Memo in Response to the JAMA article: “Analysis of Direct-to-Consumer Marketing of Platelet-Rich Plasma for Erectile Dysfunction in the US”
Introduction Or Why I Wrote This Memo
The P-Shot® is currently provided by over one thousand physicians (and physician extenders), including professors of urology at teaching institutions worldwide; but, many more providers of this procedure are needed.
So, I was pleased to read the JAMA, May 26, 2022 article, “Analysis of Direct-to-Consumer Marketing of Platelet-Rich Plasma for Erectile Dysfunction in the US,” by the prestigious group of scientists, Shahinyan et al. Moreover, I am especially grateful for their mention of the P-Shot® (Priapus Shot®)procedure. Hopefully, the discussion prompted by this fascinating article, by Shahinyan et al, will prompt more physicians to discover the benefits of the P-Shot® procedure and will help fuel more research in regard to using platelet-rich plasma (PRP) for the treatment of erectile dysfunction (ED).
The information provided by Shahinyan et al. in the article under discussion does, however, warrant clarification and correction—which is the purpose of this memorandum.
The article will be discussed in the order in which it was written.
As you explore the ideas regarding the P-Shot® procedure, I hope that if you are a physician, you will reach out to us (the Cellular Medicine Association). We have a decade of experience, meet regularly for discussion about the procedure, share nuances about the procedure that likely will not be published for another 5 to 10 years, and have new research underway that we are eager to discuss.
If you are a man suffering from sexual dysfunction, you can find licensed providers of the P-Shot® procedure here<—click<–
To clarify the discussion of the article in JAMA about the P-Shot®, first consider the science and history of PRP injections into the penis for the purpose of correction of ED.
PRP & ED HISTORY
As early as 2003, Mike Siroky pointed out in the Journal of Urology that “current therapy, while effective in circumventing vasculogenic ED, is relatively ineffective in permanently reversing the condition. Further research aimed at long-term treatment strategies in vasculogenic ED is needed (Siroky2003).”
Treatments for ED, in 2003, as pointed out by Siroky, did not reverse the underlying pathology and therefore there was (and is) a need for finding therapies for erectile dysfunction that might reverse or slow the underlying, naturally-occurring disease process; for example phosphodiesterase type 5 inhibitors (PDE5Is), and alprostadil injections, and penile implants, all do little to correct the neurovascular disease that causes most ED; they only help the diseased tissue function to achieve a harder erection without improving the health of the tissue. As the disease progresses, existing pharmaceutical therapies become less effective–requiring higher doses, and risking more side effects, until eventually, they become ineffective.
Siroky also wrote, in the same 2003 article, a suggestion for one of several therapies that show promise to actually slow or reverse the disease process of ED, “Neovascularization using vascular growth factors has recently been demonstrated to be feasible in animal models.” (Siroky and Azadzoi, 2003, p. 24.
The growth factors to which Dr. Siroky referred (that cause neovascularization and neurogenesis) are found in PRP.
Seven years later, in January 2010, Garcia, et al., published in the Journal of Sexual Medicine a demonstration of an increase in dorsal nerve nitric oxide and an improvement in the corpus cavernosi architecture in diabetic rats after the rats received injections of adipocyte-derived stem cells. But, surprisingly, the article also reported that the transferred tagged stem cells mostly died; so, the authors concluded that associated growth factors (not the growth of the transferred stem cells) were responsible for the improvements seen.
These same growth factors to which Dr. Garcia referred (that can increase nitric oxide in the dorsal nerve and improve corpus cavernosi architecture) can be found in PRP.
This same year, in 2010, after reading these and other studies of PRP in the facial aesthetics arena (specifically those by Dr. Sclafani and others showing neovascularization and neurogenesis), Charles Runels first explored the use of PRP in facial aesthetics—developing his Vampire Facelift® procedure using a very specific method of injecting hyaluronic acid fillers combined with injecting PRP as part of the same procedure (which he trademarked in 2010 with the US Patent & Trademark Office, Reg #85127646).
Then, after actually seeing the results of neovascularization in the face after injection with PRP (increased rubor and turgor), and considering the research of Siroky and Garcia regarding growth factors as a possible treatment for ED, Runels then extended these ideas and developed a specific method for injecting the penis with PRP.
So, in 2010, the author of this memorandum (Charles Runels, MD), was the first to inject a human penis with PRP (both the PRP & the penis were his own). Then, seeing improvement in both size and function, he further developed the technique in the treatment of his own patients; and then (later in 2010) he registered his idea with the US Patent & Trademark Office (USPTO) for definition and protection of the specific method: using the name Priapus Shot® (Reg#3965320), he defined for the USPTO the procedure as a specific “medical procedure using blood-derived growth factors including platelet-rich fibrin matrix to enhance the size or function of the penis.” He then registered a synonym for the Priapus Shot®, the P-Shot® (Reg#4820964).
Other considerations that prompted that first injection in 2010 by Runels included his practice at a hospital-based wound care center, practicing facial aesthetics with hyaluronic acid fillers, and caring for over three thousand menopausal women and andropausal men who came to his private internal medicine practice for help with sexual relations.
Because of this mix of offerings in his practice, and seeing the non-standard unpredictable ways in which facial aesthetics are done, Runels recognized, in 2010, the need for standardization of how the PRP might be injected into the penis.
THE NEED FOR STANDARDIZATION
To better examine the need for standardization of PRP injection techniques for the treatment of ED, by analogy, consider the situation with the injection of hyaluronic acid fillers (like Juvederm® or Restylane®) for aesthetic purposes: as of yet, there is still, in 2022, no standardization of methods of injection of HA fillers—none.
Also, there is still no medical board that governs how hyaluronic acid fillers are injected.
The techniques of injection of hyaluronic acid (HA) fillers vary so much that women often fear that, should they undergo treatment, they will be made to look “weird” or grow “duck lips.” Moreover, there is, with an improper injection of HAs, a significant danger of serious sequelae: blindness, skin necrosis, and pulmonary emboli.
Even with the serious risks of HA fillers, the license required to inject HAs varies greatly from state to state; for example, in Alabama, only MDs or DOs can inject HA fillers; in some states, an RN can inject them with physician supervision; in some states, nurse practitioners can inject them with supervision but RN’s cannot; in some states (with large rural areas and few MDs) nurse practitioners can both inject HA fillers and practice medicine (writing prescriptions for complicated medical patients on multiple medications with multiple organs failing)—with no physician supervision at all.
So, our current medical environment for all forms of medicine demonstrates a striking variability from state to state in the type of license needed to assume responsibility for the same degree of risk and the same needed skills.
Seeing the large variety of injection techniques and required licensing in the facial aesthetics arena, and anticipating that the same variability would be a huge problem if PRP were advertised for the treatment of sexual dysfunction without regard to standardization of technique or training is exactly what prompted Runels to file for a trademark: Priapus Shot® (and P-Shot®) are a type of trademark called a “service mark” that provides and demands standardization.
A “service mark” is a way of defining a specific method of doing something and then providing a legal mechanism to make sure that anyone using that service mark in advertising is using that same method; this is different from a trademark that protects a material or device: for example, Juvederm®, is a trademark which identifies a material, not a method of injecting; Vampire Faceilft® is a service mark, which identifies a specific method of injecting HA fillers combined with PRP.
The very existence and continued protection of the service mark, P-Shot® (or its synonym, Priapus Shot®) is the reason it is inaccurate to group together, in the JAMA article under consideration, those who simply advertise PRP (a material) for the penis (with no standardization of preparation or injection) with those who advertise the P-Shot® procedure (a specific method that does include standardization of injection techniques, as well as standard methods for pre and post-procedure, and specific financial policies in regards to protecting the patient).
For the standardization of the medical license required to qualify for training to do the P-Shot® and the further training required to offer the P-Shot® procedure, the policy of the Cellular Medicine Association(which oversees the licensing of the P-Shot® trademark and currently enjoys the collaborative efforts of over 3,600 physicians and their extenders in over 55 countries) established the policy that the license to inject PRP under the trademarked names (P-Shot® or Priapus Shot®) will mirror for each state the same policy within each state regarding the license to inject HA fillers. This policy would apply to anyone legally using the name P-Shot® but could not apply to anyone advertising the generic term, PRP, since the Cellular Medicine Association (CMA) has no legal ability or desire to demand a cease and desist order for using a generic term (PRP).
