CLINICAL FOCUS

CME

Primary Psychiatry. 2008;15(9):72-81

Womens Sexual Desire and Arousal Disorders

Rosemary Basson, MD

ABSTRACT
Current conceptualization of womens sexual response recognizes overlapping phases of variable order. Even without their sensing sexual desire at a particular moment, women initiate or agree to a sexual encounter for numerous reasons. Provided there is adequate attention to appropriate sexual stimulation and an ability to remain focused, subjective arousal follows. That arousal is often poorly correlated with typically prompt reflexive genital congestion. If this complex state of arousal is accompanied by positive emotions and thoughts, then sexual desire, along with further arousal, is triggered. Positive sexual experiences provide further motivation to be sexual again. Understanding this cycle allows patients and clinicians to identify points of interruption, guiding traditional and recently adopted forms of psychosexual therapy for problematic desire and arousal. Given the strong correlation between womens sexual function and their mental and relationship health, it is necessary to first address these parameters. Recommendations to change official definitions of womens sexual disorders have been published. Pharmacologic and hormonal therapies for sexual disorders are currently under investigation. There are numerous gaps in present knowledge regarding the need and safety of any testosterone supplementation.

Needs Assessment: A new conceptualization of womens sex response reflects cur-

rent data. These include the broad range of womens sexual desire, its overlap with subjective sexual arousal and the common lack of correlation between desire and subjective arousal on the one hand, and objective increases in genital congestion on the other. Recommendations to revise official definitions of womens sexual disorders of desire and arousal have followed.

Learning Objectives:

Identify two key aspects of womens sexual desire Identify two key aspects of womens sexual arousal Construct a composite model of womens variable sexual response Identify psychosexual therapies for interruptions of that response List seven complexities regarding long-term testosterone therapy in women with sexual dysfunction

Target Audience: Primary care physicians and psychiatrists. CME Accreditation Statement: This activity has been planned and implemented in

accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Mount Sinai School of Medicine and MBL Communications, Inc. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation: The Mount Sinai School of Medicine designates this educational
activity for a maximum of 3 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Faculty Disclosure Policy Statement: It is the policy of the Mount Sinai School

of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices. This information will be available as part of the course material. This activity has been peer-reviewed and approved by Eric Hollander, MD, chair and professor of psychiatry at the Mount Sinai School of Medicine, and Norman Sussman, MD, editor of Primary Psychiatry and professor of psychiatry at New York University School of Medicine. Review Date: August 8, 2008. Drs. Hollander and Sussman report no affiliation with or financial interest in any organization that may pose a conflict of interest.

To receive credit for this activity: Read this article and the two CME-des-

ignated accompanying articles, reflect on the information presented, and then complete the CME posttest and evaluation found on page 91. To obtain credits, you should score 70% or better. Early submission of this posttest is encouraged: please submit this posttest by September 1, 2010 to be eligible for credit. Release date: September 1, 2008. Termination date: September 30, 2010. The estimated time to complete all three articles and the posttest is 3 hours.

Dr. Basson is clinical professor and director of the Sexual Medicine Program in the Department of Psychiatry at the University of British Columbia in Vancouver, Canada. Disclosures: Dr. Basson reports no affiliation with or financial interest in any organization that may pose a conflict of interest. Please direct all correspondence to: Rosemary Basson, MD, British Columbia Centre for Sexual Medicine, General Hospital, 855 W 12th Ave, Vancouver, BC, Canada, V5Z 1M9; Tel: 604-875-8254; Fax: 604-875-8249; E-mail: bassonrees@telus.net.

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INTRODUCTION
Problematic low sexual desire and arousal is reported by approximately 33% of women.1-3 Sexual dissatisfaction or distress does not necessarily follow,1,4 but when it does and is ongoing, the diagnoses of sexual desire and arousal disorders are considered. Prevalence figures from recent nationally representative surveys of women in the United States suggest a prevalence of desire disorder of 8.3% and 9.5% with minimal variation across ages until a drop in women >60 years of age.2,5 Prevalence may generally reach 12.5% for surgically menopausal women, and 19.9% for women <45 years of age.5 Of women living in the US, the prevalence of dysfunction was higher in those of Japanese and Chinese backgrounds and lower in African-American women.6 Currently recommended definitions of disorder reflect the complexities of desire and arousal. Importantly, desire (ie, drive, lust, sexual need) may not be present initially, but it can be triggered during the sexual encounter along with arousal. Secondly, arousal itself includes numerous aspects, notably subjective excitement/sexual pleasure and physical genital and non-genital changes. That the mental and physical aspects are frequently poorly correlated has been repeatedly documented. Therefore, currently recommended definitions of disorder identify the different dysfunctional components of arousal. This article describes current conceptualization and supporting evidence of womens sexual response as well as recently recommended definitions of disorder. The main correlates of desire and arousal that guide the assessment and treatment of desire arousal disorders are outlined. Standard and recent additions to psychosexual therapy are clarified prior to mention of investigational medical treatments, including testosterone supplementation.

