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Libido: the biologic scenario
34 Suppl 1 (2000) S9 – S16 www.elsevier.com/locate/maturitas
Libido: the biologic scenario Alessandra Graziottin * Menopause Center, H. San Raffaele Resnati, Milan, Italy
Abstract Libido is a comprehensive and yet elusive word that indicates basic human mental states — and their biological counterparts— involved in the beginning of sexual behavior. It has three main roots: biological, motivational-affective and cognitive. All these dimensions may be variably affected in the post menopause, contributing to a progressive decrease of sexual drive that parallels the process of aging. Loss of estrogens and, specifically, of androgens deprives female libido of major biological fuel. The effect of this loss is pervading, affecting the central nervous system, the sensory organs that are the major windows to environmental sexual stimuli and the quality of sexual response, central, peripheral non-genital and genital. Prolactin increase may further inhibit libido. Arousal disorders, dyspareunia, orgasmic difficulties, dissatisfaction, both physical and emotional, may contribute to a secondary loss of libido. Depression, anxiety and chronic stress, may interfere with central and peripheral pathways of the sexual response, reducing the quality of sexual function mostly in its motivational root. Relational conflicts and/or marital delusions and partner-specific problems, erectile deficit first, may contribute to the fading of sexual drive in the post-menopausal years. Well tailored HRT, including androgens in selected cases, may reduce the biological causes of loss of libido. A comprehensive treatment requires a balanced evaluation between biological and pychodynamic factors. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Libido; Sexual hormones; Estrogens; Androgens; Sensory organs; Arousal disorders; Dyspareunia; Menopause
1. Introduction Human sexuality depends on a complex interaction among cognitive processes, neurophysiological and biochemical mechanisms and mood [1]. It also has strong relational bases. Difficulties in evaluating the relative weight of those different factors are rooted both in the complexity of the human sexual experience and in the fogginess of * Corresponding author. Present address: Via San Secondo 19, 10128 Turin, Italy. Tel./Fax: + 39-011-544283. E-mail address: [email protected] (A. Graziottin)
words and concepts that refer to it. Sexual appetite, desire and drive, sexual impulse and interest: many psychosexual and behavioral terms are used as synonims of libido [2], a latin word that means ‘desire’. It was first used by Sigmund Freud [3] to indicate the energy correspondent to the psychic side of the sex drive. Carl S. Jung [4] defined libido in a wider sense, as the psychic energy present in all that is ‘appetitus’, a kind of ‘desire towards’, not necessarily sexual. In recent literature, libido is again considered in its main sexual appetitive meaning that motivates a person to obtain sex and focuses his/her attention on that
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goal. This subjective experience is accompanied by and partly consists of various physiological changes, many of which are in preparation for sexual behaviour [1]. A useful working definition is that ‘sexual desire is normally an activated, unsatisfied mental state of variable intensity, created by external -via the sensory modalities- or internal stimuli -fantasy, memory, cognition..., that induces a feeling of a need or want to partake of sexual activity (usually with the object of desire) to satisfy the need’ [2]. This sexually activated mental state may be set against and influenced by the mood of the moment. In a depressed mood we are less likely to interpret experiences in pleasant sexual terms [1,8]. A mood of inertia, typical of depression, reduces the likelihood of initiating overt sexual action, in spite of favourable external conditions, i.e. the availability of a willing partner. The relationship between hormones and libido may therefore be studied through the effects sexual hormones have on this peculiarly activated mental state and on the different stimuli that enhance or inhibit it. From the biologist’s point of view, this sexual appetite can be further divided in ‘proceptivity’ and ‘receptivity’. The former referring to the willingness to initiate and invite sexual contact or sexual stimulation, the latter describing the preparedness of an individual (usually the female) to accept the sexual advances of another [5 – 7]. ‘I never initiate sex but I respond when my husband approaches me’ could be considered as a fairly common condition in stable couples, somehow borderline with normal female behaviour, although it may also address a disorder of proceptivity, with receptivity being intact [7]. Conversely, ‘I feel the need for sex but lose interest when my husband approaches me’ could be seen as a disorder of receptivity but not of proceptivity, clearly indicating a selective loss of desire, limited to that specific partner [7]. How much of this difference is secondary to biological or psychosexual and relational dynamics is far from being understood. Psychological processes play an important role in human libido: we learn to feel sexual drive at certain times and in certain situations, and for some this learning component dominates their sexual behaviour, as it happens in the week-end
sex of many stable couples. In recent years, the realm of libido has grown to include a deeper understanding of its biological roots [5–7] both endocrine and neurochemical, of the motivational and relational components [8–11] and of its vulnerability to personal factors and external agents. Menopause may represent a critical turning point of libido, as biological, motivational-affective and cognitive factors [5] may all undergo deep changes. Motivation to sex lose the primary biological goal, reproduction, but may well maintain the pursuit of pleasure, the ‘recreational sex’ [2,12] as well as the ‘instrumental sex’, when sex is performed as a means to obtain advantages and express motivations different from pleasure and/ or procreation [13]. In our species, libido has several roots, with a complex interplay among biological, motivational and relational factors, that may all have both an inhibiting or enhancing role [1,2,5–15].