To continue our analogy, in regards to HA fillers, the marketing to consumers of Juvederm® and other HA fillers does nothing more than identify the material to be injected (not the method of injection).
Advertisements by both manufacturers (such as Allergan) and physicians who offer HA fillers essentially say, “Come here for your Juvederm,” with no indication of the method to be used for injecting the Juvederm.
Even if one chooses a provider based on board certification (for example, going to someone boarded in plastic surgery), depending on the state, if one simply chooses the provider based on the name of the product (trademark indicating a material, not a method), the injector in the plastic surgeon’s office may very well be an RN physician extender (no prediction of the license of the injector) and the injection technique will likely also vary from office to office.
Since Shahinyan et al. did not make this distinction between surveying those advertising PRP (a material) and those advertising the P-Shot® procedure (a specific and legally-defined method involving patient selection, monetary policy, preparation of PRP, and method of injection of PRP), and instead equated all of the clinics (whether advertising a material or a method), and since the authors failed to use the ® mark to acknowledge the trademark, P-Shot® (demonstrating that the authors are unfortunately blind to the mark and to its purpose), most of the conclusions of their paper become suspect at best.
In summary (and ironically), the P-Shot® procedure methodology, to which the authors erroneously refer without using the ® symbol, actually solves the problem (standardization of method and provider qualifications) that the authors lament is lacking in the clinics surveyed by their report in JAMA.
MORE PRP HISTORY
Autologous-derived PRP has been used for decades by dentists, orthopedic surgeons, and others dealing with difficult-to-treat wounds in order to promote healthier tissue growth.
Platelets are naturally activated by the thrombin cascade to release their growth factors whenever an injury occurs (including every surgery); with this activation is formed platelet-rich fibrin matrix (PRFM) which holds in place the growth factors and chemotactic factors released from platelets—recruiting and activating local and distant pluripotent stem cells to grow new and healthier tissue.
The reason the orthopedists and dentists were interested in PRP before urologists, gynecologists, and most facial plastic surgeons took note of PRP is because orthopedists and dentists routinely deal with completely avascular tissue and so were looking for ways to improve post-op recovery in hard-to-heal tissue by injecting into avascular tissue the growth factors that would be in the blood and promote healing if the tissue were vascular. So, the devices that are now FDA-cleared to prepare PRP for injection back into the body and that are being used for the preparation of PRP for injection into the face and into the genitalia of both men and women, these devices were researched and developed in the arenas of dentistry and orthopedics for two decades before being brought into the sexual medicine arena.
As an analogy about the uneven progress of medicine between specialties, gynecologists were using endoscopic surgery for years while the general surgeons largely ignored the tools; hysterectomy was done endoscopically for years before cholecystectomy. The general surgeons became proficient with endoscopic surgery after Dr. Bill Seay (a gynecologist) demonstrated that an endoscopic cholecystectomy might be feasible and safe. Before then, the proverbial left-hand-specialty was unaware of what the right-hand-specialty was doing). In the same way, dentists and orthopedic surgeons, and the bench-scientists used PRP and worked out much of the methodology, before most urologists (dealing with vascular tissue and not needing PRP for post-op recovery) became aware of the tool.
In summary, the use of autologously-harvested platelets enriched in numbers within the patient’s own plasma and then injected into damaged or diseased tissue to encourage the growth of healthier tissue is not “homeopathy” or “alternative” medicine (as suggested by the JAMA article under review), it is just medicine—employing well-known principles of wound care and tissue healing to improve tissue health and function.
To see other areas of medicine where PRP is supported by the research, consider examples of a few of the current uses of PRP that have evolved from the work of the dentists and orthopedic surgeons (and their supporting bench scientists doing the needed in vitro and animal studies):
- The care of a sternal wound (post-CABG);
- To promote healing and to fight infection of the ulcers of the distal extremities (even in the face of diabetes);
- To treat alopecia areata
- To control pain;
- To improve function and slow degeneration in osteoarthritis of the knee;
- To remodel acne scars;
- To treat nasolabial folds to create a younger-appearing face;
- To promote hair growth,
- To help recovery post Bell’s Palsy,
- To treat urinary incontinence in women,
- To treat interstitial cystitis
- To help with the harvest of viable eggs in a postpartum woman
- To help with the pain and healing post mesh placement in women.
The list is potentially as extensive as the need for healthier tissue.
All of these uses are supported by research. And all of the uses are both autologous and homologous (in keeping with the body’s natural function in regards to platelet-derived growth factors) and so are not governed by the FDA (the FDA does not govern hair, blood, urine, and skin—those are ‘minimally manipulated” and belong to the patient; the procedures done with these tissues are the business of doctors, not the FDA).
The authors of the JAMA article state that “guidelines from professional societies, such as the American Urological Association…classify PRP as investigational and not to be provided for payment.” (Shahinyan et al., 2022, p. 1Yet, the guidelines referenced were written 4 years ago. The use of platelet-derived growth factors for the propagation of healthier tissue in the penis (as with the above-mentioned indications), with a resultant improvement in erectile function, is supported by research that has grown significantly since the publication of the guidelines referenced by the authors of the JAMA article.
It may be helpful to rethink and revise the current JAMA article through the history of the additional research, both in other fields of medicine and within the urology arena, that has educated us over the post-guideline, four-year era.
Before looking more closely at the more current research, the idea of what’s “novel” should be considered, since that is also mentioned in the JAMA article under review.
SEEKING THE “NOVEL CURE” OR THE “NEW PENIS”?
The authors also report in JAMA that the P-Shot® is marketed to men looking for “novel cures.” I suggest this statement seems to be an assumption by the authors (without significant supporting research since they called the clinics not the patients of the clinics) using clairvoyance rather than research to determine the volition of men who receive PRP for ED.
Since P-Shot® providers do, in fact, survey their patients, I can state (without assuming) that men who receive the P-Shot® procedure are educated enough to not be duped into being “driven” to treatment simply because it is “novel”; when men seek a P-Shot® procedure, what they want is not a novel treatment but a new penis: a harder erection by improving the health of the penis (instead of a ‘bandaid’ that improves function for the night but that neither addresses nor slows the progression of the underlying neurovascular pathology).
This goal of a new penis is in keeping with the goals stated as desired by Dr. Siroky in the 2003 Journal of Urology article referenced previously referenced in this memo.
Instead of “novel,” men also want something that works without the risk of blindness or stroke or the inconvenience of headache or the pain of a penis shot of vasodilators as part of foreplay, or a surgery (unless needed), or the lifetime expense of medicines (over time, such expense is greater with the PDE5Is than with an occasional P-Shot®).
TESTICLES ARE A FAD
The authors also mention, as an analogy to PRP, the recent growth of the numbers of men seeking testosterone replacement, calling the trend of increasing numbers of men seeking testosterone a “health fad” that resulted from “direct-to-consumer marketing.”
Describing the idea that testosterone replacement for men grew in popularity solely as a health fad without mentioning the simultaneous explosion of research supporting the ways testosterone replacement may benefit an andropausal man could be discussed at length; but, since that would require a whole textbook, I will forgo that discussion and simply notice that the direct-to-consumer marketing of PRP mentioned by the authors is dwarfed beyond comparison by the mammoth amount of money spent to advertise phosphodiesterase 5 inhibitors (PDE5Is).
It is unlikely that one will ever see an ad for PRP on sports TV because there can be no patent on a person’s blood, therefore there can be no profit made regarding PRP by pharmaceutical companies—the only for-profit entity in medicine that can afford such advertising.
Drugs are not bad, drugs save lives. Profit is not evil; pharmaceutical companies need profit to afford the research that finances the discovery of new drugs that save lives. Physicians also need profit to pay for their staff, their children, their car to get to work, the lights at their office, and their malpractice insurance. But, in regards to the JAMA article under discussion, the amount of profit being made and the amount of advertising being financed in regards to PDE5Is is mammoth beyond comparison with the profit and advertising associated with PRP.