CURRENT CONCEPTUALIZATION OF WOMENS SEXUAL RESPONSE

A variety of reasons prompt women (and men) to initiate or agree to sex. A recent study identified 235 discrete reasons that were divided into four domains, namely love and intimacy, physical pleasure and stress relief, goal attainment, and protection of the relationship/mate guarding. Evaluating 1,500 undergraduate psychology students, the majority of both men and women were mostly motivated for reasons related to attraction, pleasure, affection, love, romance, and emotional closeness. However, women exceeded men in their reporting emotional motivations.7 Although these motivations were not mutually exclusive, the results support the concept that even if drive is initially absent, there are numerous other reasons to engage in sexual activity.8 That womens
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desire can be triggered subsequently during the sexual encounter also has empirical support. Data from 125 women 2070 years of age showed that regardless of their reporting or not reporting sexual dysfunction, all women identified triggers of sexual desire.9 These triggers were in the domains of emotional bonding, erotica, romance and physical proximity. An absence of any initial desire was shown in the baseline Study of Women Across the Nation (SWAN), wherein the majority of 3,250 multi-ethnic middle-aged women in North America indicated that while they were moderately or extremely satisfied with their physical sexual pleasure, they never or very infrequently sensed desire.6 The highest figures were for Chinese and Japanese women (61.4% and 67.8%). If further equally large multi-ethnic studies confirm these findings, it can be concluded that beginning a rewarding sexual experience without desire is at least as common for mid-life women as beginning one with a definite sense of desire. Consistent anticipatory sexual desire is more typical of new relationships, and it may be a major reason for sexual engagement. However, that phase may be brief; one study suggests it may last only 1 year for some women.10 Current conceptualization of womens sexual response allows for the possibility that initially there is a willingness to become aroused and sense desire subsequently (Figure 1).8,11 Though the potential absence of initial desire in sexually satisfied women is now documented, the validated questionnaires used to assess sexual function are based on models of sexual response wherein desire was taken as necessary to the outset of engagement. This is unfortunately acknowledged as a serious limitation.12 It is important to note that qualitative research has shown that numerous women cannot clearly distinguish between desire and arousal.13 Some women refer to genital and nongenital physical sensations as components of their desire, which is especially true of younger women. The discrepancy between subjective sexual arousal and any measurement of the genital congestion has been frequently identified (Table 1).14-19 The genital response appears to be a reflex automatic entity that can be elicited in response to a stimulus deemed sexual but not erotic or potentially arousing (eg, viewing a video of primates mating).18,19 Moreover, womens assessment of their genital congestion is inaccurate. Thus, it is clear that womens arousal cannot be measured by their report of genital swelling lubrication response.20 Recently recommended definitions of disordered arousal include the different components of arousal, particularly genital and subjective excitement.21,22 To summarize the current understanding of sexual response, desire may or may not be present at outset.6,7,8 Even when desire is absent, the woman can choose to deliberately attend to sexual stimulation and remain focused for a sufficient amount of time to allow subjective arousal. The type of stimulation,

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the context, her ability to attend, the number of distractions, and the expected outcome influence the likelihood of her becoming aroused. When arousal follows and the stimulation continues sufficiently long, its intensity can increase and trigger desire. At that point, her focus becomes her need for sexual satisfaction. The latter may or may not include orgasm(s) but usually requires freedom from any pain or partner dysfunction or negative emotional conclusion. Positive experiences reinforce subsequent sexual motivation. The cycle shown in Figure 1 may be cycled many times during one encounter. This cyclicity and phase overlap predicts the well-documented comorbidity of desire and arousal disorders.2,3 This conceptualization includes and expands on those of Masters and Johnson23 and Kaplan.24 The latter described the phase of desire, mentioning both intrinsic/ biologic and extrinsic/responsive types, that add to the linear sequence of arousal/excitement, orgasm and resolution described by Masters and Johnson.23 Although after the publication of Human Sex Response Cycle by Masters and Johnson,23 the arousal phase in women often became equated to genital events (lubrication and swelling); the original description included both genital and subjective arousal. The focus on the minds processing of stimuli is derived from Janssen and colleagues25 information processing model
FIGURE 1

in addition to the concept of sexual excitation versus sexual inhibition as explored by Sanders and Graham.26 The circular model depicted in Figure 1 is composite, but it allows for the marked variability of response among women who consider their sexual lives as rewarding and functional.

