Johannes Bitzer1
(1)
Department of Obstetrics and Gynecology, Women’s Hospital, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland
Johannes Bitzer
Email: JBitzer@uhbs.ch
This is a shortened and adapted version of a publication in the Journal of Sexual Medicine.
14.1 Definition
DSM IV defines Hypoactive Sexual Desire Disorder (HSDD) as:
· Persistent or recurrent deficiency (or absence) of sexual fantasies and desire for sexual activity
· Causes marked distress or interpersonal difficulty
· Cannot be better accounted for by other factors (e.g. medical or psychiatric illness, drug of abuse and medication)
HSDD is not only associated with general personal distress but also has a specific negative impact on a woman’s relationship and her partner.
16 premenopausal women and 20 postmenopausal women with HSDD or decreased sexual desire who participated in five focus groups reported:
Impact on self
Women felt “sad”, “distressed”, “frustrated”, “annoyed”, “guilty”, “confused” and “bothered” about their decreased sexual desire.
Women “wanted to want sex.”
Impact on relationship
Women experienced issues with trust, changes in intimacy and often had sex to appease partners.
Impact on partner
Women perceived that they induced feelings of rejection and frustration in their partners.
Many partners understood towards the woman’s decreased desire.
14.2 Trying to Understand Desire and Lack of Desire
As a largely subjective experience, sexual desire may or may not be accompanied by externally observable changes in sexual behaviour.
14.2.1 General Factors Which Constitute Desire
Sexual desire can be described as a composite experience consisting of different elements:
· Drive (Biological component)
· Motivation (Cognitive component)
· Responsiveness to sexual stimuli (Response component)
Drive can be considered as an internal force (appetite and energy) that pushes an individual to do something. It is usually viewed as an instinct, with inborn patterns of reaction.
Motivation for sexual activity is a more complex psychophysiological phenomenon and is much more linked to cognitive processes, which are typically characterised by the concept of incentive or reward. Motivation for sexual activity may reflect a desire for sexual pleasure, intimacy, pleasing the partner, feeling desired, emotional or narcissistic satisfaction or motives not related directly to sexual desire or behaviour (e.g. financial gain).
Responsiveness to sexual stimuli refers to the ability of sexual stimuli to induce sexual desire, arousal, sexual behaviour and sexual pleasure in an individual. This component is certainly a mixture of a physical reactivity (possibly having to do with sensitisation of receptors or neurochemical systems) and cognitive processes (reward expectations, personal value system, etc.).
We can distinguish “drive” as an internal factor that pushes an individual to do something from the “incentive” as an external factor that pulls an individual towards it.
Applied to sexual behaviour, hormonal factors around ovulation push women towards sexual thoughts and behaviours, whereas the appealing features of an individual or situation would pull women towards interacting sexually with that person or in that situation.
14.2.2 Models of Understanding Desire Disorder
After the description of the sexual human response by Masters and Johnson with the phases of excitement, plateau and orgasm and the addition of the desire phase by Kaplan in a linear model of the human sexual response, it has been questioned whether this “classical model” describes the sexual experience of women.
Basson described a circular model in which the above-mentioned three dimensions of sexual drive, motivation and responsivity are integrated in a circular process in which desire is part of the flow of sexual activity, but not necessarily the first, or initiating step. There may be spontaneous desire or other motives to become sexually active or responsive to sexual stimuli. This may lead to sexual arousal, which may trigger or enhance desire, thus leading to an increase in sexual activity, arousal and sexual interaction that result in orgasm and other states of emotional reward (feelings of fulfilment, relief, etc.). In turn, such experience is thought to increase desire as an internal state of “wanting sex”.
In this model, the three elements described above are found in reciprocal interaction. “Spontaneous desire” is a drive dimension; “Various motives” describe a motivational dimension; and “Response” to “sexual stimuli” corresponds to the receptivity dimension.
Other models of understanding sexual desire have been developed:
14.2.2.1 The Incentive-Motivation Model
In contrast to Freud’s understanding of drive as an inborn instinct which needs to be satisfied to reduce inner tensions this model focuses on the individual adequacy of the sexual stimulus to induce desire. Desire as sexual motivation and action is created when an external adequate stimulus meets with an internal readiness to respond.
