USS: is diagnostic (venous diameter >3.5mm with VARICOCELE 563 Semen analysis: counts, reduced sperm motility, and abnormal morphology, either alone or in combination (OAT syndrome). varicoceles are associated with low or absent sperm Indications for varicocele repair Adolescents: Pain, bilateral large varicoceles, varicocele in a solitary testis, persistent delayed testicular growth by >20% (as compared with non- affected side). Adults: Varicocele repair improves semen parameters and is recom- mended in the United Stat es.* However, in the UK, the Cochrane review failed to identify any bene \201 t to pregnan cy rates and intervention for infer- tility reasons is not currently recommended by NICE. P atients should be fully counseled on the limitations of varicocele repair for infertility b efore being booked for treatment. Management Embolization: interventional radiological technique where the femoral vein is us ed to access the spermatic veins for venography and embolization (with coils or other scler osing agents), with success rates of 83%. Surgical ligation of spermatic veins - High retroperitoneal (Palomo) approach: made near the anterior superior iliac spine and the internal spermatic veins are ligated at that level. Inguinal (Ivanissevich) approach: the spermatic cord and the external spermatic veins are tied off as they exit the internal ring . Subinguinal (Marmar) approach: accessed and ligated via a small transverse incision below the external ring. With microscopic assistance, this technique is reported to have superio r outcomes to other approaches. Laparoscopic: retroperitoneum. a muscle-splitting incision is the inguinal canal is incised to access external spermatic veins are internal spermatic veins are occluded high in the Surgical complications Varicocele recurrence; hydrocele formation; testicular atrophy, ilio inguinal nerve damage. Surgical outcomes Ninety- \201 ve percent success rate of treating the varicocele; 70% of men have improvement of sperm parameters. Joint Committee of the American Urological Association and the American Society for Reprodu ctive Medicine recommend intervention for a palpable varicocele associated with abnormal se men analysis. CHAPTER 12 Infertility 564 Treatment options for male infertility General: aim to identify and treat reversible causes of subfertility and im- prove semen quality. Advice on modi \201 cation of lifestyle fact ors (i.e. reduce alcohol consumption, avoid hot baths). Medical treatment Antibiotics Treat any positive semen, urine, or urethral cultures with th e appropriate antibiotics. Hormonal - Secondary hypogonadism administration of human chorionic gonadotrophin (HCG) which stimulat es an increase in testosterone and testicular size. If the patient remains azoospermic afte r 6 months of treatment, FSH is added (human recombinant FSH or human menopausal gonadotrop hin). Alternatively, pulsatile LHRH can be administered subcutaneously via a minipump (used for treating Kallman \200\231s syndrome). Hyperprolactinaemia: MRI to rule out a pituitary tumor. Antioestrogens increase LHRH which stimulates endogenous gonadotrophin secretion. U sed for idiopathic oligospermia. (pituitary intact): may respond to is treated with dopamine agonists. Arrange an (clomiphene citrate 25mg od): are used empirically to Antioxidants Vitamin E supplements have been shown to improve sperm function and IVF succes s rates; zinc and folic acid may increase sperm concentrations. Erectile and ejaculatory dysfunction Erectile dysfunction may be treated conventionally (or al, intraurethral, intracavernosal drugs; vacuum devices or prostheses). Ejaculatory failur e may respond to sympathomimetic drugs (desipramine) or electroejacula- tion or vibro-ejacu lation (used in SCI), where an electrical stimulus is used to produce ejaculation. It is de livered via a rectal probe to the post-gangli- onic sympathetic nerves that innervate the p