FEMALE SEXUAL DYSFUNCTION-DRUG THERAPY. Dr. Renee Horowitz M.D FACOG Woman s Urology Center Beaumont Hospital

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1 FEMALE SEXUAL DYSFUNCTION-DRUG THERAPY Dr. Renee Horowitz M.D FACOG Woman s Urology Center Beaumont Hospital

2 CONFLICT OF INTEREST SPEAKER: AMAG PHARMACEUTICALS LUMENIS

3 DEFINITIONS DSM-IV VS DSM-V DSM IV SEPARATED HSDD AND AROUSAL DISORDERS DSM-V COMBINED THEM INTO FEMALE SEXUAL INTEREST AND AROUSAL DISORDER (FSIAD) ISSWSH AND THE INTERNATIONAL CONSULTATION OF SEXUAL MEDICINE COMMITTEE ON DEFINITIONS CONSENSUS IMPORTANT TO CHARACTERIZE THE ASSESSMENT OF EACH DISORDER WHILE UNDERSTANDING THERE IS OVERLAP TREATMENT IS BASED ON THE PRIMARY DISORDER IDENTIFIED BY WOMEN

4 ISSWSH DEFINITION PERSISTENT OR RECURRENT DEFICIENCY OR ABSENCE OF SEXUAL FANTASIES AND DESIRE FOR SEXUAL ACTIVITY WITH MARKED DISTRESS OR INTERPERSONAL DIFFICULTY NOT OTHERWISE ACCOUNTED FOR BY A GENERAL MEDICAL OR PSYCHIATRIC CONDITION.

5 ISSWSH DEFINITION MAY BE: PRIMARY OR SECONDARY GENERALIZED OR SITUATIONAL LIFELONG OR ACQUIRED

6 ISSWSH DEFINITION MAY INCLUDE ANY OF THE FOLLOWING: LACK OF MOTIVATION FOR SEXUAL ACTIVITY AS MANIFESTED BY EITHER REDUCED OR ABSENT SPONTANEOUS DESIRE ( SEXUAL THOUGHTS OR FANTASIES) OR REDUCED OR ABSENT REPONSIVE DESIRE TO EROTIC CUES AND STIMULATION OR INABLILITY TO MAINTAIN DESIRE OR INTEREST THROUGH SEXUAL ACTIVITY

7 ISSWSH DEFINITION MAY INCLUDE ANY OF THE FOLLOWING: LOSS OF DESIRE TO INITIATE OR PARTICIPATE IN SEXUAL ACTIVITY, INCLUDING BEHAVIORAL RESPONSES SUCH AS AVOIDANCE OF SITUATIONS THAT COULD LEAD TO SEXUAL ACTIVITY THAT IS NOT SECONDARY TO SEXUAL PAIN DISORDERS, AND IS COMBINED WITH CLINICALLY SIGNIFICANT PERSONAL DISTRESS THAT INCLUDES FRUSTRATION, GRIEF, INCOMPETENCE, LOSS, SADNESS, SORROW OR WORRY.

8 BIO-PSYCHO-SOCIAL MODEL FSD INTERACTION BETWEEN: BIOLOGY INTERPERSONAL RELATIONSHIP PSYCHOLOGY CULTURE

9 FSD INTERACTION

10 HYPOACTIVE SEXUAL DESIRE DISORDER

11 HSDD NEUROENDOCRINE FACTORS MAJOR DETERMINENT OF WOMEN S SEXUAL FUNCTION CENTRAL CONTRIBUTION FROM NEUROTRANSMITTERS SEX STEROIDS EXERT ACTIVATIONAL EFFECTS IN ORDER TO PRIME THE BRAIN

12 HSDD NEUROENDOCRINE BALANCE BETWEEN SEXUAL INHIBITION AND SEXUAL EXCITATION INHIBITORY FACTORS OPIOIDS ENDOCANNABINOIDS SEROTONIN EXCITATORY FACTORS DOPAMINE NE OXYTOCIN MELANACORTINS

