Sexual Dysfunction in Men and Women. Stanley Zaslau

Chapter 8. Classification and Pathogenesis of Female Sexual Dysfunction

Chad P. Hubsher, MD

■ Aimee Rogers, MD

■ Stanley Zaslau, MD, MBA, FACS

 Introduction and Classification

 Sexual dysfunction in the female population is a highly prevalent, multidimensional problem that combines biological, psychological, and interpersonal determinants.

 Approximately 40% of women experience sexual complaints. The Global Study of Sexual Attitudes and Behaviors identified that 26-43% and 18-41% of females 40-80 years old worldwide experience a low sexual desire and inability to reach orgasm, respectively.

 Laumann and colleagues conducted an analysis of the National Health and Social Life Survey, a probability sample study of sexual behavior in a demographically representative cohort of the United States.1 They found that:

 Between the ages of 18 and 59, sexual dysfunction is more prevalent in women (43%) than men (31%), and married women are less likely to experience decreased sexual desire and pleasure than unmarried women.

 African American women consistently reported the highest rates of sexual problems, whereas Hispanic women have lower rates of sexual dysfunction than do white women.

 Sexual pain, however, is most likely to occur in white women.1,2

 Although this survey has limitations, including its age restriction, cross-sectional design, and failure to adjust for the effects of menopausal status or medical risk factors, it clearly indicates that sexual dysfunction affects many women.

 In contrast to male sexual dysfunction, female sexual dysfunction has only recently become widely recognized by the urological community.

 In 1998 the Sexual Function Health Council of the American Foundation of Urologic Disease organized the first international consensus development conference on female sexual dysfunction to evaluate, revise, and identify new definitions and classifications.3

 Medical risk factors, etiologies, and psychological aspects were classified into four categories of female sexual dysfunction. Each of the diagnoses described below can be further subtyped as:

 Lifelong versus acquired

 Generalized versus situational

 Etiologic origin of organic, psychogenic, mixed, or unknown

 Table 8.1 displays the classification of female sexual dysfunction. The following bullet points provide more detail on each of the disorders.

Sexual Desire Disorders

 There are two types of sexual desire disorders that contribute to female sexual dysfunction.

 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.

Table 8.1 Classification of Female Sexual Dysfunction

 It may result from emotional or psychological factors, such as lifestyle issues, including finances, careers, and family commitments, or it may be secondary to physiological problems, such as those caused by medical or surgical interventions and hormonal deficiencies. In fact, any disruption of the female hormonal environment, such as those caused by natural menopause, surgically or medically induced menopause, or endocrine disorders, may result in an inhibited sexual desire.

 Sexual aversion disorder is the persistent or recurrent inability to have, phobic aversion to, and avoidance of sexual contact with a sexual partner, which causes personal distress.

 Unlike hypoactive sexual desire disorder, it is less likely to be related to physiological issues. Instead, it is often an emotional or psychologically based problem that can result from a variety of factors, including physical or sexual abuse or childhood trauma.

Sexual Arousal Disorder

 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.

 Disorders of arousal include, but are not limited to:

 Decreased clitoral and labial engorgement

 Diminished or lack of vaginal lubrication

 Lack of relaxation of the vaginal smooth muscle

 These conditions may be caused by psychological factors, but more commonly have medical or physiological bases. Such etiologies include:

 Prior pelvic trauma or surgery that may have disrupted the neurovasculature

 Decreased blood flow to the vagina and clitoris

 Medications, especially selective serotonin reuptake inhibitors

Orgasmic Disorder

 Orgasmic disorder is the persistent or recurrent difficulty of, delay in, or absence of attaining orgasm following sufficient sexual stimulation and arousal, which causes personal distress.

 This may be a primary condition, in which the woman has never achieved orgasm, or a secondary condition as a result of hormonal deficiencies, trauma, or surgery.

 Primary anorgasmia can be due to medical and physiological factors as well as sexual abuse or emotional trauma.

Sexual Pain Disorders

 In females, there are three classifications of pain disorders that contribute to sexual dysfunction.

