Persistent genital arousal disorder (PGAD), formerly known as persistent sexual arousal syndrome (PSAS), is an uncommonly reported sexual health concern associated with feelings of persistent, spontaneous, intrusive, unrelenting, and unwanted physical arousal such as throbbing, pulsating, pounding, engorgement and/or pressure/discomfort in the genital tissues, including the clitoris, labia, vagina perineum and/or anus; occurring in the absence of conscious thoughts of sexual desire or sexual interest; often associated with significant bother and distress; present throughout the person’s life, consistent with primary, lifelong PGAD or developed at various ages, consistent with secondary, acquired PGAD; associated with spontaneous orgasms or feelings that orgasm is imminent or feelings that orgasmic release is needed to reduce the feelings of persistent arousal; and where symptoms are not consistently diminished by achieving orgasmic release.
Little is known about the vascular, neurologic, pharmacologic, and/or hormonal biologic-related pathophysiologies of PGAD. As it concerns central neuro-pharmacologic causes, PGAD may be secondary to Tourette’s Syndrome, epilepsy, post-blunt CNS trauma, post-neurosurgical intervention of central arteriovenous malformation, to cervical and lumbosacral surgical interventions, to use of certain antidepressants, such as the serotonin receptor antagonist trazodone, or to secondary to sudden withdrawal of selective serotonin re-uptake inhibitors (SSRIs) as occurs in sudden SSRI discontinuation syndrome.There has been a report of varenicline tartrate used in a woman with primary lifelong PGAD who serendipitously was prescribed the drug for smoking cessation. In this woman varenicline treatment was observed to reduce unwanted arousal symptoms. She went through a cycle of starting treatment and encountering symptom relief and stopping treatment and experiencing symptom return which was repeated on several occasions.
Varenicline is a partial agonist at the α4ß2 nicotinic receptor subtype that decreases the ability of nicotine to stimulate the release of dopamine in a specific (mesolimbic) region of the brain. Central nervous system dopamine transmission is critical for the stimulation and maintenance of sexual arousal. Stimulation of dopamine receptors in certain critical areas of the brain (the hypothalamus and the limbic system) controls downward motor autonomic outflow to the genital region that can activate sexual reflexes in females. For example, treatment of women with a dopamine receptor agonist, apomorphine, has been shown to result in increased cavernosal artery peak systolic velocity values and clitoral engorgement. In the woman with primary lifelong PGAD whose symptoms of PGAD were alleviated by varenicline use, it was hypothesized that her PGAD was the result of hyperstimulated central nervous system dopamine release. It was further hypothesized that restoration of more normative sexual arousal was the result of varenicline-associated lowering of this hyperstimulated central nervous system dopamine release. Varenicline does not block dopamine release completely in response to external stimulation, and as such, varenicline treatment would be superior to the use of dopamine antagonists or selective serotonin reuptake inhibitors which would have a similar inhibitory action on dopamine release but with a high potential for untoward sexual side-effects such as anorgasmia or decreased sexual desire.
More research is needed with varenicline as a treatment for women who suffer from PGAD. Pharmacologic regulation of central nervous system monoamine neurotransmitters may represent a novel approach to management in some women who experience significant distress from PGAD and who currently have no known safe and effective pharmacologic strategies.