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Emerging Perspectives on the Science  and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicin

A New Frontiers Program on Women’s Health. Emerging Perspectives on the Science  and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicine and Primary Care Perspective. Program Chairman and Moderator Anita  H.  Clayton,  MD David C Wilson Professor

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Emerging Perspectives on the Science  and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicin

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  1. A New Frontiers Program on Women’s Health Emerging Perspectives on the Science and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicine and Primary Care Perspective Program Chairman and Moderator Anita  H.  Clayton,  MD David C Wilson Professor Department of Psychiatry & Neurobehavioral Sciences Professor of Clinical Obstetrics & Gynecology University of Virginia Charlottesville, VA

  2. Program Faculty PROGRAM CHAIRPERSON Anita H.  Clayton,  MD David C Wilson Professor Department of Psychiatry & Neurobehavioral Sciences Professor of Clinical Obstetrics & Gynecology University of Virginia Charlottesville, VA Jennifer E. Frank, MD, FAAFP Assistant Professor Department of Family Medicine University of Wisconsin School of Medicine and Public Health Appleton, Wisconsin Sheryl Kingsberg, PhD Division Chief, Behavioral Medicine Program University Hospitals Associate Professor of Medicine Case Western Reserve University Cleveland, Ohio Lori Brotto, PhD Assistant Professor Department of Obstetrics and Gynecology University of British Columbia Vancouver, BC

  3. A New Frontiers Program on Women’s Health Addressing Current Challenges in Female Sexual Disorders What Internal Medicine Specialists Need to Know about HSDD Program Chairman and Moderator Anita  H.  Clayton,  MD David C Wilson Professor Department of Psychiatry & Neurobehavioral Sciences Professor of Clinical Obstetrics & Gynecology University of Virginia Charlottesville, VA

  4. A New Frontiers Program on Women’s Health Clinical focus Prevalence and pathophysiology of HSDD Communication strategies Differential diagnoses Intervention and management

  5. Case Example • 26-year-old MWF presents with 1 year history of decreased libido, some problems with vaginal lubrication, and diminished orgasmic capacity. No pain with intercourse. • Change in sexual function since marriage 4 years ago, but relationship still strong • 1 year post-partum with mild depressive symptoms since delivery • No general health problems • On oral contraceptives for birth control

  6. A New Frontiers Program on Women’s Health Hypoactive Sexual Desire DisorderPrevalence and Barriers to Recognition in the Primary Care Setting Sheryl A. Kingsberg, Ph.D Chief, Division of Behavioral Medicine University Hospitals Case Medical Center Professor, Department of Reproductive Biology Case Western Reserve University School of Medicine Cleveland OH

  7. “Normal” Female Sexuality Defined by Cultural Norms • Historically given little attention • Victorian era: discovery that female orgasm irrelevant to conception • 2008: women’s sexuality hits ‘Primetime’ but not quite its ‘Prime’

  8. Human Sexual Response: Classic Models • Excitement • Plateau • Orgasm • Resolution Desire Divided Arousal Linear progression Masters WH, Johnson VE. Human Sexual Response. Boston, Mass: Little Brown; 1966. Kaplan HS. The New Sex Therapy. 1974.

  9. Female Sexual Response Cycle Orgasm Plateau Resolution Excitement Resolution Resolution (B) A B C (C) (A) Orgasm Plateau Excitement Adapted from Masters WH, Johnson VE. Human Sexual Inadequacy. Little Brown; 1970.

  10. Female Sexual Response Cycle Seeking Out and Being Receptive to Emotional Intimacy Emotional and Physical Satisfaction Sexual Stimuli Spontaneous Sexual Drive Arousal and Sexual Desire Sexual Arousal Biologic Psychological Basson R. Med Aspects Hum Sex. 2001;1:41-42.

  11. Women’s Endorsement of Models of Female Sexual Response • The Nurses’ Sexuality Study, N=133 • Equal proportions of women endorsed the Masters and Johnson, Kaplan, and Basson models of female sexual response as representing their own sexual experience. • Women endorsing the Basson model had significantly lower FSFI domain scores than women who endorsed either the Masters and Johnson or Kaplan models. Michael Sand, PhD, MPH, and William A. Fisher, PhD, JSM, 2007 4: 708-719

  12. Biopsychosocial Model of Female Sexual Response (e.g., physical health, neurobiology, endocrine function) (e.g., performance anxiety, depression) Biology Psychology (e.g., quality of current and past relationships, intervals of abstinence, life stressors, finances) (e.g., upbringing, cultural norms and expectations) Sociocultural Interpersonal 1. Rosen RC, Barsky JL. Obstet Gynecol Clin North Am. 2006;334:515-526.