Furthermore, even though the advertising dollars spent by companies advertising PDE5Is dwarfs the advertising dollars spent by physicians educating their patients about the P-Shot®, the whole issue seems irrelevant, since one will find no significant research showing that the amount of money spent on advertising correlates either negatively or positively with either the effectiveness or the need for any particular treatment.
In further discussions of profit, the authors mention their previous paper regarding the prescribing of testosterone without patient examination; the point is without question—testosterone should not be prescribed without a true history and physical exam. But, this point is again irrelevant to the P-Shot® procedure since by definition there must be an in-person encounter for the patient to undergo the procedure.
If the motivation of mentioning profits and price in regards to the P-Shot® procedure does not relate to the quality of care (and it seems that it does not), then that discussion takes the tone of labeling profits made by physicians to be unethical (while ignoring the profits made by pharmaceutical companies). Most likely, the intention of the authors was not malicious; perhaps, though there is no way to know, such views of profit (from procedures not covered by insurance) could be the inevitable unconscious worldview of authors who (as stated with their conflict-of-interest disclosures in the JAMA article) are partly fed by the payroll of pharmaceutical companies.
Before going further to understand other important clarifications regarding the research related to the referenced JAMA article, the methods of the authors should be considered: they used “secret shopper methods” (Shahinyan et al., 2022, p. 1.
As mentioned previously, even though they included providers of the P-Shot® procedure in their analysis group, their secret shopper methods did not limit them to only the P-Shot® provider directory.
Restated, in fact, they grouped (in their statistical analysis) providers of PRP who do not use the P-Shot® name or methodologies together with those who do follow P-Shot® methodologies.
But, those who do not use the P-Shot® name have no standardization and those who do use the P-Shot® name do agree to a very definite standardization. Moreover, even when they “secret shopped” those using the P-shot® name in advertising, there is no mention of whether they checked to see if the person using the name is actually licensed (by the Cellular Medicine Association) to use the name in advertising—this is a critical point to consider when understanding the limitations and conclusions of the study.
In summary, the study defined an apples and oranges group; and the study’s assumptions and conclusions apply only to the apples. Two of the endpoints of the authors, the standardization and licensing of the providers, are not controlled in any way in the advertising of PRP; but, both of those variables are controlled in those offering the P-Shot® procedure—partly by spending millions on legal fees (by the CMA) to control who advertises with the name P-Shot® and Priapus Shot®. That money is spent both in the herculean efforts of training new providers and the legal battles of forcing the cease and desist outcome in thousands of infringers.
Furthermore, in regards to money and its relation to the patient, those in the CMA who provide the P-Shot® procedure agree to offer a complete money back to anyone who is not helped. Those who simply offer PRP injections often do not provide a refund if the patient is not pleased by the results of the procedure. So, the worst that could happen with a P-Shot® provider would be most likely only lost time and inconvenience but not lost money (except by the provider who loses the cost of goods and the time it took to care for the patient). But, patients who undergo PRP could be both out of pocket and perhaps even at the risk of serious disease by a provider who does not have the proper license.
Such a tragedy is not known with PRP in the penis, but a case of HIV from a Vampire Facial® procedure occurred by unlicensed providers who pretended to be providing the procedure and used inferior devices with inferior training (notice the reference to the function of the CMA in this article in Rolling Stone)<–.
Standardization and qualifications are important, as the authors in JAMA point out, but such standardization and qualification are being done by the CMA in regards to the P-Shot® procedure.
A “NEW TRANSMISSION” OR A “NEW PENIS”?
In regards to the cost of the procedure to the patient, the amount of money charged is similar to a new set of tires, definitely worth it if it helps (and the money is refunded if it does not help).
And, since the procedure is not yet covered by insurance, unless the provider wishes to pay to go to work instead of providing for her family, it is necessary for her to recover her time and cost of goods by charging the patient instead of insurance.
To understand the cost to the provider, consider that the time involved to offer the procedure is not simply to give a shot. Also required is the time and expense of taking a history, often talking with the spouse as well, in addition to time reviewing past medical records, doing phlebotomy, processing the blood to isolate the PRP using an FDA-cleared device (also an expense), and finally doing the injection, followed by phone calls and/or visits to evaluate results and make further recommendations.
A 1-hour massage at a nice hotel is $300 and is provided by someone who attended a six-month class. In contrast, a procedure that might improve relationships and involving an expensive FDA-cleared device, and the time and skills needed to evaluate the patient, do an exam, draw blood, inject the PRP into the corpus cavernosum, and follow up with the patient are worth more than a massage and probably as much as a new set of tires.
A HISTORY OF PRP: 4-YEAR UPDATE
Since Shahinyan et al. also lament the use of PRP ‘despite a paucity of evidence for its use” but use the word “paucity” without giving reference to the current body of research so that we may judge whether or not it is indeed pauce, it may be helpful fill in that omission with an overview of the current body of evidence regarding PRP and ED that has developed since the author’s referenced opinion (issued 4 years ago in the year 2018).
In an overview of the research, the body of PRP research, in general, has over 15,000 papers referenced in PubMed, most of which can be extrapolated to other parts of the body ubiquitously.
For example, if you show with biopsy that injecting PRP into the back of the arm results in neovascularization and neurogenesis (Sclafani) do you need to do the same study for the front of the arm, for the face, or for the penis? In fact, the reason Sclafani did the study on the arm is that he was looking for a way to improve the face; since a biopsy of the face would be undesirable, he knew that demonstrating the effects in the arm was enough to allow us to at least extrapolate the possibility of the idea to the face–and the penis.
Such studies that can be extrapolated include studies with scaring (which would relate to Peyronie’s disease) and tissue growth and wound healing.
Other important studies include those that show that saline has an effect on tissue growth and repair when used to hydrodissect tissue. So, in research regarding the promotion of healthier tissue, injecting saline is not a good placebo; since saline has an effect, the measured results of the studied method would be erroneously attenuated. Blinded placebo studies with PRP are considered impossible to do by some investigators because there is a physical component to the hydrodissection (as would be a blinded study of any surgical procedure). Comparison studies, or perhaps unblinded studies where the placebo is simply inserting the needle without injection, may be the highest level that can be accurately done.
For example, in one beautiful study,Ronal Virag compared PRP injections with Xyflex for Peyronie’s disease and showed that PRP improved Peyronie’s better than Xyflex (and the side effect of PRP was a harder erection, not the penile fracture seen with Xyflex, and PRP is cheaper than Xyflex). But, Dr. Virag, a true pioneer in sexual medicine, did not do a placebo study because he considers a placebo study with PRP to be largely impractical.
Even with the possibility of the saline causing benefit, investigators did publish in the Journal of Sexual Medicine, a double-blinded placebo-controlled study of PRP injected into the corpus cavernosum that showed statistical benefit. This study was published after the guidelines referenced in the JAMA article under discussion.
A sampling of research can be found referenced in the bibliography of this memo. You’ll see papers supporting PRP to help with BXO, Peyronie’s disease, ED, penile rehabilitation post prostate surgery, and urinary incontinence post prostate surgery.
You will also find referenced at the end of this memo a collection of papers demonstrating benefits to women with sexual dysfunction. This was included because the tissue of women and men is identical in many ways: both have corpus cavernosi, corpus spongiosum, a prostate (Skene’s glands), and similar problems with the same nerves and blood flow. Because there are fewer pharmaceutical solutions for women than for men (for example, women still do not have an FDA-approved form of testosterone), there seems to be more PRP research directed toward women; and much of it may eventually be extrapolated to men.
At what point the body of research ceases to be pauce and becomes sufficient to adopt the P-Shot® procedure into an everyday clinic setting will vary from clinician to clinician, like all new ideas, based on the risks of the procedure (almost none with PRP), the logic and science behind the idea (much with PRP), the possible benefits of the procedure (better penis health and stronger family relations), and the amount of supporting research, and the understanding of the clinician of the current research—but there is no clear finish line with any procedure.
