# 13.6.4 Sexual dysfunction 2408 # 13.6.4 Sexual dysfunction 2408 section 13  Endocrine disorders 2408 percutaneous drainage under ultrasound guidance. In smokers, in- flammation around the ducts, known as periductal mastitis, leads to an abscess formation if secondary infection occurs. This can pro- gress to form a mammary fistula. Granulomatous mastitis is uncommon, the diagnosis being made after excluding infection, especially tuberculosis, and sarcoidosis. Mondor’s disease is the name given to superficial thrombophle- bitis of a chest wall vein. In the breast this results in a tender cord-​ like thickening running vertically and superficially. Benign conditions of the male breast Gynaecomastia, which is often unilateral, is hypertrophy of the ductal and stromal tissue of the male breast and is a common finding at puberty and in older men with failing testicular function. Pseudogynaecomastia, which is increase in the fat underlying the male breast, is more common than true gynaecomastia. This may be idiopathic, but a careful history of prescribed and recreational drugs may be fruitful. Common causes are digoxin, anabolic steroids, heroin, spironolactone, omeprazole, and methyldopa. Testicular tumours can cause gynaecomastia, which is also seen in Klinefelter’s syndrome. Other benign conditions of the male breast are very rare. Male breast cancers account for less than 1% of all breast can- cers in the United Kingdom, but suspicious features such as a hard, rugged lump in the breast should prompt triple assessment to ex- clude malignancy. FURTHER READING Chinyama CN (2014). Benign breast diseases, 2nd edition. Springer, London. Dixon MJ (ed) (2012). ABC of breast diseases, 4th edition. Wiley-​ Blackwell, Oxford. Hughes LE, Mansel RE, Webster DJ (1987). Aberrations of normal development and involution (ANDI): a new perspective on patho- genesis and nomenclature of benign breast disorders. Lancet, 2, 1316–​19. 13.6.4  Sexual dysfunction Ian Eardley ESSENTIALS Male sexual dysfunction, particularly erectile dysfunction, is common and becomes commoner with increasing age. It is often associated with cardiovascular disease and its risk factors. First line management should seek to identify and treat causative risk factors along with oral pharmacotherapy with a phosphodiesterase type 5 inhibitor. Premature ejaculation is a common but poorly under- stood condition that can be treated effectively by psychosexual therapy or by the use of selective serotonin reuptake inhibitors. Penile deformity is relatively uncommon and is usually due to Peyronie’s disease. It is possible to treat established disease by in- jection of collagenase, but for most patients who actually require treatment, surgical correction is the appropriate therapy. Prolonged erection or priapism is a rare medical emergency that requires ur- gent therapy or else erectile function may be lost. In women, sexual desire disorders are commoner in older postmenopausal women and a new treatment, flibanserin, has recently been licensed for this indication. Sexual arousal dis- orders in women also become more common postmenopausally and have a multifactorial aetiology. Treatment should be directed at the aetiological factor in the first instance; trials of oral pharma- cotherapy have been disappointing. While true vaginismus is un- common, dyspareunia is relatively common. Again, there may be a multifactorial aetiology, with vulvar vestibulitis being perhaps the most common aetiological condition. Treatment is often unsatisfactory. Male sexual dysfunction Male sexual function is a complex neurovascular event which can be affected by several disease processes that result in problems of penile erection, ejaculatory difficulties, and disorders of desire. Of these, the commonest dysfunctions encountered in clinical practice are erectile dysfunction, penile deformity, prolonged erections, and rapid (or premature) ejaculation. Erectile dysfunction Erectile dysfunction (ED) is defined as ‘The inability to attain or maintain an erection satisfactory for sexual intercourse’. It is a very common symptom which affects around 50% of men over the age of 40 years. The prevalence increases with age, and there are asso- ciations with a range of conditions including diabetes, hyperten- sion, dyslipidaemia, and depression. The first modern (and perhaps most important) epidemiological study was the Massachusetts Male Aging study which reported the age-​related prevalence in North American men. A plethora of subsequent epidemiological studies have explored the issues. The physiology of penile erection is complex and involves co- ordinated interaction of the neurological, vascular, and endocrine systems. As such, there are many diseases of these systems that can lead to the development of ED, some of which are listed in Table 13.6.4.1. It is now recognized that in most men with ED, both psychogenic and organic risk factors coexist, albeit to varying degrees. Certainly secondary ‘performance related anxiety’ often complicates the pathophysiology of men who have a primary or- ganic aetiology. The commonest cause of ED is that which arises secondary to vascular disease, with ED being a common coexisting symptom in men with hypertension, diabetes, hyperlipidaemia, and