Review of low libido in women

Abstract

Low libido is the most frequently reported sexual dysfunction. This is an important and complex problem with multiple causes. At present the interpretation of data on this topic remains a challenge, as the subject population is diverse and various tools are used in assessment. Coupled with this, several definitions are in use with differing emphasis on distress resulting from this state. Developments in the understanding of psychopharmacology are shedding light on the pathways involved in normal sexual response and these are being utilized in the development of treatments. This article reviews the current definitions, aetiology and treatment options and explores the recent developments in low libido in women.

Keywords

women sexual behaviour

INTRODUCTION

Sexual function is an important aspect of health and social wellbeing and problems of female sexual function are increasingly reported. The World Health Organization (WHO) defines sexual disorders as ‘the various ways in which an individual is unable to participate in a sexual relationship as he or she would wish’.¹ Thus, in assessing low libido in women, quality-of-life, sense of self and characteristics of relationships must play a part. There are many challenges in dealing with this subject: the varying triggers, stages of a woman's reproductive life, definitions, methods of appraising and the input of varied practitioners and clinicians. Many cases remain unacknowledged because only a small proportion of women seek medical advice. Nazareth et al. ² reported only 22% (39/174) of women with self-reported lack or loss of desire approached their general practitioner for help and in a national UK sample 21% of women with problems in the previous year sought help.³ Health-care workers, both in the community and in genitourinary medicine clinics, have reported lack of training and time pressures as barriers to exploring sexual problems.^4,5 Treatment pathway can be determined by the outlook of the health-care professional consulted. As women's sexual function is a multifaceted phenomenon, several treatment modalities may be required. This review will look at the available literature covering these varied aspects of low libido in women.

DEFINITION

Masters and Johnston⁶ classically divided the female sexual response into four parts: excitement, plateau, orgasm and resolution. This model stressed the physical aspects of sexual response without any reference to the underlying mental processes. Kaplan⁷ later revised this model to desire, excitement and orgasm. In this formulation desire is a component of sexual thoughts, fantasies and motivation; this may be spontaneous or responsive to sexual acts. This leads to an arousal stage with genital swelling and lubrication until orgasm.⁷ Masters, Johnston and Kaplan outlined the pathway of desire to orgasm as linear, with a period of awareness of desire leading to arousal. However, this linear sequence paradigm has been disputed. There is evidence that in an established relationship desire may actually occur after arousal, and this led Basson⁸ and Goldmeier⁹ to argue for a responsive desire pathway. This model suggests that a woman may engage in sexual activity initially for non-sexual reasons (intimacy, sense of wellbeing, ‘duty’), but the stimulation leads to arousal and this involves desire, hence responsive. Even though responsive desire is seen as normative, women complain of this and may be distressed.⁸ A questionnaire study in nurses in the United States found this model of response as prevalent as the Masters and Johnston or the Kaplan models.¹⁰

This article focuses on aspects of desire in relation to low libido in women. Arousal will not be discussed specifically, although this is intrinsically linked (Box 1). Box 1

Current definitions of hypoactive desire disorder

DSM-IV-TR definition: ‘Absent or diminished feelings of sexual interest or desire, absent sexual thoughts or fantasies and a lack of responsive desire. Motivations for attempting to become sexually aroused are scarce or absent. The lack of interest is considered to be beyond normative lessening with lifecycle and relationship duration’.¹¹

ICD 10 F52.0 definition: Sexual dysfunction, not caused by organic disorder or disease. Sexual dysfunction covers the various ways in which an individual is unable to participate in a sexual relationship as he or she would wish. Sexual response is a psychosomatic process and both psychological and somatic processes are usually involved in the causation of sexual dysfunction. Lack or loss of sexual desire. Loss of sexual desire is the principal problem and is not secondary to other sexual difficulties, such as erectile failure or dyspareunia.¹²

AFUD definition: Absence of sexual fantasies, thoughts, and/or desire for, or receptivity to, sexual activity, which causes personal distress.¹³

