AUA 2020: Disorders of ejaculation guidelines hailed as “most scientifically rigorous to date”

During the 2020 AUA Virtual Experience, Alan W. Shindel, MD, provided an expert summary and analysis of the 2020 AUA Guidelines for Disorders of Ejaculation.¹

“Disorders of the timing of ejaculation/orgasm are poorly understood, but pharmacotherapy options do exist for both premature and delayed ejaculation, explained Shindel, the chair of AUA Ejaculation Disorders Committee, and associate professor, male reproductive health, University of California, San Francisco department of urology.

The AUA Guidelines for Disorders of Ejaculation are intended to address these knowledge gaps. “The 2020 AUA Guidelines are the newest and most scientifically rigorous guidance on the subject to date,” said Shindel.

Shindel explained that the evidence level associated with statements in the guidelines is classified as high (A), moderate (B), or low (C), and that recommendations without a sufficient evidence basis are labeled as a clinical principle or expert opinion.

In his presentation, which covered premature ejaculation and delayed ejaculation, Shindel stressed that beyond pharmacotherapy, “education, mental health evaluation, and attention to the relationship are critical considerations in management” of disorders of ejaculation.

Premature Ejaculation

The AUA guidelines define lifelong premature ejaculation (LPE) as “consistently poor ejaculatory control, associated bother, and ejaculation within about 2 minutes of initiation of penetrative sex that has been present since sexual debut.”

This definition extends the ejaculatory latency time (ELT) to 2 minutes, when it had previously been 1 minute with some standard definitions. Shindel explained the adjustment was made because men with an ELT of 1 to 2 minutes are more similar in terms of symptoms/experience with men who have an ELT of less than 1 minute than those with an ELT of 2 to 5 minutes.

The guidelines define acquired PE as “consistently poor ejaculatory control, associated bother, and ejaculation latency that is markedly reduced from prior sexual experience during penetrative sex.”

There is no evidence-based consensus on ELT in patients with acquired PE. Clinical experience suggests these patients have an ELT of under 2 to 3 minutes and/or substantial reduction (ie, ≥50%) in ELT from previous experiences of partnered sex.

Regarding circumcision, a grade C recommendation in the guidelines suggests that “clinicians should advise patients that ejaculatory latency is not affected by circumcision status.”

According to Shindel, “There are certainly patients who may experience difficulties or problems relating to their foreskins, and in those men, circumcision may be considered an option, but circumcision itself is not thought to intrinsically modify ejaculation latency during partnered sex.”

The guidelines also issue a grade C recommendation in the area of mental health, stating that “Clinicians should consider referring men with premature ejaculation to a mental health professional with expertise in sexual health.”

Pharmacotherapy for premature ejaculation

The first-line pharmacotherapy options for PE, also supported with grade B evidence, include SSRIs, on-demand clomipramine or dapoxetine (where available), and topical penile anesthetics.

None of these treatments have obtained FDA approval in this setting, but they have been “utilized for a great deal of time with good clinical efficacy,” said Shindel.

He explained that SSRIs, which enhance serotonergic activity in the brain, have been used off-label for PE management for years. The SSRIs used include paroxetine, sertraline, citalopram, and fluoxetine. The most commonly used with the greatest evidence of efficacy is paroxetine.

Adverse events (AEs) associated with SSRIs include fatigue, yawning, nausea, and diarrhea, and they are contraindicated in young men with suicidal ideation and/or bipolar disorder. Clinicians should also carefully consider other drugs the patient is using to protect against drug interactions that could cause serotonin syndrome.

Also in the frontline PE paradigm, topical anesthetics are widely available and are generally tolerable but can be “cumbersome to apply and can lead to irritating AEs, such as numbness and sometimes tingling sensations in both the patient and his or her partner,” said Shindel.

Efficacy in the frontline PE setting has also been shown with the tricyclic antidepressant clomipramine. The most recent evidence came from a double-blind, randomized, placebo-controlled, fixed-dose phase 3 study of clomipramine (15 mg on demand).² The study included 159 patients with PE who were randomized to clomipramine (n = 106; 15 mg for 12 weeks) or placebo (n = 53).

The investigators assessed efficacy through scores on the IELT (Intravaginal Ejaculation Latency Time) and the PEDT (Premature Ejaculation Diagnostic Tool). The mean IELT increased 192 seconds with clomipramine compared with 87 seconds with placebo. The mean fold increase in ELT was 4.4 versus 2.7, respectively, and the mean PEDT decrease was 4.7 versus 1.3, respectively.

The investigators concluded that the overall severity of AEs was mild to moderate. However,Shindel noted that the rates of nausea (15.7%) and dizziness (4.9%) with clomipramine were unfavorable compared to those reported with SSRIs in other studies.

