Female sexual dysfunction (FSD) is a common health problem that may affect up to 43% of women.¹ Over past decades the definition of FSD has evolved. The World Health Organization’s International Classification of Diseases (ICD-10, 1980) emphasized physical factors that influence the sexual response, in contrast with the focus on psychological ones by the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM). More recently, the American Foundation for Urologic Disease (AFUD) defined FSD as disorders of libido, arousal, orgasm, and sexual pain that lead to personal distress or interpersonal difficulties.²

While the DSM-V due in 2012 is expected to make further adjustments to the current classification system, the most recent revision of the definition was generated at the Third International Consultation on Sexual Medicine (ICSM), published in 2010,³ and is a modification of the AFUD classification system. The ICSM definitions were formulated by an international panel of 21 experts in the field of female sexual medicine (Tables 18-1 and 18-2).^3,4

Although the ICSM classification system does not comment on personal distress or interpersonal difficulties, these are mandated in the definition by the DSM-IV-TR and AFUD. For example, if a woman has low sexual desire, but is not bothered by it, then it is not considered dysfunctional, and does not require treatment.

Normal sexual function in women is made possible by an interaction between mental and physical well-being; the etiology of FSD lies in physiological or psychological roots or both.

Epidemiology

A large prevalence study of 1,749 women aged 18 to 59 published in JAMA in 1999 demonstrated sexual dysfunction to be more prevalent in women (43%) than in men (31%). Younger age, poor educational status (less than high school education), and physical and emotional health were important risk factors for FSD. Race had a variable influence with black women having the highest rates of hypoactive desire and Hispanic women having the lowest rates of FSD. Moreover, sexual dysfunction was highly associated with negative experiences in sexual relationships and overall well-being.¹ However, this study was limited by excluding women over the age of 59. Later, Lindau et al. conducted a prevalence study on the sexual problems of women aged 57 to 85 years old.⁵ They reported the most prevalent sexual problem for women in this age group was low desire (43%), followed by difficulty with vaginal lubrication (34%), inability to climax (34%), and pain during intercourse (17%). Of note, women who rated their health as poor were less likely to be sexually active. While these reports were instrumental in our understanding of the prevalence of sexual complaints, they did not assess for sexual distress.

The PRESIDE study, published in 2008, reported that the age-specific point prevalence of any sexual problem was 43% in women aged 18 and older, similar to the earlier reports. However, only 12% of women reported that sexual problems were associated with personal distress.⁶ Distress was more common in women aged 45 to 64 years old than in younger or older women. Risk factors for distressing sexual problems included poor self-assessed health, low education level, depression, anxiety, thyroid conditions, and urinary incontinence. The prevalence of FSD included desire problems (39%), arousal disorder (26%), and orgasmic dysfunction (21%). Sexual pain disorders were not reported.

Sexual Response Cycle

In the 1950s, Drs William Masters and Virginia Johnson were pioneers in the study of the female sexual response. They described a linearly progressive model moving through four phases: excitement (arousal), plateau, orgasm, and resolution (Figure 18-1).⁷ Dr Helen Singer Kaplan modified the Masters and Johnson model by starting with desire, and then excitement (arousal) and finally orgasm. The plateau and resolution phases were felt to be clinically relevant in men, but less relevant in women and thus were eliminated. Except for the pain component, the Kaplan model addresses the other three pertinent disorders of FSD: desire, arousal, and orgasm. Most recently, Dr Rosemary Basson described a circular model for female sexual response, with intimacy being the emotional motivator for sexual encounters (Figure 18-2).⁸

Recent research has suggested that no one model may be appropriate for all women. In a study of 133 nurses, equal proportions of women endorsed the Masters and Johnson, Kaplan, and Basson models emphasizing the heterogeneity of women’s sexual response.⁹ Particularly noteworthy in this study, the Basson model was chosen most frequently by women with sexual problems as demonstrated by lower Female Sexual Function Index (FSFI) domain scores in that group. This suggests that the nature of the sexual response in women may be dictated by individualized sexual function.

Anatomy

Female sexual anatomy is composed of the genital organs: vagina and vulva, as well as higher processing levels in the brain. Intact sexual function occurs via an interaction between physical and emotional factors. A woman’s perception of her anatomy or body image may also play a role in her sexuality.

