The Bio-Psycho-Social Dimension in Women’s Sexual Desire: ‘Argumentum ad novitatem’

Author(s): Nur Syazwani Roslan , Nik Ruzyanei Nik Jaafar , Hatta Sidi* , Najwa Baharudin , Jaya Kumar , Srijit Das , Nik Hazlina Nik Hussain .

Journal Name: Current Drug Targets

Volume 20 , Issue 2 , 2019

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Graphical Abstract:


Sexual desire includes complex motivation and drive. In the context of biological and cognitive- emotive state art of science, it is often a neglected field in medicine. In regard to the treatment, study on women’s sexual function received less attention compared to the men’s sexuality. In the past, this endeavor was relatively not well disseminated in the scientific community. Recently, there was a revolutionized surge of drug targets available to treat women with low sexual desire. It is timely to review the relevant biological approach, especially in the context of pharmacotherapy to understand this interesting clinical entity which was modulated by numerous interactive psychosocial inter-play and factors. The complex inter-play between numerous dimensional factors lends insights to understand the neural mechanism, i.e. the rewards centre pathway and its interaction with external psychosocialstimulus, e.g. relationship or other meaningful life events. The function of hormones, e.g. oxytocin or testosterone regulation was described. The role of neurotransmitters as reflected by the introduction of a molecule of flibenserin, a full agonist of the 5-HT1A and partial agonist of the D4 to treat premenopausal women with low sexual desire was deliberated. Based on this fundamental scientific core knowledge, we suggest an outline on know-how of introduction for sex therapy (i.e. “inner-self” and “outer-self”) where the role of partner is narrated. Then, we also highlighted on the use of pharmacological agent as an adjunct scope of therapy, i.e. phosphodiasterase-5 (PDE-5) inhibitors and hormonal treatment in helping the patient with low sexual desire.

Keywords: Female sexual desire, neural basis, psychosocial dimension, flibanserin, PDE-5 inhibitor, low sexual desire.

Spencer RA, Jeffrey NS, Lois F-R, Edward HS. McKenzie. Human Sexuality.In: A World Of Diversity. 2nd ed. Canada: Pearson Education 2005.
Veney SL, Rissman EF. Immunolocalization of androgen receptors and aromatase enzyme in the adult musk shrew brain. NeuroendoCrinol 2000; 72: 29-36.
Jankowska M. Sexual functioning of testicular cancer survivors and their partners-A review of literature. Rep Pract Oncol Radiother 2012; 17: 54-62.
Regan PC, Atkins L. Sex differences and similarities in frequency and intensity of sexual desire. Soc Behav Personal 2006; 34: 95-101.
Schnarch D. Passionate marriage: Sex, love, and intimacy in emotionally committed relationships. New York: W. W. Norton & Co. 1997.
Swanson LW. Anatomy of the soul as reflected in the cerebral hemispheres: neural circuits underlying voluntary control of basic motivated behaviors. J Comp Neurol 2005; 493: 122-31.
Basson R. The female sexual response: a different model. J Sex Marital Ther 2000; 26: 51-65.
Basson R, Driscoll M, Correia S. Flibanserin for low sexual desire in women: A molecule from bench to bed? EBioMedicine 2015; 2: 772-3.
Sidi H, Shaharom MH, Hassan R. Keharmonian Jalinan Antara Jantina 2nd ed Kuala Lumpur: Dewan Bahasa dan Pustaka;. 2006.
Dawkins R. The Selfish Gene. Oxford University Press 1976.
Lorenz TK, Demas GE, Heiman JR. Interaction of menstrual cycle phase and sexual activity predicts mucosal and systemic humoral immunity in healthy women. Physiol Behav 2015; 152: 92-8.
Bass TM. Exploring female sexuality: Embracing the whole narrative. N C Med J 2016; 77: 430-2.
Meston CM, Buss DM. Why humans have sex. Arch Sex Behav 2007; 36: 477-507.
