Women's Sexual Function and Dysfunction. Irwin Goldstein MD

Psychologic-based desire and arousal disorders: treatment strategies and outcome results

Lori A Brotto

Introduction

Since the US Food and Drug Administration approval of selective phosphodiesterase type 5 inhibitors for erectile dysfunction, there has been a search for a panacea for women’s sexual difficulties. In the past 6 years, there have been at least two dozen placebo-controlled studies exploring the efficacy of various pharmacologic preparations for hypoactive sexual desire disorder and female sexual arousal disorder. This enthusiastic effort has renewed interest in female sexual dysfunction and its treatment, with more research centers in diverse disciplines turning their attention to women’s sexuality. Unfortunately, the research exploring psychologic treatments for female sexual dysfunction has not been as proliferative, and the field has not advanced significantly beyond the treatments that were developed three decades ago (see Chapter 11.1 of this book).

This chapter focuses on the evidence-based literature for treatments of desire and arousal disorders in women. This chapter does not represent an exhaustive overview of all treatments, as hormonal approaches to management are the focus of Chapters 13.1-13.3. The available data to date on psychologic as well as nonhormonal pharmacologic treatments for hypo- active sexual desire disorder and female sexual arousal disorder will be reviewed. This chapter will center on hypoactive sexual desire disorder and female sexual arousal disorder that are “psychologic-based”, defined here as having a presumed etiology that is largely psychologic, and not organic (although this is a false dichotomy with limited utility, and management of sexual complaints is best when treatment providers adopt a biopsychosocial approach) (see Chapter 17.6). As the reader will note, the evaluation of treatment efficacy rarely relies upon presumed psychologic versus organic etiology as inclusion and exclusion criteria when selecting participants - except in some cases where pharmacologic antidotes to antidepressant-induced sexual dysfunction are being investigated (see Chapter 11.2). There is a discrepancy between empirical investigations and management in the real clinical setting, the latter situation consisting of treatment regimens that follow logically from a well- conceptualized case formulation that takes etiology into consideration. With the increasing sophistication of instruments to explore the physiologic components of the sexual response (e.g., laser Doppler, functional magnetic resonance imaging) (see Chapters 10.1-10.7), we may be in a better position in the future to infer when a sexual difficulty has more of a physiologic than psychologic basis.

Much of the published outcome literature on psychologic interventions involves participants who met criteria for one of the conventional diagnoses according to the recent versions of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revised (DSM-IV-TR),1 or the International Statistical Classification of Diseases and Related Health Problems, 10th revision.2 However, the clinical picture is typically more complex with a high degree of comorbidity between sexual difficulties. Moreover, rather than unambiguous symptoms, complaints of dissatisfaction and distress3 often do not fit neatly into discrete diagnostic categories. A later chapter in this text will illustrate such complexity through a series of case vignettes.

Brief history of sex therapy approaches, beginning with Masters and Johnson

Masters and Johnson’s extensive research program can be credited for bringing research on sex therapy to the forefront (see Chapter 1.1). Their book Human Sexual Inadequacy,4 published in 1970, presents data on 790 men and women treated in their St Louis clinic along with 5-year follow-up data on a smaller subsample. The treatment consisted of education in sexual responsivity, sensate focus, and encouragement of verbal communication (for all subtypes of sexual dysfunction), followed by specific techniques tailored to the particular sexual concern. Treatment was administered daily over 2 weeks by a male-female therapist team, and outcome was assessed with one clinician-determined item based on perceived success or failure. They reported astounding success rates of 72-98% for women and only a 5% relapse rate after 5 years. Attempts to replicate these findings have been unsuccessful, and many critics attribute this to the entirely subjective endpoint used, the expensive, intensive, and unfeasible delivery of their sex therapy, and the highly selective sample of participants on which their data were based (e.g., patients had to be willing to “isolate themselves from the social or professional concerns of the moment” (p 20)).4 Their findings did, however, prompt interest in research on the efficacy of sex therapy over the next several years that aimed at determining which components of Masters and Johnson’s intensive program were most efficacious.

