Berek Novak's Gyn 2019. Chapter 17 Sexuality and Sexual Dysfunction

CHAPTER 17

Sexuality and Sexual Dysfunction

KEY POINTS

1 Sexual problems are common, especially painful sex. Dyspareunia may affect twothirds of women during their lifetime. Genito-pelvic penetration pain disorder

includes the former term “vaginismus”—an involuntary reflex precipitated by real or

imagined attempts at vaginal entry and other types of chronic dyspareunia including

the most common type— vestibulodynia, which has a prevalence of 15%.

2 Sexual response reflects the fundamental interplay between the mind and body:

psychological, interpersonal, cultural, environmental, and biologic (hormonal,

vascular, muscular, neurologic) factors interact and modulate sexual experience.

3 Factors that can affect sexual response include mood, relationship duration and

quality, age and stage in life, past sexual experiences—desired, coercive, or abusive

— personal psychological factors stemming from relationships in childhood with

parental figures, previous losses and traumas, and ways of coping with emotions,

current and past illness, fertility concerns, and use of medication, alcohol, and illicit

drugs.

4 Sexual dysfunction can arise from gynecologic diseases such as endometriosis;

procedures such as those associated with infertility; and treatments including pelvic

radiation, urinary incontinence surgeries, and medications, for example, aromatase

inhibitors or gonadotropin-releasing hormone (GnRH) antagonists. Sexual abuse can

have long-lasting effects on sexuality and women seen in gynecology clinics may

have comorbid illnesses that interrupt their sexual function.

5 Physical, psychological, and economic stressors of pregnancy may negatively affect

emotional and sexual intimacy. Sexual value systems, folklore, religious beliefs,

physical changes, and medical restrictions influence sexual attitudes and behavior

during pregnancy and postpartum.

6 Many of the sexual problems couples encounter result from a deficit of knowledge or

experience, sexual misconceptions, or inability of the couple to communicate about

969their sexual preferences.

7 Despite the importance of issues relating to sexuality, many women find it difficult to

initiate discussions with their physicians about sexual concerns, and many

physicians are uncomfortable discussing sexual issues with their patients. Asking

about sexual concerns gives physicians an opportunity to educate patients about the

risk of sexually transmitted infections (STIs), encourage safer sex practices, evaluate

the need for contraception, dispel sexual misconceptions, and identify potential

sexual dysfunction. Many men and women have a number of serial sexual partners

but use condoms inconsistently, thereby exposing themselves to STIs and

unintended pregnancies.

8 Recent research confirms that 43% of 1,202 American women, including those in

poor health, rated sexual health as an important component of quality of life—

recording 4 or 5 on a 5-point Likert scale (1). There is need to provide patients with

information about normal sexual changes that occur with puberty, pregnancy and

postpartum, menopause, and older age as well as in association with gynecologic

conditions.

SEXUALITY

The spectrum of normal sexual response varies from one woman to another

throughout a woman’s lifetime. Physicians need to be sensitive to their

patients’ sexual values, attitudes about specific practices, and concerns about

their sexuality. Maintaining open communication with patients about their

sexuality confirms the physician’s willingness to address problems when they

arise.

Sexual Activity, Sexual Orientation, and Sexual Attraction

In keeping with recent large surveys, a continuous rather than categorical

distribution of sexual orientation is described. Requesting women (and men) to

choose between heterosexual, mostly heterosexual, bisexual, mostly gay/lesbian

or gay/lesbian, showed that 71% of the total 803 women indicated heterosexual

and 6% gay/lesbian while 20% checked “mostly heterosexual” (2). The latter

group had more same-sex attraction and, although less frequent than the

occurrence of same-sex attraction, more same-sex partners than strictly

heterosexual women. This information is important to physicians, to avoid

assumptions that sexual attraction and activity necessarily conform to a limited

choice of hetero, bi, or gay label leading to potential misunderstanding risks of

STI’s pregnancy, and sexual dysfunction.

The average age for first intercourse for both men and women in the

United States is 17 years and for at least 20% this is without contraception

970(3). By age 19, 50% of women have had intercourse but while some 86%

report using contraception on their last occasion of intercourse, only 1 in 5

women use dual protection (4). Many men and women have serial sexual

partners and even older adults use condoms inconsistently, thereby exposing

themselves to sexually transmitted infections (STIs) and unintended

pregnancies. A recent large British survey found that 22.8% of women reported

one or more sexual difficulties including problematic orgasm, low sexual interest,

and arousal or painful sex. Applying the new criteria to designate a sexual

disorder as listed in the American Psychiatric Association’s Diagnostic and

Statistical Manual, fifth version (DSM-5) (5), 3.6% of the total met all three

criteria (6). These criteria include symptom persistence for >6 months, symptom

presence in >75% of occasions, and associated distress. The study excluded

nonsexually active women some of whom may have stopped activity as a result of

sexual dysfunction.

Genital Anatomy

For most women, their clitoral tissue is the most sexually sensitive part of

their anatomy, and its stimulation produces the most intense sexual feelings

and the most intense orgasms. Many women first need to experience both

nonphysical and nongenital physical stimulation before clitoral stimulation

can be enjoyed. In the absence of arousal, direct clitoral stimulation can be

unpleasant and be perceived as so intense as to be painful. Immunohistologic

studies identified neurotransmitters thought to be associated with sensation

concentrated right under the epithelium of the glans clitoris. Clitoral tissue

extends far beyond the visible portion when the clitoral hood is retracted. It

includes the clitoral head, shaft, rami running along the pubic arch, periurethral

tissue in front of the anterior vaginal wall, and the bulbar tissue under the

superficial perineal muscles surrounding the anterior distal vagina—such that

sexual sensations and arousal arise from massaging these areas, not just the

clitoral shaft and head. Other sexually sensitive areas include the nipples, breasts,

labia, much of the skin generally, and to some extent, the vagina. Although the

lower third of the vagina is responsive to touch, the upper two-thirds are sensitive

primarily to pressure. The rich supply of nerves in the fascia anterior to the upper

vagina (Halban’s fascia) and the proximity of the clitoral type of spongy tissue

around the urethra anterior to the vagina contribute to the pleasurable sensations

of intercourse. Many women experience orgasm more easily from direct clitoral

touch, possibly provided at the same time as intercourse.