13 HSDD HISTORY ARE YOU EXPERIENCING PAIN, AROUSAL AND/OR ORGASMIC PROBLEMS HOW IS YOUR RELATIONSHIP WITH YOUR PARTNER; HOW LONG WHAT DO YOU THINK IS THE ISSUE WHAT WOULD BE DIFFERENT IF I COULD SNAP MY FINGERS AND ALL WOULD BE BETTER

14 HSDD HISTORY ACQUIRED VS GENERALIZED HOW LONG HAS IT BEEN A PROBLEM ANY RECENT LIFE EVENTS ANY TRIGGERS FOR SEXUAL EXCITEMENT HOW MUCH DOES IT DISTRESS YOU HOW OFTEN DO YOU ENGAGE IN SEXUAL ACTIVITY

15 PSYCHIATRIC HSDD ETIOLOGY MOOD DISORDERS ANXIETY/DEPRESSION PSYCHOSIS CVD/HTN NEUROLOGICAL DISORDERS UROLOGIC PROBLEMS STI S

16 HSDD ETIOLOGY GYNECOLOGIC DISORDERS PELVIC FLOOR POSTPARTUM MENOPAUSE ENDOCRINE DISORDERS DIABETES THYROID HYPERPROLACTENEMIA ANDROGEN DEFICIENCY OTHER RA CANCER

17 HSDD ETIOLOGY POOR BODY IMAGE PRIVACY STRESS FATIGUE MEDICATIONS

18 HSSD MEDICATIONS PSYCHOTROPIC MEDICATIONS: SSRI, SRNI, TRICYCLIC MOOD STABLIZERS ANTIPSYCHOTICS BENZODIAZAPEMS ANTISEIZURE ANTIHYPERTINESIVE MEDICATIONS: BETA BLOCKERS ALPHA BLOCKERS DIURETICS

19 HSDD MEDICATIONS CARDIOVASCULAR MEDICATIONS: LIPID LOWERING DRUGS DIGOXIN HORMONES ORAL CONTRACEPTIVES ESTROGENS PROGESTERONE ANTI-ANDROGENS GNRH AGONISTS OTHER HISTAMINE H-2 RECEPTOR BLOCKERS OPIOIDS NSAIDS

20 HSDD NON-HORMONAL TREATMENTS FLIBANSERIN BUPROPRION BREMELANOTIDE LYBRIDO/LYBRIDOS

21 HSDD FLIBANSERIN 5-HT 1A AGONIST AND 5-HT2A ANTAGONIST BINDS WITH MODERATE AFFINITY TO DOPAMINE D4 RECEPTORS INHIBITS SEROTONONERGIC ACTIVITY AND INCREASES DOPAMINERGIC ACTIVITY ALSO INCREASES NE BY DECREASING 5-HT LEVELS

22 HSDD FLIBANSERIN SIGNIFICANT IMPROVEMENT IN THE NUMBER OF SSE S IMPROVEMENT IN LEVEL OF SEXUAL DESIRE DECREASE IN DISTRESS APPROVED FOR PREMENOPAUSAL WOMEN

23 HSDD FLIBANSERIN (ADDYI) ADVERSE EVENTS (<10%) NAUSEA DIZZYNESS FATIGUE SOMNOLENCE SYNCOPE

24 HSDD FLIBANSERIN (ADDYI) ALCOHOL INTERACTION NO ALCOHOL CONSUMPTION DUE TO HYPOTENSION AND SYNCOPE PATIENTS MUST SIGN AN AGREEMENT INTERACTION WAS NOT SEEN IN PHASE III TRIALS BUT WAS REPORTED IN A SEPARATE ALCOHOL INTERACTION STUDY DOSING: 100 MG AT BEDTIME REVALUATE AT 8 WEEKS, IF NO CHANGE THEN STOP MEDICATION

