Sexual Desire and Arousal Disorders in Women
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《新英格兰医药杂志》
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.
A 46-year-old woman, married for 16 years, reports having had a low level of sexual desire and minimal sexual arousal during sexual activity for the past 10 years. Sexual thoughts, fantasies, and orgasms are all extremely rare. Lubrication is sufficient to allow painless intercourse. She and her husband have an eight-year-old son who was born after in vitro fertilization for unexplained infertility. How should this patient be assessed and treated?
The Clinical Problem
Having too little sexual desire is the most common sexual issue among women, reported by 10 to 51 percent of women surveyed in various countries.1,2,3 Data from these surveys, as well as from other sources, indicate that a low level of desire is usually accompanied by low levels of arousal and sexual excitement and infrequent orgasms and is frequently associated with sexual dissatisfaction.4,5,6,7,8
Current definitions of sexual dysfunction in women reflect a change in our understanding of normal sexual response.9 Rather than the traditional view of a sexual response progressing through discrete phases in sequence (desire, arousal, orgasm, and resolution), it is now recognized that these phases overlap and that the sequence can vary. Also recognized is the importance to sexual satisfaction of the subjective experience and of an environment and stimuli that are conducive to sexual feelings.9
Women have many motivations and reasons for engaging in sex, including a desire for emotional closeness, whereas sexual desire is an infrequent reason for women in established relationships.10 Among the 2400 multiethnic women (Hispanic, white non-Hispanic, African American, Chinese, and Japanese) in six U.S. cities in midlife who completed baseline questionnaires in the prospective Study of Women's Health across the Nation (SWAN), 40 percent reported that they never or infrequently felt sexual desire.11 Nevertheless, the majority reported being capable of arousal, and only 13 percent expressed discontent with their sexual experiences.
Disorders of female sexual function are summarized in Table 1. The prevalence of the sexual desire/interest disorder, diagnosed when a woman fails to feel desire at any stage during the sexual experience, is uncertain. Studies have focused on a lack of desire at the initiation of and between sexual experiences, as well as on a lack of sexual thoughts. However, sexual thoughts are infrequent in many women without apparent sexual dissatisfaction,13 and the frequency of sexual fantasies or sexual thoughts has little correlation with sexual satisfaction in women.11,13 Arousal disorders are categorized according to whether there is a lack of subjective arousal alone or a lack of both subjective arousal and awareness of genital congestion (Table 1). No objective measurements are used to establish diagnoses. Arousal disorders also have an uncertain prevalence; most studies focus only on vaginal lubrication. In a survey of 979 British women who were 18 to 70 years of age, 17 percent identified problems with arousal (defined as distinct from vaginal dryness)14; 5 percent of women in SWAN did as well.11
Table 1. Definitions of Sexual Dysfunction.
Factors Influencing Desire and Arousal
The basis of desire and perceived arousal in women is poorly understood, but it appears to involve interactions among multiple neurotransmitters, sex hormones, and environmental factors.
Physiologic Factors
Genital vasocongestive responses occur in women within seconds after erotic stimulation.15 Both parasympathetic and sympathetic nerves release nitric oxide and vasointestinal polypeptide, which mediate vasodilatation, and acetylcholine, which blocks noradrenergic, vasoconstrictive mechanisms and promotes endothelial release of nitric oxide. Pelvic sympathetic nerves also release norepinephrine, which is predominantly vasoconstrictive. The mediators of vaginal vasocongestion are less clear but include vasoactive intestinal polypeptide. The relaxation of vaginal smooth muscle permits vaginal expansion, and arteriolar dilatation increases the transudation of interstitial fluid, which promotes lubrication.