CURRENT RECOMMENDATIONS FOR DEFINITIONS OF DISORDER

Womens sexual function is highly contextual, and when that context is problematic such that she reports sexual dysfunction it is questionable whether the term sexual disorder is truly appropriate. Frequently there is no evidence of innate disruption of her sexual response. Rather, a problematic sexual environment, including lack of emotional closeness or inadequate stimuli, underlies her problematic experiences. Therefore, current contextual factors, factors from the developmental or medical history, should be documented with any diagnosis of sexual disorder/dysfunction.21 Management of her dysfunction may well focus on correcting an unhealthy sexual context. It is important to note that women rate relationship difficulties as a major cause of sexual dysfunction.27
TABLE 1

SEXUAL RESPONSE CYCLE8,11

Multiple motivations Other rewards emotional intimacy, increased well being Sexual satisfaction and absence of pain Arousal triggers desire Subjective arousal + ANS response Initial Sexual desire (variable) Deliberate attention to stimuli

DATA IDENTIFYING POOR CORRELATION BETWEEN SUBJECTIVE SEXUAL AROUSAL AND MEASUREMENTS RELATING TO THE NEUROVASCULAR GENITAL RESPONSE14-19
Data Source Findings Brain imaging while viewing Activation of complex brain circuitry, includvisual erotica14,15* ing cortical, limbic, and paralimbic areas involved in cognition, motivation, emotions as well as hypothalamic areas modulating ANS. Activation in hypothalamus to increase genital congestion correlates poorly with subjective arousal. VPP in women with or without Minimal correlation between subjective problematic desire, arousal, arousal and measures of increased vasoorgasm, dyspareunia, viewing congestion erotica16,19 Genital MRI while viewing erot- Measures of increases in genital blood flow ica17* correlate poorly with subjective arousal VPP during the viewing of bio- Prompt increases in vasocongestion logically sexual but not erotic despite absence of subjective arousal. stimuli (primates mating)18*
* Sexually healthy subjects. These findings are in contrast to those in men. ANS=autonomic nervous system; VVP=vaginal photoplethysmography; MRI=magnetic resonance imaging. Basson R. Primary Psychiatry. Vol 15, No 9. 2008.

Biologic factors Processing of stimuli Psychological factors

Circular response cycle of overlapping phases: desire may or may not be present initially. It can be triggered during the experience. The sexual and nonsexual outcome influences future sexual motivation. Basson R. Female sexual response: the role of drugs in the management of sexual dysfunction. Obstet Gynecol. 2001;98(2):350-353. Adapted with permission from Lippincott Williams & Wilkins. Copyright 2001. ANS=autonomic nervous system. Basson R. Primary Psychiatry. Vol 15, No 9. 2008.

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Table 28,20-22,28 outlines the recently recommended definitions of dysfunction from an international consensus committee organized by the American Urological Association Foundation.21 Subsequent to this consensus document, other colleagues made further recommendations that uphold the basic principles, including that desire may normally be limited to a triggered type, that subjective arousal must be addressed, that
TABLE 2

the entity of genital sexual arousal disorder should be included, and that the degree of distress must be assessed.22 These definitions have not been accepted by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision20 or International Classification of Diseases, Tenth Edition29 committees. However, the former is currently beginning extensive research in order to provide official revisions in 2010.

CHANGING DEFINITIONS OF WOMENS SEXUAL DYSFUNCTIONS8,20-22,28

Sexual Symptom Category Lack of sexual desire DSM-IV-TR20 Hypoactive sexual desire disorder: persistent or recurrently deficient (or absent) sexual fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician taking into account factors that affect sexual functioning such as age and context of the persons life. Revised Definition from International Consensus Committess 200321 and 200428 Sexual desire/interest disorder: absent or diminished feelings of sexual interest or desire. Absent sexual thoughts or fantasies and a lack of responsive desire. Motivations (here defined as reasons/incentives) for attempting to become sexually aroused are scarce or absent. The lack of interest is beyond a normative lessening with life cycle and relationship duration. Revisions Suggested by Segraves and Colleagues22 Hypoactive sexual desire disorder: persistent lack of desire for sexual activity and/or lack of responsive desire. This is beyond normative lessening with relationship duration or aging. Comments Minimal spontaneous sexual thinking or desiring of sex prior to actual sexual experiences do not necessarily constitute a disorder, given the data on women in sexually satisfactory established relationships. Lack of desire triggered during the sexual encounter (ie, responsive desire) is integral to the revised diagnosis. Segraves and colleagues25 note that many women do not report presence of spontaneous desire. Thus, the and/or lack of responsive desire seems incorrect: and would appear to be more appropriate. In the two revised versions there is no sexual excitement (in the mind) and no awareness of reflexive genital vasocongestion.

