. Their cell bodies lie in the dorsal root ganglia and they terminate in the dorsal h orn of the spinal cord at S2 \200\2234, connecting with neurons that relay sensory informat ion to the brainstem and cerebral cortex. The pudendal nerve (a somatic nerve derived from spinal segments S2 \200\2234) innervates s triated muscle of the pelvic \202 oor (levator ani, i.e. the pubo-urethral sling). Bilate ral pudendal nerve block1 does not lead to incontinence because of maintenance of internal (sympathetic innervation) and external sphincter function (somatic innervation, S2 \200\223 4, nerve \201 bres traveling to the external sphincter alongside parasympathetic neurons in the nervi erigentes). CHAPTER 14 Neuropathic bladder 606 Clinical consequences of damage to the nerves innervating the LUT Bladder neck function in the female About 75% of continent young women and 50% of perimenopausal conti- nent women h ave a closed bladder neck during the bladder \201 lling phase. Twenty- \201 ve percent o f continent young women and 50% of perimeno- pausal continent women have an open bladder ne ck and yet they remain continent (because of their functioning distal sphincter mechanism, the external sphincter).2,3 Presacral neurectomy (to destroy afferent pain pathways) does n ot lead to incontinence because of maintenance of the somatic innervation of the external s phincter. Sympathetic motor innervation of the bladder Division of the hypogastric plexus of nerves d uring a retroperitoneal lymph node dissection for metastatic testis tumors results in paral ysis of the blad- der neck. This is of signi \201 cance during ejaculation where normally sympathetic activity results in closure of the bladder neck so that the ejaculate is direct ed distally into the posterior and then anterior urethra. If the bladder neck is incompeten t, the patient develops retrograde ejaculation; they remain con- tinent of urine because th e distal urethral sphincter remains functional, being innervated by somatic neurons from S2 \200\2234.