A New Frontiers Program on
Women’s Health
Emerging Perspectives on the Science and Medicine of
Hypoactive Sexual
Desire Disorder (HSDD)
The Internal Medicine and Primary Care Perspective
Program Chairman and Moderator
Anita H. Clayton, MD
David C Wilson Professor
Department of Psychiatry & Neurobehavioral Sciences
Professor of Clinical Obstetrics & Gynecology
University of Virginia
Charlottesville, VA
Program Faculty
PROGRAM CHAIRPERSON
Anita H. Clayton, MD
David C Wilson Professor
Department of Psychiatry &
Neurobehavioral Sciences
Professor of Clinical Obstetrics &
Gynecology
University of Virginia
Charlottesville, VA
Jennifer E. Frank, MD, FAAFP
Assistant Professor
Department of Family Medicine
University of Wisconsin School of
Medicine and Public Health
Appleton, Wisconsin
Sheryl Kingsberg, PhD
Division Chief, Behavioral Medicine Program
University Hospitals
Associate Professor of Medicine
Case Western Reserve University
Cleveland, Ohio
Lori Brotto, PhD
Assistant Professor
Department of Obstetrics and Gynecology
University of British Columbia
Vancouver, BC
A New Frontiers Program on
Women’s Health
Addressing Current Challenges in
Female Sexual Disorders
What Internal Medicine Specialists
Need to Know about HSDD
Program Chairman and Moderator
Anita H. Clayton, MD
David C Wilson Professor
Department of Psychiatry & Neurobehavioral Sciences
Professor of Clinical Obstetrics & Gynecology
University of Virginia
Charlottesville, VA
A New Frontiers Program on
Women’s Health
►
Clinical focus
►
Prevalence and pathophysiology of HSDD
►
Communication strategies
►
Differential diagnoses
►
Intervention and management
Case Example
► 26-year-old MWF presents with 1 year
history of decreased libido, some problems
with vaginal lubrication, and diminished
orgasmic capacity. No pain with intercourse.




Change in sexual function since marriage 4
years ago, but relationship still strong
1 year post-partum with mild depressive
symptoms since delivery
No general health problems
On oral contraceptives for birth control
A New Frontiers Program on
Women’s Health
Hypoactive Sexual Desire Disorder
Prevalence and Barriers to Recognition
in the Primary Care Setting
Sheryl A. Kingsberg, Ph.D
Chief, Division of Behavioral Medicine
University Hospitals Case Medical Center
Professor, Department of Reproductive Biology
Case Western Reserve University School of Medicine
Cleveland OH
“Normal” Female Sexuality
Defined by Cultural Norms
►
Historically given little attention
►
Victorian era: discovery that female orgasm
irrelevant to conception
►
2008: women’s sexuality hits ‘Primetime’
but not quite its ‘Prime’
Human Sexual Response:
Classic Models
►Excitement
Divided
►Plateau
Desire
Arousal
►Orgasm
►Resolution
Linear progression
Masters WH, Johnson VE. Human Sexual Response. Boston, Mass: Little Brown; 1966.
Kaplan HS. The New Sex Therapy. 1974.
Female Sexual Response Cycle
Orgasm
Orgasm
Plateau
Plateau
Excitement
Excitement
(B)
A BC
(C)
(A)
Adapted from Masters WH, Johnson VE. Human Sexual Inadequacy. Little Brown; 1970.
Female Sexual Response Cycle
Emotional
Intimacy
Seeking Out
and Being
Receptive to
Emotional and
Physical Satisfaction
Spontaneous
Sexual Drive
Sexual
Stimuli
Sexual
Arousal
Biologic
Arousal and
Sexual Desire
Psychological
Basson R. Med Aspects Hum Sex. 2001;1:41-42.
Women’s Endorsement of Models of
Female Sexual Response
►
The Nurses’ Sexuality Study, N=133
►
Equal proportions of women endorsed the
Masters and Johnson, Kaplan, and Basson
models of female sexual response as
representing their own sexual experience.
►
Women endorsing the Basson model had
significantly lower FSFI domain scores than
women who endorsed either the Masters and
Johnson or Kaplan models.
Michael Sand, PhD, MPH, and William A. Fisher, PhD, JSM, 2007 4: 708-719
Biopsychosocial Model of Female
Sexual Response
(e.g., physical health,
neurobiology,
endocrine function)
(e.g., upbringing,
cultural norms and
expectations)
Biology
Psychology
Sociocultural Interpersonal
1. Rosen RC, Barsky JL. Obstet Gynecol Clin North Am. 2006;334:515-526.
(e.g., performance
anxiety, depression)
(e.g., quality of current
and past relationships,
intervals of abstinence,
life stressors, finances)
US Adult Women Are
Sexually Active*
Random Digital Dialing Survey of Women 18-94 Years Old (N=2000)†
100
US Women Sexually Active (%)
70
66
70
65
60
50
46
40
30
20
20
10
0
18-29
30-39
40-49
(n=362)
(n=451)
(n=473)
60-94
50-59
(n=271)
(n=443)
Age Ranges
*Sexually active was defined as oral (active or receptive), vaginal, or anal intercourse in the past 3 months.
†Age-adjusted percentages.
Patel D, et al. Sex Trans Dis. 2003;30(3):216-220.
DSM-IV-TR Classification of FSDs
Sexual Desire Disorders
Hypoactive Sexual Desire
Disorder
Absence or deficiency of sexual interest
and/or desire
Sexual Aversion Disorder
Aversion to and avoidance of genital contact
with a sexual partner
Sexual Arousal Disorders
Female Sexual Arousal Disorder
Inability to attain or maintain adequate
lubrication-swelling response of sexual
excitement
Orgasmic Disorders
Female Orgasmic Disorder
Delay in or absence of orgasm after a
normal sexual excitement phase
Pain Disorders
Dyspareunia
Genital pain associated with sexual
intercourse
Vaginismus
Involuntary contraction of the perineal
muscles preventing vaginal penetration
DSM-IV TR Criteria for FSD
►
Sexual complaint or problem in desire, arousal, orgasm, or
sexual pain:
●
Judgment of severity of sexual symptom is made by the clinician,
talking into account factors that affect sexual functioning, such as
age and the context of the person’s life
►
The disturbance causes marked distress or interpersonal
difficulty
►
The sexual dysfunction is not:
●
●
Better accounted for by another primary psychiatric disorder
(except another Sexual Dysfunction)
Due exclusively to the direct physiological effects of a substance
(eg, drug of abuse, medication) or a general medical condition
American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders. 4th Ed, text revision (DSM-IV-TR). Washington, DC: American Psychiatric
Association; 2000.
