Assesment of the efficiency of conservative treatment of Peyronie’s disease

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Abstract


There were 27 men under observation who got conservative treatment for Peyronie's disease. The criteria for inclusion in the study were the maximum size of the plaque of the penis up to 1.5 cm and the angle of curvature of the penis is less than 45 degrees. Before treatment, after 6 and 12 months, patients underwent ultrasonic dopplerography of the penis, the velocity of blood flow in the cavernous and dorsal arteries and the size of the plaque were determined. All observed patients were prescribed combined therapy, such as symptomatic, immunological and physiotherapeutic treatment. In this case, the patients of the 1st group (n = 15) additionally got longidase treatment (intramuscularly for 3000 IU every 3 days, for a course of 10 injections with concurrent administration of rectal suppositories with longidase at the same dose for a course of 10 suppositories). Locally, these patients were assigned phonophoresis with lengidase on the plaque area (10 sessions). The remaining 12 patients (2nd group) didn’t got longidase treament. Six months after the start of treatment the absence of plaques was recorded in 8 (53.3%) patients in the 1st group and 4 (33.3%) in the 2nd group of patients and in 12 months in 11 (73.3%) and 6 (41.6%) patients. Thus, conservative therapy in Peyronie's disease is effective in patients in the early stages of the disease with moderate deviation of the penis and plaques up to 1.5 cm. The inclusion of longidase in the complex therapy increases the effectiveness of the treatment.


Peyronie’s disease or penile fibromatosis has become one of the most significant problems in men’s health in recent decades. Peyronie’s disease does not pose a suffer to the life of the patient, but it interferes with the sexual life of men, leads to sexual insufficiency, disrupts the family andcauses severe depression.

Peyronie’s disease was first described in 1743 by François de la Peyronie (1678–1747) the court surgeon of King Louis XV of France. Even though 275 years have passed there is currently no consensus on the causes of Peyronie’s disease because its etiology and pathogenesis are still not fullyclear [1, 2]. There are also disputes about the terminology used to describe the disease. In several cases, penile fibromatosis is defined as a disease with a predominant localization of the pathological process in the cavernous bodies of the penis and leads to penile deformity during erection. In other studies it is defined as the gradual and mildly painful induration of several sections of cavernous bodies and the formation of dense connective tissue plaques, which lead to the functional abnormality of the penis. Peyronie’s di sease is sometimes defined as a benign slowly progressing disease with an unclear etiology and is characterized by the formation of fibrous extracavernous plaques on the tunica albuginea of the penis, thus leading to phallocampsis and abnormal erectile function. Several studies indicate that Peyronie’s disease is a focal fibrosis (scarring) of the tunica albuginea of the penis, which leads to a distortion of the ratio of collagen and elastic fibers, a disorder of the elasticity of the tunica albuginea and phallocampsis during erection to the side where the tunica albuginea is not impaired. At the last revision of ICD-10 in 2005, Peyronie’s disease and penile fibrous cavernous bodies were combined into one nosological group related to penile fibromatosis.

To date, the prevalence of Peyronie’s disease is estimated to be in the range of 3% to 8% in all men [3–5]. The disease may not always be accompanied by clinical symptomatology that requires treatment. The incidence of penile fibromatosis increases with the increasing age of the patient [1].This may be a result of the decreased elasticity of penile tissues in older men, which increases the risk of microinjuries in penile tissues. The most common theories about how Peyronie’s disease develops include the following [6, 7]:

