Male sexual health and reproductive medicine: All that glitters is not gold

September 19, 2022
Navid Leelani, DO, Scott D. Lundy MD, PhD

This article is a repost which originally appeared on Urology Times.

Edited for content. The opinions expressed in this article may not reflect the opinions of this site’s editors, staff or members.

Our Takeaways:

· Telehealth is an increasingly popular method for obtaining medical services

· More studies need to be done in the areas of male sexual and reproductive medicine.

· Studies cite the prevalence of ED as high as 52%!

“With the average cost of treatment ranging from $2600 to $3900 per cycle, clinics offering radial wave therapy have an obvious financial incentive to continue marketing despite the lack of evidence of its effectiveness,” write Navid Leelani, DO, and Scott D. Lundy, MD, PhD.

With the intensified direct-to-consumer marketing of male sexual medicine treatments, the recent legislative changes in reproductive rights and their unknown long-term effect on assisted reproduction availability for infertile men, and the explosion of telehealth, the practice of male sexual medicine is evolving at a breakneck pace. Specialists in male sexual and reproductive medicine have been tasked with digesting the evolving literature and forming evidence-based treatment guidelines for men with erectile dysfunction, Peyronie disease, infertility, and a host of other conditions. Compared with other areas of urology and medicine in general, male sexual and reproductive medicine has a disappointingly small number of well-designed prospective studies, along with a significant gap in funding for male reproductive health compared with female reproductive health. Several manuscripts published in 2022 started to narrow this gap and provide valuable level 1 evidence supporting (or discounting) key areas within sexual medicine and infertility.

For men with severe male factor infertility and nonobstructive azoospermia, surgical intervention is often indicated to retrieve sperm. Testicular sperm aspiration (TESA) and microdissection testicular sperm extraction (mTESE) are 2 commonly used approaches. A recent study by Jensen et al compared the efficacy of these 2 approaches in one of the few prospective randomized-controlled trials in male infertility.1 In the study, 49 patients were randomly assigned to mTESE with a sperm retrieval rate of 43%, and 51 patients were randomly assigned to TESA with a sperm retrieval rate of 22%. Men with failed TESA then went on to salvage mTESE with a combined sperm retrieval rate of 29%. Participants in the mTESE arm, however, had decreased postoperative testosterone levels, and 24% of participants experienced de novo hypogonadism at 6 months. Prior literature has suggested the testosterone drop is transient and that it will likely recover by 12 months. In summary, the study results showed that mTESE remains the gold standard for treatment of nonobstructive azoospermia, but patients should be counseled on the risk of de novo hypogonadism.

Despite this, mTESE success rates remain modest and are subject to the expertise and skill level of the laboratory and andrologist processing the tissue. Multiple hours can be spent trying to find the few viable sperm hidden among a sea of distractors. A recent study by Lee et al examined the power of artificial intelligence to detect human sperm in semen and mTESE samples using bright-field microscopy for nonobstructive azoospermic (NOA) patients.2 They first trained the program to identify sperm from semen samples of fertile patients. After validating the effectiveness of their algorithm, they retrained it to identify sperm in tissue from NOA patients that had been spiked with large amounts of sperm. When testing it on samples containing 3000 to 6000 sperm among other cell types, they achieved 84.0% positive predictive value and 72.7% sensitivity. Finally, without retraining their algorithm, they tested it on samples containing 10 to 200 sperm, replicating the “rare sperm” phenomenon seen in patients with NOA. Their model was able to detect 2969 sperm cells out of a total 3517 with an 84.4% PPV and 86.1% sensitivity. The clinical applications of artificial intelligence and machine learning in medicine continue to expand and have made their way to male infertility. Although this is not ready for immediate clinical use, it does highlight the need for further work to harness the power of technology to improve workflow of andrologists and in turn increase the success of infertility care for patients.

