Rethinking low sexual desire in women

Transcription

1 BJOG: an International Journal of Obstetrics and Gynaecology April 2002, Vol. 109, pp Rethinking low sexual desire in women Introduction The apparent high prevalence of low sexual desire in women leads to a questioning of the traditional view of women s sexual response and the nature of their sexual desire. Is the traditional model of sexual arousal and potential orgasmic release, initiated by sexual desire (as manifested by sexual thinking, fantasising and conscious sexual neediness), actually true for women? Are other cycles of response more common and would their acknowledgement clarify causes of apparent low desire and thereby facilitate management? This review compares the traditional model of the human sexual response cycle with an alternative model whose component parts are frequently faulty or entirely missing in the experiences of women complaining of low sexual desire. Continuous modulation of this cycle occurs as feedback is obtained from genital and non-genital physical responses, as well as from emotions and perceptions. The new model illustrates the difficulty experienced by most women in distinguishing between desire and arousal and the common lack of both. There are implications for the management of low desire in the context of chronic dyspareunia, chronic infertility, gradual reduction of ovarian androgen from midlife onwards, and for the management of sudden complete loss of ovarian androgen in premature, surgical or medical menopause. Prevalence of low sexual desire in women Community studies of women point to a 33% 39% prevalence rate of self-diagnosed low sexual desire 1,2 and low desire is the most common problem for women attending sexual therapy clinics 3. Of 964 North American women attending for routine gynaecological care from family practitioners and gynaecologists, 67% reported problematic low sexual desire 4. It is accepted that whether studies are by interview or questionnaire only those women willing to be questioned about an extremely private area of their lives will be included. Rather than concluding that some onethird of women have a disorder, the reasons for this apparently common perception of failing to meet some sexual standard must be sought. To date, clinicians, including gynaecologists, have found management of low sexual desire to be highly challenging. Women speak of their lack of an emotion (sexual desire) that they once had or feel they should have. The medical response has been largely to D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII: S (02) clarify medical, including psychiatric and gynaecological history, confirm normal genital and pelvic anatomy and state that nothing organic is amiss. The relevance of a normal pelvic exam is frequently over-emphasised. Often the woman is then dismissed with the conclusion: your problem must be psychological. Indeed, being an emotion, sexual desire is a psychological entity, but it also has a biological and interpersonal basis and women expect their gynaecologist to accept their sexual difficulties as a legitimate women s health issue and be prepared and able to address it. This aspect of gynaecological care is clearly stated in Guidelines of National Regulatory Bodies 5 and the website of the International Federation of Gynaecology and Obstetrics. What is meant by low sexual desire The presence of sexual thoughts, fantasies and an innate urge to experience sexual tension and release, alone or with a partner, have been considered the markers of desire 6. The traditional model of the human sexual response cycle of Masters, Johnson and Kaplan, as shown in Fig. 1, depicts the stage of desire leading on to arousal, a plateau of heightened arousal which peaks briefly and releases in the experience of orgasm(s) to be followed by resolution 6. Management has been unclear when the woman is complaining of lack of these presumed markers of desire, but is neither depressed nor medically unwell, and not taking medication likely to interrupt her desire. If women are asked the reasons for agreeing to or instigating a sexual experience with their partner, their list is extensive 7,8. Reasons include wanting to be emotionally close, to show love and affection, to share physical pleasure for the sake of sharing, to increase a sense of attractiveness and attraction, to increase a sense of commitment and bonding, but only sometimes to satisfy a truly sexual need. These intimacy-based reasons appear particularly important in the longer term monogamous relationship. Even the need for masturbation has varied causes, including to soothe and comfort, to relax, and to sleep but only sometimes primarily to release sexual tension. Alternative model of women s sexual response A recently proposed alternative intimacy-based model appears to be relevant to women by clarifying the com-