cardiovascular disease. Indeed, there is emerging evidence that ED may be one of the very earliest features of systemic vas- cular disease. Since ED is a self-​declared symptom, the fundamental basis of diagnosis is the clinical history. Mild cases are characterized by a history of difficulty in maintaining an erection, while in more 13.6.4  Sexual dysfunction 2409 severe cases, there may be difficulty in initiating an erection or even be loss of erections altogether. Assessment should seek to identify treatable causes (Tables 13.6.4.1, 13.6.4.2) and remediable risk factors. A predominantly psychogenic aetiology is suggested by the continued presence of nocturnal or early morning erections. Current guidelines suggest a focussed physical examination of the genitalia, assessment of secondary sexual characteristics, and as- sessment of blood pressure. More extensive genitourinary and vascular examination is only performed when clinically indicated. Baseline investigations should include a fasting blood sugar, a lipid screen, and an assessment of a serum testosterone. Further assess- ment is usually unnecessary, although in selected cases vascular investigations (including colour Doppler assessment of penile vas- culature) and more complex endocrine investigations might be indicated. In a few patients, specific remedies can cure ED. For instance, in men with a predominantly psychogenic aetiology, psychosexual counselling is often valuable. In men with an endocrine cause (such as hypogonadism or hyperprolactinaemia), appropriate endocrine therapy is also helpful. Finally, in men who have developed ED fol- lowing pelvic or perineal trauma, reconstructive vascular surgery may be effective. In most men, however, treatment is symptomatic, rather than aiming to cure the underlying problem. Given the prevalence of sec- ondary psychogenic problems, patient education and counselling are always valuable. Management of risk factors is an important part of patient man- agement. Those with hypertension should have their blood pressure optimally controlled, with emerging evidence that the angiotensin receptor antagonists actually improve erectile function, while many other drugs used for hypertension have an adverse effect upon erec- tions. Similarly, there is some evidence that improved diabetic con- trol improves erections, and there are some studies suggesting that lifestyle interventions can also improve erectile function. However, the improvements seen are usually modest and some form of pharmacological treatment is usually required. The mainstay of therapy in most men who present with ED will be oral therapy using a phosphodiesterase type 5 inhibitor (PDE5i). While sildenafil was the first such licensed preparation, three other drugs—​tadalafil, vardenafil, and avanafil—​have been marketed in recent years in Europe and North America. There appears to be little difference in efficacy and tolerability between these drugs, with the major differences relating to pharmacokinetics. The drugs are usu- ally used in an ‘on demand’ fashion, with ingestion 1–​2 hours prior to sexual activity. Tadalafil can be used in a daily dosing regimen given its extended half-​life. They are ineffective in the absence of sexual stimulation and a heavy meal may delay absorption. Around Table 13.6.4.1  Common causes of erectile dysfunction System Disease Neurological disease Multiple sclerosis Spinal cord injury Multiple system atrophy Lumbar disc prolapse Cauda equine syndrome Peripheral autonomic neuropathy (e.g. diabetes) Vascular disease Atherosclerosis Hypertension Hyperlipidaemia Diabetes Endocrine disease Diabetes mellitus Hypogonadism Hyperprolactinaemia Thyrotoxicosis Psychiatric disease Depression Anxiety states Iatrogenic Pelvic surgery (with nerve damage) Pelvic radiotherapy Drugs (see Table 13.6.4.2) Multifactorial aetiologies Renal failure Table 13.6.4.2  Drugs that can cause sexual dysfunction in men Drug type Drug or class of drug Effect Antihypertensive drugs Diuretics β-​blockers Centrally acting antihypertensive agents, e.g. clonidine, methyl DOPA ED ED ED Centrally acting agents Phenothiazines Butyrophenones Serotonin reuptake inhibitors Tricyclic antidepressants Phenytoin ED, reduced libido, ejaculatory dysfunction ED ED, ejaculatory dysfunction ED, reduced libido ED, reduced libido Endocrine drugs LHRH analogues Antiandrogens Oestrogens ED, reduced libido ED, reduced libido ED, reduced libido Recreational drugs Alcohol Marijuana Cocaine Opiates Amphetamines Anabolic steroids ED, reduced libido, ejaculatory dysfunction ED ED ED, reduced libido Reduced libido, ejaculatory dysfunction ED, reduced libido Other drugs Cimetidine Metoclopramide Digoxin ED, reduced libido ED, reduced libido ED section 13  Endocrine disorders 2410 70–​80% of men will respond to such therapy, although the response rate is lower in certain patient groups, such as diabetics and in men who have undergone radical pelvic surgery. Side effects include headache, flushing, indigestion, and nasal congestion, although these are usually mild and well tolerated. Prolonged erections are ex- tremely rare with these drugs. Extensive research has not identified any significant cardiac risk with this class of drugs, although they are contraindicated