DMS-V (currently under peer review with planned publication 2013) is suggesting a combination definition of ‘lack of sexual interest/arousal’ compromising symptoms of at least 6 months duration, causing significant distress and not explained by another health cause. This would be called sexual interest/arousal disorder (SIAD)¹⁴

Hypoactive sexual desire disorder (HSDD) is the term encompassing states described as low desire, lack of sexual interest or low libido. This term was first added to the Diagnostic and Statistical Manual of Mental Disorders (DSM) in 1980 and incorporated loss of sexual thoughts or feelings causing distress. Subsequently this was updated in DSM-IV-TR, to ensure that HSDD exclusively refers to states of distress associated with low libido in the absence of other causative conditions (see Box 1).¹¹ Other definitions have been proposed. The WHO International Classification of Diseases and related health problems (ICD-10) focuses more on the physiological and biological aspects of female sexual response.¹² However, this definition is far less used worldwide and does not specifically mention distress as part of the definition. According to the consensus of the Sexual Function Health Council of the American Foundation for Urologic Disease (AFUD), HSDD is defined by the concurrent presence of the following two criteria: first, persistent or recurrent deficiency (or absence) of sexual fantasies, thoughts and/or desire for, or receptivity to, sexual activity; second, personal distress caused by the sexual dysfunction described in the first criterion.¹³ This is very similar to the DSM definition but is much clearer in outlining female receptivity and the importance of distress in making the diagnosis. The new DSM-V proposed definitions are online now for consultation and there it is suggested that desire and arousal are combined into a group called sexual interest/arousal disorder (SIAD).¹⁴ One of the difficulties with the current definitions is the tangle of desire and arousal and this may be resolved if the new DSM-V proposed definition is adopted. These two states commonly coexist and overlap and make the diagnostic process problematic.¹⁵ Additionally, all characterizations used encompass a concept that sexual distress is central to the diagnosis of dysfunction, but there are no fixed criteria to distinguish normal from abnormal levels of desire or to define when a sexual problem becomes a sexual disorder. The presence or lack of distress as a result of low desire is an important aspect of the definition because during the lifecycle women experience differing levels of desire.¹³ We do not wish to label as dysfunctional those women who maintain the ability to respond sexually but have low desire.

HSDD can be categorized further by onset (acquired or lifelong), context (generalized or situational) or cause (single or multifactorial); these subcategories have important implications on outcome.

EPIDEMIOLOGY

Wide ranges of prevalence of all female sexual dysfunctions have been described, but low desire is the most frequent dysfunction reported.¹⁶ There are many confounding factors in assessing prevalence of this problem in populations. The variety of different methods used to assess this condition and the lack of standard definitions are two of the main problems. The determined prevalence will be altered according to how the investigator differentiates between normal and abnormal sexual response. Some accounts do not specify the duration of the dysfunction or whether generalized or situational.

Due to these methodological obstacles it is difficult to derive consistent trends from the available research. For instance, the reported incidence of low desire in the literature varies from 7.2% up to 54.8%.^17,18 In one US study this varied depending on marital status, educational level and ethnicity.¹⁹ Hayes et al. ²⁰ in the National Survey of Sexual Attitudes and Lifestyles, noted that small differences in the time frame applied to low desire changed the prevalence figures significantly. In their questionnaire, covering the previous year, 17% of the men reported a lack of sexual interest for ≥1 month compared with 40.6% of the women. When asked about lasting problems of ≥6 months in the previous year, only 1.8% of the men and 10.2% of the women reported having a lack of interest in sex.²⁰ West et al. ²¹ found that low desire increased with age from 30% for women aged 30–39 years to 60% for those aged 60–70 years, but those meeting the definition for HSDD (i.e. low desire coupled with distress) were similar across the age groups ranging from 5.8% to 9.4%. Age-related changes are again highlighted by anther US group who reported that low desire in the European Union increased from 10% in women aged 20–29 years to 50% in those aged 60–70 years.²² Although low desire increases with age, HSDD remains relatively stable regardless of age. This again highlights that personal distress is not always associated with reduced desire.