The usual time frame for the widespread adoption of a new idea is around 20 years (for example the first heart catheterization was done in the 1940’s and it took about 20 years for the idea of antibiotics for peptic ulcer disease to become widely adopted).
Some of the determination of when to adopt a new treatment strategy may even vary based on whether it is the doctor who is suffering the social and psychological effects of ED with a disturbing attenuation of the effects of the usual pharmacological solutions, or it is the patient of the doctor who is suffering.
PHYSICIANS & NON-PHYSICIANS
The authors of the JAMA article under discussion found especially disturbing the “number of nonphysicians”providing PRP for ED. To emphasize what was mentioned earlier in this memo, analogous to hyaluronic acid filler use where in some states like Alabama no physician extenders can do hyaluronic acid filler where in some states RNs can inject hyaluronic acid fillers, there are no definite guidelines about who can inject PRP; so, we thought (at the CMA) the most logical strategy would be to reflect each state’s policy about which license would each state allow to inject hyaluronic acid fillers and then mirror that same official policy with PRP. The logic is that since hyaluronic acid filler injections can cause blindness, necrosis of skin, and pulmonary emboli when injected improperly, and since PRP is not associated with any of these complications, and so is safer than HAs, if we mirrored the HA policies in each state, there should be no objection.
But, there is no such governance of the injection or advertising of PRP as a generic term as we have both adopted and spent millions of dollars enforcing at the CMA.
Particularly confusing, the authors of the JAMA article were also bothered by the number of “physicians with no formal training in male sexual dysfunction, such as gynecologists.” Said another way, “gynecologists have no formal training in caring for men with sexual dysfunction and should not be allowed to do so.”
A number of years ago, ACOG, briefly, ruled that gynecologists should not take care of men–then they reversed that decision. Gynecologists have strong training in general primary care and women often bring their husbands with them to the gynecologist and want their gynecologist to care for them both as a couple. The American Board of Obstetrics and Gynecology, realizing that gynecologists have a deep understanding of endocrinology and in fact do the first male surgery that most men undergo (circumcision), wisely reversed their decision to prevent gynecologists from caring for men and determined that gynecologists are capable of caring for both women and men.
The authors of this JAMA article may disagree with the policy of the American Board of Obstetrics and Gynecology regarding the care of men by gynecologists, but perhaps it is worth considering and acknowledging the policy.
EMBARRASSING GUIDELINES AND “CONSUMERIZATION-DRIVEN” CATTLE
The authors lamented that “guideline-nonconformant care has been driven by the consumerization of sexual health.” If they mean by “guideline-nonconformant care” that the care is not in compliance with the American Urological Association written in 2018, then perhaps the previous review of the literature would reassure the authors that the guidelines may need revision.
As for men being “driven” like dumb cattle to the slaughter by “consumerization of sexual health,”perhaps, a more accurate view would be that smart men are not being driven like stupid cattle but are actually seeking help, being motivated by the pain of broken relationships and loss of self-esteem, to find therapies that match the current research so that they can, if possible, avoid the risks and expense of PDE5Is and surgery (both of which are more than that of a P-Shot® procedure).
A little more history about guidelines…
As another example of how guidelines can become out of date, a review article in Urology (Finkle1980) said, “most instances of acquired impotence are psychogenic. Any nonjudgmental, competent practitioner [urologist] can aid victims of psychogenic impotence by a ‘listening and encouragement’ method. Urologists, in particular, are commonly confronted with genital sexual problems and may be best suited as primary therapists by developing interest in urologic counseling.”
In review, in 1980, 85% of ED was thought, by the Amerian Board of Urology, to be psychogenic; so, urologists were encouraged to learn to be sex therapists.
Then, when a not-so-good blood pressure pill accidentally turned out to be a great ED pill because it improved blood flow, guidelines needed revision, and now instead of stating that 85% of ED is psychogenic, 85% of ED is now thought to be neurovascular.
When becoming attached to guidelines that are 4 years old, perhaps it is worth pausing and considering the mental anguish experienced by a man back in the 1980s who suffered ED from neurovascular disease while being told (from the guidelines) that his inability to make love to his wife would go away if he could just put his thoughts in order, so he signed up for sex-therapy with his urologist.
THE EVILS OF ADVERTISING
The authors were concerned that “advertising is associated with patient demand, particularly in men’s health.”But is not advertising associated with the demand for most anything? Is not that what advertising does? Patient demand is also associated with the degree of suffering and broken relationships and sexual dysfunction causes severe psychologica distress. The number of dollars spent advertising Viagra and male surgeries dwarfs that spent on advertising PRP treatments; because there is no drug to sell, you will likely never see an ad for PRP while watching the news or pro sports but such ads are frequent for Viagra and some male surgeries.
Still, even though Viagra® is associated with hundreds of cases of blindness every year (even when used properly), and more is spent on advertising for that than on PRP by far, such advertising is still legitimate as long as it is honest about what is possible and the risks involved.
The layperson cannot be expected to be up to date about the latest therapies, and the best advertising educates the person suffering from disease about the disease process and about possible methods of treatment. So, when used in that way, advertising is needed so that suffering people may know how to find help.
HAVE YOU EVER SEEN A PICTURE OF “THESE?”
The authors also worry that “these companies have been shown to omit appropriate medical evaluation, which may lead to patient harm.” (Shahinyan et al., 2022, p. 2 When the authors mention advertising platforms and include groups as diverse as gynecologists, chiropractors, and “unknown,” one might wonder how to recognize what “these” even means; at least if one wanted to take a picture of “these,” one might wonder where to aim the camera.
We agree, however, with the authors about the need for standardization (as stated previously in this note) and, seeing the wide variety that happened with hyaluronic acid filler injections, tried to avoid these dangers by the standardization of protocols that are embedded in the P-Shot® procedure (then we, the thousands of doctors who are members of the CMA, backed up that philosophy with a decade of teaching and millions in legal battles in 55 countries).
There is more in an “®” than meets the eye of most people.
WHAT DO PRP, SHOCK WAVE, AND STEM CELLS SHARE?
The authors classify as “experimental”three types of treatments in their statement about “experimental ED therapies, such as PRP injections, low-intensity shockwave therapy, and autologous stem cell injections.”
Experimental by policy?
If what is meant by “experimental” is that which is not yet approved by a policy that was made 4 years ago and by this paper which seems unaware of the research of the past 4 years, then perhaps the definition of what is experimental needs revision/updating.
Experimental by FDA?
If what is meant by experimental is that which is not yet approved by the FDA, then the grouping of these three is misleading since stem cells are regulated by the FDA, but PRP is still considered simply the person’s own tissue, like hair, or skin, or urine; so, PRP is not regulated by the FDA. Procedures are also not regulated by the FDA at all (not prostatectomy or hysterectomy, no procedure, ever). But devices are regulated by the FDA and the Cellular Medicine Association recommends that the P-Shot® procedure be done only with centrifuges that have been cleared by the FDA for the preparation of PRP to go back into the body (which is a different level of clearance than preparing blood for laboratory analysis).
Also, consider that there is still no FDA-approved form of testosterone for women. And testosterone for women when given by adjusting the dose of forms normally given to men is not often not covered by insurance.
Also, the research supporting shock wave therapy for neovascularization is also very compelling and the therapy has been proven to be safe and effective.
Experimental by Insurance?
Perhaps, the authors meant by “experimental” that there is still no insurance coverage for either PRP or shock wave therapy and so patients must be either treated for free (at the considerable expense of time and money to the doctor) or the patients must be charged.
This definition seems to personify the metaphor of the tail wagging the cow: should physicians really wait for the necessarily profit-driven insurance corporations to tell us what is good medicine? That seems to be a growing and pervasive attitude.
There are many examples of the gap between the recognition of what is helpful and what is covered by insurance. For example, there is no insurance coverage for Nike® shoes, but walking (when sufficient in volume) has been determined to be better at preventing heart attack than any diabetes or hypertension drug on the market.