  13. US Adult Women Are Sexually Active* 60-94 18-29 30-39 40-49 50-59 (n=362) (n=451) (n=271) (n=443) (n=473) Age Ranges Random Digital Dialing Survey of Women 18-94 Years Old (N=2000)† 100 70 66 70 65 60 50 46 US Women Sexually Active (%) 40 30 20 20 10 0 *Sexually active was defined as oral (active or receptive), vaginal, or anal intercourse in the past 3 months. †Age-adjusted percentages. Patel D, et al. Sex Trans Dis. 2003;30(3):216-220.

  14. DSM-IV-TR Classification of FSDs

  15. DSM-IV TR Criteria for FSD Sexual complaint or problem in desire, arousal, orgasm, or sexual pain: Judgment of severity of sexual symptom is made by the clinician, talking into account factors that affect sexual functioning, such as age and the context of the person’s life The disturbance causes marked distress or interpersonal difficulty The sexual dysfunction is not: Better accounted for by another primary psychiatric disorder (except another Sexual Dysfunction) Due exclusively to the direct physiological effects of a substance (eg, drug of abuse, medication) or a general medical condition American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Ed, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.

  16. Overlap of FSDs Sexual Desire Disorders Sexual Arousal Disorder Orgasmic Disorder Dyspareunia Vaginismus Basson R, et al. J Urol. 2000;163:888-893.

  17. Prevalence of FSD: A Historical Perspective Sexual Dysfunction in the United States* • OBJECTIVES: Assess the prevalence and risk of experiencing sexual dysfunction in men and women • NOT ASSESSED: Distress or interpersonal difficulty • POPULATION: 1749 women and 1410 men 18-59 years of age • RESULTS: 43% of women reported sexual dysfunction 100 Prevalence of Sexual Dysfunction in Women by Latent Class 50 43 40 30 22 Women (%) 20 14 7 10 0 Total for Sexual Low Sexual Arousal Pain Dysfunctions Desire Subsets for Sexual Dysfunctions Assessed Assessed *Sexual problems were measured in this study. NHLHS data on critical symptoms do not connote a clinical definition of sexual dysfunction. Laumann E, et al. JAMA. 1999; 281(6):537-544.

  18. Prevalence of FSD: PRESIDE • OBJECTIVES: Estimate the prevalence of self-reported sexual problems (any, desire, arousal, and orgasm), the prevalence of problems accompanied by personal distress, and describe related correlates • NOT DETERMINED: Whether low desire with sexually related personal distress was primary or secondary to another illness; pain was not assessed • POPULATION: 31,581 US female respondents ≥18 years of age from 50,002 households • RESULTS*: Response rate was 63% (n=31,581 / 50,002) Prevalence of Female Sexual Problems Associated With Distress 100 50 43.1 45 37.7 40 35 Sexual Problems US Women (%) 30 25.3 Distressing Sexual Problems 25 21.1 20 15 11.5 9.5 10 5.1 4.6 *All results are US population age-adjusted. 5 0 Desire Arousal Orgasm Any Shifren JL, et al. Obstet Gynecol. 2008;112(5):970-978.

  19. Prevalence of Sexual Problems Associated with Distress (PRESIDE) Shifren J et al Obstetrics & Gynecology, 2008, 112(5).

  20. Prevalence of Low Sexual Desire and Hypoactive Sexual Desire Disorder Nationally Representative Sample of US Women West SL et al Archives of Internal Medicine, 2008

  21. Decreased Sexual Desire With Distress Negatively Impacts Women’s Lives Decreased sexual desire is associated with negative effects including:1,2 Poor self-image Mood instability Depression Strained relationships with partners 1. Shifren JL, et al. Obstet Gynecol. 2008;112(5):970-978. 2. Leiblum SR. Menopause. 2006;13(1):46-56.

  22. Hypoactive Sexual Desire Disorder (HSDD) • Persistent or recurrent deficiency or absence of sexual thoughts, fantasies and/or desire for, or receptivity to, sexual activity • Causes marked personal distress or interpersonal difficulties • Not better accounted for by another primary disorder, drug/medication, or general medical condition

  23. Components of Sexual Desire • Drive: • Sex steroids and neurotransmitters play a role in modulating sexual desire, drive, and excitement • Expectations, beliefs, and values • Motivation Hull EM, et al. Behav Brain Res. 1999;105:105–116. Levine S. Sexual Life, 1994

  24. Social Psychology Theories: Understanding Psychosocial Aspects of Female Sexual Desire • Self-Perception Theory • People make attributions about their own attitudes by relying on observations of external behaviors (Bem, 1965) • Wundt's schema of sensory affect (aka Kingsberg’s Ice-Cream Analogy) • Increases of stimulus intensity above threshold are felt as increasingly pleasant up to a peak value beyond which pleasantness falls off through indifference to increasing unpleasantness.

