Clitoral Priapism in a Transgender Male.

INTRODUCTION: Clitoral priapism due to venous outflow obstruction is a rare event and medical emergency. Androgen-induced clitoromegaly in transgender men has not been previously identified as a risk factor. AIMS: Advance current knowledge on identification and treatment of clitoral priapism in the transgender male.
METHODS: A 32 year-old presurgical transgender male underwent gender-affirming laparoscopic total hysterectomy and bilateral salpingo-oöphorectomy without incident. Seven days postop, he developed progressive and painful clitoral engorgement that was persistent. Examination and imaging were consistent with clitoral priapism.
RESULTS: Clitoral priapism was treated with adrenergic drugs (imipramine and pseudoephedrine) with rapid resolution of symptoms.
CONCLUSION: Clitoral priapism is a rare phenomenon usually associated with use of a psychotropic medication. Whether clitoromegaly secondary to androgen administration in transgender men is a risk factor for this rare medical emergency is unknown. Prompt recognition and treatment is paramount. Kusko RE, Singhal E, Kauffman RP. Clitoral Priapism in a Transgender Male. Sex Med 2021;9:100431.

INTRODUCTION

Priapism is defined as an erection lasting 4 to 6 hours or longer in the absence of sexual stimulation. This condition is encountered primarily in the male penis with a reported incidence of 0.73 per 100,000 men per year and even less commonly in the female clitoris. Only a few scattered case reports of priapism in cis-women have been reported in the literature.2, 3, 4, 5

The mechanism of clitoral priapism is proposed to be similar to that of ischemic priapism in penile tissue, specifically obstruction of venous outflow. Severe clitorodynia associated with priapism is caused by arterial ischemia secondary to venous constriction or obstruction of the corpus cavernosa of the clitoris. A variety of pathophysiologic mechanisms have been described in cis-women, including outflow obstruction due to tumor mass, vascular invasion by neoplastic processes, or as a side effect of psychotropic medications with α2-adrenergic blockade which impair vascular smooth muscle relaxation. Sometimes, the etiology is unknown. Sickle-cell anemia is the most common cause of penile priapism in male children but has not been reported to be associated with priapism in women.

When the etiology of clitoral priapism is known or suspected, treatment includes discontinuation of the causative medication or excising the obstructing mass. In cases where the etiology is unknown, α-adrenergic agonists have been utilized with success. Injections of phenylephrine to the intracaval space have been utilized successfully in the penis and clitoris, and there are case reports of successful resolution of clitoral priapism with oral administration of medications with known arterial α-agonist properties (such as pseudoephedrine, phenylephrine, and clonidine) or adrenergic reuptake inhibition including imipramine and desipramine.,,,

In a literature search, we could identify only a single case report via scientific abstract of a presurgical transgender male with clitoral priapism (Table 1). Care for transgender individuals is a rapidly evolving area of medicine with more research needed to improve care for this medically underserved and marginalized population. Gender affirming therapies are an essential aspect of care of transgender individuals, and reporting rare events and successful treatments can aid providers in early recognition, effective management, and better outcomes. Current guidelines for transgender care do not mention priapism as a potential complication after hysterectomy, metoidioplasty, or phalloplasty, or as a potential risk of systemic androgen therapy.,

Table 1

Case reports of clitoral priapism in androgen-treated transgender men

Age	Duration of androgen exposure (years)	Putative cause	Treatment	Resolution	Reference
33	Not stated	Traumatic brain injury and trazodone 50 mg	Tapering trazodone dosage from 50 to 25 mg	Rapid	3
32	5 years	Unknown. Symptoms began 7 days after hysterectomy with general anesthesia	Oral pseudoephedrine and imipramine	Rapid	Present case