Also, since PRP is the patient’s own blood and the device manufacturers cannot channel any cost of advertising to their particular device, there is little incentive by the device manufacturers and none by any pharmaceutical company to finance research to obtain the needed data to demand insurance coverage. The research sponsored by the CMA is minuscule compared to what is possible by the manufacturers of VIagra.
As another example, a study by Ronald Virag (referenced previously) demonstrated that PRP worked better than Xyflex for Peyronie’s disease at considerably less cost, with no risk of penile fracture (compared to around 1 in 50 of those who receive Xyflex), no downtime wiht the PRP, and the side effect of ED function going up by an average of 7 on the shim score! But you do not see ads about PRP as you do for Xyflex, and you see few large-scale studies because the funding is just not there. And you do not see an insurance code to reimburse for the procedure.
Also, placebo-control studies of PRP are difficult because saline (often used as a placebo) has effects of its own and as a stand-alone therapy has been used to treat scarring and promote tissue growth. So, saline’s appropriateness as a placebo has been questioned when studies involve the injection of materials intended to regenerate tissue with a hydrodissection-like delivery.
LIMITATIONS, CORRECTIONS, AND CONVERSATIONS
The authors concede that the study does have one (and only one) limitation: “A limitation of this study is the selective focus on large metropolitan areas, which may not be representative of smaller or rural areas.” (Shahinyan et al., 2022, p. 3.
But, perhaps, the study has more than one limitation including at least all of the following:
- Assuming that a policy made 4 years ago (not having any way to predict the post-policy research of the following 4 years) would not reflect the most up do date thinking that should be applied in today’s clinic.
- Assuming that everyone using PRP is operating without any standardization ignores the fact that those who are licensed by the Cellular Medicine Association to use the “P-Shot®” name have all studied the same protocol and agreed (with a signed document) to standardization of materials, methods, indications, and agree to refund all money when the patient is not satisfied with results.
- Assuming that gynecologists are incapable of understanding men’s sexual dysfunction ignores the fact that ACOG has agreed that gynecologists are as able to care for men as are urologists to care for women.
- Assuming that those who are licensed to do the P-Shot® can be of any training ignores the fact the CMA only licenses the use of the service mark, Priapus Shot® (P-Shot®), to those whose license would also cover the use of hyaluronic acid injections in the state in which he or she practices; such license would still not qualify the provider to advertise the procedure, but would be required to pass application for training to learn how to do the procedure.
- Assuming a paucity of research to support the idea of PRP without acknowledging the noticeable and growing body of research supporting the same.
- Assuming that advertising PRP directed toward men with ED is associated with bad medicine when in fact much more is spent advertising PDE5Is which are associated with more lifetime expense and a greater risk profile (including blindness and stroke) than is PRP (which has never caused either of these when injected into the penis).
Overall, I’m very grateful to the authors for noticing the P-Shot® and would invite them to further read the research and consider helping promote and further the research by joining the Cellular Medicine Association (CMA) and its efforts. The CMA has spent millions in doing exactly what the authors wish to be done (quality control, standardization, and research) and we grieve that they seem to be, until now, unaware of our existence or purpose. We (the members of the CMA) have done hundreds of thousands of P-Shot procedures over the past decade, but we need more help to do the needed research and to supply the demand for both the training of physicians and for the provision the service to men suffering from ED.
POSSIBLE FUTURE RESEARCH
As for the needed research, first, there becomes an understanding of a concept; then, after proof-of-concept, comes the study of the infinite variabilities that may affect the results and risks: for example the following are only some of the questions that need answering regarding the use of PRP for ED by future research:
- Who is most likely to be helped by PRP injections into the corpus cavern and who is least likely to be helped?
- How can the idea be integrated into penile rehabilitation post-prostatectomy.
- What injection technique variations would work best for Peyronie’s disease, trauma (bicycle, surgery), diabetes, BXO.
- Could PRP be used to improve the effectiveness of ED drugs, and to improve outcomes with penile implants (sensation and wound healing).
- What can be done with the PRP to improve its effectiveness? For, example, studies have shown that washing the platelets or cooling the platelets, aerobic exercise just prior to phlebotomy, or fasting prior to phlebotomy can all have beneficial effects.
- What patient factors would interfere with the effectiveness of the treatment? For example, some NSAIDS will attenuate the effectiveness and of course smoking (often left out of study inclusion and exclusion criterion), nutrition status, and platelet counts—all can have effects.
- Can effects similar to PRP be seen for ED with whole blood or saline?
- If saline has effects of its own when used to hydrodissect tissue, how should PRP studies be conducted? Is it possible to have a double-blind placebo-controlled study, or is PRP similar to birth-control pills, hysterectomy, and parachutes where perhaps the mechanics and ethics of double-blind placebo control studies make them impossible.
The orthopedic surgeons and dentists have a decade-long head start in regards to how and when to use PRP in the treatment of joint disease and likely much of their observations and conversations and experimentations can be extrapolated to the sexual dysfunction, urology, and gynecology world. Our patients need us to think deeply on these topics and when the benefits outweigh the risks (and the monetary risk to the patient is made zero by offering complete refunds to whoever the patient desires), patients and providers should be encouraged to proceed in concert with the growing body of research.
References about the need for a better way and the suggestion of using blood-derived growth factors.
- Siroky MB, Azadzoi KM. Vasculogenic Erectile Dysfunction: Newer Therapeutic Strategies. Journal of Urology. 2003;170(2S):S24-S30. doi:10.1097/01.ju.0000075361.35942.17
- Reference from Sclafani that Prompted the P-Shot® Development1.Sclafani AP, McCormick SA. Induction of dermal collagenesis, angiogenesis, and adipogenesis in human skin by injection of platelet-rich fibrin matrix. Arch Facial Plast Surg. 2012;14(2):132-136. doi:10.1001/archfacial.2011.784
1980 Urology Policy Regarding Urologists Becoming Therapists
1.Finkle AL. Sexual impotency: Current knowledge and treatment I. Urology/sexuality clinic. Urology. 1980;16(5):449-452. doi:10.1016/0090-4295(80)90592-0
References about treating acne scars with PRP
1.Bhargava S, Goldust M, Singer H, Negbenebor N, Kroumpouzos G. Evaluating resurfacing modalities in aesthetics. Clin Dermatol. 2022;40(3):274-282. doi:10.1016/j.clindermatol.2021.01.019
2.Majid I, Timungpi R. Platelet rich Plasma (PRP) in treatment of Topical steroid damaged face (TSDF): a retrospective analytical study. Dermatologic Therapy. n/a(n/a). doi:10.1111/dth.15356
3.Peng GL. Platelet-Rich Plasma for Skin Rejuvenation: Facts, Fiction, and Pearls for Practice. Facial Plastic Surgery Clinics of North America. Published online 2019. doi:10.1016/j.fsc.2019.04.006
4.Cui X, Ma Y, Wang H, Huang J, Li L, Cheng B. The Anti-photoaging Effects of Pre- and Post-treatment of Platelet-rich Plasma on UVB-damaged HaCaT Keratinocytes. :38.