2 358 Fig. 1. Traditional human sex response cycle of Masters, Johnson and Kaplan. Reprinted with permission from the American College of Obstetricians and Gynecologists (Obstetrics and Gynecology, 2001, Vol. 98, pp ). ponent parts of their response cycles that may be faulty or absent 9. A woman frequently begins a sexual experience sexually neutral. She, for the intimacy-based reasons described, deliberately finds or receives sexual stimuli that potentially could move her from neutrality to a state of sexual arousal (Fig. 2). An attempt to include this receptivity component of women s sexual desire has been made in the new definitions and classifications of female sexual dysfunction by the American Foundation of Urological Disease 10. Many psychological and biological factors may potentially preclude arousal, but if the processing of the stimuli in the woman s limbic and paralimbic centres is such that a degree of arousal is experienced, she can potentially continue to focus on the stimuli. Further arousal follows and in time, in addition to her original intimacy-based motivation, she achieves definite desire in order to continue the experience for the sake of the sexual tension and sexual enjoyment. In this cycle, departing from the traditional one, sexual stimuli are integral; arousal is experienced before desire and orgasm is not mandatory for a normal or healthy response. The power behind the cycle is the couple s emotional intimacy and this power or motor may be enhanced or diminished by the experience itself. stimuli are related more to the behaviour of the partner during the day, than specifically at the moment of physical interplay. However, heterosexual women frequently express a wish both for more non-genital and genital nonpenetrative stimuli, but without sexual intercourse. Many psychological factors negatively influence the processing of sexual cues in the limbic centres. Included are non-sexual distractions, feeling sexually substandard, past negative or painful experiences, previous discrediting of the woman s sexuality, and fears of infertility, pregnancy, sexually transmitted diseases, or fear for her emotional or physical safety. Sometimes there is a dysphoric reaction to any physical arousal that takes place, perhaps more commonly when there has been past abuse 11. Biological factors are only just beginning to be clarified. Some neurotransmitters that appear to be prosexual include dopamine, oxytocin, noradrenaline, and serotonin via 5HT1A receptors. Some that are sexually negative include serotonin acting via 5HT2 and 5HT3 receptors, prolactin, and gamma amino butyric acid. The production of prosexual neurotransmitters is decreased with androgen deficiency. Depression distorts the balance of neurotransmitters, as do anti-depressants and anti-psychotics. However, the possibility that some women (and men) may have a stronger inhibitory tone that itself may be to some degree innate, is only recently being investigated 12,13. Infrequently, low thyroid or hyperprolactinemic states affect the limbic areas so that arousal is not reached. Despite achieving arousal and subsequent desire, if the outcome is negative, the woman s cycle is broken and her intimacy with her partner is not enhanced. Examples include chronic dyspareunia, partner s sexual dysfunction, effects of medication (e.g. serotonin re-uptake inhibitor-induced orgasmic disorder or deficient oestrogen or testosterone). Lack of oestrogen, by reducing the bioavailability of nitric oxide, can lead to insufficient smooth muscle relaxation in the vulval, bulbar, spongiosal and clitoral erectile tissue, limiting their engorgement. Similarly, vaginal, vascular Potential breaks in women s alternative cycle The emotional intimacy may be so minimal that the woman is not motivated to -find or receive sexual stimuli that could allow her sexual response. Gynaecologists may not wish to address the intimacy problems themselves, but they can clarify the normality of the woman s low desire in this context. This in itself is therapeutic since the woman no longer feels that she is labelled as sexually dysfunctional. If the partners are motivated to improve their emotional intimacy, professional counselling can be suggested: the problem is not inherently sexual but to do with the nonsexual interpersonal relationship. Frequently, sexual stimuli are entirely absent. The day is filled with non-sexual interactions. Often the needed Fig. 2. Alternative model of women s sexual response.

