Pharmacotherapy of retrograde ejaculation represents various medications used to treat retrograde ejaculation. Retrograde ejaculation (RE) is defined as a substantial redirection of seminal fluid from the posterior urethra into the bladder (Pic. 1) and mainly caused by bladder neck dysfunction (Pic. 2). Men suffering from RE present with total, or sometimes partial, absence of semen, despite the sensation of an orgasm, after intercourse or masturbation. Current treatment methods are based on two different strategies. The first is pharmacologic intervention or surgical management in order to restore antegrade ejaculation by increasing bladder neck tone. The second is urinary sperm retrieval or electroejaculation; this aims to facilitate fertility by obtaining spermatozoa with invasive methods and then applying artificial reproductive technologies. 

The treatment depends on the cause. Medications may work for retrograde ejaculation but only in a few cases. Nevertheless, pharmacotherapy can be tried as a first-line treatment because it is simple, time-saving, cost-effective and non-invasive.

Currently, these medications are most commonly used:

  • tricyclic antidepressants (such as imipramine or amoxapine)
  • antihistamines (such as promethazine or diphenhydramine)
  • decongestants (such as pseudoephedrine)

These medications tighten the bladder neck muscles and prevent semen from going backwards, into the bladder. However, the medications do have many side effects and they have to be taken at least 1–2 hours prior to sexual intercourse.

Clinically, imipramine, a tricyclic antidepressant agent (TCA), is commonly used to treat RE due to a variety of causes. However, the overall success rate does not exceed 50%, and adverse effects are reported frequently.

Amoxapine, a tetracyclic antidepressant that is chemically distinct from TCAs, has been reported to result in far fewer adverse events than imipramine in patients treated for depression. Amoxapine also selectively blocks neuronal reuptake of norepinephrine and, to a lesser extent, serotonin, and thus upregulates peripheral sympathetic activity to contract the bladder neck; therefore, it also exerts actions that are potentially beneficial in the treatment of RE.

Around 40% of sufferers from retrograde ejaculation have found that use of pseudoephedrine (brands names include Sudafed) noticeably improves the quantity of ejaculate. People with erectile dysfunction and retrograde ejaculation (not uncommon in those with diabetes) are strongly advised to seek medical advice about the best 'dual' treatment methods available to them, i.e. combining pseudoephedrine or an alternative with an erectile dysfunction treatments such as sildenafil.

Although medical treatment is commonly used as the first line of action in the treatment of RE, its effect largely depends on the underlying cause. Medications only work if there has been mild nerve damage caused by diabetes, multiple sclerosis or mild spinal cord injury. Medications do not help retrograde ejaculation if there has been permanent damage to the prostate or the testes from radiation. Medications also do not help if prostate surgery has resulted in damage to the muscles or nerves. A disadvantage of medical therapy is also that the medications usually need to be taken some time prior to sexual intercourse. In many cases, the medications fail to work at the right time because most men are not able to predict when they will have an orgasm.

Possible adverse outcomes of medical treatment of RE are associated with certain medications and their side effects.

TCAs, or tricyclic antidepressants, have several possible adverse reactions ranging from sedation, hypotension (low blood pressure), weight gain and seizures. Anticholinergic effects such as tachycardia (increased heart rate), urinary retention and constipation can also occur. Some rare, but reported side effects such as blood dyscrasias (disruptions of the blood cell development) are also possible. To counteract the sedative feeling caused by its antihistamine effect, TCAs may be taken at night. It is noted that with continued use, this reaction decreases. The most serious reported adverse effects, are dysrhythmias (abnormal heart rhythm) caused by cardiac toxicity. This may result from high doses of TCAs.

Antihistamines are generally divided into two generations. 

First generation antihistamines can cross the blood brain barrier (selective barrier separating nervous tissue from the blood) and interfere with neurotransmission (transmission of nerve impulses) in the central nervous system, which can cause sedation. Antihistamines also owe much of their effect to anti-cholinergic action. This can cause undesired anti-cholinergic effects including mydriasis, sedation, dry eyes, dry mouth, constipation and urinary retention. 

The second generations are less likely to cause side effects, although it is impossible to completely avoid all side effects. Only small amounts of the newer antihistamines cross the blood-brain barrier and thus do not cause as much sedation. The newer antihistamines are less likely to cause the anticholinergic effects mentioned above, but nevertheless, anticholinergic effects have still been reported, especially in the elderly.

In most cases those suffering from retrograde ejaculation are advised that a normal sex life is to be expected, however a significant number of those patients who do have it have reported reduced sensation during orgasm.

If a couple is experiencing infertility as a result of retrograde ejaculation and medications are not helping, the male's ejaculate may be centrifuged and the isolated sperm injected directly into the woman through the use of intrauterine insemination (IUI). In more severe cases, in-vitro fertilization with intracytoplasmic sperm injection (ICSI) may be used.

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