The effect of estrogen levels on sexual function is complex. Although low estrogen levels and vaginal atrophy are associated with reduced measures of vaginal congestion when the woman is not receiving sexual stimulation, the percent increase in congestion in response to erotic stimuli is similar in the presence of low and high estrogen levels.15 Similarly, changes in the volume of the vaginal wall and clitoris and the relative volume of regional blood in response to sexual stimulation are similar before and after menopause.16 Estrogen deficiency does not necessarily preclude adequate lubrication, provided that stimulation is sufficient.15 However, up to 40 percent of women may have symptomatic vaginal atrophy that adversely affects sexual function.17
Subjective arousal is poorly correlated with genital response. For example, increases in genital vasocongestion in response to erotic videos are similar among women who report problems with arousal and women who report no problems with arousal.15 Also, there is a low correlation between brain activation in areas controlling genital response (as assessed by functional magnetic resonance imaging of the brain) and simultaneous ratings of subjective arousal.18
Indirect evidence suggests that testosterone and dopamine play a role in modulating sexual response, since testosterone supplementation or treatment with a dopaminergic agonist can augment response.5,6,7,8,19 Underproduction of androgen in women — as may occur with adrenal disease, after bilateral oophorectomy, or during normal aging — is sometimes associated with reduced desire and arousal. However, large population studies have failed to find the expected positive correlations between sexual function and serum testosterone levels.20,21 One possible explanation is that serum levels do not reflect the intracellular production of testosterone from adrenal and ovarian precursors.22
Other Factors
Several factors have been associated with reduced subjective arousal. These include distractions, expectations of a negative experience (e.g., as a result of dyspareunia, the partner's sexual dysfunction, or negative experiences in the past), sexual anxiety, fatigue, and depression. Medications including selective serotonin-reuptake inhibitors23 and oral contraceptives24 have also been implicated. Oral contraceptives increase levels of sex hormone–binding globulin, which in turn reduces free testosterone levels; it is hypothesized that some women are particularly sensitive to these effects, which may be prolonged.25 In a 1-year prospective study, 19 of 79 women who received oral contraceptives reported a decline in sexual desire; 37 discontinued oral contraceptive use within 12 months, many because of sexual side effects.24
On the basis of survey data, several factors have been closely linked to women's sexual satisfaction and desire. These include stable past and current mental health,3,4,13 positive emotional well-being and self-image,13 rewarding past sexual experiences,26 positive feelings for the partner,13,26 and positive expectations for the relationship.3,11 The partner's sexual dysfunction,13 increased perceived stress,3 a history of infertility especially after extensive investigation,27 and increased duration of the relationship11,26 are all linked with reduced desire. Certain diseases such as multiple sclerosis,28 renal failure,29 and premature menopause induced by chemotherapy30 are associated with a high incidence of sexual dysfunction. In women, unlike men, vascular disease related to age does not appear to correlate with reduced sexual satisfaction.3
Strategies and Evidence
Evaluation
A detailed history is the main tool in the assessment and diagnosis of sexual dysfunction and is usually obtained from both partners (Table 2). Important aspects of the history include the quality of the couple's relationship, the woman's mental and emotional health, the quality of past sexual experiences, specific concerns related to sexual activity (such as insufficient nongenital and nonpenetrative genital stimulation), and the woman's thoughts and emotions during sexual activity.
Table 2. Information Needed to Assess and Diagnose Sexual Dysfunction.
A physical examination, including a pelvic examination (Table 3), is part of routine care, but it infrequently identifies a cause of sexual dysfunction. Its usefulness may be greater when there is associated dyspareunia. For some women with a history of coercive or abusive sexual experiences, pelvic examination may cause anxiety; explanation of what will and will not be done may reduce such anxiety.
Table 3. Features Potentially Relevant to Sexual Dysfunction That Need to Be Assessed during a Physical Examination.
The possibility that laboratory testing will identify causes of sexual dysfunction is low. Estrogen deficiency, for example, is best detected by taking a history and performing an examination. Even when signs of estrogen deficiency are present, it is not necessarily the cause of sexual dysfunction. In addition, as noted, serum levels of testosterone do not correlate with sexual function.20,21 Measurement of prolactin or thyrotropin is warranted if other symptoms or signs suggest the presence of abnormal levels.
Management
The management of sexual dysfunction in women is guided by the history. Data from randomized trials that support the use of any particular intervention are limited.
Psychological Interventions
Cognitive behavioral therapy focuses on identifying and modifying factors that contribute to sexual dysfunction, such as maladaptive thoughts, unreasonable expectations, behaviors that reduce the partner's interest or trust (such as disrespectful behavior or lack of honesty), insufficient erotic stimuli, and insufficient nongenital physical stimulation. Strategies are suggested to improve the couple's emotional closeness and communication and to enhance erotic stimulation. The sessions vary in number and usually include both partners. Sex therapy for couples is focused on similar issues but also includes sensate focus techniques, consisting initially of nonsexual physical touch, with gradual progression toward sexual touch; partners are encouraged to alternately touch each other and to provide feedback about what touches are pleasurable. These techniques help change the undue focus on a performance goal (e.g., one partner's orgasm or mutual orgasms).31 Controlled studies that provide support for the use of this approach are scant, but in one that combined both cognitive behavioral therapy and sex therapy, 74 percent of women had improved sexual and marital satisfaction.31 Satisfaction was maintained in 64 percent of women at one year, as compared with minimal improvement in a control group.
Another intervention is short-term psychotherapy, generally focused on poor sexual self-image and on nonsexual experiences in childhood that are considered to relate to current sexual function (e.g., a chaotic upbringing that predisposed a woman to need to be in control could interfere with her "letting go" sexually as an adult). Data regarding the benefits of this approach are lacking.32
Pharmacologic Interventions
Other than estrogen therapy for dyspareunia related to genitourinary atrophy, no medications are currently approved by the Food and Drug Administration for the treatment of sexual dysfunction in women. Several off-label uses of drugs have been considered, although data about effectiveness are sparse (Table 4).
Table 4. Off-Label Uses of Drugs for Investigational Treatment of Sexual Dysfunction.
