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FEMALE SEXUAL DYSFUNCTION: HOPE AND HELP FOR YOUR PATIENTS Kris Christiansen, MD Park Nicollet Sexual Medicine and Male Infertility St. Louis Park, MN March 28, 2019 DISCLOSURES • I have no financial disclosures to discuss. • Off-label use of medications will be discussed in this presentation. • The use of medications for conditions not approved by the FDA can be used by clinicians according to their discretion but needs to be disclosed to patients at the time of prescribing. OBJECTIVES • Discuss effective examples of how to take a sexual history • Review common female sexual dysfunctions • Learn about treatment options for female sexual problems 94% of U.S. adults feel sexual pleasure adds to quality of life • Brunk, Family Practice News & Internal Medicine News 5/10/2013. • C. Marwick, “Survey says patients expect little physician help on sex. • Laumann, A. Paik JAMA 1999; 281. PRINCIPLES FOR SEXUAL HISTORY TAKING • Patients prefer that health care provider initiate topic and advise (90%) • Use simple, direct language • Compassion, honesty, normalizing statements • Declare and demonstrate lack of embarrassment • Be aware of patient’s cultural background • Ensure confidentiality • Avoid judgement and assumptions Athanasiadis L, Papaharitou S, Salpiggidis G et al. J Sex Med 2006;3(1):47-55. Sadovsky R, Nusbaum M. J Sex Med. 2006;3(1);3-11. HOW TO CONDUCT THE INTERVIEW • Use words and body language that put the patient at ease • Open, non-defensive body posture • Sit and maintain eye contact • Avoid nervous gestures • Choose language appropriate to age, ethnicity, and culture of patients • Practice using sexual terminology • Ask open-ended questions • Use silences to allow patients to speak Athanasiadis L, Papaharitou S, Salpiggidis G et al. J Sex Med 2006;3(1):47-55. Sadovsky R, Nusbaum M. J Sex Med. 2006;3(1);3-11. WHEN TO TAKE A SEXUAL HISTORY • Health related conditions/life events • Prenatal/postpartum, infertility, menopause visit • Chronic illness follow-up • Urological or gynecologic surgery • New patient or annual well-woman exam Basson R. Sexuality and sexual disorders. Clin UpdatWomen's Health Care. 2003;1:1-84 BIOPSYCHOSOCIAL MODEL MEDICAL CONDITIONS CONTRIBUTING TO SEXUAL DYSFUNCTION • Cardiovascular disease • Neuromuscular disorders • Diabetes • Prolactinoma • Thyroid disease • Malignancy/treatment • Chronic pain • Breast, anal, bladder, colorectal, gynecologic • Urinary incontinence • Gynecologic problems • Spinal cord injury • Cystocele, rectocele, • Multiple sclerosis endometriosis, fibroids, lichen sclerosis, uterine prolapse, vulvodynia/vestibulodynia MEDICATIONS ASSOCIATED WITH SEXUAL DYSFUNCTION • Anticonvulsants:: carbamazepine, phenytoin, primidone • Cardiovascular medications: amiodarone, beta blockers, calcium channel blockers, clonidine, digoxin, hydrochlorothiazide • Hormonal medications: antiandrogens (flutamide, spironolactone), hormonal contraception (birth control pills, patches, and rings) • Pain relievers: NSAIDS (ibuprofen, etc.), opioids • Psychotropic meds: antipsychotics, anxiolytics, antidepressants, lithium • Chemotherapeutic agents, aromatase inhibitors • Drugs of abuse: Alcohol, amphetamines, cocaine, heroin, marijuana Kingsberg and Woodard. Obstet and Gynecol. 2015;125:477-86 Graziottin A and Lieblum SR. J Sex Med. 2005;2:133-145. Liu-Seifert H, et al. Neuropsychiatr Dis Treat. 