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International Journal of Impotence Research (2008) 20, 466–478 & 2008 Nature Publishing Group All rights reserved REVIEWWomen’s sexual function and dysfunction: current uncertainties,future directions BC Centre for Sexual Medicine, Vancouver General Hospital, Vancouver, BC, Canada There is increasing evidence that women at the outset of sexual activity do not need to have sexualdesire, as in ‘drive’, and that many do not distinguish desire from arousal. Multiple modes ofinvestigation confirm poor correlation between women’s subjective arousal and measured genitalcongestion. Suggested revisions to the DSM-IV definitions of sexual disorder have been published:there is now need to align interview assessments and screening questionnaires with contemporaryunderstanding of women’s sexual response. Whereas the psychological factors associated withwomen’s sexual function and resilience to biological insults and external stressors are welldocumented, the role of biological factors is less clear. Variations in the rate of decline of adrenaland ovarian pro-hormones, activity of converting enzymes in peripheral cells, sensitivity ofandrogen and estrogen receptors and cerebral production of sex steroids may all be involved. Thusthere is great complexity underlying the question of sex hormone supplementation, and inparticular, little clarity as to which women have decreased brain and/or peripheral androgenactivity. When psychosexual etiological factors appear to be minimal and investigationaltestosterone supplementation is considered, it would be appropriate to target women withdisordered arousal and desire in keeping with the recently recommended revised definitions.
International Journal of Impotence Research (2008) 20, 466–478; published online 12 June 2008 Keywords: women’s sexual function; dysfunction; androgens women develop sexual dysfunction will also beaddressed from both psychological and biological Clinical, empirical, psychophysiological, cultural, perspectives. The current status of hormonal ther- brain imaging and hormonal research data allow us apy for dysfunction will be highlighted: reasons for now in 2008 to identify some of the complexities of concern about the lack of safety data for long-term women’s sexual function and dysfunction. As we systemic estrogen and testosterone supplementation move away from older linear models of sexual being a major focus. Finally, other areas of needed response, and from concepts more typical of men’s sexuality, many questions emerge. This manuscriptwill focus on some of those questions: specificallywhat constitutes sexual disorder, whether women distinguish between desire and arousal and whatmotivates women to be sexually active over andbeyond ‘sexual desire’—thereby questioning the Sexual motivation, including sexual desire current focus on desire in most therapeutic trials.
Recent data allow us to conceptualize women’s Why, despite universally marked reductions in sex sexual response as highly variable for the individual hormones with menopause and age, only some woman—depending on the context and stage of herlife, as well as among different women, and betweenwomen of different cultures. Thus, the challenge isto determine whether a woman’s sexual symptomsare reflective of normal change, adaptation to Correspondence: Dr R Basson, BC Centre for Sexual current circumstances or of disorder of her sex Medicine, Vancouver General Hospital, 855 West 12th Avenue, Echelon 5, Vancouver, Canada BC V5Z 1M9.
E-mail: Although frequent in new relationships,sexual Received 25 January 2008; revised 30 April 2008; accepted desire experienced ahead of sexual activity may be 3 May 2008; published online 12 June 2008 rare for sexually content women in longer-term Women’s sexual function and dysfunctionR Basson relationships.Studying mostly younger women, the outset of a sexual experiencConsequently empirical data show that reasons for sex are women, who mostly recognize a triggered rather numerous and have been divided into the domains than spontaneous desire, are at risk of being of ‘emotional reasons’ including love and commit- inappropriately labeled as dysfunctional when these ment; ‘physical reasons’ including stress reduction and pleasure; ‘goal-attainment reasons’ includingresources, social status and revenge; and ‘insecurityreasons’ including boosting of self-esteem, duty/ Women’s experience of arousal is complex. Qualita- graduate psychology students, the majority of both tive research indicates that most women cannot men and women were motivated mostly by reasons clearly distinguish between desire and arousal.