Overlap of FSDs
Sexual Desire
Disorders
Sexual Arousal
Disorder
Orgasmic
Disorder
Dyspareunia
Vaginismus
Basson R, et al. J Urol. 2000;163:888-893.
Prevalence of FSD:
A Historical Perspective
Sexual Dysfunction in the United States*
►
OBJECTIVES: Assess the prevalence and risk of experiencing sexual dysfunction in men and
women
►
NOT ASSESSED: Distress or interpersonal difficulty
►
POPULATION: 1749 women and 1410 men 18-59 years of age
►
RESULTS: 43% of women reported sexual dysfunction
100
50
43
Prevalence of Sexual Dysfunction
in Women by Latent Class
Women (%)
40
30
22
20
14
7
10
0
Total for Sexual
Low Sexual
Dysfunctions
Desire
Assessed
Arousal
Pain
Subsets for Sexual
Dysfunctions Assessed
*Sexual problems were measured in this study. NHLHS data on critical symptoms do not connote a clinical
definition of sexual dysfunction.
Laumann E, et al. JAMA. 1999; 281(6):537-544.
Prevalence of FSD: PRESIDE
►
OBJECTIVES: Estimate the prevalence of self-reported sexual problems (any, desire,
arousal, and orgasm), the prevalence of problems accompanied by personal distress, and
describe related correlates
►
NOT DETERMINED: Whether low desire with sexually related personal distress was primary
or secondary to another illness; pain was not assessed
►
POPULATION: 31,581 US female respondents ≥18 years of age from 50,002 households
►
RESULTS*: Response rate was 63% (n=31,581 / 50,002)
Prevalence of Female Sexual Problems Associated With Distress
100
50
43.1
US Women (%)
45
40
37.7
35
30
25
Distressing Sexual Problems
21.1
20
15
11.5
9.5
10
*All results are US
population ageadjusted.
Sexual Problems
25.3
5.1
4.6
5
0
Desire
Arousal
Shifren JL, et al. Obstet Gynecol. 2008;112(5):970-978.
Orgasm
Any
Prevalence of Sexual Problems
Associated with Distress (PRESIDE)
Age-stratified
prevalence
Desire
Arousal
Orgasm
Any
2868/28,447
1556/28,461
1315/27,854
3456/28,403
18-44
8.9
3.3
3.4
10.8
45-64
12.3
7.5
5.7
14.8
65 or older
7.4
6.0
5.8
8.9
Shifren J et al Obstetrics & Gynecology, 2008, 112(5).
Prevalence of Low Sexual Desire and
Hypoactive Sexual Desire Disorder
Nationally Representative Sample of US Women
Low
Desire
N
Low
Desire
%
HSDD
N
All
1936
36.2
1920
8.3
Age 30-39
453
30.8
453
8.3
Age 40-49
542
25.3
539
9.0
Age 50-59
824
37.8
814
9.4
Age 60-70
117
60.7
114
5.8
Surgical Menopausal
635
39.7
631
12.5
Natural Menopausal
551
52.4
541
6.6
Premenopausal
750
26.7
748
7.7
Category
West SL et al Archives of Internal Medicine, 2008
HSDD
%
Decreased Sexual Desire With Distress
Negatively Impacts Women’s Lives
► Decreased
sexual desire is associated with
negative effects including:1,2
●
●
●
●
Poor self-image
Mood instability
Depression
Strained relationships with partners
1. Shifren JL, et al. Obstet Gynecol. 2008;112(5):970-978. 2. Leiblum SR. Menopause. 2006;13(1):46-56.
Hypoactive Sexual Desire Disorder
(HSDD)
► Persistent or recurrent deficiency or absence
of sexual thoughts, fantasies and/or desire for,
or receptivity to, sexual activity
● Causes marked personal distress or interpersonal
difficulties
● Not better accounted for by another primary
disorder, drug/medication, or general medical
condition
Components of Sexual Desire
► Drive:
● Sex steroids and neurotransmitters play a
role in modulating sexual desire, drive, and
excitement
► Expectations, beliefs, and values
► Motivation
Hull EM, et al. Behav Brain Res. 1999;105:105–116.
Levine S. Sexual Life, 1994
Social Psychology Theories: Understanding
Psychosocial Aspects of Female Sexual Desire
►
Self-Perception Theory
● People make attributions about their own attitudes by
relying on observations of external behaviors (Bem,
1965)
►
Wundt's schema of sensory affect (aka Kingsberg’s IceCream Analogy)
● Increases of stimulus intensity above threshold are felt
as increasingly pleasant up to a peak value beyond
which pleasantness falls off through indifference to
increasing unpleasantness.
Prevention and Treatment of
Sexual Problems
ASK!
You cannot treat a problem if
you don’t know it exists
In PRESIDE About One-Third of Women With
a Distressing Sexual Problem Sought Formal Care
Type of Help-Seeking (n=3239)
14.5%
Did not
seek help
Formal
34.5%
9.1%
Anonymous
Informal
41.9%
Formal=HCP; informal=anyone other than an HCP.
Shifren JL, et al. J Women’s Health. 2009;18(4)461-468.
Physician Questioning Increases Patient
Reporting of Sexual Dysfunction
40
Patients (%)
30
19%
20
10
3%
0
Spontaneous
Reporting
N=887.