rostate and seminal vesicles. Surgical treatment Genital tract obstruction - Epididymal obstruction: anastomosis between the epididymal tubule and vas (vasoepididymosto my). Vas deferens obstruction: ends of the vas (vasovasotomy) and is used for vasectomy rev ersal. Highest success rates for \201 nding viable sperm occur in the \201 rst 8y post- vasectomy (80 \200\22390%); overall pregnancy rates are 750%. Patency rates are better tha n pregnancy rates; success rates drop to 30% if >15y post-vasectomy.1 Ejaculatory duct obst ruction: ejaculatory ducts (TURED). Varicocele: surgical ligation. can be overcome by microsurgical is treated by microsurgical reanastomosis of requires transurethral resection of the can be treated by embolization or open or laparoscopic TREATMENT OPTIONS FOR MALE INFERTILITY 565 Assisted reproductive techniques (ART) Sperm extraction: sperm are removed directly from th e epididymis by PESA or MESA. If these methods fail, TESE by conventional biopsy or mi- cro surgical techniques, or aspiration (TESA) may be tried. Sperm undergo cryopreservation unti l required. Later, they are separated from seminal \202 uid by dilution and centrifuge me thods, with further selection of motile sperm and normal forms using Percoll gradient techn iques. Assisted conception - Intrauterine insemination are placed directly into the uterus. IVF : controlled ovarian sti mulation with gonadotrophins produces oocytes which are then retrieved by transvaginal USS- guided needle aspiration. Oocytes and sperm are placed in a petri dish for fertilization to occur. Embryos are incubated and cultured for 2 \200\2233 days and then transferred to the uterine cavity. Pregnancy rates are 20 \200\22330% per cycle. Gamete intrafallopian transf er and deposited into the Fallopian tubes via laparoscopy. Variations include zygote intraf allopian transfer (ZIFT) and tubal embryo transfer (TET). : A single spermatozoa is injecte d directly into the oocyte ICSI cytoplasm (through the intact zona pellucida). The advantag e is that fewer sperm are needed. ICSI is always combined with IVF and the clinical pregnan cy rate is 28 \200\22340% per cycle. (IUI): following ovarian stimulation, sperm (GIFT): oocytes and sperm are mixed 1 Belker AM, Thomas AJ Jr, Fuchs EF, Konnak JW, Sharlip ID (1991) Results of 1,469 microsur gical vasectomy reversals by the Vasovasostomy Study Group. J Urol 145:505 \200\22311. This page intentionally left blank 567 Chapter 13 Sexual health Physiology of erection and ejaculation 568 Erectile dysfunction: evaluation 572 Erectile dy sfunction: treatment 576 Peyronie \200\231s disease 580 Priapism 584 Retrograde ejaculation 588 Premature ejaculation 590 Other disorders of ejaculation and orgasm 592 Late-onset hyp ogonadism (LOH) 594 Hypogonadism and male hormone replacement therapy 596 Urethritis 600 No n-speci \201 c urethritis and urethral syndrome 602 CHAPTER 13 Sexual health 568 Physiology of erection and ejaculation Innervation Autonomic: sympathetic nerves originatin g from T11 \200\223L2 and parasympa- thetic nerves originating from S2 \200\2234 join to fo rm the pelvic plexus. The cav- ernosal nerves are branches of the pelvic plexus (i.e. paras ympathetic) that innervate the penis. Parasympathetic stimulation causes erection; sympa- t hetic activity causes ejaculation and detumescence (loss of erection). Somatic: somatosenso ry (afferent) information travels via the dorsal penile and pudendal nerves and enters the spinal cord at S2 \200\2234. Onuf \200\231s nucleus (segments S2 \200\2234) is the somatic center for efferent (i.e. somato- motor) innervation of the ischiocavernosus and bulbocaver nosus muscles of the penis. Central: medial preoptic area (MPOA) and paraventricular nucleu s (PVN) in the hypothalamus are important centers for sexual function and penile erection. Mechanism of erection Neuroendocrine signals from the brain, created by audiovisual or tac- tile