Lack of subjective and genital sexual arousal

There is no DSM-IV-TR definition addressing lack of subjective arousal.

Combined arousal disorder: absent or markedly reduced feelings of sexual arousal (sexual excitement and sexual pleasure) from any type of stimulation and absent or impaired genital sexual arousal (vulval swelling and lubrication).

Female sexual arousal disorder: persistent or recurrent lack of sense of building sexual excitement and pleasure during sexual activity and/or inability to attain and maintain the lubrication/ swelling response until completion of sexual activity.

Lack of subjective sexual arousal

There is no DSM-IV-TR definition addressing lack of subjective arousal.

Subjective arousal disorder: absent or There was no recommendation markedly reduced feelings of sexual to separate the different types of arousal (sexual excitement and sexual arousal that may be lost. pleasure) from any type of stimulation. Vaginal lubrication and other signs of physical response still occur. Genital arousal disorder: absent or There was no recommendation impaired genital sexual arousal. to separate different types of Minimal vulval swelling or vaginal arousal that may be lost. lubrication from any type of sexual stimulation and reduced sexual sensations from caressing genitalia. Subjective sexual excitement still occurs from non-genital sexual stimuli.

In the AUAF/AFUD definition there is no sexual excitement (in the mind) but awareness of adequate lubrication.

Lack of genital sexual arousal

Female sexual arousal disorder: persistent or recurrent inability to attain or to maintain until completion of the sexual activity an adequate lubrication/swelling response of sexual excitement.

The presence of subjective arousal (sexual excitement) from nongenital stimuli ( e.g. erotica, stimulating the partner, receiving breast stimulation, kissing) is key to the revised AUAF/AFUD diagnosis. When the concern is limited to dryness/dyspareunia then the diagnostic term is dyspareunia. This condition is poorly understood. Hypervigilance towards genital sensations and increasing anxiety that the symptoms are highly abnormal is a clinical finding. Reliable treatment has not been found.

Persistent genital arousal

Persistent genital arousal disorder: spontaneous, intrusive, and unwanted genital arousal (tingling, throbbing) when sexual interest or desire is absent. Awareness of subjective arousal is infrequent but mostly unpleasant. The arousal is unrelieved by orgasms and the feelings persist for hours or days.

NA

NA

DSM-IV-TR=Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev; AUAF/AFUD=American Urology Association Foundation, formerly American Foundation of Urologic Disease; ICUD=International Consultation on Urological Diseases; ISSR=International Society for Sexual Research; NA=not applicable. Basson R. Primary Psychiatry. Vol 15, No 9. 2008.

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PSYCHOLOGICAL FACTORS PREDISPOSING AROUSAL AND DESIRE DYSFUNCTION

The major risk factor documented in the literature is poor mental health.1,4 Even a history of major depressive disorder (MDD) without current depression or antidepressant therapy proved a risk factor for low arousal and physical pleasure in the SWAN study.30 In a recent study,31 successful antidepressant therapy improved sexual dysfunction that was initially present in 80% of 445 women with MDD, whereas dysfunction worsened if the depression continued. Even when clinical depression is formally excluded, women complaining of low desire still have lower self-esteem, more mood variability, and more anxious and depressed thoughts than control women.32 The second robust correlation with sexual arousal and desire disorders is relationship difficulties and negative feelings toward the current partner. Indeed, positive past sexual experiences and positive feelings for the partner appear to protect middle-aged women from dysfunction associated with their marked hormonal changes.33 Major factors protecting women from sexual distress have been found to be positive feelings for the partner generally and specifically at the time of sexual engagement.4 Even when medical factors are pertinent (eg, among breast cancer survivors), important predictors of their sexual satisfaction include relationship quality and mental health.34 Partner sexual dysfunction is also a major risk factor for a womans subsequent dysfunctions that typically improve with successful treatment of her partner.35

