chapter 30 Female Sexual Function and Dysfunction

Female Sexual Anatomy and Physiology

Physiology of Female Sexual Response Cycle

Urologists are well versed in the diagnosis and treatment of male sexual dysfunction. However, what is less commonly recognized but demonstrated in several studies is that male erectile dysfunction negatively impacts female sexual function and sexual quality of life (Fisher et al, 2005; Rosen et al, 2007). It was not until recently that urologists actually began to consider female sexual function as relevant to their practice. Based on the National Health and Social Life Survey, sexual dysfunction is actually more prevalent in women (43%) than in men (31%). Other studies suggest female sexual dysfunction (FSD) affects 25% to 76% of women in the United States. In one study, 98% women seeking routine gynecologic care had sexual concerns (Nusbaum et al, 2000).

Despite the high prevalence of sexual problems among women, physicians and patients alike are hesitant to initiate conversations about female sexual health. In a study of 471 physicians, only 22% stated they always screen for FSD whereas 55% screen most of the time and 23% never or rarely screen their patients (Pauls et al, 2005). Physicians cited various reasons for their lack of screening for FSD, the most common being lack of time. The majority of respondents (69%) underestimated the prevalence of FSD in their patient population. Fifty percent believed that their training and ability to treat FSD was unsatisfactory. Bachmann (2006) conducted a similar survey among physicians and health care providers attending the annual meetings of four specialty societies. Of the 1946 participants 42% did not inquire about FSD, citing limitations in time and training, embarrassment, and the absence of effective treatments as obstacles to discussing FSD. Sixty percent of participants rated both their knowledge and comfort level with FSD as fair or poor, whereas 86% rated treatment options as fair or poor.

Over the past 5 years the urologic literature has shown that a significant number of women with female pelvic floor disorders also report FSD. The aim of this chapter is to characterize female sexual function and dysfunctions while making urologists aware of the magnitude of FSD and providing them with information to diagnose and treat FSD in patients suffering from urologic conditions.

Female Sexual Anatomy and Physiology

Genital Anatomy

The organs of the female reproductive tract are classically divided into the external and the internal genitalia. The external genital organs include the mons pubis, clitoris, urethral meatus, labia majora, labia minora, vestibule, Bartholin glands, and Skene glands. The internal genital organs are located in the true pelvis and include the vagina, uterus, cervix, oviducts, ovaries, and surrounding supporting structures.

The vulva is a collective term for the female external genitalia. The vulva consists of the mons pubis, labia majora, labia minora, hymen, clitoris, vestibule, urethra, Skene glands, Bartholin glands, and vestibular bulbs. The boundaries of the vulva extend from the mons pubis anteriorly to the rectum posteriorly and laterally to the genitocrural folds.

The labia majora are two large, longitudinal, cutaneous folds of adipose and fibrous tissue that extend from the mons pubis to the posterior fourchette. The skin of the outer convex surface of the labia majora is pigmented and covered with hair follicles. The inner surface does not have hair follicles but has many sebaceous glands. Histologically the labia majora have both sweat and sebaceous glands. The labia majora are homologous to the scrotum in the male. The labia minora, which are homologous to the penile urethra, are two smaller folds located between the labia majora and the vaginal orifice. Anteriorly they divide at the clitoris to form the prepuce superiorly and the frenulum of the clitoris inferiorly. Histologically they are composed of dense connective tissue with erectile tissue and elastic fibers rather than adipose tissue. The skin of the labia minora is less cornified and has many sebaceous glands but no hair follicles or sweat glands (Katz et al, 2007). The labia minora surround a space called the vestibule, into which the orifices of the urethra, vagina, and Bartholin glands open.

Bartholin glands are vulvovaginal glands located on the posterolateral aspect of the vaginal orifice at the 4- and 8-o’clock positions. Bartholin ducts open into the groove between the hymen and the labia minora and are homologous to Cowper glands in the male.

Skene glands, or paraurethral glands, are tubular glands adjacent to the distal urethra. Skene ducts run parallel to the long axis of the urethra for approximately 1 cm before opening into the distal urethra (Katz et al, 2007). Skene glands are homologous to the prostate in the male.

Lying anteriorly to the urethra is the clitoris. The average length of the clitoris is 1.5 to 2 cm. The clitoris consists of the glans, the body, and two crura, which attach to the periosteum of the symphysis pubis. The glans is the visible external portion of the clitoris. The clitoral body has two cylindrical corpora cavernosa composed of thin-walled, vascular channels that function as erectile tissue. The clitoris is the female homologue of the penis in the male.

Deep to the labia, immediately below the bulbocavernous muscle, are two erectile bodies called the vestibular bulbs. Each bulb is attached to the inferior surface of the perineal membrane and covered by the bulbocavernosal muscle. During sexual arousal the bulbs become engorged, thereby narrowing the vaginal opening.

Central and Peripheral Nervous System

The innervation of the internal genitalia is primarily by the autonomic nervous system. The sympathetic portion of the autonomic nervous system originates in the thoracic and lumbar portions of the spinal cord, and sympathetic ganglia are located adjacent to the central nervous system. In contrast, the parasympathetic portion originates in cranial nerves and the middle three sacral segments of the cord and the ganglia are located near the visceral organs. As a broad generalization, sympathetic fibers in the female pelvis produce muscular contractions and vasoconstriction whereas parasympathetic fibers cause the opposite effect on muscles and vasodilation.