  25. Prevention and Treatment of Sexual Problems ASK! You cannot treat a problem if you don’t know it exists

  26. In PRESIDE About One-Third of Women With a Distressing Sexual Problem Sought Formal Care Type of Help-Seeking (n=3239) 14.5%Did notseek help Formal 34.5% 9.1%Anonymous Informal41.9% Formal=HCP; informal=anyone other than an HCP. Shifren JL, et al. J Women’s Health. 2009;18(4)461-468.

  27. Physician Questioning Increases Patient Reporting of Sexual Dysfunction 40 30 20 10 0 19% Patients (%) 3% Spontaneous Reporting After Reporting Direct Inquiry N=887. Bachmann GA, et al. Obstet Gynecol. 1989:73:425-427.

  28. Physician-Based Barriers • Lack of training/Inadequate knowledge or skills1 • Lack of awareness of associated comorbid conditions • “Improving quality of life” may not be considered a high priority2 • Time constraints3 • Underestimation of prevalence • No FDA approved treatments for female sexual dysfunction 1Broekman CPM, et al. Int J Impot Res. 1994;6:67-72. 2Eid JF, et al. Cliniguide® to Erectile Dysfunction. Lawrence DellaCorte Publications, Inc; 2001. 3Baum N, et al. Patient Care. Spring 1998(suppl):17-21.

  29. Training Is Not Preparing HCPs To Be Informed in the Area of FSD Curriculum Time (Hours) Dedicated to Human Sexual Health Education (N=101)* *Human sexual health education was not specifically defined in the survey but included: type of educational experiences, disciplines, subject and topics areas, clinical program, continuing medical education, total number of hours, amongst others. Solursh DS, et al. Int J Impot Res. 2003;15(suppl 5):S41-S45.

  30. Most HCPs Have Little or No Confidence in Screening for or Diagnosing HSDD Respondents who had not screened or diagnosed patients with HSDD Web-Based Survey Consisting of Residents and Faculty in an Academic Primary Care Clinic (N=53; 41.5% women, 58.5% men) 90 HCPs who felt little or no confidence in 91 diagnosing HSDD HCPs who had little confidence in 57 ability to manage HSDD 0 20 40 60 80 100 HCPs (%) Harsh V, et al. J Sex Med. 2008;5(3):640-645.

  31. HCPs Perceive Patients as Reluctant to Bring Up Sexual Issues Doesn't want to waste doctors' time Difficult area to discuss Indirect presentation (hidden by other symptoms) Patient thinks it's “normal”/lackof knowledge and awareness Patients‘ reluctance/reticence/embarrassment Patient Barriers Identified by HCPs in the Management of Sexual Dysfunction (n=133 HCPs) 2.2 4.3 5.4 15 73.1 0 20 40 60 80 Total Number of Barriers (%)* *Total number of patient barriers=93; most HCPs identified more than one barrier. Humphrey S, et al. Fam Pract. 2001;18(5):516-518.

  32. HCP Comfort Level Impacted byPatient Gender Differences in Physician Comfort Level Influenced by Gender (N=69) 50* Physician self-report ofdiscomfort with male patients 19 Female physicians (n=29) 12* Physician self-report ofdiscomfort with female patients Male physicians (n=40) 35 45 Physician perception ofmale patient discomfort 40 24* Physician perception offemale patient discomfort 53 0 10 20 30 40 50 60 70 *P<0.05. Physicians (%) Burd ID, et al. J Sex Med. 2006;3(2):194-200.

  33. Open-Ended Questions Require narrative elaboration, not yes/no or short response Directive open-ended questions focus the topic Open the door to context, understanding, & feelings Doctors ask ≈1 question/min; >90% are closed-ended Physicians can increase use open-ended questions & improve Assessment of functional impairment Adherence Patient satisfaction Open-ended dialog is efficient (≈ 90 seconds for impairment dialog)4 & effectively reveals syndromal symptoms Lipton et al. JGIM 2008;23:1145-1151. Hahn et al. Curr Med Res Opin 2008;24:1711-1718.