stimuli, activate the autonomic nuclei of the spinal erection center (T11 \200\223L2 and S2 \200\2234). Signals are relayed via the cavernosal nerve to the erectile tissue of t he corpora cavernosa, activating the veno-occlusive mechanism (Table 13.1). This triggers i ncreased arterial blood \202 ow into sinusoidal spaces (secondary to arterial and arterio lar dilatation), relaxa- tion of cavernosal smooth muscle, and opening of the vascular spac e. The result is expansion of the sinusoidal spaces against the tunica albuginea which comp resses the subtunical venous plexuses, decreasing venous out- \202 ow. Maximal stretching of the tunica albuginea, which acts to compress the emissary veins that lie within its inn er circular and outer longitudinal layers, reduces venous \202 ow even further. Rising in tracavernosal pressure and contraction of the ischiocavernosus muscles produce a rigid erec tion. Following orgasm and ejaculation, vasoconstriction (due to increased sym- pathetic ac tivity, endothelin, PGF2, and breakdown of cGMP) produces detumescence. Noradrenaline (NA) released from sympathetic nerve terminals in the corpora acts on smooth muscle cell A 1-adr enoceptors, leading to raised intracellular calcium which helps maintain penile \202 acci dity (Figs. 13.1 and 13.2). Ejaculation Tactile stimulation of the glans penis sends sensory information (via the puden dal nerve) to the lumbar spinal sympathetic nuclei. Sympathetic efferent signals (traveling in the hypogastric nerve) cause contraction of smooth muscle of the epididymis, vas defere ns, and secretory glands, pro- pelling spermatozoa and glandular secretions into the prosta tic urethra (emission). There is simultanous closure of the internal urethral sphincter and relaxation of the extrinsic sphincter, directing sperm into the bul- bourethra, but preven ting sperm from entering the bladder. Rhythmic PHYSIOLOGY OF ERECTION AND EJACULATION 569 contraction of the bulbocavernosus muscle (somatomotor innervation) leads to the pulsatile emission of the ejaculate from the urethra. During ejaculation, the alkaline prostatic secr etion is discharged \201 rst, followed by spermatozoa and \201 nally, seminal vesicle s ecretions (ejaculate vol- ume 2 \200\2235mL). The seminal vesicles contribute 2mL, prostate 0.5mL, and Cowper \200\231s glands 0.1mL of the ejaculate. There is an additional vasal an d testicular contribution (accounting for around 5 \200\22310% of the total ejaculate volum e). Table 13.1 Phases of erectile process Phase Term Description 0 Flaccid phase Cavernosal smooth muscle contracted; sinusoids empty; minimal arterial \202 ow 1 Latent ( \201 lling) phase Increased pudendal artery \202 ow; penile elongation 2 Tumescent phase Rising intracavernosal pressure; erection forming 3 Full erection phase Increased cavernosal pressure causes penis to become fully erect 4 Rigid erection phase Further increases in pressure + ischiocavernosal muscle contraction 5 Detumescence phase (initial, slow and fast phases) Following ejaculation, sympathetic discharge resumes; there is smooth muscle contraction an d vasoconstriction; reduced arterial \202 ow; blood is expelled from sinusoidal spaces Cavernosal smooth muscle Nitric oxide (NO) Vasoactive intestinal peptide (VIP) Prostaglandin E1 (PGE1) RELAXATION (erection) Decrease in calcium Noradrenaline (NA) Endothelin-1 Prostaglandin F2 (PGF2) CONTRACTION (flaccidity) Increased sensitivity to calcium Fig. 13.1 Factors in \202 uencing cavernosal smooth muscle. CHAPTER 13 Sexual health 570 L-citrulline GTP L-arginine Guanylate cyclase NO NOS PDE5 cGMP 5GMP intracellular Ca2+ Cavernosal smooth muscle relaxation ERECTION VIP + PGE1 Intracellular Ca2+ cAMP ATP Adenylate cyclase Cavernosal smooth muscle relaxation ERECTION Fig. 13.2 Secondary messenger pathways involved in erection (ATP, adenosine triphosphate; C a2+,calcium; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; GT