  1. Microinjuries of the tunica albuginea of the penis: an insignificant tearing of the tunica albuginea with the formation of a small hematoma causes fibrin to activate fibroblasts and inflammatory mediators. The disease starts with acute inflammation between the layers of the tunica albuginea. The complete process to substitute fibrin in the tunica albuginea takes 12–18 months when the curvature is completely formed.
  2. Endocrine imbalance: the disease develops because of a hormonal imbalance.
  3. Connective tissue pathology: connective tissue pathology (Dupuytren’s contracture, scleroderma, subacromial bursitis, dermomyositis, and sclerosis of the auricles) related to other diseases is noted. The chromosomal abnormalities of cells taken from plaques in Peyronie’s disease are similar to those in Dupuytren’s contracture.
  4. Toxic chemicals: there is a link between the development of Peyronie’s disease and the prolonged intake of barbiturates.
  5. Genetic associations: class II antigens of the human leukocyte antigen (HLA) system are frequently detected in Peyronie’s disease, particularly HLA-DR3 and HLA-DQW2. These antigens are associated with organ-specific autoimmune disorders and resemble the rheumatic process.
  6. Viral changes: the transformation factor TGF-B1 (cytokine) enhances the synthesis and accumulation of collagen in the cavernous tissue of the penis and stimulates the growth of fibroblasts, thus leading to a decrease in nitric oxide, as well as hypoxia and damage to the endothelium.
  7. Vegetative theory: a lesion of autonomic cavernous innervation occurs in the zone of the dorsal vascular–neural bundle.

In the pathogenesis of Peyronie’s disease, the development of fibrosis of the tunica albuginea or cavernous tissue is important because this type of fibrosis may be one of the causes of erectile dysfunction. The congenital anatomical features of the penis (e. g., chordee with connective tissue bands) and urethral diseases (hypospadias, stricture) may increase the risk of Peyronie’s disease.

The involvement of the Buck fascia, perforating vessels, and dorsal arteries of the penis leads to penile venous occlusion disruption and arterial insufficiency, which require dynamic cavernosography. The dorsal, lateral, and ventral parts of the penis are often involved in the scarring. Given the deposition of calcium salts in the indurated areas, a cartilaginous consistency is acquired. Plaques in connective tissue appear on the rear surface of one or both cavernous bodies in the form of a flat polygonal formation that grows downward and inward; one or more of these fibrous plaques may be present.

In the diagnosis of Peyronie’s disease, magnetic resonance imaging or computed tomography is used. The ultrasound dopplerography of the penis assesses the size and localization of plaques and measures the blood flow in the vessels of the penis. Conservative treatment is indicated at the early stages of the disease and in cases wherein the patient refused surgical treatment [8–10]. Conservative treatment is usually performed in the first year after the onset of the disease to the onset of plaque calcification and when the penis curvature is less than 30–45 degrees. Some of the treatments include hormonal drugs, biogenic stimulants, physiotherapy methods, shockwave therapy, close-focus roentgenotherapy, verapamil, interferons, and type 5 phosphodiesterase (PDE5) inhibitors [11–13].

The goal of this study was to evaluate the efficacy of the conservative treatment of Peyronie’s disease.

MATERIALS AND METHODS

A total of 27 men aged 25 to 66 years old (mean age 45.5 years) received conservative treatment for Peyronie’s disease at Alexandrovsky Hospital, which is the headquarters of the Department of Urology of I.I. Mechnikov North-West State Medical University. The duration of the disease was from three months to five years. All patients were married. Four patients had a history of Dupuytren’s contracture and two patients had controlled diabetes mellitus. Patients reported moderate pain in the penis, a reduction in adequate and spontaneous erections, and mild induration in the body (e. g., the root of the penis), which causes a slight curvature in the penis and worsens the quality of their life.

All patients underwent general urinary examination. Urinalysis, clinical examinations, and biochemical blood tests were performed. The levels of sexual and gonadotropic hormones and the level of prostate specific antigen (PSA) in serum were determined. The levels of sexual and gonadotropic hormones and serum glucose were normal, whereas PSA levels were below 2 ng/ml. Additionally, sexually transmitted infections were ruled out in all patients.

The examination included the ultrasound dopplerography of the penis, velocity of blood flow in the cavernous and dorsal arteries and the size of the plaques were determined. The size of the plaques of the penis did not exceed 1.5 cm in diameter and the angle of curvature of the penis was lessthan 45 degrees, which was the criteria for inclusion in this study.