  34. The Challenges of the Differential Diagnosis In Order to Meet the Diagnostic Criteria for HSDD: • Ensure that sexual dysfunction IS NOTdue exclusively to the • Physiological effects of a specified general medical condition (eg, neurological, hormonal, metabolic abnormalities)* • Ensure that sexual dysfunction IS NOTdue exclusively to the • Physiological effects of substance (prescribed or illicit) abuse† • HSDD and concomitant sexual dysfunctions (both should be noted) • Also, additional diagnosis of HSDD IS NOTmade if low sexual desire is better accounted for by another Axis I disorder (eg, major depressive disorder, obsessive-compulsive disorder, posttraumatic stress disorder) • HSDD diagnosis may be appropriate if low desire predates the Axis I diagnosis *If it is, refer to the diagnosis: Sexual Dysfunction Due to a General Medical Condition. †If it is, refer to the diagnosis is Substance-Induced Sexual Dysfunction. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text Revision, Washington, DC: American Psychiatric Press; 2000.

  35. The Challenges of Differential Diagnosis Mood disorders1 Major depression Bipolar illness Anxiety disorders2,3 Psychotic illness4 Hypertension Neurological disorders6 Endocrine disorders7 Diabetes, thyroid disorders, hyperprolactinemia7 Psychiatric Illnesses and General Health Factors May Affect Sexual Function • Urological problems8 • Sexually transmitted infections9 • Gynecological problems • Post-partum10 • Other chronic illness • Rheumatoid arthritis11 • Psoriasis12 • Breast cancer13 1. Casper RC, et al. Arch Gen Psychiatry. 1985;42:1098-1104. 2. van Lankveld JJ, Grotjohann Y. Arch Sex Behav. 2000;29:479-498. 3. Shifren J, et al. Obstet Gynecol. 2008;112:970-978. 4. Friedman S, Harrison G. Arch Sex Behav. 1984;13:555-567. 5. Okeahialam BN, Obeka NC. J Natl Med Assoc. 2006;98:638-640. 6. Rees PM, et al. Lancet. 2007;369(9560):512-525. 7. Bhasin S, et al. Lancet. 2007;369(9561):597-611. 8. Aslan G, et al. Int J Impot Res. 2005;17:248-251. 9. Smith EM, et al. Infect DisObstet Gynecol. 2002;10(4):193-202. 10. Baksu B, et al. IntUrogynecol J. 2007;18:401-406. 11. Abdel-Nasser A, Ali E. ClinRheumatol. 2006;25:822-830. 12. Sampogna F, et al. Dermatology. 2007;214:144-150. 13. Mathias C, et al. Ann Oncol. 2006;17(12):1792-1796.

  36. Other drug classes The Challenges of Differential Diagnosis Numerous Medications are Associated with Female Sexual Problems Psychotropic drug classes/agents • Chemotherapeutic agents6 • Aromatase Inhibitors7 • Triglyceride-lowering agents8 • Histamine receptors (H2) blockers9 • Weight loss agents10 • Antiepileptics11 • Immunosuppresants12 • Central alpha-adrenergic agonists13 • Opioid antagonists14 • Antipsychotics1 • SSRIs2 • Lithium3 • SNRIs4 • Tricyclic antidepressants5 1. Liu-Seifert H, et al. NeuropsychiatrDis Treat. 2009;5:47-54. 2. Serretti A, Chiesa A. J ClinPsychopharmacol. 2009;29:259-266. 3. Lithium carbonate [package insert]. 2003. 4. Venlafaxine hydrochloride [package insert]. 2003. 5. Imipramine hydrochloride [package insert]. 2007. 6. Fobair P, Spiegel D. Cancer J. 2009;15(1):19-26. 7. Mok K, et al. Breast. 2008;17(5):436-440. 8. Fenofibrate [package insert]. 2008. 9. Ranitidinehydrochloride [package insert]. 2009. 10. Sibutramine hydrochloride monohydrate [package insert]. 2009. 11. Rees PM, et al. Lancet. 2007;369:512-525. 12. Muehrer RJ, et al. West J Nurs Res. 2006;28:137-150. 13. Clonidine [package insert]. 2009. 14. Naltrexone hydrochloride [package insert]. 2003.

