Review Hypoactive sexual desire disorder

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1 /toag Hypoactive sexual desire disorder Authors Janice Rymer / Kevan Wylie / Tricia Barnes / Anthony Mander / Helen Buckler / John Dean Key content: Hypoactive sexual desire disorder (HSDD) is the persistent or recurrent deficiency and/or absence of sexual thought/fantasies and/or receptivity to sexual activity, which causes distress or interpersonal difficulties. Sexual desire is a complex issue involving physical drive and motivation; the latter is influenced by previous experiences and the quality and duration of the relationship. HSDD frequently occurs in women who have had oophorectomy because a significant source of their testosterone has been removed. They may respond to androgen replacement therapy. Learning objectives: To raise awareness of the effect that oophorectomy can have on sexual function. To acknowledge that sexual function is complex and involves biological, psychological, relationship and socio-cultural factors. Ethical issues: Should clinicians raise the subject of sexual problems more routinely? Is the treatment of sexual dysfunction an appropriate use of health service resources? Can the pharmacological treatment of HSDD lead to the medicalisation of female sexuality? Keywords androgen replacement / biopsychosocial contexts / hysterectomy / oophorectomy / testosterone Please cite this article as: Rymer J, Wylie K, Barnes T, Mander A, Buckler H, Dean J. Hypoactive sexual desire disorder. The Obstetrician & Gynaecologist. Author details Janice Rymer MD FRCOG FRANZCOG FHEA Professor of Obstetrics and Gynaecology King s College School of Medicine, Department of Women s Health, 10th Floor, North Wing, St Thomas Hospital, Westminster Bridge Road, London SE1 7EH, UK janice.rymer@kcl.ac.uk (corresponding author) Kevan Wylie MD DSM FRCP FRCPsych Consultant in Sexual Medicine Porterbrook Clinic, 75 Osborne Road, Nether Edge Hospital, Sheffield S11 9BF, UK Tricia Barnes BA MA CQSW BASRT accred UKCP Reg Psych Director of Clinical Services and Research TBA Practice, 21 Upper Wimpole Street, London W1G 6NA, UK Anthony Mander FRCOG Consultant in Obstetrics and Gynaecology The Highfield Hospital, Manchester Road, Rochdale OL11 4LZ, UK Helen Buckler BMed Sci DM FRCP Consultant Endocrinologist and Senior Lecturer Department of Endocrinology, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK John Dean FRCGP St Peter s Andrology Centre, 145 Harley Street, London W1G 6BJ, UK 237

2 The Obstetrician & Gynaecologist Introduction Sexual dysfunction affects a large proportion of women at some point in their lives. Hypoactive sexual desire disorder (HSDD) is one of the most common types of female sexual dysfunction and it can affect women of all ages. It is defined as the persistent or recurrent deficiency or absence of sexual thought, fantasies or receptivity to sexual activity, which causes distress or interpersonal difficulties. 1 Despite the prevalence of sexual dysfunction, the subject is often not a priority for physicians, many of whom may lack training in the diagnosis and treatment of such disorders. In view of the degree of personal misery that sexual dysfunction can cause, it is perhaps surprising that so little attention is devoted to it. This review focuses on the prevalence, diagnosis and treatment of HSDD and investigates the role of testosterone as both a causative factor and a possible treatment for the disorder. Sexual response among women To understand HSDD, it is useful to be aware of the current models of sexual response of women. 2 Masters and Johnson initially proposed a linear model of sexual response consisting of four stages: excitement (arousal), plateau, orgasm and resolution. 2 Later, Helen Kaplan added the concept of desire and condensed the response into a triphasic process of desire, arousal and orgasm. 2 However, in 1997, Whipple and Brash-McGreer introduced a circular model of female sexual response which described pleasure and satisfaction during sexual experience leading to a seduction phase which facilitated the desire to engage in further sexual activity. 2 Subsequently, Basson described a nonlinear model of female sexual response, with initiation of sexual activity primarily based on intimacy rather than on spontaneous sexual drive. This process is influenced by both biological and psychological factors, as well as by a satisfactory outcome of previous sexual experience (Figure 1). 3 This model fits well with published observations regarding women s motivations for sexual activity. 