Overview of Female Sexual Dysfunction for the Primary

Overview of Female Sexual Dysfunction for the Primary Care Physician WVU WOMENS HEALTH CURRICULUM – Revisions 9/2008 Stanley Zaslau, MD, MBA, FACS Program Director & Associate Professor Division of Urology West Virginia University

Objectives - 1 l In this lecture, participants will learn: – Incidence, epidemiology and pathophysiology of Female Sexual Dysfunction – Female pelvic anatomy – AFUD Classification of Female Sexual Disorders – Clinical Evaluation of the Female Sexual response

Objectives - 2 l In this lecture, participants will learn: – Treatment of FSD Oral agents l Neutraceuticals l Vacuum Clitoral Erection Device l Potential novel therapies l

Incidence 30 million men with compromised erectile function l Paucity of epidemiologic data regarding incidence of female sexual dysfunction l – – – multi-causal multi-dimensional age-related progressive highly prevalent

Incidence l National Health and Social Life Survey (1999) – 1749 Women 33% of women lack sexual interest l 25% of women do not experience orgasm l 20% of women report lubrication difficulties l 20% of women report sex is not pleasurable l Laumann E, Paik A, Rosen R. Sexual dysfunction in the United States: Prevalence and predictors, JAMA 1999; 281; 537 -544.

Incidence l Sexuality in Older Women (Diokno, 1990 and Mooradian 1990) – 448 women over the age of 60 66% are sexually inactive l 12% of married women had difficulty with intercourse; 14% experienced dyspareunia l Sexuality positively correlated with marital status l Less likely to have sex if partners in poor health l Diokno AC, et al. Sexual function in the elderly. Archives of Internal Medicine 1990; 150: 197 -200.

Incidence l Rosen (1993) Study – 329 women age 18 to 73 years – Most common areas of dysfunction 38% lack of desire l 16% lack of pleasure l – Age and relationship status predict FSD – single and older women highest incidence Rosen (1993) Journal of Sexual and Marital Therapy

Female Pelvic Anatomy l l l Vagina – Vascular supply, innervation and physiologic changes Clitoris – Vascular supply, innervation and physiologic changes Vestibular bulbs Uterus Pelvic Floor Muscles

Vagina-Anatomy & Blood Supply l l Labia minora surrounds vagina; protected by outer labia majora Labia minora enclose the vestibule which contains: – Clitoris – Vaginal opening -- Urethral opening l Innervation – Autonomic – Somatic motor fibers of S 2 -S 4 innervate bulbocavernosis and ischiocavernosus muscles – Pudendal nerve—sensory to introitus l Main arterial supply (extensive anastomosis) – Vaginal branches of the uterine arteries – Vaginal branches of the pudendal arteries – Ovarian arteries

Clitoris-Anatomy & Blood Supply l l Erectile organ similar to the penis Blood supply – Iliohypogastric-pudendal arterial bed – Internal pudendal artery branches to form common clitoral artery --> dorsal and cavernosal clitoral arteries l Consists of fused midline corpora cavernosa – Unable to trap venous blood – With sexual stimulation, engorgement, rather than erection occurs

Vestibular Bulbs l l l Paired, 3 -cm structures along the vaginal orifice Homologous to corpus spongiosum of the penis Composed of vascular smooth muscle Arterial supply: branches of internal pudendal artery Sensory innervation: posterior branches of the pudendal nerve

Uterus l l Uterine/cervical glands secrete mucus during sexual arousal Uterine/pelvic procedures interrupt vaginal innervation --> negative impact on later sexual health Disruption of uterosacral and cardinal ligaments can result in genital arousal and orgasm difficulties Role for nerve sparing procedures as similar to those performed in men

Pelvic Floor Muscles l Pelvic diaphragm formed by: – Levator ani muscles – Urogenital diaphragm – Peroneal membrane, composed of l l ischiocavernosus, bulbocavernosus and superficial transverse perinii muscles Muscles pull rectum, vagina and urethra anteriorly towards pubic bone

Pelvic Floor Muscles l l l Non-voluntary spasm of pelvic floor=vaginismus Laxity or hypotonia of pelvic floor, associated with – vaginal hypoanesthesia – anorgasmia – incontinence Question all women with voiding dysfunction about their sexual function!!

