Sexual Desire Disorders

Chapter 6 Sexual Desire Disorders study published in 1999 found that up to 30% of A women aged 18 to 59 experience lack of sexual interest. 1 Low sexual desire in women is strongly associated with women s decreased physical and emotional satisfaction with their sexual relationship, as well as with lowered general happiness with their partners (adjusted odds ratios ranging from 2.61 to 4.31, P < 0.05). The DSM-IV defines hypoactive sexual desire disorder as consisting of persistently, or recurrently deficient (or absent) sexual fantasies and desire for sexual activity that cause marked distress or interpersonal difficulty for the woman and that is not better explained by another medical, psychological, substance-related, or other sexual diagnosis. 2 In the PRESIDE study, it was found that 8.9% of American women aged 18 to 44, 12.3% aged 45 to 64, and 7.4% of those over 65 years reported decreased sexual desire accompanied by such distress. 3 HSDD symptoms in the PRESIDE study correlated with age, race, marital status, partner status, employment, and educational level. For example, older women were more likely than younger women to report lack of interest in sex, but younger women were more likely to be distressed by lack of interest. Medical conditions associated with HSDD included depression, thyroid problems, anxiety, and urinary incontinence. Women under age 45 who had undergone oophorectomy had the highest prevalence of HSDD at 20% to 26%. 4,5 Sexual desire problems strongly correlate with decreased arousal, orgasm, and pleasure, indicating that low desire is often associated with and overlaps with other sexual difficulties. 6,7 Decreased sexual desire correlates strongly with chronic pelvic pain. 8 ASSESSMENT OF WOMEN S HYPOACTIVE SEXUAL DESIRE DISORDER Models Sexual desire is initiated in the brain, which has been primed with sex steroids, including androgens, estrogens, and progestins. 9,10 The limbic system, with its connections to the hypothalamus, medial pre-optic area of the thalamus, amygdala, tegmentum, and anterior cingulated and medial frontal cortex, is core to normal sexual function. The main models of female sexual response are described in Chapter 2. While the DSM-IV has separate categories for HSDD, (female sexual arousal disorder), and female orgasmic disorder, these distinctions are frequently blurred clinically, and HSDD and female sexual arousal disorder often coexist, as do female sexual arousal disorder and female orgasmic disorder. As HSDD often coexists with other sexual concerns, deciding which is primary, and taking into account other contributing factors, is an important diagnostic challenge. An appropriate management plan requires a comprehensive assessment of a woman s current health and life, the history of her concern, the role of her partner(s), and her level of distress in addition to medical and laboratory examinations. 11 17 Although many scales have been validated for assessment of women s sexual concerns, 18,19 few are designed for use by health care providers who are not experts in managing female sexual dysfunction. The Decreased Sexual Desire Screener is one such tool 20 that specifically focuses on HSDD (Appendix). The woman is asked 4 questions to determine whether she potentially meets the criteria for the DSM-IV diagnosis, and a fifth question to assess other factors that would preclude the diagnosis of HSDD (including other medical and psychological conditions; medications, drugs and alcohol; reproductive life stages, including pregnancy and menopause; other sexual dysfunctions, including dyspareunia; relational and/or partner s sexual problems; and other stressors). A positive screen has an 85% sensitivity and specificity when compared with a standard interview by an expert, and non-expert clinicians thought it adequately diagnosed HSDD in 93% of patients. 20 When distressing low desire is diagnosed, the next step is to determine the factors that might be contributing to the problem. The following biological, psychological, relational, and sociocultural factors can all be at play. 17 Biological Factors Affecting Women s Sexual Desire General medical illness and medications. 9,15,17,21 24 Cardiovascular problems 25,26 S48 AUGUST JOGC AOÛT 2012