4 Sexual desire is a complex issue and, in cases of sexual dysfunction, sexual desire may be influenced by a wide variety of factors (Box 1). The perception of desire is associated with feelings of attraction and fantasies. Sexual desire can be seen to consist of two main components: physical drive (biological) and motivation (psychological). Physical drive is modulated mainly by age, general health, hormone requirements and mood, whereas motivation is modulated by previous experiences and factors such as relationship quality and duration. Epidemiology The complex dynamics of desire and the multifactorial aetiology of HSDD make epidemiological research difficult. It is important to recall that HSDD is distinct from low sexual desire (which is often a normal life experience) and has a number of subtly different definitions in the literature. Epidemiological data should, therefore, be examined with caution and attention paid to the precise definitions of HSDD or low desire, the population studied and other variables. For example, the prevalence of low desire has been found to vary between 11% and 53%, depending on the population studied. 5 However, only 22 65% of these women reported the associated distress required for a diagnosis of HSDD. 5 Furthermore, one study 6 reported that duration of low desire also has an impact on apparent prevalence: low desire of short duration had a prevalence of 54%, compared with 16% for low desire of long duration. Figure 1 Non-linear model of female sexual response developed by Basson 3 238

3 A recent study 7 of 2467 women aged between 20 and 70 years used validated questionnaire instruments to assess both sexual function and associated distress, to determine the relationship between HSDD and ageing. The prevalence of low desire showed a positive correlation with age, whereas the distress associated with low desire showed a negative correlation; as a consequence, the prevalence of HSDD (low desire with associated distress) showed only a slight increase with age. The prevalence of HSDD among premenopausal women aged between 20 and 49 years was 7%, rising to 9% among naturally menopausal women aged between 50 and 70 years. The prevalence was higher among surgically menopausal women, i.e. 16% among women aged between 20 and 49 years and 12% among women aged between 50 and 70 years. The high incidence of HSDD observed among surgically menopausal women suggests that there may be a hormonal factor contributing to the development of HSDD. Recognition and diagnosis Primary care is ideally placed to take a holistic and integrated approach to sexual health and represents the first port of call for many women with sexual problems. The general practitioner (GP) is a trusted and accessible resource to women seeking advice about all aspects of health care. Furthermore, the discussion of sexual issues is familiar to GPs and would not normally be perceived as inappropriate or unwelcome by women consulting. Several aspects of primary healthcare team activity, such as contraceptive care, cervical screening and Well Woman services, provide opportunities to deliver sexual health care. However, primary care is not the only point at which women with HSDD present; many women consult gynaecologists in particular, with sexual dysfunction or concerns relating to it. Consequently, it is important for physicians across a range of disciplines to develop an understanding of the diagnosis and management of this condition. For a diagnosis of HSDD to be made, a reduction or absence of sexual desire and the presence of associated personal distress must be found, with personal distress being key to the diagnosis. The reduced desire should be beyond the normative changes that may occur with the life cycle and the duration of relationship. Minimal spontaneous sexual thinking, fantasising or desire ahead of sexual activity does not necessarily constitute disorder; indeed, for many women this is completely normal. However, when motivation to be sexual for any reason is minimal, or sexual stimulation does not cause arousal and concurrent desire to continue, then disorder may be present. 1 It is crucial to avoid basing such diagnosis on normal responses to circumstances such as excessive tiredness or the adverse effects of prescribed medication. External or contextual factors, such as distractions by children, work or attempting sexual intercourse at the end of the day Any one of the factors listed below can impact on a woman s sexual desire system, but they usually present comorbidly. Biological Ageing process Menopausal symptoms Mood and psychiatric conditions Medical conditions, medications and treatments Psychological Intrapersonal difficulties Misuse of alcohol, recreational drugs, food Sense of attraction/desirability as a woman Awareness of altered sexual needs, desires and changed experience of sex Relational Changes in dynamic of relationship: conflict, lack of intimacy, distancing Changes in family structure and caretaking role Socio-cultural Life events: loss, bereavement, retirement, financial insecurity Cultural attitudes, expectations and practices Religion (when one or both partners may be exhausted), should also be taken into account. Several validated instruments for diagnosing HSDD now exist. 