The pudendal nerve and its branches supply the majority of both motor and sensory fibers to the muscles and skin of the vulvar region. The pudendal nerve arises from the second, third, and fourth sacral roots. As the pudendal nerve reaches the urogenital diaphragm it divides into three branches: the inferior hemorrhoidal, the deep perineal, and the superficial perineal. The dorsal nerve of the clitoris is a terminal branch of the deep perineal nerve.

The skin of the anus, clitoris, and medial and inferior aspects of the vulva is supplied primarily by distal branches of the pudendal nerve. The vulvar region receives additional sensory fibers from three nerves. The anterior branch of the ilioinguinal nerve sends fibers to the mons pubis and the upper part of the labia majora. The genital femoral nerve supplies fibers to the labia majora, and the posterior femoral cutaneous nerve supplies fibers to the inferoposterior aspects of the vulva.

The female sexual response is mediated primarily via spinal cord reflexes that are under descending control from the brainstem. The nucleus paragigantocellaris, which projects directly to the pelvic efferent neurons and interneurons in the lumbosacral spinal cord, is believed to play a role in female orgasm (Meston, 2000; Meston and Frohlich, 2000). The pelvic efferent neurons and interneurons in the lumbosacral spinal cord contain the neurotransmitter serotonin (Walsh et al, 2002). Serotonin applied to the spinal cord inhibits spinal sexual reflexes and may explain selective serotonin reuptake inhibitor (SSRI)-induced anorgasmia (Meston, 2000). The raphe nuclei and pallidus, the magnus and parapyramidal region, and the locus ceruleus all project to the lumbosacral spinal cord and are believed to play a role in sexual function with the periaqueductal gray area acting as a relay center for sexual stimuli (Meston, 2000; Meston and Frohlich, 2000).

In males the hypothalamic medial preoptic area, which has widespread connections to the limbic system and brainstem, functions in the ability to recognize a sexual partner. In female animals, lesions to this area increase not only lordosis but also avoidance (Meston, 2000). During orgasm and arousal oxytocin is released from neurons in the paraventricular nucleus of the hypothalamus.

c-FOS staining during copulatory testing in animals has identified the medial amygdala and the red nucleus of the stria terminalis of the forebrain as playing a role in female sexual function. Stimulation of these areas results in subjective pleasurable responses in both males and females.

More recently functional magnetic resonance imaging (MRI) studies have been used to identify specific patterns of brain activation in the female sexual response. A study by Park and coworkers (2001) reported significant activation of the inferior frontal lobe, cingulate gyrus, insula, hypothalamus, caudate nucleus, globus pallidus, and inferior temporal lobe in women watching erotic films. In another study Jeong and associates (2005) compared brain activation in premenopausal and postmenopausal women watching erotic videos. Premenopausal women were found to have greater activity in whole brain and limbic, temporal, and parietal lobes whereas postmenopausal had greater activation in the superior frontal gyrus. A study by Arnow and associates (2009) compared functional MR images after erotic videos in women with and without a history of hypoactive sexual desire disorder (HSDD) and reported significantly greater activity in the entorhinal cortex in women with no history of sexual dysfunction and higher activation in the medial frontal gyrus and putamen in women with HSDD. These findings suggest that women with HSDD have a shift in attentional focus from erotic cues to a self-monitoring of sexual response and performance concerns, underscoring the neural correlates of heightened self-focus that clinically characterizes women with HSDD (Arnow et al, 2009).

Endocrine Factors

Estrogen and Progesterone

Traditionally three sex steroids have been implicated in female sexual behavior: estrogens, progestins, and androgens. In premenopausal woman, with normal ovulation, estrogen and progesterone levels are maintained until menopause. In premenopausal women the primary source of estradiol production is from the ovaries, under the control of follicle-stimulating hormone and inhibin produced by the pituitary gland, with less contributed from the adrenal gland and ovarian androgen precursors (Simpson, 2000; Davis et al, 2004; Giraldi et al, 2004). During the late follicular phase and in the luteal phase of the menstrual cycle there is a rise in estradiol. During the luteal phase there is also a rise in progesterone. Estradiol and progesterone levels fall abruptly at the time of menopause when ovulation ceases (Simpson, 2000; Davis et al, 2004; Giraldi et al, 2004).

Recent research suggests that estrogen and progesterone have little direct influence on female desire. Schreiner-Engel and coworkers (1989) found no significant difference in the estrogen levels of women with and without clinically diagnosed HSDD. Numerous studies have also shown no change in sexual desire with the administration of exogenous estrogen therapy alone in women (Furuhjelm et al, 1984; Nathorst-Boos et al, 1993a, 1993b). However, administration of both estrogen and androgen in natural and surgically menopausal woman has been shown to restore normal levels of sexual desire (Sherwin and Gelfand, 1985a). Although lack of estrogen may not directly impair female arousal and desire, it can indirectly impair sexual function by decreasing vasocongestion and lubrication and vaginal epithelial atrophy. Because estrogen plays a role in the regulation of vaginal and nitric oxide synthase expression, both naturally and surgically induced menopause result in decreased vaginal and nitric oxide synthase expression, resulting in apoptosis of the vaginal wall, smooth muscle, and epithelium. Treatment with estrogen therapy increases nitric oxide synthase expression, restores vaginal lubrication, and decreases dyspareunia, resulting in improved female sexual satisfaction.