There is speculation about the existence of a “G-spot,” an area of the vagina,

located anteriorly midway between the symphysis pubis and cervix, which can be

exquisitely sensitive to deep pressure. Stimulation of this area can be associated

971with orgasm and loss of fluid which can be dilute urine or fluid from Skene’s

glands (7). Women who are normally continent might leak urine at orgasm;

urodynamic studies have demonstrated that orgasm may provoke uninhibited

detrusor overactivity and sometimes sphincter relaxation. Usually medical

intervention is not needed.

Sexual Response Cycle

[2] Sexual response reflects the fundamental interplay between the mind and

body: psychological, interpersonal, cultural, environmental, and biologic

(hormonal, vascular, muscular, neurologic) factors interact and modulate

sexual experience. At the outset of sexual engagement, especially in new

relationships, women may sense heightened sexual desire. However, in long-term

relationships, women (and men), may be motivated by factors other than, or

additional to, sexual desire (8). Women initiate or consent to sex for many

reasons, including a wish to increase emotional intimacy with their partners

(9,10). By directing her attention to sexual sensations from stimulation (physical,

visual, fantasy, auditory), a woman’s subjective sexual

arousal/pleasure/excitement develops and triggers sexual desire. Desire and

arousal coexist and compound each other (Fig. 17-1). Sexual satisfaction (with

one, many, or no orgasms) can be achieved if she can retain focus, continue to

enjoy sensations of arousal, if the duration of stimulation is sufficiently long, and

there is no negative outcome (e.g., pain or partner dysfunction). The response is

circular, with phases overlapping and in variable order (e.g., desire may follow

arousal, and higher arousal may follow the first orgasm). Desire, once triggered,

increases the motivation to respond to sexual stimuli and to agree to or request

more intensely erotic forms of stimulation. Any initial spontaneous desire will

augment the response. This circular type of sequence can be experienced multiple

times on any one occasion of sexual interaction. This motivation/incentives

module reflecting the importance of the mind’s appraisal of sexual stimuli is

supported by empirical research (10–12).

Physiology

Desire and Arousability

Sexual desire provides one of many motivations to be sexual. Feelings of

desire and arousal may be triggered by internal (e.g., fantasies, memories,

feelings of arousal) and external (e.g., an interested and interesting partner,

visual or written erotica) stimuli. Sexual cues are dependent on adequate

neuroendocrine function. Multiple neurotransmitters, peptides, and hormones

972modulate desire and subjective arousal (13). Substances that promote sexual

response include norepinephrine, dopamine, oxytocin, melatonin, and serotonin

acting on some receptors. Prolactin, serotonin acting on other receptors,

endocannabinoids, opioids, and γ-aminobutyric acid inhibit sexual response.

These peptides and neurotransmitters are themselves modulated by sex hormones

that direct the synthesis of enzymes involved in the production of

neurotransmitters and the synthesis of their receptors. Biologic factors do not act

independently from environmental factors, a finding in human and animal

models. Dopamine and progesterone, acting on receptors in the hypothalamus,

facilitate sexual behavior in female rats following oophorectomy and received

estrogen. The presence of a male animal in an adjacent cage caused an identical

change in sexual behavior (14). Likewise, ability to be aroused and intensity of

response can be increased in some women by giving them a modest dose of

testosterone, by administering bupropion (dopaminergic), or by a change of

partner (8,15,16). Even in rodents, complex networks exist whereby the female

assesses the context of potential sexual activity and relates it to past experience

and expectation of reward (17). In women, sexual interest is influenced by their

mood, psychological mindset, beliefs and values, expectations, sexual orientation,

preferences, and the presence of a safe and erotic environmental setting. Even in

the absence of a clinical depression, negative affect is found to negatively modify

sexual function while the sexual experiences modulate affect the next day (18,19).

Moreover, other research concludes that cognitive factors (i.e., lack of erotic

thoughts and being distracted or concerned about sexual behavior) were the best

predictors of difficulty in triggering sexual desire: other dimensions including

relationship factors, psychopathology, and medical problems appeared to have an

indirect impact on sexual desire with the cognitive factors acting as the mediators

(20). Sexual desire, interest, and arousability are most strongly influenced by

mental health and feelings for the partner, both generally and specifically, at the

time of sexual interaction (21–23). Sexual desire is strongly influenced by fatigue;

as a result, sex late at night is not usually attractive to busy individuals. Similarly,

chronic illness typically reduces desire and arousability (24).

973FIGURE 17-1 The blended sex response cycle showing the many reasons/incentives for

initiating/accepting sexual activity.

Sexual Arousal

Recent brain imaging reflects the complexity of sexual arousal, confirming

that multiple networks in the brain are involved in sexual response. Brain

imaging of healthy people during visual sexual stimulation identifies a model of

sexual arousal involving complex brain circuitry, including cortical, limbic, and

paralimbic areas known to be involved in cognition, motivation, and emotions

linked to changes within the autonomic nervous system (25). Specific inhibitory

regions deactivate these sexual responses (26). In a small study, sexually

functional surgically menopausal women, receiving no hormonal therapy, viewed

erotic videos during functional magnetic resonance imaging. The women failed to

show the brain activation typical of premenopausal women and also typical of

themselves when they were treated with both testosterone and estrogen, and yet,

they reported sexual arousal from the erotic videos with, and without, hormonal

supplementation (27). Recent work on brain activation during subliminal and

supraliminal sexual stimuli shows an interesting difference between male and

female subjects. Exposure to supraliminal sexual images was associated with

activation in arousal-related areas and in inhibitory regions in both men and

974women. Exposure to subliminal sexual images was associated mainly with

activation in the arousal-related areas, and in women there was increased

activation in some inhibitory regions, but that did not appear in men. This

suggests that when women appraise stimuli as sexual, there will be both arousal

and control responses—even when the sexual cues are subliminal. The authors

note that the various outcomes associated with sex including pregnancy and

abuse, pose a relatively bigger potential threat to women than to men (28).

