Women's Sexual Function and Dysfunction. Irwin Goldstein MD

Medical conditions associated with female sexual dysfunction

Andrea Salonia, Alberto Briganti, Patrizio Rigatti, Francesco Montorsi

Introduction

According to the National Health and Social Life Survey, approximately 43% of American women suffer from sexual disorder.1 Prevalence data on female sexual dysfunction in Europe and other parts of the world are reviewed in Chapters 2.2—2.4 of this volume. Female sexual dysfunction is frequently an unrecognized medical condition causing personal distress with a significant impact on women’s health.

Sexual dysfunction in women is a multifactorial condition with several medical, psychologic, and social components. While it is becoming more recognized that potentially all medical conditions and their treatments may have an impact on women’s quality of life and sexuality, unfortunately, well-designed, random-sample, community-based clinical and epidemiologic investigations of medical conditions associated with female sexual dysfunction are limited.

The chapter has been subdivided into four major sections evaluating female sexual dysfunction and (1) urogynecologic conditions (see Chapter 17.4); (2) endocrinologic and metabolic disorders (see Chapters 13.1-13.3); (3) psychiatric (see Chapters 16.2 and 17.3 and systemic neurologic disorders (see Chapters 16.5-16.6); and (4) cardiovascular disorders (see Chapters 5.4, 6.1, 14.1, and 14.2).

Female sexual dysfunction and urogynecologic conditions

Urinary incontinence and lower urinary tract symptoms

Urinary incontinence in women is a highly prevalent condition, both in the stress and the urge subtypes.2,3 Lower urinary tract symptoms are also commonly reported by the women popula- tion.4,5 Abnormalities of sexual function have been associated with urinary incontinence and pelvic organ prolapse.6-8 Little is known either about the prevalence of female sexual dysfunction in various subsets of patients with micturition disorders, or about the potential correlation between those female patients most frequently seen by urologists (i.e., those with urinary incontinence and/or lower urinary tract symptoms). Recently, Shaw9 reported the results of a Medline and PsychInfo review of peer-reviewed papers in English from 1980 to 2001, including all primary epidemiologic papers reporting the prevalence of urinary incontinence and its effects on sexual function in women. Although the studies concerning the impairment in sexual function were varied and methodologically heterogeneous, they reported a prevalence of female sexual dysfunction of 0.6-64%.Interestingly, in a more recent evaluation of the reliability and validity of a new quality-of-life index in both men and women with urinary incontinence, Stothers10 showed that 61% of the male patients, but only 7% of women, complaining of urinary incontinence reported a high level of impact in the sexuality domain of the index itself.

We have recently published our data regarding a cohort of 227 consecutive Caucasian women (mean age 52 years; age range 19-66 years) complaining of urinary incontinence and/or recurrent or persistent lower urinary tract symptoms.11 After a detailed clinical and urodynamic multichannel evaluation, all patients have completed the Female Sexual Function Index12 to standardize the interview regarding the patient’s sexual life. Two hundred and sixteen patients were eligible for sexual function investigation because 11 (5%) out of 227 would not answer questions regarding their own sexuality, and were thus excluded from the final evaluation results. According to the analysis of sexual history and Female Sexual Function Index scores, female sexual dysfunction was diagnosed in 99 (46%) out of the 216 patients eligible for the investigation on sexual function. Four subgroups of sexual dysfunction were identified (namely, sexual desire disorder, sexual arousal disorder, orgasmic disorder, and sexual pain disorder), in accordance with the female sexual dysfunction classification proposed by the International Consensus Development Conference on Female Sexual Dysfunction.13 Thirty-four out of 99 patients (34%) had hypoactive sexual desire disorder. Twenty-one (62%) of these were in menopause. Those patients reporting both urge incontinence and hypo- active sexual desire disorder mentioned uninterest in sexual intercourse because of a strong increase in the desire to void, with a subsequent frequent leakage of urine during such attempts. Twenty-three per cent (23 patients) had a sexual arousal disorder and complained of either subjective lack of, or reduced, vaginal sensitivity and lack of, or severely reduced, genital localized pleasure, during both noncoital sex and/or sexual intercourse, associated, at times, with reduction of vaginal lubrication. Seven (30%) of these women were in menopause, but three out of seven (47%) reported that they had poor genital arousal even prior to menopause. Eleven patients (11%) had an orgasmic phase disorder, with delayed orgasm in six patients and complete anorgasmia in the remaining five patients. Five of these women (45%) were in menopause.

Lastly, 44 patients (44%) had a history of sexual pain disorders. Thirty-seven (84%) of these women reported recurrent or persistent genital pain following sexual intercourse. We identified all these patients as having dyspareunia, in accordance with the categories described by the consensus panel on definition of female sexual dysfunction.13 Vulvar vestibulitis syndrome with sharp, burning/cutting pain highly localized in the vulvar vestibule and elicited primarily via pressure applied to the area, as defined by Bergeron et al.,14 was demonstrated in seven out of these 44 patients (16%); these women complained of both dyspareunia and noncoital sexual pain, and all of them suffered from recurrent bacterial cystitis. A total of 21 women complained of more than one sexual dysfunction. Sexual pain disorders represented the most frequent concomitant complaint, mostly in women suffering from recurrent bacterial cystitis.