2. Libido and sexual arousal Libido – or sexual desire – is considered different from sexual arousal. Sexual desire is an attitude toward an object, while sexual arousal is a state with specific feelings, usually attached to the genitals. There can be sexual arousal without sexual desire, and sexual desire without arousal. Human sexual arousal can be characterized by three components: a central arousal, a non-genital pheripheral arousal and a genital arousal [2,8]. Sexual desire and sexual arousal should therefore be kept distinguished.
3. Biological roots of libido
3.1. Hormones and the brain sexualization In men, consistent evidence shows that androgens are necessary though not sufficient factors to maintain a satisfying human libido, the best data coming from placebo controlled studies of androgen replacement in hypogonadal men [16,17]. In women, the evidence for hormone-behaviour relationships is much less consistent and often contra-
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dictory [1,7–11]. Estrogens prime the central nervous system, acting as neurotrophic and psychotrophic factors during the female life [14,15]. They contribute to primary and secondary sex characters, that nourish the inner sense of femininity. They prime as well the sensory organs including skin that are the key receptors for external sexual stimuli. Sensory organs transmit the basic information that, mixed with emotional and affective messages, contributes to the structuring of core sex identity and self image, so relevant for the personal perception of being an ‘object of desire’ and for the direction (homo- or heterosexual) of the libido itself [8,18]. Involution of sensory organs may be an overlooked contributor of the biologic loss of libido many women report after the menopause [19,20]. The interplay between estrogens and the dopaminergic system is the key process in determining the appetitive side of sexual behaviour [6,7,15], which can be further thrilled by the peak of androgens at ovulation. This link is supported by the correlation between testosterone levels and frequency of masturbation [21] or vaginal response to erotic stimuli in laboratory [22], that is with aspects of autoeroticism rather than partner sex. This latter has many more relational variables that may explain the contradictory findings in researches trying to correlate human female cycle with variations in libido [1,8,15]. Some consensus is found in the peak just before or after menstruation [23], and it is not clear how such pattern could be hormonally determined, as it is opposite to the mid-cycle peak of androgens that are assumed to be the ‘libido’ hormone in men as well as in women. The improvement of mood in the post-menstrual phase could partly account for this favourable increase [1]. Progesterone seems to have an inhibitory effect: its premenstrual fall could contribute to the perimenstrual increase in sex desire, at least in those women not suffering from premenstrual syndrome (PMS). Bancroft [1] suggests that these seemingly discrepant findings may be explained by a different brain effect of androgens during early female development, either because of different target organs sensitivities or different timing of hormonal effects (in contrast with males who are relatively overdeter-
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mined by androgens during early development). Money and Ehrhardt [18] hypothezise that the sensitivity of the female sexual behavior to hormonal variations may depend not only on the actual fluctuations and/or levels, but also on the quality of central and pheripheral estrogenic and androgenic priming. These early differences could also contribute to the biological basis of the huge variations: in libido profile in women; in female sexuality after the menopausal hormonal fall; in the different responsiveness to hormonal treatment as far as libido is concerned. Libido modifications during the female cycle may give useful suggestions on how HRT may act on the biological basis of sex drive after the menopause. In the conflict between nature and culture, psychosocial factors seem to be more important in women than in men. At the moment androgens look nevertheless the most interesting hormones for the sexuality of women [1,6,7,15,24–35]. They could have a 3-fold action: increase susceptibility to psychosexual stimulation, contributing to the ‘sexually activated mental state’, typical of a good libido; increase sensitivity of the external genitalia, facilitating the nitric oxide pathways that leads to clitoral congestion; increase the intensity of sexual gratification [26]. A specific ‘Female Androgen Deficiency Syndrome’ (FADS), with loss of libido, reduced vital energy, reduced assertiveness, loss of pubic hair and diminished muscle mass has been described after bilateral ovariectomy [24], that on average deprives the woman of 50% of her androgen production. A recent review of Rubinow and Schmidt [27] suggests that in men androgen dependence takes the form of a threshold level, below which libido and sexual function are impaired, and above which they are not, with no correlation between either the ideational or erectile components of sexual function and testosterone levels in the normal range. In women, both a positive correlation [28] and the absence of it [29] between testosterone levels and sexual interest and behaviour have been observed. Similarly, androgen replacement therapy increases libido in women who are androgen-deficient (e.g. after surgical menopause) [24,30,31] but it seems not to affect sexual arousal and behaviour in naturally menopausal women
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[32]. In humans, then, androgens play an important role in sexual function but are not its sole determinant as their action is ‘context-dependent’ [27]. Prolactin has an inhibiting effect on libido and on the sexual cascade of neurovegetative and vascular responses, via the same dopaminergic system, though it is difficult to distinguish between the direct effects of prolactin itself on behaviour and the effects of the underlying dopaminergic activity [1,6,15]. Hypothyroidism may inhibit libido, whilst hyperthyroidism seems to increase most the biopsychological rhythms, without a specific positive effect on sexual desire [8]. Oxytocin is a nonapeptide secreted by the posterior pituitary and in neurons located in the supraoptic and paraventricular hypothalamus. Estrogen and testosterone stimulate the synthesis of oxytocin binding sites and recent evidence links oxytocine with the facilitation of sexual desire in both men and women [15]. In human females, masturbation to orgasm increases plasma oxytocin levels. Oxytocin may form part of a neurochemical axis that participates in the desire to affiliate with a sexual partner, to engage in sexual contact, and to achieve sexual satiety after extended matings. It could therefore be a modulating factor in the interplay between affective and erotic components of sexual behaviour [6,15]. Hormones, in their complex interplay, seem to control the intensity of libido and sexual behaviour, rather than its direction [5]. In conclusion, estrogens contribute to the central and peripheral scenario of femininity that can be thrilled and lit up by appropriate levels of androgens, whilst oxytocine may mediate the affective quality of bonding involved in libido itself.
