XIII Congreso Español de Sexología y VII Encuentro Iberoamericano de Profesionales de la Sexología.

1. FEMALE SEXUAL DYSFUNCTIONS,
HYPOACTIVE SEXUAL DESIRE DISORDER
AND FLIBANSERIN: AN OVERVIEW
Catarina da Costa Campos1, Maria do Céu Ferreira1, Joana Mesquita Machado1
1 Department of Psychiatry and Mental Health - Hospital de Braga, Portugal
Male and female sexual disorders are very prevalent in the population: a study made in United States in which a sample of 1749 women and 1410 men aged 18
to 59 years was used demonstrated that 31% of men and 43% of women presented some form of sexual dysfunction1
1- Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA. 1999 Feb 10;281(6):537-44 2-American Psychiatric Association: DSM-IV: Diagnostic and Statistical Manual of Mental Disorders (4th Edition). Text revision. American Psychiatric Press, Washington, DC, USA (2000) 3- American Psychiatric Association: DSM-5: Diagnostic and Statistical Manual for Mental Disorders. 5th edition. American Psychiatric Press, USA (2013) 4- Hayes RD, Bennett CM, Fairley CK, Dennerstein
L. What can prevalence studies tell us about female sexual difficulty and dysfunction? J Sex Med. 2006 Jul; 3(4):589-95 5- Barros, F., Meirinha A., Baltazar P. Disfunção sexual feminina – Prevalência, etiologia, diagnóstico e tratamento médico. In: Manual de medicina sexual: visão multidisciplinar. Barros F., Figueiredo R. coord. HSJ Consultores. Portugal, 2014. 6- Clayton AH. The pathophysiology of hypoactive sexual desire disorder in women. Int J Gynaecol Obstet. 2010 Jul;110(1):7-11 7- Brotto LA. Flibanserin. Arch
Sex Behav. 2015 Nov;44(8):2103-5 8- Borsini, F., Giraldo, E., Monferini, E., Antonini, G., Parenti, M., Bietti, G., et al. BIMT 17, a 5-HT2A receptor antagonist and 5-HT1A receptor full agonist in rat cerebral cortex. Naunyn-Schmiedeberg's Arch. Pharmacol. 1995; 352:276-82 9- Boehringer Ingelheim Briefing Information, Flibanserin, for the June 18, 2010 Meeting of the Advisory Committee for Reproductive Health Drugs. Available from:
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/ucm215436.htm. [Accessed 30th September 2016] 10- Nappi RE, Albani F. Sexual dysfunction in 2015: Recovering sex drive in women - progress and opportunities. Nat Rev Urol. 2016; 13:67-8 11- Dhanuka I, Simon JA. Flibanserin for the treatment of hypoactive sexual desire disorder in premenopausal women. Expert Opin Pharmacother. 2015; 16:2523-9 12- Meixel A, Yanchar E, Fugh-Berman
A. Hypoactive sexual desire disorder: inventing a disease to sell low libido. J Med Ethics. 2015; 41:859-62 13- Fugh-Berman A. Advise Against Flibanserin. Am J Nurs. 2016; 116:13 14- Joffe HV, Chang C, Sewell C, Easley O, Nguyen C, Dunn S, et al. FDA Approval of Flibanserin - Treating Hypoactive Sexual Desire Disorder. N Engl J Med. 2016; 374:101-4 15- Woloshin S, Schwartz LM. US Food and Drug Administration Approval of Flibanserin: Even the Score Does Not Add Up. JAMA Intern Med. 2016; 176:439-42 16- Nappi RE,
Martini E, Terreno E, Albani F, Santamaria V, Tonani S, et al. Management of hypoactive sexual desire disorder in women: current and emerging therapies. Int J Womens Health. 2010; 2:167-75 17- OSPHENA (ospemifene): highlights of prescribing information. 2015. Available from: http://www.shionogi.com/pdf/pi/osphena.pdf?100898276. [Accessed 30th September 2016] 18- PREMARIN (conjugated estrogens) Vaginal Cream: highlights of prescribing information. 2012. Available from:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020216s073s074s075lbl.pdf. [Accessed 30th September 2016] 19- Clayton AH, Dennerstein L, Pyke R, Sand M. Flibanserin: a potential treatment for Hypoactive Sexual Desire Disorder in premenopausal women. Womens Health (Lond). 2010; 6:639-53.