The second part of this cross-sectional study was then dedicated to the direct comparison of the sexual function of the 216 patients, as described by the Female Sexual Function Index score, with the score of a group of 102 healthy, age-matched women (mean age 54; age range 19-63; p = 0.61), assessed in a yearly routine gynecologic evaluation for cancer prevention, and not complaining of urinary symptoms (i.e., urinary incontinence and/or lower urinary tract symptoms). The comparison of the median score of the Female Sexual Function Index demonstrated that patients reported significantly lower desire (p <0.01), lubrication (p = 0.01), and sexual satisfaction (p < 0.01) than controls. Moreover, these patients also showed a higher (p < 0.001) sexual pain rate than controls.

Finally, our survey11 revealed that 168 (74%) out of the overall 227 patients evaluated had never undergone an interview concerning their sexual life or sexual activity. All 99 patients suffering from sexual dysfunction felt that they needed to verbalize their sexual problems and wished to have them treated.

Urogynecologic pelvic surgery

Radical cystectomy for urologic malignancies

Genitourinary cancers are commonly associated with treatment-related sexual dysfunction, varying from mild to severe. However, limited peer-reviewed papers have been dedicated to the evaluation of women’s sexual function after major urologic surgery for bladder cancer.15-22 Sexual problems may occur as a result of any aspect of cancer disease and cancer 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. found that anterior exenteration in women can be performed accurately with a disciplined anatomic approach.18 Women undergoing cystectomy with the simultaneous removal of uterus, ovaries, and parts of the vaginal wall face had distress regarding their femininity as well as 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 vaginal reconstruction and continent urinary diversion provide better quality of life with maintenance of sexual function and urinary continence. Original data have been reported by Bjerre et al.,19 who evaluated the sexual profile after urinary diversion in 17 women who underwent radical cystectomy with the continent Kock reservoir and 20 women with the ileal-conduit diversion. Data from only 33 patients were eligible for analysis, but no significant differences between the groups were found. The authors found that coital frequency remained unchanged or increased among 44% of patients with a continent reservoir and among 18% of ileal- conduit patients, and did not show any statistically significant difference (p = 0.11). Among those reporting other than unchanged/increased activity, almost one-third indicated physical problems or decreased desire as the reason, and 30% felt less sexually attractive, 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 and Nyman20 reported that in their cohort of patients, five out of the six preoperatively sexually active women treated by cystectomy because of bladder cancer or inconti- nence/bladder dysfunction reported either a decrease or cessation of coital sexual activity postoperatively. The main problems were a decrease in sexual desire, dyspareunia, and vaginal dryness. One woman reported the inability to experience orgasm after surgery. Compared with women with bladder cancer, patients with incontinence/bladder dysfunction were more likely to have an active sexual life after urostomic surgery. Interestingly, seven women in this group, of whom four were sexually inactive before surgery, increased their sexual activity after the operation. For these women, the conduit operation removed the need to use incontinence pads or indwelling catheters.

Hautmann et al.21 presented data about nerve-sparing cystectomy with orthotopic bladder replacement in women. Their interesting paper showed detailed data concerning urinary continence and voiding dysfunction, emphasizing that urethral support and nerve-sparing cystectomy, with the ileal neobladder as a reservoir, guarantee excellent continence in all patients. However, authors have been unable to demonstrate any advantage of the nerve- and urethral-support-sparing cystectomy technique as far as micturition is concerned. More recently, Horenblas et al.22 reported their preliminary results of modified sexual function-preserving cystectomy in both men and women, called sexuality-preserving cystectomy and neobladder. Women’s sexuality-preserving cystectomy and neobladder consisted of pelvic lymph node dissection followed by cystectomy alone with preservation of all internal genitalia. An ileal neobladder was thus anastomosed to the urethra. Three women aged 38-71 years (mean age 55 years) were enrolled in this protocol, and all these patients reported normal vaginal lubrication throughout sexual activity.

Curiously, very recently, a case of clitoral priapism causing clitoromegaly has been described in association with the localization of a transitional cell carcinoma with papillary squamous component at the clitoral site.23

Hysterectomy and sexual function

Many studies have explored sexuality after hysterectomy. The overall estimation of the percentage of women reporting deterioration of their sexual life and sexual activities after hysterectomy is 13-37%15,24-32 (see Chapter 16.7).

In a very elegant study, Jensen et al.31 reported the results of a prospective study evaluating the longitudinal course of selfreported sexual function after radical hysterectomy in 173 patients with lymph node-negative, early-stage cervical carcinoma as compared with an age-matched control group from the general population. This case-control study showed that radical hysterectomy had a persistent and negative impact on patients’ sexual interest and vaginal lubrication, whereas the majority of other sexual and vaginal problems disappeared over time. Indeed, patients experienced severe orgasmic problems and uncomfortable sexual intercourse due to a reduced vaginal size during the first 6 months after radical hysterectomy, severe dys- pareunia during the first 3 months, and sexual dissatisfaction during the 5 weeks after radical hysterectomy. A persistent lack of libido and lubrication were reported throughout the first 2 years after radical hysterectomy. Long-term lack of sexual interest and insufficient vaginal lubrication were confirmed by the patient’s self-reported changes 12 months after radical hysterectomy compared with before the cancer diagnosis and by a pre/post comparison within patients. Interestingly, 91% of the patients who were sexually active before their cancer diagnosis were sexually active again 12 months after surgery, but with a decrease in sexual frequency reported.