DeLamater JD, Sill M. Sexual desire in later life. J Sex Res 2005; 42: 138-49.
Spector IP, Carey MP, Steinberg L. The sexual desire inventory: Development, factor structure, and evidence of reliability. J Sex Marital Ther 1996; 22: 175-90.
Wynn LL. ‘Like a Virgin’: Hymenoplasty and Secret Marriage in Egypt. Med Anthropol 2016; 35: 547-59.
Grubbs JB, Exline JJ, Pargament KI, Volk F, Lindberg MJ. internet Pornography Use, Perceived addiction, and Religious/Spiritual Struggles. Arch Sex Behav 2017; 46(6): 1733-45.
Angel K. Contested psychiatric ontology and feminist critique: ‘Female sexual dysfunction’ and the diagnostic and statistical manual. Hist Human Sci 2012; 25: 3-24.
Masters WH, Johnson VE. Human Sexual Response. 1st ed. Reno, NV: Little, Brown and Company 1966.
Kaplan HS. Hypoactive sexual desire. J Sex Marital Ther 1977; 3: 3-9.
Brotto LA, Petkau AJ, Labrie F, Basson R. Predictors of sexual desire disorders in women. J Sex Med 2011; 8: 742-53.
Sugrue DP, Whipple B. The consensus based classification of female sexual dysfunction: Barriers to universal acceptance. J Sex Marital Ther 2001; 27: 221-6.
Basson R. Clinical practice. Sexual desire and arousal disorders in women. N Engl J Med 2006; 354: 1497-506.
Ferenidou F, Kirana PS, Fokas K, Hatzichristou D, Athanasiadis L. Sexual response models: Toward a more flexible pattern of women’s sexuality. J Sex Med 2016; 13: 1369-76.
Giraldi A, Kristensen E, Sand M. Endorsement of models describing sexual response of men and women with a sexual partner: An online survey in a population sample of Danish adults ages 20-65 years. J Sex Med 2015; 12: 116-28.
Lewis RW, Fugl-Meyer KS, Corona G, et al. Definitions/epidemiology/risk factors for sexual dysfunction. J Sex Med 2010; 7: 1598-607.
Sand M, Fisher WA. Women’s endorsement of models of female sexual response: The nurses’ sexuality study. J Sex Med 2007; 4: 708-19.
Basson R, Wierman ME, van Lankveld J, Brotto L. Summary of the recommendations on sexual dysfunctions in women. J Sex Med 2010; 7: 314-26.
Sidi H, Naing L, Midin M, Nik Jaafar NR. The female sexual response cycle: do Malaysian women conform to the circular model? J Sex Med 2008; 5: 2359-66.
Nik Jaafar NR, Midin M, Sharifah Ezat WP, Sidi H. Sexual desire and sexual arousal in malaysian women: Are they of the same entity? ASEAN J Psych 2009; 10: 43-53.
Nowosielski K, Wrobel B, Kowalczyk R. Women’s endorsement of models of sexual response: Correlates and predictors. Arch Sex Behav 2016; 45: 291-302.
Giles KR, McCabe MP. Conceptualizing women’s sexual function: linear vs. circular models of sexual response. J Sex Med 2009; 6: 2761-71.
Frederick DA, Lever J, Gillespie BJ, Garcia JR. What keeps passion alive? Sexual satisfaction is associated with sexual communication, mood setting, sexual variety, oral sex, orgasm, and sex frequency in a national U.S. study. J Sex Res 2016; 22: 1-16.
Balon R, Segraves RT, Clayton A. Issues for DSM-V: sexual dysfunction, disorder, or variation along normal distribution: Toward rethinking DSM criteria of sexual dysfunctions. Am J Psychiatry 2007; 164: 198-200.
Kaplan HS. The classification of the female sexual dysfunctions. J Sex Marital Ther 1974; 1: 124-38.
American Psychiatric Association Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: Author 2013.
