Persistent genital arousal disorder (PGAD) characterized by recurrent and spontaneous orgasmic experience: a case report

Introduction

Persistent genital arousal disorder (PGAD) is a clinical condition that is currently not fully understood. Affected individuals experience persistent genital arousal symptoms without sexual desire, which seriously affects their daily life and work, and even leads to suicidal ideation in some patients (1-4). Since the disease was first described in 2001 (5), reports about this disorder are being presented by different fields of clinicians from all over the world (6,7). Until 2019, the International Society for the Study of Women’s Sexual Health (ISSWSH) issued the first expert consensus on the diagnosis and treatment of PGAD (4) and renamed it as PGAD/genito-pelvic dysesthesia (PGAD/GPD). Emphasize the disturbing arousal symptoms while acknowledging the associated sensory abnormalities involving the reproductive organs-pelvic region. There are differences in symptoms among different cases. However, the characteristic of consistent recommendations is the persistent or recurrent, unwanted or invasive, annoying genital arousal sensation, which may also include other types of sensations such as twitching, itching, pain, etc. These feelings may be accompanied by an uncontrollable orgasmic experience and/or an excessive number of orgasms. These feelings are not related to the subsequent sexual interest, thoughts, or fantasies. By reviewing previous cases, it can also be observed that some cases primarily manifest as repeated orgasmic experiences (5,8). Epidemiological study has found that a considerable portion of people are troubled by this disease, with approximately 0.6–3% of the population exhibiting symptoms (4).

The etiology of PGAD is still unclear and complex. It may be the end result of various different psychological and/or physiological conditions (2). At the same time, comprehensive treatment is also advocated in treatment (1). Physiologically, it may be related to the Tarlov cysts (4), disc impingements, annular tears, facet cysts and spinal stenosis (9). Women with pudendal neuropathy may also experience symptoms of PGAD (4). Some epilepsy patients also show similar symptoms (10,11). Some case reports have linked PGAD to the initiation or cessation of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin-norepinephrine reuptake inhibitors (SNRIs) (1,12). Some cases also seem to be related to the use of trazodone, amitriptyline, pramipexole, and lamotrigine. Psychologically, anxiety and stress seem to make PGAD worse (4). The human sexual response (in relation to arousal) involves complex interactions between many neurotransmitters, particularly the dopamine system which plays an important role in promoting sexual arousal (13). Therefore, some researchers have proposed that dopaminergic imbalance may be related to PGAD (14).

The case reported in this article conforms to the general characteristics of PGAD, where sexual arousal symptoms are characterized by repeated, spontaneous orgasmic experiences that cause distress and severely affect the patient’s daily life and social functioning. But this case has its own uniqueness. The patient had a history of epilepsy in the early years, and after detailed investigation, the possibility of epileptic seizures has been ruled out. The patient also presents with other psychotic symptoms secondary to sexual arousal symptoms. After systematic antipsychotic drug treatment (mainly with sufficient dopamine receptor blocking effects), the patient’s symptoms were fully controlled. Through the presentation of this case, we hope to provide a treatment idea for a type of PGAD symptom, including the treatment of sensory abnormalities that may involve the central nervous system. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-286/rc).

Case presentation

The patient is a 20-year-old young unmarried woman. At the age of 12 years, she had a history of epilepsy, manifested as episodic loss of consciousness without convulsions, falls, incontinence, etc. In severe cases, she experienced 2–3 seizures per day, each lasting about 10 minutes. Electroencephalogram (EEG) showed epileptic waves, confirming epilepsy and taking levetiracetam regularly for 6 years. She stopped taking the medication under medical advice. No similar symptoms have occurred since then. At the age of 14 years, she gradually showed signs of sensitivity and suspicion, such as suspecting that others had special eyesight, even thinking that others knew her thoughts, and feeling depressed about it, gradually being unable to continue her studies. At the age of 15 years, she was hospitalized for the first time in a psychiatric department and was treated with sertraline in combination with low-dose aripiprazole. She soon experiences a sensation of electricity passing from the lower abdomen to the upper abdomen, accompanied by contractions of the uterus or pelvic muscles (similar to an orgasmic experience). She experienced intermittent seizures several times a day, lasting for several seconds and then resolving. She was unable to control the seizures, and multiple EEG examinations did not detect epileptic waves. This symptom persists until the age of 18 years, and she begins to believe that the experience of orgasm is caused by someone else’s manipulation. The use of 4mg of risperidone per day has improved the symptoms of seizures and delusions, and her social function has also been restored. After a period of medication adjustment (specifically unable to recall due to feeling a decrease in memory), her symptoms began to worsen and she was unable to continue working. She took magnesium valproate, amisulpride, aripiprazole, and escitalopram without improvement. She had a harmonious family since childhood and had excellent academic performance before the onset of the disease. She denied having a family history or a history of sexual abuse. She had a brief romantic history in adulthood, but denied having sexual experience.