Nonhormonal Therapies
The involvement of nitric oxide in neurogenic vasodilatation suggests that phosphodiesterase inhibitors may ameliorate genital arousal disorder. In a small, laboratory-based, randomized trial, a single 50-mg dose of sildenafil (Viagra, Pfizer) increased subjective arousal, genital sensations, and ease of orgasm in some women with genital arousal disorder.41 The benefit was observed only among women who had a marked reduction in the normal vasocongestive response to subjectively arousing visual erotic stimulation. In two large, randomized clinical trials involving 781 women in whom arousal and desire disorders (rather than genital arousal disorder) were diagnosed, sildenafil improved no measure of sexual desire, sensation, lubrication, or satisfaction.38
Hormonal Therapies
Androgen Therapies
Supraphysiologic androgen therapy has been prescribed for sexual dysfunction since the 1930s, but more recently, testosterone at lower doses than originally prescribed have been studied in randomized trials. In one recent randomized, controlled trial involving 218 women who had undergone a natural or surgically induced menopause and who received 0.625 μg of esterified estrogens daily, the addition of 1.25 mg of methyltestosterone improved sexual responsiveness and the level of desire, as reported on one of two validated questionnaires used.43 However, the frequency of desire was not affected, and measures of desire and composite sexual function were not significantly improved, according to responses on the second questionnaire. Also, the women who had undergone natural menopause were not prescribed progestin, which limited the clinical relevance of these results. Methyltestosterone is known to lower high-density lipoprotein (HDL) cholesterol, and in this study, levels fell by a mean of 12.5 mg per deciliter (0.3 mmol per liter) after four months of treatment.
The results of four recent placebo-controlled, randomized trials involving a total of 1619 women who had undergone surgically induced menopause show the efficacy of a 300-μg testosterone patch applied twice weekly.5,6,7,8 All participants were treated with estrogen (delivered transdermally in one study,8 orally in another,6 and by either route in two studies5,7), and the number of sexually satisfying events at baseline ranged from one to three per month. Pooling the data revealed that women receiving testosterone reported 1.9 more sexually satisfying events per month than they had at baseline, as compared with 0.9 more among those receiving placebo. Scores from validated questionnaires in each of the four studies showed a significant increase in sexual desire and response, and scores in three of the studies showed significant reductions in sexual distress.5,7,8 One study also evaluated a twice-weekly patch containing 450 μg of testosterone; in contrast to the results for the lower-dose patch, no benefits were found.6 Unwanted androgenic effects, including hirsutism and acne, were uncommon in all studies, but depilation rates were not assessed. Unlike with methyltestosterone, there were no significant changes in lipid levels.
Important limitations of these four studies include their brevity (which is of particular importance, given the expected long-term use of the drug) and that their results are generalizable only to women in whom menopause was surgically induced and who also receive estrogen therapy. In some women who have undergone natural menopause, the ovaries continue to be an important source of androgens,44 and thus, the effects of androgen supplementation may differ from those in women whose ovaries have been surgically removed. Furthermore, risks associated with the long-term use of conjugated estrogens arouse concern about the use of any postmenopausal estrogen therapy over time. Prescribing testosterone alone to women who lack estrogen would raise their already high ratios of androgen to estrogen. There are no safety or efficacy data for testosterone supplementation for estrogen-deficient women.
A chief concern with long-term androgen use is a potential increase in insulin resistance, which could predispose a woman to the metabolic syndrome or exacerbate the syndrome if it is already present. In SWAN, low levels of sex hormone–binding globulin and higher circulating levels of androgen were strongly associated with markers of the metabolic syndrome, including a high body-mass index; a high waist-to-hip ratio; presence of glucose intolerance, hypertriglyceridemia, or hypertension; and a low level of HDL cholesterol.20
Dehydroepiandrosterone
Because middle-aged and older women have a physiologic decrease of as much as 70 percent in the amount of dehydroepiandrosterone produced,22 some researchers have suggested that supplementation with the steroid may improve sexual function. However, rigorous data that support such supplementation are lacking. Even among women with adrenal insufficiency, the results of randomized trials of dehydroepiandrosterone supplementation have been inconsistent.33,34,35
Estrogen
The role of systemic estrogen in increasing desire and subjective arousal remains unclear. In patients with vasomotor symptoms and insomnia or reduced levels of desire because of dyspareunia due to genital atrophy, it is logical to conclude that estrogen supplementation would increase sexual motivation, although this has not been rigorously tested. In the Women's Health Initiative trial, no significant differences were found between the estrogen and placebo groups in reported satisfaction after sexual activity.45 However, sexual dysfunction was not a primary focus of the trial, and the assessment tool was inadequate.
Sexual Dysfunction Associated with Antidepressants
The prevalence of sexual disorders that are associated with the use of antidepressants in women is estimated at 22 to 58 percent, with higher rates reported for selective serotonin-reuptake inhibitors and lower rates reported for bupropion than for other drugs.46 A recent Cochrane review of strategies to ameliorate dysfunction associated with antidepressants did not recommend any particular drug, although the potential advantages of adding bupropion were noted.46 A drug holiday (e.g., halting the use of shorter-acting selective serotonin-reuptake inhibitors over the weekend) seems to be a logical strategy but is not recommended, owing to withdrawal symptoms and compromise of compliance.