P, guanosine triphosphate; NA, noradrenaline; NO, nitric oxide; NOS, nitric oxide synthase enzyme; PDE5, phosphodiesterase type 5; PGE1, prostaglandin E1; PGF2, prostaglandin F2; VIP , vasoactive intestinal polypeptide). This page intentionally left blank CHAPTER 13 Sexual health 572 Erectile dysfunction: evaluation De \201 nition Erectile dysfunction (ED) (also called imp otence) describes the \200\230consistent or recurrent inability to attain and/or maintain a penile erection suf \201 cient for sexual intercourse \200\231.1 Epidemiology In men aged 40 \200\22370y, mild ED is found in 17%, moderate ED in 25%, and c omplete ED in 10%.2 Incidence increases with age, with complete ED affecting 715% of men in their 70 \200\231s and 30 \200\22340% in their 80 \200\231s. Etiology ED is generally divided into psychogenic and organic causes (Table 13.2). It is of ten multifactorial. History Sexual: onset of ED (sudden or gradual); duration of problem; presence of erections (nocturnal, early morning, spontaneous); ability to maintain erections (early collapse, no t fully rigid); loss of libido; relationship issues (frequency of intercourse and sexual de sire). Sexual function symptom questionnaires: International Index of Erectile Function (IIEF) \200\224full and short version (IIEF 5) (see b p. 575; Table 13.3); Brief Male Sexual Funct ion Inventory (BMSFI); quality of life questionnaire (QoL-MED). Medical and surgical: enquire about risk factors, including diabetes mellitus (ED affects 5 0% overall and 30% of treated diabetics);2 cardiovascular dis- ease; hypertension; peripher al vascular disease; endocrine or neurological disorders; pelvic and penile surgery, radiot herapy, or trauma (which dam- age innervation and blood supply to the pelvis and penis). In termediate or high risk cardiovascular disease requires further specialist assessment and t reatment prior to ED treatment. Psychosocial: assess for social stresses, anxiety, depression, coping prob- lems, patient e xpectations, and relationship details. Drugs: enquire about current medications and ED treatments already tried and their outcome. Social: smoking, alcohol consumption. An organic cause is more likely with gradual onset (unless associated with an obvious cause such as surgery where onset is acute); loss of spontaneous erections; intact libido and ej aculatory function; existing medical risk factors and older age groups. Examination Full physical examination (cardiovascular, abdomen, neurological); BP; DRE to a ssess the prostate; assess secondary sexual characteristics; exter- nal genitalia assessmen t to document foreskin phimosis, penile deformities and lesions (Peyronie \200\231s plaques ); con \201 rm presence, size, and location of ERECTILE DYSFUNCTION: EVALUATION 573 testicles. The bulbocavernosus re \202 ex can be performed to test integrity of spinal seg ments S2 \200\2234 (squeezing the glans causes anal sphincter and bulbocavernosal muscle co ntraction). Investigation - Blood tests: 11.00 a.m.); fasting lipid pro \201 le are basic work-up test s.3 SHBG; U&E; LH/FSH; prolactin; PSA; thyroid function test should be selected according t o patient \200\231s history and risk factor pro \201 le. Nocturnal penile tumescence and r igidity testing: contains two rings that are placed around the base and distal penile shaft to measure tumescence and number, duration, and rigidity of nocturnal erections. Useful fo r diagnosing psychogenic ED and for illustrating this diagnosis to patients. USS: measures arterial peak systolic and end Penile color Doppler diastolic velocities,* pre- and post-in tracavernosal injection of PGE1. Cavernosography: imaging and measurement of penile blood \202 ow after intracavernosal injection of contrast and induction of arti \201 cial erect ion, used to identify venous leaks. Penile arteriography: Pudendal arteriography is perform ed before and after drug-induced erection to identify those requiring arterial bypass surge ry (although this is less commonly indicated now with the advent of modern penile prosthese s). MRI disease. fasting glucose; serum (free) testosterone (taken 8.00 \200\223 the Rigiscan device reserved for trauma-related ED in younger men. : useful for assessing penile \201 brosis and severe cases of Peyronie \200\231s Normal values: peak systolic velocity >35cm/s; end diastolic velocity <5cm/s. 1 Montorsi F, AdaikanG, Becher E, et al. (2010) Summary of the recommendations on sexual dy sfunction in men. J Sex Med 7:3572-88. 