Gimbel et al.32 compared the impact of radical hysterectomy and subtotal hysterectomy on several clinical outcome measures in more than 300 women suffering from benign uterine diseases. No clinically important differences regarding satisfaction with sexual life were found between the two hysterectomy methods. Similarly, Zobbe et al.33 prospectively compared the impact of an abdominal radical hysterectomy and a subtotal abdominal hysterectomy. These authors showed that no significant differences were observed at the 1-year follow-up in women’s sexual desire, frequency of intercourse, frequency of orgasm, quality of orgasm, localization of orgasm, satisfaction with sexual life, and dyspareunia. Moreover, none of these sexual variables changed significantly from entry to the 1-year follow-up; on the contrary, dyspareunia was significantly (p = 0.009) reduced in both groups.

Rako34,35 underlined that the ovaries are a critical source not only of estrogen but also of testosterone; thus, on removal of the uterus, even after ovary-sparing procedures, their function can be jeopardised. The lack of a physiologic level of testosterone in women after hysterectomy can also decrease quality of life in terms of sexual libido, sexual pleasure, and sense of well-being. A review analysis by Cutler et al.36 strictly correlated the hormonal deficit impact on sexuality and overall quality of life in hysterectomized women. The combination of radical hysterectomy and a surgical bilateral oophorectomy may certainly worsen the clinical and quality-of-life picture. Indeed, owing to the fact that the ovaries provide approximately half of the circulating testosterone in premenopausal subjects, many women after surgery after surgery report impaired sexual functioning despite estrogen replacement. Thus, vaginal dryness and sexual arousal difficulties are important issues in women undergoing hysterectomy. Vaginal dryness has been associated with the estrogen deficiency which characterizes premenopausal hysterectomy with bilateral oophorectomy.29,37 Nevertheless, several reports seem to demonstrate that vaginal dryness may be peculiar also after premenopausal simple hysterectomy, owing to potential ovarian damage and failure subsequent to the surgery itself.38-40

Surgical damage to the pelvic autonomic nerves during radical hysterectomy is thought to be responsible for considerable morbidity, including impaired bladder function, defecation problems, and sexual dysfunction. Therefore, surgical preservation of the pelvic autonomic nerves in both laparoscopic and traditional radical hysterectomy deserves consideration in the quest to improve both cure and quality of life in both chronic benign conditions and cervical cancer patients.22-24 Well- designed prospective studies are of paramount importance to evaluate the real impact of this kind of common surgery on overall sexual function in both premenopausal and postmenopausal women.

Conversely, in a comprehensive review article, Carlson reported that in women undergoing hysterectomy for nonmalignant conditions there is a marked improvement in symptoms and quality of life during the early years after surgery.47 Rhodes et al.,29 for instance, recently published the results of a 2-year prospective study which longitudinally examined measures of sexual function in women undergoing radical hysterectomy. These authors showed that, in a cohort of 1101 patients, both sexual desire and frequency of sexual relations significantly (p < 0.001) increased after hysterectomy and throughout the follow-up period. Similarly, orgasm frequency significantly increased after surgery (p < 0.001), and the strength of orgasm also rose dramatically after hysterectomy (p <0.001). The total amount of women reporting vaginal dryness prior to surgery also improved after hysterectomy (p < 0.001).

Endocrine alterations

Hypothyroidism and hyperthyroidism

To the best of our knowledge, there are no peer-reviewed papers evaluating sexual function and dysfunction in women complaining of either hypothyroidism or hyperthyroidism. We48 had reported a few preliminary data about sexual function of 48 dys- thyroidal women (namely, 30 hypothyroidal women: mean age 40.3 years; range 24-63 years; and 18 hyperthyroidal subjects: mean age 42.5; range 21-66 years), compared with a control group of healthy, age-matched women asking for a routine checkup at the gynecology clinic. Those preliminary results showed an overall response rate to the study of 82% for the control group and of 98% among dysthyroidal women. The Mann-Whitney U Test for direct comparison of the median demonstrated that women complaining of dysthyroidism had significantly worse scores for both the lubrication (p <0.001) and the orgasm (p <0.001) domain of the Female Sexual Function Index than the control group. Similarly, dysthyroidal women reported a significantly (p <0.001) higher genital pain during both coital and noncoital sexual activity than controls. When comorbidities were evaluated, a high rate of depression was found (37%) in dysthyroidal women, and the Spearman correlation analysis showed that the Beck Depression Inventory49 score was significantly correlated with the desire (r = -0.78; p <0.01), the arousal (r = -0.62; p = 0.003), and the satisfaction domain (r = -0.83; p < 0.001). Higher rate of depression was also correlated with greater rate of sexual distress, as shown by the Spearman correlation analysis between the Beck Depression Inventory and the Female Sexual Distress Scale 50 (r = 0.60; p = 0.02). Similarly, when the Female Sexual Distress Scale was correlated with the different Female Sexual Function Index domains, a significant correlation was found between women’s sexual distress and overall sexual satisfaction (r = -0.83; p <0.05).