During her initial visit to our hospital, she experienced significant and frequent seizures, leading to the interruption of the interview. We observed her continuous spontaneous and uncontrollable orgasm episodes, during which she was conscious. She was troubled by this and thought that people around her were manipulating her seizures. During the hospitalization, we first considered the need to rule out the possibility of epilepsy. A 3-hour EEG was performed during the seizure period, and no epileptic waves were detected. The use or withdrawal of anti-epileptic treatment (sodium valproate and clonazepam) had no significant effect on the occurrence of seizures. We requested a consultation with neurologists to rule out seizures (based on symptom presentation and EEG examination). No abnormalities were found in the cranial magnetic resonance imaging (MRI), transrectal ultrasound of the uterus and adnexa, and sleep EEG monitoring (used to exclude seizures caused by structural abnormalities of the nervous system and pelvic cavity, as well as abnormal brain electrical activity during sleep). The initial dose of risperidone (1 mg per day) quickly controlled the symptoms, reducing the number and severity of seizures, while improving delusions. After 5 weeks of treatment, the dosage of risperidone was increased to 6 mg per day, and the symptoms were largely controlled, with only occasional subtle seizures in crowded public places. She denied that the seizures were related to sexual desire. Apart from the experience of orgasm, there are no symptoms of arousal in other reproductive organs, such as swelling, pain, or increased sensitivity. The seizures are not under herself control, and the seizures in public places during the day make her feel embarrassed, so she cannot go to school or work. After taking 6 mg per day of risperidone for one month, the experience of orgasm was significantly alleviated, but some residual delusional symptoms remained, so olanzapine was added for treatment. When olanzapine 10 mg is taken daily, the patient’s orgasmic experience and delusions are fully controlled, with almost no symptoms present, and the drug tolerance is good. After two weeks of stable drug dosage, the monitored blood drug concentration was as follows: 41.35 ng/mL (20–60 ng/mL) for nine hydroxypiperidone, 4.62 ng/mL for risperidone, and 27.95 ng/mL (20–80 ng/mL) for olanzapine. During the treatment process, the level of prolactin once increased and then decreased (when the initial treatment was effective, the prolactin level was 326 µIU/mL. With the increase in risperidone dosage, the prolactin level peaked at 4,129 µIU/mL. After combined treatment with olanzapine, the prolactin level decreased to 1,913 µIU/mL), and the patient’s symptoms of orgasmic onset continued to improve without corresponding fluctuations (during this period, the patient’s cycle remained regular). The patient’s sexual attitudes are relatively conservative, and combining psychological treatment (eliminating sexual shame and normalizing sexual desire) during hospitalization has good results.

The patient received regular outpatient treatment and the condition was basically stable. Her orgasmic symptoms have been continuously controlled, with occasional sensitive and suspicious situations. After several months, she believed that the symptoms had disappeared and stopped taking the medication on her own. One week after discontinuing the medication, symptoms reappeared, but rapidly improved within one month after resuming treatment. She denied obvious drug side effects and adverse events. Her work situation and interpersonal communication have steadily improved, but she still feels confused about the situation of being suspicious. It is recommended that the patient receive psychological intervention in the future.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

The case reported in this article has the general characteristics of PGAD, but it is characterized by repeated, uncontrollable, and invasive orgasmic experiences that are unrelated to sexual desire, leading to subjective distress and inability to study or work normally for years. Concurrently, there is a secondary delusion associated with the experience of orgasm. Although this case has a history of epilepsy, careful history inquiry and relevant examinations ruled out the possibility of seizures caused by epilepsy. The patient’s symptoms were fully controlled with antipsychotic treatment, and the treatment was clearly effective.

Reports of orgasmic seizures are rare and appear to predominate in women. Some researchers suggested that uncontrollable orgasmic seizures might be a rare manifestation of epilepsy, especially temporal lobe epilepsy (11). Some studies suggest that persistent sexual arousal may not be related to epilepsy, while other sexual manifestations, such as genital or sexual automatism, genital sensations, or sexual aura, may be symptoms of complex partial seizures (10,15-17). Otherwise, epileptic seizures also could be coexisted with PGAD symptoms, which is manifested as two different symptoms: an ictal acute sensation and a background persistent feeling (10). However, regardless of the forms of epileptic seizure, they all have the basic symptom characteristics, and therefore could be captured by EEG, showing clear epileptic waves. Sexual arousal that appears on the basis of the epileptic symptoms may participate as a trigger, a consequence, or as part of the symptoms of an epileptic seizure and, thereby, could be consequently alleviated in antiepileptic treatment. In this case, there was only a single form of orgasmic symptom, which appeared as repeated electric currents and pelvic muscle spasms that lasted for several seconds each time. The patient stayed conscious when orgasmic symptoms occurred, and the symptom could last from tens of minutes to hours. No epileptic waves were detected during the ictal and interictal periods. While antiepileptic drugs did not reduce the symptom, antipsychotic medications, which may induce epilepsy, successfully alleviated the symptom. Therefore, we temporarily eliminated the possibility of orgasmic epilepsy.

