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Emerging Perspectives on the Science and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicine and Primary Care Perspective Emerging.

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Presentation on theme: "Emerging Perspectives on the Science and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicine and Primary Care Perspective Emerging."— Presentation transcript:

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2 Emerging Perspectives on the Science and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicine and Primary Care Perspective Emerging Perspectives on the Science and Medicine of Hypoactive Sexual Desire Disorder (HSDD) The Internal Medicine and Primary Care Perspective A New Frontiers Program on Womens Health 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

3 Program Faculty PROGRAM CHAIRPERSON Anita H. Clayton, MD David C Wilson Professor Department of Psychiatry & Neurobehavioral Sciences Neurobehavioral Sciences Professor of Clinical Obstetrics & Gynecology 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

4 A New Frontiers Program on Womens Health 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 Addressing Current Challenges in Female Sexual Disorders What Internal Medicine Specialists Need to Know about HSDD

5 Clinical focus Clinical focus Prevalence and pathophysiology of HSDD Prevalence and pathophysiology of HSDD Communication strategies Communication strategies Differential diagnoses Differential diagnoses Intervention and management Intervention and management A New Frontiers Program on Womens Health

6 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. 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 Change in sexual function since marriage 4 years ago, but relationship still strong 1 year post-partum with mild depressive symptoms since delivery 1 year post-partum with mild depressive symptoms since delivery No general health problems No general health problems On oral contraceptives for birth control On oral contraceptives for birth control

7 Hypoactive Sexual Desire Disorder Prevalence 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 A New Frontiers Program on Womens Health

8 Normal Female Sexuality Defined by Cultural Norms Historically given little attention Historically given little attention Victorian era: discovery that female orgasm irrelevant to conception Victorian era: discovery that female orgasm irrelevant to conception 2008: womens sexuality hits Primetime but not quite its Prime 2008: womens sexuality hits Primetime but not quite its Prime

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

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

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

12 Womens Endorsement of Models of Female Sexual Response The Nurses Sexuality Study, N=133 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. 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. 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, :

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

14 US Adult Women Are Sexually Active* *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): US Women Sexually Active (%) Random Digital Dialing Survey of Women Years Old (N=2000) Random Digital Dialing Survey of Women Years Old (N=2000) (n=362)(n=451) (n=473) (n=271)(n=443) Age Ranges

15 DSM-IV-TR Classification of FSDs Sexual Desire Disorders Hypoactive Sexual Desire Disorder Absence or deficiency of sexual interest and/or desire Sexual Aversion Disorder Aversion to and avoidance of genital contact with a sexual partner Sexual Arousal Disorders Female Sexual Arousal Disorder Inability to attain or maintain adequate lubrication-swelling response of sexual excitement Orgasmic Disorders Female Orgasmic Disorder Delay in or absence of orgasm after a normal sexual excitement phase Pain Disorders Dyspareunia Genital pain associated with sexual intercourse Vaginismus Involuntary contraction of the perineal muscles preventing vaginal penetration

16 DSM-IV TR Criteria for FSD Sexual complaint or problem in desire, arousal, orgasm, or sexual pain: 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 persons life 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 persons life The disturbance causes marked distress or interpersonal difficulty The disturbance causes marked distress or interpersonal difficulty The sexual dysfunction is not: The sexual dysfunction is not: Better accounted for by another primary psychiatric disorder (except another Sexual Dysfunction) 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 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.

17 Overlap of FSDs Basson R, et al. J Urol. 2000;163: Sexual Desire Disorders Sexual Arousal Disorder OrgasmicDisorder Vaginismus Dyspareunia

18 Prevalence of FSD: A Historical Perspective OBJECTIVES: Assess the prevalence and risk of experiencing sexual dysfunction in men and women OBJECTIVES: Assess the prevalence and risk of experiencing sexual dysfunction in men and women NOT ASSESSED: Distress or interpersonal difficulty NOT ASSESSED: Distress or interpersonal difficulty POPULATION: 1749 women and 1410 men years of age POPULATION: 1749 women and 1410 men years of age RESULTS: 43% of women reported sexual dysfunction RESULTS: 43% of women reported sexual dysfunction *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): Prevalence of Sexual Dysfunction in Women by Latent Class Subsets for Sexual Dysfunctions Assessed Total for Sexual Dysfunctions Assessed Low Sexual Desire ArousalPain Women (%) Sexual Dysfunction in the United States* 100

19 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 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 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 POPULATION: 31,581 US female respondents 18 years of age from 50,002 households RESULTS*: Response rate was 63% (n=31,581 / 50,002) RESULTS*: Response rate was 63% (n=31,581 / 50,002) Prevalence of FSD: PRESIDE *All results are US population age- adjusted. Shifren JL, et al. Obstet Gynecol. 2008;112(5): Prevalence of Female Sexual Problems Associated With Distress DesireArousalOrgasmAny US Women (%) Sexual Problems Distressing Sexual Problems 100

20 Prevalence of Sexual Problems Associated with Distress (PRESIDE) Age-stratifiedprevalenceDesire2868/28,447Arousal1556/28,461Orgasm1315/27,854Any3456/28, or older Shifren J et al Obstetrics & Gynecology, 2008, 112(5).

21 Prevalence of Low Sexual Desire and Hypoactive Sexual Desire Disorder West SL et al Archives of Internal Medicine, 2008 Category Low Desire N %HSDDNHSDD% All All Age Age Age Age Surgical Menopausal Natural Menopausal Premenopausal Nationally Representative Sample of US Women

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

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

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

25 Social Psychology Theories: Understanding Psychosocial Aspects of Female Sexual Desire Self-Perception Theory Self-Perception Theory People make attributions about their own attitudes by relying on observations of external behaviors (Bem, 1965) People make attributions about their own attitudes by relying on observations of external behaviors (Bem, 1965) Wundt's schema of sensory affect (aka Kingsbergs Ice- Cream Analogy) Wundt's schema of sensory affect (aka Kingsbergs 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. 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.