Accompanying the subjective excitement and erotic feelings of arousal are

a number of physical changes. These changes include genital swelling;

increased vaginal lubrication; engorgement of the breasts and nipple

erection; increases in skin sensitivity to sexual stimulation; changes in heart

rate, blood pressure, muscle tone, breathing, body temperature; mottling of

the skin; and a “sex flush” of vasodilatation over the chest, breasts, and face.

With sexual stimulation, brain function in the hypothalamus and other areas

influencing the genital response is activated, triggering the autonomic nervous

system to allow increased blood flow to the vagina. Vasodilatation of the

arterioles in the submucosal vaginal plexus increases transudation of interstitial

fluid, which moves from capillaries between the epithelial intercellular spaces and

into the vaginal lumen. Simultaneously, the autonomic nervous system allows

relaxation of the smooth muscle cells surrounding blood spaces (sinusoids) in the

extensive clitoral tissue and labia, causing clitoral swelling and vasodilatation in

the labia. Immunohistologic studies indicate nerves containing nitric oxide are

present in the genital skin covering the clitoris and labia.

With arousal, the vagina lengthens, distends, and dilates, and the uterus

elevates out of the pelvis. With increased sexual stimulation, vasocongestion

reaches a maximum intensity. Genitally, the labia become more swollen and

darker red and the lower third of the vagina swells and thickens to form an

“orgasmic platform.” The clitoris becomes more swollen and elevates to a

position near the symphysis pubis, and the uterus elevates fully out of the pelvis.

The breasts become more engorged, the skin more mottled, and the nipples more

erect.

The neurobiology of arousal is incompletely understood but the genital

vasocongestive responses appear to be highly automated, occurring within

seconds of an erotic stimulus (12). Pelvic autonomic nerves release nitric oxide

and vasoactive intestinal polypeptide (VIP), mediating vasodilatation.

Acetylcholine (ACh) blocks noradrenergic vasoconstrictive mechanisms and

promotes nitric oxide release from endothelium. Some pelvic autonomic nerves

primarily release (vasoconstrictive) noradrenaline and adenosine triphosphate, but

others release ACh, nitric oxide, and VIP. Recent work suggests all pelvic

autonomic nerves are sympathetic (29). Nitric oxide is thought to be the major

975neurotransmitter involved in vulvar engorgement. In the vagina, VIP, nitric oxide,

and other unidentified neurotransmitters are involved.

Even in women without any sexual dysfunction, there is highly variable

correlation between the degree of subjective sexual excitement and the

increase in congestion around the vagina (12). This poor correlation was shown

repeatedly over the past 39 years based on psychophysiologic studies using the

vaginal photoplethysmograph. Congestion in response to a sexual video is

reduced in women with disruption of the autonomic nerves supplying the vulva

and vagina (e.g., from nonnerve-sparing radical hysterectomy). Otherwise healthy

women complaining of absent sexual arousal show increases in vaginal

congestion from erotic stimuli that are similar those in control women (12).

Laboratory-demonstrated reflexes may be involved in the physiology of

arousal. A cervicomotor reflex can be elicited from cervical touch with a balloontipped catheter to replicate penile pressure, causing a reduction in pressure in the

upper portion of the vagina and an increase in pressure in the middle and lower

portions. Simultaneously, an increase in electromyographic activity in the levator

ani and puborectalis muscles was recorded. It is thought that during intercourse

penile thrusting on the cervix might cause contraction of the pelvic muscles to

facilitate “ballooning” of the upper vagina, perhaps to facilitate pooling of semen.

The same muscle contraction constricts the lower vagina, which may afford

increased stimulation of the partner’s penis, thereby maintaining rigidity (30). A

further reflex demonstrated in laboratory studies shows reduced uterine tone in

response to mechanical or electrical stimulation of the glans of the clitoris.

Background activity of the uterine muscle was abolished by clitoral stimulation,

but not if either the glans clitoris or the uterus was anesthetized. Uterine pressure

decreased with clitoral stimulation. This reflex may underlie the known increase

in size and the elevation of the uterus with sexual arousal (30).

Orgasm

Orgasm is a brain event, typically triggered by genital stimulation, but can

occur during sleep or from stimulation of other body parts including the

breast and nipple or by fantasy, occasionally by medication, and in spinal

cord injured women by vibrostimulation of the cervix. In able-bodied

women, it involves a myotonic response of smooth and striated muscle

associated with feelings of sudden release of the sexual tension built up

during arousal. It is described as the most intensely pleasurable of the sexual

sensations. Reflex rhythmic contractions (3 to 20, 0.8/s) of the muscles

surrounding the vagina and anus occur. Some women may subjectively perceive

uterine contractions during orgasm and some may report a difference in their

perception of orgasm after hysterectomy, but this is not objectively documented.

976An objective quantitative measure was established that shows strong

correspondence with the subjective experience of orgasm. Rectal pressure while

volunteers imitated orgasm, tried to achieve orgasm and failed, or experienced

orgasm was significantly different during orgasm as opposed to both control tasks

(31).

Brain imaging studies of women during orgasm showed brain activations and

deactivations similar but not identical to those found in men (32). There is

profound deactivation in the anterior part of the orbitofrontal cortex (OFC). This

area is thought to be involved in urge suppression and behavioral release. The

medial OFC is part of the neuronal network underlying self-monitoring and is

connected to the amygdala. The latter is deactivated during the genital stimulation

and arousal and remains deactivated during orgasm. Deactivation of this network

is associated with a more carefree state of mind. The subjective description of

orgasm is very much in keeping with this depiction (33).

The majority of women experience orgasm more easily from direct clitoral

stimulation. More direct contact with the clitoris is possible from contact of

pubis to pubis after the man has ejaculated but the movements of intercourse

resume while penile size is somewhat reduced but some firmness maintained. The

bodies are more closely approximated and the woman can move her pelvis on his

at a rate that is most conducive to her orgasm. Breast stimulation, kissing, and

clitoral stimulation during intercourse are other commons means of experiencing

orgasm. Women are potentially multiorgasmic, capable of experiencing a

number of orgasms close together during one sex response cycle. Some may

resume sexual activity, possibly with more orgasms. Women do not typically

have a refractory period. However, many mid-aged and older women may

experience more rewarding sex when sexual activity is separated by a

number of days. Following the interval there is more interest in being sexual,

a more reliable and pleasurable response, and greater likelihood of more

intense arousal and orgasm.

