Radiofrequency

A novel approach for the treatment of

Erectile Dysfunction

I Gruenwald, A Greenstein, A Shechter, V Shabataev, B Appel

Neuro-urology unit,
Rambam Medical Center, Haifa, Israel
 Disclosure

Medical advisory board

Basics of erection:
- Cavernosal smooth muscle relaxation and arterial
inflow
- Compressed veins against a rigid Tunica Albuginea
- Compressed Emissary Veins Flaccid state
Arterial inflow

Erectile state

Even when there is smooth muscle relaxation- If the tunica can’t stretch enough or cannot resist strongly
enough to intracorporal pressures- the veno-occlusive mechanism fails-
resulting in poor erection & poor rigidity
Tunica Albuginea & Collagen illustration

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 The Tunica Albuginea and its role in the erectile mechanism
• It functions by compressing the sub-albugineae venulae, which promotes the diminished venous flow during
erection
• It provides a fibrous frame, and acts as the inextensible enclosing structure
which contains the erectile tissue.

• It gives the erect penis its shape.

Intracavernous pillars

• The functions of the TA result from its structure, consisting for the most part of collagen and elastic fibers.
 Tunica Albuginea, Collagen and ED
• In ED patients, a reduction in collagen and elastin fibers produces disorders in the arrangement of the collagen fibers.
• These alterations in the architecture of the tunica have a deleterious effect on the erectile mechanism.

Normal Erectile Function Venogenic Erectile Dysfunction

Shafik A, Shafik I, El Sibai O, Shafik AA. On the pathogenesis of penile venous leakage: role of the tunica albuginea BMC Urol. 2007 , 5;7:14

Iacono F1, Barra S, Cafiero G, Lotti T. Scanning electron microscopy of the tunica albuginea of the corpora cavernosa in normal and impotent subjects.
Urol Res. 1995;23(4):221-6
Collagen and ED
Normal

Venogenic ED
 Collagen and ED

CONNECTIVE TISSUE / SMOOTH MUSCLE RELAXATION

• Collagen decreases with age (2-3% a year from age 23-24y)

• Collagen defragmentation increases with age
• Collagen spatial arrangement decreases with age

Moreland RB. Pathophysiology of erectile dysfunction: the contributions of trabecular structure to function and the role of functional antagonism.
Int J Impot Res. 2000 Oct;12 Suppl 4:S39-46
RF: A new perspective to improve the erectile mechanism
Targeting the veno occlusive mechanism.

The veno occlusive mechanism hasn’t yet been properly challenged:

The tunica albuginea is directly involved in maintaining an erection.

There is no effective treatment that enables reduced output from the erect penis.

RF therapy focuses on formation of new collagen,

remodeling/re-arranging collagen fibers in the human tissue.
 Characteristics of RF energy
• RF energy is known for its heating effect on tissues:

• RF is based on a sinusoidal electrical current between 2 electrodes forcing collisions between charged
molecules and ions, which are then transformed into heat.

• RF thermal stimulation induces micro-inflammatory processes, consequently inducing the release of

VEGF, promoting neo-angiogenesis, collagen synthesis and collagen rearrangement.

• The application of low intensity RF is associated with minimal risks and there are no contraindications for
its use.

• Currently, RF devices are commonly used for skin tightening to treat lax skin, wrinkle reduction, cellulite
and body contouring, by remodeling dermal collagen.

Semin Cutan Med Surg 32:9-17 © 2013 Frontline Medical Communications

P Meyer, et al. Radiofrequency treatment induces fibroblast GF2 expression and subsequently promotes neocollagenesis and neoangiogenesis in the skin tissue,
Lasers Med Sci . 2017 Nov;32(8):1727-1736.
 Potential effects of delivering RF energy to the penis

• RF energy is easily delivered to the inner part of the penis, resulting in a mild, local and controlled
temperature increase in the tunica and the corpora cavernosal tissue.