related to attraction, pleasure, affection, love, ro- Although nearly all women may speak of desire in mance, emotional closeness and the desire to please terms of thoughts and emotions, some 80% may also but women exceeded men in reporting emotional include nongenital physical sensations and some motivations.Further empirical data confirm that 75% include genital sensatDefining disor- women’s sexual desire is commonly triggered rather dered arousal is therefore difficult. Data from many than spontaneous. Data from 125 women aged 20–70 sources identify further levels of complexity such years showed that both pre and postmenopausal that the genital neurovascular response of swelling women with and without sexual dysfunction report and lubrication is now understood to be a prompt triggers of sexual desire in the domains of emotional automatic reflex entity that can be completely bonding, erotica, romance and physical proximity.
disconnected from any subjective arousal The Study of Women Across the Nation focusing on 3250 multiethnic mid-aged women in North poor correlation between subjective arousal and the America, indicated that the vast majority are measures of congenital congestion, plus the fact that moderately or extremely satisfied with their physi- in marked contrast to men’s assessment of erection, cal sexual pleasure and yet, some 42% never or very women’s assessment of the degree of congenital infrequently sensed desire, with even higher figures congestion is inaccurate, women’s arousal cannot for Chinese and Japanese women (61.4 and 67.8%).
be assessed by their ‘report of genital swelling Anticipatory sexual desire is more common among lubrication response.’Including subjective arousal women early in relationships when it may be a major reason for sexual engagement. According to An absence of genital response may be reported one cross-sectional study that phase may only last 1 even though appropriate genital congestion may be yearTherefore, a willingness to become aroused occurring. When neither subjective nor genital and to sense desire ‘soon’, appears to be a very response is perceived the preferred term is ‘com- common initial phase.Unfortunately, validated bined sexual arousal disorder’. However, a related questionnaires for assessment of sexual function are but different clinical construct is ‘genital deadness’ based upon older models of women’s sexual re- despite retained ability to be aroused from nongenital sponse, where desire was assumed to be needed at and nonphysical stimuli. Such loss of genital sexual Table 1 Data identifying poor correlation between subjective sexual arousal and measurements relating to the neurovascular genitalresponse12–16 Brain imaging while viewing visual erotica Activation of complex brain circuitry including cortical,limbic and paralimbic areas involved in cognition,motivation, emotions as well as hypothalamic areasmodulating autonomic nervous system. Activation inhypothalamus to increase genital congestion correlatespoorly with subjective arousalb VVP in women with and without problematic Minimal correlation between subjective arousal and desire, arousal, orgasm, dyspareunia and viewing Measures of increases in genital blood flow correlatepoorly with subjective arousal VPP during the viewing of biologically sexual Prompt increases in vasocongestion despite absence Abbreviations: MRI, magnetic resonance imaging; VVP, vaginal photoplethysmography.
bThese findings are in contrast to those in men.
International Journal of Impotence Research
Women’s sexual function and dysfunction again—adding to the woman’s future list of reasons to deliberately allow stimuli to move her from a motivates
neutral to a sexually aroused state. The overlap and cyclicity predicts the known comorbidities of Many have noted the challenge in defining ‘normal’ or ‘disordered’ sexual response.Thedifficulty only increases when the variability asso- ciated with life cycle, culture, life contexts and current relationship, are taken into account. Fre- quently, for women with sexual ‘dysfunction’ there is no evidence of innate dysfunction of sexual Processed
response, rather, a paucity of reasons to begin, or responsive
problematic stimuli and/or context explain the reported dysfunctional episodes of sexual engage-ment.Thus, to assist a woman experiencing sexual Figure 1 Circular response cycle of overlapping phases: desire dysfunction, we must assess the context of her may not be present initially but triggered during experience.
