It is a little-known fact that erectile dysfunction (ED) and premature ejaculation (PE) can often come hand in hand. They can be a trigger for each other and a cycle ensues. As well as physical reasons for them both, quite often it can also be psychological reasons. It’s estimated 1 in 10 men has a problem related to having sex, such as premature ejaculation or erectile dysfunction. Sexual problems can affect any man, whether he is straight, gay, bisexual or transgender.
The prevalence of erectile dysfunction has been well researched. The Massachusetts Male Aging Study (MMAS) (Feldman, et al. 1994) found minimal erectile dysfunction in 17% of the 40– 70-year-old respondents, moderate erectile dysfunction in 25%, and complete erectile failure in 10%. Braun and colleagues (2000) found erectile dysfunction in 19.2% of their 4489 respondent over 30 years, although the authors demonstrated that not all participants with erectile dysfunction reported distress. In relation to both distress and overall prevalence, a marked age effect was found (Table 1).
Age dependence of erectile dysfunction (ED)
Age group (years)
Prevalence of ED (%)
Distress (%) (ED present and sex life described as unsatisfying)
When considering options for erectile dysfunction, many men choose to take tadalafil, it is the second most popular and well known after sildenafil (Viagra).The treatment for erectile dysfunction (ED) was revolutionized with the development of phosphodiesterase type 5 (PDE5) inhibitors. Tadalafil (Cialis®; Eli Lilly and Company, Indianapolis, IN, USA) is the most versatile PDE5 inhibitor in the clinical armamentarium for the treatment of ED. Its most unique characteristic is its long half-life of 17.5 hours, which lends itself to a longer therapeutic window with on-demand dosing and effective steady-state plasma concentrations with once-daily dosing. Clinical trials have proven its safety and efficacy with both dosing strategies for all severities and etiologies of ED, including difficult-to-treat ED.
Attempts at determining the neurotransmitter or neurotransmitters involved in creating an erection may someday lead to successful nonhormonal medical therapy [for erectile dysfunction] (Krane 1986, p. 731).
—Robert J Krane, MD, in Campbell’s Urology, Fifth Edition
The last two decades have seen a dramatic growth of understanding in the physiology of erection, the pathophysiology of erectile dysfunction (ED), and its treatment options. As the above quote from the fifth edition of Campbell’s Urology reveals, it was not long ago when little was known of erectile physiology, and adequate treatment was still “someday” away. Prior to the turn of the century, the pharmacologic treatment options for ED were cumbersome and invasive. Everything changed when oral phosphodiesterase type 5 (PDE5) inhibitors became available, completely revolutionizing the treatment of ED of all severities and etiologies. Pfizer introduced the first PDE5 inhibitor, sildenafil (Viagra®; Pfizer, New York, NY, USA), in March of 1998, and over the past 10 years, the new oral pharmacologic therapy together with an unbridled acceptance and newfound candor by the general public has not only dramatically increased the awareness and prevalence of ED but also made treatment of the disease simple and effective. Once one of the most frustrating and refractory diseases for the urologic specialist, ED is now enthusiastically discussed and treated in the primary care setting.
Mechanism of action; PDE5 inhibitors potentiate the vasodilative effect of acetylcholine, which is released from sacral parasympathetic neurons, causing an increase in blood flow to the penis, and thereby facilitating penile erection during sexual stimulation. The penile erection results when the muscarinic receptors in the endothelial cells are activated by acetylcholine. This activation leads to an increased production and release of nitric oxide. The diffusion of nitric oxide into vascular smooth muscle cells activates guanylyl cyclase and the resultant increase in the synthesis of cyclic guanosine monophosphate (cGMP), leading to muscle relaxation and vasodilation of the penis.8 PDE5 inhibitors act by hampering the breakdown of cyclic GMP by PDE5, causing an increase in the intracellular concentration of cGMP in the corpus cavernosum of the penis. This action results in vasodilation and an antiproliferative effect on the smooth muscle cells.
Tadalafil is unique in the field of ED medications in that it comes in two dosage options; once-daily dosing and as needed dosing. Until 2007, PDE5 inhibitors were taken on-demand by the majority of patients, being ingested prior to an anticipated sexual activity. For the patient, in a way, taking an on-demand therapy assumes that he has a kind of appointment.
But some patients cannot foresee their desire for sexual intercourse in time for the tablet to be absorbed and become active. They want to have sex at the same time the desire strikes them. Thus, he should have taken the pill in advance, sometimes with no certainty of having intercourse. Because of its long half-life and 36 to 48 hours of clinical efficacy, tadalafil was preferred by these patients. Some couples, for example, became accustomed to taking tadalafil Friday evening to prepare for the possibility of having intercourse during the weekend. Other patients, and especially their partners, found their sexual desires to be inhibited by the idea of taking a pill. Their solution was to separate, as much as possible, the swallowing of the pill from the onset of sexual activity, so as to ‘forget’ ingesting the pill. Here again, because of on-demand tadalafil’s particularly well-adapted pharmacokinetic properties, especially its 17.5-hour half-life assuring activity for about 2 days, patients often chose it.