Areas of Uncertainty
A better understanding is needed of the endogenous and environmental factors that mediate sexual desire and arousal. Randomized clinical trials are also needed to assess the effects of psychological and pharmacologic therapies alone and in combination. The risks and benefits of long-term testosterone therapy require further study, including studies of women with a complete loss of arousal and desire.
Guidelines
Recommendations for the evaluation and management of sexual dysfunction in women have been put forth by the American College of Obstetricians and Gynecologists,47 the Society of Obstetricians and Gynaecologists of Canada,48 the North American Menopause Society,49 and the members of the 2003 International Consensus on Sexual Medicine (organized by the International Consultation on Urological Disease, the International Society for Urology, and the International Society for Sexual Medicine).50 These organizations advocate attention to mental and overall health and to both interpersonal and personal psychological issues. Local estrogen therapy is recommended for dyspareunia that is associated with vulval atrophy that results in reduced sexual motivation.
The Society of Obstetricians and Gynaecologists of Canada notes that testosterone therapy should be viewed as investigational and should be prescribed only by clinicians who are knowledgeable about sexual dysfunction in women.48 The recent position statement of the North American Menopause Society provides cautious support for the use of testosterone "in appropriate post-menopausal women via transdermal patches or topical gels or creams administered at the lowest dose for the shortest time that meets treatment goals."49 Counseling about the potential risks and benefits of testosterone use is also advocated, as is evaluation for causes of low levels of desire (including physical and psychosocial factors and medications) before treatment.
Conclusions and Recommendations
For women with desire and arousal disorders, such as the woman described in the vignette, the evaluation involves taking a detailed history of sexual difficulties from both partners, preferably seen individually as well as together. Also included are an assessment of the woman's mental health (including self-image), feelings about the relationship, medical history, and her thoughts and emotions during sexual activity. On the basis of clinical experience and limited data on outcomes, I would recommend a combination of cognitive behavioral therapy and sex therapy (typically three to six sessions). Sessions should be focused on altering maladaptive thoughts, unreasonable expectations, and misinformation about women's sexuality, as well as on discussing strategies for improving the couple's emotional closeness and communication and enhancing erotic stimulation. If the couple is excessively focused on intercourse (as is common if there is a history of infertility), they should be advised to emphasize nongenital stimulation first. Any apparent interpersonal problems should be addressed before further sexual therapy is pursued. At the present time, I would not recommend any pharmacologic therapy, pending the availability of more (and longer-term) data in support of such treatment.
Dr. Basson reports having received an honorarium from Pfizer and an honorarium from Solvay for consulting. No other potential conflict of interest relevant to this article was reported.
I am indebted to Dr. Peter Rees for his helpful review of the manuscript and to Mrs. Maureen Piper for her assistance with the preparation of the manuscript.
Source Information
From the Departments of Psychiatry and Obstetrics and Gynaecology, University of British Columbia; and the British Columbia Centre for Sexual Medicine, Vancouver General Hospital, Vancouver, B.C., Canada.
Address reprint requests to Dr. Basson at the B.C. Centre for Sexual Medicine, Vancouver General Hospital, 855 W. 12th Ave., Vancouver, BC V5Z 1M9, Canada, or at sexmed@interchange.ubc.ca.
References
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Maravilla KR, Heiman JR, Garland PA, et al. Dynamic MR imaging of the sexual arousal response in women. J Sex Marital Ther 2003;29:Suppl 1:71-76.
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Segraves RT, Clayton A, Croft H, Wolf A, Warnock J. Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women. J Clin Psychopharmacol 2004;24:339-342.
Santoro A, Torrens J, Crawford S, et al. Correlates of circulating androgens in mid-life women: the Study of Women's Health Across the Nation. J Clin Endocrinol Metab 2005;90:4836-4845.
Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels in self-reported sexual function in women. JAMA 2005;294:91-96.
Labrie F, Luu-The V, Belanger A, et al. Is dehydroepiandrosterone a hormone? J Endocrinol 2005;187:169-196.
Clayton AH, Pradko JF, Croft HA, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002;63:357-366.
Sanders SA, Graham CA, Bass JL, Bancroft J. A prospective study of the effects of oral contraceptives on sexuality and well-being and their relationship to discontinuation. Contraception 2001;64:51-58.
Panzer C, Wise S, Fantini G, et al. Impact of oral contraceptives on sex hormone-binding globulin and androgen levels: a retrospective study in women with sexual dysfunction. J Sex Med 2006;3:104-13.
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Trudel G, Marchand A, Ravart M, Aubin S, Turgeon L, Fortier P. The effect of a cognitive-behavioral group treatment program on hypoactive sexual desire in women. Sex Relat Ther 2001;16:145-64.
