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  1. 1. Sex Across the Lifecycle: Constants, Changes, and Problems Anita H. Clayton, M.D. Professor and Vice Chair Department of Psychiatric Medicine University of Virginia Health System
  2. 2. What’s it all about anyhow? <ul><li>Psychological/Social/Emotional </li></ul><ul><li>Physiological/biological: interactions of sex steroids and neurotransmitters </li></ul><ul><li>Cognitive: thoughts, fantasies, satisfaction </li></ul><ul><li>Cultural </li></ul>APA, DSM IV, 1994
  3. 3. Phases of the Sexual Response Cycle <ul><li>Desire </li></ul><ul><li>Arousal </li></ul><ul><li>Orgasm </li></ul><ul><li>Resolution </li></ul><ul><li>Other areas to consider </li></ul><ul><ul><li>satisfaction </li></ul></ul><ul><ul><li>pain </li></ul></ul>APA, DSM-IV 1994
  4. 4. Central Effects on Sexual Function estrogen (permissive ) testosterone (initiation) progesterone (receptivity) ORGASM prolactin oxytocin Norepinephrine (NE) 5-HT Dopamine (DA) Modified from Clayton AH. Psychiatric Clinics of North America 2003; 26:673-682 + 5-HT SUBJECTIVE EXCITEMENT DESIRE + - - + + + + + - + -
  5. 5. Peripheral Effects on Sexual Function NE 5-HT 2A Nitric Oxide (NO) Cholinergic fibers Prostaglandin E NPY Substance P 5-HT Clayton AH. Psychiatric Clinics of North America 2003; 26:673-682 VIP 5-HT + - ? + - + SENSATION gonads adrenals <ul><li>Estrogen </li></ul><ul><li>Testosterone </li></ul><ul><li>Progestin </li></ul>maintain genital structure and function } VASOCONGESTION + - + + Clitoral and penile tissue
  6. 6. Changes Over the Life Cycle <ul><li>Puberty </li></ul><ul><li>Reproductive years </li></ul><ul><li>Pregnancy and the postpartum period </li></ul><ul><li>Perimenopausal period </li></ul><ul><li>Postmenopausal years </li></ul>
  7. 7. Puberty <ul><li>Development of regular menstrual cycles (monthly fluctuations in estrogen, progesterone, and testosterone) </li></ul><ul><li>Rise in testosterone linked to increasing sexual desire, perhaps mediated by social variables 1 </li></ul><ul><li>Sexual self image as a “woman” </li></ul><ul><li>Recognition of body image </li></ul>1 Halpern, Udry & Suchindran, 1997
  8. 8. Reproductive Years <ul><li>Regular sexual activity regulates menstrual cycles and reduces anovulatory cycles 1 </li></ul><ul><li>Fear of or desire for pregnancy, and infertility affect sexual experience </li></ul><ul><li>Triphasic oral contraceptives are associated with more sexual thoughts, fantasies, and sexual interest than monophasic oral contraceptives 2 </li></ul><ul><li>Premenstrual symptoms diminish desire, frequency of sexual activity, ability to achieve orgasm, and satisfaction with orgasm in the late luteal phase 3 </li></ul>1 Cutler, Garcia & Krieger 1979; Cutler, Perth, Huggins, Erickson & Garcia 1985; 2 McCoy & Matyas 1996; 3 Clayton, Clavet, McGarvey Warnock, & Weihs 1999
  9. 9. Pregnancy and the Postpartum Period <ul><li>Pregnancy may be associated with dramatic changes in desire, pain on intercourse, or decreased ability to achieve orgasm 1 </li></ul><ul><li>Restoration of sexual functioning following delivery parallels restoration of hormonal cycling (delayed with breastfeeding), 2 but this is a common period for the onset of HSDD </li></ul><ul><li>Possible change in body image (“shape” of pregnancy, full expression of being a woman, weight gain, etc.) </li></ul>1 Oruc, Esen, Lacin, Adiguzel, Uyar, Koyuncu 1999; 2 Glazener 1998; Visness & Kennedy 1996
  10. 10. Perimenopausal Period <ul><li>Dramatic fluctuations in sex hormones </li></ul><ul><li>“ Change of life” with physical symptoms, freedom from constraints (children leaving home, no longer fertile, etc.), change in body/self image 1 </li></ul><ul><li>Low levels of estrogen and testosterone may lead to decreased libido 2 , dyspareunia associated with vaginal dryness 1 , diminished sexual response, etc. </li></ul>1 Kingsberg 1998; 2 Chiechi, Granieri, Lobascio, Ferrer, Loizzi 1997