Resolution

Following the sudden release of sexual tension brought about by orgasm,

most women experience a feeling of relaxation and well-being (some may feel

energized). The gradual lessening of pelvic engorgement contrasts with the

quicker loss of penile firmness in men. Nongenital changes that took place during

arousal are reversed, and the body can return to a resting state after some 5 to 10

minutes. Women who enjoy arousal without orgasm and without any sense that

orgasm is very close but frustratingly absent, report a similar sense of well-being

and relaxation.

977FACTORS AFFECTING SEXUAL RESPONSE

[3] Numerous factors can affect sexual response (34,35): These factors

include mood; age; relationship duration and quality; personal psychological

factors stemming from relationships in childhood with parental figures;

previous losses, traumas, and ways of coping with emotions; illness; fertility

concerns; and use of medication, alcohol, and illicit drugs.

Mental Health

Studies find that mental health has the strongest links to women’s sexual

function (21,23,36–38). Depression independently determines the presence of

sexual dysfunction in women with a number of chronic illnesses including

multiple sclerosis (39), diabetes (40), renal failure (41), rheumatic disease (42).

Lack of mental well-being, even if it does not meet the criteria of a clinical

diagnosis of mental disorder, is strongly linked to women’s symptoms of low

desire (43). Epidemiologic studies confirm depression’s negative effects upon

orgasmic experience (44) and its strong association with increased sexual risk

behaviors (45). Self-stimulation/masturbation may continue in the presence of

depression (46). Many of the factors involved in partnered sex, including the

relationship itself, the need to communicate sexual needs, the need to take care of

the partner, concern about outcome, and dealing with feelings of inadequacy, do

not apply to sex alone. Self-stimulation can cause calmness, relaxation, and

improved sleep in women, but is often not a consequence of sexual urge or desire.

Aging

Aging is accompanied by the changes in ovarian function associated with

menopause, and the marked reduction of adrenal production of

prohormones (importantly dehydroepiandrosterone [DHEA]) that can

become estrogen and testosterone and have as yet poorly understood actions

on nonandrogen nuclear and membrane receptors. Previous population

studies were conflicting: some showed little increase in sexual problems with age,

whereas in others almost 40% of the sample reported reductions in responsiveness

but an increased desire for nongenital sexual expression. Recent British research

involving 6,777 women found some steady decrease in sexual function with age

up to the 55 to 65 age group followed by some improvement in function during

the following decade (37). Studying 3,205 women in the Boston area, researchers

found a strong association between age and sexual problems (21). Another

smaller study found that women’s desire decreased significantly as a function of

menopause status and age, low levels of desire were strongly associated with

other sexual problems, including difficulties with arousal and orgasm (47).

978Many studies of sexuality and aging show that older women report less

distress about lack of desire when compared with younger women (37,48). Of

6,777 women in the UK, 13.4% of those aged 16 to 24 reported distress about

sexual problems compared to 6.7% of women aged 65 to 74 (37).

Despite reports of reduced sexual interest and desire by some older

women, most retain some interest and maintain the potential for sexual

pleasure their entire lives. In older women, a strong predictor of continued

sexual interest is sexual behavior and enjoyment at an earlier age. A

discrepancy between sexual interest and actual sexual activity occurs in many

cases because an adequate partner is no longer available. In other instances, the

cessation of sexual activity with age is more an expression of emotional problems

resulting from lack of tenderness, communication, and attraction.

In addition to partner availability, an older woman’s sexuality is

influenced by her partner’s general and sexual health and the relationship

itself, which will determine how well the couple can adapt to changes in their

sexual function as they age. Although some older women may retain negative

societal attitudes toward sex that it is not “natural” (i.e., not focused intercourse),

studies show a shift from intercourse to nonpenetrative sex and to a variety of

activities that involve affection, romance, affectionate physical intimacy, and

companionship (49). For some older women, it is clear that the setting, whether a

nursing home or a grown-up child’s home, strongly influences the opportunity

and desirability for sexual expression.

Sex Hormones

Estrogen

If intercourse is perceived as a necessary component of sexual activity with a

partner, some older women will lose motivation and interest as a result of

discomfort and dyspareunia associated with lack of estrogen. Baseline vaginal

blood flow is lower in estrogen-deficient women compromising needed

lubrication. A male partner may be using a phosphodiesterase inhibitor to enhance

erection. Penile girth may then be often maximal while vaginal size is reduced.

Postmenopausal provoked vestibulodynia (PVD) is now recognized to be

sometimes comorbid with genitourinary syndrome of menopause (GSM) (50)

(AKA vulvovaginal atrophy). The latter is associated with loss of elasticity and

thinning of the vaginal epithelium, which becomes vulnerable to damage from

intercourse. Estrogen depletion predisposes women to vulvar vaginitis and urinary

tract infections, both of which contribute to dyspareunia and reduced sexual selfimage. Women who remain sexually active, alone or with a partner, may have

less vulvar and vaginal atrophy than sexually inactive women but may still be

979symptomatic (51).

Testosterone

Adrenal production of testosterone precursors gradually decreases with age,

beginning in the late 30s. Large epidemiologic studies have not shown serum

levels of testosterone to correlate with women’s sexual function (52,53).