All patients received combined therapy with symptomatic, immunological, and physiotherapeutic treatments. The latter included magnetic-laser therapy on the plaque area of the penis and local negative pressure (LNP) therapy. Fifteen patients (Group 1) also received Longidaza preparation (3,000 IU intramuscularly once every 3 days (10 injections) with the simultaneous administration of rectal suppositories with Longidaza at the same dose (10 suppositories)). Phonophoresis to the plaque area with Longidaza was prescribed locally to these patients (10 sessions), along with magnetic-laser therapy. The remaining 12 patients (Group 2) did not receive Longidaza.

Patients in both groups were simultaneously treated with magnetic-laser therapy by using the AMVL-01 device, which creates an LNP at 2 atm in the flask and causes an erection with 10–20 min duration (Figure 1). The LNP therapy included 10 procedures. In severe erectile dysfunction, a PDE5 inhibitor was prescribed in individually selected doses. The results of treatment were evaluated 6 and 12 months after its onset.

 

Fig. 1. Diagnosis of curvature of the penis on the apparatus AMVL-01 (apparatus vacuum-laser therapeutic urological) in patient A., 54 years old, with Peyronie's disease. Local negative pressure with maximum discharge in the flask affects the baro-and thermoreceptors of the skin of the penis, enhances microcirculation in its vessels. An insignificant curvature (angle of curvature - 30 degrees) of the penis

 

The data were analyzed with conventional statistical methods by using SPSS12.0 software. The mean value was calculated, and the confidence coefficient was α = 0.95 (probability of error p < 0.05).

RESULTS

In performing ultrasound dopplerography on the penis, vascular changes were detected in 16 of the 27 patients examined, and 8 patients (50%) had manifestative venogenic compensated and subcompensated erectile dysfunction (Figures 2 and 3). The remaining 11 patients had no signs of vascular changes (Table 1).

 

Fig. 2. Ultrasound dopplerography of the penis of Patient D (36 years old with Peyronie’s disease and venogenic erectile dysfunction): a) in the distal part of the penis, the plaques are from 1–2 to 8.5 mm; b) the dorsal vein did not collapse, and blood flow along it was 30 ml/min. Valsalva test was positive

 

 

Fig. 3. Ultrasound dopplerography of the penis of Patient T (55 years old with Peyronie’s disease and venogenic erectile dysfunction). The patient has Dupuytren’s contracture: a) abnormality of the structure of the cavernous arteries, i.e., anastomosis of the cavernous arteries in the crus of the penis; b) plaques in the cavernous bodies (plaque of 11.4 mm × 4.6 mm × 9.2 mm is marked), which deformed the penis; c) and d) noncollapse concurrence of the dorsal vein as a sign of venous erectile dysfunction

 

Table 1. Vascular disorders in patients with Peyronie’s disease by the ultrasound dopplerography of the penis

Таблица 1. Сосудистые нарушения у больных с болезнью Пейрони по данным ультразвуковой доплерографии полового члена

Group of patients

Vascular abnormalities by the ultrasound
dopplerography of the penis

Detected

Undetected

1 (n = 15)

9

6

2 (n = 12)

7

5

Total (n = 27)

16 (59,3%)

11 (40,3%)

 

In all 27 patients, the maximum size of the plaques before treatment was less than 1.5 cm. In 13 patients (48.1%), the plaques were >0.5 cm in diameter. Six patients (22.2%) had plaques of >1 cm, and the remaining eight patients (29.6%) had plaques of <0.5 cm in diameter (Table 2). In Group 1, the maximum plaque sizes were <0.5, >0.5, and >1 cm in five, seven, and three patients, respectively; in Group 2, the same plaque categories were found in three, six, and three patients, respectively. Six months after the start of the complex combined treatment with Longidaza, the number of patients with plaques of more than 0.5 cm (before treatment in 13 patients and after treatment in 7 patients) was reduced by almost twofold. The number of patients with plaques less than 0.5 cm decreased fourfold. The absence of plaques was achieved 6 months after the start of treatment in 8 patients (53.3%) in Group 1 and 4 patients (33.3%) in Group 2 and 12 months after the treatment in 11 (73.3%) in Group 1 and 6 (41.6%) patients in Group (see Table 2).