life and relationship, as well as the details of The sexual and nonsexual outcome influences future sexualmotivation. Copied with permission from Lippincott Williams & sexual interactions. The inclusion of etiological Wilkins from Figure 2: Basson R. Female sexual response: the role descriptors—current context, developmental history of drugs in the management of sexual dysfunction. Am Coll Obstet or medical factors, alongside any diagnosis of sexual Management may well be other than directly to her sexual response with investigational medication or sexual arousal disorder.Both retained neuronal sex hormone supplementation. Women themselves sexual sensitivity and vascular response of the rate relationship difficulties as a major perceived extensive sinusoidal tissue in the vulva including the clitoral head, body, rami, bulbs and periurethral response system itself appears disordered, means tissue seems to be necessary to allow subsequent to attend to the sexual stimuli such as the meditative physical stimulation to be sexually pleasurable and technique of mindfulness are now being studied.
exciting. When reduction of this response causes dryness and dyspareunia from reduced lubrica- established Cognitive Behavioral Therapy (CBT) tion, a diagnosis of dyspareunia and not ‘arousal techniques to alter negative thoughts and emotions, precluding or generated by the sexual arousal hasfrequently been encouraged.
American Psychiatric Association’s Diagnostic and An increasingly used model of women’s sexual Statistical Manual, 4th edn (DSM-IV-R),an inter- response reflects the overlap of phases and their national consensus committee organized by the varied order to allow patient and clinician to American Urology Association Foundation deliber- identify sites of weakness in, or interruptions of the cycle.shows that a women’s attention recent suggested revisions by three psychiatric to appropriate sexual stimulation and her ability to sexual medicine colleagues.There is some ur- stay focused on the moment, will encourage her gency to decide on ‘official definitions’ which all subjective arousal—and that arousal is variably can use and to develop instruments reflective correlated with prompt reflexive genital congestion.
of the new understanding of disorder for use in If this complex state of arousal with mental excite- clinical trials.The major recommendations are: ment and various physical responses is accompa-nied by positive emotions and thoughts, then sexual (1) To acknowledge desire limited to ‘responsive’ or desire, along with further arousal, is experienced.
‘triggered’ desire is a normal variant.
Orgasms may or may not be necessary for sexual (2) To address loss of subjective arousal.
satisfaction. More intense arousal can follow the (3) To include the entity of genital sexual arousal first orgasm(s). High arousal can allow the woman to disorder—loss of genital sexual sensitivity such be receptive to more erotic types of stimulation that that arousal, pleasure, orgasms from that mode of she previously declined or was unable to acknowl- stimulation are minimal. These symptoms may edge given her sexually unaroused mind. Thus, with time, more erotic stimuli can allow higher arousal.
decreased vasocongestion as would be expected for example after non-nerve sparing radical times during one sexual encounter. Positive sexual hysterectomy or in the context of generalized experiences provide further motivation to be sexual International Journal of Impotence Research
Table 2 Changing definitions of women’s sexual dysfunctions or diminished feelings of sexual interest sexual thinking or desiring of sex ahead of fantasies and a lack of responsive desire.
women in sexually satisfactory established sexually aroused are scarce or absent.
The lack of interest is beyond a normative ‘responsive’ desire, is integral to the lessening with life cycle and relationship revised diagnosis. Segraves et al. note in their manuscript that ‘many women do notreport the presence of spontaneous desire’.
Thus, ‘or’ (lack of responsive desire) seemsincorrect arousal (vulval swelling and lubrication) lubrication/swelling response untilcompletion of sexual activity pleasure) from any type of stimulation.
Vaginal lubrication and other signs of The presence of subjective arousal (sexual impaired genital sexual arousal—minimal vulval swelling or vaginal lubrication from example erotica, stimulating the partner, receiving breast stimulation, kissing) is key to the revised AUAF/AFUD diagnosis.
still occurs from nongenital sexual stimuli dyspareunia then the diagnostic term isdyspareunia This condition is poorly understood.
when sexual interest or desire is absent.
International
infrequent but mostly unpleasant. Thearousal is unrelieved by orgasms andthe feelings persist for hours or days excitement, there is either lack of orgasm, diagnosis is one of the arousal disorders.