25 HSDD BUPROPRIAN ANTIDEPRESSENT INHIBITS UPTAKE OF NE AND DA NO SEROTONERGIC EFFECT MILD TO MODERATE INCREASE IN DESIRE TRAZODONE ANTIDEPRESSENT 5-HT RECEPTOR ANTAGONISTS AND REUPTAKE INHIBITOR MILD INCREASES IN DESIRE

26 HSDD BUSPIRONE ANTIANXIETY PARTIAL AGONIST FOR 5-HT1A RECEPTORS APOMORPHINE CENTRAL ACTING DOPAMINE AGONIST

27 HSDD BREMELANOTIDE MELANOCORTINS MODULATE SEXUAL BEHAVIOR AT THE HYPOTHALAMIC LEVEL ANALOG OF MSH AGONISTIC AT MELANOCORTIN 3 AND 4 RECEPTORS AIDS IN TRANSLATING SEXUAL CUES INTO GENITAL RESPONSE CONFER BENEFITS ON DESIRE AND AROUSAL

28 HSDD BREMELANOTIDE PHASE II TRIALS SIGNIFICANT IMPROVEMENT IN DESIRE, AROUSAL,SSE S, ORGASM AND DECREASED DISTRESS PHASE III TRIALS ONGOING SUBCUTANEOUS SELF INJECTED

29 HSDD LYBRIDO/LYBRIDOS 2 SUBGROUPS: WOMEN WHOSE HSDD ARE TO INSENSITIVE BRAIN SYSTEMS FOR SEXUAL CUES WOMEN WHOSE HSDD DUE TO INCREASE INHIBTORY MECHANISMS

30 HSDD LYBRIDO/LYBRIDOS LOW SENSITIVITY TO SEXUAL CUES TESTOSTERONE SUBLINGUAL ( 0.5 MG) PDE5i (SILDENIFIL 50 MG) HIGH SEXUAL INHIBITION TESTOSTERONE SUBLINGUAL (0.5 MG) BUSPIRONE (10 MG)

31 SEXUAL PAIN

32 SEXUAL PAIN VULVOVAGINAL ATROPHY PART OF GSM ETIOLOGY LACK OF ESTROGEN MENOPAUSE AI S CHEMOTHERAPY RADIATION

33 VVA PATHOPHYSIOLOGY DECREASE IN SUPERFICIAL CELLS INCREASE PARABASAL CELLS DECREASE GLYCOGEN DECREASE IN LACTIC ACID INCREASE ph

34 VVA SYMPTOMS DRYNESS PAIN BLEEDING LACERATIONS FISSURES HSDD AROUSAL/ORGASM DYSFUNCTION

35 VVA CLINICAL APPEARNCE VULVAR PALLOR LABIAL RESORPTION URETHRAL TELESCOPING NARROWED INTROITUS VAGINAL PALLOR LOSS OF RUGAE INCREASED ph DECREASED ELASTICITY

36 VVA TREATMENT-HORMONAL ESTROGENS: ESTRACE CREAM PREMARIN CREAM ESTRADIOL TABLETS ESTRING

37 VVA TREATMENTS HORMONAL ESTRADIOL CREAM 1-2 GRAMS DAILY FOR 2 WEEKS THEN TWICE A WEEK PREMARIN CREAM CONJUGATED ESTROGENS GRAMS DAILY FOR 2 WEEKS THEN TWICE A WEEK SYSTEMIC ABSORBTION

38 VVA TREATMENTS HORMONAL ESTRADIOL TABLETS 10 mcg-insert DAILY FOR 2 WEEKS THEN TWICE A WEEK SYSTEMIC ABSORBTION NOT MESSY ESTRING ESTRADIOL EVERY 3 MONTHS

39 VVA TREATMENT HORMONAL CONTRAINDICATIONS: UNDIAGNOSED VAGINAL BLEEDING CURRENT/PAST HISTORY BREAST CANCER ESTROGEN-DEPENDENT CANCER VTE HEPATIC IMPAIRMENT PREGANCY PROTEIN C OR S DEFICIENCY THROMBOPHILIC DISORDER ARTERIAL THROMBOEMBOLISM W/I 12 MTH