5.Alser OH, Goutos I. The evidence behind the use of platelet-rich plasma (PRP) in scar management: a literature review. Scars, Burns & Healing. 2018;4:205951311880877. doi:10.1177/2059513118808773
References about the other indications regarding PRP
REFERENCES ABOUT IMPROVING HAIR
1.Gupta AK, Bamimore MA. The effect of placebo in split-scalp and whole-head platelet-rich plasma trials for androgenetic alopecia differs: Findings from a systematic review with quantitative evidence syntheses. J Cosmet Dermatol. Published online January 31, 2022. doi:10.1111/jocd.14813
2.Berebichez-Fridman R, Montero-Olvera PR. Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review. Sultan Qaboos University Medical Journal [SQUMJ]. 2018;18(3):e264-277. doi:10.18295/squmj.2018.18.03.002
3.Ozcan KN, Sener S, Altunisik N, Turkmen D. PRP application by dermapen microneedling and intradermal point-by-point injection methods, and their comparison with clinical findings and trichoscan in patients with androgenetic alopecia. Dermatologic Therapy. n/a(n/a). doi:10.1111/dth.15182
4.Jha AK, Vinay K, Zeeshan M, Roy PK, Chaudhary RKP, Priya A. Platelet-rich Jha, A. K., Vinay, K., Zeeshan, M., Roy, P. K., Chaudhary, R. K. P., & Priya, A. (2019). Platelet-rich plasma and microneedling improves hair growth in patients ofandrogenetic alopecia when used as an adjuvant to minoxidil. Journal of Cosmet. Journal of Cosmetic Dermatology. Published online 2019. doi:10.1111/jocd.12864
5.Contents. Dermatologic Clinics. 2021;39(3):v-vii. doi:10.1016/S0733-8635(21)00031-0
6.Anudeep TC, Jeyaraman M, Muthu S, et al. Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia. Pharmaceutics. 2022;14(3):612. doi:10.3390/pharmaceutics14030612
7.Anudeep TC, Jeyaraman M, Muthu S, et al. Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia. Pharmaceutics. 2022;14(3):612. doi:10.3390/pharmaceutics14030612
8.Wall D, Meah N, Fagan N, York K, Sinclair R. Advances in hair growth. Fac Rev. 2022;11:1. doi:10.12703/r/11-1
REFERENCES ABOUT HELPING WITH FEMALE URINARY INCONTINENCE
1.Kirchin V, Page T, Keegan PE, et al. Urethral injection therapy for urinary incontinence in women. The Cochrane Database of Systematic Reviews. 2017;2017(7). doi:10.1002/14651858.CD003881.pub4
2.Athanasiou S, Kalantzis C, Zacharakis D, Kathopoulis N, Pontikaki A, Grigoriadis T. The Use of Platelet-rich Plasma as a Novel Nonsurgical Treatment of the Female Stress Urinary Incontinence: A Prospective Pilot Study. Female Pelvic Med Reconstr Surg. 2021;27(11):e668-e672. doi:10.1097/SPV.0000000000001100
3.Samy Tahoon A, El-Din Hussein Salem H, Anwar Abdo Mousa A. The Role of Platelet Rich Plasma Injections in Cases of Stress Incontinence.; 2022. doi:10.32388/KG77ZQ
4.Joseph C, Srivastava K, Ochuba O, et al. Stress Urinary Incontinence Among Young Nulliparous Female Athletes. Cureus. 2021;13(9). doi:10.7759/cureus.17986
5.Zhou S, Zhang K, Atala A, et al. Stem Cell Therapy for Treatment of Stress Urinary Incontinence: The Current Status and Challenges. doi:10.1155/2016/7060975
6.Nikolopoulos KI, Pergialiotis V, Perrea D, Doumouchtsis SK. Restoration of the pubourethral ligament with platelet rich plasma for the treatment of stress urinary incontinence. Medical Hypotheses. 2016;90:29-31. doi:10.1016/j.mehy.2016.02.019
7.PANDIT M, DELANCEY JOL, ASHTON-MILLER JA, IYENGAR J, BLAIVAS M, PERUCCHINI D. Quantification of Intramuscular Nerves Within the Female Striated Urogenital Sphincter Muscle. Obstet Gynecol. 2000;95(6 Pt 1):797-800. Accessed October 20, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1192577/
8.Gorton E, Stanton S, Monga A, Wiskind AK, Lentz GM, Bland DR. Periurethral collagen injection: a long-term follow-up study. BJU international. 1999;84(9):966-971. Accessed August 24, 2015. http://www.ncbi.nlm.nih.gov/pubmed/10571621
9.Lee PE, Kung RC, Drutz HP. PERIURETHRAL AUTOLOGOUS FAT INJECTION AS TREATMENT FOR FEMALE STRESS URINARY INCONTINENCE: A RANDOMIZED DOUBLE-BLIND CONTROLLED TRIAL. Journal of Urology. 2001;165(1):153-158. doi:10.1097/00005392-200101000-00037
10.Ford AA, Rogerson L, Cody JD, Ogah J. Mid‐urethral sling operations for stress urinary incontinence in women. Cochrane Database of Systematic Reviews. 2015;(7). doi:10.1002/14651858.CD006375.pub3
11.Zubieta M, Carr RL, Drake MJ, Bø K. Influence of voluntary pelvic floor muscle contraction and pelvic floor muscle training on urethral closure pressures: a systematic literature review. Int Urogynecol J. 2016;27(5):687-696. doi:10.1007/s00192-015-2856-9
12.O’Connor E, Riogh AN an, Karavitakis M, Monagas S, Nambiar A. Diagnosis and Non-Surgical Management of Urinary Incontinence – A Literature Review with Recommendations for Practice. IJGM. 2021;14:4555-4565. doi:10.2147/IJGM.S289314
13.Cosmetic surgical procedures on the vulva and vagina – an overview. Indian Journal of Medical Ethics. Accessed January 18, 2022. https://ijme.in/articles/cosmetic-surgical-procedures-on-the-vulva-and-vagina-an-overview/
14.Oshiro T, Kimura R, Izumi K, Ashikari A, Saito S, Miyazato M. Changes in urethral smooth muscle and external urethral sphincter function with age in rats. Physiological Reports. 2021;8(24):e14643. doi:10.14814/phy2.14643
15.Callewaert G, Da Cunha MMCM, Sindhwani N, Sampaolesi M, Albersen M, Deprest J. Cell-based secondary prevention of childbirth-induced pelvic floor trauma. Nat Rev Urol. 2017;14(6):373-385. doi:10.1038/nrurol.2017.42
16.Perucchini D, DeLancey JOL, Ashton-Miller JA, Galecki A, Schaer GN. Age effects on urethral striated muscle II. Anatomic location of muscle loss. American Journal of Obstetrics and Gynecology. 2002;186(3):356-360. doi:10.1067/mob.2002.121090
17.Perucchini D, DeLancey JO, Ashton-Miller JA, Peschers U, Kataria T. Age effects on urethral striated muscle I. changes in number and diameter of striated muscle fibers in the ventral urethra. American Journal of Obstetrics & Gynecology. 2002;186(3):351-355. doi:10.1067/mob.2002.121089
18.Wiśniewska-Ślepaczuk K, Pieczykolan A, Grzesik-Gąsior J, Wdowiak A. A Review of Aesthetic Gynecologic Procedures for Women. Plastic Surgical Nursing. 2021;41(4):191-202. doi:10.1097/PSN.0000000000000400
19.Long CY, Lin KL, Shen CR, et al. A pilot study: effectiveness of local injection of autologous platelet-rich plasma in treating women with stress urinary incontinence. Sci Rep. 2021;11(1):1584. doi:10.1038/s41598-020-80598-2
REFERENCES REGARDING THE USE OF PRP TO HELP WITH FEMALE ORGASM
1.Handy AB, Stanton AM, Meston CM. Understanding Women’s Subjective Sexual Arousal Within the Laboratory: Definition, Measurement, and Manipulation. Sexual Medicine Reviews. 2018;6(2):201-216. doi:10.1016/j.sxmr.2017.11.001
2.Sanoulis V, Nikolettos N, Vlahos N. The use of Platelet-Rich Plasma in the Gynaecological Clinical Setting. A review. 2019;18(3):11.
3.Prodromidou A, Zacharakis D, Athanasiou S, et al. The Emerging Role on the Use of Platelet-Rich Plasma Products in the Management of Urogynaecological Disorders. Surg Innov. Published online April 28, 2021:15533506211014848. doi:10.1177/15533506211014848
4.Matz EL, Pearlman AM, Terlecki RP. Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions. Investig Clin Urol. 2018;59(1):61-65. doi:10.4111/icu.2018.59.1.61
5.Jb N. O-Shot: Platelets Rich Plasma in Intimate Female Treatment. Published online 2017:4.
6.Sharp G, Maynard P, Hamori CA, Oates J, Sarwer DB, Kulkarni J. Measuring Quality of Life in Female Genital Cosmetic Procedure Patients: A Systematic Review of Patient-Reported Outcome Measures. Aesthetic Surgery Journal. 2020;40(3):311-318. doi:10.1093/asj/sjz325
7.Zheng Z. Materials Selection for the Injection into Vaginal Wall for Treatment of Vaginal Atrophy. Published online 2021:11.