Research
Women’s sexual function and dysfunction Despite universally marked reductions in sex hormones with menopause and age there is no universal sexual decline. Studying a nationally representative probability sample of 815 women in the United States in intimate relationships, of those aged 57–64 years, 80–90% were sexually active (the lower percentage were those reporting poor health), and of those, 76% reported sex as pleasurable, and 65% reported sufficient lubrication and ability to climax. Of those aged 65–74 years, 50–70% were active, with 78% of those reporting pleasure, 57% reporting sufficient lubrication and 76% the ability Psychological factors that increase the risk of sexual Poor mental health is consistently found to be a major risk factor in cross-sectional and longitudinal research.Even when current mood and medi- cations were factored in, of the 914 mid-aged women in the SWAN (Study of Women’s Health Across the Nation) study, those with past history of major depressive illness reported less arousal, physical pleasure and emotional satisfaction in their present relationship.Of 445 women with majordepression, close to 80% had sexual dysfunction identified on a validated self questionnaire which improved with successful antidepressant therapy but worsened if depression continued.When clinical depression is excluded, women complain- ing of low desire are still shown to have lower self- esteem, more mood variability and more anxious and depressed thoughts, than control women.
Anxiety disorders can preclude women’s ability to attend to sexual stimuli and to be lost in the moment. For women with diabetrenal failure or multiple sclerosis,it is the comorbid depression that is associated with higher prevalence of sexual dysfunction compared to control women.
Positive past sexual experiences and positive feelings for the current partner are strongly corre- lated with women’s sexual satisfaction and desire and may protect them from dysfunction associated with sex hormone loss.Empirical data confirm that love and emotional bonding serves as a major cue or trigger for sexual desire.Women’s feelings for their partners, or a recent change of partner, were two of the three major determinants of women’s desire and responsivity in the longitudinal study for women transitioning menopauseand were major determi- nants in cross-sectional studiPositive feel- ings for partners generally and specifically at the time of sexual interaction, were major factors affording protection against sexual distress.Im- portant predictors of sexual satisfaction among breast cancer survivors included mental health and International Journal of Impotence Research
Women’s sexual function and dysfunctionR Basson a better quality of relationship.Also included Biological factors that may modulate sex hormone was an absence of partner-sexual dysfunction, confirmed in many other studies of women withoutbreast cancer.
Rate of decline of ovarian prohormones and ovariantestosterone personally adapt to biological changes such that Activity of converting enzymes in peripheral sexual experiences change over time but without perception of problem. Are factors such as ability to ‘be present’ for the longer duration of sexual Cerebral production and activity of sex steroids fromcholesterol stimulation that is now needed, or a more positive self-image or attitude to aging important? Numbers of sex steroid receptorsActivity of regulatory Biological factors that might increase the risk of Abbreviations: AR, androgen receptor; ER, estrogen receptor.
sexual dysfunctionAlthough psychological factors might account for addition, sometimes premature ovarian failure much of the risk of dysfunction, it remains possible involves all ovarian hormones and prohormones.
that biological factors further modulate this risk. Are In some areas of medicine, serum levels of some women more vulnerable to the inevitable hormones or other chemicals are clinically useful reduction in sex hormone activity on a biological even if they do not necessarily match intracellular basis? The roles of estrogen and testosterone in levels: for instance, serum levels of potassium.
maintaining women’s sexual health are not clearly However, the situation for mid-aged and older understood. Although the vast majority of women women is that the major production of the entity discontinuing postmenopausal estrogen supplemen- in question (testosterone and estrogen) is within the tation develop signs of vulvovaginal atrophy, peripheral cells in which the hormones exert their most epidemiological studies show little increase action, and in the case particularly of testosterone, in dyspareunia with age.Although surgical only a small portion leaks back into the blood stream menopause has been chosen as an example of to be measured.Thus, it is by no means clear that an androgen deplete state, the prevalence of any serum level of testosterone is a useful entityIt is currently thought that measurement of intracel- Indeed three recent studies showed that women lular production of hormones, as well as those of choosing (as opposed to just consenting to), bilateral oophorectomy with their simple hysterectomy Such measurement of global androgen activity might required for benign reasons, do not develop sexual clarify an association between sexual function and dysfunction over the next 1–3 years.