CASE

A 32 year-old caucasian female-to-male transgender person presented to the university transgender clinic with the complaint of acute phallic (clitoral) swelling and pain for 2 days that began rather suddenly. He initiated gender-affirming androgen therapy with intramuscular testosterone five years prior to presentation with satisfactory virilization and clitoromegaly. Seven days before this presentation, he had undergone his first step in gender affirming surgery, robotic laparoscopic total hysterectomy, bilateral salpingo-oöphorectomy, and diagnostic cystoscopy under general anesthesia. Sequential compression devices were applied to his calves during his brief hospitalization. Other than ureteral identification, no retroperitoneal dissection was performed, and the operation was uncomplicated. His preoperative serum testosterone level was therapeutic at 371 ng/dL (12.9 nmol/L). He was discharged home 12 hours after surgery with acetaminophen and codeine for postoperative pain with instruction to transition to ibuprofen. He denied recent masturbation, local trauma (straddle injury, etc.), and dysuria since hysterectomy. He smoked about half pack of cigarettes per day but denied history of depression and use of antidepressants or other psychotropic medications.

On examination, he had clitoromegaly (approximately 4.0 × 2.0 cm) although frank clitoral shaft edema or visible cutaneous lesions were not appreciated. The clitoris was only modestly tender to palpation with an otherwise normal vulva, abdominal exam, and lower extremity. No inguinal or femoral adenopathy was noted. He was afebrile (36.8⁰ C). Oral prednisolone was prescribed with a presumed diagnosis of cutaneous sensitivity to topical povidone iodine prep administered at surgery.

Two days later, he returned with significant worsening of his clitoral pain and difficulty walking due to clitoral compression with ambulation. He described a sensation of clitoral fullness and described the pain as “searing”. Acetaminophen with codeine had not diminished his pain. Examination revealed more substantial clitoral engorgement with significant tenderness to palpation compared to his examination two days before. The glans clitoris appeared unaffected. He remained afebrile, and abdominal, vaginal cuff, and bimanual pelvic examination were unremarkable. At this time, differential diagnosis included cellulitis resulting from recent surgery, clitoral venous outflow occlusion by a hematoma or thrombosis, and idiopathic clitoral priapism. He was readmitted to the hospital for pain management and further evaluation.

In the hospital, his oral temperature was 37.0⁰ C. Serum chemistries were normal, white cell count 6900/mL with normal differential, hemoglobin 14.4 g/dL, and hematocrit 45%. Sickle-cell screen and serum d-dimer were negative. His peripheral oxygen saturation was 98% on room air. Computerized tomography of the pelvis and perineum with and without IV contrast revealed mild tissue edema at the vaginal cuff (deemed normal at 1 week postop), absence of a pelvic abscess or hematoma, and clitoral enlargement (Figure 1). Based on CT findings excluding pelvic abscess or hematoma, clitoral priapism in a transgender male was considered likely. Imipramine 50 mg daily and the α-adrenergic agonist pseudoephedrine 120 mg orally twice daily were initiated. Over the next 16 hours, he experienced near complete resolution of the clitoral fullness and pain. Clitoral examination at that time revealed a right-sided superficial longitudinal laceration along the length of the clitoris suspected to be secondary to prolonged phallic engorgement (Figure 2). He was discharged home on imipramine 50 mg daily, pseudoephedrine 120 mg twice daily for seven days, and ibuprofen 800 mg every 8 hours as needed for pain. In the 6 months following hospitalization, he has experienced no further clitoral pain or swelling since the index episode. At present, he is able to functional sexually by self-stimulation with complete detumescence after orgasm.

Figure 1

CT with IV contrast at presentation to hospital. Clitoral corpus cavernosa (body) is marked with an arrow in A and B. The clitoral body and crura are outlined in C.

Figure 2

Clitoris after resolution of priapism with superficial laceration along the left clitoral shaft (arrows) secondary to prior engorgement (priapism).

DISCUSSION

Priapism is generally considered to be a malady of the male penis, and few case reports of clitoral priapism in cis-women exist in the published literature. To the best of our knowledge, only a single case of clitoral priapism in a preoperative transgender male has been reported. Current WPATH and the Endocrine Society guidelines do not list priapism as a potential complication of transmasculine androgen therapy.,

Anatomically, the clitoris has 2 paired corpora cavernosa (which separate in the perineum to form 2 crura) and a single glans clitoris, but unlike the male penis, there is no corpus spongiosum. The clitoral corpus cavernosa are surrounded by a fibrous sheath called the tunica albugenia.