26 Prevention and Treatment of Sexual Problems ASK! You cannot treat a problem if you dont know it exists

27 Type of Help-Seeking (n=3239 ) In PRESIDE About One-Third of Women With a Distressing Sexual Problem Sought Formal Care Shifren JL, et al. J Womens Health. 2009;18(4) Formal 34.5% Informal 41.9% 9.1% Anonymous 14.5% Did not seek help Formal=HCP; informal=anyone other than an HCP.

28 Physician Questioning Increases Patient Reporting of Sexual Dysfunction Spontaneous Reporting After Reporting Direct Inquiry Reporting Direct Inquiry Patients (%) N=887. Bachmann GA, et al. Obstet Gynecol. 1989:73: % 19%

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

30 Training Is Not Preparing HCPs To Be Informed in the Area of FSD Solursh DS, et al. Int J Impot Res. 2003;15(suppl 5):S41-S45. 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.

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

32 Patient Barriers Identified by HCPs in the Management of Sexual Dysfunction (n=133 HCPs) HCPs Perceive Patients as Reluctant to Bring Up Sexual Issues Patients reluctance/ reticence/embarrassment Patient thinks it's normal/lack of knowledge and awareness Indirect presentation (hidden by other symptoms) Difficult area to discuss Doesn't want to waste doctors' time Total Number of Barriers (%)* Humphrey S, et al. Fam Pract. 2001;18(5): *Total number of patient barriers=93; most HCPs identified more than one barrier.

33 HCP Comfort Level Impacted by Patient Gender Burd ID, et al. J Sex Med. 2006;3(2): Differences in Physician Comfort Level Influenced by Gender (N=69) * 45 12* 50* Physician perception of female patient discomfort Physician perception of male patient discomfort Physician self-report of discomfort with female patients Physician self-report of discomfort with male patients Physicians (%) Male physicians (n=40) Female physicians (n=29) *P<0.05.

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

35 HSDD and concomitant sexual dysfunctions (both should be noted)HSDD and concomitant sexual dysfunctions (both should be noted) Also, additional diagnosis of HSDD IS NOT made if low sexual desire is better accounted for by another Axis I disorder (eg, major depressive disorder, obsessive-compulsive disorder, posttraumatic stress disorder)Also, additional diagnosis of HSDD IS NOT made 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 The Challenges of the Differential Diagnosis Ensure that sexual dysfunction IS NOT due exclusively to theEnsure that sexual dysfunction IS NOT due exclusively to the –Physiological effects of a specified general medical condition (eg, neurological, hormonal, metabolic abnormalities)* *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. If it is, refer to the diagnosis is Substance-Induced Sexual Dysfunction. Ensure that sexual dysfunction IS NOT due exclusively to theEnsure that sexual dysfunction IS NOT due exclusively to the – Physiological effects of substance (prescribed or illicit) abuse – Physiological effects of substance (prescribed or illicit) abuse In Order to Meet the Diagnostic Criteria for HSDD: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text Revision, Washington, DC: American Psychiatric Press; 2000.

36 The Challenges of Differential Diagnosis Mood disorders 1 Mood disorders 1 Major depression Major depression Bipolar illness Bipolar illness Anxiety disorders 2,3 Anxiety disorders 2,3 Psychotic illness 4 Psychotic illness 4 Hypertension Hypertension Neurological disorders 6 Neurological disorders 6 Endocrine disorders 7 Endocrine disorders 7 Diabetes, thyroid disorders, hyperprolactinemia 7 Diabetes, thyroid disorders, hyperprolactinemia 7 Urological problems 8 Urological problems 8 Sexually transmitted infections 9 Sexually transmitted infections 9 Gynecological problems Gynecological problems Post-partum 10 Post-partum 10 Other chronic illness Other chronic illness Rheumatoid arthritis 11 Rheumatoid arthritis 11 Psoriasis 12 Psoriasis 12 Breast cancer 13 Breast cancer Casper RC, et al. Arch Gen Psychiatry. 1985;42: van Lankveld JJ, Grotjohann Y. Arch Sex Behav. 2000;29: Shifren J, et al. Obstet Gynecol. 2008;112: Friedman S, Harrison G. Arch Sex Behav. 1984;13: Okeahialam BN, Obeka NC. J Natl Med Assoc. 2006;98: Rees PM, et al. Lancet. 2007;369(9560): Bhasin S, et al. Lancet. 2007;369(9561): Aslan G, et al. Int J Impot Res. 2005;17: Smith EM, et al. Infect Dis Obstet Gynecol. 2002;10(4): Baksu B, et al. Int Urogynecol J. 2007;18: Abdel-Nasser A, Ali E. Clin Rheumatol. 2006;25: Sampogna F, et al. Dermatology. 2007;214: Mathias C, et al. Ann Oncol. 2006;17(12): Psychiatric Illnesses and General Health Factors May Affect Sexual Function