Cyranowski JM, Bromberger J, Youk A, Matthews K, Kravitz HM, Powell LH. Lifetime depression history and sexual function in women at midlife. Arch Sex Behav 2004; 33: 539-48.
de Jong DC. The role of attention in sexual arousal: Implications for treatment of sexual dysfunction. J Sex Res 2009; 46: 237-48.
Nelson AL, Purdon C. Non-erotic thoughts, attentional focus, and sexual problems in a community sample. Arch Sex Behav 2011; 40: 395-406.
Nobre PJ, Pinto-Gouveia J. Cognitions, emotions, and sexual response: analysis of the relationship among automatic thoughts, emotional responses, and sexual arousal. Arch Sex Behav 2008; 37: 652-61.
Simon JA. Low sexual desire - Is it all in her head? Pathophysiology, diagnosis, and treatment of hypoactive sexual desire disorder. Postgrad Med 2015; 122: 128-36.
Mouras HJ. [Identifying distinct components in the cerebral treatment of visual sexual information through functional neuroimaging]. Article in French. Soc Biol 2004; 198: 247-53.
Miyagawa Y, Tsujimura A, Fujita K, et al. Differential brain processing of audiovisual sexual stimuli in men: comparative positron emission tomography study of the initiation and maintenance of penile erection during sexual arousal. Neuroimage 2007; 36: 830-42.
Burbridge S, Stewart I, Placzek M. Development of the Neuroendocrine Hypothalamus. Compr Physiol 2016; 15: 623-43.
Llewellyn-Smith IJ, Verberne AJM. Central regulation of autonomic functions. 2nd ed. New York: Oxford University Press, Inc. 2011.
Arnow BA, Millheiser L, Garrett A, et al. Women with hypoactive sexual desire disorder compared to normal females: A functional magnetic resonance imaging study. Neuroscience 2009; 158: 484-502.
McFarland K, Davidge SB, Lapish CC, Kalivas PW. Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior. J Neurosci 2004; 24: 1551-60.
McFarland K, Kalivas PW. The circuitry mediating cocaineinducedreinstatement of drug-seeking behavior. J Neurosci 2001; 21: 8655-63.
McFarland K, Lapish CC, Kalivas PW. Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 2003; 23: 3531-7.
Pierce RC, Kumaresan V. The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 2006; 30: 215-38.
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 1986; 9: 357-81.
Williams DJ, Crossman AR, Slater P. The efferent projections of the nucleus accumbens in the rat. Brain Res 1977; 130: 217-27.
Goldstein I, Kim NN, Clayton AH, et al. Hypoactive sexual desire disorder: International society for the study of women's sexual health (ISSWSH) expert consensus panel review. Mayo Clin Proc 2016; S0025-6196: 30596. 2016.
Leiblum S, Bachman G, Kemmann E, Colburn D, Schwartzman L. Vaginal atrophy in the post-menopausal women: the importance of sexual activity and hormones. JAMA 1983; 249: 2195-8.
McCoy N, Davidson JM. A longitudinal study of the effects of menopause on sexuality. Mauritas 1985; 7: 203-10.
Schreiner-Engel P, Schiavi RC, White D, Ghizani A. Low sexual desire in women: the role of reproductive hormones. Horm Behav 1989; 23: 21-34.
Sherwin BB. Changes in sexual behavioural as a function of plasma sex steroid level in post-menopausal women. Mauritas 1985; 7: 225.
Sherwin BB, Gelfand MM, Brender W. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. Psychosom Med 1985; 47: 339-51.
Drellich MG, Waxenberg SE. Erotic and affective components of female sexuality. In: Masserman J ed.Science and psychoanalysis. New York: Grune & Statton Inc 1966.
Gorzynski G, Katz JL. The polycystic ovary syndrome: Psychosexual correlates. Arch Sex Behav 1977; 6: 215-22.
Simerly RB. Organization and regulation of sexually dimorphic neuroendocrine pathways. Behav Brain Res 1998; 92: 195-203.
Simerly RB, Swanson LW. Projections of medial preoptic nucleus: aPhaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J Comp Neurol 1988; 270: 209-42.