There has been a rapid rise in the need for male sexual health and reproductive specialists as the population ages and the number of comorbidities rise, although certain disease processes that fall within this specialty may be able to be addressed by a general urologist. In an analysis of the current educational landscape, Asanad et al call attention to the need for a structured educational curriculum in residency for male infertility.3 In a survey of urology residents, 54 of 72 respondents (75%) reported that male infertility comprises less than 10% of their training. Compared with residents who did not learn from infertility-trained faculty, residents who were exposed to infertility-trained faculty were 14.4 times more likely to feel confident performing infertility procedures (P < .001) and were more likely to feel confident performing fertility procedures after residency (P = .001).3 For trainees, their career depends on what they are exposed to. Smaller subdisciplines within urology may be more difficult to teach uniformly, and perhaps there are ways to improve the exposure to these areas for motivated residents (eg, visiting other programs).

Within male sexual health, one disease process that all urologists should be able to diagnose and initially manage is erectile dysfunction (ED). With studies citing the prevalence of ED as high as 52%, the demand for providers to manage ED remains sky high. Current treatment options include phosphodiesterase type 5 inhibitors (PDE5is), intracavernosal injections, vacuum erection devices, and penile prosthesis. A newcomer to the field is shock wave therapy, which uses controlled energy to induce angiogenesis.

The short-term effectiveness of focused shock wave therapy for patients with moderate ED was investigated in a double-blind, randomized, sham-controlled trial.4 In this study of 70 patients with moderate ED, 35 were randomly assigned to low-intensity shock wave therapy (LiST) and the other 35 were randomly assigned to sham therapy. After a 4 week washout from PDE5i, patients underwent LiST or sham twice weekly for 6 weeks. One month after treatment completion, 59% patients in the LiST group experienced an International Index of Erectile Function (IIEF) score improvement of at least 5 points, compared with 1 patient (2.9%) in the sham group (P < .001). This effect remained present at 3 months post treatment. Thus, the short-term data for LiST are compelling and suggest this may be a viable option in the management of vasculogenic ED for men with mild/moderate ED. Further studies are desperately needed to validate these findings, and urologists have an obligation to provide patients with an honest assessment of the data and only recommend treatments where the risks (including the financial burden) are outweighed by the benefits.

In stark contrast to focused therapy, radial shock wave therapy uses low-pressure radial shock waves to treat ED. In order to characterize its effectiveness, a randomized, double-blind, sham-controlled clinical trial enrolled 80 men with mild to moderate ED.5 Patients were treated weekly with either radial wave therapy or sham therapy for 6 weeks, and the primary outcome measured was change in the IIEF score between baseline and after treatment. Study results showed that there was no significant difference in IIEF scores between groups at 6 weeks or 10 weeks after randomization. Study results displayed the lack of evidence to support the use of radial wave therapy.

Despite the evidence of their ineffectiveness in managing ED, shock wave therapy and particularly radial wave therapy have been heavily marketed directly to consumers in the US. A recent article using a “secret-shopper” method found troubling marketing and practice trends in the US. The authors noted that patients often are not adequately educated on the different types of treatments and may not know if the administrator is a licensed medical professional.6 With the average cost of treatment ranging from $2600 to $3900 per cycle, clinics offering radial wave therapy have an obvious financial incentive to continue marketing despite the lack of evidence of its effectiveness.

Recent advancements in the field of male sexual health and reproduction present a bright future for the field with new diagnostic and therapeutic options on the horizon. However, it is apparent that demand still outpaces supply for men’s health specialty care. Urologists must work diligently to fill this void to not only increase access for patients to receive evidence-based care, but also to prevent men from falling to prey to practices looking to take advantage of this unmet demand and a vulnerable patient population.