  11. 11. Postmenopausal Years <ul><li>Aging: general health decline, medication use including hormone replacement therapy, illness-related factors 1 </li></ul><ul><li>Relationship/partner factors: emotional, physical changes in partner </li></ul>1 Meston 1997
  12. 12. Factors with Potential Sustained Effects <ul><li>Partner availability/Issues with self stimulation </li></ul><ul><li>Fear of sexually-transmitted diseases </li></ul><ul><li>History of childhood sexual abuse, or history of sexual assault </li></ul><ul><li>Cultural practices ie. female circumcision </li></ul>
  13. 13. Problems in Sexual Functioning <ul><li>43% of 1749 US women reported sexual dysfunction in the 1992 National Health and Social life Survey (NHSLS) </li></ul><ul><li>Younger women complain of low sexual desire, and difficulty achieving orgasm </li></ul><ul><li>Sexual problems decrease as we age, except for diminished lubrication, and unmarried women have 1.5 the rate of problems seen in married women </li></ul>Laumann, Paik, Rosen 1999
  14. 14. Cultural Differences in Sexual Functioning <ul><li>Hispanic women report the lowest rates of sexual problems </li></ul><ul><li>African-American women report lower sexual desire and satisfaction </li></ul><ul><li>White women describe more sexual pain </li></ul>Laumann, Paik, Rosen 1999
  15. 15. More Problems in Sexual Functioning <ul><li>Negative effects on sexual functioning 1 </li></ul><ul><ul><li>Declining social status (ie. divorce) </li></ul></ul><ul><ul><li>History of sexual trauma </li></ul></ul><ul><ul><li>Lower education attainment </li></ul></ul><ul><li>Marital difficulties are associated with: 2 </li></ul><ul><ul><li>arousal, orgasmic, and enjoyment difficulties </li></ul></ul><ul><ul><li>anxiety and depression </li></ul></ul><ul><li>Poor physical health is correlated with sexual pain 1 </li></ul>1 Laumann, Paik, Rosen 1999; 2 Dunn, Croft, Hackett 1999
  16. 16. Primary Sexual Disorders <ul><li>Disorder = dysfunction + distress </li></ul><ul><li>Desire: </li></ul><ul><ul><li>Hypoactive sexual desire disorder (HSDD) </li></ul></ul><ul><ul><li>Sexual aversion disorder </li></ul></ul><ul><li>Female sexual arousal disorder (FSAD) </li></ul><ul><li>Female orgasmic disorder </li></ul><ul><li>Pain disorders: dyspareunia, vaginismus </li></ul><ul><li>Subtypes: </li></ul><ul><ul><li>May be due to psychological factors, general medical conditions, be substance-induced, or a combination </li></ul></ul><ul><ul><li>Context: generalized or situational type </li></ul></ul><ul><ul><li>Onset: lifelong or acquired </li></ul></ul>APA, DSM-IV 1994
  17. 17. Known Causes of Sexual Dysfunction <ul><li>Psychosocial/situational factors: interpersonal relationships, body image, sexual self-esteem, prior psychosexual adjustment </li></ul><ul><li>Medical conditions: endocrine, psychiatric, cardiovascular, neurological, genitourinary </li></ul><ul><li>Substance-induced: medications, alcohol, drugs of abuse </li></ul><ul><li>Combination of factors </li></ul>
  18. 18. Desire <ul><li>Sexual desire includes: </li></ul><ul><ul><li>Physiologic </li></ul></ul><ul><ul><li>Cognitive </li></ul></ul><ul><ul><li>Behavioral components </li></ul></ul><ul><li>manifested by: </li></ul><ul><ul><li>sexual thoughts and fantasies </li></ul></ul><ul><ul><li>interest in participation in sexual activity </li></ul></ul><ul><ul><ul><li>initiation of sexual activity </li></ul></ul></ul><ul><ul><ul><li>receptivity to partner approach </li></ul></ul></ul>Kornstein & Clayton (eds.), 2002