Bachmann GA, et al. Obstet Gynecol. 1989:73:425-427.
Reporting After
Direct Inquiry
Physician-Based Barriers
►
Lack of training/Inadequate knowledge or skills1
►
Lack of awareness of associated comorbid conditions
►
“Improving quality of life” may not be considered a
high priority2
►
Time constraints3
►
Underestimation of prevalence
►
No FDA approved treatments for female sexual
dysfunction
1Broekman
CPM, et al. Int J Impot Res. 1994;6:67-72.
JF, et al. Cliniguide® to Erectile Dysfunction. Lawrence DellaCorte Publications, Inc; 2001.
3Baum N, et al. Patient Care. Spring 1998(suppl):17-21.
2Eid
Training Is Not Preparing HCPs To Be
Informed in the Area of FSD
Curriculum Time (Hours) Dedicated to Human Sexual Health Education
(N=101)*
*Human sexual health education was not specifically defined in the survey but included: type of educational
experiences, disciplines, subject and topics areas, clinical program, continuing medical education, total number
of hours, amongst others.
Solursh DS, et al. Int J Impot Res. 2003;15(suppl 5):S41-S45.
Most HCPs Have Little or No Confidence in
Screening for or Diagnosing HSDD
Web-Based Survey Consisting of Residents and Faculty
in an Academic Primary Care Clinic (N=53; 41.5% women, 58.5% men)
Respondents who had not screened or
diagnosed patients with HSDD
90
HCPs who felt little or no confidence in
diagnosing HSDD
91
HCPs who had little confidence in
57
ability to manage HSDD
0
20
40
60
HCPs (%)
Harsh V, et al. J Sex Med. 2008;5(3):640-645.
80
100
HCPs Perceive Patients as Reluctant to
Bring Up Sexual Issues
Patient Barriers Identified by HCPs in the Management of
Sexual Dysfunction (n=133 HCPs)
Doesn't want to waste
doctors' time
2.2
Difficult area to discuss
4.3
Indirect presentation
(hidden by other symptoms)
5.4
Patient thinks it's “normal”/lack
of knowledge and awareness
15
Patients‘ reluctance/
reticence/embarrassment
73.1
0
20
40
60
80
Total Number of Barriers (%)*
*Total number of patient barriers=93; most HCPs identified more than one barrier.
Humphrey S, et al. Fam Pract. 2001;18(5):516-518.
HCP Comfort Level Impacted by
Patient Gender
Differences in Physician Comfort Level Influenced by Gender (N=69)
50*
Physician self-report of
discomfort with male patients
19
Female physicians (n=29)
Male physicians (n=40)
12*
Physician self-report of
discomfort with female patients
35
45
Physician perception of
male patient discomfort
40
24*
Physician perception of
female patient discomfort
53
0
10
*P<0.05.
Burd ID, et al. J Sex Med. 2006;3(2):194-200.
20
30
40
Physicians (%)
50
60
70
Open-Ended Questions
►
Require narrative elaboration, not yes/no or short response
●
Directive open-ended questions focus the topic Open the door to
context, understanding, & feelings
►
Doctors ask ≈1 question/min; >90% are closed-ended
►
Physicians can increase use open-ended questions & improve
●
●
●
►
Assessment of functional impairment
Adherence
Patient satisfaction
Open-ended dialog is efficient (≈ 90 seconds for impairment
dialog)4 & effectively reveals syndromal symptoms
Lipton et al. JGIM 2008;23:1145-1151.
Hahn et al. Curr Med Res Opin 2008;24:1711-1718.
The Challenges of the
Differential Diagnosis
• Ensure that sexual dysfunction IS NOT due exclusively to the
– Physiological effects of a specified general medical condition (eg,
neurological, hormonal, metabolic abnormalities)*
In Order to
Meet the
Diagnostic
Criteria for
HSDD:
• Ensure that sexual dysfunction IS NOT due exclusively to the
– Physiological effects of substance (prescribed or illicit) abuse†
• HSDD and concomitant sexual dysfunctions (both should be noted)
● Also, additional diagnosis of HSDD IS NOT made if low sexual desire is
better accounted for by another Axis I disorder (eg, major depressive
disorder, obsessive-compulsive disorder, posttraumatic stress disorder)
– HSDD diagnosis may be appropriate if low desire predates the Axis I
diagnosis
*If it is, refer to the diagnosis: Sexual Dysfunction Due to a General Medical Condition.
†If it is, refer to the diagnosis is Substance-Induced Sexual Dysfunction.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text
Revision, Washington, DC: American Psychiatric Press; 2000.
The Challenges of Differential Diagnosis
Psychiatric Illnesses and General Health Factors May Affect Sexual Function
►
Mood disorders1
●
●
Major depression
Bipolar illness
►
Anxiety disorders2,3
►
Psychotic illness4
►
Hypertension
►
Neurological disorders6
►
Endocrine disorders7
●
● Urological problems8
● Sexually transmitted infections9
● Gynecological problems
— Post-partum10
● Other chronic illness
— Rheumatoid arthritis11
— Psoriasis12
— Breast cancer13
Diabetes, thyroid disorders,
hyperprolactinemia7
1. Casper RC, et al. Arch Gen Psychiatry. 1985;42:1098-1104. 2. van Lankveld JJ, Grotjohann Y. Arch Sex Behav. 2000;29:479-498. 3. Shifren J, et
al. Obstet Gynecol. 2008;112:970-978. 4. Friedman S, Harrison G. Arch Sex Behav. 1984;13:555-567. 5. Okeahialam BN, Obeka NC. J Natl Med
Assoc. 2006;98:638-640. 6. Rees PM, et al. Lancet. 2007;369(9560):512-525. 7. Bhasin S, et al. Lancet. 2007;369(9561):597-611. 8. Aslan G, et al.
Int J Impot Res. 2005;17:248-251. 9. Smith EM, et al. Infect Dis Obstet Gynecol. 2002;10(4):193-202. 10. Baksu B, et al. Int Urogynecol J.