3.2. Hormones and the sensory organs Sensory organs are well known windows for the environmental sexual stimuli. Less attention is paid to the effect of hormones on the function and morphology of sensory organs themselves, both as sexual targets and sexual determinants of libido [8,12,19,20]. A growing body of evidence shows that sexual hormones have a specific effect on the following.
3.2.1. Smell Chemoreception is the ability to receive chemical messages from the environment. In complex pluricellular organisms, specialized structures are devoted to receive chemical stimuli and to transmit them as nervous impulses to the central nervous system (CNS). Olfaction is the most refined sense based on chemoreception. The receptor organ, the olfactory epithelium, is made of specialized neurons localized in an exceptionally peripheral position. The olfactory epithelium is a perfect example of hormone-dependent neuroplasticity. It is made up of three cell types: the olfactory neurons, whose axons form the ‘fila olfactoria’; the supporting cells; the basal cells [36]. Castration elicites structural alterations of the olfactory epithelium, that can improve after administration of sexual hormones [36,37]. Moreover, in female Rhesus monkeys, the olfactory epithelium presents some changes during the preovulatory phase of the ovarian cycle that could explain the increased olfactory sensitivity occuring at the time of ovulation. In animals and in humans, the olfactory epithelium shows different appearance and different behaviour of the olfactory, supporting and basal cells in pre- and postpuberty [36]. The involutional morphologic changes of the olfactory epithelium in hypoestrogenic states (long lasting functional amenorrhea and menopause) could also contribute to the biologically determined reduction of libido, so often reported in these conditions. These changes could also reduce the responsivity to feromones, chemical messages emitted by animals and able to influence behaviour and physiology of other animals of the same species [15,19,20,36,37]. The invisible cloud of feromones that envelops humans as a second dress is a potent factor in subliminal attraction that enhances libido and activates sexual arousal. In women, reduction in the production of chemically attractive substances that contributes to the ‘scent of woman’, typical of the fertile age, could be responsible both for the reduced self-perception as an object of sex desire and for the reduced attractivity for the partner. Therefore, even in a microsmatic animal as the human being is, hormone dependent olfactory modifications may be impor-
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tant biological and functional contributors to the variation of libido in different phases of female life. Moreover, the functional model of cyclical neuroplasticity in the olfactory epithelium may add further information to the role of estrogens as central neurotrophic factors. The relative weight of this changes as causal cofactors in the post menopausal loss of libido deserves further study.
3.2.2. Taste Gustative receptors can perceive feromones as well [36]. Taste is another key biological and emotional factor in the thrilling of sex drive, especially in women. Increase of salivary secretion during sexual desire and arousal and the pleasure for the taste of skin and of kisses is a strong predictive factor of the quality of the sexual liking. Functional mouth dryness, more frequent in hypoestrogenic states, could be another understudied and underevaluated factor in the biological modulation of libido [38 – 40]. It has been reported in 45% of healthy post-menopausal women, up to 60% of those taking modifications other than HRT [40].
3.2.3. Touch A highly sexually communicative skin depends on a happy mixture of good genes, optimal endocrine impregnation, good feromone production and reception, plus excellent brain activity in the processing of peripheral information from the sensory organ enhanced with internal sexual and emotional stimuli: love, beyond libido, is the strongest attachment factor in the couple bonding through the skin touch [8,10,12,41]. Oxytocine seems to be a key neurochemical factor enhanced in response to a desired skin touch and a potent brain mediator of attachment needs and dynamics [15]. Touch, taste and smell contribute to the ‘cenesthetic channel’, that is considered the most important sensory contributor of libido in women. The sensory and emotional side of libido is deeply rooted in the quality of cenesthetic and loving bonding between mother and child, since the early infancy [41].