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Lovas K, Gebre-Medhin G, Trovik TS, et al. Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. J Clin Endocrinol Metab 2003;88:1112-1118.
van Thiel SW, Romijn JA, Pereira AM, et al. Effects of dehydroepiandrostenedione, superimposed on growth hormone substitution, on quality of life and insulin-like growth factor I in patients with secondary adrenal insufficiency: a randomized, placebo-controlled, cross-over trial. J Clin Endocrinol Metab 2005;90:3295-3303.
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Nathost-B??s J, Hammar M. Effect on sexual life -- a comparison between tibolone and a continuous estradiol-norethisterone acetate regimen. Maturitas 1997;26:15-20.
Basson R, McInnes R, Smith MD, Hodgson G, Koppiker N. Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal. J Womens Health Gend Based Med 2002;11:367-377.
Meston CM, Worcel M. The effects of yohimbine plus L-arginine glutamate on sexual arousal in postmenopausal women with sexual arousal disorder. Arch Sex Behav 2002;31:323-332.
Meston CM, Heiman JR. Ephedrine-activated physiological sexual arousal in women. Arch Gen Psychiatry 1998;55:652-656.
Basson R, Brotto LA. Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial. BJOG 2003;110:1014-1024.
Dasgupta R, Wiseman OJ, Kanabar G, Fowler CJ, Mikol DD. Efficacy of sildenafil in the treatment of female sexual dysfunction due to multiple sclerosis. J Urol 2004;171:1189-1193.
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A 46-year-old woman, married for 16 years, reports having had a low level of sexual desire and minimal sexual arousal during sexual activity for the past 10 years. Sexual thoughts, fantasies, and orgasms are all extremely rare. Lubrication is sufficient to allow painless intercourse. She and her husband have an eight-year-old son who was born after in vitro fertilization for unexplained infertility. How should this patient be assessed and treated?
The Clinical Problem
Having too little sexual desire is the most common sexual issue among women, reported by 10 to 51 percent of women surveyed in various countries.1,2,3 Data from these surveys, as well as from other sources, indicate that a low level of desire is usually accompanied by low levels of arousal and sexual excitement and infrequent orgasms and is frequently associated with sexual dissatisfaction.4,5,6,7,8
Current definitions of sexual dysfunction in women reflect a change in our understanding of normal sexual response.9 Rather than the traditional view of a sexual response progressing through discrete phases in sequence (desire, arousal, orgasm, and resolution), it is now recognized that these phases overlap and that the sequence can vary. Also recognized is the importance to sexual satisfaction of the subjective experience and of an environment and stimuli that are conducive to sexual feelings.9
Women have many motivations and reasons for engaging in sex, including a desire for emotional closeness, whereas sexual desire is an infrequent reason for women in established relationships.10 Among the 2400 multiethnic women (Hispanic, white non-Hispanic, African American, Chinese, and Japanese) in six U.S. cities in midlife who completed baseline questionnaires in the prospective Study of Women's Health across the Nation (SWAN), 40 percent reported that they never or infrequently felt sexual desire.11 Nevertheless, the majority reported being capable of arousal, and only 13 percent expressed discontent with their sexual experiences.
Disorders of female sexual function are summarized in Table 1. The prevalence of the sexual desire/interest disorder, diagnosed when a woman fails to feel desire at any stage during the sexual experience, is uncertain. Studies have focused on a lack of desire at the initiation of and between sexual experiences, as well as on a lack of sexual thoughts. However, sexual thoughts are infrequent in many women without apparent sexual dissatisfaction,13 and the frequency of sexual fantasies or sexual thoughts has little correlation with sexual satisfaction in women.11,13 Arousal disorders are categorized according to whether there is a lack of subjective arousal alone or a lack of both subjective arousal and awareness of genital congestion (Table 1). No objective measurements are used to establish diagnoses. Arousal disorders also have an uncertain prevalence; most studies focus only on vaginal lubrication. In a survey of 979 British women who were 18 to 70 years of age, 17 percent identified problems with arousal (defined as distinct from vaginal dryness)14; 5 percent of women in SWAN did as well.11
Table 1. Definitions of Sexual Dysfunction.
Factors Influencing Desire and Arousal
The basis of desire and perceived arousal in women is poorly understood, but it appears to involve interactions among multiple neurotransmitters, sex hormones, and environmental factors.
Physiologic Factors
Genital vasocongestive responses occur in women within seconds after erotic stimulation.15 Both parasympathetic and sympathetic nerves release nitric oxide and vasointestinal polypeptide, which mediate vasodilatation, and acetylcholine, which blocks noradrenergic, vasoconstrictive mechanisms and promotes endothelial release of nitric oxide. Pelvic sympathetic nerves also release norepinephrine, which is predominantly vasoconstrictive. The mediators of vaginal vasocongestion are less clear but include vasoactive intestinal polypeptide. The relaxation of vaginal smooth muscle permits vaginal expansion, and arteriolar dilatation increases the transudation of interstitial fluid, which promotes lubrication.