Hyperprolactinemia

Hyperprolactinemia, which is considered the most common endocrine disorder of the hypothalamic-pituitary axis,51 occurs more commonly in women, with a prevalence ranging from 0.4% in an unselected normal adult population to as high as 9-17% in women with reproductive disorders. Hyperprolactinemia is associated with pronounced reductions of both sexual motivation and function. Elevated levels of prolactin inhibit gonadotropin-releasing hormone pulsatility.52 Although some experimental evidence suggests that hyperprolactinemia suppresses physiologic reproductive functions while maintaining sexual drive, other studies clearly indicate that chronic prolactin elevation also negatively affects sexual libido53 (see Chapter 6.1).

Hulter and Lundberg,54 assessing both sexual function and sexual appreciation in a comprehensive interview of 48 women with well-defined hypothalamo-pituitary disorders, showed that 38 (79.2%) of the women had developed a lack of or a considerable decrease in sexual desire. Moreover, problems with lubrication or orgasm were reported by 31 (64.6%) and 33 (68.7%) of the women, respectively. In this series, interestingly, normal menstrual pattern, young age, and intrasellar tumor growth correlated better with normal sexual desire and sexual functions than did normal prolactin levels and normal testosterone levels. In a previous study,55 the same authors investigated sexuality in 109 women (aged 20-60 years) with morphologically verified hypothalamo-pituitary disorders, finding that 62.4% of them had noticed a decrease in sexual desire, especially (p <0.001) in those who had hyperprolactinemia.

Great attention has been paid to the potential correlation between hyperprolactinemia and antidepressive, antipsychotic, and neuroleptic drugs. Several drugs are known to induce negative effects on the sexual function, including psychoactive drugs (opiates), hypotensive drugs, and antihistamines.56 Antipsychotic and neuroleptic drugs also produce a pronounced reduction in sexual drive, which appears to be at least partially the result of the marked hyperprolactinemia produced by drug administration. Indeed, typical neuroleptics are commonly associated with hyperprolactinemia, which, in turn, leads to sexual dysfunction promoting both loss of libido and anorgasmia.56-61 The mechanism of action underlying this clinical phenomenon seems to be mediated by the dopamine-blocking action of typical antipsychotic medications, which results in excessive prolactin secretion and secondary effects on gonadal function.60 Indeed, neuroleptic-induced hyperprolactinemia can cause menstrual disorders, impaired fertility, galactorrhea, and sexual dysfunction, as well as hypoestrogenism secondary to disruption of the hypothalamic-pituitary-ovarian axis.

The new antidepressant agents, such as selective serotonin reuptake inhibitors, may also induce hyperprolactinemia.62 Although, to our knowledge, no research has accurately reported the prevalence and the characteristics of this phenomenon in women, this so-called secondary hyperprolactinemia induces symptoms ranging from decreased sexual drive to orgasmic disturbances such as anorgasmia and delayed orgasm.62,63

Diabetes mellitus

The incidence of sexual dysfunction in men with diabetes mel- litus approaches 50%, and this is only slightly lower in diabetic women.64-66 Neuropathy, vascular impairment, and psychologic problems have been closely implicated in the high rate of decreased libido, slow arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia in women with diabetes mellitus.65,67-68

Different types of diabetes seem to influence women’s sexual function differently.69-71 Schiel and Muller72 reported data about the prevalence of sexual disorders in a selection-free diabetic population. These authors showed that the overall prevalence of women’s sexual dysfunctions was 18% among 127 diabetes mellitus type I patients, and 42% among 117 type II diabetes mellitus patients.

More recently, Enzlin et al.73 reported data of a case-control study of the prevalence and characteristics of sexual dysfunction in a total of 120 women with type I diabetes mellitus (mean age±SD: women without diabetic complications: 34.4 ± 8.5 years; women with diabetic complications: 39.6 ± 11.3 years), as compared with an age-matched control group of 180 healthy women attending an outpatient gynecologic clinic for routine checkup. Enzlin showed that significantly more women with diabetes (27%) than age-matched controls (15%) reported sexual dysfunction (%2 = 4.5, df = 1; p = 0.04). Diabetic women presented a higher prevalence of sexual arousal dysfunction (%2=3.8, df=1; P = 0.05) and of decreased lubrication (%2 = 6.5, df = 2; p = 0.04) than healthy women. On the contrary, despite a high prevalence of reduced libido in diabetes mellitus women both with and without diabetic complications (16.3% and 17%, respectively), the direct comparison did not show any significant differences in the decrease of desire (%2 = 3.2, df = 1; p = 0.09), orgasmic phase disorders (%2 = 0.5, df=1; p = 0.52), and sexual pain disorders (%2=2.4, df = 1 ; p = 0.15) compared with the controls. Interestingly, sexual problems were not isolated in occurrence; indeed, 11% in the studied group and 75 among controls reported two or three sexual problems (%2 = 0.16, df = 2; p= 0.92). It is interesting to note that this analysis did not show any statistically significant correlation between sexual complaints and age, body-mass index, length of disease, hemoglobin A1C values, peripheral neuropathy, autonomic neuropathy, nephropathy, and retinopathy.73,74 However, a significant association was found between the number of complications and the number of sexual complaints; thus, women suffering from more complications also reported more sexual disorders (%2 = 30.9, df= 12; p = 0.002). Moreover, while the statistical analysis did not demonstrate any significant evidence due to the menopausal status (p = 0.59) or the use of hormone replacement therapy or oral contraceptive pill (p = 0.37), diabetic women reported more depressive symptoms than controls (p = 0.01) in accordance with the Beck Depression Inventory score. According to the defined cutoff for clinically significant depression of the Beck Depression Inventory, twice as many diabetic women (24%) were depressed as were controls (11%) (%2 = 6.8, df = 1; p = 0.01). More recently, Enzlin74 concluded that sexual dysfunction in women, but not in men, was related to depression and the quality of the relationship with the partner.