In general, progestins do not have a direct impact on female sexual function. Although oral contraceptives that increase progesterone levels have been associated with decreased sexual desire and interest, treatment with progesterone alone has not been shown to improve sexual desire in either premenopausal or menopausal women (Persky, 1976; Schreiner-Engel et al, 1981; Leiblum et al, 1983; Sherwin and Gelfand, 1985b). Indirectly, progesterone may affect female sexual behavior by increasing depressive moods. It is believed that progesterone and estradiol compete for receptors in the central nervous system, and higher ratios of progesterone to estradiol correlate with unpleasant feelings and depressive moods (Persky et al, 1982).

Testosterone

Premenopausal women also produce 0.3 mg of testosterone daily. Unlike in men, 50% of testosterone production in women comes directly from the ovaries and the adrenal glands, with the remaining 50% produced by testosterone precursors such as androstenedione and dehydroepiandrosterone (DHEA) in peripheral tissues (Walsh et al, 2002). Only 2% of the total testosterone is free, whereas 98% is bound to albumin or sex hormone–binding globulin (SHBG). Fluctuations in SHBG alter the bioavailability of free testosterone. The administration of exogenous estrogens, such as oral contraceptives, increases hepatically synthesized SHBG, thereby reducing the bioavailability of free testosterone. Oral contraceptives also diminish follicle-stimulating hormone and luteinizing hormone levels, thereby suppressing ovulation and inhibiting androgen production. The combination of these two mechanisms may lead to very low circulating levels of free and bioavailable testosterone. Several studies have documented the negative effects of oral contraceptives on sexual function, including diminished sexual interest and arousal, suppression of female-initiated sexual activity, and decreased frequency of sexual intercourse and sexual enjoyment (Basson et al, 2004; Davis et al, 2004; Nappi et al, 2005). In premenopausal women with regular menstrual cycles, testosterone and androstenedione rise in the late follicular and luteal phases (Vierhapper et al, 1997). In premenopausal women there is also a diurnal variation in testosterone, with levels peaking in the morning (Vierhapper et al, 1997).

Unlike estrogen and progesterone levels, which fall abruptly with menopause, testosterone levels diminish gradually throughout life. Between the ages of 30 and 60, total and free testosterone levels decrease by 50% (Basson, 2008). In addition, adrenal precursors, DHEA and DHEA sulfate, decrease with increasing age (Baulieu, 1996; Baulieu et al, 2000). Decreased androgen levels associated with aging have been associated with decreased libido, arousal, orgasm, and genital sensations.

In addition to aging there are several clinical conditions in premenopausal women that are associated with low testosterone levels. Hyperprolactinemia and adrenal insufficiency can cause hypogonadotropic hypogonadism and loss of libido. Cushing disease or endogenous or exogenous glucocorticosteroid excess leads to adrenal suppression and androgen insufficiency and indirectly inhibits sexual function. Symptoms of androgen insufficiency include diminished sense of well-being or dysphoria; unexplained fatigue; decreased libido, sexual receptivity, and pleasure; and vasomotor instability or decreased vaginal lubrication despite adequate estrogen treatment. Bone loss, decreased muscle strength, and changes in memory or cognitive function are also possible as a result of diminished androgen production.

In studies of both naturally and surgically menopausal women the administration of testosterone alone, without estrogen replacement therapy, has been shown to improve desire, arousal, and sexual fantasies (Leiblum et al, 1983; McCoy and Davidson, 1985; Sherwin and Gelfand, 1985a). However, the effect of relationship between testosterone levels and desire in premenopausal women is less well defined. Several studies have failed to find differences in testosterone levels in premenopausal women with and without HSDD (Stuart et al, 1987; Schreiner-Engel et al, 1989). New data suggest that testosterone is beneficial in premenopausal women with HSDD who have low circulating testosterone levels (Schwenkhagen and Studd, 2009). Women placed on testosterone supplementation must be counseled regarding the potential risks and side effects of therapy, which include acne, hirsutism, male pattern baldness, clitoral hypertrophy, and increased triglyceride levels.

Physiology of Female Sexual Response Cycle

Although detailed writings of female anatomy date back to medieval times it was not until the 1900s that female sexuality and the physiology of the female sexual response cycle were described. Prior to 1900 female sexuality was demonized and deemed inappropriate unless procreatory or tied to pleasuring one’s husband. It was also widely believed that mental diseases in females resulted from abnormalities or excitation of the female external genitalia. It was not until 1953 when Arthur Kinsey published the controversial Sexual Behaviour in the Human Female, the first book to candidly report on female orgasm, masturbation, premarital sex, and infidelity, that the many myths surrounding female sexuality were dispelled.

Masters and Johnson were the first to study and report on sexual function and dysfunction. Published in 1966, the Human Sexual Response described the male and female sexual response cycle as four linear, successive phases: excitement, plateau, orgasm, and resolution. In females, the excitement phase begins with engorgement of the vaginal mucosa, thickening of the vaginal walls, and transudation of fluid into the vagina. There is engorgement of labia, clitoris, and vagina, with a resultant increase in vaginal and clitoral length. The breast become slightly enlarged from engorgement and the areolae become erect. Muscular tension, heart rate, and blood pressure rise slightly. In the plateau phase the labia become more engorged, the clitoris retracts, the outer one third of the vagina becomes more congested and narrow while the inner two thirds expand, and pelvic floor muscle tension builds. Orgasm is characterized by rhythmic contractions of levator ani, vagina, and uterus with massive release of muscular tension. During the resolution phase there is gradual diminishing of sexual muscular tension and detumescence of the labia, clitoris, and vagina.