14.2.2.2 The Push–Pull Model
The underlying hypothesis is that there are two dynamic forces acting together which “produce” a feeling of desire.
One is a “pushing factor” that comprises the internal energy that pushes a person towards sexual expression and activity. This force includes inborn instinct, hormonal activity, innate or learned sexual preferences and other internal elements.
The “pulling factor” includes the attraction or incentive that pulls a person towards sexual activity. This includes the sex appeal of the partner and/or the situation, expected reward, sexual feedback and reinforcement from the partner. This model gives desire a biographical dimension that spans an individual’s experience and memory.
14.2.2.3 The Excitation/Inhibition Model
Several authors have pointed out that desire is the result of a dynamic interaction between physiological and brain mechanisms of excitation and inhibition, thus providing a dual control mechanism of sexual behaviour. The turn on/turn off balance is driven or steered by excitatory forces which are the result of specific prosexual physiological and organic mechanisms that activated by appropriate psychosocial and sociocultural events on one hand, and by inhibitory forces which are also the result of specific inhibitory physiological and organic mechanisms driven by antisexual psychosocial and sociocultural events.
These models suggest that HSDD may result from hypofunctional excitation, hyperfunctional inhibition or some mix of the two.
The biological basis for this dual response is estimated to be the following:
Steroid hormones have mainly a priming effect for the brain to respond to various neurotransmitters and increase receptivity to sexual stimuli.
Sexual excitation neurotransmitters
· Brain noradrenaline systems underlie sexual arousal, whereas brain dopamine systems (incertohypothalamic and mesolimbic) that link the hypothalamus and limbic system activate attention and incentive motivation.
· Melanocortin systems in the brain activate desire, and oxytocin systems activate preference behaviour.
Sexual inhibition neurotransmitters
· Brain opioid systems that underlie pleasure and reward, endocannabinoid systems that induce sedation and serotonin systems that induce satiety are activated during periods of sexual inhibition. These systems blunt the ability of excitatory systems to be activated by appropriate sexual incentives.
All dual control models stress the adaptive nature of excitatory and inhibitory processes to respond to the environment.
· The adaptive nature of sexual excitement would drive individuals to seek out sex partners for reproductive or reward purposes.
· The adaptive nature of sexual inhibition would guard again situations that threaten the individual including chronically stressful life events.
14.3 Prevalence
Overall, the prevalence of desire complaints ranges from 10 to 40 % depending on the study methodology, participants and geographic location/culture. When the term “distressed” is considered, prevalence of desire/arousal complaints drops by at least half, although those rates increase when the term “bothered” is used.
Low desire increases with age but low desire + distress decreases with age.
14.4 Aetiology and Pathogenesis
The best approach to distressing low desire is the multidimensional perspective of the biopsychosocial model of understanding human sexuality as the result of an interaction between biological, psychological and social factors. From this perspective, a large variety of factors may contribute to low desire.
14.5 Biological and Biomedical Factors
14.5.1 Hormones and Endocrine Changes During the Life Course of the Woman
Ovarian steroid hormones are involved on central and peripheral processes as part of female’s sexual physiology and biology. Oestrogen can be regarded as permissive or receptive signal and testosterone is not only important for desire in men but also in women.
· Oestrogens: Increases in self-reported sexual desire are highest in women during ovulation when oestradiol levels peak. Oestradiol acts mainly on ER alpha in the female brain, with highest concentrations of oestradiol measured in the hypothalamus and the preoptic area. Increased oestrogen action increases vaginal blood flow (VBF), while a decreased concentration diminishes VBF. The mechanism by which this occurs is related to oestrogen stimulation of the release of vasoactive substances such as nitric oxide by endothelial cells, which induces vasodilatation.
· Progestins: In rats and other animals, progestins like progesterone facilitate solicitations and lordosis. However, progesterone treatment to hypogonadal pre- or postmenopausal women does not facilitate measures of desire.
· Androgens: Testosterone interacts with androgen receptors with highest concentrations in the substantia nigra/ventral tegmental area, the hypothalamus and the preoptic area. Testosterone is also the primary precursor for oestradiol biosynthesis in the brain; indeed, the testosterone concentration in the brain is 7–10 times higher than the oestrogen concentration, with the highest ratio of testosterone versus oestradiol in the preoptic area. The effects of testosterone are difficult to distinguish from those of oestradiol, and combined replacement therapy using both steroids generally results in a better enhancement of sexual desire than either steroid alone.