3 359 Fig. 3. Blended sexual response cycles. and non-vascular smooth muscle relaxation is impaired reducing vaginal lubrication and accommodation, respectively. The action of vasointestinal polypeptide is also influenced by oestrogen, and is most likely the major neurotransmitter. It is possible that testosterone is also involved in the congestion of the vulva and vagina by regulating a 1 adrenergic responsiveness as is postulated for penile cavernosal smooth muscle 14. Blending of traditional and alternative cycles Clearly, some women, spontaneously or cyclically or even frequently, experience innate apparently spontaneous sexual hunger or need as in the traditional model. The two cycles may blend as shown in Fig. 3. Cyclical spontaneous desire may well be related to the mid-cycle peaks of testosterone and androstenedione. Interestingly, many women report easy spontaneous desire early on in a relationship 3. However, careful questioning clarifies that many sexual stimuli and deliberately organised sexual contexts were all part of the dating atmosphere such that spontaneity was perhaps more apparent than real. The newness itself, the unpredictability, even the lack of commitment or legitimacy, may be potent stimuli in a new relationship. men, the subsequent physical tumescence itself constitutes an additive or compounding second level sexual stimulus. The engorgement is accurately detected and enjoyed. Only men with chronic situational erectile dysfunction typically under-rate their physical response 16. By contrast, women in good health typically under-rate their physical response 17. Psychophysiological data of objective increase in the vaginal blood flow in the laboratory in response to erotic stimulation repeatedly shows lack of correlation with the woman s subjective arousal Thus, women typically do not have this genital confirmation of their arousal in any direct way. Many women need direct stimulation to their congesting vulval structures to receive that second level confirmatory stimulus 20. Clearly, some sexual styles, particularly intercourse-focused, may preclude this. There is also moment-to-moment feedback from the emotions 21. This feedback may be positive: one of enjoyment, pleasurable mood, self-affirmation, or it may be negative: one of embarrassment, shame or guilt. Feedback from the genitalia and from the emotions are depicted in Fig. 4. Although the term sexual response cycle has been in common use since Masters and Johnson s publications, the true cyclicity comprises physical, emotional and cognitive feedback. This is not appreciated in the traditional linear model. If the emotional response to any perceived physical arousal is negative (dysphoric arousal), the sexual centres may cease to transmit excitatory input to the lumbar sacral centres. For some women, it appears that excitatory neurotransmission does continue: the genitalia remain engorged but the woman does not feel sexually aroused. This response is typically shown by women diagnosed with arousal disorders, who in the laboratory setting, demonstrate a normal genital congestive response to erotic stimuli but feel no subjective arousal 18. Similarly, in clinical settings, women will report that their fingers can detect some genital swelling and lubrication, but massaging Modulation of the cycle from somatic and emotional responses In men, mental sexual arousal alters the descending neurotransmission from limbic centres to the lumbar sacral centres of the spinal cord. Probably this involves increasing oxytocinergic signalling from the paraventricular nuclei of the hypothalamus with concurrent reduction of inhibitory serotonergic input, particularly from the nucleus paragigantocellularis in the medulla 15. When this balance of signalling to the pelvic autonomic outflow occurs in Fig. 4. Somatic (genital) and affective feedback cycles.

4 360 these engorging structures is not appreciated as pleasurable sexual arousal. The genital physiological response would appear to be an involuntary reflex mediated by the (unconscious) autonomic nervous system 3 (note the occurrence of genital response in situations of genital assault and rape) 3. Clearly, the subject of sexual arousal and any lack thereof is highly complex, with the result that the role of genital vasoactive medication in women complaining of arousal difficulties is far from clear 20,22,23. To date, the only large placebo controlled studies of sildenafil given to women have failed to show benefit over placebo 23. Of note, these studies (one on oestrogenised and one on nonoestrogenised women), included women with a broad range of sexual dysfunction which included lack of arousal. The arousal disorder was not analysed in any way (e.g. to determine whether the women were complaining of lack of subjective arousal or lack of both subjective and genital arousal) 22. Current research is attempting to focus on the use of vasoactive drugs in women with an acquired reduction in genital response and a smaller placebo controlled study showing benefit of sildenafil in premenopausal women has been recently published 24. The traditional view that vaginal lubrication constitutes sexual arousal in women is thus not only restrictive but misleading when arousal disorder is under discussion. Women tend to focus mostly on how mentally exciting they find the stimulus when they rate their sexual arousal 18. Future research may profitably focus on those women who reliably respond genitally throughout the experience of sexual stimulation but have no subjective arousal. In other words, there is a need to identify the mechanisms of the disconnection between mind and genitalia. These models of blended intimacy-based and drivebased sexual response cycles with ongoing modulation from emotional, cognitive and physical feedback include many concepts of previous authors 3,6 8, However, the traditional model familiar to gynaecologists still remains that of Kaplan, Masters and Johnson where conscious sexual thinking and sexual needs initiates the sex response. Women with chronic dyspareunia Fig. 5. The repercussions of chronic dyspareunia on the woman s sex response cycle. Sharing this alternative model with women allows them to recognise the multiple consequences of their chronic dyspareunia. The woman has learned to avoid many sexual stimuli; any that remain are unlikely to lead to arousal because of the mindset associated with the anticipated painful outcome. The couple s emotional intimacy has suffered because of the repeated feelings of being hurt, being used, even abused. Confusion, resentment, anger, sadness replace feelings of closeness. The needed therapy is clearly more than pain management (Fig. 5). Women with sudden complete loss of ovarian androgen The woman with premature, surgical or medical menopause is more distressed by her inability to respond to formerly effective sexual stimuli than her lack of spontaneous sexual thoughts and fantasies. The androgen needed for processing the stimuli in generating subjective arousal is insufficient. She may also suffer the consequences of lack of peripheral testosterone action on the smooth muscle response involved in vulval and vaginal congestion. The couple s emotional intimacy may suffer from both the lack of rewarding physical times together and the confusion and misunderstanding as to its cause. The breaks in her cycle are shown in Fig. 6. In one study consecutive couples referred for female low sexual desire were assessed. Although lack of testosterone was felt to be a factor in some 20%, many other breaks in the women s (alternative) cycles were also apparent. Of note, in a recent placebocontrolled study of transdermal testosterone replacement in Fig. 6. The repercussions of sudden complete loss of ovarian androgen on the woman s sex response cycle.