2007;18:401-406. 11. Abdel-Nasser A, Ali E. Clin Rheumatol. 2006;25:822-830. 12. Sampogna F, et al. Dermatology. 2007;214:144-150.
The Challenges of Differential Diagnosis
Numerous Medications are Associated
with Female Sexual Problems
Psychotropic drug classes/agents
Other drug classes
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Antipsychotics1
SSRIs2
Lithium3
SNRIs4
Tricyclic antidepressants5
Chemotherapeutic agents6
Aromatase Inhibitors7
Triglyceride-lowering agents8
Histamine receptors (H2) blockers9
Weight loss agents10
Antiepileptics11
Immunosuppresants12
Central alpha-adrenergic agonists13
Opioid antagonists14
1. Liu-Seifert H, et al. Neuropsychiatr Dis Treat. 2009;5:47-54. 2. Serretti A, Chiesa A. J Clin Psychopharmacol. 2009;29:259-266. 3. Lithium
carbonate [package insert]. 2003. 4. Venlafaxine hydrochloride [package insert]. 2003. 5. Imipramine hydrochloride [package insert]. 2007.
6. Fobair P, Spiegel D. Cancer J. 2009;15(1):19-26. 7. Mok K, et al. Breast. 2008;17(5):436-440. 8. Fenofibrate [package insert]. 2008. 9. Ranitidine
hydrochloride [package insert]. 2009. 10. Sibutramine hydrochloride monohydrate [package insert]. 2009. 11. Rees PM, et al. Lancet. 2007;369:512525. 12. Muehrer RJ, et al. West J Nurs Res. 2006;28:137-150. 13. Clonidine [package insert]. 2009. 14. Naltrexone hydrochloride [package insert].
2003.
Thank you
Sheryl.kingsberg@uhhospitals.org
A New Frontiers Program on
Women’s Health
Pathophysiology of Decreased
Desire in Premenopausal Women
Psychological, Pharmacologic, and
Neurobiological Mechanisms
Program Chairman and Moderator
Anita H. Clayton, MD
David C Wilson Professor
Department of Psychiatry & Neurobehavioral Sciences
Professor of Clinical Obstetrics & Gynecology
University of Virginia
Charlottesville, VA
Objectives
At the conclusion of this activity, participants
should be able to:
►
Describe the psychological, pharmacological
and neurobiological factors affecting desire in
premenopausal women
What’s it all about anyhow?
►
Psychological/social/emotional
►
Physiological/biological: interactions of sex
steroids and neurotransmitters
►
Cognitive: thoughts, fantasies, satisfaction
►
Cultural
American Psychiatric Association, DSM IV, 1994
Central Effects on Sexual Function
+
-
5-HT
testosterone
+/-
progesterone
+
+
estrogen
+
+
dopamine (DA)
-
DESIRE
+
5-HT
prolactin
oxytocin
-
SUBJECTIVE
EXCITEMENT
+
norepinephrine (NE)
+
ORGASM
Modified from Clayton AH. Psych Clin
NA 2003; 26:673-682
Cohen AJ. AD-induced SD associated
with low serum free testosterone 2000.
http://www.mental-healthtoday.com/rx/testos.htm
Peripheral Effects on Sexual Function
gonads
adrenals
5-HT
• Estrogen
• Testosterone
• Progestin
}
-
maintain genital
structure and
function
Nitric
Oxide (NO)
+
-
Clitoral and
penile tissue
SENSATION
5-HT2A
VASOCONGESTION
-
+
+
NE
5-HT
Prostaglandin E
+
Cholinergic fibers
Clayton AH. Psychiatric Clinics of North America 2003; 26:673-682
+
Physiology of Sexual Function
►
Desire:
●
●
►
Excitatory: dopamine, norepinephrine,
testosterone, estrogen
Inhibitory: serotonin, prolactin
Arousal:
●
●
Excitatory: dopamine, norepinephrine, nitric
oxide, acetylcholine, estrogen, testosterone
Inhibitory: serotonin, prolactin
Pfaus JG. J Sex Med 2009;6:1506-1533.
Influences on Sexual Functioning
►
Neurobiological
●
●
●
►
Psychological
●
●
●
1Meston
Reproductive endocrinology (ie. anything that lowers
testosterone such as hyperprolactinemia, opiates,
menopause)
General health status/illness (e.g. fatigue)1 and comorbidities
Medication/substance use
Body image (e.g. obesity)
Psychological/relationship issues, partner
availability/aging1
Fears (e.g. pregnancy, infertility, STD, history of
sexual abuse/trauma, cultural practices)
C. Western Journal of Medicine 1997;167(4):285-290
DSM-IV TR Criteria for HSDD
►
Sexual complaint or problem in sexual desire and/or
fantasies
●
►
►
The judgement of severity of the sexual symptom is made by
the clinician, taking into account factors that affect sexual
functioning, such as age and the context of the person’s life
The disturbance causes marked distress or interpersonal
difficulty
The sexual dysfunction is not:
●
●
Better accounted for by another primary psychiatric disorder
(except another Sexual Dysfunction)
Due exclusively to the direct physiological effects of a
substance (e.g., a drug of abuse, a medication) or a general
medical condition
American Psychiatric Association. DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision.
Washington, DC: American Psychiatric Press; 2000
FSD may be Multi-faceted
►
Biological/Pharmacological
●
●
●
●
●
►
Medical diagnoses
Psychiatric conditions
Other sexual disorders
Medications/substances
Hormonal changes
Socio-cultural
●
●
●
●
Lower education
Religious restrictions
Social taboos
Cultural conflict
►
Psychological
●
●
●
●
●
Prior sexual or physical
abuse
Relational (conflict, lack
of partner, partner SD)
Body image, sexual
self-esteem
Negative emotional
states
Stress
Relational Problems (not HSDD)
►
Sexual dysfunction in partner
►
Interpersonal conflict
►
Extra-marital affair by either partner
►
Desire discrepancy
►
Cultural differences
►
Reproductive concerns
►
History of sexual abuse
Prevalence of Sexual Dysfunction
SEXUAL
COMPLAINT
SEXUAL
PROBLEM
PROBLEM PLUS
DISTRESS
FSD WITHOUT
DEPRESSION
Desire
Arousal
38.7%
26.1%
10%
5.4%
6.3 – 8.8%
3.3 – 4.7%
Orgasm
Any
Dysfunction
20.5%
4.7%
2.8 – 4.1%
44.2%
12%
7.6 – 10.7%
N=31,581. Definition of depression: Self-reported depressive sx’s + AD use;
AD use without current depressive sx’s; Depressive symptoms without AD use
Shifren J et al. Sexual problems and distress in United States women: Prevalence and correlates.
