Women's sexual dysfunction: a pathophysiological review
F. Montorsi, Associate Professor of Urology, University Vita-Salute San Raffaele, Istituto Scientifico San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
women's (sexual dysfunction)
spinal cord injury
upper (lower) motor neurone
Expanded Disability Status Scale
total mesorectal excision
autonomic nerve preservation
duplex Doppler ultrasonography.
Sexual dysfunction (SD) in women is a multifactorial condition with anatomical, physiological, medical, psychological and social components. Well-designed, random-sample, community-based epidemiological investigations of women with SD are limited. Current data reveal that up to 76% of women have some type of SD [1,2]. Population census data from the USA suggest that ≈ 10 million American women aged 50–74 years self-report complaints of diminished vaginal lubrication, pain and discomfort during intercourse, decreased arousal, and difficulty achieving orgasm. Laumann et al. found that SD is more prevalent in women (43%) than in men (31%), and is associated with various psycho-demographic characteristics, e.g. age, education, and poor physical and emotional health. More importantly, women's SD (WSD) is associated with negative experiences in sexual relationships. Recently, Brock et al. reported the results of an international survey aimed at assessing both the prevalence and predictors of SD among mature men and women. Among a population of 4507 subjects, decreased sexual interest was reported by 34% of women and 18% of men; moreover, 19% of women and 11% of men reported that they did not consider sex pleasurable. Of the women interviewed, 23% reported inadequate lubrication, with a significant increase in this complaint in women aged 50–69 years .
WSD includes disorders of sexual desire, arousal, orgasm and/or sexual pain, which result in significant personal distress and may compromise women's health and affect their quality of life. Although each specific condition can be separately defined in medical terms, there is significant clinical overlap in affected patients.
The report of the International Consensus Development Conference on Female Sexual Dysfunction (Appendix 1) classified SD in women into sexual desire disorders (subdivided into hypoactive sexual desire disorder and sexual aversion disorder), sexual arousal disorder, orgasmic disorder and sexual pain disorders (further subdivided into dyspareunia, vaginismus, and noncoital sexual pain disorder) . Each of the diagnoses can be further classified as lifelong vs acquired, generalized vs situational, and organic vs psychogenic vs mixed vs unknown .
THE PATHOPHYSIOLOGY OF WSD: A BRIEF UROGYNAECOLOGICAL SURVEY
WSD is a complex neurovascular phenomenon under psychological and hormonal control. Sexual desire could be described as consisting of biological roots, which are partly based on hormones (i.e. androgen, oestrogen) and of motivational roots, which are based on intimacy, pleasure and both relationship and cognitive issues (i.e. risk and wish related with sexual activities). Sexual arousal is the state with specific feelings and physiological changes usually associated with sexual activity involving the genitals.
Women's sexual arousal is the final expression of a complex process involving sexual stimulation, ascending/descending steady control by the CNS (both supraspinally and spinally), a peripheral neurovascular pathway, and an important hormonal milieu. Sexual arousal is also a haemodynamic process, involving increased arterial inflow, coordinated with clitoral smooth muscle relaxation. Thus, for any dysfunction in arousal one must consider the potential absence of coordination between an objective genital activation (i.e. with vasocongestion, enhanced local hyperaemia and increased lubrication) and/or extragenital activation (i.e. skin sensitivity, mammary tension and increased scent perception towards pheromones), and the woman's subjective perception of the arousal itself [6–8]. Indeed, some women, especially in the premenstrual period, do not seem to focus their attention on the potentially pleasant sensations delivered by genital and nongenital excitement (i.e. nipples, skin, etc.) because of the distraction or distress resulting from negative emotions (i.e. anxiety, ‘gut feeling’, etc.). The critical and objective analysis of women's sexual responses, recently proposed by Basson , underlines the need for a distinction among sexual arousal disorders between: (a) a generalized group, where there is a complete lack of mental excitement and of genital congestion; (b) missed arousal, typical of those women who do not pay much attention to normal physical excitement; and (c) an unpleasant genital engorgement, defined as a dysphoric arousal.