8.Hersant B, SidAhmed-Mezi M, Belkacemi Y, et al. Efficacy of injecting platelet concentrate combined with hyaluronic acid for the treatment of vulvovaginal atrophy in postmenopausal women with history of breast cancer. Menopause. 2018;25(10):1. doi:10.1097/GME.0000000000001122
9.Long CY. A pilot study: effectiveness of local injection of autologous platelet-rich plasma in treating women with stress urinary incontinence. Scientific Reports. Published online 2021:9.
10.Runels C. A Pilot Study of the Effect of Localized Injections of Autologous Platelet Rich Plasma (PRP) for the Treatment of Female Sexual Dysfunction. J Women’s Health Care. 2014;03(04). doi:10.4172/2167-0420.1000169
REFERENCES REGARDING THE TREATMENT OF INTERSTITIAL CYSTITIS WITH PRP
1.Trama F, Illiano E, Marchesi A, et al. Use of Intravesical Injections of Platelet-Rich Plasma for the Treatment of Bladder Pain Syndrome: A Comprehensive Literature Review. Antibiotics (Basel). 2021;10(10):1194. doi:10.3390/antibiotics10101194
2.Ke QS, Jhang JF, Lin TY, et al. Therapeutic potential of intravesical injections of platelet-rich plasma in the treatment of lower urinary tract disorders due to regenerative deficiency. Ci Ji Yi Xue Za Zhi. 2019;31(3):135-143. doi:10.4103/tcmj.tcmj_92_19
3.Mirzaei M, Daneshpajooh A, Farsinezhad A, et al. The Therapeutic Effect of Intravesical Instillation of Platelet Rich Plasma on Recurrent Bacterial Cystitis in Women: A Randomized Clinical Trial. Urol J. 2019;16(6):609-613. doi:10.22037/uj.v0i0.5239
4.Dönmez Mİ, İnci K, Zeybek ND, Doğan HS, Ergen A. The Early Histological Effects of Intravesical Instillation of Platelet-Rich Plasma in Cystitis Models. Int Neurourol J. 2016;20(3):188-196. doi:10.5213/inj.1632548.274
5.Huang YC, Chuang YC. Reply to the Commentary on “New Frontiers or the Treatment of Interstitial Cystitis/Bladder Pain Syndrome-Focused on Stem Cells, Platelet-Rich Plasma, and Low-Energy Shock Wave.” Int Neurourol J. 2020;24(4):389-390. doi:10.5213/inj.2040414.207
6.Jiang YH, Kuo YC, Jhang JF, et al. Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis. Sci Rep. 2020;10(1):15218. doi:10.1038/s41598-020-72292-0
7.Jhang JF, Wu SY, Lin TY, Kuo HC. Repeated intravesical injections of platelet-rich plasma are effective in the treatment of interstitial cystitis: a case control pilot study. Low Urin Tract Symptoms. 2019;11(2):O42-O47. doi:10.1111/luts.12212
8.Ozyuvali E, Yildirim ME, Yaman T, Kosem B, Atli O, Cimentepe E. Protective Effect of Intravesical Platelet-Rich Plasma on Cyclophosphamide-Induced Hemorrhagic Cystitis. Clin Invest Med. 2016;39(6):27514.
9.Chen YH, Man KM, Chen WC, et al. Platelet-Rich Plasma Ameliorates Cyclophosphamide-Induced Acute Interstitial Cystitis/Painful Bladder Syndrome in a Rat Model. Diagnostics (Basel). 2020;10(6):E381. doi:10.3390/diagnostics10060381
10.Jhang JF, Lin TY, Kuo HC. Intravesical injections of platelet-rich plasma is effective and safe in treatment of interstitial cystitis refractory to conventional treatment-A prospective clinical trial. Neurourology and Urodynamics. 2018;(October). doi:10.1002/nau.23898
11.Jhang JF, Jiang YH, Hsu YH, et al. Improved Urothelial Cell Proliferation, Cytoskeleton and Barrier Function Protein Expression in the Patients With Interstitial Cystitis/Bladder Pain Syndrome After Intravesical Platelet-Rich Plasma Injection. Int Neurourol J. 2022;26(Suppl 1):S57-67. doi:10.5213/inj.2142100.050
12.Riccetto CLZ. Editorial Comment: Intravesical injections of platelet-rich plasma is effective and safe in treatment of interstitial cystitis refractory to conventional treatment-A prospective clinical trial. Int Braz J Urol. 2021;47(2):456-457. doi:10.1590/S1677-5538.IBJU.2021.02.04
REFERENCES REGARDING THE TREATMENT OF MESH COMPLICATIONS IN WOMEN WITH PRP
1.Prodromidou A, Zacharakis D, Athanasiou S, et al. The Emerging Role on the Use of Platelet-Rich Plasma Products in the Management of Urogynaecological Disorders. Surg Innov. Published online April 28, 2021:15533506211014848. doi:10.1177/15533506211014848
2.Di Nicola V, Tebala GD. Platelet-Rich Fibrin-Mesh Technique for Inguinal Hernia Repair: Results of a Feasibility Pilot Study. Surg Technol Int. 2021;38:175-177.
3.Lorenz J, Al-Maawi S, Sader R, Ghanaati S. Individualized Titanium Mesh Combined With Platelet-Rich Fibrin and Deproteinized Bovine Bone: A New Approach for Challenging Augmentation. Journal of Oral Implantology. 2018;44(5):345-351. doi:10.1563/aaid-joi-D-18-00049
4.Belebecha V, Casagrande R, Urbano MR, et al. Effect of the platelet-rich plasma covering of polypropylene mesh on oxidative stress, inflammation, and adhesions. Int Urogynecol J. 2020;31(1):139-147. doi:10.1007/s00192-019-03938-5
5.Parizzi NG, Rubini OÁ, Almeida SHM de, Ireno LC, Tashiro RM, Carvalho VHT de. Effect of platelet-rich plasma on polypropylene meshes implanted in the rabbit vagina: histological analysis. International braz j urol : official journal of the Brazilian Society of Urology. 43(4):746-752. doi:10.1590/S1677-5538.IBJU.2016.0177
6.Medel S, Alarab M, Kufaishi H, Drutz H, Shynlova O. Attachment of Primary Vaginal Fibroblasts to Absorbable and Nonabsorbable Implant Materials Coated With Platelet-Rich Plasma: Potential Application in Pelvic Organ Prolapse Surgery. Female Pelvic Medicine & Reconstructive Surgery. 2015;21(4):190-197. doi:10.1097/SPV.0000000000000178
7.Castellani D, Valloni A, Piccirilli A, Paradiso Galatioto G, Vicentini C. An innovative approach to treating vaginal mesh exposure after abdominal sacral colpopexy: endoscopic resection of mesh and platelet-rich plasma; initial experience in three women. Int Urogynecol J. 2017;28(2):325-327. doi:10.1007/s00192-016-3154-x
References Supporting PRP For ED and Peyronie’s Disease
1.Siroky MB, Azadzoi KM. Vasculogenic Erectile Dysfunction: Newer Therapeutic Strategies. Journal of Urology. 2003;170(2S). doi:10.1097/01.ju.0000075361.35942.17
2.Garcia M, Fandel T, Lin G, et al. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. Published online 2010:14.