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3.2.4. Hearing This is a variable, usually strong attractive sense for women, mostly for the emotional vibration of the voice (the so called ‘feeling tone’), beyond the emotional, loving or sexual content of the message. Hormonal variations of hearing function are far from being clear; some interesting new findings begin to appear in the literature [42]. 3.2.5. Vision This is the most potent sexual sense in men, less in women. Estrogenic responsivity ophthalmic structures is now well recognized for the anterior part of the eye (conjunctiva, lacrimal glands). According to Metka [43], 35% of postmenopausal women complain of ophtalmic disturbances secondary to the lack of estrogens. Most of them improve with HRT. If the variations of eye well-being may contribute or not to modulation of libido is far from being defined. It is possible that all these subtle postmenopausal changes in sensory organ function and morphology [20] could contribute to the deterioration of libido with age and to the accelerated reduction it shows in many women in early postmenopausal years, particularly after bilateral ovariectomy, unless appropriate HRT is given [8,24,34]. 4. Hormones and genital responsiveness Physical pleasure enhances libido. Disappointment and frustration for a poor genital response inhibits it. Quality of pheripheral estrogenic and androgenic priming may be important in conditioning the quality of sexual response, as well as the central one. Bailey [46] suggests an almost linear correlation between clitoral sensitivity, the ability to be ‘turned on’ and the orgasmic capacity. Riley et al. [26] found a correlation between low libido and poorly developed external genitalia, particularly clitoris, which is often hypoplastic. These women can experience sexual arousal and can attain orgasm only with difficulty: this repeated failure may lead to a persistent block in sexual desire. Treatment with androgens seems to be helpful in such patients, probably because of its effects on the androgenic receptivity of the clitoris, but controlled studies are still lacking.
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Moreover, estrogens are important as ‘permitting’ factors that ‘translate’ libido and the neurovegetative pathway of neurotransmitters in the vaginal lubrication [33]. Vascular factors have only recently been described as potential contributors to poor genital response in women [47].
5. Menopausal changes in libido Lack of estrogens deprives the brain and all the female body of the natural lymph that contributes to the perception of the female sex identity, of a satisfying sexual function and to the sensuality and seductivity that improves the quality of sexual relationships, causing a progressive loss of libido and a crisis of the self perception as an object of desire [8,24,45]. Moreover, as previously mentioned, the lack of estrogens deprives sweat and sebaceous glands of the stimulus to produce the peculiar chemical secretion (feromones) responsible for the ‘scent of woman’, so critical in sexual attraction [36,37]. Estrogens are the permitting factors for the action of the vaso intestinal peptide (VIP), the key neu-
Fig. 1. Cybernetic model of the sexual function. This model, formulated by the presenting author, contributes to the understanding of: (1) frequent overlapping of sexual symptoms reported in clinical practice, as different dimensions of sexual response are correlated from a physiopathologic point of view; (2) potential negative or positive feedback mechanisms operating in sexual function. The model also addresses two critical aspects: (a) the ‘specificity’ of receptiveness, as the female characteristic of arousal, when coitus is involved. In this sense, dyspareunia could be considered non only a pain symptom but a specific receptiveness disorder; (b) the importance of the human dimension of ‘satisfaction’, that goes beyond the physiologic phase of resolution and encompasses both physical and emotional correlates of the erotic experience. The clinician should therefore be alerted to potential problems in any critical component of sexual function, to make appropriate differential diagnosis and suggest best medical and/or psychosexual therapy.
rotransmitter for the endothelial and vasal changes that lead to vaginal lubrication [34]. This mechanism explains why the absence of estrogens causes vaginal dryness and pain (dyspareunia) that can further inhibit libido through a negative feedback mechanism (Fig. 1). Arousal disorders, orgasmic difficulties and/or sexual dissatisfaction, both physical and emotional, may contribute to a secondary loss of libido. Enhancing and inhibiting factors, such as medicines, drugs, smoke and alcohol [6,8,45], plus other health problems, such as depression, anxiety, chronic stress [8,48] can modify the biological impact of menopause on libido. Motivational-affective and relational factors, implications and quality of couple relationship, partner’s attitude and problems, erectile deficit first, and his real desiderability, may further modulate the intensity and direction of libido [34,45] and contribute to the contradictory findings in the variability of libido in perimenopausal years [44].
6. Conclusion Problems of libido are increasingly reported during the gynecological consultation, more frequently if the clinician is willing to listen and to look at the patient as a person who is emotionally suffering. A basic sexological training should become part of routine gynecological training, to enable physicians to diagnose properly the biological conditions they could adequately treat and to encourage the patient to consult a psychosexologist if the problem reported during the consultation seems to be more rooted in intrapsychic, motivational or relational bases. Basic research is urgently needed to understand better and more the biological basis of female libido. Clinical evidence suggests that although estrogens are critical in maintaining the trophism of secondary sex characters, contributing to the inner sense of sensual femininity and genital vaginal responsiveness, androgens are the most specific thrillers of libido in women as well as in men. Nevertheless, research on optimal androgen replacement therapy in case of specific libido disorders leading to FADS is still in its infancy.