2 Feldman HA, Goldstein I, Hatzichristou D, et al. (1994) Impotence and its medical and psy cho- logical correlates: results of the Massachusetts Male Aging Study. J Urol 151:54 \200 \22361. 3 Hackett G, Kell P, Ralph D, et al. (2008) British Society for Sexual Medicine guidelines on the management of sexual dysfunction. J Sex Med 5:1841 \200\22365. 4 Catalona WJ, Carvalhal GF, Mager DE, et al. (1999) Potency, continence and complication r ates in 1,870 consecutive radical retropubic prostatectomies. J Urol 162:433 \200\2238. CHAPTER 13 Sexual health 574 Table 13.2 Causes of erectile dysfunction or \200\230impotence \200\231 In \202 ammatory Prostatitis Mechanical Peyronie \200\231s disease Psychological Depression; anxiety; relationship dif \201 culties; lack of attraction; stress Occlusive vascular factors Arteriogenic: hypertension; smoking; hyperlipidaemia; diabetes mellitus; peripheral vascula r disease Venogenic: impairment of veno-occlusive mechanism (due to anatomical or degenerative change s) Trauma Pelvic fracture; spinal cord injury; penile fracture/trauma Extra factors Iatrogenic: pelvic surgery; prostatectomy* Other: increasing age (secondary to atherosclerosis in penile arteries, leading to corporea l ischaemia and \201 brosis); chronic renal failure; cirrhosis, low \202 ow priapism (i .e. corporeal \201 brosis); smoking Neurogenic CNS: multiple sclerosis (MS); Parkinson \200\231s disease; multisystem atrophy; tumor Spinal cord: spina bi \201 da; MS; spinal cord injury; tumor PNS: pelvic surgery or radiotherapy; peripheral neuropathy (diabetes, alcohol-related) Anti hypertensives (B-blockers, thiazides, ACE inhibitors) Antiarrhythmics (amiodarone) Chemical Antidepressants (tricyclics, MAOIs, SSRIs) Anxiolytics (benzodiazepine) Antiandrogens ( \201 nasteride, cyproterone acetate) GNRH analogs Anticonvulsants (phenytoin, carbamazepine) Anti-Parkinson drugs (levodopa) Statins (atorvastatin) Alcohol (Refer to BNF) Endocrine Diabetes mellitus**; hypogonadism; hyperprolactinaemia; hypo and hyperthyroidism Of note, nerve sparing techniques for radical prostatectomy have improved post-operative po tency rates to around 50 \200\22370%.4 ** Note that this list of causes is not in the order of frequency, i.e. diabetes mellitus is one of the most important causes. MAOIs = monoamin e oxidase inhibitors; SSRIs = serotonin reuptake inhibitors; BNF = British National Formula ry (bnf.org). Table 13.3 International Index of Erectile Function short form (IIEF 5). Also known as the Sexual Health Inventory for Men (SHIM) 1. How do you rate your con \201 dence that you could get and keep an erection? Very low Low Moderate High Very high 1 2 3 4 5 2. When you had No sexual activity 0 Almost never or never 1 A few times 2 Sometimes 2 Most times 4 Almost always or always 5 erections with sexual stimulation, how often were your erections hard enough for penetratio n? 3. During sexual E R E C T Did not attempt intercourse 0 Almost never or never 1 A few times 2 Sometimes 2 Most times 4 Almost always or always 5 intercourse, how often were your erections hard enough for penetration? 