Carmita Abdo, MD PhD Medical School, University of São Paulo Program of Studies in Sexuality (ProSex)
Carmita Abdo, MD PhD As per Rule 1595/2000 of the Federal Medical Council and Resolution RDC 102/2000 of ANVISA (Brazilian Health Surveillance Agency), I declare that: I participate in clinical trials sponsored by the following Laboratories: Pfizer, Lilly, Bayer Schering Pharma and Janssen-Cilag I am/was a consulting member of the following Advisory Boards: Pfizer (Viagra), Lilly (Cialis), Janssen-Cilag (Dapoxetine), Medley (Vivanza) and Bayer Schering Pharma (Nebido) I am/was a lecturer for Pfizer, Lilly, GSK, Janssen-Cilag, Bayer Schering Pharma, MSD, Medley and Abbott
Desire Arousal Orgasm Resolution Sexual excitement Time Masters and Johnson, 1966 and Kaplan, 1977; adapted by APA, 1987
Emotional intimacy Emotional and physical satisfaction Responsive sexual desire and arousal Spontaneous sexual desire Sexual neutrality Sexual stimulus Sexual arousal Adapted from Basson R. J Sex Marital Ther. 2001;27:33-43
Physical health Neurobiology Endocrine function Biology Psychology Performance anxiety Depression Distress Upbringing and myths Cultural norms Expectations Sociocultural Interpersonal Quality of current and past relationships Intervals of abstinence Life stressors /Finances Rosen RC et al. Obstet Gynecol Clin North Amer. 2006;334;515-26
Predisposing factors Maintaining factors Early development Precipitating factors Current functioning Hawton K, Catalan J. Behav Res Ther. 1986;24(4):377-85
Psychological body image (e.g. obesity) relationship issues, partner availability/aging 1 fears (e.g. pregnancy, infertility, STD, history of sexual abuse/trauma, cultural practices) Neurobiological reproductive endocrinology (ie. anything that lowers testosterone such as hyperprolactinemia, opiates, menopause) 2 general health status/illness (e.g. fatigue) 1 and comorbidities medication/substance use 1 Meston C. West J Med. 1997;167(4):285-90; 2 Giraldi A et al. J Sex Med. 2013;10(1):58-73
Female 302.72 Female sexual Interest/Arousal disorder 302.73 Female orgasmic disorder 302.76 Genito-pelvic pain/ Penetration Disorder 302.79 Other specified sexual dysfunction 302.70 Unspecified sexual dysfunction Substance/Medication-induced sexual dysfunction Male 302.71 Male hypoactive sexual desire disorder 302.72 Erectile disorder 302.74 Delayed ejaculation 302.75 Early ejaculation 302.79 Other specified sexual dysfunction 302.70 Unspecified sexual dysfunction Substance/Medication-induced sexual dysfunction APA. DSM-5, 2013
As regards the onset of sexual dysfunction lifelong acquired As regards the occurrence of sexual dysfunction generalized situational As regards the severity (distress) mild moderate severe APA. DSM-5, 2013
It is often the result of reduced levels of estrogen, testosterone, progesterone, antioxidants, and nitric oxide; or increased levels of pro-inflammatory cytokines and monoamine oxidase in the brain, increased levels of monoamine oxidase destroy the pleasure chemical dopamine pro-inflammatory cytokines have been shown in studies to decrease sexual desire, attraction, and activity Saks BR. Psych Times. 2008;15(25)5
Neurologic Spinal cord injury, neuropathy, herniated disc, multiple sclerosis, epilepsy Endocrine Hypothyroidism, adrenal dysfunction, hypogonadism, diabetes mellitus, menopause Vascular Hypertension, arteriosclerosis, stroke, venous insufficiency, sickle cell disorder Genitourinary Urinary incontinence, vaginitis, pelvic inflammatory disease, endometriosis Systemic Illness Renal, pulmonary, hepatic diseases, advanced malignancies, infections Psychiatric Depression, anxiety disorders, psychotic illness, eating disorders, PTSD Clayton AH, Ramamurthy S. In: Balon R. Sexual Dysfunction: The Brain-Body Connection. Karger, Basel, Switzerland, 2008; Basson R, Schultz WW. Lancet. 2007;369:409-424; Kingsberg SA, Janata JW. Urol Clin North Am. 2007;34:497-506; Zemishlany Z, Weizman A. In: Balon R. Sexual dysfunction: The brain-body connection. Karger Basel, Switzerland, 2008