Distress is required for a definition of dysfunction and this may partly explain the variations in derived statistics.²³ A similar allowance needs to be made for cultural, age-related and partner-related differences. Additionally, a larger percentage of sexual dysfunction is seen in childhood sexual assault survivors compared with women with no history of this.

AETIOLOGY

There are many causal factors in female HSDD. It is not a purely physical phenomenon; biological, social and psychological aspects also have an impact. Several studies have looked at the potential link between low desire, HSDD and underlying health conditions.^24,25 In addition, some have looked at the role of centrally acting neurotransmitters involved, including noradrenaline, dopamine, oxytocin and serotonin. For instance, the dopaminergic system is thought to affect sexual behaviour through its activation of drive and motivation, especially in the pursuit of pleasure.²⁶

Oestrogen and testosterone are thought to be important in the sexual pathway. Oestrogens play an essential role in female sexuality in that they make the pelvic tissues resilient enough for comfortable intercourse. They also prime the sensory organs, the key receptors for external sexual stimuli. Oestrogens appear to affect the sense of touch perception, vibration sensation and clitoral sensitivity.²⁷ Oestrogens are also vital to the adequate functioning of the monoamines, serotonin, noradrenaline (norepinephrine) and dopamine in women.²⁸ Thus arousal is facilitated and responsive desire may occur. However, no difference in oestrogen level was found in women with HSDD compared with those without.²⁸ Progesterone contributes to receptivity but is generally not considered to be involved in the desire pathway.²⁷ Receptors for these hormones are in reproductive as well as non-reproductive organs so their effect can be systemic.²⁶

Testosterone, and its proandrogens dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEAS) and dihydrotestosterone, is primarily linked to desire and may be mediated via seratonergic activity in the hypothalamus. Some controlled studies in premenopausal women with HSDD found no difference in testosterone levels.^28–30 However, Davis et al. ³⁰ described an important response to testosterone therapy in postmenopausal women with HSDD. It is well described that circulating DHEAS decreases with chronic disease or stress and this may also contribute to the observed decrease in libido in women.³⁰

There are many causes of female HSDD. It may be secondary to other biological conditions including thyroid, metabolic disorders, depression, immunological disorders, androgen deficiency or postsurgery.²⁵ Various medications, including oral oestrogen therapy, corticosteroids, oral contraceptives and antidepressants, may trigger dysfunction.²⁴ Other dynamics include interpersonal, intrapersonal and cultural or social factors relating to the quality of relationship with, and the health of, her partner (if she has one). This may predispose, precipitate or maintain the dysfunction. Sexual desire changes throughout life with reproductive life experiences (including menstrual cycle, hormone contraceptive, pregnancy, lactation or menopause). This normal oscillation does not necessarily stipulate dysfunction.²⁷ Coexisting distress must be assessed. Age-related changes may be associated with changing hormone levels, health status and psychosocial changes, including partner sexual problems or lack of a relationship.²²

Other features likely to predispose to HSDD are psychological disorders such as depression or anxiety, previous sexual or physical abuse, stress or fatigue. Substance and alcohol abuse may be a precipitating or maintaining factor in HSDD.³¹ Physical gynaecological disorders such as atrophic vaginitis and endometriosis may also contribute to this dysfunction via pain during intercourse or the fear of pain.²⁵ The national health and social life survey³² identified the following risk factors for low desire in women: emotional problems or stress, decrease in household income, history of sexual assault, previous sexually transmitted infection, poor health and previous abortion. Low sexual desire was also associated with lower sexual and partnership satisfaction, according to Leiblum et al. ³³