The most accurate definitions of human orgasm are probably those integrating biopsychological perspectives which thus describe both the complex of genital and systemic changes and modifications, and the emotional and mental components of the peak of sexual pleasure [10,11]. Orgasm involves an altered state of consciousness associated with a primarily genital, but also nongenital, sensory input. A so-called ‘orgasmic platform’, potentially responsible for either the genital pleasure at the peak and a possible biological basis for the greater capacity for multiple orgasm, has been suggested in women as the result of genital sexual arousal [10,12,13]. Sensory trigger points have been advocated at the orgasmic platform level, including the clitoris and vagina, clitoral and periurethral glans, cervix, uterus, anal mucosa, and proprioceptive stimuli from the levator ani and perivaginal muscles . Nongenital trigger points are, e.g. the breast and nipples, skin and sensory organs [10,15]. At least two major situations have been described anatomically, i.e. clitoral vs vaginal orgasm [10,12,14]. Both anatomical and functional biological modifications of these trigger points and areas can significantly affect the women's orgasmic phase.
Dyspareunia is defined as a recurrent or persistent genital pain associated with sexual intercourse [5,16]. Most women described dyspareunia as acquired and generalized, and characterized, chronologically, by the onset of pain at the moment of penetration or when the penis is completely inserted in the vagina. This pain is chronologically linked to the period of intercourse or reported as persistent after the penis has left the vagina (urge sensation at the introitus up to 2–3 days after intercourse severe enough to interfere with normal intercourse) [17,18].
NEUROLOGICAL DISORDERS: SPINAL CORD INJURY (SCI)
There are few publications about SD in women with SCI [19–30]. Women's desire for sexuality and sexual activities seems to decrease after injury . Charlifue et al. reported that sex was less important after injury in their series of 231 women with SCI, whereas other authors found a significantly higher level of hypoactive sexual desire after injury than the sexual drive before injury (44% vs 20%) . Interestingly, a decrease in the frequency of self-masturbation in these women has been reported  with preferred sexual activities after SCI reported to be kissing, hugging and touching .
The influence of SCI on sexual response strictly depends on the degree and location of injury in the spinal cord. In women with complete upper motor neurone (UMN) injuries affecting the sacral segments, the ability for reflex but not psychogenic lubrication of the vagina should be maintained [20,26,30]. On the contrary, in women with incomplete UMN injuries affecting the sacral segments, data seem to show that they are able to maintain both the capacity for reflex and psychogenic lubrication. Sipski et al. also reported that those women with a higher ability to perceive a combination of light touch and pinprick sensation in the T11–L2 dermatomes will also have a greater likelihood of achieving psychogenic lubrication.
Most of the data available concerning WSD after SCI comes from laboratory-based research [22–29]. The pathophysiology of the orgasmic phase in women with SCI has also been studied in laboratory settings [24,25]. Sipski et al. reported the results of a study enrolling 12 women with a lower motor neurone (LMN) injury affecting the S2–S5 spinal reflex arc and 50 with UMN injuries. The ability to achieve orgasm was assessed historically and in the laboratory. Historically, only 55% of women with SCI were able to reach orgasm after injury, whereas 44% were orgasmic in the laboratory [24,25]. These authors showed that in each condition, subjects with SCI were significantly less likely to achieve orgasm than controls (both P = 0.001). Similarly, these results showed that the possibility of achieving orgasm is less likely (17%) if women have a complete LMN injury affecting the sacral segments than if they have any other levels and degrees of injury . Moreover, latency to obtain orgasm was greater in women with SCIs than in normal subjects. Sipski et al. showed a significant difference (P = 0.049) in average latency to orgasm when able-bodied subjects were compared to those with SCI. On the contrary, the so-called systemic modification which usually accompanies the orgasmic phase, e.g. blood pressure, heart rate and respiratory rate fluctuations, were generally similar between women with and without SCI. These authors concluded that an intact sacral reflex arc is needed to achieve orgasm and that orgasm may be a reflex response of the autonomic nervous system [25,34,35]. Furthermore, Sipski et al. also proposed that the orgasmic sensory experience may be partly derived from afferent autonomic innervation, which also remains after complete SCI. However, Whipple et al. suggested that the vagus nerve can provide innervation to the cervix and is the source of cerebral transmission of orgasmic sensation in women.