5 361 women whose surgical menopause was thought to be the cause of acquired low sexual desire and response, benefit only was seen in the older women and only if they achieved high normal (as opposed to mid-normal) premenopausal testosterone levels 29. No therapy other than testosterone replacement was given. Little detail is known about the exact role of testosterone in either innate sexual need or in the processing of sexual stimuli. Post mortem evidence of uptake of androgen (and oestrogen) in various areas of the brain has shown highest levels in the medial preoptic area, medial and basal hypothalamus and the substantia nigra 30. Whether testosterone needs to be converted in brain cells to both dihydrotestosterone via 5a hydroxylase and aromatised to oestradiol to exert its action, as is necessary in rodents, is not clear. The practice of giving women aromatase inhibitors after a diagnosis of breast cancer, may clarify this question. Adrenal androgen is nevertheless sufficient for many women. Clearly, the sensitivity of androgen receptors (currently not measurable in clinical practice) is likely as important as blood levels. Women with gradual loss of testosterone The usual slow decline in testosterone levels from the early 40s onwards appears to be far less often associated with unresponsiveness to formerly effective stimuli 31. Beginning in the early 40s, some but not all studies indicate testosterone levels decline progressively but not usually to undetectable levels 32,33. Although this slow decline appears often to be asymptomatic, certainly some peri and naturally postmenopausal women do complain of loss of genital response and mental response comparable with the loss experienced by some women with surgical menopause. For both groups of women, loss of energy may also be linked to the androgen lack 34. Unfortunately, scientific study of androgen replacement therapy in women is minimal 35. We lack both efficacy and safety data. Prior to the study by Shifren et al. 29, there were minimal data on physiological as opposed to pharmacological doses of prescribed androgen. Sexual benefit was seen in the oestrogen versus oestrogen plus testosterone controlled study by Davis et al. 36 using testosterone implants designed to give high normal premenopausal testosterone levels; but interestingly, the women were recruited for bone density reasons rather than sexual dysfunction. Non-physiological androgen administration (i.e. methyl testosterone), acting via the androgen receptor and via reduction of sex hormone binding globulin (SHBG), has also been associated with sexual benefit in postmenopausal women but the dose needed (2.5mg) is associated with unwanted reduction of high density lipoprotein cholesterol 37. Tibolone has oestrogenic properties as well as some androgenic activity via its D4 metabolites and its ability to reduce SHBG. It also has been shown to improve the effects of lack of oestrogen associated with dyspareunia 38. Tibolone s androgenic activity is thought to account for increased sexual desire and responsiveness in women receiving tibolone, compared with those receiving either conjugated oestrogen plus medroxyprogesterone acetate 39, or oestradiol plus norethisterone 40,41. Also, tibolone allowed comparable increases in sexual responsiveness compared with oestradiol plus dihydro-androsterone, the latter causing untoward lipid effects 42. Of note, these studies were of otherwise healthy postmenopausal women rather than women complaining of sexual dysfunction. Women of all ages are currently requesting (and in some centres being given) 43,44 testosterone supplementation in various forms, without safety and efficacy data, and without the documentation that sexual desire and responsiveness correlate with testosterone (or any other androgen) levels, other than those in the supraphysiological range. Additional basic requirements include a testosterone assay sensitive and accurate in the female range. More data are needed of androgen levels in women of different ages (and health status), who do not have sexual dysfunction. Scientific studies of testosterone replacement in peri and naturally postmenopausal women are needed, including the use of local testosterone in restoring vulval congestion without necessarily achieving high normal premenopausal testosterone levels systemically. Replacing testosterone in a pattern that varies through the four-week period to mimic a younger premenopausal ovulating cycle would be a useful strategy to study. Discussion of the alternative cycle is helpful in identifying the subgroup of menopausal women who previously experienced conscious intrinsic sexual desire, and were less aware of beginning a sexual experience from a state of sexual neutrality. This particular subgroup acknowledges that their sexual response can still occur but they are dissatisfied; they mourn the loss of their former hunger, that appeared to be spontaneous rather than triggered. Fortunately, adaptation to the need for creating a sexual Fig. 7. The repercussions of infertility on the woman s sex response cycle.