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Libido: the biologic scenario Alessandra Graziottin * Menopause Center, H. San Raffaele Resnati, Milan, Italy
Abstract Libido is a comprehensive and yet elusive word that indicates basic human mental states — and their biological counterparts— involved in the beginning of sexual behavior. It has three main roots: biological, motivational-affective and cognitive. All these dimensions may be variably affected in the post menopause, contributing to a progressive decrease of sexual drive that parallels the process of aging. Loss of estrogens and, specifically, of androgens deprives female libido of major biological fuel. The effect of this loss is pervading, affecting the central nervous system, the sensory organs that are the major windows to environmental sexual stimuli and the quality of sexual response, central, peripheral non-genital and genital. Prolactin increase may further inhibit libido. Arousal disorders, dyspareunia, orgasmic difficulties, dissatisfaction, both physical and emotional, may contribute to a secondary loss of libido. Depression, anxiety and chronic stress, may interfere with central and peripheral pathways of the sexual response, reducing the quality of sexual function mostly in its motivational root. Relational conflicts and/or marital delusions and partner-specific problems, erectile deficit first, may contribute to the fading of sexual drive in the post-menopausal years. Well tailored HRT, including androgens in selected cases, may reduce the biological causes of loss of libido. A comprehensive treatment requires a balanced evaluation between biological and pychodynamic factors. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Libido; Sexual hormones; Estrogens; Androgens; Sensory organs; Arousal disorders; Dyspareunia; Menopause
1. Introduction Human sexuality depends on a complex interaction among cognitive processes, neurophysiological and biochemical mechanisms and mood [1]. It also has strong relational bases. Difficulties in evaluating the relative weight of those different factors are rooted both in the complexity of the human sexual experience and in the fogginess of * Corresponding author. Present address: Via San Secondo 19, 10128 Turin, Italy. Tel./Fax: + 39-011-544283. E-mail address: [email protected] (A. Graziottin)
words and concepts that refer to it. Sexual appetite, desire and drive, sexual impulse and interest: many psychosexual and behavioral terms are used as synonims of libido [2], a latin word that means ‘desire’. It was first used by Sigmund Freud [3] to indicate the energy correspondent to the psychic side of the sex drive. Carl S. Jung [4] defined libido in a wider sense, as the psychic energy present in all that is ‘appetitus’, a kind of ‘desire towards’, not necessarily sexual. In recent literature, libido is again considered in its main sexual appetitive meaning that motivates a person to obtain sex and focuses his/her attention on that
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goal. This subjective experience is accompanied by and partly consists of various physiological changes, many of which are in preparation for sexual behaviour [1]. A useful working definition is that ‘sexual desire is normally an activated, unsatisfied mental state of variable intensity, created by external -via the sensory modalities- or internal stimuli -fantasy, memory, cognition..., that induces a feeling of a need or want to partake of sexual activity (usually with the object of desire) to satisfy the need’ [2]. This sexually activated mental state may be set against and influenced by the mood of the moment. In a depressed mood we are less likely to interpret experiences in pleasant sexual terms [1,8]. A mood of inertia, typical of depression, reduces the likelihood of initiating overt sexual action, in spite of favourable external conditions, i.e. the availability of a willing partner. The relationship between hormones and libido may therefore be studied through the effects sexual hormones have on this peculiarly activated mental state and on the different stimuli that enhance or inhibit it. From the biologist’s point of view, this sexual appetite can be further divided in ‘proceptivity’ and ‘receptivity’. The former referring to the willingness to initiate and invite sexual contact or sexual stimulation, the latter describing the preparedness of an individual (usually the female) to accept the sexual advances of another [5 – 7]. ‘I never initiate sex but I respond when my husband approaches me’ could be considered as a fairly common condition in stable couples, somehow borderline with normal female behaviour, although it may also address a disorder of proceptivity, with receptivity being intact [7]. Conversely, ‘I feel the need for sex but lose interest when my husband approaches me’ could be seen as a disorder of receptivity but not of proceptivity, clearly indicating a selective loss of desire, limited to that specific partner [7]. How much of this difference is secondary to biological or psychosexual and relational dynamics is far from being understood. Psychological processes play an important role in human libido: we learn to feel sexual drive at certain times and in certain situations, and for some this learning component dominates their sexual behaviour, as it happens in the week-end
sex of many stable couples. In recent years, the realm of libido has grown to include a deeper understanding of its biological roots [5–7] both endocrine and neurochemical, of the motivational and relational components [8–11] and of its vulnerability to personal factors and external agents. Menopause may represent a critical turning point of libido, as biological, motivational-affective and cognitive factors [5] may all undergo deep changes. Motivation to sex lose the primary biological goal, reproduction, but may well maintain the pursuit of pleasure, the ‘recreational sex’ [2,12] as well as the ‘instrumental sex’, when sex is performed as a means to obtain advantages and express motivations different from pleasure and/ or procreation [13]. In our species, libido has several roots, with a complex interplay among biological, motivational and relational factors, that may all have both an inhibiting or enhancing role [1,2,5–15].