in men using nitrate medication, and sexual activity is inadvisable in men with unstable cardiac disease. A detailed sum- mary of the management of ED in men with cardiac disease can be found in the ‘Princeton Consensus Statements’. In men who fail to respond to oral PDE5i therapy, several ap- proaches can be tried, although there is little evidence that use of a different PDE5i is beneficial. Regular (daily) dosing appears to help some patients, the rationale reflecting experimental evidence that a PDE5i might improve endothelial function when taken regularly. Alternatively, optimization of coexistent medical conditions is occa- sionally helpful in this respect. There is developing evidence that in some men with a low serum testosterone, the response to a PDE5i can be improved by normalizing the testosterone levels. In men who fail to respond to these manoeuvres, alternative therapies such as vacuum erection devices or intracavernosal self-​ injection of alprostadil are often effective. In a few patients, notably those with severe diabetes, even these treatments are ineffective or poorly tolerated, and under these circumstances insertion of a penile prosthesis may be indicated. Rapid (premature) ejaculation Premature ejaculation (PE) occurs when a man ejaculates before he or his partner want climax to happen. For some men, the problem starts with their first sexual experience (primary PE). For others, it happens after a period of normal sexual functioning (secondary PE). In recent years there have been consensus panels that have agreed a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by ejaculation which always or nearly al- ways occurs prior to or within about one minute of vaginal pene- tration from the first sexual experiences (lifelong PE), or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE), associated with the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences such as distress, bother, frustration, and/​or the avoidance of sexual intimacy. The aetiology of primary PE is poorly understood with many po- tential pathophysiological mechanisms being proposed and none proven. Acquired PE is commonly associated with erectile dysfunc- tion and there are known associations with thyroid disease, alcohol abuse, opiate withdrawal, and possibly with prostatitis. Many men with PE do not seek treatment, although there is evidence that there can be deleterious effects upon self-​esteem, interpersonal relation- ships, and upon quality of life. When patients do seek medical at- tention, it is important to look for coexistent sexual dysfunctions (erectile dysfunction is commonly present) and to identify potential causes, while it is also important to assess the degree to which rela- tionship issues are important. Therapeutic options include sex therapy and psychotherapy, se- lective serotonin reuptake inhibitors (SSRIs), and topical anaes- thetics. While psychological approaches are commonly successful in the short term, they typically do not lead to long term cure. There is longstanding data that ‘off-​label’ use of SSRIs is an effective treatment for PE, with both on-​demand and daily dosing regimens in use. The latter provides a greater prolongation of the intravaginal ejaculatory latency time (IELT), but the potential risks of regular dosing with these drugs are well documented. Recently, a short acting SSRI has been licensed in Europe for this indication and appears to prolong the IELT two-​ to threefold, while improving control and distress. Local anaesthetic gels or sprays are also potential treatments, but none are currently licensed for clinical use. Penile deformity and Peyronie’s disease While young men or adolescents can occasionally present with a penile deformity that develops during adolescence (congenital curvature of the penis), the commonest cause of penile deformity is Peyronie’s disease, which is a localized connective tissue dis- ease of the penis leading to fibrotic plaque formation in the tu- nica albuginea of the corpus cavernosum. It was first described by Fallopius in 1561, although the condition is named after Francois Gigot De La Peyronie, surgeon to King Louis XV of France, who described it in 1743. While in pathological studies there is subclinical disease in over 20% of men, the clinical prevalence is around 1%. In some cases the condition can be familial, and there are associations with Dupuytren’s contracture, plantar fasciitis, and tympanosclerosis. The peak incidence occurs in the sixth decade, but cases have been reported throughout adult life. The pathophysiology is poorly understood, but the most commonly held view suggests that there is damage of the tunica albuginea associated with microvascular trauma. This leads to extravasation and perivascular inflammation with a round cell infiltrate, which in turn leads to fibrin deposition and subsequently fibrosis. Patients present with a palpable plaque within the penis which is most commonly felt on the dorsum, and there is a curvature of the penis, most commonly in the dorsal direction. The clinical pic- ture usually has two distinct phases, the ‘acute phase’, characterized by painful erections with progressive change in plaque size and deformity, which typically last 9–​18 months, and the