One can readily appreciate the necessity to employ a broad-based approach for each patient encounter with concerns regarding DO/AO. A thorough history may reveal other forms of sexual dysfunction (i.e. erectile dysfunction), psychological concerns, medication side effects, idiosyncratic masturbation habits, or even relationship difficulties. Physical examination supplemented by objective studies including biothesiometry may suggest penile sensory deficits.3 Laboratory testing may support an underlying endocrinopathy such as hypogonadism or hyperprolactinemia. Yet, despite our best efforts, an obvious underlying structural or even functional etiology is not readily identified in most patients. There is no agreed-upon treatment algorithm due to the lack of rigorous data regarding any of these treatments, and many clinicians rely on anecdote or personal experience in the absence of reliable and reproducible clinical studies. To this end, different treatment approaches such as psychotherapy, penile vibratory stimulation, and a multitude of oral medications targeting various central mechanisms implicated in sexual function (and dysfunction) have been explored. Medications that are used to treat DO/AO include amantadine, bupropion, cyproheptadine, oxytocin, yohimbe, and cabergoline, amongst others.2,4 These agents target serotonin, norepinephrine, dopamine, and other central neurotransmitters. These mechanisms make sense from a neurophysiologic perspective, yet supportive clinical data is lacking.
The impetus for our current study stemmed from ongoing frustration with currently available treatments for DO/AO. We routinely encounter this condition in our high-volume sexual dysfunction practice. In fact, the estimated population prevalence of 3% is likely a vast under-representation as we have found many patients with other aspects of sexual dysfunction who endorse DO/AO when queried (although they may not readily bring this up unless prompted ).2 Attempts to treat these patients with psychosexual counseling, penile vibratory stimulation, and a host of oral medications left us feeling disheartened based on the lack of reliable efficacy. Moreover, when we explored this condition with our patients we identified a common theme – lack of concentration during sexual activity. That is, many of these men reported the sense that their “mind wanders” during intimacy. In discussion with our colleagues, many others have encountered similar experiences in their own practices, and this ultimately led to the hypothesis that lack of concentration may underlie DO/AO in some men.
Stimulant medications such as amphetamine/dextroamphetamine salts (AMP; Adderall) are routinely used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, in large part due to their ability to enhance concentration. AMP modifies norepinephrine and dopamine release and reuptake inhibition to improve focus.5 These central neurotransmitters are also involved in sexual function.1 There is also a limited body of literature suggesting that some men actually experience sexual symptom enhancement with amphetamines, and within the urologic literature, Lyons et al found that another stimulant medication (lisdexamfetamine dimseylate, also known as Vyvanse) was successful in treating neurogenic anejaculation.6,7 We took these findings to support an evidence-basis with which to consider an oral stimulant medication to treat DO/AO. We chose AMP based on ease of use, established safety profile, and ability to titrate if needed.5 A pilot study was devised to assess the outcomes of AMP on bothersome DO/AO in a cohort of men who initially presented to our clinic with this chief complaint. We had complete data available on 17 patients who were included in the cohort, although our clinical experience extends well beyond this number at this time. Of note, in all circumstances, these patients had a history of secondary (new-onset) symptoms after having self-reported normal ejaculatory function previously.
As expanded upon in the manuscript, patients were instructed to start with a low dose of 5 mg to be taken 1-2 hours prior to sexual activity. If needed, patients were allowed to up-titrate to a maximum of 20 mg. Prior to treatment, these men were all extensively screened to rule out underlying psychological conditions or cardiovascular disease, amongst others. With treatment, 47% of patients felt that AMP enhanced their sexual experience, and 35% reported a decrease in ejaculatory latency time by a mean of 72%. The median dose was 7.5 mg (interquartile range 5.0). Adverse events were rare and self-limiting – including insomnia or “jitters” in one patient each. Patient selection and oversight are of the utmost importance, given the potential risk of misuse, abuse, and medication diversion that is seen with AMP and other stimulant medications. To mitigate these risk patients are carefully counseled and educated, and only small quantities are prescribed at any given time. In this small study, no patient was found to have engaged in medication misuse, but this must be carefully considered in the context of treatment.
While at first glance these results appear modest, one must take into account the challenging nature of this clinical entity and the multiple potential underlying etiologies that prevent a one-size-fits-all approach for DO/AO. In this pilot cohort, nearly ¾ of these patients who responded to AMP had failed alternative “historical” treatments including therapy, vibration, and several medications. Given that this was a pilot study, we were not powered to identify patient-specific factors that contribute to treatment success, although treatment responders were younger than non-responders. Responders had a higher baseline score in the adult ADHD self-report scale (median score 3.0 vs 1.0, p=0.12), suggesting a possible role for this and other behavioral questionnaires in the initial evaluation for patients with DO/AO, particularly if AMP is considered. However, it is plausible that concentration difficulties may contribute to DO/AO in a specific subpopulation of these patients, and our results warrant further investigation including a placebo-controlled trial with appropriate power to further characterize the role of stimulant medications in our treatment armamentarium. Whether other types of stimulant medications may offer similar benefits with different risk profiles is unclear, but should be considered in future research endeavors as well. The ultimate goal would be to identify a specific patient phenotype (based on clinical history, examination, and possibly questionnaire response) of those most likely to respond to AMP or other treatment modalities
Written by: Laurence A Levine, M.D.,1 Hannah K Betcher, M.D.,2 Matthew J Ziegelmann, M.D.,3 Petar Bajic, M.D.1
- Division of Urology, Rush University Medical Center, Chicago, IL
- Department of Psychiatry, Mayo Clinic, Rochester, MN
- Department of Urology, Mayo Clinic, Rochester, MN
- Althof, S.E. and C.G. McMahon, Contemporary Management of Disorders of Male Orgasm and Ejaculation. Urology, 2016. 93: p. 9-21.
- Jenkins, L.C. and J.P. Mulhall, Delayed orgasm and anorgasmia. Fertil Steril, 2015. 104(5): p. 1082-8.
- Wiggins, A., et al., The Penile Sensitivity Ratio: A Novel Application of Biothesiometry to Assess Changes in Penile Sensitivity. J Sex Med, 2019. 16(3): p. 447-451.
- Sadowski, D.J., M.J. Butcher, and T.S. Kohler, A Review of Pathophysiology and Management Options for Delayed Ejaculation. Sex Med Rev, 2016. 4(2): p. 167-76.
- Heal, D.J., et al., Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol, 2013. 27(6): p. 479-96.
- Lyons, M.D., A.C. Lentz, and R.M. Coward, Lisdexamfetamine Dimesylate (Vyvanse) for the Treatment of Neurogenic Anejaculation. Am J Mens Health, 2017. 11(3): p. 618-619.
- Chou, N.H., Y.J. Huang, and B.P. Jiann, The Impact of Illicit Use of Amphetamine on Male Sexual Functions. J Sex Med, 2015. 12(8): p. 1694-702.