2. Libido and sexual arousal Libido – or sexual desire – is considered different from sexual arousal. Sexual desire is an attitude toward an object, while sexual arousal is a state with specific feelings, usually attached to the genitals. There can be sexual arousal without sexual desire, and sexual desire without arousal. Human sexual arousal can be characterized by three components: a central arousal, a non-genital pheripheral arousal and a genital arousal [2,8]. Sexual desire and sexual arousal should therefore be kept distinguished.
3. Biological roots of libido
3.1. Hormones and the brain sexualization In men, consistent evidence shows that androgens are necessary though not sufficient factors to maintain a satisfying human libido, the best data coming from placebo controlled studies of androgen replacement in hypogonadal men [16,17]. In women, the evidence for hormone-behaviour relationships is much less consistent and often contra-
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dictory [1,7–11]. Estrogens prime the central nervous system, acting as neurotrophic and psychotrophic factors during the female life [14,15]. They contribute to primary and secondary sex characters, that nourish the inner sense of femininity. They prime as well the sensory organs including skin that are the key receptors for external sexual stimuli. Sensory organs transmit the basic information that, mixed with emotional and affective messages, contributes to the structuring of core sex identity and self image, so relevant for the personal perception of being an ‘object of desire’ and for the direction (homo- or heterosexual) of the libido itself [8,18]. Involution of sensory organs may be an overlooked contributor of the biologic loss of libido many women report after the menopause [19,20]. The interplay between estrogens and the dopaminergic system is the key process in determining the appetitive side of sexual behaviour [6,7,15], which can be further thrilled by the peak of androgens at ovulation. This link is supported by the correlation between testosterone levels and frequency of masturbation [21] or vaginal response to erotic stimuli in laboratory [22], that is with aspects of autoeroticism rather than partner sex. This latter has many more relational variables that may explain the contradictory findings in researches trying to correlate human female cycle with variations in libido [1,8,15]. Some consensus is found in the peak just before or after menstruation [23], and it is not clear how such pattern could be hormonally determined, as it is opposite to the mid-cycle peak of androgens that are assumed to be the ‘libido’ hormone in men as well as in women. The improvement of mood in the post-menstrual phase could partly account for this favourable increase [1]. Progesterone seems to have an inhibitory effect: its premenstrual fall could contribute to the perimenstrual increase in sex desire, at least in those women not suffering from premenstrual syndrome (PMS). Bancroft [1] suggests that these seemingly discrepant findings may be explained by a different brain effect of androgens during early female development, either because of different target organs sensitivities or different timing of hormonal effects (in contrast with males who are relatively overdeter-
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mined by androgens during early development). Money and Ehrhardt [18] hypothezise that the sensitivity of the female sexual behavior to hormonal variations may depend not only on the actual fluctuations and/or levels, but also on the quality of central and pheripheral estrogenic and androgenic priming. These early differences could also contribute to the biological basis of the huge variations: in libido profile in women; in female sexuality after the menopausal hormonal fall; in the different responsiveness to hormonal treatment as far as libido is concerned. Libido modifications during the female cycle may give useful suggestions on how HRT may act on the biological basis of sex drive after the menopause. In the conflict between nature and culture, psychosocial factors seem to be more important in women than in men. At the moment androgens look nevertheless the most interesting hormones for the sexuality of women [1,6,7,15,24–35]. They could have a 3-fold action: increase susceptibility to psychosexual stimulation, contributing to the ‘sexually activated mental state’, typical of a good libido; increase sensitivity of the external genitalia, facilitating the nitric oxide pathways that leads to clitoral congestion; increase the intensity of sexual gratification [26]. A specific ‘Female Androgen Deficiency Syndrome’ (FADS), with loss of libido, reduced vital energy, reduced assertiveness, loss of pubic hair and diminished muscle mass has been described after bilateral ovariectomy [24], that on average deprives the woman of 50% of her androgen production. A recent review of Rubinow and Schmidt [27] suggests that in men androgen dependence takes the form of a threshold level, below which libido and sexual function are impaired, and above which they are not, with no correlation between either the ideational or erectile components of sexual function and testosterone levels in the normal range. In women, both a positive correlation [28] and the absence of it [29] between testosterone levels and sexual interest and behaviour have been observed. Similarly, androgen replacement therapy increases libido in women who are androgen-deficient (e.g. after surgical menopause) [24,30,31] but it seems not to affect sexual arousal and behaviour in naturally menopausal women
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[32]. In humans, then, androgens play an important role in sexual function but are not its sole determinant as their action is ‘context-dependent’ [27]. Prolactin has an inhibiting effect on libido and on the sexual cascade of neurovegetative and vascular responses, via the same dopaminergic system, though it is difficult to distinguish between the direct effects of prolactin itself on behaviour and the effects of the underlying dopaminergic activity [1,6,15]. Hypothyroidism may inhibit libido, whilst hyperthyroidism seems to increase most the biopsychological rhythms, without a specific positive effect on sexual desire [8]. Oxytocin is a nonapeptide secreted by the posterior pituitary and in neurons located in the supraoptic and paraventricular hypothalamus. Estrogen and testosterone stimulate the synthesis of oxytocin binding sites and recent evidence links oxytocine with the facilitation of sexual desire in both men and women [15]. In human females, masturbation to orgasm increases plasma oxytocin levels. Oxytocin may form part of a neurochemical axis that participates in the desire to affiliate with a sexual partner, to engage in sexual contact, and to achieve sexual satiety after extended matings. It could therefore be a modulating factor in the interplay between affective and erotic components of sexual behaviour [6,15]. Hormones, in their complex interplay, seem to control the intensity of libido and sexual behaviour, rather than its direction [5]. In conclusion, estrogens contribute to the central and peripheral scenario of femininity that can be thrilled and lit up by appropriate levels of androgens, whilst oxytocine may mediate the affective quality of bonding involved in libido itself.