8 For example, questionnaires such as the Brief Profile of Female Sexual Function (B-PFSF ) 9 have been validated in the clinical setting for the diagnosis of HSDD. Hand in hand with the use of such tools is the need to establish a detailed history, in order to identify comorbidities or external causes. Other sexual function problems experienced by both women and their partners may also be important. For example, women with low desire may experience associated arousal or orgasmic disorders and sexual pain. 10 Furthermore, premature ejaculation can affect sexual experience and relationship satisfaction 11 and women whose partners have erectile dysfunction are more likely to experience low desire. 12 Emotional and psychological impact of HSDD By definition, HSDD has a substantial emotional impact on those who experience it and the effects are diverse. To determine the impact of HSDD on the individual (and her partner), the clinician must assess the presenting features and subjective experiences in cultural and biopsychosocial contexts (Box 1). The predisposing, precipitating and/or maintaining nature of the various relevant factors should be positioned in a temporal relationship to the onset and nature of the sexual disorder. 13 Individuals vary in their propensity for sexual inhibition and excitation in the brain and HSDD may be protective and adaptive and, therefore, needs to be understood within the individual s intimate, social and cultural framework. Characterisation of problems presenting at these different levels is Box 1 Integrated model of sexual dysfunction 239

4 The Obstetrician & Gynaecologist Figure 2 Low sexual desire with associated distress strongly influences women s well-being and relationships 14 % HSDD Normal Concerned I was letting my partner down Unhappy Less feminine Angry Disappointed Hopeless Upset Inadequate Frustrated Insecure Sad Low self-esteem Troubled Ashamed Like a sexual failure Bitter crucial, as they have different implications for treatment. A woman may have sexual intercourse with a partner with a variety of objectives, including to increase emotional closeness; to evoke a sense of well-being; to feel more attractive, desirable and powerful; or to give and receive pleasure. 4 Equally, women may have sex to obtain or please a partner, or to manage a partner s moods. 4 Other wellrecognised motivations include avoiding the negative effects of infrequent intercourse, such as accusations of frigidity or of disinterest in a partner s needs, and fear of losing a partner if intercourse is not regular. 4 A woman with HSDD may, therefore, feel like a sexual failure both in terms of experiencing a lack of internal sexual drive or incentive for wanting sexual experiences, as well as worrying that she is not meeting the perceived or declared needs and expectations of her partner (Figure 2). 14 This can result in a loss of intimacy and attachment to her partner and may become a cause of unresolved friction in the relationship. Furthermore, sexual interest disorders frequently coexist with subjective arousal and genital arousal disorders among women, which can alter the motivational forces behind sexual desire. Such additional arousal problems can further add to a woman s sense of being a sexual failure. Communication skills It can be particularly complex to unravel the aetiology and impact of sexual desire disorders, as women frequently do not disclose the full extent of their sexual difficulties because of feelings of shame or fear of hurting their partner s feelings. However, an essential part of the history-taking process comprises both current and past sexual relationships. Unfortunately, talking about personal sexual matters, including sexual disorders and difficulties, is often an uncomfortable experience for both doctor and patient. Furthermore, in undergraduate education the teaching of communication skills does not always extend to sexual topics. 15 Importantly, in a recent review of the literature on clinicians handling of sexual issues, Cordingley et al. 15 identified that women are often reluctant to broach the subject of sexual function, but welcome their doctor raising the subject. 1 This implies that it may be good practice to initiate this conversation during consultations and that clinicians could benefit from specific training on discussing sexual topics with women. Hysterectomy and HSDD The impact of hysterectomy on sexual function has always been of great concern and a source of preoperative anxiety for women and their partners. Indeed, this concern seems justified in view of the increased incidence of HSDD among surgically menopausal women compared with premenopausal and naturally menopausal women. Unfortunately, women seldom articulate this concern and often it is not recognised or discussed by clinicians. Hysterectomy is one of the most common procedures performed by gynaecologists, with almost such procedures performed in England in , 16 suggesting that this issue is of high importance. It is good practice to provide written information on sexual function to women and their partners before hysterectomy, to enable them to understand the issues and raise any concerns. There are certain 240