There are many reasons why a woman will chose to engage in sexual activity. Some of these relate to enhancing the relationship, but others include improving self-esteem, feeling womanly and sharing.³⁴ Small numbers report ‘doing one's duty’. Studies of the emotional and psychological impact of HSDD identified various influences upon women, including a feeling that they have let their partner down, unhappiness, feeling less feminine, disappointment, frustration, low self-esteem, shame and feeling like a failure.³⁴

ASSESSMENT OF HSDD

A thorough history is the starting point for evaluation. Assess the current and past context (biological, psychosocial, sexual), symptoms, sexual response (both partners), psychological factors, emotional stability, medical history with particular attention to psychiatric history, medications, any medical history and menstrual details.²⁵ At the initial visit, investigations to find associated medical problems may include hormone profile and biochemical testing (Box 2). Box 2

Assessment of low libido

History

Sexual history

Context/circumstance

Relationship status/partners response/problems with past partner/s

Degree of distress

Psychological factors – fear/guilt/shame/distractions

Psychiatric history, especially depression

Previous STI

Contraceptive/gynaecological/obstetric history

Investigations

Total/free testosterone

Plasma oestradiol

SHBG

TFT

Prolactin

Consider

Lipid profile/glucose/LH/FSH/FBP

STI, sexually transmitted infection; SHBG, sex hormone-binding globulin; LH, luteinizing hormone; FSH, follicle-stimulating hormone; TFT, thyroid function test; FBP, contains the extracellular portion of the FSH receptor

HOW DO YOU MEASURE DESIRE?

This is essentially a clinical decision, but how do we distinguish normal from abnormal? Many tools have been developed to help the clinician decide. Most of these use questionnaires (telephone, postal, face-to-face or computer-assisted) and this means that results are all self-reported, with sexual thoughts being the most predominant aspect of desire assessed.²⁰ Some questionnaires have also included distress scores. There is a variation in the approach used which can affect our ability to compare between studies. Some studies are based on a population sample, while others focus on outpatients (genitourinary medicine, gynaecology, psychiatry, etc.). The timescales used vary, from one month to longer, ever and recent. Questionnaires might include ‘with partner’ or without.¹⁶

West et al. ²¹ conducted a telephone survey of women aged 30–70 years old in the USA. In this survey two validated scales were used to assess desire and distress: profile of female sexual function and personal distress scale. It is difficult to tease out arousal difficulties, loss of intensity of orgasm or pleasure presenting as reduced libido. There are a number of such validated tools designed to help the clinician to assess HSDD and the ensuing distress, including the female sexual distress scale (FSDS), which uses a five-point rating for 12 different items.³⁵ This scale has been revised (FSDS-R) and validated by Derogatis et al. ³⁶ The female sexual function index (FSFI) is frequently used to assess sexual function and was originally validated in five research centres with over one hundred women with and without dysfunction.³⁷ This 19-point questionnaire assesses sexual feelings and response during the previous four weeks. Clayton et al. ³⁸ looked at sexual interest and desire inventory in females as a measure of HSDD severity independent of relationship issues. There are a number of other screening tools in the literature which are less commonly used.^39,40

HOW DO YOU MANAGE LOW DESIRE?

There are many treatment options for HSDD, but as this condition is generally multifactorial response rates vary. Available therapeutic options include adjusting medications, treating underlying health conditions, counselling or psychosexual therapy, reducing stress and fatigue, hormonal therapy and other pharmacological agents.

