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Pharmacotherapy
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A variety of drugs have been reported as treatments of drug-induced delayed ejaculation [94 105] The drugs facilitate ejaculation by either a central dopaminergic or anti-serotonergic mechanism of action However, there are no published placebocontrolled studies and most reports are anecdotal case reports/series of men with anti-depressant or anti-psychotic drug induced IE
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5-HT1A receptor agonist
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Buspirone is a 5-HTIA receptor agonist [111] Othmer et al reported normalization of sexual function in eight out of 10 men with a generalized anxiety disorder and associated sexual dysfunction, using a dose range of 15 to 60 mg daily [104]
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5-HT receptor antagonists
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Cyproheptadine, a serotonin (5-HT) receptor antagonist has been shown to increase male sexual activity in the rat [106] Several anecdotal case reports and small case series mention success of the use of cyproheptadine to reverse the anorgasmia induced by the SSRI antidepressants However, controlled studies have not been published [94,97,98] The case reports suggest an effective dose range of 2 to16 mg, administration on a chronic or ondemand basis
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Dopamine reuptake inhibitor
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Bupropion is a dopamine reuptake inhibitor [112] Ashton and Rosen described reversal of SSRIinduced anorgasmia in 66% of patients studied [105]
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Future aspects
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Inhibited ejaculation has been less well researched than PE, probably because fewer cases are seen The etiology of inhibited ejaculation is multifactorial and includes organic and psychologic distur-bances; pharmacologic agents are also implicated Improved techniques for clinical evaluation are required Except where a treatable organic cause has been identi ed or a drug known to impair ejaculatory function has been withdrawn, the mainstay of treatment is by psychotherapy, but this is not evidencebased, as the most successful psychotherapeutic intervention has not been established Future research should address this shortcoming A number of pharmacologic agents are reported to treat drug-induced delayed (inhibited) ejaculation, but these observations are not based on well-controlled and adequately powered studies, but rather on single cases or small series of cases The pharmacotherapy of inhibited ejaculation requires proper evaluation
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Dopaminergic drugs
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Central dopamine activity can be increased by a variety of mechanisms ranging from the use of dopamine synthesis precursors, eg L-dopa or substitute neurotransmitters, to direct stimulation of central dopamine receptors Amantadine is an indirect stimulant of dopaminergic nerves both centrally and peripherally, and has been reported to stimulate sexual behavior, ejaculation and other sexual re exes in rats [107,108] Several authors have reported their experience with 100 to 200 mg amantadine in the reversal of SSRI antidepressant-induced anorgasmia [95 97, 99 101] Apomorphine, a central and peripheral DA-2 receptor agonist, has been reported to induce early ejaculation in rats by several authors Dopamine receptor antagonists block this effect [109,110] Yohimbine is an -2 antagonist, an -1 agonist, a
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Ejaculatory Disorders
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Retrograde Ejaculation
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Etiology and risk factors
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Antegrade ejaculation requires a closed bladder neck and proximal urethra Retrograde ejaculation (RE) may be caused by anatomic, neurologic, pharmacologic, or idiopathic factors [113 116] Anatomic causes: Anatomic causes include congenital (urethral valves, congenital defects of the hemitrigone, congenital dysfunction of the hemitrigone, or bladder exstrophy), or acquired (urethral stricture, bladder neck resection or brosis, and transurethral or open prostatectomy) Neurologic causes: These are usually secondary to disorders that interfere with the ability of the bladder neck to close during emission: spinal cord injury, multiple sclerosis, autonomic neuropathy (diabetes), retroperitoneal lymphadenectomy (usually performed for testicular cancer), sympathectomy, and colorectal and anal surgery Pharmacologic causes: Multiple drug classes may be associated with retrograde ejaculation as an adverse effect The mechanism usually involves paralysis of the bladder neck by certain types of medications including antihypertensive drugs (phenoxybenzamine, clonidine, guanethidine, thiazide diuretics), 1-blocking drugs (alfuzosin, phenoxybenzamine, prazosin, tamsulosin, terazosin), antipsychotics drugs (chlorpromazine uphenazine, levomepromazine, thioridazine, tri uoperazine, thioxitene, zuclopenthixol), and all classes of antidepressant drugs Idiopathic causes: Occasionally a clear etiology cannot be identi ed
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at 300 g or more In patients with absent ejaculation, the nding of greater than ve to 10 sperm per highpower eld in a post-ejaculation urine specimen con rms the presence of retrograde ejaculation In patients with low-volume ejaculate, the nding of more sperm in the urine than in the antegrade ejaculate indicates a signi cant component of RE [117]
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