Pycnogenol® treatment of acute hemorrhoidal episodes

Pycnogenol® Treatment of Acute Hemorrhoidal Episodes

Gianni Belcaro1, Maria Rosaria Cesarone1, Bruno Errichi1, Andrea Di Renzo1, Maria Giovanna Grossi1, Andrea Ricci1, Mark Dugall1, Umberto Cornelli1, Marisa Cacchio1 and Peter Rohdewald2

1Irvine2 Vascular Labs & Microcirculation, Physiology, Department of Biomedical Sciences, G D’Annunzio University. General Surgery, Guardiagrele (Ch)-Ortona (Pe) Pescara, San Valentino Vascular Screening Project, Italy2Institute of Pharmaceutical Chemistry, University of Münster, Hittorfstr. 58-62, 48149 Münster, Germany

We investigated the effi cacy of orally and topically applied Pycnogenol® for the management of acute hemor-rhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days’ treatment and again seven days following treatment cessation. The decrease in scores was signifi cantly more pronounced in the Pycnogenol®-treated groups than in the control group given placebo (p < 0.05), showing the effi cacy of Pycnogenol® for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol® in addition to oral Pycnogenol® the improvement in symptoms set in signifi cantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol® for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol®, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol® eases the management of acute hemorrhoidal attacks and help avoid bleedings. Copyright © 2009 John Wiley & Sons, Ltd.

Keywords: hemorrhoids; Pycnogenol®; venous insuffi ciency; hemorrhoidal bleeding.

INTRODUCTION

Hemorrhoids are one of the most common medical problems; more than 50% of the population develops hemorrhoids (Chand et al., 2008). Millions of patients both in the USA and in Europe suffer more than once from hemorrhoidal attacks. Only 20% visit a medical doctor (Pigot, 2008). However, most patients do not report signs/symptoms to their doctor until there is bleeding and most of them use over-the-counter reme-dies. Only 20% visit a medical doctor. Possibly more than 525 000 patients are treated annually for symptom-atic hemorrhoids. Of these, approximately 10–20% will require surgical treatment (Loder, 1994). According to the National Digestive Diseases Information Clearing-house, about half of the US population will have hemor-rhoids by the age of 50. Lifestyle changes, topical medications, diet and careful hygiene are all that are needed in most patients to control signs/symptoms of hemorrhoids. Even very painful hemorrhoids spontane-ously become less painful and swollen within 2–3 weeks. In a limited (<15%) percentage of cases, surgical pro-cedures are necessary to provide satisfactory, long-term relief.

Hemorrhoidal attacks involving external hemor-rhoids are characterized by sudden, severe perianal pain and by a perianal mass. An acute, intravascular throm-bus may develop in the lumen of external hemorrhoids in association with severe pain which peaks within 48–72 hours.

Acutely thrombozed external hemorrhoids cause a purple-blackish, edematous, tense mass in the perianal region which may be very tender. Occasionally ischemia and necrosis of the overlying skin may occur and cause bleeding (Loder, 1994).

Surgery may be considered when other treatments (including treatment at home) have failed. Surgery also represents an option when symptoms severely affect the lifestyle and daily routine or when hemorrhoids reach a point of medical emergency, such as uncontrolled bleedings or anal blood and pus along with severe rectal pain (Chand et al., 2008).

Basic medical management of hemorrhoids includes dietary changes excluding all constipating foods, reduc-ing sugar and alcohol, increasing intake of fl uids and the use of bulking agents (fi bers, stool softeners, etc). A change in daily routine and exercise, when possible, are very effective in improving signs and symptoms.

Anti-infl ammatory agents and fl avonoids have been used to improve signs and symptoms in acute hemor-rhoidal attacks and local agents are also frequently applied (often without a specifi c therapeutic plan) to improve the clinical picture (Basile et al., 2001; Misra, 2005).