Androgen replacement options include transdermal testosterone administration or DHEA treatment, both of which have been shown to result in significant improvements, particularly in libido and mood.^30,41 The rationale for testosterone treatment is that levels of testosterone decline with aging and oophorectomy dramatically reduces it by half. The effects of its use on body composition and muscular function are not well documented, but side-effects include hirsutism, voice deepening, acne, alopecia, liver toxicity, lipid effects and clitoromegaly.³⁰ It is important to keep in mind that the number of randomized controlled trials is still limited and that currently none of the available preparations are officially approved for use in women. The US Federal Drug Agency recently denied approval of an androgen replacement tool for women because of concerns about the paucity of long-term safety data. The testosterone patch (Intrinsa) was granted a license from the European Medicines Agency for postmenopausal women with a sexual dysfunction. The patch was shown to be safe and efficacious in this group of women with only application-site reactions and mild androgenic events (30% versus 23.1% in placebo).⁴²

Tibolone is a synthetic steroid, whose hormonal activity is reliant on the metabolism of the parent compound to various derivatives and these derivatives exerting an effect peripherally in tissues at the receptor level. Tibolone alleviates postmenopausal vasomotor symptoms without stimulating the endometrium, where its effects are predominantly progestogenic.⁴³ It also relieves vaginal dryness, may improve mood, increases bone mineral density and may not have the same thrombotic tendency as standard oestrogen therapy, although this requires verification in properly conducted randomized controlled trials.⁴³

Oestrogen therapy, in the form of rings, cream or tablets, seems to be most useful when treating vaginal dryness, atrophy, irritation and decreased sensation relating to postmenopausal oestrogen depletion but have no direct effect on desire.⁴⁴

Bupropion is a non-hormonal treatment, acting on the dopamine pathway. Segraves et al. ⁴⁵ performed randomized double-blind placebo-controlled trials in premenopausal women with HSDD using this agonist. Both orgasm and arousal scores improved significantly (P < 0.005) with bupropion, but there was no significant change in desire scores. Apomorphine also blocks dopamine receptors and has been used with mixed results.⁴⁴ Some have studied treatments better known for their effects on male sexual dysfunction: phosphodiesterase inhibitors (sildenafil, vardenafil, tadalafil) and prostaglandin E1 (alprostadil).⁴⁶ While there has been some evidence of genital arousal with these products, no consistent link with improved desire was found.⁴⁴

Melanocortin-receptor agonists have been investigated for use in sexual dysfunctions, and bremelanotide has shown better results in disorders of arousal, but trials have stopped as a result of hypertension in those receiving this treatment.⁴⁷ Another drug under investigation for the treatment of HSDD is flibanserin, a drug with both 5HT2 antagonism and 5HT1a agonism. The recent 24-week trial data for this agent found significant improvement compared with placebo. There were significant improvements in FSDS-R scores and in desire measured by eDiary at the 100 mg once daily dose in premenopausal women.⁴⁸ The other endpoints, satisfying sexual events and FSFI scores, did not meet significance for change from baseline. Flibanserin performed well in safety and tolerability aspects with no significant concerns. Dizziness (12%), nausea (11.9%), fatigue (11%) and somnolence (9.5%) were the most frequent reported side-effects.⁴⁸

Psychological treatment is an important aspect of the treatment and may take the form of relationship counselling, sex therapy, cognitive behavioural therapy or analytic psychotherapy. The mainstay will be addressing dysfunctional attitudes and thoughts about sexual behaviour.⁴⁴ In addition, attending to aspects of communication with her partner around sexual feelings and needs may help reduce maintaining factors in this disorder. When referring for therapy, it is important to ensure that the therapist is registered with a professional body and working under a code of ethics.^49,50 Although some clinical success is reported with these therapies, where the cause is thought to be predominately psychosocial, this dysfunction is often treatment refractory.⁴⁴

CONCLUSION

The definition of HSDD must include an assessment of the distress caused by low libido. This is important because it affects the reported prevalence and it may be labelling women who are normal with a dysfunction. Nevertheless, low desire has a significant impact on the quality of life in women who ‘suffer’ this. It is important that the clinician is able to listen, assess and deal sensitively with issues arising from low libido in women.