sexual hormones. Two large recent studies failed to Despite reduction with age and with menopause, find correlation of sexual function with serum sex hormone production continues, but final hor- androgen levels measured as total testosterone and monal activity may be modulated by various free androgen index in 2900 pre and perimenopau- sal multiethnic North American womeand as testosterone is produced by both the ovaries and free and total testosterone in 1021 Australian adrenals: these organs also produce precursor sex women aged 18–75 years.Even in 81 women with hormones, including prasterone (known as dehydro- premature ovarian failure, little correlation was found recently between sexual function and testos- In addition, the adrenals produce prasterone terone levelThat there is no consistent relation- sulfate (known as DHEAS), androstene-5-ene-3b ship between sexual function and any of the and 17b-diol. These precursor sex hormones or prohormones has been well documented.Total ‘prohormones’ can be converted to estrogen and/or androgen activity is currently thought to be best testosterone in peripheral cells, including those of reflected by the measurement of serum androgen the brain, breast, bone and genitalia. From the glucuronides, most notably androsterone glucuro- age of mid 30s to early 60s adrenal production nide (ADT-G).These metabolite levels reflect reduces by some two-thirds. Postmenopause, ovarian both availability of substrate and activity of the production of estrogen ceases and only intracellular steroidogenic hormones in the peripheral cells.
production remains.The situation for androgens is These steroidogenic enzymes include P450 C17 more complex in that ovarian production continues (17, 20 lyase), 3b-hydroxysteroid dehydrogenase to a variable degree. Prohormones that can poten- tially become androgens continue to be produced 5a-hydroxylase. In the case of vulnerability to but in increasingly smaller quantities from both vasomotor symptoms rather than sexual symptoms adrenal glands and ovaries. Moreover, women with (the latter not studied), women in the SWAN study bilateral oophorectomy lose all ovarian production who had two alleles for the polymorphism CYP19 of testosterone and sex hormone precursors. In 11r (CYP19 being an aromatase enzyme converting International Journal of Impotence Research
Women’s sexual function and dysfunction androstenedione and testosterone to estrone and estra- attractive male mouse or placing her in a cage diol), had more frequent and more severe associated with past sexual encounters will result in But, measurement of metabolites (which have the same behavior.In women, sexual desire and been studied far more from androgens than estro- satisfaction is strongly correlated with change in partner and with positive past sexual experiences.
How well the sex hormone produced within a cell That none of this is simple is endorsed by a recent can activate its receptor to ultimately cause protein albeit preliminary study of surgically menopausal production depends on a number of factors includ- women receiving no hormone therapy, but who were ing the numbers and activities of co-regulators. Once sexually functional as tested by the BISF-W ques- the testosterone (or estrogen) binds to the receptor, tionnaire. Viewing erotica failed to show the brain there is conformational change in the receptor such activation typical of premenopausal women and that it can recruit co-activators or co-repressors. It is typical of themselves when treated with both this complex of sex hormone, sex hormone receptor testosterone and androgen—yet they reported sexual and co-regulators that binds to the specific DNA arousal from the erotic videos without as well as response elements. At present there is no way of measuring numbers or activity of co-regulatorsin the human. Polymorphisms of the androgenreceptor gene may be a further confound. Future studies may evaluate risk of sexual dysfunction withvarious androgen receptor polymorphisms.