Previously available assays were not sufficiently sensitive in the female range of

serum testosterone to detect particularly low levels. When mass spectroscopy was

used, the serum testosterone levels in 121 women who were carefully assessed

and diagnosed with disorders of low desire and arousability were similar to the

levels in 125 women similarly carefully assessed but who lacked any sexual

dysfunction (54). Sexual dysfunction was not associated with mass spectroscopy

measures of serum testosterone in a recent study investigating hormonal and

psychosocial factors associated with desire (23). Another difficulty, besides past

unreliable assays for serum testosterone, was the fact that intracellular production

of testosterone in peripheral tissues (from adrenal and ovarian) precursor

hormones—DHEA, DHEA sulfate (DHEAS), and androstenedione (A4)—

previously could not be measured. Total testosterone activity (ovarian and

peripherally produced “intracrine” production) has been measured using mass

spectrometry assays for androgen metabolites, most notably androsterone

glucuronide (ADT-G). There appears to be a wide range of ADT-G among

women of any given age, and levels decrease with age. Importantly there were

no group differences in ADT-G between 121 women carefully diagnosed with

desire and arousal disorders and 124 sexually healthy controls (52) nor in a

second similar study with less stringent exclusion criteria (55), nor in a cross

sectional study of 428 premenopausal women were androgen metabolites

associated with sexual dysfunction (23).

11β-Hydroxyandrostenedione

An important recent finding is that neither accurately measured serum

testosterone, nor testosterone metabolites as reflected by serum ADT-G,

distinguish women with sexual dysfunction is of importance. However, it is

possible that neither of these two values, nor “bio-available testosterone,” that is,

free testosterone plus that which is loosely bound to albumin is an adequate

measure of androgen activity. The C19 adrenal steroid 11β-

hydroxyandrostenedione, previously considered a by-product of adrenal steroid

metabolism is now confirmed to serve as a precursor to the androgenic steroid 11-

ketotestosterone. This molecule in turn is converted to 11-ketodihydrotestosterone

(11KDHT) which acts on androgen receptors in a similar way to

dihydrotestosterone (DHT) (56). Thus significant androgen action results from the

980peripheral synthesis of both DHT and 11KDHT which have minimal release into

the circulation.

Dehydroepiandrosterone

The recent research of 246 women strictly recruited for presence or absence of

desire disorder, found similar serum testosterone and serum androgen metabolites

in the two groups, but found that serum DHEA was significantly higher in the

controls. This is in keeping with previous large epidemiologic studies (52,53).

Thus DHEA appears to be acting in nonandrogenic ways. Research now turns to

DHEA’s many known but as yet not fully understood actions on nonandrogenic

nuclear and membrane receptors (57).

Age-Associated Health Conditions

Illnesses that accompany aging may have an impact on sexual dysfunction. The

association is weaker than that between male erectile dysfunction and

hypertension, hyperlipidemia, diabetes, and coronary artery disease. Depression

is the major factor influencing sexual function in women with chronic illness,

including end-stage renal disease (41), multiple sclerosis (39), or diabetes

(40). Some sexual activities (e.g., intercourse) or responses (e.g., orgasmic

intensity) may be limited by arthritic, cardiac, or respiratory disorders.

Personality Factors

Studies show that, compared with functional women, those who have

concerns about low levels of desire and arousability are characterized as

having vulnerable self-esteem, high levels of anxiety and guilt, negative body

image, introversion, and somatization (58). Higher levels of anxiety can be

particularly disruptive to healthy sexual response (59). Because sexual arousal

involves increased sympathetic nervous system activity, in addition to increasing

women’s genital congestion there are nongenital sensations which may be

misinterpreted as threatening and negate any potential sexual pleasure. These

symptoms of “anxious arousal” include shortness of breath, increased

temperature, muscle tension, and palpitations. The clinical impression of women

with orgasmic disorder is that many are extremely uncomfortable in conditions in

which they are not in control of circumstances or their bodily reactions, and

research confirms strong links between orgasmic disorder and obsessivecompulsive traits and somatization (44). For many women with vaginismus,

there is a phobic quality to the fear of vaginal penetration. Many women

with PVD show a marked fear of negative evaluation by others, ultraconscientiousness, and self-criticism, as well as an increase in somatization

981and anxiety (60).

Relationships

Most women who report loss of desire and arousability to physicians indicate

that their partnerships are stable and satisfactory. However, an environment

free of conflict, abuse, and the threat of separation or divorce is insufficient to

nurture a woman’s sexual desire. Commonly, the woman reports that her partner

is not emotionally intimate with her, unwilling to reveal his (or her) feelings,

fears, and hopes. In addition, the woman’s need for eroticism and variety of

sexual stimulation may not be met. These women frequently classify their

relationship as being that of “very good friends.” Such a context is insufficiently

sexual for nurturing or triggering a woman’s sexual desire. Change of partner is

shown to be a major factor in increasing women’s desire and responsiveness, and

there is a lessening of innate desire with the duration of a relationship (23,61).

Not being happy in her relationship was a major determinant of sexual function in

a recent large British survey (37). The woman’s feelings for her partner, or a

change of partner, were major determinants of a woman’s sexual response in an

11-year longitudinal Australian study (61).

Sexual Dysfunction in the Partner

Of the multiple aspects of a woman’s circumstances that can influence her

sexual function, sexual dysfunction in a male partner is an important one.

Successful treatment of a male partner’s erectile dysfunction can result in

reversal of the woman’s sexual problems, including difficulties with sexual

arousal, lubrication, orgasm satisfaction, and pain (62).

Infertility

Infertility evaluation and assisted reproductive techniques can have negative

effects on a woman’s body image and feelings of sexual self-worth. Infertility

may cause her to feel hopeless and sexually undesirable. The loss of sexual

spontaneity resulting from the goal-oriented approach to sex while trying to

conceive with scheduled intercourse (coinciding with ovulation naturally or after

hormonal stimulation) may lead to sexual dysfunction and is considered a major

problem for many women (63). Erectile dysfunction may be a consequence,

compounding the couple’s fertility difficulties and the woman’s sexual

satisfaction. The stress of testing and waiting for results may disrupt emotional

intimacy, causing further damage to sexual function. These changes do not

always reverse with a successful pregnancy. Often there are unresolved feelings

of guilt over personal responsibility for the infertility and feelings of resentment

982of the multiple procedures required for women compared with one semen analysis

for men.

Drugs

1. Prescription and nonprescription medications, including alcohol and

illicit drugs, can alter the normal sexual response (Table 17-1).

Adjustments in dosage or formulation of medication may be required.