Psychotropic medications Antihypertensives SSRIs/SNRIs/TCAs Mood stabilizers Antipsychotics Beta-blockers Alpha-blockers Benzodiazepines Antiepileptic drugs Diuretics Cardiovascular agents Lipid-lowering agents Digoxin Hormones Oral contraceptives Estrogens Progestins Antiandrogens GnRH agonists Other Histamine H2-receptor blockers Narcotics Non-steroidal anti-inflammatory drugs Clayton AH, Ramamurthy S. In: Balon R. Sexual Dysfunction: The Brain-Body Connection. Karger, Basel, Switzerland, 2008; Basson R, Schultz WW. Lancet. 2007;369:409-424; Kingsberg SA, Janata JW. Urol Clin North Am. 2007;34:497-506
Etiology Biological factors hormonal imbalance or insufficiency neurotransmitter imbalances medications and side effects acute or chronic illnesses Development factors lack of sexual education or permission sexual abuse sexual coercion Psychological factors anxiety depression other psychiatric disorders Interpersonal factors relationship conflicts partner sexual dysfunction Cultural factors religious or customs moral issues Contextual factors privacy comfort safety Leiblum SR. Treating sexual desire disorders. New York-London: Guildford Press, 2010
Etiology Introital / midvaginal pain inflammatory muscular psychosexual hormonal/dystrophic traumatic neurological vascular Deep pain endometriosis pelvic inflammatory disease iatrogenic referred abdominal pain pelvic varicose veins chronic pelvic pain Graziottin A. J Endocrinol Invest. 2003:26(3):115-21
Recurrent or persistent involuntary contraction of the perineal muscles surrounding the outer third of the vagina, that prevent vaginal penetration and cause marked distress or interpersonal difficulty Lifelong personality disorders childhood sexual abuse negative attitudes toward sex religious orthodoxy Acquired: secondary to psychogenic cause World Health Organization. ICD-10, 1993; APA. DSM-IV-TR, 2002
Desire and arousal are preserved To evaluate whether the sexual stimulus was adequate regarding focus duration intensity
Sexual interest/arousal disorder Orgasmic disorder Genito-pelvic pain/penetration disorder Basson R et al. J Urol 2000;163:888-93
Free testosterone Sex hormone binding globulin (SHBG) Plasma level of estrogens Progesterone levels Prolactin levels Thyroid-stimulating hormone (TSH), T 3 and free T 4 LH FSH Giraldi A et al. J Sex Med.2013;10(1):58-73
Treatment of Female Sexual Dysfunction Process Action Outcome IDENTIFICATION OF SEXUAL DYSFUNCTION Sexual, medical and psychosocial history Physical examination Laboratory tests Sexual dysfunction diagnosis confirmed Additional testing and/or referral as needed ASSESSMENT AND EDUCATION CHANGE REVERSIBLE ETIOLOGIES SEXUAL/COUPLE THERAPY Review of initial findings Patient and partner education Assessment of referral needs Lifestyle modification Medication change if it promotes sexual difficulties Pharmacological therapy Assess sexual dysfunction (sexual interest/arousal, orgasmic disorders) Identification of patient and partner needs and/or preferences Referral if indicated and desired by patient Sexual dysfunction resolution with follow-up and reassessment OR Referral to psychologist/psychiatry Sexual dysfunction resolution with follow-up and reassessment An algorithm for clinical decision-making in the assessment and treatment of sexual dysfunction. Stages are identified in the model, with each stage reflecting specific processes, actions, and outcomes. The importance of assessment and follow-up, as well as patient education and communication aspects are shown throughout the model Adapted from Process of Care Consensus Panel. Int J Impot Res. 1999;11:59 70
Primary care physicians Education (dispelling myths) Exercise Healthy diet Adequate rest Stress reduction Psychotherapy Cognitive-behavioral therapy Sensate-focus Controlled self-stimulation Couples counseling Physical therapy Vaginal dilators Biofeedback Bitzer J, Brandenburg U. Maturitas.2009;63:160-3
Hormonal estrogen testosterone* Psychotropic medications bupropion* Phosphodiesterase-5 inhibitors* *Not FDA approved for this indication
Hormonal topical or systemic estrogen therapy tibolone (synthetic steroid with estrogen, progesterone and weak androgenic effect that lower SHBG): more research are needed topical vaginal DHEA Non hormonal PDE-5 inhibitors (poor results) bupropion flibanserin central action (CNS) vaginal lubricants (reduce symptoms of vaginal atrophy) Giraldi A et al. J Sex Med.2013;10(1):58-73