40 VVA TREATMENT NON-HORMONAL OSPHENA: SERM AGONISTIC ON VAGINAL TISSUE AND ENDOMETRIUM EFFECT ON BREAST DAILY ORAL PILL

41 VVA TREATMENT NON-HORMONAL OPSHENA-CONTRAINDICATIONS UNDIAGNOSED VAGINAL BLEEDING CURRENT OR PAST HX BREAST CANCER ESTROGEN DEPENDENT CA OR HX VTE ARTERIAL THROMBOEMBOLISM PREGNANCY

42 VVA TREATMENT NON-HORMONAL INTRAROSA (PRASTERONE) DHEA CONVERTS TO ESTRADIOL AND TESTOSTERONE NO SYSTEMIC ABSORBTION NO EFFECT ON ENDOMETRIUM DAILY INTRAVAGINAL TABLET Q HS

43 VVA TREATMENT NON-HORMONAL INTRAROSA-CONTRAINDICATIONS UNDIAGNOSED ABNORMAL GENITAL BLEEDING CAUTIONARY USE IN PATIENTS WITH PAST OR CURRENT HISTORY OF BREAST CANCER

44 FEMALE SEXUAL AROUSAL DISORDER

45 FEMALE SEXUAL AROUSAL DISORDER SUBJECTIVE VS. OBJECTIVE SUBJECTIVE REFERS TO A WOMAN S PERCEPTION REGARDING HER GENITAL RESPONSE OBJECTIVE REFERS TO THE PHYSIOLOGIC GENITAL AROUSAL THAT OCCURS SUCH AS VAGINAL LUBRICATION AND VASOCONGESTION LOW CONCORDANCE

46 FSAD LOW CONCORDANCE VAGINAL PHOTPLETHYSMOGRAPHY EXTERNAL GENITALIA

47 FSAD ASSESSMENT OF SUBJECTIVE AROUSAL HOW OFTEN DO YOU NOTICE YOURSELF BEING SEXUALLY AROUSED? WHAT SITUATITONS HELP YOU FEEL EXCITED? DO YOU HAVE SEXUAL FANTASIES? IS THERE A CERTAIN SCENARIO IN A FANTASY THAT AROUSES YOU? HOW EASY IS IT TO GET AROUSED WITH YOUR CURRENT PARTNER?

48 FSAD ASSESSMENT OF SUBJECTIVE AROUSAL WHAT SENSATIONS DO YOU NOTICE IN YOUR GENITAL AREA WHEN YOU GET EXCITED? DO YOU HAVE EROTIC DREAMS? DO YOU BELIEVE YOUR SEXUAL EXCITEMENT IS HEALTHY? WHAT DO YOU THINK IS INTERFERING WITH YOUR AROUSAL?

49 FSAD PSYCHOSOCIAL FACTORS DISTRACTIONS STRESS ATTACHMENT AND MOOD DISORDER AGING AND MENOPAUSE CULTURAL /RELIGIOUS FACTORS RELATIONSHIP ISSUES SEXUAL TRAUMA

50 FSAD TREATMENTS HORMONAL THERAPY TESTOSTERONE IMPROVES SEXUAL AROUSAL AND DESIRE DIRECT EFFECT ON VAGINA AND GENITAL STRUCTURES INDEPENDENT OF ESTROGEN NO APRROVED FORMULATION FOR WOMEN SERUM LEVELS DO NOT NECESSARILY CORRELATE WITH EFFECT

51 TIBOLONE FSAD TREATMENT HORMONAL THERAPY SELECTIVE TISSUE ESTROGENIC ACTIVITY REGULATOR ENHANCES MOOD, LIBIDO, AROUSAL ACTS LIKE ESTROGEN ON BRAIN,VAGINA AND BONE BUT NOT ON BREAST,UTERUS 19 NORTESTOSTERONE DERIVATIVE METABOLIZED INTO 3 METABOLITES 2 WHICH ARE ESTROGENIC 1 PROGESTIONAL AND ANDROGENIC EFFECT

52 FSAD TREATMENT SO WHY DO WE NOT USE TIBOLONE?

53 FSAD TREATMENT BECAUSE AS WITH SO MANY OTHER DRUGS FOR FSD, IT IS NOT APPROVED BY THE FDA FOR DISTRIBUTION IN THE U.S.