BIOLOGIC RISK FACTORS

The importance of biologic factors is less clear. Regarding estrogen, the vast majority of untreated postmenopausal women will show signs of vulvovaginal atrophy36 that can reduce sexual motivation, but dyspareunia is by no means universal and most epidemiologic studies show little increase in dyspareunia with age. The (albeit diminishing) intracellular production of estrogen from adrenal and ovarian prohormones, including dihydroepiandrosterone (DHEA) and DHEA sulphate, may be sufficient for some women. Rather than amounts of substrate (ie, prohormones), the activity of the various steroidogenic enzymes including aromatase in the different peripheral tissues may be the key factor. Variations in estrogen receptor numbers and sensitivities may also be relevant. Regarding lack of androgen, this too is far from straightforward. Surgical menopause has been cited as an example of an androgen-deplete state. However, the prevalence of subsequent desire or arousal dysfunction is unknown. Elective bilateral
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oophorectomy along with required simple hysterectomy apparently may not lead to sexual dysfunction. This has been confirmed recently in three different studies.37-39 This seems to be in conflict with cross-sectional studies of women with surgical menopause who appear to have more distressing low desire and low satisfaction than naturally post-menopausal women.2,3 However, these latter studies give no details on the degree of choice the women had regarding the bilateral oophorectomy. The complexities of the intracellular production of sex hormones is an area of active research.40 Adrenal production of precursors is said to decrease by 66% between late 30s and early 60s, but the amount of variation among individual women is unknown. Moreover, the decreased production may still be sufficient if the necessary enzymes in the cells to convert the precursors to testosterone and estrogen remain active.40 However, there are other complexities, including sensitivity of androgen receptors and availability and numbers of cofactors. Moreover, the brain can synthesize sex hormones from the basic building block of cholesterol.41 There is early evidence that with menopause this intracerebral production of neurosteroids increases.42 There is little research into how that production might be modulated with exogenous sex hormone supplementation. There is consensus43 that the large studies exploring any correlation between (physiologic) serum levels of testosterone and womens sexual function have been negative.44,45 Though studies are in process, whether a measure of total androgen production via androgen metabolites will show any such correlation remains to be seen. Benefit has been shown in the recent transdermal testosterone supplementation randomized controlled trials (RCTs),8 but the evidence of benefit is limited. This may be partially due to the fact that the women recruited for these studies were already having on average of three sexually satisfying events per month at baseline. In view of recently recommended definitions of disorder, it is questionable whether these women had any sexual disorder. Nevertheless, their arousal and orgasm scores on the questionnaires used in the study improved with testosterone compared to placebo. An important question is, would benefit have been greater if women unable to have any sexually satisfying events had been recruited?46 There is need to study benefits of testosterone supplementation for loss of response and, therefore, absence of triggered desire.

ASSESSMENT OF DESIRE AND AROUSAL DISORDERS

Assessment involves evaluating the stages in the womans sex response cycle (Figure 1). Involving both partners and seeing them both together and separately are advocated. The womans reasons or motivations to be sexual are assessed along with the

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suitability of the context (ie, circumstances, timing, interpersonal context). Further, her intrapersonal context, in terms of selfimage, past sexual experiences, and mood, require careful examination. The variety and usefulness of the stimuli are assessed as is her proneness to distract. The nature of any distractions is clarified. These distractions might concern the sexual experience and the outcome or, more commonly, non-sexual issues. The actual sexual details are then assessed such as the extent to which intercourse is the focus, its timing, her need or experience of orgasm, any discomfort with sexual stimulation or intercourse, and any partner dysfunction. In addition, the emotional outcome both immediately and over the next few hours or days are noted. While the couple is together, the evolution of their sexual difficulties and each partners reaction to them can be evaluated. Then, when the couple is separated, inquiry as to the womans own sexual experience with self-stimulation and further details she would like to add is possible now that she is alone. Her past sexual experiences, developmental history, and past and present medical details are also needed. The same information can be obtained from the partner when he or she is seen alone. The rather simplistic AG guide to sexual assessment is offered at least to screen and decide whether referral or care within ones own practice is most appropriate (Table 3).47,48

sensory loss in the genitalia, renal disease where there may be anemia and vulvovaginal atrophy, states of hyperprolactinemia where there may be galactorrhea and in hypoadrenal states where there may be loss of pubic hair), an examination is necessary. Genital examination is necessary when there is lost genital sexual sensitivity to exclude conditions such as lichen sclerosis. In addition, genital and pelvic examination is often used for reasons of reassurance and as a means to encourage the woman to consider what is going in her mind when she is sexual rather than believing the etiology of her arousal dysfunction is confined to her genitalia. In these situations, a psychiatrist not focusing his or her practice on sexual medicine may consider it more appropriate to have a colleague perform the physical examination.

Validated Questionnaires
Validated questionnaires are available but are best considered as survey instruments, for example in epidemiologic studies, since they provide only a cursory picture of sexual functioning and are not intended for use to make diagnoses. The algorithms in Figure 2 show how the diagnostic label stems from the assessment questions.28,48

LABORATORY INVESTIGATIONS
Laboratory investigations are of limited use for sexual assessment. When there are other symptoms of, for example, thyroid disease or hyperprolactinemia (eg, galactorrhea, irregular menses, infertility), appropriate testing is conducted.

MANAGEMENT OF DISORDERED SEXUAL AROUSAL AND DESIRE

The approach is to address the problematic areas in a womans sex response cycle that have been identified during the detailed assessment. It is guided by the documented robust correlations between womens sexual satisfaction and their mental health, including self-image and their emotional intimacy with their partner. It is important to note that assessment typically continues throughout treatment as new information emerges.

