Low-Intensity Shockwave Therapy for Treatment of Erectile Dysfunction – Does it work?

20% of all men have erectile dysfunction (ED) with men of increasing age being disproportionally affected. The incidence of ED can be as high as 60% in men with Diabetes or cardiovascular disease. Although previously considered a quality of life issue, the presence of erectile dysfunction in an otherwise healthy man is now considered a harbinger of cardiovascular disease. Vascular factors are the leading cause of ED. A multitude of treatment options exists for those men with minimal or moderate erectile dysfunction, including pills, injections, and external devices. Unfortunately, these don’t work for every man and may interact with medications or underlying diseases. Also, they treat the symptoms and not the underlying cause of ED. Besides, most man would like not to have to take drugs to function sexually.

What is LI-SWT?

Low intensity extracorporeal (i.e., outside the body) shockwave therapy (LI-SWT) is a treatment that has been in use since 2010. Patients are usually treated in the office setting once or twice a week for 4 to 6 weeks. The device applies a low-intensity shockwave to the surface of the penis using an ultrasound gel as the coupling agent.  LI-SWT appears to have minimal side effects and is well-tolerated without any anesthesia. However, it has not received FDA approval for treatment of erectile dysfunction as of the date of this writing. It has been approved for the treatment of plantar fasciitis. Most of the current research has been directed towards erectile dysfunction. A few studies have evaluated the use of LI-SWT in Peyronie’s disease. This article will address the use of LI-SWT in the treatment of erectile dysfunction.

How Does LI-SWT Work?

It is not definitively known how LI-SWT works. However, the current theory is that the shockwave produced by the device causes stress on cell-membranes and release of growth factors and recruitment of stem cells that promote the development of new penile arteries and reducing inflammatory and cellular stress. In animal studies, there is also evidence to suggest nerve regeneration (Fode et al., Nat. Rev. Urolo. 14:593, 2017). LI-SWT is unique in that it could provide a treatment option that corrects the underlying problem instead of just treating the symptoms of erectile dysfunction.

Literature Reviews of LI-SWT?

Several reviews of studies evaluating the use of LI-SWT have been published this year. The first was an analysis of ten randomized controlled studies completed over the past two years by Sokolakis and Hatzichristodoulou (Int Jour Impot Res, 31:177-194, 2019) has concluded that LI-SWT significantly improved erectile function in patients with vascular ED. All ten studies used a validated questionnaire as the assessment tool and included men with moderate to severe ED. Their analysis also contained only 873 studies followed for less than one year. Three studies also measured penile hemodynamics.

A second systematic review by Brunckhorst et al. (Int Urol Neph, 51:773-781, 2019) reviewed eleven studies with 799 patients. Nine studies found an improvement in ED at six months after treatment with the improvement remaining above baseline out to 12 months.

A third review included seven randomized controlled studies evaluating the effect of LI-SWT on erectile function (Dong et al., Am J Men’s Health, March-April:1-14, 2019). Evaluating outcomes by validated questionnaires (ie., International Index of Erectile Function – erectile function domain [IIEF-EF] and the Erectile Hardness Score [EHS]) they found improvement in erectile function after treatment with LI-SWT.

Although the results have been encouraging, there are still many questions to be answered. What patients will respond to LI-SWT? Will the patients with worse erectile dysfunction, Diabetes and/or heart disease respond better or worse? Does patient age or use of oral or injectable medications used to treat erectile dysfunction affect the results of LI-SWT? What are the contraindications for the use of LI-SWT? Should we be treating men on blood thinners? How does the frequency and length of treatments affect the results? Is it better to use fewer treatments/week over a longer period of time? How does the intensity and number of shocks affect the outcome? Does the type of device matter (linear vs. focused shockwaves)? Focused shockwaves have shown their effectiveness while the results of linear shockwaves are still conflicting. When do the effects of LI-SWT occur and how long does the improvement last? These, among other questions, will need to be answered

Current literature demonstrates an improvement of erectile dysfunction with LI-SWT. However, large, multicentered, randomized controlled studies which include not only qualitative (e.g. validated questionnaires) but also quantitative data (e.g. spectral ultrasound vascular data) are needed before LI-SWT becomes the standard of care. For additional information, please contact us.

iButterfly: Changing the Practice of Urology!