2009;5:47-54. Clayton A. J Sex Med. 2007;4:260-268 NON-MEDICAL FACTORS CONTRIBUTING TO SEXUAL HEALTH CONCERNS • Co-morbid psychiatric • Trauma history concerns (e.g., depression; • Sexual performance anxiety anxiety; eating disorders; chemical dependency) • Fear with resultant muscle tension and/or anxiety • Body image struggles • Distress related to medical • What it means to be a factors (systemic impact) man/woman in our culture (e.g., bilateral mastectomy) • Maladaptive relationship dynamics Pfaus JG. Pathways of sexual desire. J Sex Med. 2009;6:1506-1533 Bancroft J, Graham CA, Janssen E, Sanders SA. The dual control model: current status and future directions. J Sex Res. 2009;46(2- 3):121-142. Clayton AH. Epidemiology and neurobiology of female sexual dysfunction. J Sex Med. 2007;4(supplement 4):260-268. ANATOMY AND PATHOPHYSIOLOGY THE VESTIBULE • Lateral border is Hart’s line • Medial border is the hymen and urethra • Openings of the Bartholin’s, Skene’s, and minor vestibular glands • Derived from the primitive urogenital sinus • Different blood supply from the vagina • Rich in androgen receptors (Androgen receptors > Estrogen receptors) Reprinted with permission from Andrew Goldstein, MD, FACOG, IF THE CLITORIS COTTON SWAB TEST • Use a moistened cotton swab • Apply uniform pressure around the entire vestibule. • Outside Hart’s line • Inside labia minora • Around “clock face”(6:00 posterior) • Esp. glands and where pt. indicates pain in history COMMON FEMALE SEXUAL DYSFUNCTION PROBLEMS COMMON FEMALE SEXUAL DYSFUNCTION PROBLEMS • Low Desire • Hypoactive sexual desire disorder • Pain with sexual activity • Female genital-pelvic pain disorder • Vulvodynia, vestibulodynia • Vaginismus/Pelvic floor dysfunction • Genitourinary syndrome of menopause • Female arousal disorder • Female orgasm disorder Johannes CB, Clayton AH, Odom DM, et al. J Clin Psychiatry. 2009;70:1698-1706. HYPOACTIVE SEXUAL DESIRE DISORDER Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Obstet Gynecol 2008;112: 970-978. Mayo Clin Proc. 2018;93(4):467-487. Clayton AH, Goldfischer ER, Goldstein I, Derogatis L, Lewis-D’Agostino DJ, Pyke R. J Sex Med. 2009;6:730-738. TREATMENT OPTIONS TREATMENT OPTIONS FOR WOMEN WITH FEMALE SEXUAL DYSFUNCTION (GENERALIZED TREATMENT APPROACH) • Address any contributing factors • Depression, anxiety, meds • Fatigue, stress • Relationship problems: refer for counseling • Optimize diabetes and chronic medical conditions • Treat sexual pain if present • Lubricants that do not contain parabens, glycerin, or propylene glycol • Vaginal Moisturizers (Luvena, Yes VM, Sylk Natural Intimate) • Localized vaginal estrogen • Lifestyle, exercise, Mediterranean diet • Refer for sex therapy Giugiano et al. J Sex Med. 2010 May:7(5):1883-90. Wing et al. Diabetes Care. June 11, 2013 LIFESTYLE AND HEALTH-RELATED FACTORS ASSOCIATED WITH SEXUAL ACTIVITY • Increased • Decreased • Mediterranean diet • Smoking • Exercise/walking • Depression/ Somatization • Resilience • SSRI/SNRIs • Normal weight/BMI • CAD/ Inactivity • Social support • Obesity/M. Synd. (↑TGs) • Diabetes (psychosocial • Social activity factors) SSRI/SNRI= selective serotonin reuptake inhibitor/serotonin norepinephrine • Sleep difficulties reuptake inhibitor CAD= coronary artery disease • Vasomotor symptoms TG= triglycerides Met S= metabolic syndrome TREATMENT OPTIONS FOR HYPOACTIVE SEXUAL DESIRE DISORDER (HSDD) Clayton AH et al. Mayo Clin Proc. 2018;93(4):467-487. BIOLOGICAL APPROACHES FOR LOW DESIRE • Increase androgens (locally and systemically) • Increase dopamine • Increase norepinephrine • Modulate serotonin • Melanocortins TREATMENT OPTIONS FOR HYPOACTIVE SEXUAL DESIRE DISORDER (HSDD) • Psychotherapy/sex therapy • Central nervous system agents • Flibanserin (Addyi®) for premenopausal women • Bupropion (off label) • Buspirone (off label) • Hormonal agents for late peri- and postmenopausal women • Estrogen/progesterone • testosterone (off label) • Shifren J. Menopause 2006;Davis SR. NEJM 2008, Wierman ME et al., Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice GuidelineJCEM 2014; 99(10):3489–3510 Caruso et al. J Sex Med 2012;9:2057-2065. Caruso et al., Fertil Steril 2006. Clayton, A, Hamilton D. Female Sexual Dysfunction. Obstet Gynecol Clin N Am 2009; 36. 