3.2. Hormones and the sensory organs Sensory organs are well known windows for the environmental sexual stimuli. Less attention is paid to the effect of hormones on the function and morphology of sensory organs themselves, both as sexual targets and sexual determinants of libido [8,12,19,20]. A growing body of evidence shows that sexual hormones have a specific effect on the following.
3.2.1. Smell Chemoreception is the ability to receive chemical messages from the environment. In complex pluricellular organisms, specialized structures are devoted to receive chemical stimuli and to transmit them as nervous impulses to the central nervous system (CNS). Olfaction is the most refined sense based on chemoreception. The receptor organ, the olfactory epithelium, is made of specialized neurons localized in an exceptionally peripheral position. The olfactory epithelium is a perfect example of hormone-dependent neuroplasticity. It is made up of three cell types: the olfactory neurons, whose axons form the ‘fila olfactoria’; the supporting cells; the basal cells [36]. Castration elicites structural alterations of the olfactory epithelium, that can improve after administration of sexual hormones [36,37]. Moreover, in female Rhesus monkeys, the olfactory epithelium presents some changes during the preovulatory phase of the ovarian cycle that could explain the increased olfactory sensitivity occuring at the time of ovulation. In animals and in humans, the olfactory epithelium shows different appearance and different behaviour of the olfactory, supporting and basal cells in pre- and postpuberty [36]. The involutional morphologic changes of the olfactory epithelium in hypoestrogenic states (long lasting functional amenorrhea and menopause) could also contribute to the biologically determined reduction of libido, so often reported in these conditions. These changes could also reduce the responsivity to feromones, chemical messages emitted by animals and able to influence behaviour and physiology of other animals of the same species [15,19,20,36,37]. The invisible cloud of feromones that envelops humans as a second dress is a potent factor in subliminal attraction that enhances libido and activates sexual arousal. In women, reduction in the production of chemically attractive substances that contributes to the ‘scent of woman’, typical of the fertile age, could be responsible both for the reduced self-perception as an object of sex desire and for the reduced attractivity for the partner. Therefore, even in a microsmatic animal as the human being is, hormone dependent olfactory modifications may be impor-
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tant biological and functional contributors to the variation of libido in different phases of female life. Moreover, the functional model of cyclical neuroplasticity in the olfactory epithelium may add further information to the role of estrogens as central neurotrophic factors. The relative weight of this changes as causal cofactors in the post menopausal loss of libido deserves further study.
3.2.2. Taste Gustative receptors can perceive feromones as well [36]. Taste is another key biological and emotional factor in the thrilling of sex drive, especially in women. Increase of salivary secretion during sexual desire and arousal and the pleasure for the taste of skin and of kisses is a strong predictive factor of the quality of the sexual liking. Functional mouth dryness, more frequent in hypoestrogenic states, could be another understudied and underevaluated factor in the biological modulation of libido [38 – 40]. It has been reported in 45% of healthy post-menopausal women, up to 60% of those taking modifications other than HRT [40].
3.2.3. Touch A highly sexually communicative skin depends on a happy mixture of good genes, optimal endocrine impregnation, good feromone production and reception, plus excellent brain activity in the processing of peripheral information from the sensory organ enhanced with internal sexual and emotional stimuli: love, beyond libido, is the strongest attachment factor in the couple bonding through the skin touch [8,10,12,41]. Oxytocine seems to be a key neurochemical factor enhanced in response to a desired skin touch and a potent brain mediator of attachment needs and dynamics [15]. Touch, taste and smell contribute to the ‘cenesthetic channel’, that is considered the most important sensory contributor of libido in women. The sensory and emotional side of libido is deeply rooted in the quality of cenesthetic and loving bonding between mother and child, since the early infancy [41].