As far as second-line pharmacotherapy options for PE, the guidelines include on-demand dosing of tramadol (grade C) and alpha blockers (expert opinion).

Shindel said that tramadol, which is an opioid analgesic agonist and analog, “Has a number of effects that may be relevant to ejaculation-delaying properties; however, as it is an opioid drug there is some concern that it could lead to potential for addiction and/or interactions with SSRI, and should therefore be used only cautiously in men with premature ejaculation.”

Regarding alpha blockers, Shindel explained, “There is a week body of evidence suggesting they may have some efficacy in men with premature ejaculation. But this evidence is limited enough that we do not recommend this as a first-line agent of choice.”

He also noted that expert opinions in the guidelines recommend against using alternative therapies in treating patients with PE, and that surgical management for PE, such as injecting bulking agents, should only be offered as part of a clinical trial.

Delayed Ejaculation

The guidelines define lifelong delayed ejaculation (DE) as “lifelong, consistent, bothersome inability to achieve ejaculation, or excessive latency of ejaculation, despite adequate sexual stimulation and the desire to ejaculate.”

Acquired DE comprises the same symptoms, with the condition being acquired and not a lifelong complication.

Treatment advice in the guidelines for patients with DE includes referral to a mental health professional with expertise in sexual health, as well suggesting patients modify their sexual practices, including sexual positions, which may increase arousal and lead to ejaculation.

A clinical principle recommendation also suggests that clinicians evaluate the medications the patient is taking that may contribute to DE and recommend staged cessation, dose adjustment, or replacement. Prior to taking making any changes, particularly when advising a patient to stop a therapy, there should be consultation with the prescribing physician.

Regarding medical management of DE, an expert opinion in the guidelines notes that, “Clinicians should inform patients that there is insufficient evidence to assess the risk-benefit ratio of oral pharmacotherapy for the management of delayed ejaculation.”

Noting this opinion, Shindel said, “There are a number of pharmacotherapy options that may be considered in the management of DE but only after careful consideration and a discussion with the patient that none of these have FDA approval, and have a limited evidence basis.”

An expert opinion in the guidelines also indicates that physicians should counsel patients with DE that there is no clinical support for the use of invasive non-pharmacological approaches in this setting.

Shindel concluded his discussion with a review of some of the existing medical treatment options for patients with DE, starting with penile vibratory stimulation (PVS),which he said is“intended to intensify arousal.”

A small study³ of 36 patients with secondary anorgasmia for ≥3 months treated with intermittent PVS to frenulum showed “some evidence of utility in men with delayed ejaculation,” said Shindel. In the study, 72% (n = 26) of patients experienced at least some level of restoration of orgasm.

“This is a relatively low-risk intervention that may be incorporated into sexual interactions for the patient,” said Shindel.

Bupropion, an antidepressant agent with both central dopaminergic and noradrenergic activity, has shown potential for DE management in a small body of evidence. Studies, which have generally been conducted in young men with DE, have demonstrated some improvement versus baseline status; however, “these studies are limited in their absence of a placebo arm,” said Shindel.

Another agent with some potential is cabergoline, a D2 dopamine and 5HT2b agonist that is most commonly used to suppresses prolactin-producing tumors. In a study of men with DE, 66% (n = 87) of 131 patients who received cabergoline experienced an improvement in ejaculation latency.4 The study did not have a control arm, however, thus limiting the significance of the results.

The final DE treatment Shindel covered was testosterone, which the guidelines address in an expert opinion stating, “Clinicians may offer treatment to normalize serum testosterone levels in patients with delayed ejaculation and testosterone deficiency.”

References

1. Shindel AW. AUA Guidelines 2020: Disorders of Ejaculation. Presented during 2020 AUA Virtual Experience. June 27-28, 2020.

2. Choi JB, Kang SH, Lee DH, et al. Efficacy and safety of on demand clomipramine for the treatment of premature ejaculation: a multicenter, randomized, double-blind, phase III clinical trial. J Urol. 2019;201(1):147-152. doi: 10.1016/j.juro.2018.07.089

3. Nelson CJ, Ahmed A, Valenzuela R et al. Assessment of penile vibratory stimulation as a management strategy in men with secondary retarded orgasm. Urology. 2007;69:552-555. doi: 10.1016/j.urology.2006.02.048

4. Hollander AB, Pastuszak AW, Hsieh T-C, et al. Cabergoline in the treatment of male orgasmic disorder-a retrospective pilot analysis. Sex Med. 2016;4(1):e28-33. doi: 10.1016/j.esxm.2015.09.001