Female Sexual Physiology: Normal l Physiological changes during arousal – Enlargement of clitoris – Dilation of arterioles, increased vaginal and clitoral blood flow – Seeping of vascular transudate across vaginal membrane ---> lubrication – Expansion and tenting of upper 1/2 of vagina – Response mediated by nitric oxide (role for sildenafil)

AFUD Classification and Definition of Female Sexual Disorders l Consensus classification (AFUD Consensus Panel, 1998) – Hypoactive Sexual Desire Disorder – Sexual Aversion Disorder – Orgasmic disorders – Sexual pain disorders l Dyspareunia l Vaginismus – Other sexual pain disorders

Hypoactive Sexual Desire Disorder l Hypoactive sexual desire disorder – Persistent or recurrent deficiency (or absence) of sexual fantasies/thoughts or desire for a receptivity to sexual activity – Causes personal distress – Differential diagnosis: surgical or medical menopause l endocrine disorders l

Sexual Aversion Disorder l Sexual Aversion Disorder – Persistent or recurrent phobic aversion to and avoidance of sexual contact with a sexual partner – Causes personal distress – Results from: l childhood trauma (physical or sexual abuse)

Sexual Arousal Disorder Persistent or recurrent inability to attain or maintain sufficient sexual excitement l Causes personal distress l Differential diagnosis: medical causes, prior pelvic trauma, pelvic surgery, medications l May be expressed as l – lack of subjective excitement or lack of genital lubrication/swelling

Orgasmic Disorder l l Persistent or recurrent difficulty, delay in or absence of attaining orgasm following sexual stimulation Causes personal distress Primary (never attained orgasm)--emotional trauma or sexual abuse Secondary – Surgery – Hormone deficiency -- Trauma

Sexual Pain Disorders l Dyspareunia – Recurrent or persistent genital pain with sexual intercourse – Consider: vestibulitis l vaginal atrophy l vaginal infection l

Sexual Pain Disorders l Vaginismus – Recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with vaginal penetration. – Conditioned response to painful penetration (? psychological or emotional)

Other Sexual Pain Disorders Herpes Simplex Virus l Vestibulitis l Prior genital mutilation l Trauma l Endometriosis l Interstitial cystitis l

Interstitial Cystitis (IC) and Female Sexual Dysfunction (FSD) l Pain associated with intercourse – Entry dyspareunia – Deep dyspareunia

IC and FSD 100 patients with IC l FSFI administered l – Assess 6 domains of sexual function l l l Desire Arousal Orgasm Lubrication Satisfaction Pain Zaslau, et al. WVMJ 2008

IC and FSD l Results: – Mean age 39 years – Impairment in all domains “ 50 -75% of the time” l Conclusions – FSD in IC involves more than pelvic pain Zaslau, S et al FSFF, Vancouver, BC 2002

FSD in IC: 1 st 400 Patients 400 IC patients l FSFI administered on line at IC-Network l Compared to two groups l – Controls (131) – Female sexual arousal disorder (129)

FSD in IC 1 st 400 Patients l Results – Statistically significant decrease in all domains when compared to controls – Stastically significant decrease in all domains when compared to Arousal Disorder Group – Lowest scores: pain Zaslau, et al AUA 2003, Chicago, IL.

Conclusions: IC and FSD Global sexual dysfunction affecting all domains l May be age related and progressive l Pain domain has lowest scores l Treatment is multimodal and may involve counseling, sex therapy and physical therapy l

Etiologies of Female Sexual Dysfunction Vasculogenic l Neurogenic l Hormonal/Endocrine l Musculogenic l Psychogenic l

Vasculogenic l l l Risk factors: hypertension, hypercholesterolemia, smoking, heart disease Associated with ED in men and sexual dysfunction in women Diminished vaginal and clitoral blood flow (atherosclerosis) Results in symptoms of vaginal dryness and dyspareunia Alteration of circulating estrogen levels: atrophy of vaginal and clitoral smooth muscle Traumatic arterial disruption: pelvic fracture, blunt trauma, surgical disruption, chronic perineal pressure (bicycle riding)

Neurogenic Spinal cord injury (SCI) to the central or peripheral nervous system l Diabetes mellitus l Complete upper motor neuron lesions of the sacral cord l Incomplete SCI: capacity for psychogenic arousal and vaginal lubrication l

Hormonal/Endocrine l l l Disorders of the hypothalamic-pituitary axis Medical or surgical castration Premature ovarian failure Chronic birth control use Symptoms: decreased desire, vaginal dryness, lack of sexual arousal

Musculogenic l l l Lavator ani muscles Perineal membrane – bulbocavernosus and ischiocavernosus muscle Contraction contributes to arousal and orgasm Hypertonicity ---> vaginismus or dyspareunia Hypotonicity ---> vaginal hypoanesthesia, coital anorgasmia, urinary incontinence during sexual intercourse or orgasm

Psychogenic l Emotional and relational issues – self esteem – body image – quality of the relationship with the partner l Medications – serotonin re-uptake inhibitors