Obstet Gynecol 2008;112:970-978; Johannes CB et al. Distressing Sexual Problems in United
States Women Revisited: Prevalence after Accounting for Depression. J Clin Psychiatry
2009;70(12):1698-1706
Proportion of Partnered Women with HSDD
By Age and Menopausal Status
30
P=0.002
25
20
P=0.067
15
10
5
0
Premenopausal
Surgically
postmenopausal
Age 20-49 years
Naturally
Surgically
postmenopausal postmenopausal
Age 50-70 years
Leiblum SR et al.Hypoactive sexual desire disorder in postmenopausal women: US results from the
Women’s International Study of Health and Sexuality (WISHeS). Menopause. 2006;13:46-56.
Medical Conditions that may
Impact Sexual Function
Neurologic
Genitourinary
Spinal cord injury, neuropathy,
herniated disc, MS, epilepsy
Urinary incontinence,
vaginitis, PID, endometriosis
Endocrine
Systemic Illness
Hypothyroidism, adrenal
dysfunction, hypogonadism,
diabetes mellitus, menopause
Vascular
Hypertension, arteriosclerosis,
stroke, venous insufficiency, sickle
cell disorder
Renal, pulmonary, hepatic
diseases, advanced
malignancies, infections
Psychiatric
Depression, anxiety
disorders, psychotic illness,
eating disorders, PTSD
Clayton & Ramamurthy in Sexual Dysfunction: The Brain-Body Connection. Ed: R Balon, 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 & Weizman in Sexual Dysfunction: The Brain-Body
Connection. Ed: R Balon, Karger Basel, Swithzerland 2008
Pharmacotherapies and Risk of FSD
PSYCHOTROPIC
MEDICATIONS
SSRIs/SNRIs/TCAs
Mood stabilizers
Antipsychotics
Benzodiazepines
Antiepileptic drugs
ANTIHYPERTENSIVES
Beta-blockers
Alpha-blockers
Diuretics
CARDIOVASCULAR AGENTS
Lipid-lowering agents
Digoxin
HORMONES
Oral contraceptives
Estrogens
Progestins
OTHER
Ant-iandrogens
GnRH agonists
Histamine H2-receptor blockers
Narcotics
NSAIDs
Clayton & Ramamurthy in Sexual Dysfunction: The Brain-Body Connection. Ed: R Balon, 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.
Correlates of Distress with HSDD:
PRESIDE
►Psychological
• Having a partner (OR 4.63)
• Demographics: Greatest age < 45 years; to lesser
degree < 65 years; white race
►Neurobiological
• Untreated depression > treated depression
• Presence of anxiety
• Urinary incontinence
• Use of hormonal contraceptives or HRT
Rosen RC, et al. Correlates of sexually related personal distress in women with low sexual desire.
J Sex Med 2009;6:1549-1560.
Decreased Sexual Desire Screener
(DSDS)
©Boehringer Ingelheim International GmbH 2005. All rights reserved.
Sensitivity 0.836, 0.946, 0.956, and specificity 0.878
Goldfischer ER et al. Obstet Gynecol 2008;111:109S
Clayton A et al. J Sex Med 2009;6:730–738
Nappi R et al. J Sex Med 2009;6(suppl 2):46
Conclusions
►
Multiple factors may affect sexual functioning
in women across the life cycle
►
Appropriate assessment is important in
management
A New Frontiers Program on
Women’s Health
Addressing Current Challenges in
Female Sexual Disorders
What Internal Medicine Specialists
Need to Know About HSDD
Lori Brotto, PhD
Assistant Professor
Department of Obstetrics and Gynecology
University of British Columbia
Vancouver, BC
Outline
► Physician-patient
communication
► Screening
strategies
► Differential
► Interview
► PLISSIT
diagnosis
techniques
/ ALLOW
Why is inquiry about
sexual function difficult?
► Topic not important enough
► It is a private experience
► Embarrassment
► “I don’t exactly know why I am asking”
► Lack of training
► Absence of norms
► Sexual behaviour is a topic only when it is
deviant or when others are at risk
► Incorrect beliefs about the benefit of asking
Is Marriage Good for Your Health?
New York Times Magazine, April 12, 2010
Complicating factors:
Symptom or disorder?
Lutfey et al., 2008, Arch Sex Behav
n = 3,205; Black, Hispanic, White
►
Factoring in distress, rates
of low desire drop by half in
all studies
►
Note, DSM-IV-TR criteria for
HSDD and all sexual
dysfunctions require
distress
Complicating Factors: Low Desire
Does Not Always Imply Dissatisfaction
► Oberg et al. (2004) found a prevalence of manifest distress despite the absence of any
sexual symptoms of 12.4%
► Bancroft, Loftus, and Long (2003) found that 8% of women reported distress about the
relationship and 5.4% reported personal distress despite absence of sexual symptoms
► Lutfey, Link, Rosen, Wiegel, and McKinlay (2008) reported that 5.5% of women were
dissatisfied or very dissatisfied despite not having any sexual symptoms.
► Cain et al. (2003) in the SWAN study found that 70% of women reported thinking about
sex less than once/week but 86% remained sexually satisfied.
► King et al. (2007) found that 19% of women did not have an ICD-10 diagnosed sexual
dysfunction but still reported significant low sexual satisfaction.