In response to much criticism, Basson, in 2000, described a more contemporary nonlinear model of female sexual response, integrating emotional intimacy, sexual stimuli, and relationship satisfaction (Fig. 30–1). This model recognizes that female sexual functioning is more complex and is less linear than male sexual functioning. It also emphasizes that many women initially begin a sexual encounter from a point of sexual neutrality, with the decision to be sexual stemming from the conscious need for emotional closeness or as a result of seduction from a partner. As demonstrated by the model, arousal stems from intimacy and seduction and often precedes desire. This model emphasizes that women have many reasons for engaging in sexual activity other than spontaneous sexual drive. Sexual neutrality or being receptive to, rather than initiating sexual activity, is considered a normal variation of female sexual functioning.

Figure 30–1 Female sexual response cycle.

Classification and Epidemiology

Unlike male erectile dysfunction, female sexual disorders are more difficult to assess, diagnose, and treat. One of the initial barriers in the field of FSD was the lack of consensus of the definitions and criteria of these disorders. In 1998 the American Foundation of Urologic Disease Consensus convened to create a classification system and common terminology. It was at this conference that FSD was divided into four categories: sexual desire disorders, sexual arousal disorders, orgasmic disorders, and sexual pain disorders. In 2000 the panel reconvened and changed the classification schema to add “causing personal distress” as a criterion for diagnosis (Basson et al, 2000). This distinction is important because many studies on the prevalence of FSD have not qualified if the sexual symptoms reported caused “personal distress.” In 2004 the Second International Consensus of Sexual Medicine, consisting of over 200 multidisciplinary experts from 60 countries, convened and revised the definitions for FSD (Table 30–1).

Table 30–1 Revised Definitions for Female Sexual Dysfunction from the Second International Consensus of Sexual Medicine

Hypoactive Sexual Desire Disorder: Absent or diminished feelings of sexual interest or desire, absent sexual thoughts or fantasies, and a lack of responsive desire. Motivations for attempting to become sexually aroused are scarce or absent. The lack of interest is considered to be beyond the normal decrease experienced with increasing age and relationship duration.

Subjective Sexual Arousal Disorder: Absent or markedly diminished feelings of sexual arousal from any type of sexual stimulation. However, vaginal lubrication or other signs of physical response still occur.

Genital Sexual Arousal Disorder: Complaints of impaired genital sexual arousal, which may include minimal vulvar swelling or vaginal lubrication from any type of sexual stimulation and reduced sexual sensations from caressing genitalia. However, subjective sexual excitement still occurs with nongenital sexual stimuli.

Combined Genital and Subjective Arousal Disorder: Absent or markedly diminished feelings of sexual arousal from any type of sexual stimulation plus complaints of absent or impaired genital sexual arousal.

Persistent Sexual Arousal Disorder: Spontaneous, intrusive, and unwanted genital arousal in the absence of sexual interest and desire. Arousal is unrelieved by orgasms and the feelings of arousal persist for hours or days.

Women’s Orgasmic Disorder: Despite the self-report of high sexual arousal or excitement, there is either lack of orgasm, markedly diminished intensity of orgasmic sensations, or marked delay of orgasm from any kind of stimulation.

Dyspareunia: Persistent or recurrent pain with attempted or complete vaginal entry and/or penile-vaginal intercourse.

Vaginismus: Persistent or recurrent difficulties to allow vaginal entry of a penis, finger, or other object, despite the woman’s desire to participate.

Sexual Aversion Disorder: Extreme anxiety or disgust at the anticipation of or attempt at any sexual activity.

Estimates on the prevalence of FSD varies greatly depending on the definitions, the assessment tool used, and the demographics of the population (age, race, educational and marital status). Hayes and colleagues (2008) compared the difference in the prevalence of the types of FSD among 356 women using four different instruments and found that the prevalence varied substantially depending on the instrument used, leading to the conclusion that the instrument chosen to assess for FSD significantly affects prevalence estimates. U.S. population census data suggest that roughly 10 million American women aged 50 to 74 years self report complaints of diminished lubrication, pain during intercourse, decreased arousal, and difficulty achieving orgasm (Salonia et al, 2004).

Several studies have shown that the prevalence of FSD varies depending on age, with women older than age 45 years at an increased risk of having FSD (Shifren et al, 2008). Among women aged 40 and older, the most common reported sexual problem was low desire (38.7% to 54%), difficulty with lubrication (21.5% to 39%), and inability to orgasm (20.5% to 34%) (Shifren et al, 2008).

Female pelvic floor disorders (incontinence, lower urinary tract symptoms, and pelvic organ prolapse) have also been shown to have a negative impact on female sexual function. Women with incontinence are up to three times more likely to experience decreased arousal, infrequent orgasms, and increased dyspareunia (Handa et al, 2004; Hansen, 2004; Laumann et al, 1999; Salonia et al, 2004). Several recent large studies have found a statistically significant improvement in sexual function scores among women who underwent successful surgery for incontinence and prolapse (Brubaker et al, 2009; Handa et al, 2007).

Key Points

Physiology

• Sex steroid hormones are critical for normal female sexual structure and function.

• Androgen sex steroid hormone values decline gradually in menopausal women whereas estrogen and progesterone decrease abruptly.

• Lack of estrogen may not directly impair female arousal and desire, but it can indirectly impair sexual function by decreasing vasocongestion and lubrication and vaginal epithelial atrophy.

• Progestins do not have a direct impact on female sexual function, but they may indirectly affect female sexual behavior by increasing depressive moods. Progesterone and estradiol compete for receptors in the central nervous system, and higher ratios of progesterone to estradiol correlate with unpleasant feelings and depressive moods.