37 Other drug classes Chemotherapeutic agents 6Chemotherapeutic agents 6 Aromatase Inhibitors 7Aromatase Inhibitors 7 Triglyceride-lowering agents 8Triglyceride-lowering agents 8 Histamine receptors (H2) blockers 9Histamine receptors (H2) blockers 9 Weight loss agents 10Weight loss agents 10 Antiepileptics 11Antiepileptics 11 Immunosuppresants 12Immunosuppresants 12 Central alpha-adrenergic agonists 13Central alpha-adrenergic agonists 13 Opioid antagonists 14Opioid antagonists Liu-Seifert H, et al. Neuropsychiatr Dis Treat. 2009;5: Serretti A, Chiesa A. J Clin Psychopharmacol. 2009;29: Lithium carbonate [package insert] Venlafaxine hydrochloride [package insert] Imipramine hydrochloride [package insert] Fobair P, Spiegel D. Cancer J. 2009;15(1): Mok K, et al. Breast. 2008;17(5): Fenofibrate [package insert] Ranitidine hydrochloride [package insert] Sibutramine hydrochloride monohydrate [package insert] Rees PM, et al. Lancet. 2007;369: Muehrer RJ, et al. West J Nurs Res. 2006;28: Clonidine [package insert] Naltrexone hydrochloride [package insert] Psychotropic drug classes/agents Antipsychotics 1Antipsychotics 1 SSRIs 2SSRIs 2 Lithium 3Lithium 3 SNRIs 4 SNRIs 4 Tricyclic antidepressants 5Tricyclic antidepressants 5 Numerous Medications are Associated with Female Sexual Problems The Challenges of Differential Diagnosis

38 Thank you

39 Pathophysiology of Decreased Desire in Premenopausal Women Psychological, Pharmacologic, and Neurobiological Mechanisms A New Frontiers Program on Womens Health 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

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

41 Whats it all about anyhow? Psychological/social/emotional Psychological/social/emotional Physiological/biological: interactions of sex steroids and neurotransmitters Physiological/biological: interactions of sex steroids and neurotransmitters Cognitive: thoughts, fantasies, satisfaction Cognitive: thoughts, fantasies, satisfaction Cultural Cultural American Psychiatric Association, DSM IV, 1994

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

43 NE+ Peripheral Effects on Sexual Function 5-HT 2A Nitric Oxide (NO) Cholinergic fibers Prostaglandin E 5-HT- + - Clayton AH. Psychiatric Clinics of North America 2003; 26: SENSATION gonads adrenals Estrogen Testosterone Progestin maintain genital structure and function } VASOCONGESTION +5-HT- + Clitoral and penile tissue

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

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

46 DSM-IV TR Criteria for HSDD Sexual complaint or problem in sexual desire and/or fantasies 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 persons life 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 persons life The disturbance causes marked distress or interpersonal difficulty The disturbance causes marked distress or interpersonal difficulty The sexual dysfunction is not: The sexual dysfunction is not: Better accounted for by another primary psychiatric disorder (except another Sexual Dysfunction) 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 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

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

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

49 Prevalence of Sexual Dysfunction SEXUALCOMPLAINTSEXUALPROBLEM PROBLEM PLUS DISTRESS FSD WITHOUT DEPRESSION Desire38.7%10%6.3 – 8.8% Arousal26.1%5.4%3.3 – 4.7% Orgasm20.5%4.7%2.8 – 4.1% Any Dysfunction 44.2%12%7.6 – 10.7% Shifren J et al. Sexual problems and distress in United States women: Prevalence and correlates. Obstet Gynecol 2008;112: ; Johannes CB et al. Distressing Sexual Problems in United States Women Revisited: Prevalence after Accounting for Depression. J Clin Psychiatry 2009;70(12): N=31,581. Definition of depression: Self-reported depressive sxs + AD use; AD use without current depressive sxs; Depressive symptoms without AD use

50 Leiblum SR et al.Hypoactive sexual desire disorder in postmenopausal women: US results from the Womens International Study of Health and Sexuality (WISHeS). Menopause. 2006;13: Naturallypostmenopausal Surgicallypostmenopausal Premenopausal % of Patients Surgicallypostmenopausal Proportion of Partnered Women with HSDD By Age and Menopausal Status Age years P=0.002 Age years P=0.067

51 Medical Conditions that may Impact Sexual Function Neurologic Spinal cord injury, neuropathy, herniated disc, MS, epilepsy Endocrine Hypothyroidism, adrenal dysfunction, hypogonadism, diabetes mellitus, menopause Vascular Hypertension, arteriosclerosis, stroke, venous insufficiency, sickle cell disorder Genitourinary Urinary incontinence, vaginitis, PID, endometriosis Systemic Illness Renal, pulmonary, hepatic diseases, advanced malignancies, infections Psychiatric Depression, anxiety disorders, psychotic illness, eating disorders, PTSD Clayton & Ramamurthy in Sexual Dysfunction: The Brain-Body Connection. Ed: R Balon, Karger, Basel, Switzerland, 2008; Basson R, Schultz WW. Lancet. 2007;369: ; Kingsberg SA, Janata JW. Urol Clin North Am. 2007;34: ; Zemishlany & Weizman in Sexual Dysfunction: The Brain-Body Connection. Ed: R Balon, Karger Basel, Swithzerland 2008

52 Pharmacotherapies and Risk of FSD PSYCHOTROPIC MEDICATIONS SSRIs/SNRIs/TCAs Mood stabilizers Antipsychotics Benzodiazepines Antiepileptic drugs ANTIHYPERTENSIVES Beta-blockers Alpha-blockers Diuretics CARDIOVASCULAR AGENTS Lipid-lowering agents Digoxin HORMONES Oral contraceptives Estrogens Progestins Ant-iandrogens GnRH agonists OTHER Histamine H2-receptor blockers Narcotics NSAIDs Clayton & Ramamurthy in Sexual Dysfunction: The Brain-Body Connection. Ed: R Balon, Karger, Basel, Switzerland, 2008; Basson R, Schultz WW. Lancet. 2007;369: ; Kingsberg SA, Janata JW. Urol Clin North Am. 2007;34:

53 Correlates of Distress with HSDD: PRESIDE Psychological Psychological Having a partner (OR 4.63) Having a partner (OR 4.63) Demographics: Greatest age < 45 years; to lesser degree < 65 years; white race Demographics: Greatest age < 45 years; to lesser degree < 65 years; white race Neurobiological Neurobiological Untreated depression > treated depression Untreated depression > treated depression Presence of anxiety Presence of anxiety Urinary incontinence Urinary incontinence Use of hormonal contraceptives or HRT Use of hormonal contraceptives or HRT Rosen RC, et al. Correlates of sexually related personal distress in women with low sexual desire. J Sex Med 2009;6:

54 Decreased Sexual Desire Screener (DSDS) ©Boehringer Ingelheim International GmbH All rights reserved. Sensitivity 0.836, 0.946, 0.956, and specificity Goldfischer ER et al. Obstet Gynecol 2008;111:109S Clayton A et al. J Sex Med 2009;6:730–738 Nappi R et al. J Sex Med 2009;6(suppl 2):46

55 Conclusions Multiple factors may affect sexual functioning in women across the life cycle Multiple factors may affect sexual functioning in women across the life cycle Appropriate assessment is important in management Appropriate assessment is important in management

56 Addressing Current Challenges in Female Sexual Disorders What Internal Medicine Specialists Need to Know About HSDD A New Frontiers Program on Womens Health Lori Brotto, PhD Assistant Professor Department of Obstetrics and Gynecology University of British Columbia Vancouver, BC

57 Outline Physician-patient communication Physician-patient communication Screening strategies Screening strategies Differential diagnosis Differential diagnosis Interview techniques Interview techniques PLISSIT / ALLOW PLISSIT / ALLOW

58 Why is inquiry about sexual function difficult? Topic not important enough Topic not important enough It is a private experience It is a private experience Embarrassment Embarrassment I dont exactly know why I am asking I dont exactly know why I am asking Lack of training Lack of training Absence of norms Absence of norms Sexual behaviour is a topic only when it is deviant or when others are at risk Sexual behaviour is a topic only when it is deviant or when others are at risk Incorrect beliefs about the benefit of asking Incorrect beliefs about the benefit of asking

59 Is Marriage Good for Your Health? New York Times Magazine, April 12, 2010

60 Complicating factors: Symptom or disorder? Factoring in distress, rates of low desire drop by half in all studies Factoring in distress, rates of low desire drop by half in all studies Note, DSM-IV-TR criteria for HSDD and all sexual dysfunctions require distress Note, DSM-IV-TR criteria for HSDD and all sexual dysfunctions require distress Lutfey et al., 2008, Arch Sex Behav n = 3,205; Black, Hispanic, White

61 Oberg et al. (2004) found a prevalence of manifest distress despite the absence of any sexual symptoms of 12.4% Oberg et al. (2004) found a prevalence of manifest distress despite the absence of any sexual symptoms of 12.4% Bancroft, Loftus, and Long (2003) found that 8% of women reported distress about the relationship and 5.4% reported personal distress despite absence of sexual symptoms Bancroft, Loftus, and Long (2003) found that 8% of women reported distress about the relationship and 5.4% reported personal distress despite absence of sexual symptoms Lutfey, Link, Rosen, Wiegel, and McKinlay (2008) reported that 5.5% of women were dissatisfied or very dissatisfied despite not having any sexual symptoms. Lutfey, Link, Rosen, Wiegel, and McKinlay (2008) reported that 5.5% of women were dissatisfied or very dissatisfied despite not having any sexual symptoms. Cain et al. (2003) in the SWAN study found that 70% of women reported thinking about sex less than once/week but 86% remained sexually satisfied. Cain et al. (2003) in the SWAN study found that 70% of women reported thinking about sex less than once/week but 86% remained sexually satisfied. King et al. (2007) found that 19% of women did not have an ICD-10 diagnosed sexual dysfunction but still reported significant low sexual satisfaction. King et al. (2007) found that 19% of women did not have an ICD-10 diagnosed sexual dysfunction but still reported significant low sexual satisfaction. Dunn et al. (2000) found that 79% of women were very sexually satisfied but 24% had no sexual activity in the past 3 months. Dunn et al. (2000) found that 79% of women were very sexually satisfied but 24% had no sexual activity in the past 3 months. Laumann et al. (2005) in the GSSAB found that 7.7% % of women reported not finding sex pleasurable/satisfying. Laumann et al. (2005) in the GSSAB found that 7.7% % of women reported not finding sex pleasurable/satisfying. Complicating Factors: Low Desire Does Not Always Imply Dissatisfaction

62 Sexual dysfunction is common Sexual dysfunction is common Integral component of quality of life and general well-being Integral component of quality of life and general well-being Why assess sexual function?

63

64 Lindau et al., NEJM, 2007

65 Physician-patient communication

66 53 primary care physicians (or internal medicine residents) at UVA completed questionnaire about their experience asking about HSDD 53 primary care physicians (or internal medicine residents) at UVA completed questionnaire about their experience asking about HSDD 86.3% had not screened for HSDD 86.3% had not screened for HSDD 90% had not diagnosed HSDD 90% had not diagnosed HSDD 53% felt not confident at all, 38% little confidence 53% felt not confident at all, 38% little confidence Harsh et al., J Sex Med 2008 Are physicians asking?