5 preoperative factors that may be predictive of sexual dysfunction after hysterectomy, such as pre-existing sexual dysfunction, depression, poor relationship with the partner or lack of support. Postoperative risk factors include physical and hormonal changes and changes in the woman s perception of herself and her body image. 16 Equally, dissatisfaction with the indication or outcome of the operation are also risk factors. This underlines the importance of both preoperative counselling and psychological preparation for surgery and post-hysterectomy assessment and psychotherapy if indicated in most UK units none of these occur at present. There has been a considerable decline in the number of hysterectomies performed by the National Health Service, largely because of the increasing use of the levonorgestrel-releasing intrauterine system or LNG-IUS (Mirena, Bayer plc, Newbury, UK) for women with heavy periods. A recently published randomised, controlled study 17 compared the effects of hysterectomy or the LNG-IUS on sexual function among women with menorrhagia. The results demonstrated that sexual satisfaction increased and sexual problems decreased among women treated with hysterectomy, whereas satisfaction with the partner was reduced among women treated with the LNG-IUS. 17 Treatment of HSDD The multifactorial aetiology of HSDD means that the contributory factors will vary widely between women, indicating that there may be no single treatment option suitable for all. Taking a detailed history, therefore, allows treatment to be tailored to the individual. The treatment of HSDD should begin with an examination of possible aetiological factors, such as underlying medical conditions, which may need to be addressed. Subsequent referral to a specialist or sex therapist allows various options to be explored, such as cognitive behavioural therapy (CBT), psychosexual therapy, mindfulness, shortterm psychotherapy or couple therapy. If judged to be appropriate, a pharmacological approach may be taken. In view of the multifactorial aetiology of HSDD, a multifaceted approach to therapy is likely to be the most appropriate. Indeed, this is well supported by the literature, and a detailed review and case summary of this approach has been presented previously. 18 HSDD management from an endocrine perspective It has been proposed that androgens have a part in female sexual behaviour. They are involved with sexual desire, arousal and orgasm, as well as playing a key role in bone physiology and muscle mass. In particular, reduced levels of testosterone among women have been associated with loss of libido, reduced sexual activity, fatigue and diminished feelings of physical well-being. 19 In order to evaluate the role of testosterone in HSDD, it is important to understand the changes in testosterone levels that occur at the menopause. The production rate of testosterone among premenopausal women is approximately 300 g per day, but during the menopause the serum concentration of testosterone is reduced. 20,21 However, there is no further age-related decline in testosterone after the menopause and the postmenopausal ovary remains an important source of testosterone. In contrast, women who undergo bilateral oophorectomy, either before or after the menopause, experience a sudden and significant decline in testosterone levels, resulting in significant androgen deficiency. 22 Notably, a greater proportion of surgically menopausal women have low sexual desire compared with premenopausal or naturally menopausal women and such women are more likely to have HSDD. 23 This suggests that testosterone deficiency may be a causative factor for HSDD. However, because of the complexity of the endocrine system and interindividual variation, direct evidence of a link is difficult to discern. For example, a communitybased cross-sectional study 24 did not find any significant association between androgen levels and sexual dysfunction, concluding that the measurement of androgens in women is not an accurate diagnostic tool for sexual dysfunction. Despite this, there is accumulating evidence that the addition of testosterone to conventional hormone replacement therapy has a beneficial effect on sexual functioning among surgically menopausal women. 