• Decreased androgen levels associated with aging have been associated with decreased libido, arousal, orgasm, and genital sensations.

• Studies have also shown no change in sexual desire with the administration of exogenous estrogen therapy alone in women.

• The administration of testosterone alone, without estrogen replacement therapy, in both naturally and surgically menopausal women has been shown to improve desire, arousal, and sexual fantasies. However, the effect of relationship between testosterone levels and desire in premenopausal women is less well defined.

• Female pelvic floor disorders (incontinence, lower urinary tract symptoms, and pelvic organ prolapse) have also been shown to have a negative impact on female sexual function. Women with incontinence are up to three times more likely to experience decreased arousal, infrequent orgasms, and increased dyspareunia.

Diagnosis

The first step in diagnosing FSD is to identify women with the problem. Plouffe (1985) and colleagues found three simple questions as effective at identifying sexual problems as a lengthy interview (Kammerer-Doak and Rogers, 2008).

1. Are you sexually active?

2. Are there any problems?

3. Do you have pain with intercourse?

Validated questionnaires are also valuable tools to help identify the presence or absence of a sexual problem. A list of questionnaires recommended by the 4th International Consultation on Incontinence for evaluation of sexual function and health in women with urinary symptoms by grade is shown in Table 30–2. For additional information regarding commonly used and validated sexual function assessment tools the reader is referred to the Baylor College of Medicine website (http://femalesexualdysfunctiononline.org/resources/) (Kingsberg and Janata, 2007).

Table 30–2 Questionnaires Recommended by the 4th International Consultation on Incontinence for Evaluation of Sexual Function and Health in Women with Urinary Symptoms

After identifying patients at risk for FSD, the diagnosis of a problem relies on a careful clinical evaluation consisting of a detailed history, which includes sexual, medical, surgical, and psychosocial history; medications (including over-the-counter medications and supplements); physical examination; and validated questionnaires. At times blood tests and specialized laboratory tests may be appropriate. Although FSD can be purely physiologic, many cases are multifactorial owing to a combination of physiologic and psychological/social factors. It is advised that women with sexual health concerns undergo a separate and concomitant psychological interview by a psychologically focused health care professional (Basson, 2000; Basson et al, 2003, 2004).

History

If a problem is elicited a detailed and more thorough sexual history is warranted and should include past and present assessment of physiologic sexual responses (desire, arousal, and orgasm) to determine the following:

• What the sexual problem is

• When it began

• How often it occurs

• If it occurs only with the current partner or also with previous partners

• If there were any precipitating events (physiologic or psychologic)

• If sex is associated with pain, whether the problem occurs both with a partner and with self-stimulation

• Whether the onset of the problem temporally coincides with starting a new medication or the diagnosis of any disease/condition

• If there are new significant life stressors

• Whether the patient’s partner has any sexual problems

• Whether either the patient or her partner has received any treatment (medications, surgery, counseling)

• If there is any history of sexual or emotional abuse

The medical history should include focused questions on the patient’s medical conditions, surgeries, and medication use. Current and medical history should focus on the following:

• Reproductive history: age of menarche and menses, use of chronic birth control, number of pregnancies, obstetric trauma, infertility, sexually transmitted diseases, sexual abuse

• Chronic medical conditions: diabetes, renal failure, congestive heart failure, hypertension, coronary artery disease, atherosclerosis, hyperlipidemia

• Neurologic conditions: multiple sclerosis, spinal cord injuries, spina bifida

• Endocrinologic illnesses: hypogonadism, thyroid disorders

• Pelvic/genital trauma: pelvic fractures, female mutilation

• Urologic history: incontinence, prolapse, interstitial cystitis, urinary tract infections, fecal incontinence, pelvic surgery

• Psychiatric history: anxiety, depression

• Medications that have been found to negatively affect sexual function (Table 30–3): hormones, prescription drugs, and over-the-counter and recreational drugs including alcohol, marijuana, cocaine, steroids, street drugs

Table 30–3 Medications with Known Sexual Side Effects

See Tables 30-4 and 30-5 for the components of a complete patient history.

Table 30–4 Components of Comprehensive Sexual History

Table 30–5 Components of Comprehensive Medical and Surgical History

Physical Examination

The goals of the physical examination in women with sexual concerns are to confirm normal anatomy, assess for abnormalities, and reproduce and/or localize pain or tenderness (if tolerable). Given the intimate nature of the physical examination it is recommended that it be conducted in the presence of a female chaperone.

Although the physical examination of a woman with sexual concerns should focus on the genital examination, the examination should also include vital signs, particularly blood pressure, peripheral pulses, and a neurologic evaluation, including a sensory assessment. For women with neurologic disorders, anal and vaginal tone, voluntary tightening of the anus, and bulbocavernosal reflexes should be evaluated.

The genital examination should begin with visual inspection. Atrophy, abnormal discharges, signs of vaginitis, vulvar skin abnormalities, Bartholin or Skene gland cysts, urethral diverticuli, and signs of former episiotomy scars should be noted. The clitoris should be exposed to inspect for adhesions.

The second portion of the physical examination is palpation. The levator ani muscles should be palpated to assess for vaginismus and levator ani myalgia. A bimanual examination should be done to assess for motion tenderness, adnexal masses, endometriosis, and fibroids. Finally, a speculum examination should be performed to evaluate for pelvic organ prolapse. Table 30–6 is a list of physical examination findings that may impair female sexual function.