- The increased temperature triggers collagen synthesis and collagen rearrangement at the level of the

Tunica Albuginea

- In addition, By initiating micro-inflammatory processes, applying RF to the penis may trigger the
release of multiple cellular angiogenic factors, initiating angiogenesis and neovascularization

- Heat will cause vasodilatation and will Increase blood inflow, enhancing oxygenation of the
cavernosal tissue including endothelial cells

• To achieve intracavernosal heating , it is necessary to maintain normal penile

skin temperature by a local cooling mechanism.
 Radio frequency: Current clinical use
• In dermatology -it is widely used for skin tightening and for eliminating wrinkles, for treatment
of hypertrophic scars and keloids, facial rejuvenation, reduction of cellulite.
Fritz K, et al. Efficacy of monopolar radiofrequency on skin collagen remodeling: a veterinary study. Dermatol Ther. 2015 May-Jun;28(3):122-5
radiofrequency therapy significantly increases collagen remodeling.

Kao HK, Li Q, Flynn B et al. Collagen synthesis modulated in wounds treated by pulsed radiofrequency energy. Plast Reconstr Surg. 2013 Apr;131(4):490e-8e:
significantly increasing dermal cell proliferation and collagen synthesis.

Meyer PF, de Oliveira P, Silva FKBA et al .Radiofrequency treatment induces fibroblast growth factor 2 expression and subsequently promotes neocollagenesis and
neoangiogenesis in the skin tissue. Lasers Med Sci. 2017 Nov;32(8):1727-1736.

J Moffett, et al. Pulsed radio frequency energy field treatment of cells in culture: Increased expression of genes involved in angiogenesis and tissue remodeling during
wound healing. The Journal of Diabetic Foot Complications, 2011; Volume 3, Issue 2, No. 3,Pages 30-39

• In orthopedics- for joint capsular strengthening

Akamatsu FE, et al. Radiofrequency preserves histoarchitecture and enhances collagen synthesis in experimental tendon injury . Histol Histopathol. 2016 May;31(5):515-22

• In sexual medicine- for vaginal rejuvenation

Magon N , Alinsod R . ThermiVa: The Revolutionary Technology for Vulvovaginal Rejuvenation and Noninvasive Management of Female SUI. J Obstet Gynaecol
India. 2016 Aug;66(4):300-2..

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Histologic studies showing collagenesis and
remodeling of collagen after RF treatment

http://www.endymed.com/VALIDATION#SCIENTIFIC%20ARTICLES

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 Could an RF medical device be used for the therapy of ED?

• Medical devices applying RF technology have undergone extensive use in clinical trials and are proven to be
safe.
• As opposed to the past, the concept that medical devices can effect biological and molecular processes has
currently become widely accepted, and this is also true for ED.
• RF technology has never been applied or studied for the treatment of ED.
• Men are looking for a permanent solution for their ED!!!
• It is painless, non-invasive, safe, no need for medication or surgery and it has a rehabilitative perspective.

RF -a logical option as a potential therapy that may enhance erectile function!!

 Clinical Pilot Study

Aim: Treat/improve/prevent/cure Erectile dysfunction with Ohhmed-RF energy

delivered to the corpora cavernosa

Pilot study:
Aim: to assess feasibility, efficacy and safety of Ohhmed-RF penile therapy

Outcome measures of success: Positive changes in subjective and objective

measures of erectile function, achieved without adverse events.

Method: During the past year, 28 patients received 12 treatments, twice a week
during 4 weeks and once a week for another 4 weeks.
Treatments were self- applied (following instructions)
 Evaluating Success

Potent ……………..……………………………….. 26-30

Mild …………………………………………………. 17-25
IIEF EF domain score
Moderate ………………………………………….. 11-16
Severe ……………………………………………….. 6-10

Erection Hardness Score 1-4,

Score of 1-2 not able to penetrate

Flow Mediated Dilatation (FMD)

 Inclusion/ exclusion criteria
Inclusion Exclusion
Men age 40-80 years old Investigator’s impression of expected poor patient compliance

Premature Ejaculation
IIEF-EF score of 11-20 with or without the use
of medication Any psychiatric disorder
Erectile Dysfunction for at least 6-months
Epilepsy
Steady relationship for at least 6- months
Peyronie's disease\ penile curvature