861-876. Sayuk et al. Diabetes Care 2011 Feb; 34 ADDYI® (FLIBANSERIN) • Indicated for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. • Studied in > 11,000 women • Action: • 5-HT1A receptor agonist and 5-HT2 receptor antagonist • Increases norepinephrine and dopamine • Decreases serotonin • Side effects: drowsiness, dizziness, nausea, low BP, and syncope ADDYI® (FLIBANSERIN) • Contraindications • Alcohol – increased risk of severe hypotension and syncope • Strong or moderate CYP3A4 inhibitors (eg, ketoconazole, ritonavir, atazanavir, clarithromycin etc.) • Hepatic impairment • Providers and pharmacies must be REMS certified to prescribe and dispense Addyi®. • Patients and prescribers must sign an agreement form acknowledging the risks of hypotension and syncope and that alcohol is contraindicated when taking Addyi ®. • Cost: $400+ for 1 month supply BUPROPION AND PDE-5 INHIBITORS (OFF LABEL USE) • Bupropion increases norepinephrine/dopamine which appears to improve: libido, arousal, orgasm and satisfaction • One RCT showed benefit of sildenafil in premenopausal women with type 1 DM and Cialis 5 mg qd to help with arousal, orgasm, enjoyment and decreased pain Caruso et al. J Sex Med 2012;9:2057-2065. Caruso et al., Fertil Steril 2006. Clayton, A, Hamilton D. Female Sexual Dysfunction. Obstet Gynecol Clin N Am 2009; 36: 861-876. Sayuk et al. Diabetes Care 2011 Feb;34 ZESTRA • Zestra (OTC) botanical oils and extracts. • “clinically proven” to improve sexual desire, arousal, and sexual satisfaction • Directions indicate to apply to the clitoris and labia 5 -10 minutes before SA. • Recommend applying to mons pubis to avoid burning sensation (14.6%, experienced mild to moderate genital burning) Ferguson et al.Randomized, placebo-controlled, double-blind, parallel design trial of the efficacy and safety of Zestra in women with mixed desire/interest/arousal/orgasm
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  • Intrarosa™ (Prasterone)

    Intrarosa™ (Prasterone)

    Intrarosa™ (prasterone) – New Drug Approval • On November 17, 2016, the FDA announced the approval of Endoceutics’ Intrarosa (prasterone), for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause. • Approximately 50% of postmenopausal women suffer from VVA. The symptoms of VVA are vaginal dryness, pain during sexual activity (dyspareunia) and irritation and itching. • Intrarosa contains the active ingredient, prasterone that is also known as dehydroepiandrosterone (DHEA). Prasterone is an inactive endogenous steroid and is converted into active androgens and/or estrogens. — Although DHEA is included in some dietary supplements, the efficacy and safety of those products have not been established for diagnosing, curing, mitigating, treating or preventing any disease. • The efficacy of Intrarosa was evaluated in two 12-week placebo-controlled trials enrolling 813 postmenopausal women with moderate to severe dyspareunia. The four co-primary efficacy endpoints were severity of dyspareunia, the % of vaginal superficial cells, the % of parabasal cells, and vaginal pH. — The mean change in severity of dyspareunia was -0.87 vs. -1.27 (p = 0.0132) in trial 1 and -1.06 vs. -1.42 (p = 0.0002) in trial 2 for placebo vs. Intrarosa, respectively. — The mean change in % superficial cells was 0.91% vs. 5.62% (p < 0.0001) in trial 1 and 1.75% vs. 10.2% (p < 0.0001) in trial 2 for placebo vs. Intrarosa, respectively. — The mean change in % parabasal cells was -1.62% vs. -47.4% (p < 0.0001) in trial 1 and -11.98% and -41.51% (p < 0.0001) in trial 2 for placebo vs.