References

1. Jensen CFS, Ohl DA, Fode M, et al. Microdissection testicular sperm extraction versus multiple needle-pass percutaneous testicular sperm aspiration in men with nonobstructive azoospermia: a randomized clinical trial. Eur Urol. Published online May 19, 2022. doi:10.1016/j.eururo.2022.04.030

2. Lee R, Witherspoon L, Robinson M, et al. Automated rare sperm identification from low-magnification microscopy images of dissociated microsurgical testicular sperm extraction samples using deep learning. Fertil Steril. 2022;118(1):90-99. doi:10.1016/j.fertnstert.2022.03.011

3. Asanad K, Nusbaum D, Fuchs G, Rodman JCS, Samplaski MK. The impact of male infertility faculty on urology residency training. Andrologia. 2022;54(8):e14457. doi:10.1111/and.14457

4. Kalyvianakis D, Mykoniatis I, Pyrgidis N, et al. The effect of low-intensity shock wave therapy on moderate erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial. J Urol. 2022;208(2):388-395. doi:10.1097/JU.0000000000002684

5. Sandoval-Salinas C, Saffon JP, Martínez JM, Corredor HA, Gallego A. Are radial pressure waves effective for the treatment of moderate or mild to moderate erectile dysfunction? A randomized sham therapy controlled clinical trial. J Sex Med. 2022;19(5):738-744. doi:10.1016/j.jsxm.2022.02.010

6. Weinberger JM, Shahinyan GK, Yang SC, et al. Shock wave therapy for erectile dysfunction: marketing and practice trends in major metropolitan areas in the United States. Urol Pract. 2022;9(3):212-219. doi:10.1097/UPJ.0000000000000299

Nitroglycerin Gel for ED: Pros, Cons, & Practical Information

About Nitroglycerin Gel for Erectile Dysfunction

Medically reviewed by Matt Coward, MD, FACS — Written by Sara Lindberg on December 16, 2020

This article is a repost which originally appeared on Healthline

Edited for content

Erectile dysfunction (ED) may affect as many as 30 million men in the United States. People with ED experience an inability to get or keep an erection firm enough for sex.

You may be familiar with some of the more common treatments for ED, including lifestyle modifications, oral medications that include phosphodiesterase type 5 inhibitors (PED5 inhibitors), and penis pumps.

But a study published in the Journal of Sexual Medicine also looked at the use of nitroglycerin gel or cream as a topical treatment for ED. Although results look promising, it’s important to note that nitroglycerin gel or cream isn’t approved by the Food and Drug Administration (FDA) to treat ED.

Here’s what you need to know about nitroglycerin as a topical treatment for erectile dysfunction.

What is nitroglycerin?

Nitroglycerin is part of a class called vasodilators, which widen the blood vessels and improve blood flow to allow oxygen-rich blood to reach the heart.

It comes in a variety of forms, including sublingual (under-the-tongue), topical cream or gel, and as a transdermal patch. Nitroglycerin is most often used to prevent angina or attacks of chest pains.

Nitroglycerin for ED

“The idea of treating ED with topical nitroglycerin is not new and was first described in the 1980s,” says Dr. Joseph Brito, a urologist at Yale New Haven Health, Lawrence + Memorial Hospital. Brito is also a member of Healthline’s clinical review network.

In general, Brito says nitroglycerin works by dilating the blood vessels, which is why it’s traditionally used for patients with angina or chest pain due to poor cardiac vessel blood flow.

The concept is the same for ED, although Brito says it may have a dual mechanism of action:

  • It widens blood vessels helps blood flow.
  • It relaxes penile smooth muscle, which in turn compresses penile veins and impedes blood flow out of the penis, which causes rigidity.

How does nitroglycerin gel work?

According to Brito, nitroglycerin gel or cream differs from other ED treatments such as oral medications:

“[Topical nitroglycerin] acts as a nitrogen donor to increase local levels of nitric oxide, which works through molecular signaling (cGMP pathway) to cause this response,” he says.

On the other hand, Brito says PDE5 inhibitors (like tadalafil and sildenafil) work at a later step in the chain by inhibiting the breakdown of cGMP.

