Into the Mind of the Penis: Premature Ejaculation Through the Veil More than 400 years ago Leonardo da Vinci said that the penis has a mind of its own. When his master is asleep, he can not only have an erection at will (nocturnal erection), but also excrete semen on his own (nocturnal dream emission). When the penis does not work properly, such as erectile dysfunction, abnormal ejaculation (premature ejaculation, difficulty in ejaculation), his master is often helpless. For centuries, his master has been trying to get into the mind of the penis, trying to unravel his mysteries so that when he is not working properly, his master can help him get out of the situation. For penile erectile dysfunction, the master now has a winning weapon. Today, let’s enter the mind of the penis and explore the secrets of premature ejaculation through the layers of the veil. What is considered premature ejaculation Exactly what happens when the penis ejaculates is considered premature ejaculation? Sexologists have scientifically investigated and argued that premature ejaculation takes into account four factors: short ejaculation time, poor ejaculation control, negative emotions and sexual interaction disorders. From the first time of sexual intercourse, the penis always ejaculates in less than 1 minute after vaginal penetration; if the ejaculation time has always been normal, it gradually or suddenly becomes shorter in a certain period of time, ejaculating in less than 3 minutes. Ejaculation before vaginal penetration is the most severe form of premature ejaculation and these patients face difficulties in natural reproduction. When suffering from premature ejaculation, 90% of patients feel poor ejaculatory control, 78% feel unsatisfied with their sexual life, 75% are accompanied by numerous negative emotions such as endless distress, worry and frustration, and 50% avoid sexual interactions due to fear of intercourse, which eventually leads to distancing from intimacy with sexual partners. The incidence of premature ejaculation is a common sexual dysfunction in men, with a prevalence of 20%-30% and an equal chance for people of all ages, with no age preference. It is estimated that the number of people suffering from premature ejaculation in China is not less than 20 million. Although the number of people suffering from premature ejaculation is large, many patients tend to seek medical treatment in private or in private for personal privacy and embarrassment, and there are more misdiagnosis and mistreatment; on the other hand, many non-professional physicians lack a clear understanding of premature ejaculation and do not master effective treatment methods, so they are often helpless in the face of premature ejaculation patients. With the change in people’s perception of sexuality, the impact of premature ejaculation on the quality of life of patients and sexual partners is gaining more and more attention, and it is urgent to get effective treatment from professional physicians. Unfortunately, only 9% of premature ejaculation patients actively seek the help of a medical professional. Milestone drug therapy Decades ago, it was noticed that a class of drugs specifically designed to treat mood disorders, SSRIs, had a side effect of inhibiting ejaculation, and doctors began experimenting with them to treat premature ejaculation, excitedly observing satisfactory results. The SSRI drugs, such as Dapsiglitazone, can rapidly increase 5hydroxytryptamine in just 1.5 hours after entering the body, which can prolong the ejaculation time by 2-3 times, and is quickly cleared by the body after it works. The retention time in the body does not exceed 24 hours. This drug has been used in more than 6,000 cases around the world, making it a landmark drug for premature ejaculation. Despite the good results of oral medications, about 15-20% of patients do not achieve satisfactory results. Premature ejaculation involves not only the central nervous control of ejaculation, but also the over-sensitivity of the glans penis. The glans penis is the key site for sensing and uploading ejaculatory stimuli. If the glans penis is overly sensitive, it can greatly reduce the threshold of stimulation needed to stimulate ejaculation. Therefore, some topical medications or behavioral therapies have been effective in treating premature ejaculation by reducing glans sensitivity, such as glans anesthetics, wearing condoms, masturbating before intercourse, and behavioral therapies (“stop-and-go” and “squeeze and pinch” techniques). Internal and external treatments, i.e. oral medication combined with external anesthetics or condoms, or combined with behavioral therapy. Numerous studies have confirmed that both internal and external treatment can free more patients from the dilemma of premature ejaculation than internal medication alone. The combination of ED and premature ejaculation is a common problem in 30%-50% of patients with erectile dysfunction (ED) who also suffer from premature ejaculation, and ED patients generally have a strong sense of sexual anxiety and tend to resort to high levels of self-stimulation during intercourse to obtain an erection, or consciously enter into the act of intercourse immediately, leading to premature ejaculation. PDE5 inhibitors are an effective treatment for ED, shortening the time to re-erection reflex after ejaculation, maintaining a better erection, helping to relieve sexual anxiety and raising the ejaculation threshold. In patients with ED and premature ejaculation, PDE5 inhibitors combined with SSRI therapy can improve ejaculatory control and prolong ejaculation time more than pharmacotherapy alone, greatly improving overall satisfaction with sexual life. Unknown Etiology and Future Challenges The etiology of premature ejaculation is still not fully understood, but many risk factors for premature ejaculation have been identified, including mental anxiety and stress, genetic susceptibility, erectile dysfunction, prostatitis, thyroid hormone disorders, poor general fitness, excessive obesity, and experience of failed intercourse. The prevalence of premature ejaculation in first-degree male relatives of premature ejaculation patients can be as high as 91%, and a survey of 1196 male twins also showed that the genetic predisposition to premature ejaculation is 28%, which indicates a certain genetic predisposition to premature ejaculation. It is known that 5hydroxytryptamine and dopamine are two important neurotransmitters that inhibit and promote ejaculation, respectively. In-depth research on the genetic susceptibility to premature ejaculation of 5hydroxytryptamine and dopamine-related genes has given people hope to fully unveil the veil of premature ejaculation.