Prevalence and predictors of sexual dysfunction in diabetes mellitus type II women have been reported by Erol et al.71 A direct comparison of the FSFI questionnaire showed a mean ± sd overall score of 29.3 ± 6.4 in 72 diabetic type II women versus 37.7 ±3.5 in 60 age-matched, healthy controls (p<0.05). Of the diabetic cohort, 77% reported reduced libido; diminished clitoral sensation was reported by 62.5% of the diabetes mellitus women, while 37.5% complained of vaginal dryness, 41.6% described vaginal discomfort, and 49% complained of orgasmic dysfunction.

We reported the preliminary results of a cross-sectional study aiming at evaluating prevalence and predictors of sexual dysfunction in both diabetes mellitus type I and type II women.75 Among 72 diabetic women (mean ± SE age: 42.6 ± 13.6 years), 42 (58.3%) with type I and 30 (41.7%) with type II diabetes mellitus, the Mann-Whitney U Test for direct comparison of the median demonstrated that patients had worse scores for the desire (p < 0.001), the lubrication (p <0.001), and the orgasm (p <0.001) domains of the Female Sexual Function Index than a healthy, age-matched control group. Similarly, diabetic women reported significantly higher sexual pain at the genitalia level (p <0.001) (both coital and noncoital sexual activity) than controls. Depression was as frequent as in 48% of diabetic women, as documented by the Beck Depression Inventory. The Beck Depression Inventory score was significantly (r = -0.54, p = 0.003) correlated with the arousal domain, the orgasm domain (r = -0.39, p <0.05) as well as the satisfaction domain of the Female Sexual Function Index (r = -0.48, P=0.04). Moreover, the Spearman correlation analysis was also statistically significant between Beck Depression Inventory and Female Sexual Distress Scale scores: (r = -0.47, p = 0.02). A significant correlation was also found in our series of patients between aging and reduced desire (r = -0.47, p = 0.04) and between aging and lubrication (r = -0.55, p = 0.001).

While the results of studies confirm that sexual dysfunction is highly prevalent in diabetic women, investigations aimed at better understanding the real contribution of both the psychologic and diabetes-related somatic factors in inducing and characterizing sexual disorders in these women are needed.

Chronic renal failure

Sexual dysfunction is a highly prevalent problem in both men and women with chronic renal failure, with significant impact on their overall quality of life. The genesis of sexual dysfunction is multifactorial, including physiologic, psychologic, and organic factors. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes.77,78 These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic renal failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis, but continue to worsen once both hemodialysis or continuous ambulatory peritoneal dialysis is initiated.79-81 Apparently, impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamo-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women.

In a case-control study, Toorians et al.82 attempted to determine whether the mode of treatment (namely, hemodialysis, continuous ambulatory peritoneal dialysis, or kidney transplantation), as well as biochemical and endocrine variables and neuropathy, may affect sexual functioning. They reported that transplanted patients suffered significantly less from hypoactive sexual desire disorder than the other three groups; the prevalence of other sexual dysfunctions did not differ between the groups. Moreover, genital responses during psychophysiologic assessment had no relationship to the duration of renal replacement treatment, biochemical/endocrine variables, or the presence/ absence of neuropathy. A high prevalence of loss of sexual interest, subjectively ascribed to fatigue, was also found in women on both hemodialysis and continuous ambulatory peritoneal dialysis.

During the early 1980s, some studies reported on the correlation between hyperprolactinemia and sexual disturbances among uremic women on hemodialysis.83,84 Mastrogiacomo et al. reported that the rate of sexual intercourse and the ability to reach orgasm among 99 women on maintenance hemodialysis were significantly lower than in age-matched control women.83 Eighty per cent declared a reduction in their sexual desire, and the frequency of intercourse was also lower than in the period prior to dialysis. Ageing, acting as an unmodifiable risk factor, decreased sexual activity in both the ill and healthy population, but in uremic patients sexual activity ended at an earlier age. Patients with hyperprolactinemia reported lower frequencies of intercourse as well as lower percentages of orgasm than normo- prolactinemic ones.