Recently the iButterfly received FDA clearance and was released for sale. This hand-held marvel is an iOS compatible ultrasound device that weighs in under 0.7 lbs and costs around $2,000 (not including the required yearly subscription for unlimited cloud storage. Their ‘semiconductor-based’ ultrasound provides for all body ultrasound with one handheld transducer. It provides for B-mode, M-mode and color Doppler. With a 2 to 30 cm depth of penetration and presets, the transducer can be instantaneously changed to interrogate almost any organ in the body as it mimics a linear array, curvilinear or sector scanner.

We have started using it at the time of surgery to localize the lesion of interest. We have also expanded its use to the bedside for the resident to quickly identify urinary retention, hydronephrosis, catheter or stent placement as well as to help in the identification of the character of fluid collections.

My initial thoughts on using it for several months:

Resolution is good, similar to many portable laptop units, but not in the same league as current free-standing units. It is unique in that a single probe can be used for all organ systems. We have found a great use for it in the operating room to provide pre-incision guidance, in the emergency room for urinary retention, catheter placement, and genital injury as well as on the floor for postoperative urologic evaluation. It does provide for the ability to annotate and measure….but not as easy as a desktop or freestanding unit. It would be nice to have presets for easy annotation. I will continue to update as I find new user applications. BRG

Testosterone replacement and the aging male

I recently read the following about testosterone and testosterone replacement  “Last summer I took Bruno, my ten-year-old cairn terrier, to the vet for his annual check-up.  “Wow, he has some energy level for an older dog,” commented my vet as he watched Bruno dart around the exam room. My vet started to examine Bruno. “Aha”, he exclaimed. “He’s intact. That’s why he’s still so quick moving and trim. It’s all that testosterone.”

The Vet’s findings are similar to what we find in men. Adequate testosterone levels benefit the aging male. Over the last ten years, prescriptions for testosterone for men over forty have tripled. Testosterone is essential for maintaining muscle and lean body mass, strength and energy levels, fertility, libido and sexual performance. It is needed to maintain normal bone density and prevent osteoporosis. It also positively impacts cognitive function and mood. Unfortunately for men, testosterone progressively declines as they age. Sometimes to levels low enough to impair the numerous functions listed above, leading to adverse health conditions and significant changes in quality of life. So it is easy to see why healthcare providers and their aging male patients would consider testosterone replacement therapy to reverse symptoms related to low testosterone and restore better quality of life.

Several recent studies, however, indicate that testosterone replacement therapy may not be as beneficial to the aging male as originally thought. We need to consider the balance between the risks and benefits.  Their findings link testosterone replacement therapy to an increase in cardiovascular problems. The New York Times and several other national news outlets ran features last month highlighting the findings of a recent study that showed a correlation between testosterone replacement therapy and increased cardiac risk, setting off a bit of a frenzy over the need to better scrutinize how and to whom this medication should be dispensed. There is also discussion over the need for pharmaceutical companies to put a warning label on testosterone replacement therapies and their relevant advertising material, and for doctors to have patients sign a consent indicating an awareness of the potential side effects of testosterone prior to being prescribed this drug.

So how concerned should you be if you are currently on testosterone replacement therapy, or you are experiencing symptoms of low testosterone and are considering discussing testosterone replacement therapy with your health care provider? Will testosterone replacement therapy increase your risk of having an adverse cardiac event?

The study receiving so much recent media attention was funded by the National Institute of Health (NIH) and was published in the journal PLoS ONE. It found that men over the age of 65 had double the rate of heart attacks within the first 90 days of starting testosterone. Men younger than 65 with a history of heart disease had triple the rate of heart attacks within the first 90 days of starting testosterone. Men younger than 65 with no history of heart disease showed no increased risk of heart attack.  Other studies have also produced similar findings. None of these studies have been able to demonstrate specifically how testosterone is causing adverse cardiovascular incidents. Some are suggesting increased physical activity elicited by the physical improvements gained from testosterone replacement therapy is placing too much stress on the cardiovascular systems of men already at risk. However, if you are over 65 or have a history of cardiovascular disease, testosterone replacement therapy may not be for you.