NEUROLOGICAL DISORDERS: MULTIPLE SCLEROSIS (MS)
Current prevalence rates for MS are 1 per 1000 Americans and 2 per 1000 Northern Europeans . SD is reportedly as frequent as 72% among women with MS [36–39]; sexual activity ceases or is significantly unsatisfactory in 39% of women with MS . Symptoms reported include fatigue in 68%, reduced sensation in 48%, reduced vaginal lubrication and difficulty with arousal in 35%, difficulty reaching orgasm or anorgasmia in 72%, and dyspareunia and other types of sexual pain disorder [37–39].
In a case-control study, Zorzon et al. reported data on sexuality in a series of 70 consecutive women with MS compared with a control group of age-matched women with chronic disease (rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis and ankylosing spondylitis), and another of healthy subjects. These authors found that more patients with MS reported a reduction in sexual desire than in both patients with a chronic disease and normal subjects. However, the same authors found a significant difference in sexual desire only between patients and healthy controls (P < 0.01). Moreover, in this series, women with MS reported less vaginal lubrication than healthy controls (P < 0.001), while the difference from chronic disease controls was not statistically significant. The authors also reported that changes in vaginal sensation were very common (27.1%) and were also more common in MS than in both chronic disease controls and healthy subjects (P < 0.01). Overall, more than a third of women had a decrease in vaginal lubrication, and a reduced libido.
Similar frequencies in modifications of vaginal lubrication and vaginal sensation, orgasmic capacity and diminished sexual desire were also reported by others [39,41–44]. Hulter and Lundberg  showed that more frequent and severe changes in sexual function were characteristic of women complaining of advanced MS (i.e. a median Expanded Disability Status Scale, EDSS, score of 6.5). Zivadinov et al. also reported data from a Spearman correlation analysis in the same cohort of women with MS, between symptoms of SD and characteristics of both patients and the clinical type of MS. MS is generally described as relapsing-remitting (RR) or primary-progressive (PP). The former is characterized by episodes of neurological dysfunction followed by remissions, when a patient notices complete or partial improvement in neurological deficits after each exacerbation and no further progression of neurological decline between attacks. In the latter, on the contrary, patients present a continuous insidious or rapid decline in neurological function. When patients with RR-MS have a more chronic progressive course, the form is called secondary progressive (SP) MS. SD was significantly correlated with RR-MS (r = −0.33, P = 0.0106) but not with both the PP (P = 0.06) and the SP types (P = 0.08). There was also a close correlation between SD and age at onset of symptoms (r = 0.31, P = 0.0168), the current age of the woman (r = 0.37, P = 0.0043), but curiously not with the duration of the neurological disease itself (P = 0.25). Similarly, there was a significant correlation between sexual and physical disorders (r = 0.42, P = 0.0017), sphincteric and bladder dysfunction (r = 0.39, P = 0.0025 and 0.37 and 0.0035, respectively), fatigue score (r = 0.30, P = 0.0284) and both cognitive deterioration, as assessed by the Mini Mental State Examination , and the neurological impairment, as assessed by the EDSS  (r = 0.30, P = 0.0280 and 0.28, 0.0306, respectively). Other studies have shown a correlation between sexual and bladder dysfunction in patients with MS [49,50]. Nortvedt et al. also reported a significant reduction in the quality of life in MS patients with both sexual disorders and bladder dysfunction.