The effect of estrogen levels on sexual function is complex. Although low estrogen levels and vaginal atrophy are associated with reduced measures of vaginal congestion when the woman is not receiving sexual stimulation, the percent increase in congestion in response to erotic stimuli is similar in the presence of low and high estrogen levels.15 Similarly, changes in the volume of the vaginal wall and clitoris and the relative volume of regional blood in response to sexual stimulation are similar before and after menopause.16 Estrogen deficiency does not necessarily preclude adequate lubrication, provided that stimulation is sufficient.15 However, up to 40 percent of women may have symptomatic vaginal atrophy that adversely affects sexual function.17
Subjective arousal is poorly correlated with genital response. For example, increases in genital vasocongestion in response to erotic videos are similar among women who report problems with arousal and women who report no problems with arousal.15 Also, there is a low correlation between brain activation in areas controlling genital response (as assessed by functional magnetic resonance imaging of the brain) and simultaneous ratings of subjective arousal.18
Indirect evidence suggests that testosterone and dopamine play a role in modulating sexual response, since testosterone supplementation or treatment with a dopaminergic agonist can augment response.5,6,7,8,19 Underproduction of androgen in women — as may occur with adrenal disease, after bilateral oophorectomy, or during normal aging — is sometimes associated with reduced desire and arousal. However, large population studies have failed to find the expected positive correlations between sexual function and serum testosterone levels.20,21 One possible explanation is that serum levels do not reflect the intracellular production of testosterone from adrenal and ovarian precursors.22
Other Factors
Several factors have been associated with reduced subjective arousal. These include distractions, expectations of a negative experience (e.g., as a result of dyspareunia, the partner's sexual dysfunction, or negative experiences in the past), sexual anxiety, fatigue, and depression. Medications including selective serotonin-reuptake inhibitors23 and oral contraceptives24 have also been implicated. Oral contraceptives increase levels of sex hormone–binding globulin, which in turn reduces free testosterone levels; it is hypothesized that some women are particularly sensitive to these effects, which may be prolonged.25 In a 1-year prospective study, 19 of 79 women who received oral contraceptives reported a decline in sexual desire; 37 discontinued oral contraceptive use within 12 months, many because of sexual side effects.24
On the basis of survey data, several factors have been closely linked to women's sexual satisfaction and desire. These include stable past and current mental health,3,4,13 positive emotional well-being and self-image,13 rewarding past sexual experiences,26 positive feelings for the partner,13,26 and positive expectations for the relationship.3,11 The partner's sexual dysfunction,13 increased perceived stress,3 a history of infertility especially after extensive investigation,27 and increased duration of the relationship11,26 are all linked with reduced desire. Certain diseases such as multiple sclerosis,28 renal failure,29 and premature menopause induced by chemotherapy30 are associated with a high incidence of sexual dysfunction. In women, unlike men, vascular disease related to age does not appear to correlate with reduced sexual satisfaction.3
Strategies and Evidence
Evaluation
A detailed history is the main tool in the assessment and diagnosis of sexual dysfunction and is usually obtained from both partners (Table 2). Important aspects of the history include the quality of the couple's relationship, the woman's mental and emotional health, the quality of past sexual experiences, specific concerns related to sexual activity (such as insufficient nongenital and nonpenetrative genital stimulation), and the woman's thoughts and emotions during sexual activity.
Table 2. Information Needed to Assess and Diagnose Sexual Dysfunction.
A physical examination, including a pelvic examination (Table 3), is part of routine care, but it infrequently identifies a cause of sexual dysfunction. Its usefulness may be greater when there is associated dyspareunia. For some women with a history of coercive or abusive sexual experiences, pelvic examination may cause anxiety; explanation of what will and will not be done may reduce such anxiety.
Table 3. Features Potentially Relevant to Sexual Dysfunction That Need to Be Assessed during a Physical Examination.
The possibility that laboratory testing will identify causes of sexual dysfunction is low. Estrogen deficiency, for example, is best detected by taking a history and performing an examination. Even when signs of estrogen deficiency are present, it is not necessarily the cause of sexual dysfunction. In addition, as noted, serum levels of testosterone do not correlate with sexual function.20,21 Measurement of prolactin or thyrotropin is warranted if other symptoms or signs suggest the presence of abnormal levels.
Management
The management of sexual dysfunction in women is guided by the history. Data from randomized trials that support the use of any particular intervention are limited.
