Hyaluronic acid is a polysaccharide existing in the intercellular matrix of dermal layers of the skin of all species (7, 9, 11). Therefore, when we apply HA in the field of plastic surgery, on the one hand, its high biocompatibility makes foreign body reactions rarely occur, and on the other hand, its ability to link water molecules and form hydrated polymers of high viscosity makes it an ideal soft tissue filler (7, 9, 11, 12). Thanks to mentioned properties, hyaluronic acid has been used as a safe soft-tissue filler for decades in various plastic surgery operations (7, 13). With the gradual application of HA in the field of andrology, it has shown a certain effect in the treatment of premature ejaculation(3, 4, 6, 12).
Generally, we can draw a conclusion from the current studies that patients received HA injection prolonged the latency of vaginal ejaculation (2, 14). The effect of injecting HA gel into glans penis to increase IELT may be due to the reduced glans sensation of glans penis, the formation of obstacles between the stimulating factor and receptor and enhancing confidence explained by placebo effect (3, 15). According to previous literature, it was mainly through the injection of HA into the proximal one-third of the glans to achieve the effect of penis augmentation and also to extend IELT(6, 14). Abdallah et al. reported the improvement in IELT in 49 patients after enlargement of the glans penis with HA from a mean of 127.2 to 462.6 and 319.2 s after 1 and 3 months respectively (6). Analogously, a randomized controlled cross-over study by Littara et al. indicates IELT improves from a mean of 88.34s to 293.14s in 110 patients after 6 months (4). In our study, the mean age of the patients was 34.30 6.72 years old. The mean IELT increase from 127.2 49.6 s to 452.1 121.7 s after one month. At three month follow-up, IELT dropped to 331.2 81.2 s (Figure 2). In addition, through evaluating PEP and patient satisfaction, we found that there is no significant difference in efficacy between the two injection methods.
It is worth noting that although HA injection has achieved satisfactory results in the treatment of premature ejaculation, the side effects produced cannot be ignored. Up till now, there is no recognized surgery for premature ejaculation. As an affordable, nonsurgical alternative for correcting contour defects and soft tissue augmentation (16), HA injecting has its own unique advantages of simple operation, low incidence of complications and ability to combine with other surgeries. Although the incidence of complications is low owing to the high biocompatibility, several common complications are still observed. JJ Kim et al. reported 9 patients with adverse reactions in 45 patients who received dorsal nerve neurectomy with HA injection, the incidence is 20%, however, the patients who only received HA injection did not have any adverse reactions (3). Abdallh et al. reported 7 patients having complications with multiple puncture technique and 7 patients having complications with fan technique and the percentage was 26.9% and 30.4% respectively (6). However, Littara et al. reported no adverse reactions in 171 patients (4). In addition to studied above, Amr Alahwany et al. reported 6 patients in 30 patients (20%) with adverse effects after 1 week of HA injection (12). What’s more, Dae Yul Yang et al. reported 3 patients in 33 patients (9.1%) in a study of comparison of HA and polylactic acid filler (10). Overall, the incidence is between 9.1%-30.4% which are not some numbers that could be ignored facilely.
Among these adverse effects, HA nodules, edema, erythema, granulomatous foreign body reaction and ischemic necrosis are most common (5, 11). The possible causes of side effects include the low purity of HA gel, excessive gel injection, the incorrect layer of location, or injection into the blood vessels (17). In our study, similar types of complications as above were observed. On the basis of reducing complications, our technique is to reduce HA nodules and vascular embolism. As the most common complications, HA nodules are mainly caused by uneven distribution of HA gel. Although we can speed up the redistribution of HA by massaging the nodules, if the injection is too fast or the nodules are too large, the nodules will not disappear easily even after 1-2 months of massage. Oversized nodules and too long recovery time both bring troubles or depression, which even prolonged some patients’ time to restart sex life. Compared to fan technique, one advantage of our injecting technique decreases HA nodules after HA injection. Compared to glans penis surface, the stratum corneum of coronal sulcus is thicker, which means more space for HA and less likely to be swelling and form HA nodules. A slice of literature may not consider the hyaluronic acid nodules formed after injection as a complication, but this does bring troubles and aesthetic dissatisfaction to a number of patients. When we inject in the glans penis, it is equivalent to injecting on a flat surface, and injecting in the coronal sulcus is equivalent to linear injection, so our modified injection method can significantly reduce the fluctuation of the glans penis after injection and obtain a more ideal effect. Our simplified injection method significantly reduces the occurrence of hyaluronic acid nodules (Figure 3). In our study, the percentage of complication of group 1 and group 2 are 25.8% and 1.9% respectively. After observing and comparing the mentioned data, we find that when close to the glans penis, the complication rate increased significantly. When we injected HA around coronary sulcus, there are no severe complications observed (Figure 4).