2. Two recently approved antidepressants appear to be sexually neutral.

Vortioxetine has a range of effects on the serotonin system: an antagonist at 5-

HT3, 5-HT7, and 5-HT1D receptors; an agonist at 5-HT1A receptors; a partial

agonist at 5-HT1B receptors; and an inhibitor of the 5-HT transporter (64).

Vilazodone is a serotonin reuptake inhibitor and 5-HT1A receptor partial

agonist (65).

3. Theoretically, pharmacologic agents might improve or reverse the loss of

arousal, desire, and orgasm commonly associated with serotonergic

antidepressants (SSRIs) and less frequently serotonergic noradrenergic

antidepressants (SNRIs). A number of “antidotes” have been suggested but

only three have evidence in the form of randomized controlled trials using

approved medications: adding bupropion can reverse SSRI-induced

dysfunction (66), as can the addition of aripiprazole (67). Recently

vortioxetine has been shown to improve AISD from SSRIs in patients in

remission from depression, to a greater degree than did escitalopram (68).

Table 17-1 Medications Potentially Affecting Sexual Response

• Antihypertensives: β-blockers, thiazides

• Antidepressants: serotonergic antidepressants

• Lithium

• Antipsychotics

• Antihistamines

• Narcotics

• Benzodiazepines

983• Oral contraceptives and oral estrogen therapy

• Gonadotropin-releasing hormone (GnRH) agonists

• Spironolactone

• Cocaine

• Alcohol

• Anticonvulsants

Chronic Illness and Cancer

Chronic illness and living with a cancer diagnosis can affect sexual function in a

number of ways (Table 17-2) (20).

Table 17-2 Sex and Chronic Illness

• Biologic disruption of the sexual response, e.g., multiple sclerosis damaging pelvic

autonomic nerves

• Negative psychological consequences of the illness affecting sexual response, e.g.,

feeling sexually unattractive as a result of disfigurement from surgery, medication,

stomas

• Increased fatigue

• Chronic pain

• Incontinence or stomas reducing sexual self-confidence

• Accompanying depressive illness

• Treatment of chronic illness, e.g., chemotherapy-inducing ovarian failure

• Limited mobility, e.g., arthritis precluding intercourse, Parkinson disease precluding

masturbation

• Cardiac or respiratory compromise such that orgasm or movements of intercourse

cause angina or intense dyspnea

984Chronic Pelvic Inflammatory Disease and Endometriosis

Chronic dyspareunia, remitting temporarily or not at all with surgical or

medical therapy, typically is associated with loss of sexual motivation or

interest. Although definitive therapy is the overall goal, encouragement of

nonpenetrative sex is very important for preservation of the woman’s sexual

enjoyment, sexual self-esteem, and relationship. GnRH therapy producing a

temporary medical menopause can add further difficulties with reduced

arousability and vaginal discomfort from the low estrogen state.

Polycystic Ovarian Syndrome

There is no evidence that the higher androgen levels associated with

polycystic ovarian syndrome (PCOS) afford protection from low sexual

desire or low sexual arousability. Some but not all studies of women with PCOS

report reduced sexual satisfaction compared to controls. The limited data suggest

that lower satisfaction is related to obesity and cosmetic androgen–related effects

of hirsutism and acne. Metformin may improve sexual function in women with

PCOS (69).

Recurrent Herpes

Fear of spreading an STI may reduce sexual motivation and arousability.

Guidance regarding safer sexual practices is needed, along with a discussion of

the causes of the woman’s lowered sexual motivation. A recognized difficulty

with recurrent herpes is asymptomatic viral shedding possibly despite long-term

antiviral therapy.

Lichen Sclerosis

Tethering of the clitoral hood may cause pain with clitoral stimulation.

Introital involvement may cause dyspareunia or prevent entry of penis, dildo, or

fingers. Reduced sexual sensitivity of the involved vulvar skin is a common

complaint. Topical corticosteroid administration is the primary treatment,

although topical testosterone cream may benefit loss of sexual sensitivity.

Breast Cancer

Sexual dysfunction following breast cancer treatment is likely to persist more

than 1 year after diagnosis of breast cancer (70). Chemotherapy appears to be

responsible for most of the resulting sexual difficulties, including loss of desire,

subjective arousal, vaginal dryness, and dyspareunia. A small study of women

with past breast cancer and complex endocrine status resulting from ongoing

antiestrogen therapy found that, whereas relationship factors predicted desire, a

history of chemotherapy predicted disorders of arousal lubrication, orgasm, and

985dyspareunia. There was no connection between sexual function and androgen

levels, including androgen metabolites (71). A model for predicting sexual

interest, function, and satisfaction after breast cancer has evolved from two large

independent groups of breast cancer survivors (70). The most important

predictors of sexual health were absence of vaginal dryness, presence of

emotional well-being, positive body image, better quality of relationship, and lack

of partner sexual problems.

Dyspareunia is present in at least 45% of women with breast cancer (72).

Mechanisms of pain include (1) changes from chemotherapy-induced estrogen

deficiency; (2) chemotherapy-induced peripheral neuropathy which can affect the

relatively lengthy pudendal nerve; (3) central sensitization underlying PVD

possibly induced by the estrogen lack and all the stress of the illness.

Management is initially with ointment such as Aquaphor or oils including olive,

safflower, or coconut which can all be applied frequently—typically after voiding

or bowel movements. Low-dose topical estrogen is often needed. In the past

application has been to the vaginal canal only but given the sensitivity of the

introitus and vestibule, direct application is often recommended (72).

Pharmaceutical products may not be initially tolerated because of preservatives

and a temporary use of custom-compounded hormones in a neutral base such as

Glaxal base may be of benefit. Nightly application for some 2 to 4 weeks will

frequently allow the use of pharmaceutical products including creams,

intravaginal tablet, or silastic ring.