Psychological Interventions
Cognitive behavioral therapy focuses on identifying and modifying factors that contribute to sexual dysfunction, such as maladaptive thoughts, unreasonable expectations, behaviors that reduce the partner's interest or trust (such as disrespectful behavior or lack of honesty), insufficient erotic stimuli, and insufficient nongenital physical stimulation. Strategies are suggested to improve the couple's emotional closeness and communication and to enhance erotic stimulation. The sessions vary in number and usually include both partners. Sex therapy for couples is focused on similar issues but also includes sensate focus techniques, consisting initially of nonsexual physical touch, with gradual progression toward sexual touch; partners are encouraged to alternately touch each other and to provide feedback about what touches are pleasurable. These techniques help change the undue focus on a performance goal (e.g., one partner's orgasm or mutual orgasms).31 Controlled studies that provide support for the use of this approach are scant, but in one that combined both cognitive behavioral therapy and sex therapy, 74 percent of women had improved sexual and marital satisfaction.31 Satisfaction was maintained in 64 percent of women at one year, as compared with minimal improvement in a control group.
Another intervention is short-term psychotherapy, generally focused on poor sexual self-image and on nonsexual experiences in childhood that are considered to relate to current sexual function (e.g., a chaotic upbringing that predisposed a woman to need to be in control could interfere with her "letting go" sexually as an adult). Data regarding the benefits of this approach are lacking.32
Pharmacologic Interventions
Other than estrogen therapy for dyspareunia related to genitourinary atrophy, no medications are currently approved by the Food and Drug Administration for the treatment of sexual dysfunction in women. Several off-label uses of drugs have been considered, although data about effectiveness are sparse (Table 4).
Table 4. Off-Label Uses of Drugs for Investigational Treatment of Sexual Dysfunction.
Nonhormonal Therapies
The involvement of nitric oxide in neurogenic vasodilatation suggests that phosphodiesterase inhibitors may ameliorate genital arousal disorder. In a small, laboratory-based, randomized trial, a single 50-mg dose of sildenafil (Viagra, Pfizer) increased subjective arousal, genital sensations, and ease of orgasm in some women with genital arousal disorder.41 The benefit was observed only among women who had a marked reduction in the normal vasocongestive response to subjectively arousing visual erotic stimulation. In two large, randomized clinical trials involving 781 women in whom arousal and desire disorders (rather than genital arousal disorder) were diagnosed, sildenafil improved no measure of sexual desire, sensation, lubrication, or satisfaction.38
Hormonal Therapies
Androgen Therapies
Supraphysiologic androgen therapy has been prescribed for sexual dysfunction since the 1930s, but more recently, testosterone at lower doses than originally prescribed have been studied in randomized trials. In one recent randomized, controlled trial involving 218 women who had undergone a natural or surgically induced menopause and who received 0.625 μg of esterified estrogens daily, the addition of 1.25 mg of methyltestosterone improved sexual responsiveness and the level of desire, as reported on one of two validated questionnaires used.43 However, the frequency of desire was not affected, and measures of desire and composite sexual function were not significantly improved, according to responses on the second questionnaire. Also, the women who had undergone natural menopause were not prescribed progestin, which limited the clinical relevance of these results. Methyltestosterone is known to lower high-density lipoprotein (HDL) cholesterol, and in this study, levels fell by a mean of 12.5 mg per deciliter (0.3 mmol per liter) after four months of treatment.
The results of four recent placebo-controlled, randomized trials involving a total of 1619 women who had undergone surgically induced menopause show the efficacy of a 300-μg testosterone patch applied twice weekly.5,6,7,8 All participants were treated with estrogen (delivered transdermally in one study,8 orally in another,6 and by either route in two studies5,7), and the number of sexually satisfying events at baseline ranged from one to three per month. Pooling the data revealed that women receiving testosterone reported 1.9 more sexually satisfying events per month than they had at baseline, as compared with 0.9 more among those receiving placebo. Scores from validated questionnaires in each of the four studies showed a significant increase in sexual desire and response, and scores in three of the studies showed significant reductions in sexual distress.5,7,8 One study also evaluated a twice-weekly patch containing 450 μg of testosterone; in contrast to the results for the lower-dose patch, no benefits were found.6 Unwanted androgenic effects, including hirsutism and acne, were uncommon in all studies, but depilation rates were not assessed. Unlike with methyltestosterone, there were no significant changes in lipid levels.
Important limitations of these four studies include their brevity (which is of particular importance, given the expected long-term use of the drug) and that their results are generalizable only to women in whom menopause was surgically induced and who also receive estrogen therapy. In some women who have undergone natural menopause, the ovaries continue to be an important source of androgens,44 and thus, the effects of androgen supplementation may differ from those in women whose ovaries have been surgically removed. Furthermore, risks associated with the long-term use of conjugated estrogens arouse concern about the use of any postmenopausal estrogen therapy over time. Prescribing testosterone alone to women who lack estrogen would raise their already high ratios of androgen to estrogen. There are no safety or efficacy data for testosterone supplementation for estrogen-deficient women.