There was also a similar correlation between SD and low educational level (r = 0.37, P = 0.0040) and both a high value either for depression, as assessed by the Hamilton Depression Rating Scale  or anxiety, as assessed by the Hamilton Anxiety Rating Scale  (r = 0.40, P = 0.0018, and 0.40 and 0.0017, respectively) . After a 2-year follow-up the percentage of patients with at least one sexual disorder remained stable at > 70%. Interestingly, men reported at least one SD more frequently than women, both at the start and at the end of the study (P= 0.002). However, when both men and women were considered together in a univariate analysis, changes in sexual function throughout time correlated with modifications in bladder function (r = 0.47, P < 0.001) and EDSS score (r = 0.41, P < 0.001). After removing the effect of psychological aspects, only changes in bladder function maintained a significant correlation with fluctuations in sexual function (r = 0.36, P = 0.003).
When compared with groups of women with chronic diseases and healthy subjects, Zorzon et al. reported that anorgasmia and hyporgasmia (i.e. loss of the capacity to achieve orgasm and/or difficulty in achieving orgasm and/or reduction of orgasmic sensation) were the more commonly reported (37.1%) SD in patients with MS, followed by decreased vaginal lubrication (35.7%) and reduced libido (31.4%). These authors showed that fewer women with MS were able to achieve orgasm than their peers (chronic disease controls, P < 0.05; healthy controls, P < 0.001) . Moreover, more than a third of women reported difficulty or inability in achieving orgasm than before the disease, with a statistically significant difference compared with chronic disease controls (P < 0.01). Anorgasmia or hyporgasmia was reported more frequently, with a statistically significant difference compared with healthy controls (P < 0.001). Yang et al. recently showed that the most common sexual complaint was difficult or no orgasm, even in their series of 14 women with MS; this complaint was statistically highly associated with an abnormal or absent pudendal somatosensory evoked potential (χ2 test, P < 0.01).
Curiously, Hennessey et al. reported the results of a survey of urinary, fecal and SD in 68 men and 106 women with MS, finding that although sexual problems occurred in 52% (55/106) of women enrolled, 65/106 (61%) were satisfied with their sexual activity.
PELVIC SURGERY FOR RECTAL CANCER
Sexual and bladder function are often sacrificed when a conventional low anterior and abdominoperineal resection with an extended lymphadenectomy is used to achieve radical surgery in patients with advanced lower rectal cancer [56–58]. Indeed, oncological resection of rectal cancer has been reported to be associated with a 10–60% rate of sexual and urinary dysfunction . In both locally advanced primary rectal carcinomas and locally recurrent rectal cancer, extended circumferential margins are required for a complete resection. Multimodal treatment, combining, e.g. preoperative external beam radiation therapy, radical surgery and intraoperative radiotherapy, has been suggested to improve the cure rate of both these types of rectal cancer [58–63].
These genitourinary dysfunctions are usually caused by a surgical approach that is not nerve-sparing during the procedure, which implies damage to one or more of the autonomic nerves, including the sympathetic hypogastric nerve, sacral splanchnic nerves and the pelvic autonomic nerve plexus. Several techniques of nerve-sparing surgery for organ-confined or advanced rectal cancer have been developed to preserve genitourinary function while achieving complete surgical radicality [56,63–75]. Enker et al. reported that in patients undergoing abdominoperineal resection for primary cancer of the rectum, in accordance with the principles of total mesorectal excision (TME) and autonomic nerve preservation (ANP), sexual function was preserved in ≈ 57% of patients undergoing abdominoperineal resection, vs 85% of patients undergoing sphincter preservation.
Data on this topic in women are very rare and conflicting. A few papers reported the results of both prospective and retrospective studies aiming at evaluating urinary, bowel and sexual function in both men and women, but unfortunately with no type of standardized method from the women's perspective. In addition, most of the outcome studies enrolling both men and women considered only the male experience.