► Dunn et al. (2000) found that 79% of women were very sexually satisfied but 24% had
no sexual activity in the past 3 months.
► Laumann et al. (2005) in the GSSAB found that 7.7% - 17.4% of women reported not
finding sex pleasurable/satisfying.
Why assess sexual function?
► Sexual dysfunction is common
► Integral component of quality of life and
general well-being
Lindau et al., NEJM, 2007
Physician-patient communication
Are physicians asking?
►
53 primary care physicians (or internal medicine
residents) at UVA completed questionnaire about
their experience asking about HSDD
●
●
●
86.3% had not screened for HSDD
90% had not diagnosed HSDD
53% felt not confident at all, 38% little
confidence
Harsh et al., J Sex Med 2008
Percentage of survey participants
providing estimate
Survey Participants and Patients who
Initiate First Discussion of FSDs
Survey participants initiating
first discussion of FSD
J Sex Med 2006;3:639-645
Patients initiating
first discussion of FSD
Who should I ask about sexuality?
►
EVERYONE!
►
Legitimizes the patient’s concerns with and
interest in sex
►
Allows the patient to ask questions
►
Identifies the provider as a potential resource
for sexual information
►
Maximizes the chances that patients will get
help for sexual and relationship problems
Screening Strategies
Screening questions
►
Are you satisfied with your sexual response (sex
life)? If not, why not?
►
Are you currently active with a sexual partner?
●
●
Men, women or both
Frequency (activity including masturbation)
►
How often do you have difficulty _________?
►
What questions or problems related to sex
would you like to discuss?
When to ask?
1. During routine inquiry
►
►
Include it in a standard set of questions
during developmental and psychosocial
periods
Include it on self-report questionnaire
“you were telling me about your male friendships
growing up…Do you remember when you first
became aware of sexual feelings?”
When to ask?
2. After direct presentation
►
►
Patient directly states problem
Ask permission and collect information
3. After indirect presentation
►
►
►
Patient is indirect and vague, hoping the
clinician will ask about sexual complaints
e.g., medication non-compliance
Know about that particular condition and
side-effect profiles of medications
How to ask?
1. Need clinical knowledge, a non-
judgmental attitude, and fundamental
interviewing skills
►
►
►
Observing and monitoring
Interpreting skills
Responding skills
How to ask?
2. Clarify the problem
Patient: I’ve lost my nature
Clinician: Tell me what a nature is? I haven’t
heard that expression before.
3. Use personalized language
►
►
Use the correct term and allow the patient
to pick up on it
Sometimes may be appropriate to use
patient’s language
How to ask?
4. Use open-ended questions
►
►
Use: “to what extent…what…how…”
Don’t use: “do you…did you…are you…have
you…”
“What were the circumstances that led you to
be sexual with him?”
5. Be empathic
►
►
Is an expression of professional understanding
“that must have been really difficult for you…”
How to ask?
6. Facilitate
►
Encourage the patient to continue by
nodding, leaning forward, using “yes…go
on.”
7. Provide information
►
►
Anticipate worries and speculate
Confirm understanding of the problem
before proceeding
Differential Diagnosis
Comorbidity of
Women’s Sexual Difficulties
• desire and
lubrication – 65%
• desire and orgasm
- 53%
• desire and
vaginismus – 75%
• lubrication and
orgasm – 28%
• lubrication and
dyspareunia – 61%
Basson et al., 2003
J Psychosom Obstet Gynaecol
Desire
difficulties
Arousal
difficulties
Orgasm
difficulties
Pain
Vaginismic
difficulties
Depression?
Interview Techniques
Self-report measures
Use of Validated Questionnaires
►
Decreased Sexual Desire Screener (DSDS)
Clayton et al. 2009, J Sex Med
►
Female Sexual Function Index (FSFI)
Rosen et al. 2000, J Sex Marital Ther
►
Profile of Female Sexual Function
McHorney et al. 2004, Menopause
►
Female Sexual Distress Scale (FSDS)
Derogatis et al. 2002, J Sex Marital Ther
Decreased Sexual Desire Screener
Clayton, Goldfischer, Goldstein, DeRogatis, Lewis-D’Agostino, Pyke,
J Sex Med 2009;6:730-738
1. In the past was your level of sexual desire or interest
good and satisfying to you?
2. Has there been a decrease in your level of sexual
desire or interest?
3. Are you bothered by your decreased level of sexual
desire or interest?
4. Would you like your level of sexual desire or interest to
increase?
5. Please check all the factors that you feel may be
contributing to you current decrease in sexual desire or
interest.
Use of a Validated Structured Interview
►Women’s
Sexual Interest
Diagnostic Interview
DeRogatis et al. 2008, J Sex Med
*39 items assessing desire, arousal, orgasm, pain and distress, partner sexual
dysfunction, relationship problems, depression
* Permission to use the WSID can be obtained by contacting Solvay Pharmaceuticals,
Inc. (+1-770-579- 7374, chun-yuan.guo@solvay.com)
►Sexual
Interest and Desire
Inventory-Female Version (SIDI)
Clayton et al. 2005, J Sex Marital Ther
*13-item clinician administered measure of sexual interest, desire and arousability
Interview Techniques
Face-to-face interview
PLISSIT
►
Permission
●
●
►
Limited Information
●
►
Basic education regarding anatomy & sexual response
Specific Suggestions
●
●
►
Acceptance, empathy
“I ask all my patients about sex. Is it OK to do so now?”
Medical-medication, procedures to relieve discomfort
Psychological-behavioral strategies, communication skills
Intensive Therapy
●
●
Individual or couples therapy to manage sexual or
relationship issues
Surgery (penile implants, vestibulectomy)
ALLOW
Sadovsky, 2002
Goals of a Comprehensive Sexual History
►
Identify the primary complaint
►
Determine patient’s perspective of their
problem
►
Develop hypotheses about etiology
►
Decide on an appropriate course of treatment
(including referral)
Elements of a Comprehensive
Sexual History
►
Assess sexual
functioning
►
Assess risk
behaviours
►
Assess
medical/organic
contributors
►
Assess partner status
►
Ask about history of
childhood sexual or
physical abuse
►
Assess mood
►
Assess relationship
satisfaction and
functioning
Sample Assessment Questions
►
What is your sexual interest like? What factors
enhance and/or inhibit your desire?