67 Survey Participants and Patients who Initiate First Discussion of FSDs J Sex Med 2006;3: Survey participants initiating first discussion of FSD Patients initiating first discussion of FSD Percentage of survey participants providing estimate

68 Who should I ask about sexuality? EVERYONE! EVERYONE! Legitimizes the patients concerns with and interest in sex Legitimizes the patients concerns with and interest in sex Allows the patient to ask questions Allows the patient to ask questions Identifies the provider as a potential resource for sexual information Identifies the provider as a potential resource for sexual information Maximizes the chances that patients will get help for sexual and relationship problems Maximizes the chances that patients will get help for sexual and relationship problems

69 Screening Strategies

70 Screening questions Are you satisfied with your sexual response (sex life)? If not, why not? Are you satisfied with your sexual response (sex life)? If not, why not? Are you currently active with a sexual partner? Are you currently active with a sexual partner? Men, women or both Men, women or both Frequency (activity including masturbation) Frequency (activity including masturbation) How often do you have difficulty _________? How often do you have difficulty _________? What questions or problems related to sex would you like to discuss? What questions or problems related to sex would you like to discuss?

71 When to ask? 1. During routine inquiry Include it in a standard set of questions during developmental and psychosocial periods Include it in a standard set of questions during developmental and psychosocial periods Include it on self-report questionnaire Include it on self-report questionnaire you were telling me about your male friendshipsyou were telling me about your male friendships growing up…Do you remember when you first became aware of sexual feelings?

72 2. After direct presentation Patient directly states problem Patient directly states problem Ask permission and collect information Ask permission and collect information 3. After indirect presentation Patient is indirect and vague, hoping the clinician will ask about sexual complaints Patient is indirect and vague, hoping the clinician will ask about sexual complaints e.g., medication non-compliance e.g., medication non-compliance Know about that particular condition and side-effect profiles of medications Know about that particular condition and side-effect profiles of medications When to ask?

73 1. Need clinical knowledge, a non- judgmental attitude, and fundamental interviewing skills Observing and monitoring Observing and monitoring Interpreting skills Interpreting skills Responding skills Responding skills How to ask?

74 2. Clarify the problem Patient: Ive lost my nature Clinician: Tell me what a nature is? I havent heard that expression before. 3. Use personalized language Use the correct term and allow the patient to pick up on it Use the correct term and allow the patient to pick up on it Sometimes may be appropriate to use patients language Sometimes may be appropriate to use patients language How to ask?

75 4. Use open-ended questions Use: to what extent…what…how… Use: to what extent…what…how… Dont use: do you…did you…are you…have you… Dont use: do you…did you…are you…have you… What were the circumstances that led you to be sexual with him? 5. Be empathic Is an expression of professional understanding Is an expression of professional understanding that must have been really difficult for you… that must have been really difficult for you… How to ask?

76 6. Facilitate Encourage the patient to continue by nodding, leaning forward, using yes…go on. Encourage the patient to continue by nodding, leaning forward, using yes…go on. 7. Provide information Anticipate worries and speculate Anticipate worries and speculate Confirm understanding of the problem before proceeding Confirm understanding of the problem before proceeding How to ask?

77 Differential Diagnosis

78 Comorbidity of Womens Sexual Difficulties Desire difficulties Arousal difficulties Orgasm difficulties Pain Vaginismic difficulties Basson et al., 2003 J Psychosom Obstet Gynaecol desire and lubrication – 65% desire and orgasm - 53% desire and vaginismus – 75% lubrication and orgasm – 28% lubrication and dyspareunia – 61%

79 Depression?

80 Interview Techniques Self-report measures

81 Use of Validated Questionnaires Decreased Sexual Desire Screener (DSDS) Decreased Sexual Desire Screener (DSDS) Clayton et al. 2009, J Sex Med Female Sexual Function Index (FSFI) Female Sexual Function Index (FSFI) Rosen et al. 2000, J Sex Marital Ther Profile of Female Sexual Function Profile of Female Sexual Function McHorney et al. 2004, Menopause Female Sexual Distress Scale (FSDS) Female Sexual Distress Scale (FSDS) Derogatis et al. 2002, J Sex Marital Ther

82 Decreased Sexual Desire Screener Clayton, Goldfischer, Goldstein, DeRogatis, Lewis-DAgostino, Pyke, J Sex Med 2009;6: In the past was your level of sexual desire or interest good and satisfying to you? 2.Has there been a decrease in your level of sexual desire or interest? 3.Are you bothered by your decreased level of sexual desire or interest? 4.Would you like your level of sexual desire or interest to increase? 5.Please check all the factors that you feel may be contributing to you current decrease in sexual desire or interest.

83 Use of a Validated Structured Interview Womens Sexual Interest Diagnostic Interview Womens Sexual Interest Diagnostic Interview DeRogatis et al. 2008, J Sex Med *39 items assessing desire, arousal, orgasm, pain and distress, partner sexual dysfunction, relationship problems, depression * Permission to use the WSID can be obtained by contacting Solvay Pharmaceuticals, Inc. ( , Sexual Interest and Desire Inventory-Female Version (SIDI) Sexual Interest and Desire Inventory-Female Version (SIDI) Clayton et al. 2005, J Sex Marital Ther *13-item clinician administered measure of sexual interest, desire and arousability

84 Interview Techniques Face-to-face interview

85 PLISSIT Permission Permission Acceptance, empathy Acceptance, empathy I ask all my patients about sex. Is it OK to do so now? I ask all my patients about sex. Is it OK to do so now? Limited Information Limited Information Basic education regarding anatomy & sexual response Basic education regarding anatomy & sexual response Specific Suggestions Specific Suggestions Medical-medication, procedures to relieve discomfort Medical-medication, procedures to relieve discomfort Psychological-behavioral strategies, communication skills Psychological-behavioral strategies, communication skills Intensive Therapy Intensive Therapy Individual or couples therapy to manage sexual or relationship issues Individual or couples therapy to manage sexual or relationship issues Surgery (penile implants, vestibulectomy) Surgery (penile implants, vestibulectomy)