Researchers have suggested that one potential cause of PGAD may be hyperactive dopamine release (18). At least two dopamine systems in the brain are known to control sexual arousal and desire. The medial preoptic area (MPOA) located at the head of the hypothalamus is important for regulating male sexual behavior. The results showed that male sexual behavior was impaired after MPOA injury and enhanced under MPOA stimulation, which supported this conclusion (19). The mesolimbic dopamine system originates in the ventral tegmental area of the midbrain and extends to the limbic system, including the nucleus accumbens (nACC). During sexual arousal in female rats, dopamine increases in the nACC and MPOA (20,21), and the release of dopamine in the nACC and MPOA is crucial for the expression of sexual behavior and normal mating patterns in rats. Consistent with this hypothesis, the dopamine agonist apomorphine appears to produce more subjective and objective changes in the sexual arousal phase of women with orgasmic sexual dysfunction than placebo, which may increase the peak systolic velocity of clitoral engorgement (22). A bursting patterned response was observed in the sympathetic uterine nerves of anesthetized female rats treated with the dopamine receptor agonists, apomorphine and piribedil. These results suggest that activation of dopamine D2-like receptors on supraspinal neurons can lead to excitation of the intraspinal neuronal network that controls orgasm (23). In contrast, risperidone, as a dopamine receptor antagonist, could decrease genital engorgement in postmenopausal women with persistent genital arousal during the night (24). The use of paliperidone also has a therapeutic effect in PGAD, and symptoms worsen after discontinuing paliperidone (25). In other cases, the subchronic treatment of Pramipexole both reduced the phasic dopamine release in the mesolimbic terminals (such as the nucleus accumbens) and reduced the discharge of dopamine cells by 40% (9). The net effect of varenicline is to reduce this overstimulated central dopamine release by acting on cholinergic receptors (18). In both cases, the disruption of phasic dopamine cell firing and release may reduce or eliminate the sensation of PGAD.

The treatment in this case effectively supports this hypothesis, suggesting that excessive activity in the dopamine system may be associated with PGAD symptoms and trigger other psychotic symptoms such as delusions. Adequate antipsychotic treatment can effectively control PGAD symptoms and psychotic symptoms. In this case, the initial treatment with risperidone was effective. In addition to their strong dopamine receptor blocking effects, risperidone (including olanzapine used later) also has a strong 5-hydroxytryptamine receptor 2 (5-HT2) antagonistic effect. Previous study has shown that the antagonistic effect of 5-HT2 receptors can lead to an increase in orgasm, which may be due to its promotion of dopamine release in the cortex (26). This is considered to be contrary to the therapeutic effect in this case. It is speculated that the efficacy of risperidone and olanzapine in this case is mainly related to the blockade of dopamine receptors, especially D2 receptors. In addition, a previous study has suggested that acute and chronic increases in prolactin may affect sexual function (27). In this case, the symptoms were alleviated when treated with low-dose risperidone (with normal prolactin levels). During the treatment process, there were significant fluctuations in prolactin levels, but the patient’s symptoms of orgasmic onset continued to improve without corresponding fluctuations. Therefore, we believe that the improvement of orgasmic symptoms is not caused by the influence of prolactin. The case reported in this article exhibits the general characteristics of PGAD. The persistent genital arousal symptoms primarily manifest as recurrent, uncontrollable, and intrusive orgasmic experiences, without any significant other symptoms involving the genital organs, such as swelling, pain, increased sensitivity or other sensory abnormalities (1). This is the unique aspect of this case. Based on this analysis, the disorder may primarily involve sensory abnormalities in the central nervous system, and it also suggests that antipsychotic drugs may be one of the treatment options for such symptoms (or those accompanied by such symptoms).

Conclusions

PGAD is a group of syndromes that have only recently been proposed and described, thus the comprehension of PGAD is still progressing. Based on the nature of the symptoms and the patient’s subjective experience, this case meets all the diagnostic criteria for PGAD. The patient’s symptoms were completely controlled through adequate treatment with antipsychotic drugs. This suggests that the dopamine system may play an important role in pathological processes involving sensory abnormalities, and the treatment with antipsychotic drugs may be one of the treatment directions.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-286/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-286/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-286/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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