subsequent ‘chronic’ phase where the deformity stabilizes (and occasionally im- proves) and pain with erection disappears. Numerous medical treatments have been tried in men with Peyronie’s disease. The oral agents that are most commonly used in clinical practice are vitamin E, tamoxifen, colchicine, and Potaba (potassium para-aminobenzoate, a form of vitamin B), but con- trolled studies have failed to demonstrate a consistent benefit for any agent. The most commonly used intralesional (injectable) agents are steroids, verapamil, and collagenase—​and following formal ran- domized controlled trials, the latter has been licensed for this indi- cation. In patients in the chronic phase of the disease, collagenase is injected into the plaque on several occasions with evidence that the deformity is improved in many, even if it does not disappear com- pletely. The cost of the treatment and the variability of the response currently limit the clinical utility of collagenase. Surgical treatment is reserved for those patients whose penile de- formity prevents sexual activity or those in whom sexual activity is painful either for the patient or his partner because of the deformity. The disease needs to be stable prior to surgical intervention. This point is particularly important, since disease progression after corrective surgery should be avoided. The most common surgical 13.6.4  Sexual dysfunction 2411 procedure is a Nesbit’s Procedure which involves surgical excision of an ellipse of a tunica albuginea on the opposite side of the penis to the plaque. The edges of the ellipse are apposed. Occasionally a grafting procedure can be performed whereby the plaque is incised and grafted typically with a patch of saphenous vein. In severe cases associated with coexistent erectile dysfunction, a penile prosthesis is indicated. Priapism A priapism is a penile erection which is unduly prolonged and which persists in the absence of a sexual stimulus. The classification of priapism divides cases into those where the aetiology is arterial (so-​called high flow priapism), and those cases where the aetiology reflects reduced venous drainage of the corpus cavernosum (so-​ called low flow priapism). Low flow priapism is by far the most common form of priapism and reflects stasis of blood within the penis, with sludging within the cavernosal sinusoids and subsequent thrombosis. Ischaemia, hypoxia, and acidosis develop as a consequence, and this prevents contraction of the penile smooth muscle which in turn exacerbates the condition. Low flow priapism is a medical emergency and re- quires urgent treatment to avoid irreversible damage to the vascular endothelium and smooth muscle of the penis and its erectile cap- acity. While comprehensive evidence is lacking, there are data to suggest that if treatment is successful within 24 hours, 56% of men will recover erectile function, while if treatment is delayed beyond that only 11% will recover potency. Causes of low flow priapism are shown in Table 13.6.4.3. The commonest are intracavernosal injec- tions, sickle cell disease, other hyperviscosity syndromes, and the use of some psychotropic drugs. Men with low flow priapism typically present with a painful erec- tion, in contrast to high flow priapism which is usually painless, but a careful assessment should seek to differentiate the low flow from the high flow condition (Table 13.6.4.4) and to identify the underlying cause. Aspiration of penile blood reveals thick dark venous blood, which on blood gas analysis shows hypoxia, hypercapnia, and acid- osis. Doppler scanning confirms lack of blood flow within the penis. Treatment for low flow priapism initially involves aspiration of enough blood via a wide bore cannula to produce detumescence and, if necessary, irrigation with warm heparinized normal saline (Fig. 13.6.4.1). If the erection reappears then intracavernosal in- jection of a smooth muscle α-agonist such as phenylephrine is appropriate, with concurrent monitoring of the systemic blood pres- sure. If this fails, then a surgical shunting procedure is appropriate. If treatment is delayed too long (see earlier) then even shunting procedures fail and the only hope for long term potency is a penile prosthesis. When there is a coexistent condition, such as sickle cell disease, specific treatment may be appropriate alongside treatment of the priapism. However, the traditional regime of oxygen, intravenous hydration, and analgesia is often unsuccessful, and only in selected cases is exchange transfusion indicated. High flow or non​ischaemic priapism develops following perineal trauma, when the penile artery is lacerated, resulting in a fistula be- tween the artery and the sinusoidal spaces of the penis. The priapism may appear at the time of injury, but more commonly it develops some time later, following spasm of the artery. Because the blood flowing through the penis is arterial (i.e. there is no ischaemia), there Table 13.6.4.3  Causes of low flow priapism Type Example Hypercoagulability disorders Sickle cell disease Myeloma Leukaemia Thalassaemia Total parenteral nutrition Drugs Intracavernosal agents (e.g. alprostadil) Psychotropic agents (e.g. phenothiazines, butyrophenones, trazadone) Anticoagulants (e.g. warfarin, heparin) Antihypertensives (e.g. α-blockers, calcium channel blockers) Miscellaneous Lumbar disc disease Solid tumours affecting the base of the penis Genitourinary sepsis Amyloidosis Table 13.6.4.4  Features that help to differentiate low flow from high flow priapism Findings Low flow priapism High flow priapism History of perineal trauma Rare Common History of coexistent blood disorder Sometimes Rare History of recent intracavernosal injection Sometimes Rare Corpora cavernosa rigid Usually Rare Penile pain Usually Rare Cavernosal blood gases Hypoxia, hypercapnia, acidosis Similar to arterial blood Colour Doppler penis Sluggish or absent flow Normal flow with evidence of arterial turbulence Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Urology (Gonzalez-​Cadavid NF, Rajfer J, 2005, Mechanisms of Disease: new insights into the cellular and molecular pathology of Peyronie’s disease, Nat Clin Pract Urol, 2, 291–​7), copyright © 2005. Initial measures Aspiration Irrigation Injection Surgery * Shunting procedure * Inject 200 μg phenylephrine directly into corpus cavernosum at the 3 o’clock or 9 o’clock positiona (monitor BP) * If fails consider repeat * If fails again, consider 500 μg * Irrigate by injecting and aspirating warm 0.9% salline * Compress penis * Use wide bore needle (18 G or 20 G) inserted either through the lateral penile shaft or through the glans penis to aspirate 50 ml blood from each corpus cavernosum * Specific measures (see text) * Oral drugs may help (Terbutaline, pseudoephedrine) * Analgesia Fig. 13.6.4.1  Treatment of low flow priapism. a Phenylephrine ampoules are available as 10 mg in 1 ml; dilute in 49 ml 0.9% saline to make a solution containing 200 µg/ml section 13  Endocrine disorders 2412 can be some circumspection in relation to treatment. The diagnosis is usually made by Doppler scanning and subsequent selective pu- dendal arteriography, which typically shows an arterial blush in the penile artery. The treatment of choice is embolization of the fistula with autologous blood clot. There is a rare variant of ischaemic priapism called ‘stuttering pri- apism’ where men present with recurrent episodes of painful erec- tions, usually at night. These episodes often resolve spontaneously. The commonest cause is sickle cell disease, but in some cases there is no obvious explanation. Treatment is difficult, with a variety of ap- proaches including androgen suppression being used. Female sexual dysfunction The sexual problems of women have, until recently, received much less attention from the medical and scientific community than male sexual problems. This is reflected in a less well-​developed under- standing of physiological and pathophysiological processes, in a less well-​defined classification of dysfunctions, and in a smaller range of therapeutic interventions. One classification of female sexual dysfunction is shown in Table 13.6.4.5. Epidemiological studies, al- though relatively immature, suggest that female sexual disorders are common and that they relate in part to age and to hormonal status. Comorbidities are common and should be identified, when present. The different sexual dysfunctions commonly coexist. One contentious area involves the recent DSM-​5 classification, which introduces the diagnosis of female sexual interest/​arousal dis- order, and eliminates the previous separate diagnoses of hypoactive sexual desire disorder and female sexual arousal disorder. This re- classification has been controversial and for ease of presentation the conditions are described here in a traditional format, since that is how much of the clinical data has been developed. Sexual desire disorders Hypoactive sexual desire disorder (HSDD) can be defined as ‘absent or diminished feelings of sexual interest or desire, absent thoughts or fantasies, and a lack of responsive desire’. This lack of interest will be greater than that which is normally seen with ageing and with the length of a relationship. Epidemiological studies suggest that it affects up to 32% of women under the age of 50 years. It becomes commoner with increasing age and with the onset of the menopause, whether natural or sur- gically induced. Around half the women who have this condition are ‘distressed’ by it, with the degree of distress diminishing with increasing age. Women with a surgically induced menopause are more likely to be distressed than those who have undergone a nat- ural menopause. The physiology and pathophysiology of desire is poorly under- stood, but probably resides biologically in the limbic system of the brain, where hormonal influences, including oestrogens and an- drogens, are important. Other hormonal abnormalities including hyperprolactinaemia and thyroid dysfunction can also result in sexual desire disorders. The dominant neurotransmitters include dopamine, which is important in the seeking-​appetite-​lust system, and oxytocin. Aetiology is often difficult to ascertain. There may be biological factors including natural or premature menopause, urinary in- continence, alcohol excess, and recreational drug abuse, while there are certain drug classes that can be associated with HSDD, including psychotropic agents, antihypertensive agents, drugs with an endocrine mechanism, and anticholinergics (Table 13.6.4.6). Psychological factors including a history of sexual abuse, anxiety and (especially) depression are also important, and their interaction with the biological issues makes this condition notoriously difficult to treat. Finally, the close relationship to other female sexual dis- orders and to male sexual dysfunction means that these aspects should be explored. Clinical assessment includes a sexual history and a full medical history. A careful history will seek to identify any psychological or physical issues, and it is important to find out whether the problem is universal or situational, and whether it is acquired or lifelong. A careful gynaecological assessment is important and a full endo- crine evaluation may be appropriate, which will include measure- ment of serum testosterone, dehydroepiandrosterone sulphate, prolactin, 17-​β oestradiol, and SHBG. Table 13.6.4.5  A classification of female sexual dysfunction Category Subcategory Disorders of desire Interest desire disorders Sexual aversion disorders Disorders of arousal Subjective arousal disorders Genital arousal disorders Combined subjective and genital arousal disorders Persistent arousal disorder Orgasmic disorders Pain disorders Dyspareunia Vaginismus Table 13.6.4.6  Drugs that cause sexual dysfunction in women Medication Desire disorder Arousal disorder Orgasm disorder Psychotropics Antipsychotics Benzodiazepines Lithium SSRIs Venlafaxine + + + + + + + + + + + CV drugs Beta blockers Clonidine Digoxin Spironolactone + + + + + + Hormonal preparations Contraceptive pill Antiandrogens Tamoxifen GnRH analogues + + + + + + + + Other H2 receptor antagonists Ondomethicin Ketoconazole Phenytoin Anticholinergics Antihistamines + + + + + + 13.6.4  Sexual dysfunction 2413 Treatment has been difficult and often unsuccessful, partly be- cause the aetiology is commonly multifactorial; partly because of the complex interaction with relationship issues; but also because the motivation to be treated is often low. Where physical causes can be identified, they should be treated, and indeed outcomes are best in the group of patients who have definite endocrine abnormalities and who are highly motivated. Recently a new agent, flibanserin, has been licensed in the United States for the treatment of this condition. Flibanserin is a non-​ hormonal 5-​HT1A receptor agonist and 5-​HT2A receptor antag- onist. In two 24-​week clinical trials, treatment was associated with significant improvements in sexual desire, increased sexually sig- nificant experiences, and a decrease in sexual distress. The most commonly reported adverse events were dizziness, nausea, feeling tired, sleepiness and trouble sleeping, and drinking alcohol while on flibanserin resulted in low blood pressure in some patients. Although there is some data regarding the use of testosterone for this indication, the evidence is mixed and its use is not recommended. Non​pharmacological treatments include sex therapy and cognitive behavioural therapy, but the results are often disappointing. Sexual aversion disorders Defined as ‘severe anxiety or disgust at the thought of sexual ac- tivity’, sexual aversion disorder may arise as a result of incest, rape, molestation, and psychological abuse. It may coexist with other anxiety disorders, and psychosexual therapy is the mainstay of treatment. Sexual arousal disorders Female sexual arousal includes the physiological responses of in- creased blood flow to the clitoris, the labia, and the vagina, leading to vasocongestion and engorgement. Vaginal lubrication appears to be a purely hydrostatic event with transudation from the vaginal capil- laries into the extracellular space. The physiology of these responses is poorly understood, but involves parasympathetic activation, with release of several neurotransmitters of which VIP and nitric oxide are almost certainly the most important. There is concurrent relax- ation of the vaginal smooth muscle with lengthening and dilation of the vagina. Systemically, there is an increase in the heart rate, flushing, and erection of the nipples. There are three categories of arousal disorder. Firstly, there is the so-​called subjective arousal disorder, associated with a reduction in the feelings of sexual arousal (including sexual excitement and sexual pleasure), but with normal vaginal lubrication still occurring. Alternatively, there may be genital sexual arousal disorder, when there is a definite and reduced degree of genital arousal in response to a sexual stimulus. Finally, the two may be found in combination. Sexual arousal disorders affect up to 24% of women. They are com- moner in older women, especially after the menopause, and the aeti- ology may be multifactorial. Psychological factors include reduced desire, sexual inhibition, anxiety, lack of intimacy, and male erec- tion problems. Physical factors that may be important include endo- crine abnormalities (e.g. reduced oestrogens, hyperprolactinaemia), vascular disease (e.g. diabetes), neuropathy (e.g. diabetes, mul- tiple sclerosis), drugs (Table 13.6.4.6), iatrogenic problems (e.g. posthysterectomy, postpelvic radiotherapy) and pain disorders (e.g. genital pain such as vaginismus, bladder pain due to recurrent urinary tract infection (UTI) or interstitial cystitis). Assessment should involve a careful history and examination, seeking to identify the range of risk factors that are present in an individual. Investigations might include an endocrine screen and, when indicated, Doppler assessment or plethysmography can evaluate vaginal and clitoral blood flow. Treatment should be directed towards the predominant aetio- logical issues. Psychosexual methods are important for cases where ‘subjective’ problems predominate. Physical treatments that may be of value include local lubricants, topical oestrogens (when vaginal atrophy is present and oestrogen deficiency is present), and local physical devices analogous to the vacuum erection devices used in male erection difficulties. Systemic hormone replacement therapy may be appropriate in some, but there are no licensed non​ hormonal therapies for this condition. Given the physiological finding that nitric oxide was important in the control of vaginal blood flow, it was thought that the phosphodiesterase inhibitors such as sildenafil might have a role, but the results of clinical trials were disappointing. Persistent sexual arousal disorder This is a poorly documented but uncommon condition character- ized by persistent genital arousal in the absence of a sexual stimulus. The pathophysiology is unknown, and there is no recognized therapy. Orgasmic disorders in women Anorgasmia is reported to occur in up to 37% of women, while in some there may be marked delay or diminution in the intensity of the orgasm. The female orgasm is characterized by a transient sen- sation of intense pleasure, associated with rhythmic contractions of the pelvic floor musculature, often associated with uterine and anal muscular contractions. Although the nature of the orgasm changes with age (becoming shorter and less intense), there is no evidence that the prevalence of orgasmic disorders becomes commoner with increasing age. The physiology of the female orgasm is poorly understood, but in most cases involves clitoral stimulation in association with an intact sacral reflex arc. While it would seem logical that intact ascending neural pathways are necessary for a woman to ex- perience an orgasm, patients with complete spinal cord transac- tion can, on occasions, experience them. It has been suggested therefore that ascending fibres within the vagus nerve may be important. There are multiple psychological and cultural influences on the ability of a woman to experience an orgasm. Similarly, there are number of physical and psychological problems that influence the ability of a woman to experience orgasm, including neuropathy, endocrine changes, thyroid disease, drugs (Table 13.6.4.6) and the presence of a weak pelvic floor. Psychological and social issues can be important: for instance, there is an inverse relationship between the degree to which a woman holds serious religious views and her ability to experience an orgasm. From a physical perspective, arousal disorders can result in delayed or absent orgasm. Therapy is primarily psychosexual, particularly when the problem is lifelong. When the problem is more recent in onset and associ- ated with a physically induced sexual arousal disorder, then therapy should be directed at the arousal disorder. No pharmacological agents have shown any value in the treatment of this condition. section 13  Endocrine disorders 2414 Sexual pain disorders in women Dyspareunia is pain associated with attempted or complete vaginal entry, while vaginismus indicates difficulties in the woman allowing entry of a penis (or any other object) into the vagina, despite her desire for this to happen. It is traditional to separate these two con- ditions, although in reality they may overlap, both in causality and in clinical presentation. Dyspareunia is reported by up to 15% of sexually active women, and it becomes much commoner in the postmenopausal population. Vaginismus is much less common, af- fecting less than 1% of sexually active women. Dyspareunia can be caused by several different conditions (see Table 13.6.4.7), and while these conditions can also cause vagin- ismus as well, there are cases where no clear organic aetiology ap- pears to exist. Clinically, it is important to identify such causes when they are present, and to identify and treat any sexual comorbidities. Vulvar vestibulitis is one of the most important causes of vagin- ismus and is characterized by pain with penetration or attempted penetration, tenderness of the vestibular area to even light touch, and erythema of the vestibular area. Its aetiology is unknown, but there is evidence of chronic inflammation, although the mechanism by which this arises is unclear. Treatment is often unsatisfactory, and involves analgesia (perhaps including tricyclic antidepressants and gabapentin), preventative hygienic measures, and sexual ab- stinence. There is preliminary evidence that vaginal electromyog- raphy (EMG) biofeedback, pelvic floor physiotherapy, and possibly vestibulectomy may have a role in treatment, although controlled studies are required for confirmation. FURTHER READING Basson R (2006). Clinical practice: sexual desire and arousal disorders in women. N Engl J Med, 354, 1497–​506. Basson R, et al. (2004). Revised definitions of women’s sexual dysfunc- tion. J Sex Med, 1, 40–​8. BAUS Section of Andrology Genitourethral Surgery (2018). BAUS consensus document for the management of male genital emergen- cies: priapism. BJU Int, 121, 835–9. Broderick GA, et  al. (2010). Priapism:  pathogenesis, epidemiology, and management. J Sex Med, 7, 476–​500. Brotto LA, et al. (2010). Women’s sexual desire and arousal disorders. J Sex Med, 7, 586–​614. Buvat J, et al. (2011). Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). J Sex Med, 8, 284–​93. Clayton AH, Vallardares Juarez EM (2017). Female sexual dysfunc- tion. Psychiatr Clin North Am, 40, 267–84. Ciocanel O, Power K, Eriksen A (2019). Interventions to treat erectile dysfunction and premature ejaculation: an overview of systematic reviews. Sex Med, 7, 251–69. Eardley I (2013). The incidence, prevalence, and natural history of erectile dysfunction. Sex Med Rev, 1, 3–​16. Eardley I, et al. (2010). Pharmacotherapy for erectile dysfunction. J Sex Med, 7, 524–​40. Feldman HA, et al. (1994). Impotence and its medical and psycho- social correlates:  results of the Massachusetts Male Aging Study. J Urol, 151, 54–​61. Fugl-​Meyer KS, et al. (2013). Standard operating procedures for female genital sexual pain. J Sex Med, 10, 83–​93. Gandaglia G, et al. (2014). A systematic review of the association be- tween erectile dysfunction and cardiovascular disease. Eur Urol, 65, 968–​78. Gelbard MK, Chagan L, Tursi JP (2015). Collagenase clostridium histolyticum for the treatment of Peyronie’s disease:  the devel- opment of this novel pharmacologic approach. J Sex Med, 12, 1481–​9. Gonzalez-​Cadavid NF, Rajfer J (2005). Mechanisms of disease: new insights into the cellular and molecular pathology of Peyronie’s dis- ease. Nat Clin Pract Urol, 2, 291–​7. Gupta BP, et al. (2011). The effect of lifestyle modification and cardio- vascular risk factor reduction on erectile dysfunction: a systematic review and meta-​analysis. Arch Intern Med, 171, 1797–​803. Hackett G (2009). The burden and extent of comorbid condi- tions in patients with erectile dysfunction. Int J Clin Pract, 63, 1205–​13. Hackett G (2011). Cardiovascular drugs and sexual dysfunction. Primary Care Cardiovascular Journal, 4, 124–​6. Hatzichristou D, et al. (2010). Recommendations for the clinical evalu- ation of men and women with sexual dysfunction. J Sex Med, 7, 337–​48. Table 13.6.4.7  Causes of dyspareunia Organic Superficial and introital Infections (vulvitis, vulvar vestibulitis, cystitis, vaginitis) Hormonal (vaginal atrophy) Anatomic (fibrous hymen, vaginal agenesis) Muscular (hyperactivity of levator ani) Iatrogenic (postsurgical, postradiation) Neuropathic Deep Endometriosis Pelvic inflammatory disease Chronic pelvic pain syndrome Iatrogenic (postsurgical, postradiation) Psychological Comorbidity with other disorders of female sexual function Previous sexual abuse or rape Depression and anxiety Couple related Inadequate foreplay Couple conflicts Sexual dissatisfaction Anatomic compatibility issues 13.6.4  Sexual dysfunction 2415 Hatzimouratidis K, et al. (2010). Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol, 57, 804–​14. Hatzimouratidis K, et al. (2012). EAU guidelines on penile curvature. Eur Urol, 62, 543–​52. Ishak WW, et al. (2010). Disorders of orgasm in women: a literature review of etiology and current treatments. J Sex Med, 7, 3254–​68. Jaspers L, et al. (2016). Efficacy and safety of flibanserin for the treat- ment of hypoactive sexual desire disorder in women: a systematic review and meta-​analysis. JAMA Intern Med, 176, 453–​62. Kheirandish P, Chinegwundoh F, Kulkarni S (2011). Treating stut- tering priapism. BJU Int, 108, 1068–​72. Leiblum S, et al. (2005). Persistent sexual arousal syndrome: a descrip- tive study. J Sex Med, 2, 331–​7. Lewis RW, et  al. (2010). Definitions/​epidemiology/​risk factors for sexual dysfunction. J Sex Med, 7, 1598–​607. Nehra A, et al. (2012). The Princeton III Consensus recommenda- tions for the management of erectile dysfunction and cardiovas- cular disease. Mayo Clin Proc, 87, 766–​78. Pryor JL, et  al. (2006). Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-​blind, randomised controlled trials. Lancet, 368, 929–​37. Romeo JH, et al. (2000). Sexual function in men with diabetes type 2: association with glycemic control. J Urol, 163, 788–​91. Salonia A, et al. (2014). European association of urology guidelines on priapism. Eur Urol, 65, 480–​9. Seftel AD, Sun P, Swindle R (2004). The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol, 171, 2341–​5. Serefoglu EC, et  al. (2014). An evidence-​based unified definition of lifelong and acquired premature ejaculation:  report of the second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. J Sex Med, 11, 1423–​41. Sharma KL, Alom M, Trost L (2019). The etiology of Peyronie’s disease: pathogenesis and genetic contributions. Sex Med Rev, pii: S2050- 0521(19)30069-1. doi: 10.1016/j.sxmr.2019.06.004. Sungur MZ, Gunduz A (2014). A comparison of DSM-​IV-​TR and DSM-​5 definitions for sexual dysfunctions: critiques and challenges. J Sex Med, 11, 364–​73. Tommola P, Unkila-​Kallio L, Paavonen J (2010). Surgical treatment of vulvar vestibulitis:  a review. Acta Obstet Gynecol Scand, 89, 1385–​95.