In a modified Masters and Johnson sex therapy approach that involved weekly sessions by one therapist (versus daily therapy with a male-female therapist team), Hawton et al.found that only 61% of the 140 couples completed treatment. By the end of treatment, 26% of couples had their sexual problem completely resolved with at least partial remission in another 50%. The authors do not provide recurrence rates for each sexual dysfunction separately, though they note that results for vaginismus were “excellent, so that total resolution of this problem can be expected in most couples”; however, results for inhibited female desire were not as positive. Seventy-six per cent were available for follow-up, which took place, on average, 3 years after treatment. Interestingly, whereas 75% of couples had either recurrence or continuing difficulties at follow-up, only 34% were concerned about this. Another, more recent, large-scale study involved 365 married couples presenting to a sex therapy clinic with heterogeneous sexual complaints.Treatment was behavioral and occurred weekly over 7 weeks, and outcome was defined dichotomously as success or failure.

Sixty-five per cent of all couples responded favorably to behavior therapy, equal numbers of men and women showing improvement. Less than 50% of those who benefited from treatment returned at the 3-month follow-up. Of those, 74% reported having maintained treatment gains.

Overall, the data from the outcome research of Masters and Johnson and other large-scale studies that followed suggest that psychologic treatment of sexual dysfunction appears to be beneficial with good maintenance effects. Approximately 65-98% of participants reported at least moderate improvement by the end of treatment, and 5-34% experienced relapse, depending on the type of therapy employed and the degree of sexual difficulty (Table 11.3.1). However, methodological limitations prevent one from drawing any firm conclusions about the effects of therapy on specific sexual dysfunctions. Specifically, these limitations include the lack of comparison control groups that account for nonspecific factors, and highly subjective endpoint measures.

Psychologic treatment approaches for desire disorder

Low sexual desire in women represents the most frequent complaint (approximately 30-34%) among women in recent large- scale nationally representative samples in the USA7 and Sweden.8 Interestingly, female low desire and erectile difficulty appear to be related, as recent data show that 60% of female partners of men with erectile dysfunction meet criteria for hypoactive sexual desire disorder.9 There have been a number of studies (Table 11.3.2) evaluating the efficacy of Masters and Johnson’s treatment or other treatments derived from it, specifically for hypoactive sexual desire disorder, which DSM-IV-TR defines as “persistent or recurrent deficiency or absence of sexual thoughts, fantasies, desire for, or receptivity to sexual activity which causes personal distress”.1 Schover and LoPiccolo10 assessed the efficacy of 15-20 weekly behavior therapy sessions on couples in which either partner experienced low desire. The dropout rate was negligible at 2-3%. They found significant improvements in initiation of sexual activity, sexual satisfaction, and frequency of sexual activity, but only a minor improvement in marital satisfaction, with relatively stable maintenance after 1 year. In the UK,11 a modified Masters and Johnson approach applied over 12 sessions for couples in which women experienced low desire, found significant improvement for 57% of the couples. Improvement was defined as intercourse either with no difficulties or minor difficulties. However, unlike the prior study, there was a significant attrition rate of 37% that was found to be largely dependent upon the male partner’s level of motivation before treatment. One significant limitation of this study was the sole reliance on clinician-determined perceived intercourse ability as the primary outcome variable. Theorizing that treatment of orgasmic difficulties may lead to improvements in sexual desire, Hurlbert12 compared the effects of marital sex therapy with and without orgasm consistency training in women with hypoactive sexual desire disorder. Treatment was a primarily cognitive-behavioral approach that incorporated elements of directed masturbation, sensate focus, and the coital alignment technique. Whereas all women improved on measures of sexual desire and arousal, those who also received orgasm consistency training had even greater levels of sexual arousal and assertiveness, and these group differences were maintained at the 6-month follow-up assessment.

Table 11.3.1. Published studies that have evaluated Masters and Johnson's sex therapy, or one of its modified versions, complaints in couples on heterogeneous sexual

Publication

Participants

Therapy details

Efficacy rates

Misc.

