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Persistent Genital Arousal Disorder—Fact or Fiction?
Persistent Genital Arousal Disorder—Fact or Fiction? James G. Pfaus, PhD, IF We have all seen tabloid headlines such as “Nurse Has 100 Orgasms a Day!”1 Many might ask, “What’s the problem? We should all be so lucky!” It is easy to laugh it off or relegate it to the lurid cesspool of media hype. However, for women who have this condition, including the nurse who made the news, the distended clitoral and labial engorgement is painful, obtrusive, and distressing and consumes much time in self-medication, from topical application of ice or lidocaine cream, to frequent masturbation to induce short-term relief in the form of orgasmmediated vasodilation . to suicide. Although priapism in men has long been considered a serious condition requiring immediate medical attention, it was not until 2001 that Leiblum and Nathan2 described persistent genital arousal disorder (PGAD) in women as a distressing condition that was not clitoral priapism or some form of hypersexual disorder. Five criteria were assigned for the condition: (i) involuntary genital and clitoral arousal that persists for an extended period (hours, days, or months); (ii) the physical genital arousal reappears, despite one or more orgasms; (iii) the genital arousal is unrelated to subjective feelings of sexual desire; (iv) the persistent feelings of genital arousal are intrusive and unwanted; and (v) there is distress associated with the persistence of the genital arousal. Those criteria have been reiterated in the consensus nomenclature of the International Society for the Study of Women’s Sexual Health (ISSWSH) taskforce on women’s sexual disorders3 and are included in the recommendations made by the Fourth International Consensus on Sexual Medicine4 and for the sexuality and gender identity workgroup of the International Classification of Diseases, Eleventh Revision.5 According to the current consensus, PGAD is a very real and growing sexual health concern. It is associated with feelings of persistent, spontaneous, intrusive, unrelenting, and unwanted genital arousal, with throbbing, pulsating, pounding, engorgement, and/or pressure or discomfort in the genital tissues, including the clitoris, labia, vagina perineum, and/or anus. It occurs in the absence of conscious thoughts of sexual desire or sexual interest and carries significant bother and distress. It is present throughout the person’s life, consistent with primary or lifelong PGAD, or develops at various ages, consistent with secondary or acquired PGAD. It is sometimes associated with Received December 31, 2016. Accepted January 3, 2017. Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, QC, Canada Copyright ª 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jsxm.2017.01.001
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spontaneous orgasms, feelings that orgasm is imminent, or feelings that orgasmic release is needed to decrease feelings of persistent engorgement. As noted, many women with PGAD report that orgasmic release through masturbation decreases symptoms, although engorgement typically returns minutes to hours later. To obtain the putative diagnosis, one must have these symptoms for a period of 6 months. Little is known about the pathophysiology of PGAD, although there are increasing clinical reports suggesting that it is associated with vascular, neurologic, pharmacologic, and/or hormonal etiologies. For example, arterial vascular causes can include pelvic arteriovenous malformations with unregulated arterial flow to the genitalia. Venous vascular causes might be secondary to pelvic congestion with ovarian venous incompetence. Central neurologic causes include the presence of Tourette syndrome, epilepsy, blunt trauma to the central nervous system, post-neurosurgical intervention of central arteriovenous malformations, or cervical and lumbosacral surgical interventions. Peripheral neurologic causes include pudendal nerve entrapment, hypersensitivity, or the presence of Tarlov cysts near the entry of one or all genital sensory nerves (pudendal, hypogastric, and pelvic) into the spinal cord. An overarching neuropathic syndrome also could be involved. Indeed, Waldinger et al6 reported comorbidity of PGAD in some women with restless leg syndrome and/or overactive bladder syndrome. Evidence of static mechanical hyperesthesia and neuropathy of the dorsal clitoral nerve also were found. Pharmacologic causes include the use of certain antidepressants, such as the serotonin receptor antagonist trazodone, or the sudden withdrawal of selective serotonin reuptake inhibitors. Hormonal causes are correlated with initiation and discontinuation of hormone replacement therapy in postmenopausal women or excess use of herbal estrogens in over-the-counter agents. Psychologically, PGAD can accompany stress, anxiety, or depression, and relaxation strategies are known to lower PGAD symptoms temporarily.3 As with priapism, knowledge of the etiology for PGAD comes from case reports or studies with small patient populations. Because of this, a hierarchy of potential causes to rule out has not been established empirically. Obviously, there are no approved treatments for a disorder that has not been classified or coded in the Diagnostic and Statistical Manual of Mental Disorders or the International Classification of Diseases. However, serendipitous long-term amelioration with off-label medications, such as the partial nicotinic receptor agonist verenicline7 and the g-aminobutyric acid potentiator zolpidem,8 has helped refine a neurochemical model of hypothalamic control over the autonomic systems that regulate genital blood flow.9,10 In particular, dopamine in J Sex Med 2017;14:318e319
319
Persistent Genital Arousal Disorder—Fact or Fiction?