Perhaps an even more important confound is the fact that the brain can synthesize sex steroids There is consensus that any of the approved local de novo, such that those entering from the peripheral formulations of local estrogen are useful to reduce circulation may be less relevant than has been symptoms of dyspareunia and improve genital assumed.The evidence to date suggests that synthesis can directly start from cholesterol and is Given the (albeit minimal) systemic absorption, a generalized process within the central nervous individualized advice is given to women having system: of note, androgen receptors are prominent in the forebrain as well as in the well-characterizedareas of the hypothalamus and limbic regions.
Adaptive changes occur in the brain to reductions in serum levels of sex hormones associated with age Available molecules that bind to the estrogen and with menopause: in women, there is upregula- receptor with agonistic action in some tissues and antagonism in others, do not ameliorate the genital tors.Regulatory proteins such as those allowing sexual symptoms of estrogen lack—these symptoms the first step in steroid production, that is, being more frequent from raloxifene than t movement of cholesterol from the outer to the inner Investigational lasofoxifene appears promising.
mitochondrial membrane may also show increasedactivity, as in rodent models.However, the wholearea of biological adaptation to reduced amounts of sex hormones is only just the beginning.
Tibolone, a molecule possessing androgenic, pro- The interplay between sex hormones and brain gestogenic and estrogenic activity, reduces vulval amines including serotonin, dopamine and noradrena- atrophy in women recruited for reasons other than line has yet to be clarified. Neurotransmitters such as sexual dysfunction, and has comparable sexual benefit dopamine can activate the androgen receptor. When to transdermal norerthisterone acetate plus estradiol in an oophorectomized mouse is given estrogen and then women with sexual dysfunctiAvailable in Europe, primed with progesterone, she becomes sexually tibolone was found ‘not approvable’ by the Food and proceptive. Giving her dopamine without either sex Drug Administration in June 200There is concern hormone causes the same behaviorSome women regarding possible higher risks of breast cancer from given dopaminergic drugs, such as bupropion, report tibolone compared to estrogen only, as shown in increased sexual responseand some women with women in the million women studyFurthermore, Parkinson’s disease when given dopamine agonists there was a doubled incidence of stroke compared to report increased desire and responsivity such that sex placebo in the Long-Term Intervention on Fractures It is clear also that the environment can trigger circuits typically triggered by sex hormones. Again,this can be established in the laboratory in therodent: instead of giving the oophorectomized female rodent either sex hormones or dopamine, Effective for sexual symptoms of estrogen defi- simply placing her adjacent to a cage holding an ciency, systemic estrogen is also a prerequisite for International Journal of Impotence Research
Women’s sexual function and dysfunctionR Basson benefit from systemic testosterone. Prescribing only patches or other formulations—adapting those ap- testosterone would create a highly nonphysiological proved for men or using compounded creams and state. Within a context of needed estrogen defi- gels. A recent RCT confirmed benefit from a 300 mg ciency, for example women with past histories of patch in naturally menopausal womeAnother breast cancer, no observed benefit to sexual desire showed marginal benefit from one of three doses of was seen from testosterone supplementation.
transdermal testosterone in premenopausal women Long-term safety data for sexually symptomatic with early morning serum free testosterone of less perimenopausal women given systemic estrogen, than or equal to 1.1 pg/ml.The highest of the three are not known with any certainty. Data from the doses, aimed to raise free testosterone levels to at (mostly asymptomatic) younger women in the least the 75th percentile failed to show benefit Women’s Health Initiative study and data from the beyond placebo as did the smallest (one-third) dose.