The vulva is composed of the labia majora, labia minora, vestibule, and clitoris. The labia majora are the external “lips” of the vulva and are homologous to the scrotum of the male. Normal labial size varies widely, particularly with respect to the labia minora. Labia majora range from 7 to 12 cm (average 9 cm) in length, whereas labia minora are 2 to 10 cm (average 6 cm) in length and 0.7 to 5 cm (average 2 cm) in width (Figure 18-3).¹⁰ The labia minora may be very long or asymmetric, which could result in physical symptoms. The vestibule is the involution of the urogenital membrane, at the terminal end of the urogenital sinus (Figure 18-4). Congenital neuronal hyperplasia in the primitive urogenital endoderm may be due to increased density of C-afferent nociceptors in the vestibular mucosa, resulting in vestibulodynia.¹¹ This condition may also develop in other women over time, with potential triggers including vulvovaginal infections, such as candidiasis or desquammative inflammatory vaginitis or hormonal alterations including oral contraceptive pills, menopause, oophorectomy, or infertility treatments.¹¹

The vagina is a fibromuscular tube with a squamous, nonkeratinizing epithelium. While average vaginal length is 9.6 cm, there is considerable variation in both length and caliber of the vagina. During genital arousal, the proximal vagina distends and the vessels of the vaginal subepithelium become engorged, allowing a transudative fluid to diffuse across the vaginal epithelium. Hormonal influences, particularly estrogens, are felt to be critical to the blood supply and engorgement of the vagina. Often, postmenopausal women experience vaginal dryness due to loss of estrogen. Other conditions may cause alterations in the length and caliber of the vagina, which could interfere with sexual satisfaction. Certain pelvic reconstructive surgeries may result in a shortened vaginal length, or narrowed vaginal introitus, and could lead to dyspareunia. Vaginal delivery may be associated with laxity of the vaginal muscles or tissues and lead to less sensation with sexual intercourse. Indeed, while the vagina may be regarded as a female sexual organ, studies have confirmed that nerves occur regularly throughout the proximal, distal, anterior, and posterior vagina and cervix without any area of increased nerve density¹² or “g-spot,” which is in sharp contrast to the nearby clitoris that consists mostly of dense nerve tissue.

Strategically placed within the vulva and distal vagina lies the clitoris, which is the predominant sexual end organ of the female. The clitoral complex is a term referring to the distal vagina, urethra, and clitoris¹³ and this complex is the embryonic homologue to the male penis (Figure 18-5),^14,15 although it differs from the male version most notably in its size. On closer examination, the clitoris is in essence a smaller, more compact version of its male counterpart with the major difference that the sole function of the clitoris is to provide sexual pleasure. Clitoral anatomy has been well described using MRI and cadaver studies (Figures 18-6 and 18-7).^13,16 The only visual external component of the clitoris is the glans with its accompanying hood or “prepuce.” Due to its external nature, it is considered a part of the vulva. The nonvisual portions of the clitoris lie deep to the vulva and include the erectile tissues of the paired body (corpora), crura, and bulbs that connect at the root. The clitoral root is of great importance to female sexuality and is highly responsive to direct stimulation. The majority of the neurovascular supply to the vulva, distal vagina, and clitoris is supplied by the pudendal nerve and artery.

Some consider the brain to be the ultimate sexual organ; thus, several recent studies have used functional MRI (fMRI) to illustrate the brain regions associated with love including passionate, companionate, maternal, and unconditional love types. For this review, we will focus on passionate love, although all forms of love have a common subcortical dopaminergic reward-related brain system involving dopamine and oxytocin receptors.¹⁷ Passionate love specifically recruits the ventral tegmental area, which is the central platform for pleasurable feelings and pair-bonding, rich in dopamine, oxytocin, and vasopressin receptors and caudate nucleus associated with representation of goals, reward detection, expectation, and the preparation for action.¹⁷ Thus, passionate love is a complex emotion that is reward-based and goal-directed, usually toward a specific partner.

Other research has utilized fMRI to illustrate regions of the brain associated with sexual desire. In a recent fMRI study comparing women with hypoactive sexual desire disorder (HSDD) with normal females, there was a greater activation of the frontal gyri (Brodmann areas 10 and 47) suggesting that women with HSDD allocated significantly more attention to monitoring and/or evaluating their sexual responses/performance compared with the normal participants who had the majority of the activation in the midbrain regions (Figure 18-8).¹⁸ Mindfulness is an eastern practice with roots in Buddhist meditation that focuses on present moment and nonjudgmental awareness. Mindfulness or “being in the moment” may be decreased or lacking in women with FSD where the frontal cortex is activated when it should be quiescent. In other words, normal sexual response requires deactivation of the higher thought processes and executive function of the frontal lobe and activation of the instinctual limbic system of the midbrain. Our current understanding of the female sexual response in relation to brain activation patterns suggests differences between women with and without sexual dysfunction in encoding arousing stimuli and/or retrieval of past erotic experiences.¹⁸