Women experience typical transitional periods in their life which are characterised by changes in ovarian steroid hormones. These are natural experiments to better understand the role of these hormones in real-life situations for the sexual desire and activity of women.
· Menopause transition: The menopausal transition has been associated with a decline in desire and subjective arousal among women. HSDD as the most frequently reported sexual problem in women, ranging from 15 to 25 % in premenopausal women to 40–50 % in postmenopausal women. Although the role of hormones as isolated factors is controversial, well-designed longitudinal studies have shown an increase in sexual dysfunction with a major negative impact on desire and a correlation with the decline in oestrogen. It must be noted, however, that the decline in circulating oestrogens is correlated with an increase in dyspareunia and lubrication difficulties. Those could lead secondarily to diminished desire or avoidance of sexual activity.
· Postpartum period: The postpartum period is associated with high sustained levels of prolactin and oestradiol that may induce inhibitory feedback on brain mechanisms that excite sexual desire. Accordingly, reports indicate that a woman’s interest in sexual activity changes after childbirth. A substantial proportion of women (range: 47–57 %) interviewed at 3-month postpartum noted a decreased interest in sexual activity. However, decreased desire during this period could also be attributed to fatigue, pain and concern over injury. Despite any changes in desire, more than 80 % of women resume sexual activity by 6-week postpartum. Similarly, in female rats the postpartum period is associated with high oestradiol and prolactin levels, and a complete avoidance of sexual activity with males. Those levels decrease precipitously after weaning or removal of pups and sexual activity is resumed when cyclic hormonal rhythms are re-established.
· Oral contraceptives: Combined oral contraceptives containing ethinyl oestradiol increase SHBG titres and thus decrease available free testosterone. This could contribute to a lack of desire and subjective arousability [83]. Due to the fact that oral contraceptives are linked to myriad psychological and biological actions, some of which may have a positive impact on sexuality (e.g. reduce anxiety about unwanted pregnancy, diminish dysmenorrhoea, attenuate acne, etc.), it is very difficult to discern the clinical effect of the decrease of free testosterone in users of some oral contraceptives and clinical studies have been inconclusive some reporting decreased desire, some no change in desire and others increased sexual desire.
14.5.2 Diseases and Drug Use
A large number of clinical conditions and medications can lead to decreased sexual desire.
The three most important factors are major depression, cancer and medication
· Major depression: Major depression is the most important clinical condition having an impact on desire. This disorder or group of disorders has a complex pathogenesis and certainly is not defined and determined by purely neurotransmitter dysregulation. It is now generally accepted that there is a neurobiological component which is characterised by altered functions, especially of the noradrenergic and serotonergic systems.
· Cancer: Malignant diseases, especially in the urogenital region, may have various negative consequences for the female patient’s sexual function and thereby affect indirectly or directly desire. The disease itself and the subsequent surgery and radiation can lead to destruction of sexual organs, as occurs in vulvar, vaginal, uterine and ovarian cancers. These are often accompanied by disfigurement of the body that impacts negatively on sexual self-image.
· Medications: Both prescription and over-the-counter medications have the capability to alter arousal, desire and orgasm. The mechanisms can be divided into central nervous, peripheral nervous, neurovascular and neuromotor, endocrine and local. Any medication that alters blood flow (e.g. antihypertensives), affects the CNS (e.g. psychotropics) or dries the skin or mucous membranes (e.g. antihistamines) may disrupt normal sexual function.
One of the major classes of medications that impacts sexuality is the selective serotonin reuptake inhibitors (SSRIs), frequently used to treat depression in both pre- and perimenopausal woman. The risk/benefit ratio with use of these agents is based on individual need and response. When depression is severe, SSRIs may allow a short-term increase in sexual activity by treating the underlying process. However, in many patients, chronic therapy can diminish sexual desire and alter or eliminate arousal and orgasm. The mechanisms for this inhibition may be through decreased dopamine transmission (leading to increased prolactin levels), or by stimulation postsynaptic serotonin receptors that blunt sexual arousal and desire. Stimulation of 5-HT1b, 5-HT2 and 5-HT3 receptors appears to inhibit sexual desire.