  37. Thank you Sheryl.kingsberg@uhhospitals.org

  38. A New Frontiers Program on Women’s Health Pathophysiology of Decreased Desire in Premenopausal Women Psychological, Pharmacologic, and Neurobiological Mechanisms Program Chairman and Moderator Anita  H.  Clayton,  MD David C Wilson Professor Department of Psychiatry & Neurobehavioral Sciences Professor of Clinical Obstetrics & Gynecology University of Virginia Charlottesville, VA

  39. Objectives At the conclusion of this activity, participants should be able to: • Describe the psychological, pharmacological and neurobiological factors affecting desire in premenopausal women

  40. What’s it all about anyhow? • Psychological/social/emotional • Physiological/biological: interactions of sex steroids and neurotransmitters • Cognitive: thoughts, fantasies, satisfaction • Cultural American Psychiatric Association, DSM IV, 1994

  41. Central Effects on Sexual Function - DESIRE - - + SUBJECTIVEEXCITEMENT + + + + + + - + +/- 5-HT progesterone testosterone estrogen dopamine (DA) 5-HT prolactin norepinephrine (NE) oxytocin ORGASM Modified from Clayton AH. Psych Clin NA 2003; 26:673-682 Cohen AJ. AD-induced SD associated with low serum free testosterone 2000. http://www.mental-health-today.com/rx/testos.htm

  42. } • Estrogen • Testosterone • Progestin maintain genital structure and function gonads adrenals - - - VASOCONGESTION SENSATION + + + + + Clitoral andpenile tissue Peripheral Effects on Sexual Function 5-HT Nitric Oxide (NO) 5-HT2A NE 5-HT Prostaglandin E Cholinergic fibers Clayton AH. Psychiatric Clinics of North America 2003; 26:673-682

  43. Physiology of Sexual Function • Desire: • Excitatory: dopamine, norepinephrine, testosterone, estrogen • Inhibitory: serotonin, prolactin • Arousal: • Excitatory: dopamine, norepinephrine, nitric oxide, acetylcholine, estrogen, testosterone • Inhibitory: serotonin, prolactin Pfaus JG. J Sex Med 2009;6:1506-1533.

  44. Influences on Sexual Functioning • Neurobiological • Reproductive endocrinology (ie. anything that lowers testosterone such as hyperprolactinemia, opiates, menopause) • General health status/illness (e.g. fatigue)1 and co-morbidities • Medication/substance use • Psychological • Body image (e.g. obesity) • Psychological/relationship issues, partner availability/aging1 • Fears (e.g. pregnancy, infertility, STD, history of sexual abuse/trauma, cultural practices) 1Meston C. Western Journal of Medicine 1997;167(4):285-290

  45. DSM-IV TR Criteria for HSDD • Sexual complaint or problem in sexual desire and/or fantasies • The judgement of severity of the sexual symptom is made by the clinician, taking into account factors that affect sexual functioning, such as age and the context of the person’s life • The disturbance causes marked distress or interpersonal difficulty • The sexual dysfunction is not: • Better accounted for by another primary psychiatric disorder (except another Sexual Dysfunction) • Due exclusively to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition American Psychiatric Association. DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Washington, DC: American Psychiatric Press; 2000

  46. FSD may be Multi-faceted • Biological/Pharmacological • Medical diagnoses • Psychiatric conditions • Other sexual disorders • Medications/substances • Hormonal changes • Socio-cultural • Lower education • Religious restrictions • Social taboos • Cultural conflict • Psychological • Prior sexual or physical abuse • Relational (conflict, lack of partner, partner SD) • Body image, sexual self-esteem • Negative emotional states • Stress

  47. Relational Problems (not HSDD) Sexual dysfunction in partner Interpersonal conflict Extra-marital affair by either partner Desire discrepancy Cultural differences Reproductive concerns History of sexual abuse

  48. Prevalence of Sexual Dysfunction N=31,581. Definition of depression: Self-reported depressive sx’s + AD use; AD use without current depressive sx’s; Depressive symptoms without AD use Shifren J et al. Sexual problems and distress in United States women: Prevalence and correlates. ObstetGynecol2008;112:970-978; Johannes CB et al. Distressing Sexual Problems in United States Women Revisited: Prevalence after Accounting for Depression. J Clin Psychiatry 2009;70(12):1698-1706

  49. Proportion of Partnered Women with HSDD By Age and Menopausal Status 30 P=0.002 25 20 P=0.067 % of Patients 15 10 5 0 Naturally postmenopausal Premenopausal Surgically postmenopausal Surgically postmenopausal Age 20-49 years Age 50-70 years Leiblum SR et al.Hypoactive sexual desire disorder in postmenopausal women: US results from the Women’s International Study of Health and Sexuality (WISHeS). Menopause. 2006;13:46-56.

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