Table 30–6 Physical Examination Findings That May Impair Female Sexual Function

EXAMINATION	CONDITION	SEXUAL SYMPTOMS
Inspection of Genitalia
Vaginal or labial atrophy	Low estrogen levels	Decreased arousal, dyspareunia
Sparse pubic hair	Low androgen levels	Decreased desire
Vulvar skin lesions	Lichen sclerosis, Candida, sexually transmitted infections	Dyspareunia
Vaginal discharge	Infection	Dyspareunia
Hypertonic muscle tone	Vaginismus, vestibulitis	Dyspareunia
Clitoral hood retraction	Adhesions	Anorgasmia
Vaginal wall cysts	Infected Bartholin or Skene gland	Dyspareunia
Manual Examination
Urethral fullness	Urethral diverticulum	Dyspareunia
Levator tenderness	Levator ani myalgia	Vaginismus, deep dyspareunia
Fixed retroverted uterus	Endometriosis, masses	Deep dyspareunia
Narrowed vaginal canal	Stricture/stenosis	Dyspareunia
Speculum Examination
Pelvic organ prolapse		Dyspareunia, decreased desire
Stress incontinence		Vaginitis, decreased desire

Data from from Kingsberg, 2007, and Frank, 2008.

Laboratory Testing

Vaginal pH

Vaginal pH should be measured in women with vaginal discharges, odors, or atrophic vaginitis. Normal vaginal pH in women is 3.5 to 4.5. An acidic pH rules out a bacterial vaginitis other than candidiasis. A pH of 4.5 or more is suggestive of vaginitis, vaginosis, and/or atrophic vaginitis.

Wet Mount Testing

During the speculum portion of the examination samples should be taken of any abnormal discharge for wet mount and culture. Normal vaginal secretions are odorless and are not associated with the clinical complaint of itching or irritation.

Clue cells on wet mount are suggestive of bacterial vaginosis. Women diagnosed with bacterial vaginosis should be treated with oral or vaginal administration of metronidazole (Flagyl). Partners do not require treatment. If a patient is diagnosed with bacterial vaginosis it is important to also screen for gonorrhea and chlamydia.

The observation of an increased white blood cell count on a wet mount, more than 1 white blood cell per epithelial cell, may occur under the following conditions: vaginitis secondary to Trichomonas, yeast, and/or atrophy; cervicitis secondary to gonorrhea, chlamydia, and/or herpes; and upper genital/reproductive tract disease such as endometritis and/or pelvic inflammatory disease (Haefner, 1999; Anderson et al, 2004).

Blood Testing

Currently there are no recommended routine laboratory tests for women with sexual concerns. Therefore laboratory testing should be tailored to the results of the history and physical examination.

There are 10 sex steroids, including 7 androgens and 3 estrogens. Measurement of multiple sex steroids may be of clinical relevance to gain a better understanding of the hormonal integrity in a woman with sexual health concerns. Certain clinical scenarios might suggest checking estrogen (estradiol and estrone) and androgen values (DHEA sulfate, androstenedione, total testosterone, free testosterone, SHBG, and dihydrotestosterone). For example, measuring SHBG values might be of value in a premenopausal woman on oral contraceptive therapy with sexual complaints or measuring dihydrotestosterone levels in a woman who develops acne or alopecia after treatment with testosterone.

There are multiple concerns and limitations in determining serum hormone levels in women with sexual health concerns (Södergård et al, 1982; Zumoff et al, 1995; Shifren et al, 2000; Basson et al, 2004; Davis et al, 2005; Davison et al, 2005). First, although two studies have suggested normative ranges of androgens in women, the Endocrine Society’s Clinical Guidelines on Androgen Therapy in Women state that there are insufficient data to determine normal ranges of testosterone concentration values for women of different ages (Guay et al, 2004; Davison et al, 2005; Wierman et al, 2006). Second, the accuracy, precision, and reliability of the assays used to measure testosterone levels in women are not uniformly sensitive or reliable to accurately measure the low serum concentrations typically found in women (Wierman et al, 2006). However, newer testosterone assays, using mass spectroscopy, have shown promise in measuring testosterone more accurately and precisely (Rosner et al, 2007). Free testosterone is more important than total testosterone in sexual function. Only 1% to 2% of testosterone is found in its free biologically available form, with the remainder bound to either SHBG or albumin (Shufelt and Braunstein, 2002). The gold standard for measuring free testosterone is equilibrium dialysis. DHEA is usually measured in the sulfated form because it is easier to measure and does not vary during the menstrual cycle. Several studies have shown a consistent, age-related decline in DHEA sulfate levels (Zumoff et al, 1995; Munarriz et al, 2002; Basson et al, 2004). If low levels of DHEA sulfate are found, a morning cortisol level should be drawn to rule out adrenal insufficiency.

Specialized Testing

Vascular Testing

The female sexual response cycle is a complex interplay of physiologic, hypothalamic and emotive factors that relies on an intact neurovascular system. During sexual arousal, engorgement of the clitoral, labial, and vaginal erectile tissues occurs as a result of increased blood flow through the iliohypogastric-pudendal arterial bed. Just as atherosclerosis can cause impotence in men it can also cause sexual dysfunction in women. Diminished genital blood flow to the iliohypogastric-pudendal arterial bed secondary to atherosclerosis resulting in clitoral and vaginal vascular insufficiency syndromes can lead to decreased engorgement and arousal (Goldstein and Berman, 1998). In return, diminished blood flow and atherosclerotic changes lead to clitoral fibrosis, which interferes with normal smooth muscle relaxation and dilation to sexual stimulation (Tarcan et al, 1999).