Physical Examination
The physical examination is of major importance when there is comorbid dyspareunia. In the context of chronic medical disease (eg, neurologic disease where there may be
TABLE 3

Psychosexual Therapy
Figure 3 outlines the progression through psychosexual therapy options, initially addressing any mood disorder or interpersonal difficulties.48 Psychosexual education is often therapeutic. The couple is informed about womens (and mens) sexual response cycles, clarifying that suitable context and sexual stimuli are needed by all women to trigger desire on many, if not all, occasions. Cognitive-behavioral therapy (CBT) techniques clarify and challenge inaccurate thoughts, beliefs, and myths about the womans sexual response, herself, and frequently, misunderstandings about her partner. Behavioral therapy includes sensate focus treatment that targets anticipatory anxiety and performance anxiety about

QUICK REVIEW OF ASSESSMENT AG47,48

Questions for all dysfunctions About ? what happens, feelings, thoughts Both partners sex response Context relationship, environment, culture, why now? Depression ? mental health, including self-image Experiences in the past Feelings for partner then and generally General health including medication
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sexual activity. Briefly, these exercises involve the partners taking turns in providing pleasurable low-key sensual and then sexual stimulation to each other, with the recipient guiding as to the type of stimulation they would like. Once the couple has practiced with the low-key types of stimulation, more areas of the body are included, but intercourse itself is still off-limits. Focusing on the moment, guiding the partner, finding the pace at which she is more comfortable to progress with sexual activity, and realizing that sexual times can be planned in advance are all potential benefits of sensate focus therapy. When distractions are a difficulty, discussion of the mindfulness

FIGURE 2

DIAGNOSTIC ALGORITHMS FOR WOMENS SEXUAL DYSFUNCTIONS28

Detailed Sexual Inquiry

technique is warranted. Relevant literature or preferably classes can be suggested. Initially, mindfulness practice in non-sexual everyday life is encouraged and only later guidance on how to specifically use this skill during sexual activity is given. Psychotherapy can include either psychodynamic treatment or psychoanalysis. The latter would be prescribed when there was belief that the sexual dysfunction is at least partially due to pathologic processes in personality development. To help the woman relate intimately to her partner, she works through conflicts from the past that were present in nonsexual relationships. While psychotherapy is supported by the clinical literature, there is minimal empirical support.49 In practice, commonly these methods are mixed. For example, psychoeducational therapy can involve CBT techniques, sexual information, sex therapy, and mindfulness practice. It has proven beneficial for women with desire and arousal disorders particularly if they have a history of sexual abuse50 as well as for women with genital sexual arousal disorder due to gynecologic cancer.51 Larger studies with wait-list controls are in process.

Persistent lack of sexual interest, inability to sense desire at any time during the sexual experience?

Persistent inability to become aroused?

Persistent lack, delay, reduced intensity of orgasm despite high arousal?

Recurrent pain from attempted or completed intercourse

Sexual interest/ desire disorder

Sexual arousal disorder Orgasm disorder

Difficulty with vaginal entry, variable fear, avoidance, muscle tightening?

Hormonal Therapy
Estrogen-related dryness and dyspareunia improve with topical/local or systemic estrogen supplementation. Indirectly, sexual motivation may be improved. Although less well studied, genital sexual sensitivity may also respond to estrogen in the postmenopausal woman. Supplemental testosterone for postmenopausal women is not approved in the US, but it has been prescribed since the 1930s, off-label, using formulations approved for men or using compounded creams. The previously mentioned recent RCTs8 of transdermal testosterone to surgically (four studies) and naturally (one study) menopausal estrogen supplemented women all by the same sponsor and using the same protocol showed modest benefit from the 300 mcg/day but not the 450 mcg/day dose. At recruitment, the women on average reported three sexually satisfying events each month and these increased to approximately five with active drug and to four with placebo.8 On the basis of this documented benefit, transdermal testosterone has been approved by the European Union for surgically menopausal women. More recently, minimal or no benefit was seen from transdermal testosterone in estrogen-deficient women.52 In pre-menopausal women only one of three doses aimed to increase pre-testosterone levels to the high normal range proved beneficial, and that benefit was in the order of 0.8 more sexually satisfying events per month and was not associated with any improvements beyond placebo as measured by a validated sexual function and satisfaction questionnaire.53 However, consistently, the focus has been on increasing the sexual frequency, recruiting

Dysparuenia Vaginismus

Does non genital stimulation excite movies, books, breast stimulation, kissing?
Yes
Genital sexual arousal disorder

No

Is there awareness of some genital swelling, sexual sensations from genital touch, or vaginal lubrication despite absent excitement?
Yes No
Combined sexual arousal disorder

Subjective sexual arousal disorder

Basson R, Leiblum S, Brotto L, et al. Revised definitions of womens sexual dysfunction. J Sex Med. 2004;1(1):40-48. Adapted with permission from Wiley Blackwell. Copyright 2004. Basson R. Primary Psychiatry. Vol 15, No 9. 2008.