Masters and Johnson 19704

790 men and women

Daily therapy for 2-3 weeks by male-female team; 5-year follow-up data available

72-98% for women with only 5% relapse rate after 5 years

Efficacy determined by one clinician-determined item of success vs failure

Hawton et al. 19865

140 couples

Modified Masters and Johnson treatment with 15 weekly sessions; 3-year follow-up data available

26% had complete resolution of problem with at least partial remission in another 50%; 75% had either recurrence or continuing difficulties at follow-up

Despite recurrence, the majority were not bothered by their symptoms

Sarwer and Durlak 19976

365 couples

Behavioral sex therapy with 7 weekly sessions (4-hour group sessions); 3-month follow-up data available for < 50% of couples

64% of women and men showed significant improvement. 70% reported maintained treatment gains at follow-up. Treatment success for HSDD, impaired orgasm, and dyspareunia were 65%, 65%, and 58%, respectively

Limitation: treatment outcome defined dichotomously as “successful" or “unsuccessful"

HSDD = hypoactive sexual desire disorder.

Cognitive-behavioral therapy for low desire has also been investigated (see Chapter 11.1). In one uncontrolled study, cognitive-behavioral therapy was helpful for approximately

50% of women that met criteria for various sexual complaints, including low desire.13 In a recent controlled study, Trudel and colleagues14 compared the effects of cognitive-behavioral therapy with wait-list control in 74 couples in which women met criteria for hypoactive sexual desire disorder. Treatment consisted of 12 weekly, 2-h group-therapy sessions that included homework exercises and reading assignments. The treatment included psychoeducation, couple exercises, sensate focus, communication training, emotional communication training, mutual reinforcement training, cognitive challenging, and sexual fantasy training. Seventy-four per cent of women no longer met diagnostic criteria for hypoactive sexual desire disorder by the end of the treatment, and this stabilized to 64% at 1-year follow-up.14 Nearly all other measures of individual and interpersonal dimensions improved with treatment, including quality of marital life, and individual, sexual, and cognitive functioning. Notably, the perception of sexual arousal also increased in this group of women with hypoactive sexual desire disorder. At the end of treatment, women reported a high level of satisfaction with treatment, and added that they would recommend the treatment to others. There have been other investigations of psychologic treatments for women’s low desire; however, failure to present data for specific sexual complaints limits our ability to drawn conclusions from them.15,16

Table 11.3.2. Support for psychologic interventions for hypoactive sexual desire disorder (HSDD) in women

Mode of treatment

Empirical support

Level of efficacy

Modified Masters and Johnson treatment

Hawton et al. 199111

Significant improvements in 57% of sample

Behavioral sex therapy

Schover and LoPiccolo 198210

Significant improvements in marital adjustment, sexual satisfaction, sexual frequency, initiating of sexual activity, sexual responsivity, and masturbation

Marital sex therapy plus orgasm consistency training

Hurlbert 199312

Significant improvements in sexual arousal and sexual assertiveness with sex therapy plus orgasm consistency training vs sex therapy alone

Cognitive-behavioral therapy

McCabe 200113 Trudel et al. 200114

< 50% improved

74% no longer met diagnostic criteria; significant improvements in quality of marital life, individual sexual and cognitive functioning, sexual arousal, satisfaction

Systemic and multielement treatments

No empirical data

Clinical reports of treatment utility in treating low desire in a couple

To date, there are no published empirical studies on the efficacy of treatments for low desire despite the rich clinical literature supporting these treatments among individuals and couples.17,18 This is probably due to the difficulty in manualizing treatment protocols for psychodynamic and systemic treatments. Multielement treatments that incorporate cognitive and behavioral ingredients with systemic approaches have also been described, and appear especially useful for the difficult-to-treat couple.19 The treatments require rigorous scientific testing before any definitive conclusions can be drawn as to their efficacy.