Neurologic and psychiatric disorders

Spinal cord injury

Peer-reviewed literature has reported that women’s desire for sexuality and sexual activities seems to decrease after injury in women with spinal cord injury.85-88 Several authors, indeed, have shown a significantly higher level of hypoactive sexual desire disorder after injury.89,90 Interestingly, a decrease in the frequency of self-masturbation in these women has been reported,91 with preferred sexual activities after spinal cord injury reported to be kissing, hugging, and touching.89

From a pathophysiologic point of view, the influence of spinal cord injury on sexual response strictly depends on the degree and location of injury in the spinal cord. In women with complete upper motor neuron injuries affecting the sacral segments, the ability for reflex, but not psychogenic, lubrication of the vagina should be maintained.92-94 On the contrary, in women with incomplete upper motor neuron injuries affecting the sacral segments, data seem to demonstrate the ability to maintain both the capacity for reflex and psychogenic lubrication.

Women with higher ability to perceive a combination of light touch and pinprick sensation in the T11-L2 dermatomes seem also to have a greater likelihood of achieving psychogenic lubri- cation.88 Historically, only 55% of spinal cord injury women were able to reach orgasm after injury.87,95 These authors demonstrated that spinal cord injury subjects were significantly less likely to achieve orgasm than controls (%2=14.3; p = 0.001). Similarly, these results showed that the possibility to achieve orgasm is less likely (17%) if women have a complete lower motor neuron injury affecting the sacral segments than if they have any other levels and degrees of injury.95

Multiple sclerosis

Sexual dysfunction has been described as high as 72% among women suffering from multiple sclerosis.96-99 Moreover, sexual activity ceases or is significantly unsatisfactory in 39% of multiple sclerosis women.96 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 typologies of sexual pain disorder.97-98,100

In a case-control study, Zorzon et al.101 found that the number of multiple sclerosis patients who reported a reduction in sexual desire was higher than in both patients suffering from a chronic disease (namely, rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, and ankylosing spondylitis) and healthy subjects. Moreover, in this series, multiple sclerosis women reported significantly (p <0.001) decreased vaginal lubrication compared with healthy controls; changes in vaginal sensation were also very common (27.1%), and more common in patients than in both chronic disease controls and healthy subjects (p < 0.01). Similar data have been previously shown by other researchers.100,102 More frequent and severe changes in sexual function seemed characteristic of women complaining of advanced multiple sclerosis (i.e., median Expanded Disability Status Scale104 score 6.5).105 Sexual dysfunction was significantly correlated with relapsing-remitting multiple sclerosis (r = -0.33, p = 0.0106), but not with both the primary-progressive (p = 0.06) and the secondary progressive type (p = 0.08). A significant correlation was found between sexual and physical disorders (r = 0.42, p = 0.0017), sphincteric and bladder dysfunction (r = 0.39, p = 0.0025 and r = 0.37, p = 0.0035, respectively), fatigue score (r = 0.30, p = 0.0284), and both cognitive deterioration (r = 0.30, p = 0.0280) and the overall neurologic impairment (r = 0.28, p = 0.0306), as assessed by the Expanded Disability Status Scale.

More recently, the same group reported that Spearman’s rank correlation analysis showed a relationship between symptoms of sexual dysfunction and patient’s age (r = 0.73, p <0.0001), cognitive performances (r = -0.63, p < 0.0001), level of independence (r = -0.63, p <0.0001), disability (r = 0.56, p <0.001), symptoms of anxiety (r = 0.55, p < 0.001) and depression (r = 0.50, p <0.005), disease duration (r = 0.42, p <0.02), and parenchymal atrophy in the pons (r = -0.38, p = 0.031), as detected by cranial and cervical spinal cord magnetic resonance imaging.106 In multiple regression analysis, sexual dysfunction was predicted only by T1 lesion load of the pons.

Nortvedt et al.107 also reported a significant reduction in the quality of life in multiple sclerosis patients with both sexual disorders and bladder dysfunction. A similar correlation was also demonstrated between sexual dysfunction and low educational level (r = 0.37, p = 0.0040) and a high value for either depression (r = 0.40, p = 0.0018) or anxiety (r = 0.40, p = 0.0017).105 Interestingly, men reported at least one sexual dysfunction 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 altogether, in a univariate analysis, changes in sexual function throughout time correlated with modifications in bladder function (r = 0.47, p < 0.0001) and Expanded Disability Status Scale score (r = 0.41, p <0.0001). After removing the effect of psychologic aspects, only changes in bladder function maintained a significant correlation with fluctuations in sexual function (r = 0.36, p = 0.003). Very recently, a new magnetic resonance imaging study found a relationship between sexual dysfunction and pontine atrophy, and confirmed the correlation of sexual dysfunction with bladder dysfunction, while also highlighting the role of psychologic factors in determining sexual dysfunction.108

Curiously, Hennessey et al.109 reported the results of a survey regarding urinary, fecal, and sexual dysfunction in 68 men and 106 multiple sclerosis women, and found that, although sexual problems occurred in 52% (55/106) of multiple sclerosis women enrolled, 65/106 (61%) were satisfied with their sexual activity. Coping strategies and levels of cognitive functioning were important predictors of sexual satisfaction, sexual dysfunction, and relationship satisfaction for women with multiple sclerosis.110,111