Patient with established organic ED Coagulopathy

Any active malignancy in the pelvic or penile region within the

last 3 years, post radical prostatectomy
Study protocol

month 1 month 1 month 1

Treatment Treatment No Treatment
sessions x2/w sessions x1/w

Total 8 sessions Total 4 sessions

Assessment Assessment Assessment

(Full IIEF, EHS, FMD*). (Full IIEF, EHS). (Full IIEF, EHS, FMD*,
QEQ,BSW, SQOL
EDITS).

months 3
 Ohhmed Prototype RF Device- first 10 patients

Virtual Dynamic Rotation

• Maximum power output : 25W

• 15 minute ‘Ring’ treatment
• 15 minute ‘Pad’ treatment
• Safety: Double trigger, thermode
per electrode
• Virtual rotation time: 2 sec
 Ohhmed Prototype Mobile RF Device- following 18 patients
Device characteristics identical to the professional (non-mobile) device
Patient Screening Screened
N=42

6- Severity of ED (IIEF-EF 11-22) Screen Failure

3- Age
1- Low testosterone level
N=10
1-Urgent trip abroad
1-Partner left him
RF treatment 1-Did not comply
N=32 1-Unexpected findings in lungs

Discontinued
N=4

Completed
N=28
IIEF-EF Score before and 1-month after treatment
 Pilot Study Results (n=10)
Test Baseline ± SD After 1 month ± SD Improvement
IIEF-EF 16.7 ± 2.8 24.21 ± 4.8 + 45%
EHS 2.6 3.25 + 25%
Flow Mediated dilatation (FMD) :
Base 3.2 4.9 +53%
Max flow 5.1 11.4 +124%
AUC 150.7 340.8 +126%
EDITS 71.2

QEQ 69.4

 Safe  Patients treat themselves

 Painless  Patients highly satisfied
Results: Baseline characteristics (n=28):

• Mean age: 57.1 ± 11.7y.

• BMI: 27.2 ± 2.7
• Average ED duration: 43 ± 31m. (range 6-70m)
• Average Penile length: 10.5 ± 1.9cm (range 7-14cm)
• Testosterone level: 18 ± 6.1 (range 12-24 nmol/l, inclusion criteria)
 Results: n=28

Baseline 1-month P Value

Total IIEF 44.4 ± 7.3 60.5 ± 10.8 IIEF-EF BEFORE AND AFTER RF TREATMENT
25
Sexual satisfaction domain 7.9 ± 2.5 11.3 ± 2.7
20
Total satisfaction domain 5.7 ± 1.9 8.3 ± 1.8
15
EF Domain 16.8 ± 3.1 24.4 ± 4.4
Normalized: EF Domain>25 14/28 (50%) 10

IIEF-EF scores met MCID 25/28 (89%) 5

criteria
0
EHS 2.1 ± 0.8 3.2 ± 0.5 Baseline 1-month

Improved morning erections 12/28

No pain or any other side effects were noted nor reported

Results: n=28
• EDITS (Erectile Dysfunction Index of Treatment Satisfaction):
Average final score: 76.8 ± 20.3 (>50=satisfied)
Only 4/28 (14.2%) were below 50 points

• QEQ (Quality of Erections Questionnaire): (>75=good quality erections)

Average final score: 73.4 ± 23.8
10/28 (36%) were below 75
• SQOL (Sexual Quality of Life): (> 60=positive SQOL)
Average final score: 67.6 ± 29.4
10/28 (36%) were below 60
• BSW (Treatment Benefit, Satisfaction, and Willingness to Continue) (0-6)
Average final score: 4.83 ± 1.1
 Conclusions
Normal spontaneous erections
Restoring spontaneous sexual activity
Self treatment and home use
No side effects
Adhering to the concept of enhancing and improving erectile function (not on-demand trt.)
 The first RF device with unique technology that improves ED.
 In some of our cases, RF therapy was able to reverse
PDE5-I non-responders to responders, and reduced dose of ICI