Therefore Doppler ultrasonography, vaginal and clitoral photoplethysmography, and selective pudendal arteriography have all been used to assess the integrity of the female pelvic vascular supply. However, none of these measures has been validated or standardized. In addition, no normative data for control subjects exist for comparison. Therefore the clinical relevance of diagnostic hemodynamic investigations in women with sexual dysfunction has not yet been established (Basson et al, 2004).

Indications for vascular testing include (1) women with sexual arousal disorders who have exposure to multiple vascular risk factors, (2) women who have suffered pelvic fractures, and (3) women with sexual arousal disorders unresponsive to other therapies.

Vaginal photoplethysmography, the most commonly used noninvasive vascular testing in women with FSD, measures vaginal blood flow and vaginal pulse amplitude, thereby providing quantitative data on the extent of vaginal engorgement (Pasqualotto et al, 2005). However, this test has many drawbacks, including movement artifact (not suitable for use during stimulation or orgasm), the fact that it provides arbitrary rather than absolute units of measure, and that it provides no anatomic information (Verit et al, 2006).

Duplex Doppler ultrasonography before and after stimulation—visual, vibratory, or after topical alprostadil—has been used to record vaginal, clitoral, and labial blood flow during arousal. It also can be used to obtain changes in peak systolic velocity that occur in the vaginal, clitoral, cavernosal, and labial arteries during sexual arousal as well as the changes in clitoral and labial diameter associated with sexual stimulation. Drawbacks include paucity of “control” of duplex Doppler ultrasound values in women without sexual dysfunction and lack of standardized technique (Akkus et al, 1995; Khalife et al, 2000; Bechara et al, 2003; Munarriz et al, 2003; Pasqualotto et al, 2005).

MRI is one of the newest technologies being used to assess sexual function and arousal in women. MRI provides noninvasive, unparalleled multiplanar high-resolution imaging of the female pelvic floor without ionizing radiation. It can also be used to obtain dynamic quantitative physiologic information regarding changes in tissue volume, regional blood flow changes, and regional metabolite composition. MRI can be used to define the normal anatomic relationships of the female genital structures in vivo, providing a more accurate picture and a better understanding of the functional anatomy of women compared with cadaveric studies (Deliganis et al, 2002; Maravilla et al, 2002; Suh et al, 2003, 2004). During arousal, MR images show characteristic engorgement that is most pronounced in the clitoris, especially in the crura and body of the clitoris. The vaginal mucosa does not show any increase in size and signal intensity because it is only a few cell layers thick, below the limit of resolution of the MRI technique (Suh et al, 2003).

Functional brain imaging or functional MRI represents the ability to observe anatomic sites of brain activation in response to a specific task performed by a subject using rapid dynamic MRI. This technique is an experimental tool for exploring brain function associated with emotional attraction, feelings of pleasure, and even sites of activation associated with sexual arousal. There have been a number of studies applying functional MRI techniques to the evaluation of sexual arousal or emotional response in women. Brain regions that activated with sexual arousal were related with visual association areas (posterior temporo-occipital cortices, paralimbic areas, anterior cingulate cortex) (Komisaruk and Whipple, 2005).

As discussed earlier, a study by Arnow and associates (2009), comparing functional MRI in women with HSDD with women without sexual dysfunction found greater activation in the bilateral entorhinal cortex in women without FSD but greater activation of the medial frontal gyrus, right inferior frontal gyrus, and bilateral putamen in women with HSDD, suggesting that women with HSDD shift focus from erotic cues to self-monitoring of sexual response and performance concerns.

Treatment

The treatment of FSD is complicated owing to the many causes for these disorders. Optimal female sexual health requires physical, emotional, and mental well-being, which often makes medical treatment alone insufficient. Therefore, treatment requires a multimodal approach, often involving a multidisciplinary team of urologists and a mental health specialist with expertise in sexual medicine/sex therapy. Known anatomic, metabolic, and infectious causes should be corrected first. After correcting medical causes, treatment should begin with patient education.

Women should be educated about average sexual behaviors and frequencies (Kammerer-Doak and Rogers, 2008). Often women are led to believe they have a sexual dysfunction based on misinformation about what is “normal.” Behavioral changes such as changes in sexual practices and routine (e.g., initiating a sexual encounter in the morning instead of when exhausted at the end of a long day), smoking cessation, a healthy diet, and adequate rest and exercise should be discussed. Psychological referrals should be made to those providers who specialize in sexual disorders.

Once these issues have been addressed the use of pharmacotherapy should be discussed when appropriate. It is important to inform patients that to date the only U.S. Food and Drug Administration (FDA)–approved pharmacologic treatment of any female sexual disorder is that of conjugated estrogens (Premarin Vaginal Cream) for moderate to severe dyspareunia.

Hypoactive Sexual Desire Disorder

HSDD is defined as the absence or diminution of sexual interest or desire, absence of sexual thoughts or fantasies, and a lack of responsive desire. This is the most common type of female sexual disorder, and the cause can be physiologic, psychological, or both (Laumann et al, 1999; Nicolosi et al, 2004).

Although desire disorders are the most common sexual disorder they are challenging for physicians to treat. Desire is a complex concept composed of three discrete yet interrelated components: drive, cognition, motivation (Althof et al, 1992; Kingsberg and Althof, 2009). It is imperative for physicians to determine which component or components are causative because the treatments for impaired sex drive are different from those of impaired motivation.