54 FSAD TREATMENT NON-HORMONAL THERAPY PHOSPHODIESTERASE TYPE 5 INHIBITORS INCREASE BLOOD FLOW TO CLITORIS AND VAGINA INCREASES AROUSAL?? DATA LACKING IN EFFICACY MAYBE SECONDARY TO DISCORDANCE BETWEEN SUBJECTIVE AND GENITAL AROUSAL INCREASES PHYSIOLOGIC BUT NOT SUBJECTIVE AROUSAL

55 PDE5i FSAD TREATMENT NON-HORMONAL MAY BE OF BENEFIT IN PREMENOPAUSAL WOMEN WITH MEDICAL CONDITIONS THAT EFFECT NEUROVASCULAR COMPONENTS TYPE 1 DM SPINAL CORD INJURIES MS SSRI USE

56 L-ARGININE FSAD TREATMENT NON-HORMONAL PRECURSOR TO NITRIC OXIDE DOUBLE BLINDED STUDY WITH YOHIMBINE (ADRENERGIC ANTAGONIST) INCREASE VAGINAL FLOW NO EFFECT ON SUBJECTIVE AROUSAL

57 FSAD TREATMENT NON-HORMONAL ARGINMAX L-ARGININE,GINSENG, GINKGO,DAMIANA,VITAMINS A,C,E,B COMPLEX,MINERALS, IRON CALCIUM AND ZINC DOUBLE BLINDED PLACEBO TRIAL INCREASED CLITORAL SENSATION,DESIRE, ORGASM FREQUENCY WITH NO SIGNIFICANT SIDE EFFECTS

58 FSAD TREATMENTS NON-HORMONAL DOPAMINE AGONISTS OPEN LABEL, DOSE ESCALATING STUDY SUBLINGUAL APOMORPHINE INCREASE IN HSDD, FSAD AE-NAUSEA, DIZZYNESS BUPROPRION COCHRANE REVIEW-SSRI INDUCED FSD 5 RANDOMIZED TRIALS-579 WOMEN IMPROVEMENT IN SEXUAL RATING SCORE OXYTOCIN NEUROPEPTIDE DOUBLE BLINDED,PLACEBO CONTROLLED INTRANASAL ADMINISTRATION IMPROVENT IN INTENSITY OF ORGASM AND CONTENTMENT

59 ZESTRA FSAD TREATMENT NON-HORMANAL OTC MASSAGE OIL-BORAGE SEED OIL, NAGELICA EXTRACT, EVENING PRIMROSIE, COLEUS EXTRACT, VITAMINS C AND E SMALL (N=10) RANDOMIZED, DOUBLE BLINDED PLACEBO CONTROLLED STUDY INCREASE IN SATISFACTION, ORGASM, AROUSAL DESIRE IN WOMEN WITH/WITHOUT FSAD

60 FSAD TREATMENT MECHANICAL VIBRATORS EROS BATTERY OPERATED DEVICE APPLIES VACUUM TO CLITORIS INCREASES BLOOD FLOW TO ERECTILE CHAMBERS OF THE CLITORIS AND THE VULVA FIERA AROUSER FIRST WEARABLE INTIMACY ENHANCER SMALL RECHARGEABLE BATTERY VIBRATING DEVICE ADHERES TO CLITORIS BY GENTLE SUCTION WORN IN PREPARATION FOR SEXUAL ACTIVITY

