Delayed orgasm (DO) and anorgasmia (AO) are 2 of the most difficult conditions to treat in male sexual medicine. DO and AO likely exist on a spectrum, and are defined by the persistent delay or inability to achieve sexual climax. An alternative definition for DO is 2 standard deviations above the median intravaginal latency time (5.4 minutes), or approximately 25 minutes. DO and AO occur in approximately 5% of men, though the prevalence is likely underreported.¹ Patients with DO/AO can experience significant relationship distress, sexual dissatisfaction and psychological trauma. Achieving orgasm involves not only a physiological response to physical stimulation, but also emotional and cognitive arousal. Psychological/emotional unrest, relationship friction and suboptimal sexual stimulation can contribute to DO/AO.

DO and AO should also be differentiated from anejaculation and retrograde ejaculation due to medical conditions, prior pelvic surgery or radical prostatectomy. Use of medications such as selective serotonin reuptake inhibitors (SSRIs), hypogonadism, hyperprolactinemia and decreased penile sensitivity are also recognized causes of DO/AO. Therefore, the initial evaluation of DO/AO includes a review of medications, obtaining a complete hormone profile and, possibly, biothesiometry when the patient reports diminished penile sensitivity (evaluation of vibratory sensation, which is considered a useful surrogate for sexual sensation). Patients with SSRI-associated DO/AO should discuss medication adjustment with their prescribing psychiatrist. Patients with evidence of hypogonadism should be treated appropriately. If abnormal penile sensitivity is identified through biothesiometry, patients should be instructed to trial penile vibratory stimulation. One study evaluating 157 men with DO demonstrated 82% success when SSRIs were stopped, 60% success with penile vibratory stimulation in men with abnormal penile sensitivity and 24% success with testosterone supplementation in hypogonadal men.²

After organic etiologies have been addressed, patients may benefit from psychosexual evaluation with a sex therapist. Patients can also consider lifestyle modifications such as decreasing alcohol consumption, adjusting sexual behavior with their partner and changing masturbation habits. Communication between partners is key. Partners should clarify their goals for each sexual encounter, and positive feedback should be provided when aspects of a sexual encounter yield encouraging results.

Unfortunately, there are no U.S. Food and Drug Administration-approved drugs and no consensus on a reliable treatment algorithm for DO/AO due to the absence of rigorous data. There have been several studies reporting successful off-label pharmacotherapy for DO. However, these studies are often underpowered, and caution should be taken when recommending these therapies to patients. Cabergoline is a dopamine receptor agonist used to treat hyperprolactinemia. One study found that 66% of patients (131) with DO/AO responded to twice-weekly 0.5 mg cabergoline.³ However, many men in this trial also received concurrent testosterone therapy, which may have confounded treatment success. Furthermore, long-term use of cabergoline is associated with pulmonary fibrosis, cardiac valve regurgitation and heart failure. In another large-scale retrospective study of 596 psychiatric patients, yohimbine, amantadine and cyproheptadine were utilized as antidotes for SSRI-induced DO/AO.⁴ Bupropion has also been successfully used as an antidote for SSRI-induced sexual dysfunction.⁵ A number of other medications such as oxytocin, buspirone, midodrine, bethanechol and loratadine have been used to treat DO/AO in select situations, but data are limited.⁶

Many men remain refractory to currently available treatments, which is frustrating both to patients and to providers. When patients with DO/AO were questioned more in depth, many patients reported difficulty in maintaining focus and sexual intimacy with their partners. In a sense, some patients experienced a lack of concentration resulting in wandering thoughts, which contributed to diminished arousal and difficulty reaching orgasm. With this hypothesis, off-label use of amphetamine/dextroamphetamine salts (AMP) was trialed in men with DO/AO.⁷ AMP (Adderall^®) is a stimulant that blocks the reuptake of norepinephrine, dopamine and serotonin from the synaptic space. It is commonly used to treat attention-deficit/hyperactivity disorder (typically 20–60 mg Adderall XR per day), and is known to improve focus and attention. For the treatment of DO/AO, patients are started with 5 mg immediate release Adderall on an as-needed basis 1–2 hours prior to sexual activity. The timing of the medication can be adjusted to up to 4 hours before sexual activity based on each individual patient’s reported optimal timing. If results are not satisfactory, the dose is gradually increased to a maximum of 20 mg as needed.

Of the 17 patients trialed on AMP, 8 patients (47.1%) reported subjective improvement of sexual experience. Six of these 8 patients had previously failed other therapies. Patients with DO had a higher response rate (55%) compared to patients with AO (33%). In DO patients who responded to AMP, the mean orgasmic latency time decreased from 40.7 to 11.1 minutes (72%). Six of the 17 patients (35%) reported decreased latency time and increased frequency of orgasms. Minimal side effects of insomnia and jitters were noted in 2 (11%) patients. This study was limited by the small sample size and short followup period. Long-term use of AMP is known to lead to addiction, and AMP abuse is known to cause serotonin syndrome. There are also reports that illicit amphetamine use has been associated with variable sexual dysfunction, including increased latency time and erectile dysfunction. Further investigation of AMP with a larger patient cohort, randomization with placebo and long-term followup is needed to further evaluate its safety and efficacy.

In conclusion, DO and AO are challenging conditions to treat without a clear treatment algorithm. While there are many off-label pharmacological options, none is reliable and further investigation is required to improve our ability to treat DO/AO. At this point, an individualized treatment plan including a multidisciplinary assessment (urology and psychology) represents the optimal approach for the management of DO/AO patients.