Drive, the biologic component of desire, is based on neuroendocrine function and manifested by spontaneous sexual interest: sexual fantasies, dreams, and thoughts. Cognition is the woman’s sexual expectations, beliefs, and values. The third component of desire is motivation or the willingness to engage in sexual activity and is commonly related to psychosocial factors.

Treatment should begin with educating the patient that it is normal for drive to decline with increasing age, which reflects decreased androgen and testosterone production.

If desire is diminished secondary to psychosocial factors the patient should be referred to a sex therapist or psychologist to discuss lifestyle changes, stress management, or couples therapy.

If the cause appears to be related to drive, exogenous testosterone therapy with tibolone (a synthetic steroid with selective estrogenic, androgenic, and progesterogenic properties) may be an appropriate option, particularly for postmenopausal women. Centrally acting agents also are being investigated for the treatment of HSDD in both premenopausal and postmenopausal women.

Androgens for the Treatment of Desire Disorders

Despite testosterone being one of the most commonly prescribed drugs for desire disorders, its use is controversial and not FDA approved in women. Although testosterone is linked to sexual desire, studies have shown that low serum testosterone levels are not predictive of low desire nor do they correlate well with the likelihood of a therapeutic response (Davis et al, 2005).

In 2005 a Cochrane review of 23 trials with 1957 participants looking at the benefits of adding testosterone to hormonal therapy in perimenopausal and postmenopausal women concluded that although there was insufficient evidence in perimenopausal women, postmenopausal women did experience improved sexual function with the addition of testosterone to hormonal therapy (Somboonporn et al, 2005).

Several subsequent randomized controlled trials in postmenopausal women and surgically castrated women have shown that the addition of testosterone to hormonal therapy improved not only desire but also arousal and orgasm (Shifren et al, 2000, 2006; Braunstein et al, 2005; Davis et al, 2005).

The data regarding testosterone therapy in premenopausal women is lacking owing to a paucity of studies, but in two studies an improvement in sexual desire in premenopausal women with low libido treated with transdermal testosterone was suggested (Goldstat et al, 2003; Davis et al, 2005).

When prescribing testosterone therapy physicians must be aware of the potential adverse side effects and contraindications. Complications include acne, hirsutism, seborrhea, menstrual irregularities, virilization, hyperlipidemia, liver dysfunction, and male pattern baldness. Transdermal preparations may minimize adverse effects. Any patient on testosterone should be seen and have laboratory studies done routinely to avoid having levels reach superphysiologic levels.

Contraindications to testosterone therapy include androgenic alopecia, hirsutism, seborrhea or acne, polycystic ovary syndrome, liver dysfunction, and estrogen depletion (Basson et al, 2004).

For the androgen precursors DHEA and DHEA sulfate there are limited data regarding their effectiveness. One small retrospective study showed DHEA (50 mg/day) to improve desire, arousal, orgasm, and sexual satisfaction in both premenopausal and postmenopausal women (Munarriz et al, 2002).

Other Medication for the Treatment of Desire Disorders

Tibolone, a synthetic steroid, has been used in Europe for more than 20 years given its positive effects on sexual function. In one randomized control study of postmenopausal women with arousal and desires disorders, tibolone in combination with hormonal therapy was shown to significantly improve sexual function scores and increase clitoral circulation.

Arousal Disorders

Sexual arousal disorders can be treated, depending on the etiology, with counseling to change sexual practice patterns, medical therapy, or a combination of the two.

Estrogen replacement therapy has shown beneficial effects in women with postmenopausal arousal disorder by improving vaginal lubrication and blood flow.

Bupropion, an aminoketone antidepressant, has been shown to improve arousal in both premenopausal and postmenopausal women and both depressed and nondepressed women with arousal disorder (Modell et al, 2000; Segraves et al, 2001, 2004).

Alprostadil, a topically applied prostaglandin applied to the external genitalia, is currently under investigation for use in women given its beneficial effects on male arousal.

Arginmax, a nutritional supplement containing L-arginine, a precursor of nitric oxide, showed an increase in sexual arousal in both premenopausal and postmenopausal women in two small randomized control studies (Ito et al, 2001, 2006).

Zestra, botanical massage oil applied to the vulva, has been shown in one randomized control trial to significantly improve arousal in women with arousal disorders (Ferguson et al, 2003).

Phentolamine and yohimbine are α-androgenic antagonists that cause vasodilatation through smooth muscle relaxation. Although phentolamine has been shown to improve arousal and lubrication for menopausal women with arousal disorder, yohimbine failed to show any clinical improvement in arousal (Raina et al, 2007).

Sildenafil, a selective phosphodiesterase-5 inhibitor used to treat erectile dysfunction in men via smooth muscle relaxation, has also been used in women with arousal disorder with mixed results. Kaplan and colleagues (1999) reported no overall improvement in 33 postmenopausal women with arousal disorder treated with 50 mg of sildenafil despite improved vaginal lubrication and clitoral sensitivity. Basson and associates (2002) also reported no improvement in 781 premenopausal and postmenopausal women with arousal disorder with sildenafil. However, several studies have shown significant improvement in sexual arousal, orgasm, and overall satisfaction in women with arousal disorders treated with sildenafil (Caruso et al, 2001; Berman et al, 2003).

The EROS clitoral therapy device, an FDA-approved device that applies gentle suction to the clitoris, enhancing clitoral engorgement, has proven beneficial in women with arousal disorders (Wilson et al, 2001).