the medial preoptic area plays a key role in the integration of sexual arousal and desire as the body prepares itself for sexual interaction.9,10 Dopamine transmission in this area is driven by genital nerve stimulation and other sex-related cues and might be hyperfunctional in response to more continuous genital nerve irritation or in response to certain pharmacologic treatments. It also might be dysregulated in vascular or endocrine disorders. Varenicline and zolpidem are hypothesized to decrease the hyperstimulation of dopamine in the medial preoptic area, leading to a decrease in genital blood flow. Tarlov cysts and several other anatomic pathologies that induce neuropathy or vascular occlusion (discussed earlier) can be treated surgically, if diagnosed properly. How prevalent is PGAD? No epidemiologic studies have been published to date, although more and more clinicians are describing patients with PGAD symptoms. What are the best treatments? That will depend on a logical diagnostic procedure that rules out a hierarchy of potential causes once such a hierarchy can be established. What is clear is that PGAD should no longer be misdiagnosed as hypersexuality, “sex addiction,” or anything else that suggests women enjoy the symptoms or their attempts at self-management. Some might. Most definitely do not. The ISSWSH consensus has laid the foundation for PGAD to become a full-fledged diagnostic classification, transforming it from an empirical “fiction” to a diagnosable fact.
Corresponding Author: James G. Pfaus, PhD, IF, Department of Psychology, Concordia University, 7141 Sherbrooke W, Montreal, QC H4B 1R6, Canada; E-mail: [email protected] Conflicts of Interest: J.P. is on the Scientific Advisory Board and serves as a consultant at Acadia Pharmaceuticals, Emotional Brain LLB, and Palatin Technologies. Funding: J.P. has received funding from Canadian Institutes for Health Research (CIHR), Fonds de la recherche en santé du Québec (FRSQ), and the Natural Sciences and Engineering Research Council (NSERC).
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design James G. Pfaus (b) Acquisition of Data James G. Pfaus (c) Analysis and Interpretation of Data James G. Pfaus
J Sex Med 2017;14:318e319
Category 2 (a) Drafting the Article James G. Pfaus (b) Revising It for Intellectual Content James G. Pfaus Category 3 (a) Final Approval of the Completed Article James G. Pfaus
REFERENCES 1. Mills J. Nurse has 100 orgasms a day. The Sun August 26, 2012. Available at: https://www.thesun.co.uk/archives/ news/868330/nurse-has-100-orgasms-a-day/#ixzz24rmgGcek. Accessed February 27, 2016. 2. Leiblum SR, Nathan SG. Persistent sexual arousal syndrome: a newly discovered pattern of female sexuality. J Sex Marital Ther 2001;27:365-380. 3. Parish SJ, Goldstein AT, Goldstein SW, et al. Toward a more evidence-based nosology and nomenclature for female sexual dysfunctions—part II. J Sex Med 2016;13:1888-1906. 4. McCabe MP, Sharlip ID, Atalla E, et al. Definitions of sexual dysfunctions in women and men: a consensus statement from the Fourth Consultation on Sexual Medicine 2015. J Sex Med 2016;13:135-143. 5. Reed GM, Drescher J, Krueger RB, et al. Disorders related to sexuality and gender identity in the ICD-11: revising the ICD-10 classification based on current scientific evidence, best clinical practices, and human rights considerations. World Psychiatry 2016;15:205-221. 6. Waldinger MD, Venema PL, van Gils APG, et al. New insights into restless genital syndrome: static mechanical hyperesthesia and neuropathy of the nervous dorsalis clitoridis. J Sex Med 2009;6:2778-2787. 7. Korda JB, Pfaus JG, Goldstein I. Persistent genital arousal disorder: a case report in a woman with lifelong PGAD where serendipitous administration of varenicline tartrate resulted in symptomatic improvement. J Sex Med 2009;6:1479-1486. 8. King SA, Goldstein I, Pfaus JG. Mechanism of action and preliminary clinical experience with zolpidem, a non-benzodiazepine indirect GABA A receptor agonist, for symptomatic treatment of persistent genital arousal disorder (PGAD). Paper presented at: Annual Meeting of the International Society for the Study of Women’s Sexual Health. 2016; Charleston, SC. 9. 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 2017;92:114-128. 10. Pfaus JG. Pathways of sexual desire. J Sex Med 2009; 6:1506-1533.