  19. 19. Influences on Libido <ul><li>Reproductive endocrinology (ie. anything that lowers testosterone such as hyperprolactinemia, opiates, menopause) </li></ul><ul><li>Body image (ie. obesity) </li></ul><ul><li>General health status/illness (ie. fatigue) </li></ul><ul><li>Medication/substance use </li></ul><ul><li>Psychological/relationship issues </li></ul><ul><li>Fears (ie. pregnancy, infertility, STD, history of sexual abuse, cultural practices ) </li></ul>
  20. 20. Reproductive-Related Periods of Low Libido <ul><li>Pre-puberty </li></ul><ul><li>Late luteal phase in women with premenstrual symptoms 1 </li></ul><ul><li>Monophasic oral contraceptive users 2 </li></ul><ul><li>Pregnancy 3 </li></ul><ul><li>Postpartum 4 </li></ul><ul><li>Perimenopause </li></ul><ul><li>Menopause 5 </li></ul>1 Clayton, Clavet, McGarvey, Warnock, Weihs 1999; 2 McCoy & Matyas 1996; 3 Oruc, Esen, Lacin, Adiguzel, Uyar, Koyumcu 1999; 4 Glazener 1998; Visness & Kennedy 1997; 5 Chiechi, Granieri, Lobascio, Ferrer, Loizzi 1997
  21. 21. Biology of Libido <ul><li>Physiologic </li></ul><ul><ul><li>Primary sex steroid is testosterone: progesterone may influence sexual receptivity 1 </li></ul></ul><ul><ul><li>Neurotransmitters: dopamine and serotonin </li></ul></ul><ul><li>Chronobiology </li></ul><ul><ul><li>Estrogen plus androgen replacement enhances desire in postmenopausal women 2 </li></ul></ul><ul><ul><li>Testosterone levels in premenopausal women inconclusively linked to desire, 3 but higher testosterone levels linked to increased response to bupropion SR in SSRI-induced SD 4 </li></ul></ul><ul><ul><li>Supplemental testosterone cypionate injections (100 mg/month IM) improved sexual desire to normal levels despite no difference in testosterone levels at baseline between women with HSD and aged-matched women without sexual complaints 5 </li></ul></ul>1 Frye, Rhodes, Walf, Petralia 2001; 2 Sherwin 1991; 3 Persky et al. 1978; Udy et al. 1986; 4 Clayton, McGarvey, Warnock, Kornstein 2001; 5 van Anders SM, Chernick AB, Chernick BA, et al 2005.
  22. 22. Arousal <ul><li>Phase of sexual excitement manifested by pelvic vasocongestion, vaginal lubrication, and swelling of the external genitalia </li></ul>
  23. 23. Physiology of Arousal <ul><li>Hormones </li></ul><ul><ul><li>Estrogen </li></ul></ul><ul><ul><li>Vasoactive intestinal peptide (VIP) may mediate autonomic effects on pelvic blood flow 1 </li></ul></ul><ul><li>Neurotransmitters: </li></ul><ul><ul><li>Central dopamine stimulation 2 </li></ul></ul><ul><ul><li>Modulation of cholinergic-adrenergic balance 2 </li></ul></ul><ul><ul><li>Alpha-1 adrenergic agonism 2 </li></ul></ul><ul><ul><li>Presence of nitric oxide 3 </li></ul></ul>1 Levin 1992; 2 Segraves 1989; 3 Burnett, Lowenstein, Bredt, Chang, Snyder 1992
  24. 24. Orgasm <ul><li>Process of physiologic release of sexual tension, associated with rhythmic contractions of perineal and reproductive organ structures with cardiovascular and respiratory changes </li></ul>
  25. 25. Physiologic Mechanism of Orgasm <ul><li>Hormones: </li></ul><ul><ul><li>Estrogen </li></ul></ul><ul><ul><li>Oxytocin 1 </li></ul></ul><ul><li>Unclear neurotransmitters involved: Can disrupt orgasm with stimulation of 5-HT 2 receptors 1 , or with alpha-adrenergic antagonism 2 </li></ul>1 Watson & Gorzalka 1992; 2 Segraves 1989
  26. 26. Etiology of Sexual Dysfunction <ul><li>Medical </li></ul><ul><ul><li>Primary (eg. HSDD) </li></ul></ul><ul><ul><li>Secondary: psychiatric, neurological, endocrine, genitourinary </li></ul></ul><ul><li>Situational/Psychosocial </li></ul><ul><li>Substance-induced: psychotropics, non-psychotropics, drugs of abuse </li></ul>
  27. 27. Medical Conditions & Sexual Dysfunction <ul><li>Neurological illness </li></ul><ul><li>Endocrine disorders </li></ul><ul><li>Genitourinary conditions </li></ul><ul><li>Infectious processes </li></ul><ul><li>Cardiovascular disease </li></ul><ul><li>Autoimmune disorders </li></ul>