6 362 context (and removing their often self-imposed label of dysfunction) is possible. Women with chronic infertility Emotional intimacy frequently suffers due to the stressors of multiple medical appointments, investigations, adverse effects of fertility drugs, failed cycles, and failed in vitro fertilisation. The experience of intercourse being required on certain days, can lead to mechanical emotionally unrewarding experiences. The woman s sense of sexual self-confidence and attractiveness may suffer, thereby inhibiting the processing of any stimuli. The outcome can remain unrewarding owing to the limited psychosexual interaction, the focus for so long being on the mechanical act of intercourse, dispensing with erotic play. Illustrated in these common clinical situations is the multifactorial nature of the complaint of low sexual desire (Fig. 7). Careful integration of any future libido enhancing medication will be critical 20. Conclusion Understanding her sexual response cycles and identifying faulty or absent components motivates the woman to address them. Her difficulties are explicable, stemming not only from herself but from her general circumstances, including her partner and her past experiences. She may also see the fallacy of the idea that a medical solution in the form of a pill (hormonal or otherwise) will suffice. Even when biological factors are strong, she can see that focusing only on them without addressing the rest of her cycle will be ineffectual. Gynaecologists can address the subject of low sexual desire by understanding women s sex response cycles, keeping up-to-date with the biological components and being aware of the psychological components. When lack of emotional intimacy weakens sexual motivation, the appropriate referral to a relationship therapist can be made. Similarly, when sexual stimuli and context are minimal, gynaecologists can clarify their normal necessity especially in the longer term monogamous relationship. Future research might profitably include combining psychosexual and biological management. Biological areas in need of scientific study include the development of testosterone assays sensitive and accurate for the range found in women, documentation of testosterone levels in women of various ages and various health status, who do not have sexual complaints, testosterone replacement in ways which more accurately reflect the variable levels of younger women, and the potential benefit of genital as opposed to systemic androgen replacement. The use of agents to enhance genital vasocongestion in women with acquired loss of genital responsiveness merits further investigation. A much-needed area of psychosexual research is the disconnection between subjective arousal and genital congestive response. Acknowledgements The author would like to thank Dr P. M. Rees for his editorial comments and Mrs M. Piper for her secretarial skills. Rosemary Basson a,b a University of British Columbia Departments of Psychiatry and Obstetrics and Gynaecology, Vancouver Hospital, Canada b B.C. Centre for Sexual Medicine, Vancouver Hospital, Vancouver, Canada References 1. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281: Fisher WA, Boroditsky R, Bridges ML. The 1998 Canadian contraception study. Can J Hum Sexuality 1999;8: Everaerd W, Laan E, Both S, van der Velde J. Female sexuality. In: Szuchman L, Muscarella F, editors. Psychological Perspectives on Human Sexuality. New York: John Wiley, Nusbaum MRH, Gamble G, Skinner B, Heiman J. The high prevalence of sexual concerns amongst women seeking routine gynaecological care. J Fam Pract 2000;49: Consensus statements of the Society of the Obstetricians and Gynecologists of Canada. J Soc Obstet Gynecol Can 1998;6: Kaplan HS. Hypoactive sexual desire. J Sex Marital Ther 1979;3: Regan P, Berscheid E. Belief about the state, goals and object of sexual desire. J Sex Marital Ther 1996;22: Tiefer L. Historical, scientific, clinical and feminist criticisms of the human sex response cycle. Ann Rev Sexual Res 1991;2: Basson R. The female sexual response revisited. J Soc Obstet Gynecol Can 2000;22: Basson R, Berman J, Burnett A, et al. Consensus panel: Report of the International Consensus Development Conference of female sexual dysfunction: definitions and classifications. J Urol 2000;163: Maltz W. Identifying and healing the sexual repercussions of incest: a couple s therapy approach. J Sex Marital Ther 1988;14: Redouté J, Stoléru S, Grégoire