318
spontaneous orgasms, feelings that orgasm is imminent, or feelings that orgasmic release is needed to decrease feelings of persistent engorgement. As noted, many women with PGAD report that orgasmic release through masturbation decreases symptoms, although engorgement typically returns minutes to hours later. To obtain the putative diagnosis, one must have these symptoms for a period of 6 months. Little is known about the pathophysiology of PGAD, although there are increasing clinical reports suggesting that it is associated with vascular, neurologic, pharmacologic, and/or hormonal etiologies. For example, arterial vascular causes can include pelvic arteriovenous malformations with unregulated arterial flow to the genitalia. Venous vascular causes might be secondary to pelvic congestion with ovarian venous incompetence. Central neurologic causes include the presence of Tourette syndrome, epilepsy, blunt trauma to the central nervous system, post-neurosurgical intervention of central arteriovenous malformations, or cervical and lumbosacral surgical interventions. Peripheral neurologic causes include pudendal nerve entrapment, hypersensitivity, or the presence of Tarlov cysts near the entry of one or all genital sensory nerves (pudendal, hypogastric, and pelvic) into the spinal cord. An overarching neuropathic syndrome also could be involved. Indeed, Waldinger et al6 reported comorbidity of PGAD in some women with restless leg syndrome and/or overactive bladder syndrome. Evidence of static mechanical hyperesthesia and neuropathy of the dorsal clitoral nerve also were found. Pharmacologic causes include the use of certain antidepressants, such as the serotonin receptor antagonist trazodone, or the sudden withdrawal of selective serotonin reuptake inhibitors. Hormonal causes are correlated with initiation and discontinuation of hormone replacement therapy in postmenopausal women or excess use of herbal estrogens in over-the-counter agents. Psychologically, PGAD can accompany stress, anxiety, or depression, and relaxation strategies are known to lower PGAD symptoms temporarily.3 As with priapism, knowledge of the etiology for PGAD comes from case reports or studies with small patient populations. Because of this, a hierarchy of potential causes to rule out has not been established empirically. Obviously, there are no approved treatments for a disorder that has not been classified or coded in the Diagnostic and Statistical Manual of Mental Disorders or the International Classification of Diseases. However, serendipitous long-term amelioration with off-label medications, such as the partial nicotinic receptor agonist verenicline7 and the g-aminobutyric acid potentiator zolpidem,8 has helped refine a neurochemical model of hypothalamic control over the autonomic systems that regulate genital blood flow.9,10 In particular, dopamine in J Sex Med 2017;14:318e319
319
Persistent Genital Arousal Disorder—Fact or Fiction?