4. during sexual I L E D Y S F U N C T O N Did not attempt intercourse 0 Extremely dif \201 cult 1 Very dif \201 cult 2 Dif \201 cult 3 Slightly dif \201 cult 4 Not dif \201 cult 5 intercourse, how dif \201 cult was it to maintain your erection to completion of intercour se? I Did not attempt intercourse Almost never or never A few times Sometimes Most times Almost always or always 5. When you attempted : E V A L U A T O N sexual intercourse, how often was it satisfactory to you? 2 2 4 1 5 0 I IIEF 5 is scored from 1 \200\22325. Scores 1 \200\2237 = severe ED; 8 \200\22311 = moderate ED; 12 \200\22316 = mild to moderate ED; 17 \200\22321 = mild ED; 22 \200\22325 = no ED. 5 7 5 CHAPTER 13 Sexual health 576 Erectile dysfunction: treatment Correct any reversible causes (i.e. alter lifestyle, stop s moking, change medication, etc.) (Table 13.2). Psychosexual therapy Aims to understand and address underlying psychological issues and pro vides information and treatment in the form of sex education, psycho- sexual counseling, in struction on improving partner communication skills, cognitive therapy, and behavioral ther apy (programmed relearning of couple \200\231s sexual relationship). Pharmacotherapy may be a useful adjuvant. Drug therapy Phosphodiesterase type-5 (PDE5) inhibitors: \201 rst-line therapies which in clude sildena \201 l (Viagra ), tadala \201 l (Cialis ), vardena \201 l (Levitra ) (T able 13.4). PDE5 inhibitors enhance cavernosal smooth muscle relaxation and erection by blo cking the breakdown of cGMP by phosphodiesterase. Sexual stimulus is still required to init iate events. Success is reported in up to 80%. Early use of PDE5 inhibitors following radic al prostatectomy can help optimize the return of spontaneous erections (penile rehabilitati on). Contraindications: patients taking nitrates, recent myocardial infarction, recent stroke, h ypotension, unstable angina, non-arteritic anterior ischae- mic optic nerve neuropathy (NAI ON). Cautions: intermediate and high risk cardiovascular disease requires cardiac review pr ior to treatment, use with A-blockers, groups with predisposition to priapism. Dopamine rec eptor agonist: apomorphine (Uprima ), taken sublingually, acts centrally on dopaminergic r eceptors in the paraventricular nucleus of the hypothalamus to enhance and coordinate the e ffect of sexual stimuli. Side effects: nausea, headache, dizziness. Not commonly used. Intraurethral therapy: second-line therapy when oral therapies have been ineffective. A syn thetic prostaglandin E1 (PGE1) pellet (alprostadil) is placed into the urethra via a specia lized applicator (Medicated Urethral System for Erection (MUSE)TM device). Once inserted, t he penis is gently rolled to encourage the pellet to dissolve into the urethral mucosa from where it enters the corpora. PGE1 acts to increase cAMP within the cor- poral smooth muscl e, resulting in muscle relaxation. Side effects: penile and urethral pain, priapism, local reactions. Intracavernosal injection therapy - - TM). Alprostadil (Caverjet Papaverine ( PDE inhibitor). Usually given in combination with either phentolamine (A-adrenoceptor antagonist) or PGE1 in patients who have failed oral or singl e-agent injectable therapies. Training of technique and \201 rst dose is given by a health professional. Needle is inse rted at right angles into the corpus cavernosum on the lat- eral aspects of mid-penile shaf t. Discontinuation rates from penile injec- tion techniques are high. Contraindications: si ckle cell disease or high-risk candidate for priapism. Adverse effects: pain, priapism, hae matoma. ERECTILE DYSFUNCTION: TREATMENT 577 Vacuum erection device Used when pharmacotherapies have failed. It contains three components: a vacuum chamber, pu mp, and constriction band. The penis is placed in the chamber and the vacuum created by the pump increases blood \202 ow to the corpora cavernosa to induce an erection. The constri ction band is placed onto the base of the penis to retain blood in the corpora and main- ta in rigidity. Relative contraindication: anticoagulation therapy. Side effects: penile coldn ess, bruising. Microvascular arterial bypass and venous