Premature ejaculation is the most common form of sexual dysfunction in men. It is defined as the persistent or repeated occurrence of ejaculation before, during, or shortly after penetration, over which the individual has little or no control and not accompanied by a feeling of orgasmic satisfaction. Around 20% to 25% of surveyed adult men in modern industrialized nations report premature ejaculation associated with distress. In seeking to present valid prevalence data one encounters two problems: On the one hand, the normal interval between penetration and ejaculation is to a large extent a subjective judgment, and subject to wide individual and cultural variation. And on the other hand, this is an area in which it is particularly clear that biological dysfunction is not synonymous with a clinically relevant disorder.
PE is highly prevalent and, due to the nature of the disorder, is likely to be under-reported and undertreated. Reported prevalence has also been variable due to the previous lack of an evidence-based definition. In the past, physicians generally considered PE to have a psychological element, hence the historical use of psychotherapy to treat the condition. However, in recent years, the biological component has become more widely understood, and pharmacotherapy is the new focus for the treatment of PE.
Two types of PE have been widely recognized, lifelong (primary) and acquired (secondary) PE. Lifelong PE is present from the first sexual experience onwards, occurs in almost all attempts at intercourse, and is considered to have a neurobiological aetiology. Secondary PE occurs later in life after a period of perceived normal ejaculatory control and may have a psychological and neurobiological aetiology. This type of PE may be triggered by stress or linked to adverse events associated with medications.
The phosphodiesterase type 5 inhibitors, which are licensed for the treatment of erectile dysfunction, have been evaluated for use in PE. Despite their success in treating erectile dysfunction, there are limited data to support their use in PE alone.
When considering treatment for premature ejaculation there is a particularly popular medication; dapoxetine (priligy). Dapoxetine belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRIs). The mechanism of action of dapoxetine in premature ejaculation is presumed to be linked to the inhibition of neuronal reuptake of serotonin and the subsequent potentiation of the neurotransmitter‘s action at pre- and post-synaptic receptors. Dapoxetine overwhelms the neuronal compensatory mechanism. Dapoxetine is quickly absorbed with an onset of action within an hour and a half and is rapidly cleared, avoiding accumulation. It quickly increases the synaptic levels of serotonin, improving the symptoms of PE. Dapoxetine is absorbed and eliminated more quickly than conventional SSRIs and the unique pharmacology makes it ideal for on-demand dosing.
Do not drink alcohol whilst taking dapoxetine, as it might increase the sedative effects of the alcohol. It can also increase the risk of fainting.
Can I take tadalafil and priligy at the same time? No, it is recommended that you leave 48 hours between the two medications, this is due to the fact that they both cause a lowering of blood pressure so taking the two together could potentially cause dizziness, lightheadedness and fainting. It has been found that when treating ED with PDE5 inhibitors, sometimes PE resolves itself. The psychological effects of treating ED may in itself allow you to become more relaxed which lessens the chances of PE occurring. Options for treating are not limited to medication; You may find that increasing the frequency of sex (either intercourse or masturbation) solves the problem. After one orgasm, it is normal for the next one to take a little longer. Some men find it helpful to masturbate first (with or without their partner) so it takes longer to have an orgasm whilst having sex. Wearing a condom reduces sensation and this may be helpful. Premature ejaculation is less likely if you have sex with your partner on top. You may want to try the ‘squeeze technique’. Just before ejaculation, the head of the penis should be squeezed for 1-20 seconds. Either you or your partner can do this. The squeezing is usually done during masturbation (stimulation) of the penis but also can be done by stopping during intercourse. The squeezing reduces an erection and delays your orgasm. The process must be repeated three times before having an orgasm. It requires a lot of practice. The ‘start-stop’ technique is similar but you simply stop the stimulation or the intercourse just before ejaculating. Wait for your erection to subside a little, before carrying on. Again, the idea is to repeat three times before having an orgasm. You need the practice to recognise the moment just before an orgasm in order to be able to stop in time. Psychological treatments are sometimes used but no one is sure just how effective they are.
A review of phosphodiesterase type 5 inhibitors Schellack N, BCur, BPharm, PhD(Pharmacy), Senior Lecturer Agoro A, BPharm, Academic Intern Department of Pharmacy, Faculty of Health Sciences, University of Limpopo (Medunsa Campus)
Assured Pharmacy is not liable for the currency or accuracy of the information contained in this blog post. For specific information about your personal medical condition, please contact our doctors or pharmacists for advice on [email protected].