► Many people engage in self-stimulation. Is this part
of your sexual experiences?
► Some people avoid sexual activity for any variety of
reasons? Can you relate to this?
► Many women talk about difficulties with lubrication
or sexual activity that is painful. What is your
experience with this?
► Most men experience occasional difficulties with
their erection. Has this been the case for you?
Sample Assessment Questions
►
Do you notice any difference between your
erections during sexual intercourse, during
masturbation, and those when you wake up?
► When you’re experiencing this difficulty, can you
recall what you’re thinking or feeling at the time?
How about right before?
► Of your last 10 sexual encounters, on how many of
them did you experience this difficulty?
► What do you do in response to this difficulty?
What does your partner do?
► Can you describe the sensation of the pain? Is it
burning, throbbing, or sharp? When do you
experience it?
Problems to Avoid During
the Sexual Interview
► Meddling: always rationalize your questioning
► Preoccupation: focus on each response
► Identification: consult with a colleague if you’re
not able to be objective
► Sexual arousal: be aware of your own feelings
Putting the Sexual History
in Context
►
What explanations does the patient have
(their theory)?
►
What have they done to try to resolve the
problem?
►
Are there problems in multiple areas of sexual
functioning? What is the relationship between
these?
►
What have they discussed with their partner
and what was the reaction?
Multi-Factorial Model
Maintaining
Factors
Predisposing
Factors
Early
Development
Precipitating
Factors
Current
Functioning
Download free of charge at:
http://www.kinseyinstitute.org/resources/maurice.html
A New Frontiers Program on
Women’s Health
Current and Emerging Therapies for
Hypoactive Sexual Desire Disorder
Jennifer Frank, MD, FAAFP
Assistant Professor
Department of Family Medicine
University of Wisconsin School of Medicine
and Public Health
Learning Objectives
►
Describe a multimodal treatment approach to
HSDD
►
Identify components of nonpharmacologic
treatment of HSDD
►
Describe current pharmacologic treatment
options for HSDD in both postmenopausal
and premenopausal women
►
Identify emerging pharmacologic treatment
options for HSDD
HSDD Treatment Starts with
Nonpharmacologic Approaches
►
Foundation of therapy
►
Includes treatment initiated and
managed by the primary care physician
►
May include treatment by specialist
partners
●
●
●
●
Sex therapist
Physical therapist
Cognitive behavioral therapist
Marital/relationship counselor
Nonpharmacologic Treatment
PCP based
►
Education
●
Dispelling myths
Specialist based
►
CBT
►
Sensate-focus
►
Controlled selfstimulation
►
Exercise
►
Healthy Diet
►
Adequate Rest
►
Couples counseling
►
Stress Reduction
►
Physical therapy
●
●
Vaginal dilators
Biofeedback
Bitzer J, Brandenburg U. Psychotherapeutic interventions for female sexual dysfunction. Maturitas
2009;63:160-3.
Sex Therapy for the PCP
► Education


What is normal?
Basics of anatomy and physiology?
► Lubrication

Basic familiarity with 3 or 4 different products
► Maximize intimacy and opportunities for intimacy
► Introduce novelty – different positions, venues, toys, etc.
► Getting into a sexual frame of mind

►
►
►
►
“Men are like light switches, women are like ovens.”
Patient focused reading
T.L.C.
Redistribution of childcare and household responsibilities
Improving body image
Potter JE. A 60-year-old woman with sexual difficulties. JAMA 2007;297:620-33.
UpToDate and www.sexedsolutions.com
Barriers to Nonpharmacologic
Treatment
►
Physician’s unfamiliarity with counseling and
recommendations
►
Physician’s discomfort with this role
►
Patient’s resistance to relationship work
►
Patient’s perceived barriers to implementing
change
►
Patient’s unwillingness to change
►
Patient’s belief in a “little blue pill”
►
Lack of or paucity of hope
►
Reward not worth the work
Current Pharmacologic Treatment
Options for FSD
►
Hormonal
●
●
►
Psychotropic medications
●
►
Estrogen
Testosterone*
Buproprion*
Phosphodiesterase inhibitors
●
Sildenafil*
*Not FDA approved for this indication
Local Estrogen Therapy for
Vaginal Atrophy (Level C)
►
Postmenopausal women without a history of
hormone-dependent breast cancer
►
Low dose as long as symptoms persist
►
Not indicated for HSDD but can be helpful if
pain/dryness is contributing to low desire
►
Consider if prescribing testosterone
Consider Testosterone for PostMenopausal Women with HSDD
►
Good evidence (Level A) to support its use in
estrogen replete women1-3
►
300 mcg patch for 24 weeks
►
Both naturally4 and surgically1-3 menopausal
women
►
Improvements seen in desire, orgasm frequency
and total number of sexually satisfying
encounters
1. Braunstein et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women.
Arch Intern Med 2005;165:1582-9.,
2. Buster et al. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol 2005;105:944-52.,
3. Davis et al. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a
randomized, placebo-controlled trial. Menopause 2006;13:387-96.
4. Shifren et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE
NM1 study. Menopause 2006;5:770-9.,
Testosterone’s Role in
Postmenopausal Women without ERT
►
DBRCT of placebo vs. testosterone patch
►
Increase in SSEs/month at 300 mcg daily dose
●
2.1 (active) vs. 0.7 (placebo)
►
Increase in desire
►
Decrease in distress
►
Treatment effect similar in naturally and surgically
menopausal women
►
4 episodes of breast cancer in study participants
(n=537)
Davis et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl
J Med 2008;359:2005-17.