CHAPTER 6: Sexual Desire Disorders Endocrine disorders Diabetes 21,27 Thyroid disorders 26 Hypothalamic pituitary ovarian disorders Menopause 3,5,11,28 30 Neuropsychopharmacology 31,32 Psychological Factors Affecting Women s Sexual Desire 14,22,33 42 There are many lifestyle and health issues that can affect a woman s level of interest in sexual activity. Past sexual trauma, mood disorder, stress, fatigue, and medication can have an effect on desire. Treatment of depression often contributes to decreased desire, especially if SSRIs are prescribed. Relationship Factors Affecting Women s Sexual Desire 43 48 The quality of a woman s relationship can affect her sexual interest and function. The level of intimacy, the partner s sexual interest and function, as well as his or her physical and mental health can affect the woman s sexual interest and function. Role of Testosterone in Treating Women s HSDD Testosterone therapy has been used for the treatment of sexual disorders in women since 1938. 49 A quarter century has gone by since Sherwin et al. 50 in Montreal showed that androgens help maintain sexual function in surgically menopausal women. Alexander et al. 51 reviewed available RCTs of hormonal therapies, including testosterone, on female sexual function. Hubayter and Simon 52 have reviewed potential testosterone formulations for women with postmenopausal HSDD that include pills, patches, creams, gels, transdermal sprays, and vaginal rings. A Cochrane Review 53 showed that adding testosterone to hormone therapy improves sexual function for postmenopausal women. Testosterone can help premenopausal women s HSDD 54 ; however, trials to date have been small, and safety data are sparse. Controversies in Measuring Testosterone Levels in Women The measurement of testosterone, free-testosterone, and sex hormone binding globulin, and their role in the assessment of low sexual desire are a source of controversy in sexual medicine. In the peripheral blood, 66% of testosterone has high affinity binding to SHBG, 30% is loosely bound to albumin, and only 2% to 3% is free testosterone. The combined albumin-bound and free portion of testosterone is called bioavailable testosterone and is thought to be the fraction that is able to enter target cells and exert its biological activity through binding to intracellular androgen receptors. 55 The SHBG bound fraction is not easily available to the tissues. There is good correlation between free testosterone and bioavailable testosterone, except in acute illness, pregnancy, and chronic illness, such as cirrhosis of the liver. Investigators are concerned about the accuracy of measuring these levels in women using currently available assays, which vary by 77%. 56 Measurement is unreliable in the low levels seen in women s sera, leading to overestimation of testosterone concentrations by 46%. None of the immunoassays were felt to have sufficient reliability to be used for children and women. 57 A more sensitive technique may be the free androgen index, which measures testosterone/shbg 100. 58 60 Testosterone Therapy for Women with HSDD The North American Menopause Society issued a position statement in 2005 regarding the role of testosterone in postmenopausal women. They stated that postmenopausal women may be candidates for testosterone therapy if they present with HSDD and have no other identifiable cause for their sexual concerns. 61 The North American Menopause Society recommended transdermal patches or gels may be preferred to prevent first-pass liver damage. Because of the lack of safety and efficacy trials, they could not recommend the use of testosterone without concomitant estrogen (and if indicated, progesterone) therapy. No level of serum testosterone is considered diagnostic for HSDD. Many questions remain about the use of androgen therapy for women, including premenopausal women with HSDD, 62 and about the role of androgens in natural menopause. The Women s Health Initiative study raised questions about the safety of estrogen and progestin therapy in menopause 63 and has created anxiety by extrapolation, without evidence, to possible adverse effects of androgens. At this point, no testosterone products are currently licensed for the treatment of female sexual dysfunction in North America. 64 Testosterone patches developed for women who have HSDD associated with bilateral oophorectomy have been licensed in Europe and elsewhere. 3 The Endocrine Society published a clinical practice guideline on androgen therapy in women in 2006. 65 At that time, they recommended against making a diagnosis of AUGUST JOGC AOÛT 2012 S49