Women with HSDD present in many different settings: psychiatry, obstetrics, gynaecology, genitourinary medicine, general practitioner and counselling services. Often HSDD is mentioned surreptitiously in clinic with another reason given for the consultation. The assessment of low desire is felt, by some, to be time consuming and difficult. The perspective of the clinician involved may influence the treatment pathway and the therapeutic options will vary depending on the underlying trigger. There have been many recent developments in tightening the definition of HSDD, validated instruments for epidemiological collection and in new treatments. As has been stated, the heterogeneous nature of this population will make generalizations unhelpful and full assessment by an interested clinician is the gold standard.

References

Nazareth

, Boynton

, King

. Problems with sexual function in peopleattending London general practitioners: cross sectional study. BMJ 2003;327:423

Mercer

, Fenton

, Johnson

, Sexual function problems and help seeking behaviour in Britian: national probability sample survey. BMJ 2003;327:426–7

Gott

, Galena

, Hinchliff

, Elford

. ‘Opening a can of worms’: GP and practice nurse barriers to talking about sexual health in primary care. Fam Pract 2004;21:528–36

Emerson

, Goldmeier

, Green

. Assessing training in sexual dysfunction for genitourinary medicine registrars. Int J STD AIDS 2009;20:745–7

Masters

, Johnston

. Human Sexual Response. Boston, MA: Little, Brown & Co, 1966

Kaplan

. Hypoactive sexual drive. J Sex Marital Ther 1979;3:3–9

Basson

. Human sex-response cycles. J Sex Marital Ther 2000;27:33–43

Goldmeier

. ‘Responsive’ sexual desire in women – managing the normal? Sex Rel Ther 2001;16:381–7

10.

Sand

, Fisher

. Women's endorsement of models of female sexual response: the nurses' sexuality study. J Sex Med 2007;4:708–19

11.

American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. 4th edn, text revision [DSM-IV-TR]. Washington, DC: The Association, 2000

12.

World Health Organization. ICD-10: International statistical classification of diseases and related health problems, 10th revision. See http://www.who.int/classifications/apps/icd/icd10online/ (last checked December 2009)

13.

Basson

, Berman

, Burnett

, Report of the international consensus development conference on female sexual dysfunction: definitions and classifications. J Urol 2000;163:888–93

14.

15.

Hartmann

, Heiser

, Ruffer-Hesse

, Kloth

. Female sexual desire disorders: subtypes, classification, personality factors and new directions for treatment. World J Urol 2002;20:79–88

16.

Mitchell

, Mercer

, Wellings

, Johnston

. Prevalence of low sexual desire among women in Britain: associated factors. J Sex Med 2009;6:2434–44

17.

Bancroft

, Loftus

, Long

. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav 2003;32:193–208

18.

Richters

, Grulich

, de Visser

, Smith

AMA

, Rissel

. Sex in Australia: sexual difficulties in a representative sample of adults. Aust N Z J Public Health 2003;27:164–70

19.

Laumann

, Paik

, Rosen

. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281:537–44

20.

Hayes

, Bennett

, Fairley

, Dennerstein

. What can prevalence studies tell us about female sexual difficulty and dysfunction? J Sex Med 2006;3:589–95

21.

West

, D'Aloisio

, Agans

, Kalsbeek

, Borisov

, Thorp

. Prevalence of low sexual desire and hypoactive sexual desire disorder in a nationally representative sample of US women. Arch Intern Med 2008;168:1441–9

22.

Hayes

, Dennerstein

, Bennett

, Koochaki

, Leiblum

, Graziottin

. Relationship between hypoactive sexual desire disorder and aging. Fertil Steril 2007;87:107–12

23.

Hayes

. Assessing female sexual dysfunction in epidemiological studies: why it is necessary to measure both low sexual function and sexually-related distress? Sexual health 2008;5:215–8

24.

Clayton

, Pradko

, Croft

, Prevalence of sexual dysfunctions among new antidepressants. J Clin Psychiatry 2002;63:357–66

25.

Warnock

. Female hypoactive sexual desire disorder: epidemiology, diagnosis and treatment. CNS Drugs 2002;16:745–53

26.