Clinical Evaluation of the Female Sexual Response Medical/Physiologic Evaluations l Psychosocial/Psychosexual Assessment l

Medical/Physiologic Evaluations Full history, physical exam, pelvic exam l Hormonal profile (FSH, LH, prolactin, free testosterone, SHBG, estradiol) l Evaluation of the sexual response l – Genital blood flow (Duplex doppler ultrasound) – Vaginal p. H – Vaginal compliance/elasticity – Genital sensation by vibratory perception threshold

Psychosocial/Psychosexual Assessment Address emotional and relational issues l Subjective assessment of sexual function l – Brief Index of Sexual Function (BISF-W) – Inventory of Female Sexual Function (IFSF)

Therapy Sildenafil l Dehydroepiandesterone (DHEA) l Alprostadil (PGE 1) l Apomorphine l L-arginine and Yohimbine l Vacuum Clitoral Therapy Device l

Sildenafil and Female Sexual Dysfunction 33 post menopausal women in prospective study l Excluded: heart disease, uncontrolled psych disorder, poorly controlled DM, alcohol abuse, CVA, history of MI or concurrent nitrate therapy l Took sildenafil 50 mg 1 hour prior to planned sexual activity l Given a 9 item Index of Female Sexual Function Questionnaire l

Sildenafil and Female Sexual Dysfunction l Results – 3 patients dropped out because of adverse effects Clitoral hypersensitivity in 7 (21%) l Headache, dyspepsia, dizziness l – No differences in intercourse satisfaction and sexual desire after 3 months of therapy – Women on HRT had an increased overall score (not statistically significant)

Sildenafil and Female Sexual Dysfunction l Comments – No placebo arm – Raises several questions What is the potential role for other oral agents such as phentolamine and apomorphine? l Would higher doses of sildenafil produce a better response? l Role for combination therapy? l Role for topical therapy? l

Sildenafil in SCI Women with FSD l l l 50% of women achieve orgasm regardless of injury type (complete vs. incomplete) Sildenafil given to 19 women with SCI Results in significant increases in – subjective arousal – sexual stimulation – heart rate and decreases in blood pressure Sipski M, Grand Master Lecture #2, Female Sexual Function Forum, 2000

Sildenafil for FSD in Women with Depression l l 50% of patients on SSRI have some sexual dysfunction Study: 10 women with depression on SSRI with FSD 50 mg sildenafil prior to sexual activity Results: 9/10 had reversal of anorgasmia or delayed orgasm; most with 1 st dose of sildenafil Hensley et al. Sildenafil for Iatrogenic Seritonergic antidepressant medication induced sexual dysfunction. Female Sexual Function Forum, 2000.

Sildenafil after Hysterectomy? l l 35 women evaluated after hysterectomy BISF-Q survey used for pre/post treatment assessment 100 mg sildenafil given for 6 weeks Results: – “Improved” sensation – “Improved” ability to reach orgasm – “Decreased” pain and discomfort Berman, et al. Hysterectomy and Sexual Function: A Role for Sildenafil? , Female Sexual Function Forum, 2000.

Dehydroepiandosterone (DHEA) l l l Adrenal gland hormone, precursor to sex steroids testosterone and estradiol Given in daily doses of 50, 75 and 100 mg Included women with sexual dysfunction for more than 6 months and low testosterone levels Treatment duration 2 to 6 months Results: – Increase in mean and free testosterone levels – Improvement in Sexual Distress Scale Scores Suggests: DHEA may be useful for women with FSD and low testosterone Munnariz, et al. Lowered Personal Sexual Distress Scale Scores Following DHEA Treatment for Multi-dimensional FSD and Low Testosterone. Female Sexual Function Forum, 2000.

Topical Alprostadil l l 1% alprostadil formulation (0. 25 m. L gel) Placed on glans penis, allowed to dry, then vaginal intercourse 36 healthy volunteer couples (16 treatment; 16 controls). All men had Erectile Dysfunction Results: – No changes in vital signs in either partner – Females: some noted improved clitoral/vaginal sensation Taintor, et al. Tolerance of Topical PGE 1 Gel as a Topical Treatment for Erectile Dysfunction during Vaginal Intercourse, Female Sexual Function Forum, 2000.

Alprostadil (PGE 1) Pellets l l 2 women with vaginismus Given 1000 mcg alprostadil pellets to insert vaginally prior to sex Evaluated after for improvement in vaginal muscle spasm Results: – both able to have intercourse without difficulty Benet, A. Intravaginal Alprostadil Pellets for Treatment of Vaginismus, Female Sexual Function Forum, 2000.