Interestingly, in a multiple sclerosis population, the acceptance of disability and perceived impairment increase significantly over time for both men and women. For men, however, being married was associated with a greater acceptance of disability and less perceived impairment; moreover, men were more concerned than women about how multiple sclerosis affected their sexual relationships.112

Depression and antidepressants

Chronic depression, which is more common in women than in men, represents an important public health concern in the former group113,114 (see Chapter 16.2). Major depression is certainly underrecognized and undertreated, and it is associated with significant functional impairment and high rates of comorbidity. Women may experience illness onset at an early age and experience more severe psychosocial impairment than men.113

Female sexual dysfunction associated with major depression has been described in 48-70% of patients.115-118 Indeed, changes in sexual interest/satisfaction and loss of libido are frequently and consistently related to major depression.118,119 Nevertheless, a good sex life is regarded by 70% of general population and by as many as 75% of depressed patients as a fundamental to quality of life.120 In a large cross-sectional population survey, Dunn et al.121 reported that in women the predominant association with arousal, orgasmic, and enjoyment problems was marital difficulties, but all female sexual dysfunction were associated with anxiety and depression.

Interestingly, Cyranowski et al.122 separately examined the effects of depression, selective serotonin reuptake inhibitors treatment, and sexual partner availability on women’s sexual function. Random regression models assessing changes in sexual function were conducted. Controlling for the other variables, depressive symptoms were associated with decrements in sexual desire, sexual cognition/fantasy, sexual arousal, orgasmic function, and global evaluations of sexual function. On the other hand, treatment with selective serotonin reuptake inhibitors was associated with orgasmic difficulty only. The availability of a sexual partner was associated with increased sexual arousal, orgasmic function, and sexual behaviour. Moreover, depression seems to be an independent risk factor (odds ratio 3.4; 95% confidence interval, 1.9-6.1) for decreased libido in the late reproductive years.123 Depression was also shown to increase pain during sexual intercourse.124

Antidepressant drugs and medications can exacerbate preexisting sexual dysfunction or even induce new sexual disorders.63,115,125-129 Sexual dysfunction has been reported to be associated with all classes of antidepressants (monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitor, and new- generation antidepressants) in patients with depression and various anxiety disorders.130

The negative effects of selective serotonin reuptake inhibitors on sexual function appear strongly dose-related. Men taking selective serotonin reuptake inhibitors report higher rates of sexual side effects than women taking them; however, women seem to experience more severe sexual dysfunction.126 Absent or delayed orgasm is the sexual side effect most commonly associated with selective serotonin reuptake inhibitors.128 Sexual desire and arousal disorders are also frequently reported.63 Frequently, sexual dysfunction which lasts during long-term administration of antidepressants becomes a major problem and may even result in treatment discontinuation.129,131 This places patients at increased risk of recurrence, relapse, chronicity, and death (e.g., suicide).

Very recently, Nappi et al.132 demonstrated that depression may be bimodally related to women’s sexual dysfunction. In a cross-sectional study, the frequency of self-reported sexual symptoms in women (n = 355; age range 46-60 years) attending menopausal clinics was investigated and related to other vasomotor, psychologic, physical, and genital complaints. As expected, sexual complaints were significantly more frequent with age and years since menopause. Moreover, examining the intensity of sexual symptoms according to the presence of other complaints, these authors found that physical, psychologic, and genital well-being significantly affect components of sexual response after the menopause, and that depressive symptoms are more common in women with sexual complaints.132

Lastly, depression is an important cofactor in many diseases that are potentially associated with sexual dysfunction in women. For instance, very recently, some authors underlined its role in worsening the quality of life and the sexual function in multiple sclerosis patients.108,133 Janardhan and Bakshi. demonstrated that depression and fatigue were independently associated with impaired quality of life in multiple sclerosis, after accounting for physical disability. In other words, after accounting for disability and fatigue, depression was associated with lower quality of life with respect to health perception (p = 0.02), sexual dysfunction (p = 0.03), health distress (p = 0.03), mental health (p = 0.006), overall quality of life (p = 0.006), emotional dysfunction (p = 0.04), and limitations due to emotional dysfunction (p = 0.03).133

Cardiovascular diseases

Hypertension and antihypertensive drugs

Little is available in peer-reviewed literature about sexual dysfunction in hypertensive women or in women taking antihypertensive drugs.134-140 Burchardt et al.,138 for instance, reported data on 67 women with hypertension (mean age of 60.4 years), revealing highly prevalent untreated sexual dysfunction of long duration. Of their cohort of patients, 81.3% had a sex partner; 42.6% had untreated sexual dysfunction with a duration of more than 5 years in 70.9% of them, and a duration of more than 10 years in 41.7%. Whereas 54.8% reported sexual activity as important, only 5.3% initiated sexual activity, while 36.6% reported less sexual activity than desired. Duncan et al.140 reported that women with hypertension had more difficulty than did healthy controls in achieving lubrication and orgasm. Moreover, formal Spearman correlation analysis suggested that hypertensive women might have an overall impaired physiologic sexual response.140 Hanon et al.,139 analyzing 459 hypertensive subjects (aged 59 ± 12 years) living in France and referred to hypertension specialists, reported that sexual disturbance was declared by 38% of the subjects (148/390), but the prevalence rate was significantly higher in men than women (49% vs 18%; p < 0.01). In women, the interest in sexuality was decreased in 41% of subjects but unchanged for 59%; similarly, sexual pleasure was decreased for 34% and unchanged for 66% of patients. Logistic regression analysis indicates that gender (p <0.001), greater number of antihypertensive tablets (p <0.01), prescription of diuretics (p = 0.03), and presence of coronaropathy (p = 0.01) were independent determinants for sexual disturbance in treated hypertensive patients.