25 Although there is a certain degree of controversy surrounding this issue, several clinical trials have demonstrated significantly increased sexual desire associated with testosterone therapy Most of the early studies of testosterone therapy for HSDD used preparations designed for androgen replacement therapy among men with hypogonadism. Depot preparations, such as subcutaneous implants and injectable testosterone, may produce supraphysiological levels of testosterone among women, potentially resulting in unwanted virilising effects and hepatic impairment. Oral preparations also produce supraphysiological levels, with wide interindividual variation in testosterone levels and unpredictable absorption. 30 Consequently, transdermal testosterone delivery systems specifically designed for women, which deliver testosterone through the skin with a physiological pharmacokinetic profile, have been developed. The low-dose transdermal testosterone system (TTS) has been demonstrated in several clinical trials to be an effective treatment for HSDD among surgically menopausal 241

6 The Obstetrician & Gynaecologist women receiving concomitant estradiol therapy. A 300 g/day dose of testosterone (equivalent to endogenous levels of testosterone among premenopausal women), delivered transdermally, gave rise to significant improvements in sexual function, with increases in sexual desire and in frequency of satisfying sexual activity and decreased distress Furthermore, TTS at 300 g/day was not associated with significant virilising effects or other adverse events A study 31 of women using the 300 g/day TTS patch for 2 years also demonstrated that longer-term use did not confer an increased risk of adverse effects. Possible effects of low-dose testosterone on metabolism or on the breast and endometrium have not yet been elucidated. Following the menopause, either surgical or natural, the decline in estradiol levels may affect female sexual function because of associated hot flushes, sweats, sleep disturbance, mood changes and vaginal dryness. All women for whom these factors influence HSDD, therefore, should receive adequate estrogen replacement as part of a holistic approach to therapy. Conjugated equine estrogens and oral estrogens are not suitable: they cause a large increase in sex hormone-binding globulin, which decreases free testosterone levels. This may either blunt or ameliorate the action of testosterone. However, it is interesting to note that one study 31 of postmenopausal women undergoing testosterone therapy without concomitant estrogen reported significant improvements in sexual function. This suggests that testosterone therapy alone may represent a valuable treatment option for a wide range of HSDD sufferers, although further research is required. Discussion Sexual dysfunction is a considerable cause of unhappiness and distress, yet for many doctors it remains a subject about which they lack knowledge or are uncomfortable discussing. Hypoactive sexual desire disorder is characterised by reduced or absent sexual desire and associated personal distress. It is a common female sexual dysfunction, with significant numbers of women affected at some point in their lives. Unfortunately, women are often reticent with regard to sexual problems and may not mention them during consultations. However, many women appreciate their doctors introducing the topic, therefore, a key aim for gynaecologists should be the development of communication skills to facilitate open discussions on this subject. To avoid overdiagnosing HSDD, it is important to rule out lifestyle factors such as excessive tiredness, the effects of medication or comorbid sexual dysfunction. Validated tools, such as the B-PFSF, can be a useful aid to diagnosis. Sexual desire is complex and multifactorial, meaning that one size does not necessarily fit all when it comes to treating HSDD. It is, therefore, important to understand a woman s symptoms in a bio-psychosocial context. Taking a detailed history is an essential step in developing treatment strategies tailored to the individual. Women presenting with HSDD may be referred to a specialist or sex therapist, where a variety of short-term psychotherapy or psychosexual therapy interventions can be utilised. However, a pharmacological approach may also be considered, particularly for surgically menopausal women. Transdermal testosterone patches have been developed specifically for women, to deliver physiological levels of testosterone. Several clinical studies have demonstrated significant improvements in sexual activity with this therapy, with minimal androgenic adverse effects. 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