14.5.3 Others
Other frequent contributing factors are Lower Urinary Tract Disorders and Diabetes
· Urinary Incontinence: Prevalence rates from 0.6 to 64 % are reported. In a case–control study, women with urinary problems had significantly more incidents of low desire, arousal difficulties and pain.
· Diabetes: The predominant symptoms are largely arousal based, including arousal dysfunction and decreased lubrication in women. No statistical significant difference in desire was found compared with the control groups used in those studies.
Neurological diseases often have a direct impact on the neuroregulation of the female sexual physiology. Their impact on desire is mainly indirect
· Spinal cord injuries, MS and neuromuscular disorders: There is a direct impact of these disease states on the neuromuscular and neurovascular elements of the sexual response. These mechanisms are very prominent in neurological diseases like MS, spinal cord injuries, etc. The effect on desire is in general indirect, and mediated by arousal disorders and pain.
· Parkinson’s disease, Dementia and Schizophrenia: It is known that hypothalamic sexual centres are connected to central nervous neurotransmitter pathways and may be therefore influenced by disturbances of dopaminergic, serotonergic, adrenergic and GABAergic action. Examples of this are the disturbances occurring in patients with Parkinson’s disease, dementia and various psychiatric diseases. The changes can result not only in decreased desire but also in increased desire and hypersexual behaviour (e.g. as occurs in patients with decreased frontal lobe function in dementia). Sexual dysfunction is estimated to affect 30–80 % of patients with schizophrenia and is a major cause of poor quality of life.
· Pituitary tumours and Hyperprolactinaemia: The main mechanism is supposedly the inhibitory impact of elevated prolactin on the dopaminergic system although dopamine acts as a prolactin inhibitory factor, and decreased dopaminergic function in general may lead to HSDD and hyperprolactinaemia by two different mechanisms.
14.6 Individual Psychologic Factors
A large number of psychological factors can lead to low sexual desire.
These factors can be subdivided in those which have occurred in the past (predisposing and indirect factors) and those which are still now contributing to the symptom (maintaining and immediate factors).
Predisposing, Indirect Factors
· Negative early environment: Bad quality of attachment to parents and caregivers can predispose to negative internal scripts of sexuality and sexual pleasure.
· Sexual abuse and emotional neglect in childhood: One of the sequelae of this experience is low desire and sexual aversion disorder.
· Traumatic experiences during puberty: Negative sexual experiences and especially humiliation and offense may have harmful long-term consequences also in reducing motivation for being sexually active.
Maintaining, Immediate Factors
· Perceived distress: Distress may induce physiological responses like cortisol increase, which may counteract testosterone secretion and thus contribute to low desire in addition to cognitive distraction and anxiety which may accompany chronic stress and thus counteract sexual desire.
· Distraction: Distraction has been shown to be detrimental to female sexual function, especially subjective arousal and desire linked with sexual arousal.
· Performance anxiety (concerns) and anxious apprehension: For women, there is a large array of sexual concerns (worries about pleasing her partner, fear of partner rejection, fear of pregnancy and STIs, unease related to the ability to reach orgasm, etc.) which may induce performance anxiety.
· Expectations (Anticipation) of a negative experience: Low self-esteem combined with anticipation of negative outcomes may diminish the receptivity for erotic and sexual cues.
· Body image self-consciousness: Negative or insecure concepts and concerns about the body may lead to inhibition and sexual desire.
14.7 Relationship Factors
There is a close link between relationship and sexual satisfaction, which may indirectly impact sexual desire.
· Partner’s sexual dysfunction : Sexual dysfunction of the male partner, especially erectile dysfunction and premature ejaculation, has a negative impact on the female partner’s desire.
· Duration of the relationship and routine: Habituation and routine may contribute to the fact that the duration of relationship is inversely correlated to sexual desire and arousal.
· Communication deficits: Difficulties in the ability to express sexual needs, wishes and fears between partners are often an immediate and direct factor, which impacts negatively on a woman’s desire to engage in sexual activity.
14.8 Sociocultural Factors
14.8.1 Diagnosis
Due to the lack of objective criteria, the importance of subjective experience, and the multifactorial aetiology of HSDD, it is necessary to use a diagnostic pathway that takes those characteristics into account.
14.8.1.1 Initiation
A physician–patient discussion about sexual problems is likely very different from one about blood pressure:
· It can be uncomfortable for both physician and patient.
