Negative impact of PGAD/GPD
The consensus panel identified several contributors to the overall morbidity of this complex disorder, including end organ pathology, peripheral nerve, spinal cord and central sensory processing malfunction, and significant psychological issues. PGAD/GPD also may be associated with spinal cysts, cauda equina pathology, and withdrawal from selective serotonin reuptake inhibitors (SSRIs). Functional magnetic resonance imaging has identified specific brain regions (for example, the paracentral lobule) that are active during clitoral stimulation and that also activate during patients’ experience of persistent genital arousal.
PGAD/GPD negatively impacts sexual function, mental health, and ability to function in daily life. Of major importance is that a large proportion of people with this disorder have significant mental health disorders; in a survey, 54% of patients with PGAD reported suicidal ideation, compared with 25% of participants in a control group.
Evaluation and management recommendations
Diagnosis and management of PGAD/GPD are directed at the 5 areas of evaluation:
- end organ
- pelvis and perineum (assess for pelvic floor tension myalgia, pudendal neuropathy, pelvic congestion syndrome, or pelvic arteriovenous malformation)
- cauda equina (evaluate for neurologic deficits related to cysts compressing S2-S3 nerve roots)
- spinal cord (serotonin and norepinephrine pathways modulate nociceptive sensory activity; either SSRI/serotonin and norepinephrine reuptake inhibitor (SNRI) withdrawal or treatment could impact PGAD/ GPD based on their actions in the spinal cord)
- brain.
The consensus panel recommends an integrated biopsychosocial model for evaluation and treatment of PGAD/GPD. Comorbid mental health conditions, such as depression and anxiety, are common. Small studies suggest that a history of sexual trauma may contribute to catastrophizing and the experience of distressing persistent genital sensations, either arousal or dyesthesia, with 46.7% to 52.6% of patients reporting childhood sexual abuse.3
WHAT THIS EVIDENCE MEANS FOR PRACTICE
PGAD/GPD is a poorly recognized source of major distress to a small but significant group of patients. Diagnosis and management require a multidisciplinary team to identify end organ, pharmacologic, neurologic, vascular, and emotional components that contribute to the syndrome. Treatment requires a biopsychosocial approach that addresses the various sources of aberrant sensory processing, including end organ disease, neuropathic signaling, spinal cord pathways, and brain signal processing. Recognizing the existence of, and approaches to, this disorder will help gynecologists understand the considerable distress and potential life-threatening consequences our patients with PGAD/GPD experience.
Future possibilities and current actualities for patient care
Research dollars and investment in female sexual dysfunction remain inadequate to address the considerable gaps that exist in evidence-based clinical guidelines. ISSWSH is working to help clinicians approach these evidence gaps with guidelines and consensus statements to help women’s health professionals identify and manage our patients with sexual concerns and symptoms. An expert consensus guideline on the assessment and management of female orgasmic disorder is currently under development (personal communication, Dr. Sheryl Kingsberg). In addition, a phase 2b trial is underway to assess the impact of topical sildenafil cream for the treatment of female arousal disorder. Stay tuned for the results of these studies.
For now, women’s health professionals have 2 FDA-approved treatment options for premenopausal women with arousal disorder, flibanserin (a daily oral medication that requires abstinence from alcohol) and bremelanotide (an injectable medication that can be used just prior to a sexual encounter). For postmenopausal women, there are no FDA-approved therapies; however, based on the ISSWSH guideline summarized above, transdermal testosterone may be offered to postmenopausal women with distressing loss of sexual desire in doses approximately one-tenth those used to treat men with androgen deficiency. These small doses are challenging to achieve consistently with the delivery systems available for FDA-approved products sold for men.
The National Academies of Science, Engineering, and Medicine advise against the use of compounded hormonal products due to the potential for inconsistency and lack of FDA oversight in the manufacturing/compounding process. I have found and used some compounding pharmacies that are dedicated to safety, quality control, and compliance; test their products; and provide consistent, reliable compounded drugs for my patients. Consideration of compounded testosterone should be discussed with patients, and they should be informed of the current professional association guidelines. Testosterone creams may be compounded to a 1% product—20 mg/mL. Researchers in Australia have demonstrated that 5 mg of transdermal testosterone cream (one-quarter of a mL) results in typical premenopausal testosterone levels.4 When prescribing testosterone for postmenopausal women, check in with them after 6 weeks of treatment to assess impact and check blood levels to ensure that levels are not too high.
Testosterone pellets and intramuscular testosterone are not recommended and in fact should be actively avoided. These methods of administration are associated with extreme variation in hormone levels over time. There are typically supraphysiologic and quite high levels immediately after implantation or injection, followed by fairly significant drop-offs and rapid return of symptoms over time. This may lead to more and more frequent dosing and markedly elevated serum levels.
Management of PGAD/GPD is difficult, but knowing it exists as a valid syndrome will help clinicians validate patients’ symptoms and begin to approach appropriate evaluation and workup targeted to the 5 domains suggested by the ISSWSH expert panel. It is useful to understand the possible relationship to initiation or withdrawal from SSRIs or SNRIs and how aberrant norepinephrine signaling along the sensory pathways may contribute to genital dysesthesia or chronic sensations of arousal. Nonpharmacologic therapies, such as cognitive-behavioral therapy and others, are essential components of the multifaceted approach to treatment. Finally, many complex problems, such as chronic pelvic pain, vestibulodynia, vulvodynia, and chronic fatigue syndrome, are associated with childhood adverse experiences and sexual trauma. Approaching these patients with trauma-informed care is important to create the trust and therapeutic environment they need for successful multidisciplinary care. ●