Testosterone for Premenopausal
Women may Have a Role

DBRPCT of 261 premenopausal women


Not depressed
Low serum testosterone

Testosterone at 90 microliters/day (spray) daily x 16
weeks

Increase of 0.8 SSEs/month over placebo



Strong placebo effect
SSE not related to testosterone levels
Levels returned to baseline at 20 weeks (4 weeks after study) but SSEs
did not
Davis et al. Safety and efficacy of a testosterone metered-dose transdermal spray for treating
decreased sexual satisfaction in premenopausal women. Ann Intern Med 2008;148:569-577.
Testosterone Treatment Limitations
► Androgen levels not clearly associated with decreased desire

Difficult to measure testosterone levels accurately
► Role in premenopausal women is not established1
► Off label indication
► Long term efficacy/safety not known1-3
► Study population (definition of decreased desire)1
► Relationship between arousal and desire1
► Need for concomitant use of estrogen (?)1
1. Basson R. Pharmacotherapy for women’s sexual dysfunction. Expert Opin Pharmacother
2009;10:1631-48.
2. NAMS. The role of testosterone therapy in postmenopausal women: position statement of the North
American Menopause Society. Menopause 2005;12:497-511.
3. Wierman et al. Androgen therapy in women: an Endocrine Society clinical practice guideline. J Clin
Endocrinol Metab 2006;91:3697-3710.
Buproprion has Limited Data to
Demonstrate Efficacy in HSDD (Level B/C)

Buproprion (300 mg/day) x 112 days in non-depressed premenopausal
women with normal serum testosterone1



268 women ages 20-40 diagnosed with HSDD (Level B)2




1.
2.
3.
4.
Premenopausal, not depressed, normal testosterone
12 weeks of buproprion SR 150 mg/day
Improvement in rating scale of sexual function (globally and specific
subsets)


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
Greatest improvement in frequency of sexual activity, thoughts/desire, and
pleasure/orgasm
Decrease in personal distress score
Add-on or substitute therapy for SSRI induced sexual dysfunction(Level
B)3,4
Segraves et al. Buproprion SR for the treatment of HSDD in premenopausal women. J Clin Psychopharm 2004;24:339-42.
Safarinejad et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of buproprion for treating hypoactive sexual
desire disorder in ovulating women. BJU International Feb 2010 [Epub].
Safarinejad . Reversal of SSRI-induced female sexual dysfunction by adjunctive buproprion in menstruating women: a double-blind, placebocontrolled and randomized study. J Clin Psychopharm Jan 2010 [Epub].
Seretti A, Chiesa A. Treatment-emergent sexual dysfunction and anti-depressants: a meta-analysis. J Clin Psychopharm. 2009;29:259-66.
Phosphodiesterase Inhibitors
►
No demonstrable role in the treatment of
HSDD
►
Use in antidepressant associated FSD1
●
►
Potential use in women with neurovascular
mediated sexual dysfunction2
●
1.
2.
Main effect on orgasmic capacity
Primarily arousal, orgasmic dysfunction
Nurnberg et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction.
JAMA 2008;300:395-404.
Brown DA et al. Assessing the clinical efficacy of sildenafil for the treatment of female sexual
dysfunction. Ann Pharmacother 2009;43:1275-85.
Emerging Pharmacologic Therapies
►
Hormonal
●
►
Testosterone
Centrally acting agents
●
Flibanserin
►
Phosphodiesterase Inhibitors
►
Others
●
Prostaglandin gel
Testosterone in the Future1
►
Premenopausal women
●
►
Search for an FDA approved
preparation
●
●
►
Effects of long term use are unknown
LibiGel
Intrinsa2
Tibolone3 - estrogenic, progestogenic,
androgenic synthetic hormone
►
1.
2.
3.
Combined with ERT?
Krapf and Simon. The role of testosterone in the management of hypoactive sexual desire disorder in
postmenopausal women. Maturitas 2009;63:213-9.
Davis et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med
2008;359:2005-17.
Wylie and Malik. Review of drug treatment for female sexual dysfunction. Int J STD AIDS 2009;20:671-4.
Centrally Acting Agents1
►
Bremelanotide3
●
●
►
Flibanserin1
●
●
1.
2.
3.
Melanocortin agonist
FSAD
Acts as a partial serotonin agonist/antagonist
Specifically being studied for HSDD
Wylie and Malik. Review of drug treatment for female sexual dysfunction. Int J STD AIDS 2009;20:671-4.
Baldwin. Agomelatine in the treatment of mood and anxiety disorders. Brit J Hospital Med 2010;71:153-6.
Safarinejad. Evaluation of the safety and efficacy of bremelanotide, a melanocortin receptor agonist, in female
subjects with arousal disorder: a double-blind placebo-controlled, fixed dose, randomized study. J Sex Med
2008;887-97.
Other Agents
►
Phosphodiesterase inhibitors
●
●
►
Role will likely be focused to specific
populations
No demonstrable effect on desire
Alprostadil (Prostaglandin E1) in
trials for FSAD (vasodilatory
properties)
Conclusions
►
The foundation of HSDD treatment is
nonpharmacologic including PCP directed and
specialty directed modalities.
►
Pharmacotherapeutic options are limited at
this time.
►
Most promising treatments for HSDD include
hormonal (testosterone) and centrally acting
agents (buproprion and flibanserin).
►
Other medications may have role for different
types of FSD.
Case Example
► 26-year-old MWF presents with 1 year
history of decreased libido, some problems
with vaginal lubrication, and diminished
orgasmic capacity. No pain with intercourse.
 Change in sexual function since marriage 4 years
ago, but relationship still strong
 1 year post-partum with mild depressive
symptoms since delivery
 No general health problems
 On oral contraceptives for birth control
Differential Diagnosis
Evaluation/Interventions
►
Consider labs such as TSH
►
Consider change from birth control pills to
non-hormonal contraceptive
►
Specific suggestions
►
Consider adding bupropion to treat
depression and enhance sexual functioning
►
If no improvement, check testosterone levels
before supplementing