Female Sexual Health Consensus Clinical Guidelines androgen deficiency, because there is neither a well-defined clinical syndrome nor normative data on testosterone or free testosterone concentrations in blood in women across their lifespans that can be used to define the disorder. While acknowledging that evidence exists for short-term efficacy of testosterone in selected populations, such as surgically menopausal women, they recommend against the generalized use of testosterone by women because the indications are inadequate and evidence of safety in long-term studies is lacking. 65 They emphasized that female sexual dysfunction results from the interplay of personal, interpersonal, contextual and medical factors and that in a particular woman it may, or may not be, due to changing androgen levels. Dennerstein et al. 29 showed that prior sexual function and relationship factors were more important than androgen levels in women transitioning through natural menopause. They cautioned that assays used to measure the lower range of women s testosterone levels lack sensitivity and precision. Naturally menopausal women with HSDD have benefited from transdermal testosterone along with estrogen (and progestin as needed for endometrial protection). 66 Given the concerns expressed in the Women s Health Initiative study, many women are reluctant to take estrogen therapy. A trial, with 814 women, of testosterone patches without concurrent estrogen therapy also showed benefit across all of the domains of sexual function. 67 In the treatment arm, breast cancer was diagnosed in 4 women over the 2 years of the trial (1 had symptoms before randomization, and another developed breast cancer within 4 months of starting the trial), and in the control group, no breast cancer was diagnosed. This was within the realm of a chance result. The accompanying editorial acknowledged a dose response benefit from the use of the testosterone patch, but expressed caution, and a need for further elucidation of whether there is a link between testosterone therapy and breast cancer. 68 Female-to-male transsexuals have been treated with supraphysiological testosterone in the male range for decades. Although their situation is not directly comparable to that of women treated within the female range, these patients can provide data regarding potential safety issues. Most female-to-male transsexuals show endometrial atrophy, but increased endometrial hyperplasia has been shown in some; however, no increase was observed in total cancer mortality. 69 Abnormal bleeding patterns need to be investigated. A long-term European study of 365 femaleto-male transsexuals on male levels of testosterone therapy for more than a decade showed no increased mortality when compared with the general population. 69 In a 2010 review of the literature on testosterone safety in femaleto-male transsexuals, Traish and Gooren 57 concluded that pharmacological doses of testosterone had no serious adverse effects, including breast cancer and cardiovascular disease, and suggested that the risks associated with the much lower physiological doses of testosterone used in the treatment of women with HSDD would be even more minimal. In 2009, the Third International Consultation on Sexual Medicine 30 updated recommendations 16 on the use of testosterone for postmenopausal women with HSDD. 70 The International Consultation on Sexual Medicine suggested that testosterone therapy can be effective for HSDD, that the decision to implement testosterone therapy needs to be individualized with patients making an informed choice, and that transdermal delivery is best to reduce adverse effects. They noted that data were not adequate to support use of testosterone for pre- and perimenopausal women. As long-term safety data were lacking, the International Consultation on Sexual Medicine did not support long-term therapy. They recommended annual health monitoring, with breast and pelvic examinations and mammograms. The British Society for Sexual Medicine 71 guidelines support the use of testosterone in appropriate patients. They recommend lipid and metabolic monitoring, and routine breast screening, including mammography, for patients taking androgens, but do not suggest increased cervical screening. Data on the safety and risks of the use of testosterone therapy continue to accumulate. Table 6.1 lists some of these risks for oral, parenteral, supraphysiological (female-to-male transsexuals compared with patients with polycystic ovary syndrome), and transdermal therapies treating to the premenopausal physiological range. Testosterone therapy for women with HSDD is off label in Canada. Women need to understand possible benefits and risks and give informed consent to the use of any such therapies. No androgens are licensed in Canada for the treatment of women with HSDD. Integrating Treatment for Women s Hypoactive Sexual Desire Disorder Therapies integrating medical, psychological, and relational treatments for a woman s decreased desire hold promise for helping women and their partners better deal with HSDD. Neither medical nor psychological therapies alone have been able to provide a lasting solution for many women. Integration of the 2 may lead to better outcomes. 39 S50 AUGUST JOGC AOÛT 2012