· There is no real example of an “ideal” conversation.
· There is a lack of clarity regarding definition, assessment and objective measures.
The challenge of talking appropriately with patients about sex needs to be met because sexual problems:
· Are highly prevalent.
· May affect overall well-being and self-image more than many other conditions.
Most patients feel a sense of relief when they understand that their sexual problems are common. Therefore, it is the responsibility of the physician to initiate the conversation and to use appropriate communication skills. Communication skills include the use of open questions, encouragement, generalising and normalising the issue of sexuality.
14.8.1.2 The Narrative: Understanding the Individual Profile of HSDD
The narrative describes the story of the patient in her own words. It allows the physician to get inside into the world of the patient (her feelings and thoughts) by listening to the content, the words used, the tone, the phrasing, the pauses, etc.
The physician must be able to understand the individual profile of the desire problem and the multifaceted phenomenology of each individual case.
Several aspects of the desire problem should be attended to with great care:
· Dimensions: This refers to the internal comparison a woman makes regarding her desire problem. Is it less desire compared to the partner’s desire? Less than in past experience? Less than she might perceive other women’s to be? Less than some internal ideal of desire that she might have?
· Elements and composition: Which parts of the desire experience are affected, such as internal (cognitive and emotional elements example fantasies, daydreams, feeling sexy and feeling sexual appetite) or external behavioural elements (active seeking of sexual stimuli and/or sexual activity with or without partners).
· The distress caused by the low desire: This can be elucidated by asking the patient what the impact of low desire is on her individual mental well-being, the relationship and her general quality of life?
14.8.1.3 Differentiating Questions
After understanding the individual profile of the HSDD, the physician needs to differentiate clinical subtypes. The following subtypes are of importance and can be differentiated by questions:
A)
B)
C)
D)
14.8.1.4 The Descriptive Diagnosis of HSDD
The descriptive diagnosis of HSDD describes the dimensions, elements, the degree of bother or distress, the possible combination with arousal disorder, orgasmic disorder, sexual pain disorder and distinguish between primary versus secondary, global versus situational, gradually developing versus abrupt beginning and single versus combined disorder.
14.8.1.5 Exploring Conditioning Factors
The multifactorial aetiopathogenesis of HSDD is well documented in the literature.
Two major groups of conditioning factors can be distinguished, which have to be elucidated by history taking:
A)
B)
The gynaecological examination should include:
· Vulva: check for labial and clitoral structure and morphology (agglutination, etc.), check for atrophy, lichen, inflammation, check for painful points in vestibulum.
· Vagina: check for atrophy, ph, signs of infection, descensus, cysto and rectocele
· Pelvic floor: check for hypertonicity of pelvic floor muscles, muscular insufficiency, ability to voluntary contract pelvic floor muscles
· Uterus: check for fixed retroflexion, painful sensations especially of uterosacral ligaments and fibromas
· Adnexal region: painfulness on examination and adnexal masses
Ultrasound examinations to assess uterine adnexal pathology are also recommended.
Usually, there is no indication for laboratory investigation. Oestrogen deficiency can be detected by history and physical exam. Androgen deficiency can be detected by history and checking into the combination of symptoms. I think we need to add other blood test that can be recommended if indicated as glucose, thyroid hormones, prolactin and maybe more specialised as FSH, LH? What about blood pressure is that also on the list? However, I agree that the message should be that blood tests are taken when there is a clinical indication, not routinely.
14.8.1.6 The Explanatory Comprehensive Diagnosis
The biopsychosocial assessment should be summarised and organised in two major dimensional lines as an explanatory diagnosis.
A)
B)
In each dimension, there are factors that have a direct immediate impact on sexual function: for example, on the biological level, this may be drugs or hormonal changes; on the psychological level, these can be ignorance, performance anxiety, distraction; on the level of the relationship, it maybe the partner’s way of stimulating or partner’s dysfunctions. Distant indirect factors are those that date back in the life story of the patient but still have an impact like previous operations (biological level), early neglect and abuse (psychological level), previous traumatic experiences in relationships (relational level) and education (sociocultural level).
14.9 Therapeutic Options
14.9.1 Basic Counselling
Basic counselling comprises several elements as given below:
· It gives the patient the opportunity to talk about her own sexuality. Through active listening the patients will feel accepted and understood and may get emotional relief (Catharsis effect).