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women with satisfactory sexual experiences. Numerous unresolved issues are shown in Table 4.8,3739,52,53 A major concern is lack of long-term safety data. Recent reviews of potentially increased risk of breast cancer,54 metabolic syndrome,55 and cardiovascular disease clarify the current clinical dilemma. Testosterone supplementation requires co-administration of estrogen, which presents further difficulty. Despite cardiovascular benefit identified in non-randomized prospective trials of systemic estrogen initiated at menopause, women are currently advised against on-going systemic estrogen on the basis of cardiovascular harm shown in RCTs of women beginning estrogen supplementation many years post menopause.56 A 2006 guideline42 reviews some of these complexities underlying the American Endocrine Societys advising against testosterone supplementation.

not amount to androgen deficiency; note the studies showing elective bilateral oophorectomy at the time of perimenopausal hysterectomy does not lead to sexual dysfunction.37-39 As previously mentioned, serum levels of testosterone do not correlate with sexual function and androgen metabolites have not yet been shown to correlate with sexual function.

Investigational Therapy
Table 5 outlines some investigational drugs.57-68 The ongoing interest in addressing deficient genital congestion with various drugs, including phosphodiesterase inhibitors, alpha blockers, selective estrogen receptor modulators, and peptidase inhibitors is somewhat puzzling given the documented lack of correlation between womens sexual symptoms and any measurable deficit in genital congestion. However, these drugs might benefit women with deficient congestion due to, for example, non-nerve-sparing radical hysterectomies.

Identification of Women with Androgen Deficiency

Identifying women with androgen deficiency is currently not possible.43 The hypopituitary state would be a clear indication of androgen deficiency, but there is little clarity beyond that. Intracellular production of testosterone continues indefinitely as some supply of prohormones from adrenal glands (and ovaries in some women) continues indefinitely. Loss of ovarian androgens from surgery may

CONCLUSION
Current understanding of womens sex response cycle allows patients and clinicians to consider the points of interruption when difficulties with arousal and desire are reported. Womens sexual motivation is broad such that interpersonal or personal psychological issues can readily deter women from instigating or accepting sex.
TABLE 4

FIGURE 3

ALGORITHM OF PSYCHOLOGICAL THERAPY48

Address mood disorder, low self-image Address interpersonal issues Psychosexual education : womens sexual response cycle Create this patients sex response cycle showing interruptions/points of vulnerability

COMPLEXITIES OF TESTOSTERONE SUPPLEMENTATION8,37-39,52,53

Identification of women with low androgen activity is not possible Women with inability to be aroused and trigger desire such that sexually satisfying events are never possible have not been studied Surgically menopausal women were mostly recruited for the recent RCTs, but such women are not necessarily sexually symptomatic: none became symptomatic in three recent studies37-39 Transdermal testosterone at a dose of 300 mcg/day proved significantly beneficial compared to placebo on increasing sexual desire and frequency, but 150 mcg/day and 450 mcg/day was not8
Loss of genital sexual sensitivity, lubrication: topical or systemic estrogen

Maladaptive thoughts, problematic behaviors: CBT

Conflicts from early life precluding intimate relationships: psychotherapy

Self-monitoring, Sexual anxiety, distractions, catastrophizing anxiety, distractions, undue focus learned on genital sex. dissociation: poor mindfulness communication: sex therapy

Any benefit to premenopausal women from transdermal testosterone is unclear53 Estrogen-deficient postmenopausal women have shown no benefit from supplemental testosterone52 There are no long-term safety data and treatment is presumably life long, as women usually only give up on sex when they no longer have a functional partner There remain concerns about long-term systemic estrogen
RCTs=randomized controlled trials. Basson R. Primary Psychiatry. Vol 15, No 9. 2008.

Young C, Tovey D, Martin A, et al. Congestive heart failure. BMJ. Point-of-Care. 2008. Available at: www.pointofcare.bmj.com. Accessed August 7, 2008. Copied with permission. Copyright 2008. CBT=cognitive behavioral therapy Basson R. Primary Psychiatry. Vol 15, No 9. 2008.