Intranasal Apomorphine l l Acts centrally to facilitate erectile response 12 healthy women studied at 3 doses of Apomorphine Pharmacokinetics, nasal tolerance well tolerated thus far. Efficacy studies “at-home” currently underway Khan, et al. Evaluation of Nasal Apomorphine for FSD and Male ED as a function of dose, Female Sexual Function Forum, 2000.

Neutraceutical Therapy l l l Contents: Gingko balboa, Korean ginseng, Larginine, calcium, iron, zinc and multi-vitamins 93 women (age 22 -73 years); 46 treatment and 47 controls Subjects: – 58 premenopausal women – 16 perimenopausal women – 19 post menopausal women

Neutraceutical Therapy l Results: – PERI: l 73% improvement in sexual desire l 73% improvement in clitoral sensation l 73% improvement in sexual satisfaction – POST: l 64% improvement in sexual satisfaction – PRE: l 71% increase in sexual desire l 68% increase in sexual satisfaction Trant A. Clinical Study on a Nutritional Supplement for the enhancement of Female Sexual Function, Female Sexual Function Forum, 2000.

L-arginine & Yohimbine l l l 6 g arginine and 6 mg yohimbine 23 post menopausal women with female sexual arousal disorder Physiological arousal measured by vaginal pulse amplitude Subjective arousal measured by questionnaire Erotic film shown after medication given Results: – Increased VPA responses vs. placebo at 60 minutes but not 30 or 90 min. – Drugs reach peak plasma levels at 40 min Meston CM. The effects of L-arginine and Yohimbine in Sexual Arousal in Postmenopausal Women with Female Sexual Arousal Disorder, Female Sexual Function Forum, 2000.

Vacuum Clitoral Therapy Device l l l Treatment designed to increase clitoral blood flow, enhance clitoral engorgement and improve arousal 32 subjects (20 with FSD and 12 without FSD) Results: Parameter Greater sensation Increase lubrication Ability to achieve orgasm Increased sexual satisfaction FSD 90% 80% 55% 80% No FSD 58% 33% 42% 25%

Vacuum Clitoral Therapy Device l Results: – No side effects noted with use of device – Study by same authors in 5 diabetic women with FSD Parameter Greater sensation Increase lubrication Ability to achieve orgasm Increased sexual satisfaction Diabetic with FSD 4/5 (80%) 3/5 (60%) 4/5 (80%) Billups et al. Vacuum Induced Clitoral Engorgement for treatment of Female Sexual Dysfunction, female Sexual Function Forum, 2000.

Conclusions An exciting area applicable to all physicians. l Physicians need to learn through research and patient care about: l – Epidemiology – Diagnosis – Pathophysiology – Treatment

References l l l Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, et al. The female sexual function index (FSFI): A multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000; 26: 191 -208. Basson R, Berman J, Burnett A, Derogatis L, Ferguson D, Fourcroy J, et. al. Report of the International Consensus Development Conference on Female Sexual Dysfunction: Definitions and classifications. J Urol. 2000; 163: 888 -893. Nicolosi A, Laumann EO, Glasser DB, Moreira ED, Pail A, and Gingell C. Sexual Behavior Sexual Dysfunctions Age 40: The Global Study of Sexual Attitudes and Behaviours. Urology. 2004; 54(5): 991 -997.

References l l l Laumann EO, Paik A, Rosen RC: Sexual Dysfunction in the United States: Prevalence and Predictors. JAMA. Feb 10, 1999: Vol 281, No 6: 537 -544. Peters KM, Killinger KA, Carrico DJ, Ibrahim IA, Diokno AC, and Graziottin A: Sexual Function and Sexual Distress in Women with Interstitial Cystitis: A Case Control Study. Urology. 2007; 70(3): 543 -547. Zaslau S, Triggs J, Morgan L, Osborne J, Subit M, Riggs D: “Characterization of Female Sexual Dysfunction in Patients with Interstitial Cystitis. ” Presented at the American Urological Society Meeting, Chicago, IL, April 27, 2003.

References l l Zaslau S, Subit MJ, Mohseni HF, Riggs D, Jackson B, Kandzari S: “Sexual Dysfunction in Patients with Interstitial Cystitis. ” Presented at the American Urogynecology Meeting, Hollywood, FL, September 12, 2003. Zaslau S, Subit MJ, Mohseni HF, Riggs D, Jackson B, Kandzari S. “Sexual Dysfunction in Patients with Interstitial Cystitis: Initial Analysis of Under 40 Cohort. ” Presented at the Mid-Atlantic Section of the American Urological Society Meeting, Boca Raton, FL, October 2629, 2003.