 Dyspareunia is recurrent or persistent genital pain associated with sexual intercourse. It can be due to physiological and/or psychological factors.

 Pain with sexual intercourse can also develop secondary to irritative conditions such as friction as a result of inadequate lubrication, or medical problems, including vaginal infection, vaginal atrophy, or vestibulitis.

 Vaginismus is the recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with vaginal penetration, and causes personal distress.

 Vaginismus generally develops as a conditioned response to painful penetration.

 It can also develop secondary to emotional or psychological factors.

 Recurrent or persistent genital pain induced by noncoital sexual stimulation is referred to as noncoital sexual pain disorder.

 Etiologies of Female Sexual Dysfunction

 The etiology of sexual dysfunction in women is often multifactorial, and may include:

 Emotional issues relating to prior physical or sexual abuse or conflicts within the relationship

 Psychological problems such as fatigue, stress, depression, or anxiety disorders

 Physical problems that may make sexual activity uncomfortable

 Additionally, some medications and various medical conditions may significantly impair sexual function.

 The following sections describe each of these etiologies in more detail.

Vasculogenic

 In men, high blood pressure, heart disease, high cholesterol levels, diabetes, and smoking are associated with vasculogenic impotence. Similar to Leriche’s syndrome in men, secondary to aortoiliac occlusive disease, clitoral and vaginal vascular insufficiency syndrome results from decreased inflow to the clitoris or vagina and is primarily due to atherosclerosis of the iliohypogastric and pudendal arterial bed.

 Park et al. further characterized this phenomenon and determined that the diminished pelvic blood flow leads to loss of corporal smooth muscle in the clitoris, with replacement by fibrous connective tissue, and atherosclerosis of clitoral cavernosal arteries.4

 In addition, any traumatic injury to the iliohypogastric pudendal arterial bed from surgical disruption, blunt trauma, pelvic fractures, or chronic perineal pressure, as may be seen from riding a bicycle for an extended period of time, can result in diminished vaginal and clitoral blood flow and result in sexual complaints.

Neurogenic

 The same neurological disorders that cause erectile dysfunction in men can also cause sexual dysfunction in women.

 Neurogenic female sexual dysfunction can result from spinal cord injury or disease of the central or peripheral nervous system, including diabetes and multiple sclerosis.

 In fact, Hutler and Lundberg determined that 62% of women with advanced multiple sclerosis have sensory dysfunction in the genital region.5

 Spinal cord injury does not always limit a woman’s ability to become pregnant, but it may compromise female sexual function in a variety of ways, including psychological and physical effects.

 Women with complete upper motor neuron injuries that affect the sacral spinal segments are unable to achieve psychogenic lubrication, while women with incomplete injuries often retain this capacity.

 In addition to affecting lubrication, the level of spinal injury may affect the ability to reach orgasm and sexual desire.

 Sexual dysfunction has also been reported in women who have epilepsy, due to the side effects of the anti-epileptic drugs lamotrigine, gabapentin, and topiramate.

Menopause and Aging

 The effect of age on female sexual function is somewhat controversial. The National Health and Social Life Survey indicated that sexual problems may decrease with age, while the Prevalence of Female Sexual Problems Associated with Distress and Determinants of Treatment Seeking (PRESIDE) study, a survey completed by over 31,000 women, randomized to be a demographically representative sample of United States women and analyzed by Shifren and colleagues, found that sexual problems tend to increase with age.6

 Regardless, it is understood that menopause is associated with physiological and psychological changes that influence sexuality.

 The primary biological change that postmenopausal women experience is a decrease in circulating estrogen levels.

 Initially, estrogen deficiency accounts for irregular menstruation and diminished vaginal lubrication, leading to vaginal dryness, atrophy, and dyspareunia.

 Further estrogen loss is associated with changes in the muscular, vascular, and urogenital systems, as well as alterations in sleep, mood, and cognitive functioning that may directly and indirectly influence sexual function.

 Furthermore, the degree of impairment of sexual function may depend on whether the woman experiences surgical or natural menopause.