Chou TC, Bjorkum AA, Gaus SC, Lu J, Scammell TE, Saper CB. Afferents to the ventrolateral preoptic nucleus. J Neurosci 2002; 22: 997-0.
Clancy AN, Whitman C, Michael RP, Albers HE. Distribution of androgen-like receptor immunoreactivity in the brains of intact an castrated male hamsters. Brain Res Bull 1994; 33: 325-32.
Simerly RB, Chang C, Muramatsu M, Swanson LW. Distribution of androgen and estrogen receptor mRNA containing cells in the rat brain: an in situ hybridization study. J Comp Neurol 1990; 204: 76-95.
Traish AM, Botchevar E, Kim NN. Biochemical factors modulating female genital sexual arousal physiology. J Sex Med 2010; 7: 2925-46.
Dennerstein L, Randolph J, Taffe J, Dudley E, Burger H. Hormones, mood, sexuality, and the menopausal transition. Fertil Steril 2002; 77: s42-8.
Labrie F. Intracrinology LF. Mol Cell Endocrinol 1991; 78: C113-8.
Davis S, Davison S, Donath S, Bell R. Circulating androgen levels and self-reported sexual function in women. JAMA 2005; 294: 91-6.
Kupfermann I. Hypothalamus and limbic system: Peptidergic neurons, homeostasis, and emotional behavior. Principles of Neural Science. 3 ed. ER Kandel JSTJ, editor. Norwalk: Appleton & Lange; 1991.
Bancroft J. The endocrinology of sexual arousal. J Endocrinol 2005; 186: 411-27.
Cushing BS, Carter CS. Prior exposure to oxytocin mimics the effects of social contact and facilitates sexual behavior in females. J Neuroendocrinol 1999; 11: 765-9.
Melis MR, Argiolas A. Central oxytocinergic neurotransmission: A drug target for the therapy of psychogenic erectile dysfunction. Curr Drug Targets 2003; 4: 55-66.
Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. New York: Cambridge University Press 2000.
Laan E, van Lunsen RHW. Hormones and sexuality in postmenopausal women: A psychophysiological study. J Psychosom Obstet Gynaecol 1997; 18: 126-33.
Voisey J, Carroll L, Van Daal A. Melanocortins and their receptors and antagonists. Curr Drug Targets 2003; 4: 586-97.
Van der Ploeg LH, Martin WJ, Howard AD, et al. A role for the melanocortin 4 receptor in sexual function. Proc Natl Acad Sci USA 2002; 99: 11381-6.
Becker JB. Estrogen rapidly potentiates amphetamine-induced striatal dopamine release and rotational behavior during microdialysis. Neurosci Lett 1990; 118: 169-71.
Wallen K. Sex and context: hormones and primate sexual motivation. Horm Behav 2001; 40: 339-57.
Stahl SM. Stahl’s Essential Psychopharmacology. 3rd ed. New York: Cambridge University Press 2008.
Putnam SK, Sato S, Riolo JV, Hull EM. Effects of testosterone metabolites on copulation, medial preoptic dopamine, and NOS-immunoreactivity in castrated male rats. Horm Behav 2005; 47: 513-22.
Kleitz-Nelson HK, Dominguez JM, Cornil CA, Ball GF. Is sexual motivational state linked to dopamine release in the medial preoptic area? Behav Neurosci 2010; 124: 300-4.
Pfaus JG. Pathways of sexual desire. J Sex Med 2009; 6: 1506-33.
Meyerson BJ. Central nervous monoamines and hormone-induced estrous behaviour in the spayed rat. Acta Physiol Scand 1964; 1-32.
Shen WW, Hsu JH. Female sexual side effects associated with selective serotonin reuptake inhibitors: a descriptive clinical study of 33 patients. Int J Psychiatry Med 1995; 25: 239-48.
Corona G, Ricca V, Bandini E, et al. Selective serotonin reuptake inhibitor-induced sexual dysfunction. J Sex Med 2009; 6: 1259-69.