During sexual stimulation, parasympathetic tone increases compared to sympathetic tone in the corpus cavernosa allowing vascular smooth muscles relaxation and engorgement. The intracavernous pressure in the clitoris rises only 2 fold during tumescence compared to the penis where the pressure increases at least 15 fold during erection. After orgasm, clitoral tumescence diminishes rapidly compared to the penis. These differences have been attributed to the differences in the anatomy of the tunica albuginea between men and women and in the compliance properties of the corpora cavernosa between sexes., Ischemic priapism occurs in men and women when venous outflow is impaired in some manner (anatomic obstruction or α-adrenergic blockade).

A number of medications such as psychotropics, dopamine agonists, α-adrenergic blockers, and H2 blockers have been implicated in the development of penile and clitoral priapism. Among these, psychotropic medications, particularly trazodone, is the drug most commonly implicated. Trazodone is an α1-adrenergic antagonist and serotonin reuptake inhibitor. The only reported case of clitoral priapism described in a presurgical transgender male was associated with trazodone administration and resolved with tapering of the medication.

Venous outflow obstruction as a cause of clitoral priapism has been associated with pelvic malignancies, vascular invasion, and infection. Smoking has been weakly associated with development of penile priapism, and the patient in this case smoked half pack per day. Parenthetically, he continues to smoke despite smoking cessation counseling.

Since his symptoms developed 7 days postoperatively, the possibility of general anesthesia or intraoperative medications were considered as potential causative agents, but a review of his operative records revealed no drugs that have been implicated in priapism other than induction of anesthesia with propofol. Propofol and all other intraoperative medications should have been cleared from his system prior to the reported onset of persistent clitoral tumescence. Development of a pelvic abscess and hematoma was rule out by CT scan. Trauma from uterine manipulation during laparoscopic hysterectomy and cystoscopy was ruled out given the interval between surgery and the onset of priapism. Localized postoperative clitoral venous thrombosis cannot be ruled out by the conducted imagery, but d-dimer markers were negative. Given the medical emergency and severe pain experienced by the patient, color-flow clitoral ultrasound was not pursued in favor of immediate medical treatment. Color-flow ultrasound in experienced hands may detect minimal cavernosal artery velocity leading to ischemia. The rapid resolution of distressing symptoms following administration of imipramine and pseudoephedrine further supports the diagnosis of clitoral priapism. Oral adrenergic medications may be more effective in women and transgender men with priapism due to the smaller anatomic size of the corpus cavernosa and lower intracavitary pressures compared to cis-men. Had administration of oral medications been ineffective in this case, intracavernosal injection of phenylephrine would have been pursued as described by Goldstein.

In the absence of a clear etiology, it is possible that this case of clitoral priapism in a transgender male was idiopathic. Priapism of the clitoris has not been reported as a complication of virilizing androgen administration in transgender men.

The degree to which sustained androgenic therapy in presurgical transgender men changes anatomical aspects of the clitoral corpus albuginea and physiologic function of the corpus cavernosa is an area for future investigation. Testosterone administration in postmenopausal women (at dosages far less than virilizing dosages administered to transgender men) may improve the arousal response, and animal models have shown testosterone upregulates the nitrous oxide pathway which drives clitoral tumescence. Furthermore, anatomic changes of the clitoris in response to testosterone may adversely affect venous outflow. As transgender hormone therapy becomes more accepted and accessible, better epidemiologic data may answer the question whether androgen therapy is a risk factor for priapism in the transgender male.

In conclusion, clitoral priapism should be considered in transgender men in the presence of prolonged phallic engorgement and pain. A careful assessment of medication use should be at the forefront. Imaging will assist ruling out pelvic masses, thrombosis, or malignancies which might impair venous outflow. Color flow ultrasonography of the cavernosal arteries, where available, may detect pathologic low flow. It is unknown whether clitoral priapism is more common in presurgical transgender men compared to cis-women despite phallic enlargement and possible effect on chemical signaling associated with systemic testosterone administration. Further epidemiological and anatomic research is needed in this understudied population.

Statement of Authorship

REK and ES performed background and literature research and had a significant role in manuscript preparation. RPK managed the patient and also played a significant role in manuscript preparation. All authors have approved the final manuscript.