Brown

, Blagg

, Reynolds

. Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today 2007;12:757–66

27.

Frank

, Mistretta

, Will

. Diagnosis and treatment of female sexual disfunction. Am Fam Physician 2008;77:635–42

28.

Schreiner-Engel

, Schiavi

, White

, Ghizzani

. Low sexual desire in women: the role of reproductive hormones. Horm Behav 1989;23:221–34

29.

Stuart

, Hammond

, Pett

. Inhibited sexual desire in women. Arch Sex Behav 1987;16:91–106

30.

Davis

, Moreau

, Kroll

, Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med 2008;359:2005–17

31.

Johnson

, Phelps

, Cottler

. The association of sexual dysfunction and substance use among a community epidemiological sample. Arch Sex Behav 2004;33:55–63

32.

Laumann

, Gagnon

, Michael

, Michaels

. The Social Organisation of Sexuality. Sexual Practices in the United States. Chicago: University of Chicago Press, 1994

33.

Leiblum

, Koochaki

, Rodenburg

, Barton

, Rosen

. 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

34.

Graziottin

. Prevalence and evaluation of sexual health problems-HSDD in Europe. J Sex Med 2007;4:211–9

35.

Derogatis

, Rosen

, Leiblum

, Burnett

, Heiman

. The female sexual distress scale (FSDS): initial validation of a standardized scale for assessment of sexually related personal distress in women. J Sex Marital Ther 2002;28:317–30

36.

Derogatis

, Clayton

, Lewis-D'Agostino

, Wunderlich

, Fu

. Validation of the female sexual distress scale-revised for assessing distress in women with hypoactive sexual desire disorder. J Sex Med 2008;5:357–64

37.

Rosen

, Brown

, Heiman

, 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

38.

Clayton

, Segraves

, Leiblum

, Reliability and validity of the sexual interest and desire inventory-female (SIDI-F), a scale designed to measure severity of female hypoactive sexual desire disorder. J Sex Marital Ther 2006;32:115–35

39.

Rust

, Derogatis

, Rodenburg

, Koochaki

, Schmitt

, Golombok

. Development and validation of a new screening tool for hypoactive sexual desire disorder: the Brief Profile of Female Sexual Function (B-PFSF). Gynecol Endocrinol 2007;23:638–44

40.

Derogatis

, Allgood

, Rosen

, Leiblum

, Zipfel

, Guo

. Development and evaluation of the Women's Sexual Interest Diagnostic Interview (WSID): a structured interview to diagnose Hypoactive Sexual Desire Disorder (HSDD) in standardized patients. J Sex Med 2008;5:2827–41

41.

Braunstein

, Sundwall

, Kratz

. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch Intern Med 2005;165:1582–9

42.

Davis

, Moreau

, Kroll

, Testosterone for low libido in postmenopausal women not taking estrogen. New Engl J Med 2008;359:2005–7

43.

Laan

, Van Lunsen

, Everaerd

. The effect of tibilone on vaginal blood flow, sexual desire and arousability in postmenopausal women. Climacteric 2001;1:28–41

44.

Segraves

, Woodard

. Female hypoactive desire disorder: history and current status. J Sex Med 2006;3:408–18

45.

Segraves

, Clayton

, Croft

, Wolf

, Warnock

. Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women. J Clin Psychopharmacol 2004;4:339–42

46.

Berman

, Berman

, Toler

, Gill

, Haughie

. Safety and efficacy of Sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo controlled study. J Urol 2003;170:2333–8

47.

Wylie

, Malik

. Review of drug treatment for female sexual dysfunction. Int J STD AIDS 2009;20:671–4

48.

Nappi

, Dean

, Van Lunsen

, Herbert

, Kimura

, Pyke

. Efficacy of flibanserin as a potential treatment for hypoactive sexual desire disorder in European premenopausal women: results from the ORCHID trial. J Sex Med 2009;6:409 (abstract)

49.

50.