Stahl SM. The psychopharmacology of sex, Part 1: Neurotransmitters and the 3 phases of the human sexual response. J Clin Psychiatry 2001; 62: 80-1.
Keltner NL, McAfee KM, Taylor CL. Mechanisms and treatments of SSRI-induced sexual dysfunction. Perspect Psychiatr Care 2002; 38: 111-6.
Carroll JL, Volk KD, Hyde JS. Differences between males and females in motives for engaging in sexual intercourse. Arch Sex Behav 1985; 14: 131-9.
Kingsberg SA, Rezaee RL. Hypoactive sexual desire in women. Menopause 2013; 20: 1284-300.
Althof SE, Rosen RC, DeRogatis L, Corty E, Quirk F, Symonds T. Outcome measurement in female sexual dysfunction clinical trials: review and recommendations. J Sex Marital Ther 2005; 31: 153-66.
Clayton AH. The pathophysiology of hypoactive sexual desire disorder in women. Int J Gynaecol Obstet 2010; 110: 7-11.
Mimoun S. Hypoactive sexual desire disorder, HSDD. Gynécol Obstét Fertil 2011; 2011: 1.
Simon JA. Low sexual desire-is it all in her head? Pathophysiology, diagnosis, and treatment of hypoactive sexual desire disorder. Postgrad Med 2010; 122: 128-36.
Bachmann GA. Influence of menopause on sexuality. Int J Fertil 1995; 40: 16-22.
Semens JF, Wagner G. Estrogen deprivation and hormonal function in postmenopausal women. JAMA 1982; 445: 248-53.
Bachmann G, Leiblum S, Grill J. Brief sexual inquiry in gynecologic practice. Obstet Gynecol 1989; 73: 425-7.
Berman JR. Physiology of female sexual function and dysfunction. Int J Impot Res 2005; 17: S44-51.
Labrie F, Cusan L, Gomez JL, et al. Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women. Menopause 2009; 16: 30-6.
Laan E, van Lunsen RH, Everaerd W. The effects of tibolone on vaginal blood flow, sexual desire and arousability in postmenopausal women. Climacteric 2001; 4: 28-41.
Nijland EA, Weijmar Schultz WC, Nathorst-Boös J, et al. Tibolone and transdermal E2/NETA for the treatment of female sexual dysfunction in naturally menopausal women: results of a randomized active-controlled trial. J Sex Med 2008; 5: 646-56.
Brown AD, Blagg J, Reynolds DS. Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today 2007; 12: 757-66.
Davis SR, van der Mooren MJ, van Lunsen RH, et al. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: A randomized, placebo-controlled trial. Menopause 2006; 13: 387-96.
Vigersky RA. Goldilocks and menopause. Arch Intern Med 2005; 165: 1571-2.
Berman JR, Berman LA, Lin H, et al. Effect of sildenafil on subjective and physiologic parameters of the female sexual response in women with sexual arousal disorder. J Sex Marital Ther 2001; 27: 411-20.
Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil: A double-blind, cross-over, placebo-controlled study. BJOG 2001; 108: 623-8.
Cavalcanti AL, Bagnoli VR, Fonseca AM, et al. Effect of sildenafil on clitoral blood flow and sexual response in postmenopausal women with orgasmic dysfunction. Int J Gynaecol Obstet 2008; 102: 115-9.
Rosen RC, Phillips NA, Gendrano NC 3rd, Ferguson DM. Oral phentolamine and female sexual arousal disorder: A pilot study. J Sex Marital Ther 1999; 25: 137-44.
Rubio-Aurioles E, Lopez M, Lipezker M, et al. Phentolamine mesylate in postmenopausal women with female sexual arousal disorder: A psychophysiological study. J Sex Marital Ther 2002; 28: 205-15.
Goldstein I, Bassam D, Frank D, Hachicha M, Fernando Y, Schupp J. Results of a phase 3 clinical trial for female sexual arousal disorder (FSAD) with Femprox, A topical alprostadil 0.4% cream with a novel transdermal delivery technology. J Sex Med 2012; 9: 22.