Recently, Pocard et al. studied prospectively the urinary and sexual function before and after surgery in patients who had a sphincter-preserving operation for rectal carcinoma by means of a curative TME with ANP, with no irradiation beforehand. In this series, seven women underwent TME by the ANP technique, with a complete surgical identification and subsequent preservation of both hypogastric and sacral splanchnic nerves. There was no difference in urinary function before and after surgery in women or men. Four of the seven women were sexually active before surgery, and this activity and ability to achieve orgasm was unchanged in these women, with no dyspareunia reported. Chorost et al. similarly reported the results of a retrospective review of the medical records of 52 consecutive patients who had potentially curative procedures for rectal cancer. The first interesting result described was the discovery that a discussion before surgery about the potential risk of SD was not documented in the consent in 37 of 52 patients (71%). However, of all the women, only one of 16 reported SD afterward.
In addition, multimodal treatment can increase the chances of damaging the urogenital nerves and organs, which might result in voiding and sexual disorders [56,62,71]. Only a few reports are restricted to the evaluation of the impact on women's sexual function of both surgery alone or multimodal treatment. Mannaerts et al. reported the sexual outcome of a population of both men and women with locally advanced primary (32 men and 23 women) and locally recurrent rectal cancer (41 men and 25 women) aged 39–86 years. Using a parallel and repeated set of questionnaires, after a multimodal aggressive approach, these authors evaluated sexual and voiding function during the last 6 months before therapy and at the 14-month follow-up (range 4–60). The incidence of SD was higher before and after surgery in women. Interest in sexual activity decreased in women from 63% to 26% after the treatments (P = 0.002). Similarly, the preoperative ability to have an orgasm had disappeared in half the women, and overall in 45% of patients after locally advanced primary and in 57% after locally advanced recurrent rectal cancer treatment. The mean quality of orgasm, as described on a 5-cm visual analogue scale, was reduced from 60% to 28% in the primary group, and from 50% to 22% (both P < 0.001) in the locally recurrent group. A multivariate analysis showed that age > 60 years significantly reduced the ability to have orgasm after treatment (P = 0.046) and the ability to have sexual intercourse (P = 0.04) . More recently the same authors, reporting the long-term functional outcome after multimodal treatment for locally advanced primary and locally recurrent rectal cancer, found that patients complained of fatigue in 44%, perineal pain in 42%, radiating pain in the leg(s) in 21%, walking difficulties in 36%, and voiding dysfunction in 42% as symptoms of ongoing morbidity. Dramatically, sexual inactivity was reported by 56% of the respondents . In a retrospective small survey including 43 patients with low rectal cancer who had a low anterior resection associated or not with neoadjuvant or adjuvant radiotherapy, Chatwin et al. found that general SD was reported by nine of the 13 sexually active men and two of the 11 sexually active women. However, despite their reported fecal, urinary and sexual dysfunction, most patients were satisfied with their quality of life.
Recently Quah et al. reported the results of a retrospective analysis of bladder and sexual function before and after surgery in patients treated with laparoscopically assisted and conventional open mesorectal resection for cancer. Of the respondents to the postal questionnaires and telephone interviews (72%), 40 had had laparoscopically assisted resection and 40 an open approach. There was no significant deterioration in bladder function after surgery, although two patients in the laparoscopic group required long-term intermittent self-catheterization. There was a significant difference in male, but not female, sexual function, with seven of 15 sexually active men in the laparoscopic group reporting impotence or impaired ejaculation, compared with only one of 22 having an open operation (P = 0.004).
RADICAL CYSTECTOMY FOR UROLOGICAL MALIGNANCIES
To our knowledge, to date no report has been restricted to evaluating women's sexual function after major urological surgery for bladder cancer [82–88]. Genitourinary cancers are commonly associated with treatment-related SD, varying from mild to severe. Sexual problems or SD may occur as a result of any aspect of cancer disease and treatment. Sexual function is sensitive to the effects of trauma, both physical and emotional. This is particularly the case for patients whose cancer affects their genital organs.