For women with breast cancer the American College of Obstetricians and

Gynecologists consensus is that current low-dose estrogen vaginal products do

not raise serum estrogen levels above those in untreated menopausal women and

are not associated with higher breast cancer recurrence rates or endometrial

stimulation (73). Within a few weeks of topical estrogen application the

epithelium recovers and absorption becomes undetectable so that initiating

treatment early during cancer therapies before marked injury occurs from

estrogen lack will allow the lowest systemic exposure. When the woman is on

aromatase inhibitors the optimal management of her pain is unclear given the

preference to avoid even minor systemic increase in estrogen. However, poor

compliance in some 30% of women as a result of medication side effects is of

concern (74). There is early evidence of safety in terms of minimal rise in serum

estrogen plus and sexual benefit from the use of either an estradiol ring (7.5

microgram/d) or intravaginal testosterone (75). Vaginal DHEA, with recent FDA

approval, appears useful for women with breast cancer given the lack of systemic

increases in either testosterone or estrogen but its use has not been studied

specifically in the context of breast cancer. A temporary switch from an

aromatase inhibitor to a selective estrogen-receptor modulator such as tamoxifen

986can be used—tamoxifen does not consistently lead to dyspareunia (73).

Recent research showed hyaluronic acid to be as effective as low-dose estradiol

when used nightly in an 8-week study (76). Topical lidocaine applied to the

vestibule for 10 minutes before intercourse proved beneficial in a trial of women

with breast cancer (77). Ospemifene—a selective estrogen-receptor modulator

with estrogen agonist activity in the vagina appears to have a neutral effect on

breast tissue but experience is limited.

Fertility preservation is considered along with the overall treatment plan for

younger women, and a number of options are emerging. Delaying cancer

treatment to allow one cycle of hormone stimulation followed by

cryopreservation of either a mature oocyte or an embryo may be a very difficult

decision. In some situations, including after a hormone receptor–positive breast

cancer, pregnancy may increase the risk of recurrence. The more established

option of using embryos can prove difficult as the embryo becomes shared

property with the current partner. When time is insufficient for these two

approved options, ovarian tissue cryopreservation can be considered (78).

Diabetes

The majority of studies clearly identified a strong link between sexual

dysfunction and comorbid depression but not with diabetic control, duration,

or complications. Data are limited in quality given that many studies have neither

control groups nor clarify estrogen status, different assessments of sexual function

are used, and many publications study only women who remain sexually active—

excluding those who simply do not have a partner or may have discontinued

activity as a result of severe dysfunction (79). Most studies find the prevalence of

low sexual desire to be similar in women with and without diabetes, yet

difficulties with lubrication are approximately two times more common in women

with diabetes. Some but not all studies show increased prevalence of dyspareunia,

orgasmic difficulties, and sexual dissatisfaction (80). In the long-term

Epidemiology of Diabetes Interventions and Complications (EDIC) study, more

than half of the women had problems with orgasm, arousal, and lubrication. In

multivariate analysis, only depression and marital status predicted sexual

dysfunction (79). Recently, young women on multiple insulin dosage had

impaired arousal and lubrication whereas those using an insulin pump had sexual

function comparable to healthy age-matched women (40). Again depression was

the independent predictor of sexual dysfunction.

[4] Gynecologic Conditions: Sexual Dysfunction Can Arise From

Gynecologic Diseases, Procedures, and Treatments

987Stress Incontinence Surgeries

Mid-urethral slings are now commonly placed for stress urinary incontinence.

While most women report same or overall improved sexual function, orgasm

preservation is more certain with transvaginal tapes than with transobturator tapes

which may pose more risk to the neural integrity of the anterior vaginal wall (81).

Hysterectomy

Simple Hysterectomy

A recent review of English publications to 2015 concluded that in the shorter term

the majority of women reported improved or unchanged sexual function. In the

longer term deterioration in function was attributed to normative changes with

aging (82). Despite speculation that there might be different sexual outcomes

depending on whether hysterectomy was vaginal, abdominal—open or

laparoscopic, subtotal or total, any difference is not supported by study (82).

Radical Hysterectomy

Techniques were developed to avoid the portions of the inferior hypogastric

plexus in the cardinal and broad ligaments, and studies suggest minimal reduction

of vaginal congestion in response to sexual stimulation in a laboratory setting

(83).

Gynecologic Cancer

Some 55% of women with gynecologic cancer report dyspareunia (84) which has

multiple causes in addition to estrogen deficiency. These include neuroma from

transecting nerves, radiation-associated scarring causing nerve compression or

entrapment, and damage to vasculature. Careful physical examination can identify

which pelvic nerves may be generating the pain to allow targeted diagnostic

injections of local anesthetic. Chemotherapy-induced peripheral neuropathy may

follow the use of taxanes, vinca alkaloids, platinum analogs, and 5-fluorouracil.

Vaginal stenosis may be caused by radiation and/or graft versus host disease and

the use of dilators can be challenging both technically and psychologically.

Strong support from the oncology team, optimally with inclusion of a pelvic floor

physiotherapist, is frequently recommended. Neuropathic pain does not respond

to opioid medications, but there is some evidence of benefit from the use of

duloxetine and low-dose amitriptyline (85). Mindfulness-based cognitive therapy

programs have shown benefit for women’s sexual dysfunction, including pain,

that is subsequent to gynecologic cancer (86).

988Cervical Cancer

Sexual symptoms encountered in women with cancer of the cervix include

reduced vaginal lubrication secondary to surgical menopause, radiation

damage, and/or interruption of the autonomic nerves. Compared to women

who underwent cervical conization, women receiving radical hysterectomy

reported worse sexual function in all domains with the female sexual function

index questionnaire (87). Nerve sparing radical hysterectomy has been associated

with improved sexual function compared to traditional radical hysterectomy (87).

A meta-analysis of nerve sparing radical surgery for cervical cancer identified no

worsening of prognosis and improved sexual function as compared to nonnervesparing surgery (88).

There is marked synergy between cancer of the cervix and sexual abuse as

a cause of sexual dysfunction (89). An absence of sexual satisfaction was

reported by 20% of women with neither abuse nor cancer of the cervix, by 31% of

women who were sexually abused and did not have cancer of the cervix, by 28%

of women with cancer of the cervix and who were not abused, but by 45% of

women with a history of both abuse and cancer of the cervix. Dyspareunia was

extremely rare in women without cancer of the cervix, but it was reported by 12%

of those with cancer of the cervix and by 30% of those with cancer of the cervix

and past sexual abuse.