  28. 28. Secondary Sexual Disorders: Psychiatric <ul><li>70% of patients with MDD report diminished libido 1 </li></ul><ul><li>41% of women with hypomania experienced increased sexual intensity 2 </li></ul><ul><li>Decreased sexual interest seen in women with eating disorders 3 , and women with histrionic personality disorder 4 </li></ul><ul><li>60% of women with schizophrenia report never experiencing an orgasm vs. 13% of normal volunteers 5 </li></ul>1 Casper, Redmond, Katz, Schaffer, Davis, Koslow 1985; 2 Goodwin & Jamison 1990; 3 Morgan, Wiederman, Pryor 1995; 4 Apt & Hurlbert 1994; 5 Friedman & Harrison 1984
  29. 29. Antidepressant Effects on Sexual Functioning <ul><li>Diminished desire and/or function </li></ul><ul><ul><li>SSRIs 1 </li></ul></ul><ul><ul><li>Venlafaxine 1 </li></ul></ul><ul><ul><li>TCAs 2 </li></ul></ul><ul><ul><li>MAOIs 2 </li></ul></ul><ul><li>Few negative effects on desire or function </li></ul><ul><ul><li>Bupropion-SR 1 </li></ul></ul><ul><ul><li>Mirtazapine 3 </li></ul></ul><ul><ul><li>Nefazodone 1 </li></ul></ul><ul><ul><li>Selegiline transdermal system 4 </li></ul></ul>1 Clayton, Leadbetter, Bass, Bolden-Watson, Donahue, Jamerson, Metz, DeVeaugh-Geiss 2000; 2 Segraves 1992; 3 Boyarsky, Haque, Rouleu, Hirschfeld 1999; 4 Clayton, Campbell, Favit, et al. 2007
  30. 30. Assessment of Sexual Dysfunction <ul><li>Sexual history </li></ul><ul><li>Assessment of current level of sexual functioning </li></ul><ul><li>Documentation of medical and psychiatric history/diagnosis </li></ul><ul><li>Identification of substances with effects on sexual functioning </li></ul><ul><li>Endocrine measures as indicated: free and total testosterone, sex hormone binding globulin, TFTs, Hgb A 1C , prolactin, estradiol, FSH, and LH levels, lipid profile </li></ul><ul><li>Neurological and/or genitourinary exam </li></ul>
  31. 31. Treatment of Primary Sexual Dysfunctions <ul><li>Psychotherapy, especially with history of negative sexual experiences </li></ul><ul><li>Use of erotica in sex therapy 1 </li></ul><ul><li>Insure adequate levels of sex hormones ie. low libido </li></ul><ul><ul><li>In postmenopausal women, with adequate estrogen replacement, if free testosterone < 2.0 pg/ml, consider testosterone supplementation to physiologic androgen levels 2 </li></ul></ul><ul><ul><li>Oral micronized methyl-T (0.25 mg, 0.50 mg, or 0.75 mg tablets) compounded </li></ul></ul><ul><ul><li>Soon to be available, testosterone gel and/or patch </li></ul></ul>1 Striar & Bartlik 1999; 2 Warnock 2001
  32. 32. Treatment of Sexual Disorders <ul><li>Hypoactive Sexual Desire Disorder 1 </li></ul><ul><ul><li>66 women with HSDD were randomized to bupropion SR (n=31) or placebo (n=35) for 3 months </li></ul></ul><ul><ul><li>Receptivity to partner initiation was significantly greater with bupropion SR; CSFQ desire scores were also greater </li></ul></ul><ul><ul><li>Bupropion SR also significantly increased measures of sexual arousal, orgasm/completion, and sexual satisfaction as measured by the CSFQ 1 </li></ul></ul><ul><li>Testosterone levels in the upper half of the normal range may enhance response to bupropion 2 </li></ul><ul><li>For FSAD, consider sildenafil 3 +/- hormones (estrogen or SERMs) in peri- and postmenopausal women </li></ul>1 Segraves, Clayton, Croft, Wolf, Warnock 2004; 2 Clayton, McGarvey, Warnock, Kornstein 2001; 3 Warnock 2001
  33. 33. Conclusions <ul><li>Multiple factors may affect sexual functioning in women across the life cycle </li></ul><ul><li>Appropriate assessment is important to direct treatment </li></ul><ul><li>Some recent successes in the management of sexual dysfunction in the context of physiologic, psychosocial, cognitive, and cultural factors </li></ul>