Recent efforts to redefine hypoactive sexual desire disorder20 to make it more consistent with the evidence-based literatureand the clinical presentations of women21,22 has called into question the utility of the traditional four-stage Masters and Johnson human sexual response cycle as a way of understanding women’s sexuality. It has also been argued that previous reports of the prevalence of hypoactive sexual desire disorder are markedly inflated, given that survey questions did not simultaneously assess levels of distress.3 Instead, newer models22 focus on the normalization of age- and relationship duration-related declines in spontaneous sexual desire, and encourage couples to focus treatment on aspects of the interpersonal relationship or context that may not promote responsive sexual desire. Also central to this reconceptualization is the notion of sexual arousability, or the ease with which women become sexually aroused when the context and stimuli that promote sexual response are adequate. What makes newer models unique and especially relevant for women in long-term relationships is the focus on sexual motivation that is intimacy-based.23 Efforts to incorporate this new model in the treatment of couples where low desire is the primary complaint have been promising;24,25 however, future studies that assess the model’s efficacy in the context of controlled clinical trials are needed. Another notable attempt to provide a more useful classification of women’s sexual problems is the “new view of women’s sexual problems”,26 which has replaced diagnostic labels such as “hypoactive sexual desire disorder” with descriptions that relate to a number of sociocultural, interpersonal, psychologic, and medical factors. To date, there are no published data on treatment efficacy in women who are diagnosed according to the “new view”.

Sexual aversion disorder is included in the sexual desire disorders section of the DSM-IV-TR,1 but it has received considerably less attention than hypoactive sexual desire disorder. Moreover, because of the avoidance component, the precise prevalence for this distressing condition is unknown. In general, it has been found that sexual aversion disorder is less responsive to behavioral treatment than is hypoactive sexual desire disorder.10 However, systematic desensitization in the context of behavior therapy (akin to the approaches used in the treatment of anxiety disorders) has been described as very effective in two published case studies.27,28

Psychologic treatment approaches for arousal disorder

Epidemiologic data suggest that the prevalence of problematic sexual arousal, according to the DSM-IV-TR definition of female sexual arousal disorder as “persistent or recurrent inability to attain, or to maintain until completion of the sexual activity an adequate lubrication, swelling response of sexual excitement”, is approximately 12—21%.7,8 In the clinical setting, however, arousal complaints that are independent of desire and/or orgasm complaints are rarely seen. This has led some to dispute the validity of female sexual arousal disorder as a discrete clinical entity.29 Others have suggested that there may be a subgroup of women with genital vascular insufficiency that interferes specifically with vaginal engorgement and clitoral erectile capacity while desire remains unaffected.30 Certainly, the literature on treatment for female sexual arousal disorder reflects this lack of consensus, as there are no published trials of a psychologic intervention for female sexual arousal disorder. Instead, owing to the success of vasoactive agents in the treatment of male erectile dysfunction, various pharmaceutic companies have initiated an eager search for a comparable medication in the treatment of women’s impaired arousal.

Factors associated with favorable outcome in sex therapy

Before we review the literature on pharmacologic approaches to desire and arousal disorders, the variables that have been linked to a positive treatment outcome in psychologic outcome studies will first be addressed. Although very little has been published on this topic recently, the work of Hawton and colleagues5,11,31,32

has been helpful in identifying important prognostic variables. Better long-term treatment outcome was associated with couples who reported being able to communicate about angerand the general functioning of the relationship5,33 (with ratings by women being more strongly predictive than those of men).31 Compliance with homework early on,31 as well as in the final sessions of treatment,6 was found to be highly predictive of outcome success. Pretreatment motivation by both partners, but especially of the male,34 was a strong positive predictor of a favorable outcome,31,33 as well as of which couples would complete treatment.11 Looking specifically at treatment outcome for hypoactive sexual desire disorder, Hawton32 found that degree of physical attraction between partners and interpersonal communication were important positive predictors. Others have shown that attention to systemic issues in the relationship is also positively related to outcome.35,36

Factors that predict a poorer outcome have also been identified. These include having a history of psychiatric disorder, and marital separation in the past.5,31 Variables not found to predict significantly outcome success have included age or social class of the couples,31 whether one or both partners experienced a sexual problem, presence of prior treatment (although this has been found to be a predictor in one study11), perception of the sexual problem, how well the partners were informed about sexuality, number of children, duration of the relationship, and strength of religious beliefs.31

Investigational, nonhormonal, pharmacologic treatments for hypoactive sexual desire disorder and female sexual arousal disorder

At the time of writing (July 2004), there are no approved nonhormonal pharmacologic treatments for either hypoactive sexual desire disorder or female sexual arousal disorder. The androgens, estrogen, and progestins have been the topic of a number of investigations, but their potential role in women’s sexual complaints is the focus of Chapters 13.1-13.3, and therefore they are not covered here. The place for pharmacologic treatment of desire and arousal complaints in women is still unclear (see Chapters 14.1 and 14.2). As knowledge about the precise etiologies of sexual dysfunction continues to advance, we may be in a position in the future to determine which pharmacologic agent might be useful for which specific aspect of impaired sexual response.