A chief concern with long-term androgen use is a potential increase in insulin resistance, which could predispose a woman to the metabolic syndrome or exacerbate the syndrome if it is already present. In SWAN, low levels of sex hormone–binding globulin and higher circulating levels of androgen were strongly associated with markers of the metabolic syndrome, including a high body-mass index; a high waist-to-hip ratio; presence of glucose intolerance, hypertriglyceridemia, or hypertension; and a low level of HDL cholesterol.20
Dehydroepiandrosterone
Because middle-aged and older women have a physiologic decrease of as much as 70 percent in the amount of dehydroepiandrosterone produced,22 some researchers have suggested that supplementation with the steroid may improve sexual function. However, rigorous data that support such supplementation are lacking. Even among women with adrenal insufficiency, the results of randomized trials of dehydroepiandrosterone supplementation have been inconsistent.33,34,35
Estrogen
The role of systemic estrogen in increasing desire and subjective arousal remains unclear. In patients with vasomotor symptoms and insomnia or reduced levels of desire because of dyspareunia due to genital atrophy, it is logical to conclude that estrogen supplementation would increase sexual motivation, although this has not been rigorously tested. In the Women's Health Initiative trial, no significant differences were found between the estrogen and placebo groups in reported satisfaction after sexual activity.45 However, sexual dysfunction was not a primary focus of the trial, and the assessment tool was inadequate.
Sexual Dysfunction Associated with Antidepressants
The prevalence of sexual disorders that are associated with the use of antidepressants in women is estimated at 22 to 58 percent, with higher rates reported for selective serotonin-reuptake inhibitors and lower rates reported for bupropion than for other drugs.46 A recent Cochrane review of strategies to ameliorate dysfunction associated with antidepressants did not recommend any particular drug, although the potential advantages of adding bupropion were noted.46 A drug holiday (e.g., halting the use of shorter-acting selective serotonin-reuptake inhibitors over the weekend) seems to be a logical strategy but is not recommended, owing to withdrawal symptoms and compromise of compliance.
Areas of Uncertainty
A better understanding is needed of the endogenous and environmental factors that mediate sexual desire and arousal. Randomized clinical trials are also needed to assess the effects of psychological and pharmacologic therapies alone and in combination. The risks and benefits of long-term testosterone therapy require further study, including studies of women with a complete loss of arousal and desire.
Guidelines
Recommendations for the evaluation and management of sexual dysfunction in women have been put forth by the American College of Obstetricians and Gynecologists,47 the Society of Obstetricians and Gynaecologists of Canada,48 the North American Menopause Society,49 and the members of the 2003 International Consensus on Sexual Medicine (organized by the International Consultation on Urological Disease, the International Society for Urology, and the International Society for Sexual Medicine).50 These organizations advocate attention to mental and overall health and to both interpersonal and personal psychological issues. Local estrogen therapy is recommended for dyspareunia that is associated with vulval atrophy that results in reduced sexual motivation.
The Society of Obstetricians and Gynaecologists of Canada notes that testosterone therapy should be viewed as investigational and should be prescribed only by clinicians who are knowledgeable about sexual dysfunction in women.48 The recent position statement of the North American Menopause Society provides cautious support for the use of testosterone "in appropriate post-menopausal women via transdermal patches or topical gels or creams administered at the lowest dose for the shortest time that meets treatment goals."49 Counseling about the potential risks and benefits of testosterone use is also advocated, as is evaluation for causes of low levels of desire (including physical and psychosocial factors and medications) before treatment.
Conclusions and Recommendations
For women with desire and arousal disorders, such as the woman described in the vignette, the evaluation involves taking a detailed history of sexual difficulties from both partners, preferably seen individually as well as together. Also included are an assessment of the woman's mental health (including self-image), feelings about the relationship, medical history, and her thoughts and emotions during sexual activity. On the basis of clinical experience and limited data on outcomes, I would recommend a combination of cognitive behavioral therapy and sex therapy (typically three to six sessions). Sessions should be focused on altering maladaptive thoughts, unreasonable expectations, and misinformation about women's sexuality, as well as on discussing strategies for improving the couple's emotional closeness and communication and enhancing erotic stimulation. If the couple is excessively focused on intercourse (as is common if there is a history of infertility), they should be advised to emphasize nongenital stimulation first. Any apparent interpersonal problems should be addressed before further sexual therapy is pursued. At the present time, I would not recommend any pharmacologic therapy, pending the availability of more (and longer-term) data in support of such treatment.
Dr. Basson reports having received an honorarium from Pfizer and an honorarium from Solvay for consulting. No other potential conflict of interest relevant to this article was reported.
I am indebted to Dr. Peter Rees for his helpful review of the manuscript and to Mrs. Maureen Piper for her assistance with the preparation of the manuscript.
Source Information
From the Departments of Psychiatry and Obstetrics and Gynaecology, University of British Columbia; and the British Columbia Centre for Sexual Medicine, Vancouver General Hospital, Vancouver, B.C., Canada.
Address reprint requests to Dr. Basson at the B.C. Centre for Sexual Medicine, Vancouver General Hospital, 855 W. 12th Ave., Vancouver, BC V5Z 1M9, Canada, or at sexmed@interchange.ubc.ca.
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