Marshall et al. reported that anterior exenteration in women can be accurate when using a disciplined anatomical approach. Women undergoing cystectomy with the simultaneous removal of uterus, ovaries and parts of the vaginal wall face had problems with their femininity and doubts about future sexual functioning. Excision of the uterus, a portion of the vagina and the urethra seems to reduce the potential for pelvic recurrence, but a vaginal reconstruction and continent urinary diversion provide a better quality of life, with maintenance of sexual function and urinary continence.
Original data were reported by Bjerre et al., who evaluated the sexual profile after urinary diversion in 17 women who had a radical cystectomy with the continent Kock reservoir, and in 20 with an ileal conduit diversion. Thirty-seven women completed the questionnaire, of whom 17 had a continent and 20 an ileal conduit diversion; the median (range) follow-up was 0.8 (0.5–4.4) and 4.6 (2.8–12.0) years, respectively. Data from only 33 patients were eligible for analysis, but there were no significant differences between the groups. Coital frequency remained unchanged or increased in 44% of patients with a continent reservoir and in 18% of those with an ileal conduit (not statistically significantly different, P = 0.11). Among those reporting other than unchanged/increased activity, almost a third indicated physical problems or decreased desire as the reason, and 30% felt less sexually attractive, with cystectomized patients reporting a higher percentage than others. A higher frequency of dyspareunia among patients with a continent reservoir was an unexpected finding (P = 0.06).
Nordstrom et al. described the sexual function outcome of 66 patients (40 men and 26 women) who had an ileal conduit urinary diversion because of bladder cancer (44) or incontinence/bladder dysfunction (22). Five of the six women treated by cystectomy, who were sexually active beforehand, reported either a decrease or cessation of coital sexual activity afterward. The main problems were a decrease in sexual desire, dyspareunia and vaginal dryness. One woman reported being unable to experience orgasm after surgery. Compared with women with bladder cancer, those with incontinence/bladder dysfunction were more likely to have an active sexual life after urostomy surgery. Interestingly, seven women in this group, of whom four were sexually inactive before surgery, reported increased their sexual activity after surgery. For these women the conduit operation removed the need to use incontinence pads or indwelling catheters.
Hautmann et al. presented data on a nerve-sparing cystectomy with orthotopic bladder replacement in women. While the rationale for a nerve-sparing approach is progressively increasing even in women, results on sexual function are always neglected. Indeed, this interesting paper presents detailed data on urinary continence and voiding dysfunction, underlining that urethral support- and nerve-sparing cystectomy plus the ileal neobladder as a reservoir guarantee excellent continence in all patients but, despite their efforts, the authors were unable to show any advantage of the nerve- and urethral support-sparing cystectomy technique for voiding.
More recently, Horenblas et al. reported their preliminary results of a modified sexual function-preserving cystectomy in both men and women, intended to achieve maximal tissue conservation, potentially resulting in preserved normal sexual function and satisfactory urinary tract reconstruction. The procedure in women consisted of pelvic lymph node dissection followed by cystectomy alone, preserving all internal genitalia. An ileal neobladder was thus anastomosed to the urethra. This type of surgical approach was suggested for women with bladder cancer stages T1–T3 with no tumour growth in the bladder neck and no invasive tumour in the bladder trigone. Three women (mean age 55 years, range 38–71) were enrolled in this protocol and all reported normal vaginal lubrication throughout sexual activity.