the medial preoptic area plays a key role in the integration of sexual arousal and desire as the body prepares itself for sexual interaction.9,10 Dopamine transmission in this area is driven by genital nerve stimulation and other sex-related cues and might be hyperfunctional in response to more continuous genital nerve irritation or in response to certain pharmacologic treatments. It also might be dysregulated in vascular or endocrine disorders. Varenicline and zolpidem are hypothesized to decrease the hyperstimulation of dopamine in the medial preoptic area, leading to a decrease in genital blood flow. Tarlov cysts and several other anatomic pathologies that induce neuropathy or vascular occlusion (discussed earlier) can be treated surgically, if diagnosed properly. How prevalent is PGAD? No epidemiologic studies have been published to date, although more and more clinicians are describing patients with PGAD symptoms. What are the best treatments? That will depend on a logical diagnostic procedure that rules out a hierarchy of potential causes once such a hierarchy can be established. What is clear is that PGAD should no longer be misdiagnosed as hypersexuality, “sex addiction,” or anything else that suggests women enjoy the symptoms or their attempts at self-management. Some might. Most definitely do not. The ISSWSH consensus has laid the foundation for PGAD to become a full-fledged diagnostic classification, transforming it from an empirical “fiction” to a diagnosable fact.
Corresponding Author: James G. Pfaus, PhD, IF, Department of Psychology, Concordia University, 7141 Sherbrooke W, Montreal, QC H4B 1R6, Canada; E-mail: [email protected] Conflicts of Interest: J.P. is on the Scientific Advisory Board and serves as a consultant at Acadia Pharmaceuticals, Emotional Brain LLB, and Palatin Technologies. Funding: J.P. has received funding from Canadian Institutes for Health Research (CIHR), Fonds de la recherche en santé du Québec (FRSQ), and the Natural Sciences and Engineering Research Council (NSERC).
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design James G. Pfaus (b) Acquisition of Data James G. Pfaus (c) Analysis and Interpretation of Data James G. Pfaus
J Sex Med 2017;14:318e319
Category 2 (a) Drafting the Article James G. Pfaus (b) Revising It for Intellectual Content James G. Pfaus Category 3 (a) Final Approval of the Completed Article James G. Pfaus
REFERENCES 1. Mills J. Nurse has 100 orgasms a day. The Sun August 26, 2012. Available at: https://www.thesun.co.uk/archives/ news/868330/nurse-has-100-orgasms-a-day/#ixzz24rmgGcek. Accessed February 27, 2016. 2. Leiblum SR, Nathan SG. Persistent sexual arousal syndrome: a newly discovered pattern of female sexuality. J Sex Marital Ther 2001;27:365-380. 3. Parish SJ, Goldstein AT, Goldstein SW, et al. Toward a more evidence-based nosology and nomenclature for female sexual dysfunctions—part II. J Sex Med 2016;13:1888-1906. 4. McCabe MP, Sharlip ID, Atalla E, et al. Definitions of sexual dysfunctions in women and men: a consensus statement from the Fourth Consultation on Sexual Medicine 2015. J Sex Med 2016;13:135-143. 5. Reed GM, Drescher J, Krueger RB, et al. Disorders related to sexuality and gender identity in the ICD-11: revising the ICD-10 classification based on current scientific evidence, best clinical practices, and human rights considerations. World Psychiatry 2016;15:205-221. 6. Waldinger MD, Venema PL, van Gils APG, et al. New insights into restless genital syndrome: static mechanical hyperesthesia and neuropathy of the nervous dorsalis clitoridis. J Sex Med 2009;6:2778-2787. 7. Korda JB, Pfaus JG, Goldstein I. Persistent genital arousal disorder: a case report in a woman with lifelong PGAD where serendipitous administration of varenicline tartrate resulted in symptomatic improvement. J Sex Med 2009;6:1479-1486. 8. King SA, Goldstein I, Pfaus JG. Mechanism of action and preliminary clinical experience with zolpidem, a non-benzodiazepine indirect GABA A receptor agonist, for symptomatic treatment of persistent genital arousal disorder (PGAD). Paper presented at: Annual Meeting of the International Society for the Study of Women’s Sexual Health. 2016; Charleston, SC. 9. 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 2017;92:114-128. 10. Pfaus JG. Pathways of sexual desire. J Sex Med 2009; 6:1506-1533.