observational Nurses study, suggest that such early The one-half dosage allowed 0.7 more sexually initiation of estrogen therapy is advantageous to satisfactory events per month than placebo, but cardiovascular healtheven if combined with outcome as measured by the Sabbatsberg Sexual progesterone—however, a small increase risk of Self-rating Scale was similar to placebo. It is very important that the limits of long-term safety oftestosterone supplementation are explained to ourpatients and to colleagues entering the field of Long-term systemic supplementation of testosterone sexual medicine. Recent reviews have acknowl- edged that prospective studies of physiologic tes- There are limitations in our understanding of the tosterone administration have been limited to 2 consequences of systemic sex hormone therapy years or less and that prospectively collected long- given for the duration of a woman’s sexual life- term safety studies are needed.In vitro and in time—usually an indefinite period dependent to vivo studies have reported both proliferative and marked extent on the availability of a sexually antiproliferative effects on growth of breast cancer cells brought about by testosterone. Epidemiological Recent randomized controlled trials (RCTs) have review has suggested that endogenous androgen focused on estrogenized surgically menopausal levels are positively correlated with breast cancer women who report less desire and less frequentsex since oophorectomy. Sexual benefit beyond placebo has been demonstrated from 300 mg, butnot from 450 mg, transdermal testosterone daily Further clarification of what is a sexual disorder: when is the Benefit was modest and varied across studies, all of woman’s sex response system dysfunctional and when is it which used similar protocols. In most studies, the simply adaptive to problematic stimuli, context and outcome? Identification of markers of low androgen activity: these frequency of ‘sexually satisfying events’ increased might include serum levels, for example of androgen with active drug—from approximately 3, to 5 per metabolites as well as the woman’s androgen receptor month. Pooling the data showed that women receiving testosterone reported 1.9 more such events Investigation of any correlation between such marker andsexual dysfunction per month than at baseline whereas women receiv- RCTs of testosterone and estrogen supplementation in women ing placebo reported 0.9 more. Increased scores in unable to have any sexually satisfying experiences the desire domain of the psychometrically validated Tailoring of any testosterone substitution based on androgen (but unpublished) questionnaire were seen in all trials. In some but not all trials, scores in the arousal, Clarification of the role of de novo synthesis of sex steroids inthe brain throughout a woman’s life and its modulation by pleasure, orgasm, responsivity domains were in- supplementation of exogenous sex steroids creased, and distress scores were decreased. Needed Development of drugs that effectively and safely increase now are trials recruiting women having sexual women’s sexual arousal and desire once they are sexually disorder according to contemporary understanding SERMS to allow genital congestion in estrogen-deficient of women’s sexual response and the current recom- states but with desirable profile on estrogen receptors mended definitions of disorderSuch studies would focus on women who are still motivated to ARMS for possible benefit to lost genital sexual sensitivity sexually engage for reasons other than desire, but who since bilateral oophorectomy, report that their RCTs of topical testosterone for possible benefit to lost genitalsexual sensitivity minds and/or bodies fail to arouse or respond to past Further development of nerve-sparing techniques for surgery sexual triggers so that their baseline number of for pelvic cancer, continence and, prolapse sexually satisfying events is set near zero. Recruit- Further empirical data on psychosexual therapy including ment criteria would comprise acquired sexual mindfulness, CBT, sex therapy—both with and withoutpharmacological adjuncts arousal disorder (combined, subjective or genital),plus sexual desire interest disorder Abbreviations: ARMS, androgen receptor modulators; CBT, Clinicians in various countries are prescribing cognitive behavioral therapy; RCTs, randomized controlled trials; systemic testosterone using either recently approved SERMS, selective estrogen receptor modulators.
International Journal of Impotence Research
Women’s sexual function and dysfunction responses to viewing erotic videos 15 min after intranasal drug but increased arousal during subsequent activity in eight women occurring inverse agonist known to inhibit also reduces the amount of MCRmolecules accessible to melanocortins atthe cell surface agonists thought to be D2 receptor related.