Numerous studies on nonhormonal agents have been conducted or are underway, and the limited published data available from those placebo-controlled investigations will be briefly reviewed. In general, the nonhormonal investigational agents for desire and arousal fall into the following categories:37 (1) dopaminergic agonists, (2) melanocortin-stimulating hormone and its agonists, (3) adrenoceptor antagonists, (4) prostaglandins, and (5) nitric oxide system agents (see Chapters 14.1 and 14.2).

Among the dopaminergic agonists, bupropion has been the subject of a few investigations based on the assumption that dopaminergic dysregulation may underlie some forms of hypoactive sexual desire disorder. A single-blind study of bupropion HCl (150 mg twice daily) in nondepressed women with hypoactive sexual desire disorder was found to have a 29% response rate.38 In a more recent, double-blind, placebo- controlled investigation in women with hypoactive sexual desire disorder,39 buproprion sustained release (300 mg) had no effect on the traditional markers of desire as defined by the DSM (e.g., spontaneous sexual thoughts or fantasies). On the other hand, the drug significantly improved sexual arousability - or the ease with which women become sexually aroused when the context and stimuli that promote sexual response are adequate. The lack of effect on spontaneous desire coupled with the recent reconceptualization of hypoactive sexual desire disorder that focuses on responsive desire20 has implications for future pharmacologic agents that might help women with low desire. It is possible that as clinical trial endpoints begin to shift focus away from spontaneous desire or fantasies and toward more relevant aspects of responsive desire and sexual arousability, beneficial drug effects, if any, may become more apparent. The dopaminergic agonist, sublingual apomorphine, was also investigated in a study of 55 premenopausal women with comorbid hypoactive sexual desire disorder and female sexual arousal dis- order.40 There was no significant drug effect when apomorphine (2 or 3 mg) was taken “as needed”, but there were significant improvements in desire, arousal, orgasm, enjoyment, satisfaction with sexual frequency, and overall intercourse frequency when sublingual apomorphine was taken daily.

Another agent with potential utility for the treatment of low desire in women is the melanocortin agonist, PT-141, which selectively binds to central melanocortin receptors. When solicitation behavior in the female rodent was taken as an analog of human female desire, PT-141 was found to facilitate significantly and selectively this aspect of appetitive sexual behavior.41 Although these findings are promising, until safety and efficacy data are available in women, any speculation about the role of melanocortin agonists in women’s desire is highly tentative.

Phentolamine mesylate acts as an antagonist via the alpha- 1 and alpha-2 receptors and has been used for decades in the treatment of erectile dysfunction through intracavernosal injections. In a single-blind, placebo-controlled pilot study of six postmenopausal women,42 40 mg of the drug was found to improve self-reported lubrication and tingling sensations significantly, with no effect on physiologic sexual arousal, subjective pleasure, or arousal. In a double-blind replication with 41 postmenopausal women by Rubio-Aurioles et al.,43 vaginally applied, but not oral, phentolamine, resulted in a statistically significant increase in physiologic arousal in women receiving hormone therapy. Moreover, only among women receiving hormone therapy did both vaginally applied and oral phento- lamine significantly improve subjective measures of arousal, lubrication, tingling, and warmth with no effect on pleasure. To my knowledge, there have been no other published reports of phentolamine since Rubio-Aurioles et al. published this paper in 2002.

Prostaglandins have a long history in the successful treatment of erectile dysfunction, and few studies have examined their potential efficacy for female sexual dysfunction. Prostaglandin E1 was the focus of a randomized, double-blind, placebo-controlled investigation in 94 premenopausal women with female sexual arousal disorder.44 There were no significant effects of prostaglandin E1 (500, 1000, or 1500 |J.g) over placebo on the mean arousal success rate, Female Sexual Function Index total score, or sexual distress, and only a marginal trend toward increased satisfaction with arousal. Prostaglandin E1-based formulations are currently being studied in a number of investigations.