86 ALLOW Sadovsky, 2002

87 Goals of a Comprehensive Sexual History Identify the primary complaint Identify the primary complaint Determine patients perspective of their problem Determine patients perspective of their problem Develop hypotheses about etiology Develop hypotheses about etiology Decide on an appropriate course of treatment (including referral) Decide on an appropriate course of treatment (including referral)

88 Elements of a Comprehensive Sexual History Assess sexual functioning Assess sexual functioning Assess medical/organic contributors Assess medical/organic contributors Assess relationship satisfaction and functioning Assess relationship satisfaction and functioning Assess risk behaviours Assess risk behaviours Assess partner status Assess partner status Ask about history of childhood sexual or physical abuse Ask about history of childhood sexual or physical abuse Assess mood Assess mood

89 Sample Assessment Questions What is your sexual interest like? What factors enhance and/or inhibit your desire? What is your sexual interest like? What factors enhance and/or inhibit your desire? Many people engage in self-stimulation. Is this part of your sexual experiences? Many people engage in self-stimulation. Is this part of your sexual experiences? Some people avoid sexual activity for any variety of reasons? Can you relate to this? Some people avoid sexual activity for any variety of reasons? Can you relate to this? Many women talk about difficulties with lubrication or sexual activity that is painful. What is your experience with this? Many women talk about difficulties with lubrication or sexual activity that is painful. What is your experience with this? Most men experience occasional difficulties with their erection. Has this been the case for you? Most men experience occasional difficulties with their erection. Has this been the case for you?

90 Do you notice any difference between your erections during sexual intercourse, during masturbation, and those when you wake up? Do you notice any difference between your erections during sexual intercourse, during masturbation, and those when you wake up? When youre experiencing this difficulty, can you recall what youre thinking or feeling at the time? How about right before? When youre experiencing this difficulty, can you recall what youre thinking or feeling at the time? How about right before? Of your last 10 sexual encounters, on how many of them did you experience this difficulty? Of your last 10 sexual encounters, on how many of them did you experience this difficulty? What do you do in response to this difficulty? What does your partner do? What do you do in response to this difficulty? What does your partner do? Can you describe the sensation of the pain? Is it burning, throbbing, or sharp? When do you experience it? Can you describe the sensation of the pain? Is it burning, throbbing, or sharp? When do you experience it? Sample Assessment Questions

91 Problems to Avoid During the Sexual Interview Meddling: always rationalize your questioning Meddling: always rationalize your questioning Preoccupation: focus on each response Preoccupation: focus on each response Identification: consult with a colleague if youre not able to be objective Identification: consult with a colleague if youre not able to be objective Sexual arousal: be aware of your own feelings Sexual arousal: be aware of your own feelings

92 Putting the Sexual History in Context What explanations does the patient have (their theory)? What explanations does the patient have (their theory)? What have they done to try to resolve the problem? What have they done to try to resolve the problem? Are there problems in multiple areas of sexual functioning? What is the relationship between these? Are there problems in multiple areas of sexual functioning? What is the relationship between these? What have they discussed with their partner and what was the reaction? What have they discussed with their partner and what was the reaction?

93 Multi-Factorial Model Predisposing Factors Maintaining Factors Precipitating Factors Early Development Current Functioning

94 Download free of charge at:

95 Jennifer Frank, MD, FAAFP Assistant Professor Department of Family Medicine University of Wisconsin School of Medicine and Public Health Current and Emerging Therapies for Hypoactive Sexual Desire Disorder A New Frontiers Program on Womens Health

96 Learning Objectives Describe a multimodal treatment approach to HSDD Describe a multimodal treatment approach to HSDD Identify components of nonpharmacologic treatment of HSDD Identify components of nonpharmacologic treatment of HSDD Describe current pharmacologic treatment options for HSDD in both postmenopausal and premenopausal women Describe current pharmacologic treatment options for HSDD in both postmenopausal and premenopausal women Identify emerging pharmacologic treatment options for HSDD Identify emerging pharmacologic treatment options for HSDD

97 HSDD Treatment Starts with Nonpharmacologic Approaches Foundation of therapy Foundation of therapy Includes treatment initiated and managed by the primary care physician Includes treatment initiated and managed by the primary care physician May include treatment by specialist partners May include treatment by specialist partners Sex therapist Sex therapist Physical therapist Physical therapist Cognitive behavioral therapist Cognitive behavioral therapist Marital/relationship counselor Marital/relationship counselor

98 Nonpharmacologic Treatment PCP based Specialist based Education Education Dispelling myths Dispelling myths Exercise Exercise Healthy Diet Healthy Diet Adequate Rest Adequate Rest Stress Reduction Stress Reduction CBT CBT Sensate-focus Sensate-focus Controlled self- stimulation Controlled self- stimulation Couples counseling Couples counseling Physical therapy Physical therapy Vaginal dilators Vaginal dilators Biofeedback Biofeedback Bitzer J, Brandenburg U. Psychotherapeutic interventions for female sexual dysfunction. Maturitas 2009;63:160-3.