Endocrinology/Physiology

Hormones and neurotransmitters modulate sexual function and, in general, dopamine, estrogen, progesterone, and testosterone play an excitatory role in sexual desire, while serotonin, opioids, and prolactin play an inhibitory role.¹⁹ It is hypothesized that FSD may be due to a reduced level of excitatory activity, an increased level of inhibition, or both. Receptors for hormones are expressed in both the brain and genital tissues suggesting a central (desire) as well as peripheral (arousal) component. During genital arousal, many neurotransmitters are involved in the sexual response. The most important neurotransmitters are nitric oxide (NO) and vasoactive intestinal peptide (VIP), and both are enhanced by estrogen.²⁰

The major androgens in women, listed in descending order of serum concentration, are dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione, testosterone, and dihydrotestosterone (DHT). DHEA and androstenedione are produced by the ovaries and adrenals, whereas DHEAS is mostly produced by the adrenal glands. DHEAS, DHEA, and androstenedione are pro-androgens and require conversion to testosterone to exert androgenic effects. Testosterone appears to be the primary sex steroid influencing desire, while progesterone may mediate receptivity to partner approach. The production rate of testosterone in the normal female is 0.2 to 0.3 mg per day with 25% secreted by the ovary, 25% secreted by the adrenal, and 50% from peripheral conversion.²¹ Circulating levels are in the range 0.2 to 0.7 ng/mL (0.6–2.5 nmol/L)²² (Figure 18-9).²³

Normative ranges of androgen levels in women have not been established due to poor sensitivity and reliability of assays. Symptoms of androgen insufficiency may include diminished well-being, fatigue, diminished desire, reduced sexual receptivity, and diminished sexual pleasure.²⁴ These symptoms may resemble depression and environmental stressors, making diagnosis difficult. Although an androgen insufficiency syndrome (AIS) in women was initially proposed in 2001, it remains controversial and ill-defined. Etiologies for AIS include:

1. 
   

   Ovarian (chemotherapy, radiation therapy, oophorectomy)

   
   
2. 
   

   Adrenal (adrenal insufficiency, adrenalectomy)

   
   
3. 
   

   Hypothalamic-pituitary (hypopituitarism)

   
   
4. 
   

   Drug related (corticosteroids, antiandrogenic agents, oral contraceptives, oral estrogen replacement therapies)

   
   
5. 
   

   Idiopathic²⁴

Testosterone levels gradually begin to decline in the third decade in females. By menopause the levels may be half of their peak, leading to greater likelihood of symptoms at this time.²⁵ However, it is important to note that the ovarian stroma continues to secrete androgens throughout a woman’s lifetime. Androgens are converted into estrone, the dominant form of estrogen in menopause, by aromatase in the peripheral tissues. Premenopausal and postmenopausal women undergoing oophorectomy will have androgen and estrogen deficiencies, with an abrupt decrease in testosterone levels by approximately 50%.²⁶

Estrogen deficiency results in a myriad of symptoms including mood changes, memory loss, sleep disturbances, decreased libido, decreased intensity of arousal/orgasm, decreased vaginal lubrication, and decreased sense of well-being. Estrogens have vasodilatory and vasoprotective effects that increase vaginal, clitoral, and urethral arterial flow.²⁷ Estradiol is produced at the rate of 100 to 300 mg per day²¹ prior to menopause and then falls precipitously causing reduced overall blood flow to the hormonally responsive urogenital system and resultant vulvovaginal atrophy. Estradiol levels less than 50 pg/mL are associated with vaginal dryness, increased frequency and intensity of dyspareunia, pain with penetration, and burning.²⁸ Vaginal dryness with associated dyspareunia is the most common sexual problem related to low estrogen in menopausal women.