Selective phosphodiesterase type 5 inhibitors have been the subject of a handful of conflicting investigations. Although the large-scale studies failed to find benefit of selective phosphodiesterase type 5 inhibitors for women with mixed sexual dysfunction that included arousal complaints,45,46 findings are more promising in more diagnostically homogeneous groups of women. For example, selective phosphodiesterase type 5 inhibitors were found to improve arousal and orgasm significantly in 53 premenopausal women with female sexual arousal disorder limited to genital arousal complaints.47 In postmenopausal women with adequate estrogen repletion, selective phosphodiesterase type 5 inhibitors (adjustable to 25 or 100 mg) were found to improve significantly genital sensation/feeling and satisfaction with intercourse/foreplay only in women who did not experience comorbid desire complaints, and whose plasma free testosterone was within a narrow range.48 Another investigation found that the vaginal photoplethysmograph was useful in identifying this small subsample of women with genital arousal complaints (and no comorbid problematic desire) who might respond positively to a selective phosphodiesterase type 5 inhibitor.49 Given these findings, it is likely that a beneficial effect, if any, of selective phosphodiesterase type 5 inhibitors in women might be detected only among specific subsamples of women (e.g., spinal cord injury50).

The nitric oxide precursor, L-arginine, has been the focus of a double-blind, placebo-controlled investigation combined with yohimbine, an adrenergic antagonist, in women with female sexual arousal disorder.51 The combination significantly facilitated physiologic arousal (measured by a vaginal photo- plethysmograph) but had no effect on subjective measures of arousal or affect.

At present, there is one product approved by the US Food and Drug Administration for the treatment of female sexual arousal disorder. The EROS clitoral therapy device (CTD; Urometrics, St Paul, MN, USA) is a small, hand-held, battery- operated device that is placed over the clitoris and increases vasocongestion through a gentle suction. In a noncontrolled design, this device was found to improve significantly all measures of sexual response and satisfaction in women with female sexual arousal disorder.52 However, because this device has not been subject to placebo-controlled designs, the specific effects of the gentle vacuum above and beyond nonspecific attentional effects are unknown.

Future directions

Based on the findings from both psychologic and pharmacologic trials, we might conclude that specific prognostic variables will guide future studies to target their interventions to specific subsamples of women. The data on sildenafil suggest that female sexual arousal disorder itself may be a heterogeneous diagnostic entity comprised of different subtypes that may differentially respond to vasoactive agents. The published recommendations for revising the female sexual dysfunctions20 (see Chapter 9.1) include the division and expansion of female sexual arousal disorder into “genital sexual arousal disorder”, “subjective sexual arousal disorder”, and “combined genital and subjective sexual arousal disorder”. Because women with subjective sexual arousal complaints have adequate genital vasocongestive responses, it is highly unlikely that a pharmaceutic agent designed to promote blood flow will be useful in ameliorating the sexual concerns in this group of women.53 Instead, it is in this group that psychologic interventions designed to target lack of sexual excitement and pleasure, and promote the seeking of adequate sexual stimuli and context, may prove most useful. It is anticipated that in addition to continued investigation into compounds similar to those described earlier, we may see an increasing number of investigations using herbal remedies or other natural products.54

There is an urgent need for more empirical investigations into psychologic treatments of female sexual arousal disorder and hypoactive sexual desire disorder. Methodological strictness must be integrated in order for new conclusions about efficacy to be reached. For example, accurate documentation of sexual difficulty in addition to distress are necessary, and endpoints that reflect the important aspects of sexuality for women must be addressed (e.g., pleasure, enjoyment, satisfaction, or passion)instead of intercourse frequency as the reference standard. Both participant- and investigator-derived definitions of success should be outlined, given that these can often be discordant. The differentiation between statistical and clinical significance is also essential. An extensive review of the literature in 199755 recommended that better descriptions of therapeutic technique, larger sample sizes, adequate control groups, group randomization, and inclusion of long-term follow-up data will help to build our evidence-based repertoire of treatments. Again, identification of prognostic variables will allow researchers to tailor both psychologic and pharmacologic treatments to samples of women. We hope that by the next edition of this textbook on female sexual dysfunction, more data on psychologic as well as combined psychologic-pharmacologic treatments will be available.

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