URINARY INCONTINENCE (UI) AND LUTS
Recently, we extensively evaluated 227 consecutive women (mean age 52 years, range 19–66) complaining of UI and/or LUTS, using a comprehensive history (including several validated questionnaires), a complete physical examination, and a urodynamic multichannel evaluation . A group of 102 age-matched women (mean age 54 years, range 19–63), assessed for an annual routine gynaecological evaluation and not complaining of urinary symptoms, were enrolled as cross-sectional controls and investigated in accordance with the Female Sexual Function Index. SD was diagnosed in 99 of 216 patients (46%), of whom 34 reported hypoactive sexual desire, 23 reported sexual arousal disorder, 11 complained of orgasmic deficiency and 44 had sexual pain disorder (e.g. dyspareunia or noncoital genital pain). Women reporting low sexual desire commonly had stress UI (47%); 60% of the women with sexual arousal disorders and 61% of those with sexual pain disorders also complained of recurrent bacterial cystitis. Of those complaining of orgasmic phase difficulties, 46% also reported a troublesome urge UI. The Female Sexual Function Index scores in both groups were (patients vs controls, median value, P): desire, 2.0 vs 3.2 (<0.01); arousal, 2.8 vs 3.6 (>0.05); lubrication, 3.2 vs 4.4 (0.01); orgasm, 4.1 vs 4.4 (>0.05); sexual satisfaction, 2.7 vs 4.0 (<0.01); and sexual pain, 1.8 vs 4.0 (<0.001). Thus we concluded that significantly more women reporting UI or LUTS also complained of SD than in a general, healthy female population not complaining of urinary symptoms. An investigation of female sexuality is suggested for these patients.
THE ESSENTIAL DIAGNOSTIC APPROACH TO SD IN WOMEN
Management of women with SD begins with the identification and diagnosis of any problems in their relationships and is based on the patient's self-report in conjunction with a clinical evaluation.
MEDICAL AND SEXUAL HISTORY
A detailed and comprehensive sexual history should include a past and present assessment of sexual desire (libido), arousal and orgasmic capabilities. In addition to physiological sexual responses, overall sexual satisfaction should also be assessed. The medical history should focus on the patient's medical illness, i.e. chronic/medical illness such as diabetes, anaemia or renal failure; neurological illness, e.g. SCI, MS or lumbosacral disc disease; endocrinological diseases like hypogonadism, hyperprolactinaemia and thyroid disorders; atherosclerotic vascular risk factors such as hypercholesterolaemia, hypertension, diabetes, the smoking habits, or family history. Moreover, focused questions should investigate previous pelvic/perineal/genital trauma (e.g. bicycling injury), genital pain, surgical (e.g. hysterectomy, laminectomy, vascular bypass surgery) and psychiatric history (e.g. depression, anxiety). Any medications or recreational drug use/abuse (e.g. antihypertensives, antidepressants, alcohol, cocaine) should also be identified.
The potential causes of genital/sexual pain are:
- • Infectious/inflammatory
- • Genital herpes
- • Sexually transmitted diseases
- • Recurrent vaginal infections
- • Vestibular adenitis
- • Tumours
- • Neuroma
- • Fibroepithelial polyp
- • Inclusion cysts
- • Papillomas
- • Melanoma
- • Squamous cell carcinoma
- • Genital myofascial pain syndrome
- • Vaginismus
- • Endometriosis
- • Uterine fibromas
- • Ovarian cyst and tumours
- • Adhesions
- • Pelvic inflammatory disease.
Given the personal, interpersonal, social and occupational implications of sexual problems, a brief psychosocial history must be compiled for every patient. Current psychological state, self-esteem, history of sexual trauma/abuse, and past and present relationships and social and occupational performance, should be addressed.
In addition to a detailed vascular and neurological examination, a careful and systematic examination of the external genitalia, using magnifying surgical loupes, and cotton-bud evaluation of the external genitalia can confirm aspects of the medical history (e.g. vestibular adenitis and neuropathies), and occasionally reveal unsuspected physical findings such as paraclitoral neuromas.