 Natural menopause is associated with low estrogen, but ovarian androgen output continues to be maintained at premenopausal levels.

 The PRESIDE study demonstrated that surgical, not natural, menopause was associated with orgasm difficulties. Additionally, the decrease in arousal experienced in postmenopausal women was determined to be greater in women after surgical menopause.

 On the other hand, hormonal changes alone may not account directly for changes in sexual function, as women of advanced age often simultaneously experience physical and psychosexual changes that may contribute to lower self-esteem and diminished sexual responsiveness and desire. Additionally, a woman’s health status, medication use, changes in or dissatisfaction with her partner, and socioeconomic status may also affect sexuality.

Emotional and Psychiatric Factors

 Despite the presence or absence of organic disease, emotional and relational issues significantly affect sexual arousal in women.

 Female sexual function is greatly impacted by a woman’s:

 Relationship with her partner

 Body image

 Self-esteem

 Ability to communicate her sexual needs

 In the Women’s International Study of Health and Sexuality (WISHeS), emotional and psychological issues, as well as decrements in mental and physical health, were both independently associated with hypoactive sexual desire disorder.7

 Additionally, a history of sexual or physical abuse is a major risk factor for sexual problems, as was demonstrated by Lutfey and colleagues.8 These researchers conducted an epidemiological study of over 3000 women to conclude that the odds of female sexual dysfunction were doubled when childhood or adult abuse had occurred.

 Psychiatric disorders are also strongly associated with female sexual dysfunction.

 In the PRESIDE study, both depression and anxiety were significant correlates of distressing sexual problems.

 Also, medications used to treat depression can greatly affect the female sexual response cycle.

 The most frequently used medications for uncomplicated depression are selective serotonin reuptake inhibitors, which often cause women to complain of decreased sexual desire, decreased sexual arousal, and decreased genital sensation with an associated difficulty in achieving orgasm.

 Recently, however, Nurnberg et al. noticed that sildenafil can be successfully used to treat selective serotonin reuptake inhibitor-induced sexual dysfunction.9

 Antipsychotic medications are also associated with sexual dysfunction in both men and women.

 The mechanism of action of these medications is inhibition of dopamine, which, as a side effect, causes an increase in prolactin, resulting in gonadal suppression.

 Atypical (second generation) antipsychotic medications raise prolactin to a lesser degree than the typical antipsychotics, and thus may have less of an impact on sexual function.

Gynecologic Issues

 Table 8.2 shows some of the gynecologic disorders that contribute to female sexual dysfunction.

Table 8.2 Gynecologic Etiologies of Female Sexual Dysfunction

 The etiology of female sexual dysfunction in the postpartum period is multifactorial.

 In addition to anatomical and hormonal changes, the birth of an infant is associated with extraordinary fatigue and stress for the postpartum mother.

 Nevertheless, Handa has indicated that within three months postpartum, 80-93% of women have resumed sexual intercourse.10

 Sexual complaints, including dyspareunia and decreased desire, are common in the postpartum period and are expected to decrease with time.

■ Barett and associates demonstrated that 83% of primiparous women reported sexual difficulties at three months, and 64% at six months.11

 However, due to the continued alterations in hormones, lactation may lead to a prolonged decrease in sexual activity, desire, and satisfaction.

 Pelvic floor or bladder dysfunction is an important cause of sexual dysfunction in women. In fact, as described in the PRESIDE study, urinary incontinence is a significant correlate to distressing sexual problems.

 Salonia and colleagues determined that 26-47% of women with urinary incontinence report sexual dys- function,12 while Serati et al. stated that between 10 and 27% of women with urinary incontinence will experience leakage of urine during sexual intercourse, most often during penetration or orgasm.13

 Pelvic floor prolapse is also associated with female sexual complaints, and the rate of complaints is likely greater in those women who experience both prolapse and urinary incontinence.

 Dyspareunia, or genital pain associated with sexual intercourse, may indicate a variety of underlying problems.