DSM-IV-TR DSM-5
Female sexual dysfunctions
• Hypoactive Sexual Desire Disorder * Merged into “Female Sexual Interest/Arousal
Disorder”• Female Arousal Disorder
• Female Orgasmic Disorder Unchanged
• Dyspareunia Merged into “Genito-Pelvic Pain/Penetration
Disorder”• Vaginismus
Other sexual dysfunctions (both ♀ and ♂)
• Sexual Aversion Disorder Excluded
• Sexual Dysfunction Due to a General
Medical Condition
Excluded
• Substance/Medication-induced Sexual
Dysfunction
Unchanged
Classification of Female Sexual Dysfunctions
* Hypoactive sexual desire disorder (HSDD) is the most
common form of female sexual dysfunction, especially
among pre-menopausal women, emerging between
32 to 58% of the female sexual disorder cases.
It is estimated that HSDD occurs in approximately 1 in
10 adult women in the USA and its prevalence appears
to be similar in Europe.
Hypoactive Sexual Desire Disorder - according to DSM-IV-TR
 The essential feature of HSDD is a deficiency or absence of sexual fantasies and desire for sexual activity (Criterion A).
 The disturbance must cause marked distress or interpersonal difficulty (Criterion B).
 The dysfunction is not better accounted for by another Axis I disorder (except another sexual dysfunction) and is not due exclusively to the direct
physiological effects of a substance (including medications) or a general medical condition (Criterion C).
Pathophysiology of Hypoactive Sexual Desire Disorder
Sexual desire seems to be controlled by an equilibrium of inhibitory and excitatory components in the brain, where hormonal, neurobiological and
psychological factors take action.
Dopamine
Testosterone
Progesterone
Estrogen
Serotonin
Endogenous opioids
Prolactin
Excitatory
role
Inhibit-
ory role
Sexual
desire
The low sexual desire observed on HSDD is due to an imbalance that may be caused by a reduced level of excitatory activity, an increased level of inhibition,
or both. This asymmetry can disrupt the sexual response at any point during the sexual response cycle.
HSDD is actually the unique female sexual disorder to have a drug approved by US Food and Drug Administration (FDA) for its treatment in premenopausal
woman: flibanserin. It is a 5-HT1A post-synaptic receptor full agonist and a 5-HT2A receptor antagonist that was initially studied as an antidepressant drug.
Flibanserin failed to show consistent antidepressant efficacy, but proved to be useful for the treatment of acquired, generalized HSDD in premenopausal women
for which it was approved by FDA on 18 August 2015. However some experts show some scepticism with respect not only to flibanserin, but also HSDD itself: while
some recognize flibanserin as the current best pharmacological treatment for the disorder since it provides a safe treatment, that may reduce the adverse side
effects due to improper use of “off label” drugs, others defend that HSDD is an example of a disorder that was sponsored by industry to prepare the market for a
specific treatment and still defend that flibanserin´s benefit-risk profile is unfavourable. There are no other drugs approved to treat HSDD and literature reported
that HSDD is generally refractory to psychotherapeutic interventions, however some benefits were found in cognitive behavioral approaches. Besides HSDD, only
postmenopausal women who suffer from dyspareunia can count on a drug approved by the FDA for the treatment of their sexual dysfunction.
 In spite of the big impact of the HSDD in couples’ lives, this disorder remains underrecognized, underdiagnosed and undertreated. There is an obvious medical
need of therapeutic options in sexual dysfunction. Since there are still a lot of concerns regarding the current pharmacological options, it is important to
critically listen all expert´s impressions in order to form an informed opinion. For those who choose to use flibanserin it is vital to follow the prescribing guidelines,
since this drug is very recent on the market, and be attentive to the post-market experience concerning both its safety and efficacy.
 There is also a long path to be covered in what concerns our knowledge on the great complexity of sexuality and sexual dysfunctions, and further research is
needed in order to better understand all the variables that may take a role in the development of this group of diseases. As the secrets of sexual dysfunction
are disclosed, we will have more scientific bases to the development of both pharmacological and non-pharmacological treatments that meet women´s
needs and expectations.
Hypoactive Sexual Desire Disorder and Flibanserin
Conclusions
Psychosocial variables:
 Emotional and physical distress
 Sexual and relationship satisfaction
and expectations
 Past sexual experiences
 Current mental health
 Emotional well-being
 Self-image
 Aging
 Perimenopause/menopause
 Comorbidities
 Medications