Postmenopausal women without a history of hormonedependent breast cancer Low dose as long as symptoms persist Not indicated for Sexual Interest/Arousal disorder but can be helpful if pain/dryness is contributing to low desire Consider if prescribing testosterone Basson R. et al. J Sex Med. 2010;7(1 Pt 2):314-26
Good evidence (Level A) to support its use in estrogenreplete women 1-3 300 mcg patch for 24 weeks (avoids hepatic metabolism) Both naturally 4 and surgically 1-3 menopausal women Improvements seen in desire, orgasm frequency and total number of sexually satisfying encounters 1. Braunstein GD et al. Arch Intern Med. 2005;165:1582-9; 2. Buster JE et al. Obstet Gynecol. 2005;105:944-52; 3. Davis SR et al. Menopause. 2006;13:387-96; 4. Shifren JL et al. Menopause. 2006;5:770-9
Androgen levels not clearly associated with decreased desire difficult to measure testosterone levels accurately Role in premenopausal women is not established 1 Off label indication Long term efficacy/safety not known 1-3 Study population (definition of decreased desire) 1 Relationship between arousal and desire 1 Need for concomitant use of estrogen 1 1. Basson R. Expert Opin Pharmacother. 2009;10:1631-48; 2. NAMS. Menopause. 2005;12:497-511; 3. Wierman ME et al. J Clin Endocrinol Metab. 2006;91:3697-710
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) no statistically significant improvement in desire 268 women ages 20-40 diagnosed with HSDD (Level B) 2 premenopausal, not depressed, normal testosterone 12 weeks of buproprion SR 150 mg/day improvement in rating scale of sexual function (globally and specific subsets) greatest improvement in frequency of sexual activity, thoughts/desire, and orgasm decrease in personal distress score Add-on or substitute therapy for SSRI-induced sexual dysfunction (Level B) 3,4 1. Segraves R. et al. J Clin Psychopharm. 2004;24:339-42; 2. Safarinejad MR et al. BJU Int. 2010 Sep;106(6):832-9; 3. Safarinejad MR. J Psychopharmacol. 2011;25(3):370-8; 4. Seretti A, Chiesa A. J Clin Psychopharm. 2009;29:259-66
Use in antidepressant associated female sexual dysfunction 1 Potential use in women with sexual dysfunction secondary to neurodegenerative diseases 2 (?) 1. Nurnberg HG et al. JAMA. 2008;300:395-404; 2. Brown DA et al. Ann Pharmacother. 2009;43:1275-85
Hormonal Tibolone: estrogenic, progestogenic, androgenic synthetic hormone (postmenopausal women) 1 Centrally acting agents Flibanserin (partial serotonin agonist/antagonist) 2 Bremelanotide (melanocortin agonist) 3 Other Prostaglandin gel 4 1. Ziaei S et al. Climacteric. 2010;13(2):147-56; 2. Katz M et al. J Sex Med. 2013;10(7):1807-15; 3. Safarinejad MR. J Sex Med. 2008;5(4):887-97; 4. Goldstein I et al. J Sex Med. 2012;9 (suppl 1):22
Lybrido and Lybridos LibiGel TBS-2 (Tefina) van der Made F et al. J Sex Med. 2009;6(2):429-39 van der Made F et al. J Sex Med. 2009;6(3):777-90 White WB et al. Am Heart J. 2012;163(1):27-32 BioSante rises after ending LibiGel safety study. www.businessweek.com/ap/ 2012-09-04/biosante-rises-after-endinglibigel... van Gorsel H et al. Poster presented at: International Society for the Study of Women s Sexual Health Annual Meeting (ISSWSH); February 19-22, 2012, Jerusalem, Israel Efficacy and safety of TBS-2 testosterone gel in premenopausal women with acquired female orgasmic disorder. Clinical Trials Identifier: NCT01607658 Alprostadil (Femprox) Goldstein I et al. J Sex Med. 2012;9(suppl 1):22 Apomorphine Bechara A et al. J Sex Med. 2004;1(2):209-14 MSH Analog (Bremelanotide) Safarinejad MR. J Sex Med. 2008;5(4):887-97 Intravaginal DHEA suppositories Labrie F et al. Menopause. 2009;16(5);923-31 Ospemifene Bachmann GA, Komi JO. Menopause. 2010;17(3):480-6 The Viveve procedure Millheiser LS et al. J Sex Med. 2010;7(9):3088-95
The foundation of treatment of female sexual dysfunctions is nonpharmacologic including primary care physicians directed, psychotherapy directed modalities and physical therapy Most promising pharmacological treatments include hormonal and centrally acting agents Other medications may have role for different types of female sexual dysfunction Frank J. Current and emerging therapies for hypoactive sexual desire disorder. 2012