Regional vascular embolism was the most severe complication. If vascular embolism is severe, skin necrosis will occur further. The main reason of vascular embolism is that HA is injected into the vessels in the corpus cavernosum of penis. If the injection is too superficial, the above-mentioned HA nodules and fluctuations will occur, but if it is too deep, there is a risk of injecting HA into the blood vessel and thus vascular embolism (14). It can effectively avoid the risk of vascular embolism by our injection technique, because the coronary sulcus is farther away from the blood vessel. The use of this technique in our study did not produce any serious complications including vascular embolism and necrosis.
On the basis of less adverse reactions, the effect of treating premature ejaculation by coronary sulcus injection is as promising as the previously reported injection method. Because of the more complicated and scattered distribution of nerves on the glans, surgical procedures on this area of the penis may result in some serious adverse effects. Therefore, incisions in the glans should be limited, and if needed, should be made as distally and little as possible (18, 19). We noticed that anatomy does not acquire importance in previous studies and the principle of avoiding the distal end is not taken into account. Based on the above clinical anatomy, we believe that HA injection at the margin of coronary sulcus is safer than that at glans.
In addition to the advantages mentioned above, our injection method has the following strongpoints. First of all, the difficulty of injection technique is the challenge of using HA injection to treat premature ejaculation. Combined with multipuncture technique, it decreases HA nodules or fluctuation on the glans by HA injecting around coronary sulcus, which actually simplifies the injecting technique. As a result, inexperienced doctors can quickly master this technique, which is beneficial to verify efficacy. And it standardizes the injection procedure by stipulating the total injection sides, injection areas around coronal sulcus and quantity of HA of each injection. Second, as some patients do not have any obstacles to the appearance of the penis, such as concealed penis and small penis syndrome, their purpose of coming to see a doctor is simply to improve the symptoms of premature ejaculation caused by hypersensitivity of dorsal nerve branches or psychological factors. One advantage of our surgical method is that it meets the demands of patients who only want to treat premature ejaculation rather than enlargement of the glans. At last, multiple injections of HA will increase the incidence of complications (14), but our technology will not produce severe complications, which makes multiple injections possible. It has the hope of becoming a feasible standard procedure for the treatment of premature ejaculation.
From assembled data, we think that injection around coronary sulcus has several advantages over technique of injection at glans penis. However, the limitation of our study is that we did not divide the glans and the coronal sulcus into several areas for injection separately to compare the aesthetic effect and the incidence of complications. In addition, large enough patients and long-term follow-up are necessary to determine further efficacy. And we did not have a control group considering the effect of injecting HA at glans penis have been verified in lots of literatures. In addition, according to ISSM definition, the primary premature ejaculation is defined as within 1 minute. However, most of the patients come for consultation when they are depressed when the IELTs does not meet their criteria. As mentioned in this study, the IELTs is 124.7 39.01 seconds and 121.9 36.58 seconds in two groups respectively. Strictly speaking, this IELTs is apparently longer than the definition of ISSM, as a result, we hold the belief that we could enlarge the sample size, and sub-group participants, so that we could list a group and which meet the ISSM criteria, and we could probe into the efficacy and complications of the subgroup.