 In addition to being very prevalent in women with painful bladder syndrome/interstitial cystitis, dyspa- reunia is also a cardinal symptom of endometriosis.

 Furthermore, women with uterine fibroids may experience pain with intercourse, especially if the fibroids are located on the anterior surface or fundus of the uterus.

 In addition to the above mentioned, there are many other gynecologic causes of female sexual dysfunction that contribute to physical, psychological, and sexual difficulties.

 Also, women who have undergone gynecologic surgeries, such as hysterectomies or excisions of vulvar malignancies, may experience feelings of decreased sexuality attributed to an alteration in or loss of psychological symbols of femininity.

Medications and Substance Effects on Female Sexual Dysfunction

 Although often extensively researched in men, the effects of medications on sexual dysfunction in females are not as widely studied.

 Conclusions about medications derived in the male population are frequently generalized to females.

 Often these conclusions are based on observation, as not all drug effects have been tested in randomized trials.

 Nevertheless, as described by Raina and associates, the most frequently cited agents that contribute to female sexual dysfunction include medications such as:

 Anti-androgens

 Antihypertensive agents

 Drugs that act on the central nervous system, including antidepressants, anticonvulsants, and antipsychotics

 Some recreational or illicit drugs14

Contraceptive Agents

 Contraceptive agents not only have profound effects on sexual behavior and beliefs, but may also elicit changes in sexual function.

 The two most widely used contraceptive medications are oral contraceptive pills (OCPs) and progestin-only agents.

 OCPs act by suppression of pituitary lutenizing hormone secretion, which causes a decrease in ovarian testosterone levels. Also, the estrogen component of the pill increases sex hormone-binding globulin, resulting in a further decrease in free testosterone.

 However, it remains unproven whether any effect on sexual function from OCP use is caused by the ensuing decrease in androgen activity.

• Bancroft and colleagues showed that there is no correlation between inhibited sexual desire and testosterone levels.15 These researchers treated OCP users who complained of decreased libido with exogenous androgens, and found no improvement of sexual function.

 Furthermore, the decision to use OCPs is often associated with changes in sexual desire. Freedom from fear of unwanted pregnancy may enhance desire, while internal conflict over postponed pregnancy may lead to decreased desire.

 Overall, there is little evidence that use of OCPs directly affect sexual desire or cause other sexual dysfunction.

 On the other hand, progestin-only agents may in fact have an effect on sexual function.

 As determined by Matson and associates, depot medroxyprogesterone acetate may cause decreased libido in up to 15% of women, along with weight gain, depression, vaginal atrophy, and dyspareunia.16

 Similarly, injectable progestins can lead to atrophic vaginitis and dyspareunia. However, these side effects can be easily alleviated with application of local estrogen cream.

Antihypertensive Medications

 Antihypertensives and cardiac drugs have been reported to affect sexual function by acting on the central or peripheral nervous system, the vascular system, or by having hormonal effects. These drugs include:

 Adrenergic inhibiting agents

 Diuretics

 Vasodilators

 Monoamine oxidase inhibitors

 Anti-arrhythmics

 Hypolipidemic agents

 Digitalis

 Hanon and colleagues conducted a survey of over 450 patients treated for hypertension, and found that 49% of men and 18% of women reported sexual dysfunction.17

 However, women who have hypertension commonly experience sexual dysfunction before treatment is initiated, often making it difficult to determine the true sexual side effect of the medication.

 Although sexual side effects of antihypertensive medication have been more extensively studied in men than women, adrenergic-inhibiting drugs are the most likely class of antihypertensives to elicit sexual complaints in both males and females.

 Alpha-adrenergic agents such as clonidine have been reported to diminish desire, as well as to reduce subjective and physiological arousal in women, as described by Meston and colleagues through use of a vaginal plethysmograph.18

 However, in general, there is still little known about the sexual effects of antihypertensive drugs in women.

Antidepressant Medications

 Sexual dysfunction is common in the general population, but is more common in those with depression.