Endometrial Cancer

The safety of vaginal estrogen for GSM is still in question although the evidence

does not support any increase in recurrence rates with its use (90).

Ovarian Cancer

Sexual response and satisfaction is compromised with all forms of treatment but

particularly when there is both surgery and chemotherapy and when disease is

advanced such that only chemotherapy is possible (87). Importantly, the majority

of ovarian cancer patients continue to feel sexual health is important (87).

Vulvar Cancer

There are conflicting results as to whether the extent of surgical resection

determines the extent of sexual dysfunction, but women undergoing laser or

partial resection of the clitoris have more severe dysfunction than women whose

clitoris can be spared (91).

Pregnancy

[5] Physical, emotional, and economic stressors of pregnancy may negatively

989affect emotional and sexual intimacy. Sexual value systems, folklore,

religious beliefs, physical changes, and medical restrictions influence sexual

attitudes and behavior during pregnancy and postpartum. In the absence of

preterm labor, antepartum bleeding, or an incompetent cervix, there is no

evidence that sexual activity, orgasm, or intercourse increases the risk of

pregnancy complications. Normal changes that occur with sexual activity during

pregnancy include increased breast tenderness, increased sensitivity to uterine

contractions with orgasm, general discomfort, less mobility, and fatigue. Sexual

satisfaction in pregnancy is closely related to feeling happy about the pregnancy,

continuing to feel attractive, and understanding that in a healthy pregnancy sexual

activity and orgasm do not harm the fetus.

Toward the end of the third trimester the need for closeness, emotional support,

and nurturing may be far greater than any desire for orgasms or intercourse.

Nevertheless, a study noted that 39% of 188 women reported being engaged in

intercourse during their birth week (92). Difficulties may arise from the partner’s

reaction to the woman’s pregnancy, the physical changes of pregnancy, lack of

information regarding sex and pregnancy, and lack of direction from the

physician when complications arise. A general lessening of sexual desire in

both pregnancy and the postpartum period is common and considered

normal. Couples can be encouraged to continue their usual patterns of

lovemaking during pregnancy if they are emotionally and physically

comfortable and there are no contraindications to either orgasm or

intercourse.

Dyspareunia and Method of Delivery

A recent prospective study found obstetric intervention including emergency

cesarean section, vacuum extraction, or elective cesarean section to be associated

with increased odds (2.4, 2.3, and 1.7 respectively) of the women reporting

persistent dyspareunia at 18 months postpartum (93). Two previous studies

showed that operative vaginal delivery conferred the highest risk of dysfunction

(94,95).

Postpartum

The ongoing vaginal bleeding and discharge, perineal discomfort, hemorrhoids,

sore breasts, and decreased vaginal lubrication associated with nursing,

compounded by fatigue from disturbed nights, all contribute to decreased

motivation for sexual activity. Further complicating factors include fear of waking

the baby, a decreased sense of attractiveness, change of body image, or mood

change. Many couples resume sexual activity and include intercourse by 6 to 8

weeks postpartum, but some couples wait as long as a year before resuming their

990prepregnancy level of sexual intimacy. Typically women who nurse report less

sexual activity and less sexual satisfaction than those who bottle feed.

Physicians can provide considerable help to patients and their partners by

acknowledging and discussing the normal fluctuations in sexual desire and

frequency of sexual activity during and after pregnancy.

ASSESSMENT OF SEXUAL PROBLEMS

[7] Despite the importance of issues relating to sexuality, many women find it

difficult to announce their preferences or initiate discussions of sexual

concerns with their physicians and many physicians are uncomfortable

discussing sexual issues with their patients. Through the use of a structured

questionnaire and review of the records of 1,065 women who consecutively

attended 37 family practices in areas of high, medium, and low socioeconomic

status, 40% of women had at least one form of sexual dysfunction according to

diagnostic criteria of the International Statistical Classification of Disease (ICD-

10). Only 4% had a prior entry in their medical record relating to sexual problems

(96).

There are numerous reasons physicians are reluctant to discuss issues relating

to sexuality with their patients. Anxiety about physicians’ perceived inability to

treat sexual problems, unwillingness to spend the time required to accurately

assess sexual concerns, personal discomfort when discussing sexual matters with

patients, and distress arising from their patients’ history of sexual-related violence

are all potential barriers. Not asking about sexual function suggests to patients

that sexuality is not important and should not to be discussed. [8] Many

gynecologic interventions and a number of gynecologic conditions interrupt

sexual function, necessitating the inclusion of sexual health in gynecologic

assessment. Asking about sexual concerns gives physicians an opportunity to

educate patients about the risk of STIs, encourage safer sex practices,

evaluate the need for contraception, dispel sexual misconceptions, and

identify sexual dysfunction. Many sexual concerns can be resolved by providing

factual information and reassurance. Management of sexual dysfunction requires

appropriate biopsychosocial assessment and intervention. Even when patients

appear to have no sexual problems, if gynecologists routinely inquire about sexual

health, they demonstrate that future sexual issues can be addressed in a

professional, confidential, and nonjudgmental setting.

Interviewing Techniques

To be sufficiently comfortable to establish rapport and trust with patients,

physicians need to be familiar with the components of a sensitive, detailed,

991sexual assessment and the general principles of management of dysfunction.

Good listening skills and attention to nonverbal cues are helpful. The use of

straightforward language that patients can understand while recognizing

that many people find it difficult to discuss these sensitive, intimate and

extremely common issues is necessary.

A few open-ended questions can initiate the subject of sexual function (Fig.

17-2). Sexual inquiry is part of the medical history taken during a routine

gynecologic assessment. There is evidence that an introductory sentence would

greatly increase the chance a woman will identify her sexual problem. Listed in

Table 17-3 are some examples of screening questions related to particular

obstetric–gynecologic circumstances.

FIGURE 17-2 Algorithm for screening sexual dysfunction.

Table 17-3 Screening for Sexual Problems

Situation in

Which

Screening

Question Is

Necessary

ObGyncases (Healthcare Touch)

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Berek Novak's Gyn 2019. Chapter 17 Sexuality and Sexual Dysfunction

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