99 Sex Therapy for the PCP Education Education What is normal? What is normal? Basics of anatomy and physiology? Basics of anatomy and physiology? Lubrication Lubrication Basic familiarity with 3 or 4 different products Basic familiarity with 3 or 4 different products Maximize intimacy and opportunities for intimacy Maximize intimacy and opportunities for intimacy Introduce novelty – different positions, venues, toys, etc. Introduce novelty – different positions, venues, toys, etc. Getting into a sexual frame of mind Getting into a sexual frame of mind Men are like light switches, women are like ovens. Men are like light switches, women are like ovens. Patient focused reading Patient focused reading T.L.C. T.L.C. Redistribution of childcare and household responsibilities Redistribution of childcare and household responsibilities Improving body image Improving body image Potter JE. A 60-year-old woman with sexual difficulties. JAMA 2007;297: UpToDate and

100 Barriers to Nonpharmacologic Treatment Physicians unfamiliarity with counseling and recommendations Physicians unfamiliarity with counseling and recommendations Physicians discomfort with this role Physicians discomfort with this role Patients resistance to relationship work Patients resistance to relationship work Patients perceived barriers to implementing change Patients perceived barriers to implementing change Patients unwillingness to change Patients unwillingness to change Patients belief in a little blue pill Patients belief in a little blue pill Lack of or paucity of hope Lack of or paucity of hope Reward not worth the work Reward not worth the work

101 Current Pharmacologic Treatment Options for FSD Hormonal Hormonal Estrogen Estrogen Testosterone* Testosterone* Psychotropic medications Psychotropic medications Buproprion* Buproprion* Phosphodiesterase inhibitors Phosphodiesterase inhibitors Sildenafil* Sildenafil* *Not FDA approved for this indication

102 Local Estrogen Therapy for Vaginal Atrophy (Level C) Postmenopausal women without a history of hormone-dependent breast cancer Postmenopausal women without a history of hormone-dependent breast cancer Low dose as long as symptoms persist Low dose as long as symptoms persist Not indicated for HSDD but can be helpful if pain/dryness is contributing to low desire Not indicated for HSDD but can be helpful if pain/dryness is contributing to low desire Consider if prescribing testosterone Consider if prescribing testosterone

103 Consider Testosterone for Post- Menopausal Women with HSDD Good evidence (Level A) to support its use in estrogen replete women 1-3 Good evidence (Level A) to support its use in estrogen replete women mcg patch for 24 weeks 300 mcg patch for 24 weeks Both naturally 4 and surgically 1-3 menopausal women Both naturally 4 and surgically 1-3 menopausal women Improvements seen in desire, orgasm frequency and total number of sexually satisfying encounters Improvements seen in desire, orgasm frequency and total number of sexually satisfying encounters 1.Braunstein et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women. Arch Intern Med 2005;165: , 2.Buster et al. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol 2005;105: , 3.Davis et al. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Menopause 2006;13: Shifren et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 study. Menopause 2006;5:770-9.,

104 Testosterones Role in Postmenopausal Women without ERT DBRCT of placebo vs. testosterone patch DBRCT of placebo vs. testosterone patch Increase in SSEs/month at 300 mcg daily dose Increase in SSEs/month at 300 mcg daily dose 2.1 (active) vs. 0.7 (placebo) 2.1 (active) vs. 0.7 (placebo) Increase in desire Increase in desire Decrease in distress Decrease in distress Treatment effect similar in naturally and surgically menopausal women Treatment effect similar in naturally and surgically menopausal women 4 episodes of breast cancer in study participants (n=537) 4 episodes of breast cancer in study participants (n=537) Davis et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med 2008;359:

105 Testosterone for Premenopausal Women may Have a Role DBRPCT of 261 premenopausal women DBRPCT of 261 premenopausal women Not depressed Not depressed Low serum testosterone Low serum testosterone Testosterone at 90 microliters/day (spray) daily x 16 weeks Testosterone at 90 microliters/day (spray) daily x 16 weeks Increase of 0.8 SSEs/month over placebo Increase of 0.8 SSEs/month over placebo Strong placebo effect Strong placebo effect SSE not related to testosterone levels SSE not related to testosterone levels Levels returned to baseline at 20 weeks (4 weeks after study) but SSEs did not Levels returned to baseline at 20 weeks (4 weeks after study) but SSEs did not Davis et al. Safety and efficacy of a testosterone metered-dose transdermal spray for treating decreased sexual satisfaction in premenopausal women. Ann Intern Med 2008;148:

106 Testosterone Treatment Limitations Androgen levels not clearly associated with decreased desire Androgen levels not clearly associated with decreased desire Difficult to measure testosterone levels accurately Difficult to measure testosterone levels accurately Role in premenopausal women is not established 1 Role in premenopausal women is not established 1 Off label indication Off label indication Long term efficacy/safety not known 1-3 Long term efficacy/safety not known 1-3 Study population (definition of decreased desire) 1 Study population (definition of decreased desire) 1 Relationship between arousal and desire 1 Relationship between arousal and desire 1 Need for concomitant use of estrogen (?) 1 Need for concomitant use of estrogen (?) 1 1. Basson R. Pharmacotherapy for womens sexual dysfunction. Expert Opin Pharmacother 2009;10: NAMS. The role of testosterone therapy in postmenopausal women: position statement of the North American Menopause Society. Menopause 2005;12: Wierman et al. Androgen therapy in women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2006;91:

107 Buproprion has Limited Data to Demonstrate Efficacy in HSDD (Level B/C) Buproprion (300 mg/day) x 112 days in non-depressed premenopausal women with normal serum testosterone 1 Buproprion (300 mg/day) x 112 days in non-depressed premenopausal women with normal serum testosterone 1 Global improvement in sexual functioning and on subsets of arousal, orgasm completion and pleasure on one of the scales used(Level C) Global improvement in sexual functioning and on subsets of arousal, orgasm completion and pleasure on one of the scales used(Level C) No statistically significant improvement in desire No statistically significant improvement in desire 268 women ages diagnosed with HSDD (Level B) women ages diagnosed with HSDD (Level B) 2 Premenopausal, not depressed, normal testosterone Premenopausal, not depressed, normal testosterone 12 weeks of buproprion SR 150 mg/day 12 weeks of buproprion SR 150 mg/day Improvement in rating scale of sexual function (globally and specific subsets) Improvement in rating scale of sexual function (globally and specific subsets) Greatest improvement in frequency of sexual activity, thoughts/desire, and pleasure/orgasm Greatest improvement in frequency of sexual activity, thoughts/desire, and pleasure/orgasm Decrease in personal distress score Decrease in personal distress score Add-on or substitute therapy for SSRI induced sexual dysfunction(Level B) 3,4 Add-on or substitute therapy for SSRI induced sexual dysfunction(Level B) 3,4 1.Segraves et al. Buproprion SR for the treatment of HSDD in premenopausal women. J Clin Psychopharm 2004;24: Safarinejad et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of buproprion for treating hypoactive sexual desire disorder in ovulating women. BJU International Feb 2010 [Epub]. 3.Safarinejad. Reversal of SSRI-induced female sexual dysfunction by adjunctive buproprion in menstruating women: a double-blind, placebo- controlled and randomized study. J Clin Psychopharm Jan 2010 [Epub]. 4.Seretti A, Chiesa A. Treatment-emergent sexual dysfunction and anti-depressants: a meta-analysis. J Clin Psychopharm. 2009;29:

108 Phosphodiesterase Inhibitors No demonstrable role in the treatment of HSDD No demonstrable role in the treatment of HSDD Use in antidepressant associated FSD 1 Use in antidepressant associated FSD 1 Main effect on orgasmic capacity Main effect on orgasmic capacity Potential use in women with neurovascular mediated sexual dysfunction 2 Potential use in women with neurovascular mediated sexual dysfunction 2 Primarily arousal, orgasmic dysfunction Primarily arousal, orgasmic dysfunction 1.Nurnberg et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction. JAMA 2008;300: Brown DA et al. Assessing the clinical efficacy of sildenafil for the treatment of female sexual dysfunction. Ann Pharmacother 2009;43:

109 Emerging Pharmacologic Therapies Hormonal Hormonal Testosterone Testosterone Centrally acting agents Centrally acting agents Flibanserin Flibanserin Phosphodiesterase Inhibitors Phosphodiesterase Inhibitors Others Others Prostaglandin gel Prostaglandin gel

110 Testosterone in the Future 1 Premenopausal women Premenopausal women Effects of long term use are unknown Effects of long term use are unknown Search for an FDA approved preparation Search for an FDA approved preparation LibiGel LibiGel Intrinsa 2 Intrinsa 2 Tibolone 3 - estrogenic, progestogenic, androgenic synthetic hormone Tibolone 3 - estrogenic, progestogenic, androgenic synthetic hormone Combined with ERT? Combined with ERT? 1.Krapf and Simon. The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. Maturitas 2009;63: Davis et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med 2008;359: Wylie and Malik. Review of drug treatment for female sexual dysfunction. Int J STD AIDS 2009;20:671-4.

111 Centrally Acting Agents 1 Bremelanotide 3 Bremelanotide 3 Melanocortin agonist Melanocortin agonist FSAD FSAD Flibanserin 1 Flibanserin 1 Acts as a partial serotonin agonist/antagonist Acts as a partial serotonin agonist/antagonist Specifically being studied for HSDD Specifically being studied for HSDD 1.Wylie and Malik. Review of drug treatment for female sexual dysfunction. Int J STD AIDS 2009;20: Baldwin. Agomelatine in the treatment of mood and anxiety disorders. Brit J Hospital Med 2010;71: Safarinejad. Evaluation of the safety and efficacy of bremelanotide, a melanocortin receptor agonist, in female subjects with arousal disorder: a double-blind placebo-controlled, fixed dose, randomized study. J Sex Med 2008;

112 Other Agents Phosphodiesterase inhibitors Phosphodiesterase inhibitors Role will likely be focused to specific populations Role will likely be focused to specific populations No demonstrable effect on desire No demonstrable effect on desire Alprostadil (Prostaglandin E1) in trials for FSAD (vasodilatory properties) Alprostadil (Prostaglandin E1) in trials for FSAD (vasodilatory properties)

113 Conclusions The foundation of HSDD treatment is nonpharmacologic including PCP directed and specialty directed modalities. The foundation of HSDD treatment is nonpharmacologic including PCP directed and specialty directed modalities. Pharmacotherapeutic options are limited at this time. Pharmacotherapeutic options are limited at this time. Most promising treatments for HSDD include hormonal (testosterone) and centrally acting agents (buproprion and flibanserin). Most promising treatments for HSDD include hormonal (testosterone) and centrally acting agents (buproprion and flibanserin). Other medications may have role for different types of FSD. Other medications may have role for different types of FSD.

114 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. 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 Change in sexual function since marriage 4 years ago, but relationship still strong 1 year post-partum with mild depressive symptoms since delivery 1 year post-partum with mild depressive symptoms since delivery No general health problems No general health problems On oral contraceptives for birth control On oral contraceptives for birth control

115 Differential Diagnosis

116 Evaluation/Interventions Consider labs such as TSH Consider labs such as TSH Consider change from birth control pills to non-hormonal contraceptive Consider change from birth control pills to non-hormonal contraceptive Specific suggestions Specific suggestions Consider adding bupropion to treat depression and enhance sexual functioning Consider adding bupropion to treat depression and enhance sexual functioning If no improvement, check testosterone levels before supplementing If no improvement, check testosterone levels before supplementing


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