As stated previously, dopamine is the key neurotransmitter that modulates sexual desire. Increasing levels of serotonin (eg, reuptake inhibition, as with the selective serotonin reuptake inhibitors [SSRIs]) can diminish dopaminergic effects on sexual function. Additionally, endogenous opioids may reduce pleasure-seeking and thus orgasmic experience, resulting in an inhibitory effect on sexual desire (Figure 18-10).¹⁹

Pain Disorders

Although sexual pain is considered a domain of FSD, it also may be part of the physiology of further sexual dysfunction. A potential cascade of responses stem from an initial pain experience including anticipation of subsequent pain, pelvic floor hypertonicity/levator myalgia/vaginismus that may lead to worsening pain, low desire, sexual avoidance, poor arousal and/or orgasmic capacity, and development of subsequent untoward relationship effects. This may lead to a downward spiral of repetitive pain that in its most severe form may lead to apareunia. The location of the pain, with either entry or deep penetration, provides information of the etiology. Entry pain is associated with vestibulodynia, vaginal dryness or atrophy, levator hypertonicity, or vaginal stenosis while deep pain may be secondary to endometriosis, pelvic inflammatory disease, painful bladder syndrome/interstitial cystitis, levator hypertonicity, and other causes.

With the widespread use of synthetic polypropylene mesh for the treatment of stress urinary incontinence and/or pelvic organ prolapse, mesh exposures and mesh contractures may occur and have been associated with dyspareunia. A recent multicenter randomized controlled trial evaluating vaginal mesh for the treatment of pelvic organ prolapse reported a 15.6% mesh erosion (or exposure) rate within three months of placement, although some mesh exposures were asymptomatic.²⁹ Others have suggested that scar tissue incorporation of the synthetic materials may lead to a 50% or greater contraction of the implanted size, with subsequent dyspareunia and tension on the lateral pelvic attachments.³⁰

Mental Health

Relationship problems (marital discord, lack of intimacy, etc) and potential stressors (financial, job, health) contribute to FSD. Concurrent Axis I psychiatric diagnoses should be delineated during the workup of FSD including depression, anxiety, and anorexia. Often, a history of a sexual trauma may be elucidated, as 17.6% of US women report a history of prior sexual assault.³¹ Women with the highest risk of sexual violence (82%) are female veterans with a history of posttraumatic stress disorder.³² Recently, normal variations in personality, such as introversion, emotional instability, and not being open to new experiences, have been identified as risk factors for FSD, specifically orgasmic dysfunction.³³

Female sexual function is a complex entity composed of physiological, psychological, cultural, and environmental factors. Any alterations may lead to increased or decreased sexual satisfaction. Despite the common nature of sexual complaints, dealing with these problems in the office setting may be challenging. Provider comfort, bias, and degree of training can impact patients being screened for this information.³⁴ In addition, patients are often unlikely to volunteer intimate and sensitive information without being asked.

Providers can start the conversation by commenting on the frequency of sexual problems in the population. Questions should be open ended and nondirective. Appropriate pauses and time for the patient to elaborate are important.³⁵ Later in the interview, direct questions may elucidate more detailed information about the complaint. Another technique is to use a standardized intake form and questionnaires to identify patients with concerns related to FSD. Following identification of a problem, a comprehensive evaluation should be performed.

The evaluation for FSD should include a medical, sexual, and psychosocial history, physical examination, and laboratory testing. If necessary, the patient may need to schedule a second appointment, as the process can be time consuming.

Medical History

The medical history should include medical, surgical, obstetrical, and gynecological information. Cardiovascular disease has been linked to female arousal disorders, due to concurrent atherosclerosis of the vessels supplying the vagina and clitoris. This phenomenon has been documented in studies of men showing erectile dysfunction to be a precursor of coronary artery disease.³⁶ Neurologic disease such as multiple sclerosis, spinal cord injury, or diabetes can affect sexual function by impairing both arousal and orgasm.³⁷ Additionally, general medical health is directly correlated with sexual health.

Previous surgery should be ascertained. In many cases, sexual function improves or is unchanged after pelvic surgery. Many studies have documented positive impact of hysterectomy on sexual function, with no significant differences based on removal or preservation of the cervix.^38,39 However, certain patients have reported diminished sensation, impaired lubrication, and vaginal changes following such procedures. Additionally, removal of the ovaries may lead to FSD secondary to estrogen and/or androgen depletion. Other surgical repairs such as Burch bladder suspension with posterior colporrhaphy may be associated with increased rates of dyspareunia postoperatively.⁴⁰ Postoperative vaginal stenosis, while rare, can result from levatorplasty at the time of posterior colporrhaphy and/or aggressive trimming of the vaginal mucosa at the time of colporrhaphy, leading to dyspareunia or apareunia.⁴¹ With the widespread use of synthetic mesh for the treatment of stress incontinence and/or pelvic organ prolapse, mesh exposures and contractures may be a potential cause of postoperative pain.