Another source of concern is the growing number of health clinics that cater to the needs of men interested in extending the vigor and virility of youth into old age with the help of testosterone replacement therapy.  Many of these “male rejuvenation” clinics are billing testosterone as a panacea for all that ails the aging male. These clinics are prescribing testosterone without properly screening for this condition and without properly following up with those patients given prescriptions and refills.  Testosterone replacement therapy benefits many aging men, but it is not for all.  Like all medications, testosterone can pose health risks if prescribed to men who do not need it or have pre-existing conditions that contradict it.

Because of the steep increase in the number of prescriptions being written for testosterone, as well as the number of clinics actively marketing testosterone replacement to aging men, the Endocrine Society updated its clinical practice guideline in 2010 to provide a better protocol for evaluating and treating patients with low testosterone.

If you are currently on testosterone replacement therapy (TRT) or considering seeing a healthcare professional about starting it, your initial and follow-up evaluations should adhere to the Endocrine Society’s guidelines.  A healthcare professional should never, ever prescribe testosterone based solely on a patient having symptoms of low testosterone. Your initial examination should include a serum (blood) sample evaluated by a reference lab using a standardized method for testosterone measurement. Initial blood tests often include a total and free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), prostate specific antigen (PSA), prolactin, and hematocrit (measurement of red blood cells). The sample should be drawn between 7:00am and 11:00am particularly for men under 50, as testosterone levels are highest in the morning.

Due to the lack of standardization in testosterone measurement there is not a level below which testosterone is considered ‘low’.  However, a total testosterone level below 300 ng/dl is usually considered the lower limit of normal.  If your total testosterone level is low, evaluating hormones secreted by the pituitary, LH and FSH will help your healthcare provider determine if the cause is impaired production in the testes (primary hypogonadism) or a problem with the hypothalamus and/or pituitary (secondary hypogonadism). If secondary hypogonadism is suspected, additional testing should be done to determine the cause. If your total testosterone level is low or borderline-low, bone mineral density should be evaluated with a DEXA scan to determine if you have decreased bone density (eg osteopenia or osteoporosis).

A clinical diagnosis of low testosterone based on symptoms and blood work demonstrating low serum testosterone makes you a good candidate for TRT. However your healthcare provider might not suggest TRT if:

  1. You are 65 years of age and older.
  2. You have a history of cardiovascular disease.
  3. You have prostate cancer or a PSA level above 4 ng/ml. (TRT can stimulate the growth of prostate cancer in men with prostate cancer.)
  4. You have severe lower urinary tract symptoms.
  5. You have who have a history of breast cancer.
  6. You have hematocrit above 50%. (TRT stimulates the production of red blood cells. Excessive levels can cause formation of blood clots.)
  7. You have severe sleep apnea. (Severe sleep apnea might be a sign of cardiovascular disease.)
  8. You are concerned about your fertility. (TRT impairs sperm production in testes.)

Once you have started testosterone replacement therapy, your healthcare provider should monitor your progress. You should be evaluated every three to six months to determine if your symptoms are improving. Your serum testosterone level and several other hormones should be measured, and the goal should be to maintain a testosterone level in mid-normal range (ie, 400 to 600 ng/dl). You should be assessed for any adverse effects (cardiovascular disease, PSA/prostate cancer, hematocrit/erythrocytosis). You bone density should be re-evaluated by DEXA scan every one to two years.  Your healthcare provider should not be refilling your prescription without doing this type of periodic assessment.

Before I end this blog, I want to mention that life style interventions have been shown to improve testosterone levels. Studies show there is a link between obesity and low testosterone. Men who are overweight tend to have lower testosterone levels than men who are normal weight. Weight loss, improved diet, and exercise have been shown to boost testosterone levels.

Testosterone replacement therapy, when prescribed and monitored properly, has been proven to be safe and effective for men over forty with low testosterone. It has been shown to improve energy level, libido, muscle and bone loss, and mood. Studies have shown it can lower blood pressure and blood sugar and can improve cholesterol levels.  Studies also demonstrate that men with normal testosterone levels have a 40% lower death rate compared with men who have low testosterone levels.  If you think you suffer from low testosterone, testosterone replacement therapy could be of great benefit. Just make sure you are evaluated and monitored by a physician who is experienced with hormone replacement therapy in men.