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3.2.4. Hearing This is a variable, usually strong attractive sense for women, mostly for the emotional vibration of the voice (the so called ‘feeling tone’), beyond the emotional, loving or sexual content of the message. Hormonal variations of hearing function are far from being clear; some interesting new findings begin to appear in the literature [42]. 3.2.5. Vision This is the most potent sexual sense in men, less in women. Estrogenic responsivity ophthalmic structures is now well recognized for the anterior part of the eye (conjunctiva, lacrimal glands). According to Metka [43], 35% of postmenopausal women complain of ophtalmic disturbances secondary to the lack of estrogens. Most of them improve with HRT. If the variations of eye well-being may contribute or not to modulation of libido is far from being defined. It is possible that all these subtle postmenopausal changes in sensory organ function and morphology [20] could contribute to the deterioration of libido with age and to the accelerated reduction it shows in many women in early postmenopausal years, particularly after bilateral ovariectomy, unless appropriate HRT is given [8,24,34]. 4. Hormones and genital responsiveness Physical pleasure enhances libido. Disappointment and frustration for a poor genital response inhibits it. Quality of pheripheral estrogenic and androgenic priming may be important in conditioning the quality of sexual response, as well as the central one. Bailey [46] suggests an almost linear correlation between clitoral sensitivity, the ability to be ‘turned on’ and the orgasmic capacity. Riley et al. [26] found a correlation between low libido and poorly developed external genitalia, particularly clitoris, which is often hypoplastic. These women can experience sexual arousal and can attain orgasm only with difficulty: this repeated failure may lead to a persistent block in sexual desire. Treatment with androgens seems to be helpful in such patients, probably because of its effects on the androgenic receptivity of the clitoris, but controlled studies are still lacking.
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Moreover, estrogens are important as ‘permitting’ factors that ‘translate’ libido and the neurovegetative pathway of neurotransmitters in the vaginal lubrication [33]. Vascular factors have only recently been described as potential contributors to poor genital response in women [47].
5. Menopausal changes in libido Lack of estrogens deprives the brain and all the female body of the natural lymph that contributes to the perception of the female sex identity, of a satisfying sexual function and to the sensuality and seductivity that improves the quality of sexual relationships, causing a progressive loss of libido and a crisis of the self perception as an object of desire [8,24,45]. Moreover, as previously mentioned, the lack of estrogens deprives sweat and sebaceous glands of the stimulus to produce the peculiar chemical secretion (feromones) responsible for the ‘scent of woman’, so critical in sexual attraction [36,37]. Estrogens are the permitting factors for the action of the vaso intestinal peptide (VIP), the key neu-
Fig. 1. Cybernetic model of the sexual function. This model, formulated by the presenting author, contributes to the understanding of: (1) frequent overlapping of sexual symptoms reported in clinical practice, as different dimensions of sexual response are correlated from a physiopathologic point of view; (2) potential negative or positive feedback mechanisms operating in sexual function. The model also addresses two critical aspects: (a) the ‘specificity’ of receptiveness, as the female characteristic of arousal, when coitus is involved. In this sense, dyspareunia could be considered non only a pain symptom but a specific receptiveness disorder; (b) the importance of the human dimension of ‘satisfaction’, that goes beyond the physiologic phase of resolution and encompasses both physical and emotional correlates of the erotic experience. The clinician should therefore be alerted to potential problems in any critical component of sexual function, to make appropriate differential diagnosis and suggest best medical and/or psychosexual therapy.
rotransmitter for the endothelial and vasal changes that lead to vaginal lubrication [34]. This mechanism explains why the absence of estrogens causes vaginal dryness and pain (dyspareunia) that can further inhibit libido through a negative feedback mechanism (Fig. 1). Arousal disorders, orgasmic difficulties and/or sexual dissatisfaction, both physical and emotional, may contribute to a secondary loss of libido. Enhancing and inhibiting factors, such as medicines, drugs, smoke and alcohol [6,8,45], plus other health problems, such as depression, anxiety, chronic stress [8,48] can modify the biological impact of menopause on libido. Motivational-affective and relational factors, implications and quality of couple relationship, partner’s attitude and problems, erectile deficit first, and his real desiderability, may further modulate the intensity and direction of libido [34,45] and contribute to the contradictory findings in the variability of libido in perimenopausal years [44].
6. Conclusion Problems of libido are increasingly reported during the gynecological consultation, more frequently if the clinician is willing to listen and to look at the patient as a person who is emotionally suffering. A basic sexological training should become part of routine gynecological training, to enable physicians to diagnose properly the biological conditions they could adequately treat and to encourage the patient to consult a psychosexologist if the problem reported during the consultation seems to be more rooted in intrapsychic, motivational or relational bases. Basic research is urgently needed to understand better and more the biological basis of female libido. Clinical evidence suggests that although estrogens are critical in maintaining the trophism of secondary sex characters, contributing to the inner sense of sensual femininity and genital vaginal responsiveness, androgens are the most specific thrillers of libido in women as well as in men. Nevertheless, research on optimal androgen replacement therapy in case of specific libido disorders leading to FADS is still in its infancy.
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