Laboratory testing is strongly recommended in all patients. Standard serum chemistry, complete blood count and lipid profiles may identify vascular risk factors such as hypercholesterolaemia, diabetes mellitus and renal failure. A measurement of serum thyroid-stimulating hormone may also be indicated. The functioning integrity of the hypothalamic-pituitary-gonadal axis should be examined in every women with SD. Adrenal and ovarian androgens, oestrogens and FSH and LH testing are strongly recommended. Total androgen production is best reflected by the total testosterone, but the available testosterone is best measured as free testosterone, as determined by equilibrium dialysis. Whenever total or free testosterone is measured, the value of circulating sex hormone-binding globulin must be taken into consideration. To evaluate adrenal androgen status an assessment of dehydroepiandrosterone sulphate levels is recommended. Androgen values should be ideally determined in the morning and in the mid-third of the menstrual cycle, but this recommendation makes clinical practice extremely difficult.
SPECIALIZED DIAGNOSTIC TESTING
Diagnostic methods such as vaginal photoplethysmography, duplex Doppler ultrasonography (DUS), vaginal and clitoral temperature and vibration sensory testing, and selective pudendal arteriography increase the physician's and patient's understanding of the pathophysiological mechanisms, but lack of normative data may limit the use of specialized testing.
Vaginal, labial and clitoral warm, cold and vibratory sensory thresholds can be reliably measured with a thermal sensory analyser/vibratory sensory analyser system (e.g. GSATM, Medoc, Israel) and compared with currently available validated nomograms, allowing a quantitative neurological assessment of the women's genitalia . This valuable noninvasive diagnostic tool is helpful in managing women with SD.
Clinically useful and noninvasive vascular testing of women with SD includes vaginal photoplethysmography and genital DUS. The former is the most widely used vascular testing technique, and measures the vaginal pulse amplitude, reflecting phasic changes in vaginal engorgement with each heart beat, providing quantitative data on the extent of vaginal vasocongestion .
The role of DUS in managing women with SD remains to be determined. Although several investigators have reported small series using DUS before and after stimulation (i.e. visual and vibratory, even combined with topical application of 2% alprostadil) as a diagnostic tool in women with SD, a standard technique is not yet available to maximize diagnostic information [92,93].
Both everyday clinical practice and scientific reports show that WSD is age-related, progressive and highly prevalent, affecting 30–50% of women, according to different surveys. Although the reports on the anatomy, physiology and pathophysiology of women's sexual function and SD are very limited, it is interesting to speculate on the future possibilities of obtaining reliable experimental models and clinical tools for investigating normal sexual function. Similarly, pathophysiological data from clinical prospective studies are becoming increasingly necessary to find efficient and safe therapeutic options for patients complaining of WSD. Thus, further research is needed both to better define WSD from a clinical perspective and subsequently to obtain adequate therapeutic results.
Classification of SD in women, according to the International Consensus Development Conference on Female Sexual Dysfunction 
Sexual desire disorders
Hypoactive sexual desire disorder is the persistent or recurrent deficiency (or absence) of sexual fantasies/thoughts, and/or desire for, or receptivity to, sexual activity, which causes personal distress.
Sexual aversion disorder is the persistent or recurrent phobic aversion to and avoidance of sexual contact with a sexual partner, which causes personal distress.
Sexual arousal disorders
Female sexual arousal disorder is the persistent or recurrent inability to attain or maintain sufficient sexual excitement, causing personal distress. It may be expressed as a lack of subjective excitement or a lack of genital (lubrication/swelling) or other somatic responses.
Orgasmic disorder is the persistent or recurrent difficulty, delay in, or absence of attaining orgasm following sufficient sexual stimulation and arousal, which causes personal distress.
Sexual pain disorders
Dyspareunia is recurrent or persistent genital pain associated with sexual intercourse.
Vaginismus is recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with vaginal penetration, which causes personal distress.
Noncoital sexual pain disorder is recurrent or persistent genital pain induced by noncoital sexual stimulation.