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Sexual stimuli in appropriate contexts are needed for the sexual response to unfold and trigger arousal and desire. Commonly, these are lacking or problematic. Distractions, low self-image, and difficulties with trust may preclude sufficient arousal to allow pleasure and more intense arousal along with desire. Concern about a negative outcome physically or emotionally may similarly lessen arousal. Having first addressed any mental health or interpersonal issues, combinations of psychoeducation, CBT, and sex therapy are the mainstay of therapy. Teaching mindfulness techniques appears to be a promising addition. Identifying women whose sexual disorder is based on deficiency of sex hormone activity remains challenging. Testosterone supplementation for loss of both initial and triggered
TABLE 5

desire requires investigation. Pharmacologic adjuncts are being investigated and may have a role especially for genital sexual arousal disorder. PP

REFERENCES
1. Lutfey KE, Link CL, Rosen RC, Wiegel M, McKinlay JB. Prevalence and correlates of sexual activity and function in women: results from the Boston Area Community Health (BACH) survey. Arch Sex Behav. 2008. Epub ahead of print. 2. Leiblum SR, Koochaki PE, Rodenberg CA, Barton IP, Rosen RC. Hypoactive sexual desire disorder in postmenopausal women: US results from the Womens International Study of Health and Sexuality (WISHeS). Menopause. 2006;13(1):46-56. 3. Dennerstein L, Koochaki P, Barton I, et al. Hypoactive sexual desire disorder in menopausal women: a survey of western European women. J Sex Med. 2006;3(2):212-222. 4. Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav. 2003;32(3):193-211. 5. West SL, DAloisio AA, Agans RP, et al. The prevalence of low sexual desire and hypoactive sexual desire disorder in a nationally representative sample of US women. Arch Int Med. In press. 6. Cain VS, Johannes CB, Avis NE, et al. Sexual functioning and practices in a multi-ethnic study of midlife

INVESTIGATIONAL DRUGS57-68
Drug Type/Name Bremelanotide: synthetic peptide: MSH stimulating hormone analogueagonist at MCR1, MC3R, and MC4R receptors. Rationale/Comments -MSH implicated in male and female sexual responses in rodents probably via MCR4. Of note, MC4R also involved in satiety for food, stress response, and nocioception. Possible limitation of benefit from melanocortins is due to agouti-related protein (a naturally occurring inverse agonist known to inhibit G-protein coupled receptor activity) that not only blocks MCR signaling but also reduces the amount of MCR molecules accessible to melanocortins at the cell surface. Published Trials No significant differences in psychophysiologic or questionnaire responses to viewing erotic videos 15 minutes after intranasal drug but increased arousal during subsequent activity in eight women compared to the seven women given placebo.57 Recent small RCT showed benefit for womens arousal disorder with in-home use of nasal drug 45 minutes before sex58 Recent discontinuation of RCTs by sponsor.

Flibanserin: 5-HT1A agonist and 5-HT2A Serotonin acting on 5-HT1A receptors has prosexual None antagonist, weak partial agonist D4 59 effects in rodents. Selective D3 agonists Adverse effects of non-selective dopamine agonists None thought to be D2 receptor related. Selective D3 agonist investigated for erectile dysfunction.60 Less likely to cause medication-associated dysfunction One small 4-month study, in non-depressed pre-menopausal when used as an antidepressant and may ameliorate women showed increased arousability and sexual response, SSRI-induced dysfunction.61 no increase in initial desire.62 NO is a major neurotransmitter involved in vasodilatation of the clitoral structures and is also present in vagina. However, most women with arousal disorders have normal genital congestion. Increased genital congestion benefited women with diabetes63 and multiple sclerosis64 in small RCTs. Large multisite RCTs of women with arousal and desire disorders showed no benefit.65

Bupropion: blocks noradrenaline and dopamine reuptake. Phosphodiesterase inhibitors: sildenafil

NEP inhibitors66

NEP degrades VIP, a major neurotransmitter allowing None vasodilatation in the vagina. However, most women with arousal disorders have normal genital congestion. SEP also involved in VIP degradation None Arginine is a substrate for NO. However, most women with One RCT has shown some benefit in sexual dysfunction in prearousal disorders have normal genital vasocongestion. and peri-menopausal but not post-menopausal women.67

Dual NEP and SEP inhibitors L-Arginine: arginmax

Basson R. Womens sexual function and dysfunction; current uncertainties future directions. Int J Impot Res. 2008. Epub ahead of print. Adapted with permission from Nature Publishing. Copyright 2008. MSH=melanocyte-stimulating hormone; MCR=melanocortin receptor; RCT=randomized control trial; 5-HT=serotonin; D=dopamine; SSRI=selective serotonin reuptake inhibitor; NO=nitric oxide; NEP=neutral endopeptidase; VIP=vasoactive intestinal polypeptide; SEP=soluble endopeptidase.
Basson R. Primary Psychiatry. Vol 15, No 9. 2008.

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