References:

 Bhasin S, Cunningham GR, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun; 95(6): 2536-2559.

Finkel W, Greenland S, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLOS ONE. 2014 Jan; DOI: 10.1371.

Brawer MK. Testosterone replacement in men with andropause: an overview. Rev Urol. 2004; 6(Suppl 6): S9-S15.

O’Connor A. New concern about testosterone and heart risks. NYT, Jan 29, 2014.

La Puma J. Don’t ask your doctor about low T. NYT, Feb 3, 2014.

Male menopause: testosterone therapy marketing frenzy draws skepticism. From voxxi.com, Sep 9, 2012.

 

 

 

 

Fertility Preservation and Gender Transition: The Decision to Bank Sperm

The desire to have children is common among individuals transitioning with 38% of respondents of the National Transgender Discrimination Survey indicating they are parents1. A Belgium study surveyed 121 patients transitioning and found that 40% would want children and that half of these would like a biologic child2.  Also in this study, 77% of 101 trans women wanted the professionals treating them to discuss fertility options with 51% stating that they would have cryopreserved sperm, or at least seriously considered this, if it had been discussed.

The World Professional Organization for Transgender Health (WPATH, http://www.wpath.org) first developed the Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People in 1979. However, it wasn’t until 2011 that they introduced specifics on the Reproductive Health needs of transgender people3. In the current WPATH Standards (http://bit.ly/2msEoQl) they recommend that prior to the initiation of therapy fertility preservation options are discussed, even if the person is currently not interested in future fertility.

Ideally, sperm should be collected before hormones are prescribed. However, it is possible in male to female transitioning that stopping feminizing hormones might provide a window to retrieve sperm. Even in the individual who does not have sperm in the ejaculate, or cannot produce an ejaculate, the potential for sperm retrieval and banking is possible with other modalities. Testicular biopsy with banking of tissue excised during the procedure can be used for conception with in vitro fertilization (IVF) couple with single sperm injection (ICSI). In addition, a recent study4 found normal spermatogenesis in 24% of testes removed at the time of sex reassignment surgery for individuals on long term estrogen therapy.  This suggests that banking of testicular tissue may still be possible in 1/4 of patients treated with long term hormonal therapy.  However, it must be noted that 75% of patients treated with long term estrogen therapy did not have sperm in the ejaculate or on biopsy.

At one fertility clinic511 patients were referred for sperm banking between January 2010 and May 2014. Nine of these patients banked sperm for future potential use. During this 52 month period, 1 couple used the stored sperm, which resulted in a pregnancy. It should be noted however, that the mean age of the patients preserving sperm was 26.5 years of age which might account for the low usage rate of the banked sperm during this study. What was interesting in this study is that there was an increase in yearly referrals to their clinic over the 4.3 years they collected data. However, they found that referrals remained low which they postulated was due to both cost of sperm banking as well as lack of awareness that fertility preservation was an option.

Unfortunately, the reproductive needs of transgender individuals are still largely unmet6. Hopefully, this will be changing as more health professionals provide much needed information on reproductive health to individuals undergoing gender transitioning.

References:

  1. James SE, Herman JL, Rankin S, Keisling M, Mottet L, Anafi M. 2015 U.S. Transgender Survey. December 2016:1-302.
  2. De Sutter P, Kira K, Verschoor A, Hotimsky A. The Desire to Have Children and the Preservation of Fertility in Transsexual Women: a Survey. International Journal of …; 2002.
  3. Coleman E, Bockting W, Botzer M, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. International Journal of Transgenderism. 2012;13(4):165-232. doi:10.1080/15532739.2011.700873.
  4. Schneider F, Neuhaus N, Wistuba J, et al. Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS). The journal of sexual medicine. 2015;12(11):2190-2200. doi:10.1111/jsm.13022.
  5. Jones CA, Reiter L, Greenblatt E. Fertility preservation in transgender patients. International Journal of Transgenderism. 2016;17(2):76-82. doi:10.1080/15532739.2016.1153992.
  6. HUNGER S. Commentary: Transgender People Are Not That Different after All. Cambridge Quarterly of Healthcare Ethics. 2012;21(2):287-289. doi:10.1017/S0963180111000818.