A few interesting studies have also been published regarding the potential actual impact of antihypertensive treatments over women’s sexual function.

Ten premenopausal and eight postmenopausal women with mild hypertension and unimpaired sexual function were recruited by Hodge et al.134 in a crossover, active-drug controlled pilot study using self-administered daily diaries. By analysis of variance, no significant difference in the levels of sexual function of women receiving placebo, clonidine, and prazosin was found. However, of the women who received clonidine first, fewer were receptive to partner approach during medication therapy (49%) than during placebo (61%). Moreover, a smaller number of women wished for their partners to approach them (WISH) during therapy (41% and 53% for clonidine and prazosin, respectively) than during placebo (60%). In the group that received prazosin first, WISH was affected (32% for prazosin, 31% for clonidine, 45% for placebo).

The Treatment of Mild Hypertension Study,135 a doubleblind, randomized, controlled trial, provided an excellent opportunity for examination of sexual function and effects of treatment on sexual function in 557 men and 345 women with stage I diastolic hypertension and treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate), because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. Sexual function was ascertained by physician interviews at baseline and annually during followup. At baseline, 4.9% of women reported a problem with sexual function; 2.0% of women reported difficulties in having an orgasm. Interestingly, the rate of reported sexual problems in hypertensive women was similar, regardless of the type of drug suggested.

Coronary artery disease

While erectile dysfunction is a common and well-known problem in men suffering from coronary artery disease, and it may herald a systemic vasculopathic state, such as ischemic heart disease, to our knowledge, investigations of sexual function and dysfunction in women with coronary artery disease are fewer and rarely complete.

For better evaluation of chronologic, epidemiologic, and etiologic correlations between women’s sexual dysfunction and coronary artery disease, we enrolled 60 consecutive women, from February 2001, presenting with angina pectoris at the emergency unit of our institution.141 A total number of 30 (50%) out of the 60 patients presenting with angina pectoris (mean ± SE age: 56 ± 1.66 years) were ultimately enrolled in this still ongoing cross-sectional study, and underwent morphologic and functional evaluation of the coronary arteries by coronary angiography. Their Female Sexual Function Index results were thus compared with those of 102 age-matched, consecutive women assessed at a yearly routine checkup at the gynecology clinic. The overall prevalence of sexual dysfunction among these coronary artery disease women was 30% (9/30). Seventy- seven per cent (7/9) of the coronary artery disease women complained of female sexual arousal disorder, while a low lubrication score was reported by eight (88.9%) out of these nine women. The direct comparison of the Female Sexual Function Index scores showed that the total index value was significantly higher (p = 0.02) for controls than for women suffering from coronary artery disease. Patients also reported a significantly higher amount of sexual arousal (p = 0.002) as well as lubrication (p = 0.10) disorders. Moreover, patients also had significantly lower (p = 0.01) scores on the orgasmic phase domain of the Female Sexual Function Index. The Beck Depression Inventory demonstrated that 33% (10/30) suffered from mild depression, while severe depression affected three (10%) out of the patients. Beck’s Depression Inventory score was significantly correlated with the Female Sexual Function Index desire domain (p = 0.008, r = -0.48) as well as with the arousal domain (p = 0.0005, r= -0.64), the lubrication domain (p = 0.0008, r = -0.63), the orgasm domain (p = 0.0004, r = -0.66), and the overall sexual satisfaction domain (p = 0.0007, r = -0.63). Interestingly, female sexual dysfunction became evident prior to symptoms of ischemic heart disease in seven (23%) out of the 30 patients. Therefore, seven (78%) out of nine patients in this series developed the sexual disorders before (median of 51 months; range: 12-96 months) angina or myocardial infarction. Although these findings need to be confirmed in a larger patient population, this preliminary report suggested that sexual dysfunction is an important health issue in women with coronary artery disease.

Conclusions

There are several scientific observations that female sexual dysfunctions are age-related, progressive, highly prevalent, and strongly associated with medical conditions exactly like erectile dysfunction in the male population. However, little is known about the impact on women’s sexual life of many of the more common medical diseases. Thus, data from clinical prospective studies are needed to clarify the pathophysiologies of female sexual dysfunction.

A new outlook should be available to the doctor attending an everyday clinical practice, in order to avoid comments such as the following in the future: “I am a 62-year-old woman who had a heart attack last year. Overall, my medical care has been excellent, and my doctors answer most of my questions even before I ask them. The one exception is any question about sexual activity. I want to know if it is dangerous and whether the medications I’m taking will affect my sex drive. Why won’t my doctors address these issues?”142

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