Islam A, Mitchel J, Rosen R, et al. Topical alprostadil in the treatment of Female Sexual Arousal Disorder: A pilot study. J Sex Marital Ther 2001; 27: 531-40.
Krychman ML. Female sexual disorders: Treatment options in the pipeline Formulary Watch. United States: Modern Medicine Network 2013.
Caruso S, Agnello C, Intelisano G, Farina M, Di Mari L, Cianci A. Placebo-controlled study on efficacy and safety of daily apomorphine SL intake in premenopausal women affected by hypoactive sexual desire disorder and sexual arousal disorder. Urology 2004; 63: 355-9.
Oh KJ, Chae MJ, Lee HS, Hong HD, Park K. Effects of Korean red ginseng on sexual arousal in menopausal women: Placebo-controlled, double-blind crossover clinical study. J Sex Med 2010; 7: 1469-77.
Ferguson DM, Hosmane B, Heiman JR. Randomized, placebo-controlled, double-blind, parallel design trial of the efficacy and safety of Zestra in women with mixed desire/interest/arousal/ orgasm disorders. J Sex Marital Ther 2010; 36: 66-86.
Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas 1996; 23: 259-63.
Ückert S, Bannowsky A, Albrecht K, Kuczyk MA. Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: Results from basic research and clinical studies. Expert Opin Investig Drugs 2006; 23: 1477-83.
Bloemers J, van Rooij K, Poels S, et al. Toward personalized sexual medicine (Part 1): Integrating the “Dual Control Model” into differential drug treatments for hypoactive sexual desire disorder and female sexual arousal disorder. J Sex Med 2013; 10: 791-809.
Lodise NM. Hypoactive sexual desire disorder in women: treatment options beyond testosterone and approaches to communicating with patients on sexual health. Pharmacotherapy 2013; 33: 411-21.
Stahl SM. Circuits of sexual desire in HSDD (hypoactive sexual desire disorder). J Clin Psychiatry 2010; 71: 518-9.
Jin J. Flibanserin for treating low sexual desire in women. JAMA 2015; 314: 1312.
Dhanuka I, Simon JA. Flibanserin for the treatment of hypoactive sexual desire disorder in premenopausal women. Expert Opin Pharmacother 2015; 16: 2523-9.
Kennedy S. Flibanserin: Initial evidence on sexual dysfunction, in patients with major depressive disorder. J Sex Med 2010; 7: 3449-59.
Thorp J, Simon J, Dattani D, et al. Treatment of hypoactive sexual desire disorder in premenopausal women: efficacy of flibanserin in the DAISY study. J Sex Med 2012; 9: 793-804.
Jaspers L, Feys F, Bramer WM, Franco OH, Leusink P, Laan ET. Efficacy and safety of flibanserin for the treatment of hypoactive sexual desire disorder in women: A systematic review and meta-analysis. JAMA Intern Med 2016; 176: 453-62.
Yeoh SH, Razali R, Sidi H, et al. The relationship between sexual functioning among couples undergoing infertility treatment: a pair of perfect gloves. Compr Psychiatry 2014; 55: S1-6.
Creed KE, Carati CJ, Keogh EJ. The physiology of penile erection. Rev Reprod Biol 1991; 13: 73-95.
O’Carrol R, Shapiro C, Androgens BJ. Behavior and nocturnal erection in hypogonadial men: the effects of varying the replacement dose. Clin Endocrinol 1985; 23: 527-38.
Levin RJ. The mechanisms of human female sexual arousal. Annu Rev Sex Res 1992; 3: 1-14.
Meston CM. The psychophysiological assessment of female sexual function. J Sex Educ Ther 2000; 25: 6-16.
Meston CM, Gorzalka BB. The differential effects of sympathetic activation on sexual arousal in sexually functional and dysfunctional women. J Abnorm Psychol 1996; 105: 582-91.

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Year: 2019
Page: [146 - 157]
Pages: 12
DOI: 10.2174/1389450118666170622090337
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