CHAPTER 6: Sexual Desire Disorders Table 6.1. Adverse effects of androgen therapy for women. Risk Supraphysiological. (female-to-male transsexuals) Physiological treatment. (transdermal) Hirsutism 62,72,73 100% 7% Tt patch vs. 5% placebo, 73 up to 30% 67 Acne 62,73 9% 300 μg vs. 7% placebo 73 Skin rash (patches) 66 30% mild 66 Virilization clitoromegally 67,74 + < 1% 67 Vocal cord changes + Metabolic syndrome & insulin Increased in PCOS, but NOT. 60,62 resistance 60,62,75 FTM transsexuals 75 HDL decrease 73 73 + 75 73 Cardiac 57,66,67,74,76 57 66,67 Breast cancer 60,66,74,76,77 60,76 60,66,77 Endometrial stimulation 60,62,66,76,78 +/ 60 78 62,66,76 Emotional lability/hostility 76 76 + : increased risk : no increased risk Summary Statements 29. Lowered desire accompanied by distress (hypoactive sexual desire disorder) is highly prevalent and is most common in mid-life. (II-1) 30. Treating medical, psychological, and relationship problems, addressing sociocultural issues, and providing androgen therapy when appropriate can be effective in helping women and their partners dealing with hypoactive sexual desire disorder. (I) 31. Distressing female hypoactive desire is contextdependent, and this needs to be considered in treatment planning. A woman s sense of connection to her partner and her own psychological and physical health are more closely linked to desire than are estrogen and testosterone. (II-2) Recommendations 32. Health care providers should give women the opportunity to discuss their sexual concerns at the beginning of a therapeutic process. (III-A) 33. Health care providers should consider caring for women with hypoactive sexual desire, rather than referring them, even if they require the assistance of an interdisciplinary team. (III-A) 34. Well-designed and adequately powered studies should be carried out to assess the health benefits and long-term risks of androgen therapies for women with hypoactive sexual desire. (III-L) REFERENCES 1. Lauman EO, Paik A, Rosen RC. Sexual dysfunction in the United States. Prevalence and predictors. JAMA 1999;281:537 44. 2. American Psychiatric Association; DSM-IV-TR. Diagnostic and statistical manual of mental disorders: DMS-IV-TR. 4th ed., text revision. Washington DC: 2000. 3. Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Sexual problems and distress in United States women. Prevalence and correlates. Obstet Gynecol 2008;112: 970 8. 4. West SL, D Aloisio AA, Agans RP, Kalsbeek WD, Borisov NN, Thorp JM. Prevalence of low sexual desire and hypoactive sexual desire disorder in a nationally representative sample of US women. Arch Intern Med 2008;1168(13):1441 9. 5. Leiblum SR, Koochaki PE, Rodenberg CA, Barton IP, Rosen RC. Hypoactive sexual desire disorder in postmenopausal women: US results from the Women s International Study of Health and Sexuality (WISHes). Menopause 2006;13(1):46 56. 6. Dennerstein L, Koochaki P, Barton I, Graziottin A. Hypoactive sexual desire disorder in menopausal women: a survey of Western European women. J Sex Med 2006;3:212 22. 7. Mimoun S, Wylie K. Female sexual dysfunctions: definitions and classification. Maturitas 2009;63:116 8. 8. Verit FF, Verit A. Validation of the female sexual function index in women with chronic pelvic pain. J Sex Med 2007;4:1635 41. 9. Rees PM, Fowler CJ, Maas CP. Sexual dysfunction 2: sexual function in men and women with neurological disorders. Lancet 2007;369:512 25. 10. Pfaus JG. Pathways of sexual desire. J Sex Med 2009;6:1506 33. 11. Basson R. Female sexual response: the role of drugs in the management of sexual dysfunction. Obstet Gynecol 2001;98(2):350 3. 12. Basson R, Althof S, Davis S, Fugl-Meyer K, Goldstein I, Leiblum S, et al. Summary of the recommendations on sexual dysfunctions in women. J Sex Med 2004;1(1):24 34. AUGUST JOGC AOÛT 2012 S51

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Shufelt CL, Braunstein GD. Testosterone and the breast. Menopause Int 2008;14:117 22. 78. Perrone AM, Cerpolini S, Salfi NCM, Ceccarelli C, di Giorgi LB, Formelli G, et al. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med 2009;6:3193 200. AUGUST JOGC AOÛT 2012 S53