 

Table 2. Results of treatment of patients with Peyronie’s disease (n = 27)

Таблица 2. Результаты лечения пациентов с болезнью Пейрони (n = 27)

Group
of patients

Maximum size of plaques according to ultrasound dopplerography, cm

No plaques 6 and
12 months, n (%)

Before
treatment

Six months after
the treatment

Twelve months
after the treatment

< 0.5

> 0.5

> 1

< 0.5

> 0.5

> 1

< 0.5

> 0.5

> 1см

1 (n = 15)

5

7

3

1

4

2

3

1

8 (66.6%)/

11 (73.3%)

2 (n = 12)

3

6

3

2

4

2

1

3

2

4 (33.3%)/

6 (50%)

Total (n = 27)

8

13

6

2

7

4

1

6

3

14 (51.8%)/
17 (63%)

 

The results of the study reveal the efficacy of conservative complex therapy at the early stage of the disease, as well as the pathogenetic justification of the treatment and its good tolerability. At the same time, the effectiveness of treatment was higher in the group of patients receiving Longidaza.

CONCLUSIONS

Conservative therapy in Peyronie’s disease is effective in patients at the early stages of the disease, with moderate deviation of the penis and plaques of up to 1.5 cm. The inclusion of Longidaza in the complex therapy increases the treatment efficacy.

Svetlana N. Kalinina

North-Western State Medical university named after I.I. Mechnikov

Author for correspondence.
Email: kalinina_sn@mail.ru

Russian Federation, Saint Petersburg

Doctor of Medical Science, Professor, Urology Department

Vladimir N. Fesenko

North-Western State Medical university named after I.I. Mechnikov

Email: fesvn_spb@mail.ru

Russian Federation, Saint Petersburg

Candidate of Medical Science, Associate Professor, Urology Department

Anton V. Nikolskii

Aleksandrovskaya Hospital

Email: fesvn_spb@mail.ru

Russian Federation, Saint Petersburg

Candidate of Medical Science, Urologist, Department of Urology

Oleg O. Burlaka

Aleksandrovskaya Hospital

Email: burlaka@list.ru

Russian Federation, Saint Petersburg

Candidate of Medical Science, Head of Department of Urology

Natalia V. Marchenko

Aleksandrovskaya Hospital

Email: burlaka@list.ru

Russian Federation, Saint Petersburg

Head of Department of Physiotherapy

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Supplementary files

Supplementary Files Action
1. Fig. 1. Diagnosis of curvature of the penis on the apparatus AMVL-01 (apparatus vacuum-laser therapeutic urological) in patient A., 54 years old, with Peyronie's disease. Local negative pressure with maximum discharge in the flask affects the baro-and thermoreceptors of the skin of the penis, enhances microcirculation in its vessels. An insignificant curvature (angle of curvature - 30 degrees) of the penis View (173KB) Indexing metadata
2. Fig. 2. Ultrasound dopplerography of the penis of Patient D (36 years old with Peyronie’s disease and venogenic erectile dysfunction): a) in the distal part of the penis, the plaques are from 1–2 to 8.5 mm; b) the dorsal vein did not collapse, and blood flow along it was 30 ml/min. Valsalva test was positive View (485KB) Indexing metadata
3. Fig. 3. Ultrasound dopplerography of the penis of Patient T (55 years old with Peyronie’s disease and venogenic erectile dysfunction). The patient has Dupuytren’s contracture: a) abnormality of the structure of the cavernous arteries, i.e., anastomosis of the cavernous arteries in the crus of the penis; b) plaques in the cavernous bodies (plaque of 11.4 mm × 4.6 mm × 9.2 mm is marked), which deformed the penis; c) and d) noncollapse concurrence of the dorsal vein as a sign of venous erectile dysfunction View (649KB) Indexing metadata

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Copyright (c) 2018 Kalinina S.N., Fesenko V.N., Nikolskii A.V., Burlaka O.O., Marchenko N.V.

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