Selective D3 agonist investigated forerectile dysfunction Less likely to cause medication-associated in vasodilatation of the clitoral structures neurotransmitter allowing vasodilatationin the vagina. However, most women witharousal disorders have normal genitalcongestion Abbreviations: MCR, melanocortin receptor; MSH, melanocyte stimulating hormone; NEP, neutral endopeptidase; NO, nitric oxide; RCT,randomized controlled trial; SEP, soluble endopeptidase; SSRI, selective serotonin reuptake inhibitors; VIP, vasoactive intestinalpolypeptide.
risk.However, recent research has shown testos- case-controlled study, showed weak trends toward terone’s reduction of the typical proliferative effects increased risk of CVD among women having higher of postmenopausal estrogen and progesterone ther- androgen/estrogen ratios: among postmenopausal apyThe risk of cardiovascular disease (CVD) from women not taking any hormone therapy, women supplementing androgens is unknown. A link with lower SHBG or with high free androgen between higher androgens and CVD continues to indexes were at increased risk of CVD events.
be debated. Evaluation of 600 healthy postmeno- Basic sciencand clinicaldata suggest that pausal women in the SWAN study suggested that exogenous testosterone administration to women central obesity was associated with lower sex may promote abdominal fat deposition.
hormone-binding globulin (SHBG), higher free an- The North American Endocrine Society Clinical drogen levels, and insulin resistance, and that Practice Guideline recommends against the general- androgens are associated with hemostatic and ized use of testosterone by women because the inflammatory factors at midlife.Other investiga- indications are inadequate and evidence of long- tors have suggested that SHBG, not androgen term safety is lacking—this recommendation came production, is the primary marker of insulin about in the knowledge that there is evidence for resistance, and that the SHBG level has independent short-term efficacy of testosterone in selective predictive power for cardiovascular risk for wo- populations such as surgically menopausal wo- Both of these studies were cross-sectional men.Guidelines from the North American Meno- pause Society are less restrictive but somewhat International Journal of Impotence Research
Women’s sexual function and dysfunctionR Basson confusing suggesting treatment must be ‘adminis- tered at the lowest dose for the shortest time that Hypnosis can be associated with remission of the meets treatment goals’.There is no evidence that neurological inflammation of vulvar vestibulitis testosterone-related sexual symptoms are short term syndrome (VVS)—typically considered a ‘biological’ (for instance, analogous to estrogen related vasomo- entity.The marked placebo response to drugs for sexual dysfunction notable in older women and inwomen further research: what is its neurochemical basis? An increasing acknowledgement of women’s sexu-ality as a legitimate health concern may allow some of the aims listed in to be realized.
Current evidence-based conceptualization of wo-men’s sexual response has led to various recom-mendations for revised definitions of disorder.
Specifically, it is now advocated that desire disorder Contrary to the unwanted sexual side effects of some be defined as the absence of both any initial desire antidepressants, the activation of sex receptors by and any desire triggered along with arousal during certain amines has encouraged the development of the attempted sexual experience. Definitions of molecules having actions on dopamine, serotonin, arousal disorder must recognize the importance of melanocortin and noradrenaline receptors that are subjective arousal (excitement). The past focus on lubrication and swelling is no longer tenable given it There has been interest in treating deficient is not the means by which women judge their genital congestion with various drugs including arousal, is not accurately assessed by women, and phosphodiesterase inhibitors, a-blockers, selective when the increases in genital vasocongestion are estrogen receptor modulators (SERMS) and pepti- measured, they correlate minimally with subjective dase inhibitors. However, the documented lack of arousal. Although the psychosexual factors protect- correlation between women’s sexual symptoms and ing women from sexual dysfunction subsequent to any measurable deficit in genital congestion limits dramatic changes in sex hormones with life cycle this approach. Focusing on women with expected are well established, biological factors are less clear.
deficient congestion due for instance to non-nerve Thus, which women might benefit from supple- sparing radical hysterectomies, would be useful.
mental testosterone, has not been established— Understanding the molecular actions of estrogen neither by biological nor by clinical parameters. It in restoring vaginal health is increasing and may is recommended that hormonal or pharmacological allow development of nonhormonal therapies tar- approaches focus on women whose response is geted at vaginal atrophy (VA). Changes in gene deemed disordered using currently recommended expression after estrogen treatment of VA include genes involved in several signaling pathways thatpromote tissue repair, remodeling, vascularizationand defense against microbes in the vagina.
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