61 FEMALE ORGASMIC DISORDER

62 FEMALE ORGASMIC DISORDER ABSENCE OF ORGASM DIFFICULTY REACHING ORGASM DECREASED INTENSITY LIFELONG/ACQUIRED ISOLATED TO SPECIFIC PARTNERS, SITUATIONS ACTIVITIES DISTRESS

63 FOD GENERALLY ASSOCIATED WITH ONE OTHER FACTOR IN FSD RULED OUT IF BETTER EXPLAINED BY MEDICATION, ILLNESS, PARTNER

64 FOD PRIMARY ANORGASMIA SITUATIONAL ANORGASMIA

65 FOD VAGINAL VS. CLITORAL DSM-V DE-PATHOLIGIZED CLITORAL AND CONSIDERED A NORMAL VARIATION AT LEAST ONE THIRD OF POPULATION CANNOT EXPERIENCE VAGINAL ORGASM MOST CAN REACH ORGASM THROUGH MASTURBATION, ORGASM WITH PARTNERED ACTIVITY LESS CONSISTENT

66 FOD ASSESSMENT NATURE, ONSET, DURATION OTHER SEXUAL ISSUES DEGREE OF DISTRESS RELATIONSHIP ISSUES MASTURBATION GENERALIZED/SITUATIONAL PRIMARY/SECONDARY

67 FOD RISK FACTORS LOWER SOCIOECONOMIC CLASS POOR PHYSICAL HEALTH POOR MENTAL HEALTH RESTRICTIVE ATTITUDES AND BELIEFS LESS SEX EDUCATION PRIMARY YOUNGER LESS EXPERIENCE UNREALISTIC EXPECTATIONS SECONDARY ASK ABOUT CONDITIONS WHERE THEY WERE ORGASMIC RULE OUT CONTEXTUAL FACTORS, INADEQUATE PARTNER STIMULATION,PHYSIOLOGIC FACTORS

68 FOD TREATMENTS EDUCATION SEXUAL THERAPY DIRECTED MASTURBATION SENSATE FOCUS VIBRATORS EROTICA

69 FOD TREATMENTS PATHOPHYSIOLOGY CONTEXT OF AROUSAL AND DESIRE DISORDERS EFFERENT PART OF THE ORGASMIC REFLEX NORADRENERGIC, CHOLINERGIC ACTIVITY ENZYMATIC ACTION ON GUANOSINE MONOPHOSPHATE SYSTEM AFFERENT PART OF THE ORGASMIC REFLEX INCREASES INTENSITY OF STIMULUS INCREASES THE RECEPTIVITY OF GENITALIA BY INCREASING BLOOD FLOW AND STRUCTURAL INTEGRITY

70 FOD TREATMENTS PDE 5i MIXED RESULTS PHYSIOLOGIC STUDIES SHOW INCREASE VASOCONGESTION SYSTEMIC ESTROGEN/TESTOSTERONE INCREASES AROUSAL, DESIRE,ORGASM IN WOMEN WITH OOPHERECTOMY RECEPTIVE CNS EFFECTS,VVA IMPROVEMENT, EXCITATORY EFFECT OF TESTOSTERONE ON LIMBIC SYSTEM TIBOLONE

71 FOD TREATMENTS CONTEXT OF SUFFICIENT AROUSAL FEW STUDIES DESCRIBED AS A STOP IN THE INCREASING INTENSITY OF AROUSAL TOWARD ORGASM GOAL- INTENSIFY THE STIMULATION IN STRENGTH, FREQUENCY

72 FOD TREATMENT OXYTOCIN FACILTATES MUSCLE CONTRACTION EROTICA FIERA EROS VIBRATORS

73 CONCLUSION ACKNOWLEDGE THAT SEXUAL DYSFUNCTION CAUSES SIGNIFICANT DISTRESS AND IS NOT A LIFESTYLE ISSUE REALIZE THAT WE MUST UTILIZE BIOPSYCHOSOCIAL APPROACH TO DEAL WITH FSD MUST HAVE DISCUSSIONS WITH OUR PATIENTS REGARDING FSD

74 THANK YOU