· Information can be disseminated about frequency of problems, differences and similarities between female and male sexuality, knowledge about sexual physiology and anatomy (Psychoeducation).
· Counselling can increase knowledge and dispel myths and misinformation about human sexuality (Empowerment).
14.9.2 Hormonal treatments
Hormone replacement therapy is indicated for the following:
· HSDD with a clinically significant drive deficiency component
· Medical conditions leading to hormone deficiency states
· Menopause transition and aging
· Hormonal contraception
· Add-back therapy in patients with mixed aetiology
A large majority of studies show positive effects of hormone replacement therapy in different aspects of female sexual function and sexual satisfaction.
Clinical trials with testosterone therapy in women with HSDD have shown treatment efficacy in:
· Surgically menopausal women treated with oestrogen and progesterone
· Naturally menopausal women treated with oestrogen and progesterone
· Surgical and natural menopausal women without oestrogen and progesterone treatment and in premenopausal women
Tibolone had beneficial effects on HSDD in two studies [117, 118].
DHEA has not proven effective in controlled studies. There are, however, interesting results indicating that DHEA and DHEAS may serve as important precursors for androgen production, and thus substitution with these substances may correct some subclinical deficiencies in testosterone levels.
14.9.3 Centrally Active Drugs
These would be indicated for women with HSDD in whom no major endocrine or psychosocial factors contribute to low desire. Although no drugs have yet been approved for the specific treatment of HSDD, some are used off-label to promote sexual desire in women suffering from HSDD.
One is the antidepressant bupropion [121], which can increase arousability, responsiveness and sexual desire in women with major depression. This drug blocks the reuptake of dopamine and acts as a noradrenergic and cholinergic receptor antagonist, which may augment the activation of excitatory systems in the brain for sexual desire.
Several drugs are currently undergoing clinical trials for the treatment of HSDD.
· The melanocortin agonist drug bremelanotide [122] promotes dopamine release in the preoptic area of the hypothalamus and has shown initially promising results in men and women. But unexpected cardiovascular side effects have led to the stop of further research with this drug.
· Flibanserin, a drug that acts at serotonin receptors to reduce the inhibitory influence of serotonin, showed partial efficacy and would have been an interesting venue for the pharmacological treatment of low desire. The FDA asked the producer to provide further evidence about efficacy and risks which led to a situation in which the drug was not registered for this indication.
14.9.4 Psychotherapeutic Interventions
Psychotherapy is indicated when there is ambivalent motivation to be sexually active with a partner, but in which the partner does not suffer from sexual dysfunction and both partner and patient are motivated to fix the problem. The lack of desire may stem from interpersonal relationship issues, lack of knowledge and experience with sexual pleasure, low sexual self-esteem, patterns of sexual activity that have become “routine”, etc. The treatment of HSDD by psychotherapeutic interventions is not well documented as far as evidence-based medicine requirements are concerned. Although the sensate focus therapy of Masters and Johnson was reported to be successful, it had limited outcome measurements assessed in the short term. It is not clear how long the therapeutic effect lasted, or whether it translated well from the therapeutic environment back to the patients’ home environment. There is only one randomised controlled trial in the past 6 years, in which group cognitive behaviour therapy was shown to improve HSDD in 74 % of women [124]. More recent studies have reported good efficacy in treating both sexual arousal and desire disorders in women using elements of mindfulness, meditation and yoga in addition to psychotherapy [129]. It is likely that therapeutic approaches must be tailored to the particular subtype of HSDD along with the particular needs of the patient. It is also likely that drug therapy in conjunction with psychotherapy will be beneficial for many patients, especially if the psychotherapeutic intervention can build upon a faster amelioration induced by the drug effect.
References
1.
Bitzer J, Giraldi A, Pfaus J (2013) Sexual desire and hypoactive sexual desire disorder in women. Introduction and overview. Standard operating procedure (SOP Part 1). J Sex Med 10(1):36–49PubMedCrossRef
2.
Bitzer J, Giraldi A, Pfaus J (2013) A standardized diagnostic interview for hypoactive sexual desire disorder in women: standard operating procedure (SOP Part 2). J Sex Med 10(1):50–57PubMedCrossRef