Nitroglycerin for ED doesn’t have enough research

That said, Brito points out that nitroglycerin gel or cream is currently not approved by the FDA to treat ED.

Moreover, Brito points out that the American Urological Association guideline on erectile dysfunction published in 2018 didn’t include topical nitroglycerin as a suggested treatment for men with ED.

“Though this therapy was not specifically mentioned, the authors did state ‘the use of these treatments may preclude the use of other treatments known to be effective,’ and felt more research was needed,” he explains.

And there’s another factor to consider: Nitroglycerin cream on the outside of the penis might be transferred to your partner.

Why are people interested nitroglycerin gel for ED?

“Nitroglycerin may have some benefits over standard oral ED medications,” Brito says.

The onset of topical nitroglycerin is between 10 and 20 minutes, which Brito says is better than the quickest acting oral agents, with sildenafil taking at least 30 minutes.

In fact, the 2018 study published in the Journal of Sexual Medicine found that 44 percent of patients saw erection beginning within 5 minutes of application. Seventy percent of the men noticed an erection within 10 minutes.

The randomized, double-blind, placebo-controlled study included 232 men with ED who participated in two 4-week trials. One trial used a 0.2 percent glyceryl trinitrate topical gel before sex, and the other used a placebo gel.

“This may help with spontaneity, which can be an issue for couples using oral agents,” Brito explains.

Another benefit, Brito says, is that unlike other ED treatments like oral agents, nitroglycerin doesn’t need to pass through the gastrointestinal (GI) tract.

“Since absorption of oral agents like sildenafil is strongly affected by food intake, the medications are much more effective when taken on an empty stomach,” he says. This requires more planning and doesn’t always allow for spontaneity.

Where to buy nitroglycerin for ED

Nitroglycerin gel or cream is currently not approved by the FDA to treat ED.

If you have questions about this topical treatment, you need to talk with a doctor who knows your medical history. A prescription is needed for nitroglycerin.

How to take nitroglycerin gel for ED

Nitroglycerin use is managed by your doctor. Don’t use or apply this topical treatment without guidance.

According to the Journal of Sexual Medicine, the concentration studied was 0.2 percent, which Brito says likely explains why the effect was best for men with mild ED.

He also points out that other studies used concentrations of 0.2 to 0.8 percent for patients with more severe ED, who likely needing higher concentrations.

In general, Brito says people prescribed nitroglycerin by their doctor should apply a small amount (pea-sized) to the head of the penis.

Side effects and contraindications

Nitroglycerin is certainly not for everyone. According to a 2018 review, taking nitroglycerin-based medications with certain PDE5 inhibitors like Viagra is contraindicated. Using them together can result in a sudden and serious decrease in blood pressure and potentially death.

According to Brito, some drawbacks of topical nitroglycerin include possible transmission to the partner, which can lead to the partner sharing in side effects, especially low blood pressure. This can lead to headache and nasal congestion.

Other treatments for ED

There are several treatments available for ED, including:

  • oral medications that include PDE5 inhibitors such as sildenafil (Viagra) and tadalafil (Cialis). Other oral medications include vardenafil HCL (Levitra), and avanafil (Stendra)
  • erectile dysfunction pump (penis or vacuum pump)
  • penile injections
  • inflatable penile prosthesis
  • psychotherapy (talk therapy) for emotional or psychological issues related to ED
  • suppositories (Alprostadil)
  • counseling
  • diet modifications
  • exercise
  • stress reduction

The takeaway

Although some research points to the effectiveness of nitroglycerin gel or cream for improving the symptoms of ED, it’s currently not approved by the FDA as a treatment for erectile dysfunction.

If you have ED or think you may have ED, it’s important that you talk with a doctor about any treatment options. They can talk with you about the range of options, including lifestyle modifications, counseling, oral agents, penis pumps, surgery, and implants.