MC, et al. Brain processing of visual sexual stimuli in human males. Hum Brain Mapping 2000;11: Bancroft J. Central control and inhibitory mechanisms in male sexual response. Int J Impot Res 1998;10(Suppl):S40 S Reilly C, Stopper V, Mills T. Androgens modulate the alpha adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum. J Androl 1997;18: McKenna K. Central nervous system pathways involved in the control of penile erection. Annu Rev Sex Res 1999;10: Barlow DH. Causes of sexual dysfunction. J Consult Clin Psychol 1986;54: Laan E, Everaerd W. Physiological measures of vaginal vasocongestion. Int J Impot Res 1998;10:S107 S Laan E, Everaerd W, van der Velde J, Geer JH. Determinants of subjective experience of sexual arousal in women: feedback from

7 363 genital arousal and erotic stimulus content. Psychophysiol 1995;32: Wouda JC, Hartman PM, Bakker RM, Bakker JO. Vaginal plethysmography in women with dyspareunia. J Sex Res 1998;35: Basson R. Female sexual response: the role of drugs in the management of sexual dysfunction. Obstet Gynecol 2001;98: Andersen BL, Cyranowski JM. Women s sexuality: behaviours, responses and individual differences. J Consult Clin Psychol 1995;63: Basson R. The female sexual response: a different model. J Sex Marital Ther 2000;26: Basson R, McInnes R, Smith M, Hodgson G, Spain T, Koppiker N. Efficacy and safety of sildenafil in women with sexual dysfunction associated with female sexual arousal disorder. J Womens s Health Gender Based Med 2002;11: Caruso S, Instelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with Sildenafil: a double blind, crossover, placebo-controlled study. Br J Obstet Gynaecol 2001; 108: Singer B, Toates FM. Sexual motivation. J Sex Res 1987;23: Levine S. Intrapsychic and individual aspects of sexual desire. In: Leiblum SR, Rosen RC, editors. Sexual Desire Disorders. New York: Guilford, Bancroft J. Human Sexuality and its Problems. Edinburgh: Churchill- Livingstone, Basson RJ. Using a different model for female sex response to address women s problematic low sexual desire. J Sex Marital Ther 2001; 27: Shifren JL, Brownstein GD, Simon JA, Casson PR, Buster JE, Redmond GP. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000;343: Bixo M, Bäckström T, Winblad B, Andersson A, Santoro N. Estradiol and testosterone in specific regions of human female brain in different endocrine states. J Steroid Biochem Molec Biol 1995;55: Dennerstein L, Dudley E, Hopper JL, Burger H. Sexuality, hormones and the menopausal transition. Maturitas 1997;26: Zumoff B, Strain GW, Miller LK, Rosner W. Twenty-four hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab 1995;80: Mushayandebvu T, Castracane DV, Gimpel T, Adel T, Santoro N. Evidence for diminished mid-cycle ovarian androgen production in older reproductive aged women. Fertil Steril 1996;65: Friedrich MJ. Can male hormones really help women? JAMA 2000;283: Lobo RA. Androgens in postmenopausal women: production, possible role, and replacement options. Obstet Gynecol Surv 2001;58: Davis SR, McCloud PI, Srauss BJG, Burger HG. Testosterone enhances estradiol s effect on postmenopausal bone density and sexuality. Maturitas 1995;21: Sarrel P, Dobay B, Wiita B. Estrogen and estrogen androgen replacement in postmenopausal women dissatisfied with estrogen only therapy. J Reprod Med 1998;43: Rymer J, Chapman MG, Fogelman I, Wilson POG. A study of the effect of tibolone on the vagina in postmenopausal women. Maturitas 1994;18: Kökçü A, Çetinkaya MB, Yanik Filiz, Alper T, Malatyalioğlu E. The comparison of effects of tibolone and conjugated estrogen medroxyprogesterone acetate therapy on sexual performance in postmenopausal women. Maturitas 2000;36: Nathörns-Boööos J, Hammar M. Effects on sexual life: a comparison between tibolone and a continuous estradiol norethisterone acetate regiment. Maturitas 1997;26: Albertazzi P, Natale V, Barbolini C, Teglio L, Di Micco R. The effect of tibolone versus continuous combined norethisterone acetate and oestradiol on memory, libido and mood of postmenopausal women: a pilot study. Maturitas 2000;36: Castelow-Branco C, Vicente JJ, Figueras F, et al. Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women. Maturitas 2000;34: Rako S. Testosterone deficiency and supplementation for women: matters of sexuality and health. Psychiatr Ann 1999;29: Bartlik B, Legere R, Andersson L. The combined use of sex therapy and testosterone replacement therapy for women. Psychiatr Ann 1999;29:27 33.