 Many antidepressant medications are reported to affect sexual function, but controlling for pre-existing sexual dysfunction is difficult.

 Selective serotonin reuptake inhibitors, a commonly prescribed class of antidepressants, are reported to inhibit desire and impair orgasm in both men and women.

 In a cross-sectional patient survey of over 500 patients conducted by Williams and associates, 34% of men and approximately 33% of women were classified as experiencing antidepressant-induced sexual dysfunction.19

 Furthermore, Detke and colleagues determined that patients treated with the selective serotonin reuptake inhibitor paroxetine or serotonin-norepinephrine reuptake inhibitor duloxetine had a 62% and 46% incidence of acute treatment-emergent sexual dysfunction, respec- tively.20 However, males and females were not differentiated in this study.

 Other antidepressant medications, such as bupropion, have been reported to have fewer sexual side effects than selective serotonin reuptake inhibitors.

• In fact, Coleman et al. noted that more women treated with sertraline, a selective serotonin reuptake inhibitor, had orgasmic dysfunction than those treated with bupropion or a placebo.21

Antipsychotic Medications

 Similar to depression, sexual dysfunction is common in patients who have psychiatric disease, thus often making it difficult to distinguish the effects of the drug from the effects of the disease.

 Antipsychotics inhibit dopamine, resulting in an increase in serum prolactin, which can lead to a hypogonadal state and, in females, amenorrhea. A high serum prolactin is associated with inhibited sexual desire.

 Furthermore, atypical antipsychotic medications cause a greater increase in serum prolactin levels than typical antipsychotic agents, and are thus more likely to elicit sexual complaints in women, as well as in men.

Anti-epileptic Agents

 Sexual dysfunction is commonly reported in patients with epilepsy who are taking anti-epileptic medication such as lamotrigine, gabapentin, and topiramate.

 Of the three major anti-epileptic drugs, lamotigine is reported to cause the least change in sexual desire/ frequency of desire in women, as described by Gil-Nagel and colleagues.22

 Grant and Oh, and Sun and associates, reported that gabapentin and topiramate, respectively, could induce orgasmic dysfunction in women,23,24

Illicit and Recreational Drugs

 In addition to prescription medications, illicit drugs and substance use may cause female sexual dysfunction.

 However, randomized, controlled trials of the effects of illicit drugs on sexual behavior are difficult to perform.

 Acute alcohol intoxication has been observed to affect sexual function by decreasing libido, interfering with arousal, and impeding orgasm in women.

 Chronic alcohol abuse in women leads to a hypogonad- otropic state and resultant defeminization and loss of sexual function associated with dyspareunia and vaginal dryness.

 Similarly, Johnson, Phelps, and Cottler noted an association between marijuana use and dyspareunia and inhibited orgasm in an epidemiological study of over 3000 men and women that controlled for demographics, health, and psychiatric comorbidities.25

 The use of cocaine has been observed to cause sexual dysfunction in females via hyperprolactinism and decreased sexual desire.

• Additionally, the use of cocaine is socially associated with sexual abuse, which often results in female sexual dysfunction.

 In men and women, the use of narcotics, especially methadone, is associated with decreased frequency of sexual contact and orgasm in women, as noted by Crowley and Simpson.26

 Nicotine may also inhibit physiological sexual arousal in women, as demonstrated by Harte and Meston in a randomized, double-blind, placebo-controlled crossover trial.27

 Furthermore, in addition to endocrine changes, substance abuse is frequently associated with relationship problems, poor physical and mental health, and financial burdens and lowered socioeconomic status, all of which may predispose a female to sexual dysfunction.

 Conclusions

 Female sexual dysfunction is a highly prevalent, multidimensional problem with biological, psychological, and interpersonal determinants.

 The AFUD classification of FSD provides definitions and classifications that can assist clinicians with the diagnosis of these conditions.

 The effects of medications on FSD are not as widely studied, thus, conclusions about medication side effects on female sexual function are derived from what we know about male ED.

 Illicit drugs and substance abuse may cause FSD. This includes chronic alcohol abuse.

■ References

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