ligation surgery Used in: specialist centers where there is a clear-cut diagnosis of a vascular disorder. Acts to increase arterial in \202 ow and decrease venous out \202 ow. Rarely used now as it is uncommon for success rates to exceed 50%. Penile prosthesis Semi-rigid, malleable, and in \202 atable penile prostheses are availabl e when other therapies have failed or are unsuitable. Also indicated for Peyronie \200\231s disease, trauma, and penile \201 brosis (i.e. secondary to priapism). The device is surg ically implanted into the corpora to provide penile rigidity and gen- erally has high satis faction rates, up to 90% (Fig. 13.3). Side effects: infec- tion, erosion, mechanical failur e, penile shortening, glans may not fully engorge. Testosterone replacement therapy Indicated for hypogonadism and is available in oral, bucca l, intramuscular, pellet, transdermal patch, and gel forms. Most guidelines recommend PSA, Hb, and LFT checks before and after starting treatment (see b pp. 596 \200\2237). It can im prove the results of PDE5 inhibitors in hypogonadal men. Table 13.4 A comparison of PDE5 inhibitors PDE5I Doses (mg) Half-life Effective Duration of action Common side effects within Sildena \201 l (Viagra) 25/50/100 3.7h 30 \200\22360min Up to 4 \200\2235h Headache, dizzy, GI upset, \202 ushing, nasal congest ion, blurred vision Vardena \201 l (Levitra) 5/10/20 3.9h 25 \200\22360min Up to 4 \200\2235h As above Tadala \201 l (Cialis) 2.5/5/10/20 17.5h 30min to 2h Up to 36h As above Free NHS prescription (SLS Schedule 11) applies for certain conditions including: diabetes, spinal cord injury, multiple sclerosis, Parkinson \200\231s disease, polio, spina bi \201 da, one gene neurological disease, severe pelvic injury, prostate cancer, prostatectomy, r adical pelvic surgery, renal failure (treated by dialysis or transplant), for \200\230seve re distress \200\231 and patients already receiving NHS ED treatment on 14th September, 199 8. CHAPTER 13 Sexual health 578 (a) Reservoir Penile cylinders Scrotal pump (b) Fig. 13.3 (a) AMS 700 TM Series Tactile Pump penile prosthesis. (b) In \202 ated prosthesi s in situ. (Reproduced with permission, courtesy of American Medical Systems Inc., Minnesot a.) This page intentionally left blank CHAPTER 13 Sexual health 580 Peyronie \200\231s disease De \201 nition An acquired benign penile condition characterize d by deformity of the penile shaft secondary to the formation of a \201 brous inelastic s car on the tunica albuginea.1 Epidemiology Prevalence is 3 \200\2239%,1 predominantly affecting men aged 40 \200\22360y. Pathophysiology Histologically, plaques have excessive connective tissue ( \201 brosis) an d increased cellularity with random orientation of collagen \201 bres. Dorsal penile plaq ues are most common (66%). The corpus cavernosus underly- ing the lesion cannot lengthen fu lly on erection, resulting in penile curva- ture. The disorder has two phases: - Active phase erections and changing penile deformity. Quiescent (stable) phase disappears w ith resolution of in \202 ammation and there is stabilization of the penile deformity. (1 \200\2236 months): early in \202 ammatory phase with painful (9 \200\22312 months): disease \200\230burns out \200\231. Pain The natural history of Peyronie \200\231s plaques over 18 months is that 40% will progress, 47% will remain stable, and 13% will improve.2 Etiology The exact cause is unknown, but it is currently considered to be a wound healing d isorder which occurs after penile trauma in genetically predis- posed men.1 It is likely th at repeated minor trauma during intercourse causes microvascular injury and bleeding into t he tunica, resulting in in \202 ammation and \201 brosis (exacerbated by transforming gr owth factor-B (TGF-B). Presentation Peyronie \200\231s disease may present with penile pain, a palpable lump (plaq ue), penile curvature, ED (in 40%), a more complex deformity (shortening, indentation, hour glass deformity), or a combination of these features. Common comorbidities Diabetes mellitus (in 30%); ED; arterial disease; Dupuytren \200\231s contractures (25%); plantar fascial contracture; tympanosclerosis; raised cholesterol or tr iglycerides; hypertension; low testosterone. Evaluation A full medical and sexual history (including erectile function) are taken. Patie nt photographs or outpatient injection of intracavernosal PGE1 can be used to assess the de gree of curvature. Assess the location and size of the plaque (is it tender?). Record stret ched penile length preoperatively to help advise patients that loss of penile length is par tly due to the disease and not all due to the surgical correction. Color Doppler USS is use ful in assessing the plaque and any vascular abnormalities whereas contrast- enhanced MRI i s indicated for complex and extensive cavernosal \201 brosis. PEYRONIE \200\231S DISEASE 581 Management Early disease with active in \202 ammation (<3 months, penile pain, chang- ing deformity) may bene \201 t from medical therapy. Surgery is indicated for stable, mature d isease (present for 12 months; stable for 3 months), with signi \201 cant deformity preven ting intercourse. Non-mechanical components of ED can be treated conventionally (e.g. oral PDE5 inhibitors or intrac- avernosal pharmacotherapy). Conservative treatment Medical treatment - Oral therapy: have been shown to improve curvatu re, ED, and reduce plaque size. Colchine combined with vitamin E signi \201 cantly improve s pain, plaque size, and curvature. Other treatments, including vitamin E, tamoxifen, POTAB A (para-aminobenzoate), and colchicines, have not shown signi \201 cant effects on penile deformity. Intralesional injection: verapamil (10mg in 10mL saline) injected into lesion ev ery 2 weeks for 24 weeks.3 Alternatives are collagenase and interferon A2-B injection. Iont ophoresis: small amounts of electric current are used to transfer drugs (verapamil 9 dexame thasone and lidocaine) transdermally to act on the plaque.4 pentoxifylline, a non-speci \201 c PDE, and TGF- 1 inhibitor ESWL: has little effect on penile deformity, but may help reduce pain. Peyronie \200\231s vacuum therapy: exercises using mechanical stretching. Surgery (Box 13.1) - Nesbit procedure: incision. An arti \201 cial erection is induced by intracavernosal saline injection. On the opposite side of maximal deformity, an ellipse is excised (a width of 1mm is taken for every 10 of penile curvature) and the defect closed with sutures. Success rates are 88 \200\22394%. A circumcision is recommended for those wit h phimosis or previous surgery. Risks: all will have penile shortening (often 2 \200\2233cm ), bleeding, infection, residual deformity, recurrence, ED (71%). Simple plication techniqu e: of maximal deformity to straighten the penis. Success rates tend to be lower (740%). Pla que incision and grafting (Lue procedure): incision of plaque with insertion of a venous pa tch to lengthen the affected side (and minimize penile shortening). Success rates 75 \200 \22396%. Alternative graft materials: temporalis fascia, Surgisis (porcine small intestinal submucosa), and bovine pericardium. Risks: ED 5 \200\22312%, bleeding, infection, residual deformity, penile shortening (0 \200\22320%). Penile prosthesis: reserved for patients wit h moderate to severe ED, cavernosal \201 brosis, and complex deformities (see b p. 578). Residual curvature after prosthesis placement will require correction with manual modeling or if this fails, incision 9 graft insertion. the penis is degloved via a circumglanular sutures are placed on the opposite side CHAPTER 13 Sexual health 582 Box 13.1 Choice of surgical intervention for Peyronie \200\231s disease Patients with adequ ate erectile function preoperatively (with or without the use of pharmacotherapy) - : 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.