3.Towe M, Peta A, Saltzman RG, Balaji N, Chu K, Ramasamy R. The use of combination regenerative therapies for erectile dysfunction: rationale and current status. Int J Impot Res. Published online July 12, 2021:1-4. doi:10.1038/s41443-021-00456-1
4.Raheem AA, Garaffa G, Raheem TA, et al. The role of vacuum pump therapy to mechanically straighten the penis in Peyronie’s disease. BJU International. 2010;106(8):1178-1180. doi:10.1111/j.1464-410X.2010.09365.x
5.Israeli JM, Lokeshwar SD, Efimenko IV, Masterson TA, Ramasamy R. The potential of platelet-rich plasma injections and stem cell therapy for penile rejuvenation. Int J Impot Res. Published online November 6, 2021:1-8. doi:10.1038/s41443-021-00482-z
6.Matz EL, Pearlman AM, Terlecki RP. Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions. Investig Clin Urol. 2018;59(1):61-65. doi:10.4111/icu.2018.59.1.61
7.Liu MC, Chang ML, Wang YC, Chen WH, Wu CC, Yeh SD. Revisiting the Regenerative Therapeutic Advances Towards Erectile Dysfunction. Cells. 2020;9(5):1250. doi:10.3390/cells9051250
8.Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020;21(20):7794. doi:10.3390/ijms21207794
9.Matz EL, Scarberry K, Terlecki R. Platelet-Rich Plasma and Cellular Therapies for Sexual Medicine and Beyond. Sexual Medicine Reviews. 2022;10(1):174-179. doi:10.1016/j.sxmr.2020.07.001
10.Poulios E, Mykoniatis I, Pyrgidis N, et al. Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. Journal of Sexual Medicine. 2021;18(5):926-935. doi:10.1016/j.jsxm.2021.03.008
11.Schirmann A, Boutin E, Faix A, Yiou R. Pilot study of intra-cavernous injections of platelet-rich plasma (P-shot®) in the treatment of vascular erectile dysfunction. Progrès en Urologie. Published online June 2022:S1166708722001300. doi:10.1016/j.purol.2022.05.002
12.Chung E. medical sciences A Review of Current and Emerging Therapeutic Options for Erectile Dysfunction. Published online 2019:1-11.
13.Pruimboom L, Muskiet FAJ. Intermittent living; the use of ancient challenges as a vaccine against the deleterious effects of modern life – A hypothesis. Medical Hypotheses. 2018;120:28-42. doi:10.1016/J.MEHY.2018.08.002
14.Calabrese EJ. Hormesis: Why it is important to toxicology and toxicologists. Environmental Toxicology and Chemistry. 2008;27(7):1451-1474. doi:10.1897/07-541.1
15.Ruffo A, Franco M, Illiano E, Stanojevic N. Effectiveness and safety of Platelet rich Plasma (PrP) cavernosal injections plus external shock wave treatment for penile erectile dysfunction: First results from a prospective, randomized, controlled, interventional study. European Urology Supplements. 2019;18(1):e1622-e1623. doi:10.1016/S1569-9056(19)31175-3
16.Bosma-Den Boer MM, Van Wetten ML, Pruimboom L. Chronic inflammatory diseases are stimulated by current lifestyle: How diet, stress levels and medication prevent our body from recovering. Nutrition and Metabolism. 2012;9. doi:10.1186/1743-7075-9-32
17.Casabona F, Gambelli I, Casabona F, Santi P, Santori G, Baldelli I. Autologous platelet-rich plasma (PRP) in chronic penile lichen sclerosus: the impact on tissue repair and patient quality of life. Int Urol Nephrol. 2017;49(4):573-580. doi:10.1007/s11255-017-1523-0
18.Chung. A Review of Current and Emerging Therapeutic Options for Erectile Dysfunction. Medical Sciences. 2019;7(9):91. doi:10.3390/medsci7090091
19.Lee PJ, Jiang YH, Kuo HC. A novel management for postprostatectomy urinary incontinence: platelet-rich plasma urethral sphincter injection. Scientific Reports |. 123AD;11:5371. doi:10.1038/s41598-021-84923-1
20.Littara A, Palmieri B, Rottigni V, Iannitti T. A clinical study to assess the effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation. International Journal of Impotence Research. 2013;25(3). doi:10.1038/ijir.2013.13
21.Kumar CS. 265 Combined Treatment of Injecting Platelet Rich Plasma With Vacuum Pump for Penile Enlargement. The Journal of Sexual Medicine. 2017;14(1):S78. doi:10.1016/j.jsxm.2016.11.174
REFERENCES REGARDING THE USE OF PRP TO HELP WITH INFERTILITY IN WOMEN
1.Merhi Z, Seckin S, Mouanness M. REPRODUCTIVE ENDOCRINOLOGY: CASE STUDY Intraovarian PRP Injection Improved Hot Flashes in a Woman With Very Low Ovarian Reserve. doi:10.1007/s43032-021-00655-7
2.Sills ES, Li X, Rickers NS, Wood SH, Palermo GD. Metabolic and neurobehavioral response following intraovarian administration of autologous activated platelet rich plasma: First qualitative data. Neuro endocrinology letters. 2019;39(6):427-433. Accessed October 31, 2019. http://www.ncbi.nlm.nih.gov/pubmed/30796792
References regarding the dangers of hyaluronic acid filler injection
1.Urdiales-Gálvez F, Delgado NE, Figueiredo V, et al. Treatment of Soft Tissue Filler Complications: Expert Consensus Recommendations. Aesthetic Plast Surg. 2018;42(2):498-510. doi:10.1007/s00266-017-1063-0
2.The combination of platelet−rich plasma with botulinum toxin A in the treatment of hyaluronic acid embolic cutaneous necrosis and alopecia. Accessed March 15, 2022. https://onlinelibrary.wiley.com/doi/epdf/10.1111/dth.15442
References Showing that Saline Injected in a Study of Tissue Repair is Not a Placebo
1.Saltzman BM, Leroux T, Meyer MA, et al. The Therapeutic Effect of Intra-articular Normal Saline Injections for Knee Osteoarthritis: A Meta-analysis of Evidence Level 1 Studies. Am J Sports Med. 2017;45(11):2647-2653. doi:10.1177/0363546516680607
2.El-Amawy HS, Sarsik SM. Saline in Dermatology: A literature review. Journal of Cosmetic Dermatology. 2021;20(7):2040-2051. doi:10.1111/jocd.13813
3.Searle T, Al-Niaimi F, Ali FR. Saline in dermatologic surgery. Journal of Cosmetic Dermatology. 2021;20(4):1346-1347. doi:10.1111/jocd.13996
4.Bagherani N, R Smoller B. Introduction of a novel therapeutic option for atrophic acne scars: saline injection therapy. Glob Dermatol. 2016;2(6). doi:10.15761/GOD.1000159
5.Asghar A, Tahir Z, Ghias A, Iftikhar U, Ahmad TJ. Efficacy and Safety of Intralesional Normal Saline in Atrophic Acne Scars. Annals of King Edward Medical University. 2019;25(2). doi:10.21649/akemu.v25i2.2867
6.Sharma R, Gupta M, Rani R. Delineating injectable triamcinolone-induced cutaneous atrophy and therapeutic options in 24 patients—A retrospective study. Indian Dermatol Online J. 2022;13(2):199. doi:10.4103/idoj.idoj_483_21
7.Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments_ A systematic review and meta-analysis of randomized trials | Elsevier Enhanced Reader. doi:10.1016/j.semarthrit.2016.04.003
References regarding shock wave therapy for ED
1.Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial.
2.Kalyvianakis D, Hatzichristou D. Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial. The Journal of Sexual Medicine. 2017;14(7):891-897. doi:10.1016/j.jsxm.2017.05.012
3.Yuan P, Ma D, Zhang Y, et al. Efficacy of low‐intensity extracorporeal shock wave therapy for the treatment of chronic prostatitis/chronic pelvic pain syndrome: A systematic review and meta‐analysis. Neurourology and Urodynamics. 2019;38(6):1457-1466. doi:10.1002/nau.24017
4.Yuan P, Ma D, Zhang Y, et al. Efficacy of low-intensity extracorporeal shock wave therapy for the treatment of chronic prostatitis/chronic pelvic pain syndrome: A systematic review and meta-analysis. Neurourology and Urodynamics. 2019;38(6):1457-1466. doi:10.1002/nau.24017
Reference showing that Viagra works no better than placebo after prostate surgery
1.Placebo Responses Among Men With Erectile Dysfunction Enrolled in Phosphodiesterase 5 Inhibitor Trials: A Systematic Review and Meta-analysis | Clinical Pharmacy and Pharmacology | JAMA Network Open | JAMA Network. Accessed June 15, 2022. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2762993?widget=personalizedcontent&previousarticle=2792726