* Correspondence to: Prof. P. Rohdewald, Institute of Pharmaceutical Chemistry, University of Münster, Hittorfstr. 58-62, 48149 Münster, Germany.E-mail: [email protected]

Received 27 July 2009Copyright © 2009 John Wiley & Sons, Ltd. Accepted 19 August 2009

PHYTOTHERAPY RESEARCHPhytother. Res. 24: 438–444 (2010)Published online 29 December 2009 in Wiley InterScience(www.interscience.wiley.com) DOI: 10.1002/ptr.3021

PYCNOGENOL® TREATMENT OF ACUTE HEMORRHOIDAL EPISODES 439

Copyright © 2009 John Wiley & Sons, Ltd. Phytother. Res. 24: 438–444 (2010)DOI: 10.1002/ptr

The aim of this study was to evaluate the effi cacy and the tolerability of high-dose oral Pycnogenol® on symptoms/signs of acute hemorrhoidal episodes either administered alone or in combination with additional Pycnogenol® applied topically.

Pycnogenol®, a trademark of Horphag Research, is a standardized extract of French maritime pine bark (Rohdewald, 2002; 2005). Pycnogenol® improves endo-thelial function and has important anti-infl ammatory, antithrombotic and venotropic properties which may be benefi cial in patients with hemorrhoids both for acute and for chronic treatment, preventing new attacks (Blazsó et al., 2004; Belcaro et al., 2005; Cesarone et al., 2006a; Nishioka et al., 2007).

PATIENTS AND METHODS

A total number of 84 patients suffering from an acute episode of external hemorrhoids (lasting since 24–48 h prior to inclusion), were participating in this random-ized, controlled, comparative study. Patients presenting with severe complications or those requiring surgery were excluded.

The most frequently observed signs and symptoms typical of a hemorrhoidal attack were evaluated during the study period of two weeks. In addition, the duration of the persistence (in hours) of peak pain and pain intensity were also scored as evaluation targets.

Treatment. The patients were randomly allocated to a treatment group (Table 1). They were treated with Pyc-nogenol® for 7 days and were followed-up for another 7 days after cessation (14-day total observation period).

Group A: Pycnogenol® 300 mg (six 50 mg tablets) per day for four days then 150 mg (three tablets) per day for three days (at 8 am, 4 pm and 12 pm). Group B: comparable placebo (identical tablets without active ingredient). Group C: topical 0.5 % Pycnogenol® cream in combination with Pycnogenol® oral treatment as above as in Group A. Group D: Oral Pycnogenol® as in Group B in combination with topical sham cream.

Concomitant management. All groups received the ‘best’ available concomitant lifestyle management of hemorrhoids. The management consisted of dietary alterations (elimination of constipating foods such as cheese, bananas); addition of bulking agents (dietary fi bers, stool softeners); increased intake of fl uids; change in daily routines; and moderate, continuous exercise.

Symptoms and signs of hemorrhoidal attacks were assessed with an analogue scale line at 0 (inclusion), 7 and 14 days (predefi ned periods of the study). Signs and symptoms were scored on a 4-point severity grading scale ranging from 1 = absent to 4 = severe (Table 2).

The duration of peak pain and severe symptoms was observed and recorded from the beginning of signs/symptoms to the disappearance of severe, incapacitat-ing pain requiring treatment and rest/immobility or severely altering social functions.

Defi nition of severe pain. The Karnofsky Scale (Table 3; Karnofsky and Burchenal, 1949), which shows 10 defi nitions (100-point score Karnofsky-scale – by which a normal subject scores 100%), allows the rapid evalu-ation of the patient’s condition on a given day or moment, without going through several, complex multiple-choice questions or calculating signs and symptoms surveys, which are very demanding for both patients and staff during treatment of acute health problems. The Karnofsky scale is predominantly used for more severe clinical conditions (i.e., tumors) but it may have a good application in any incapacitating (even temporarily) condition, such as hemorrhoidal attacks.

Evaluation of hemorrhoidal attacks with the Karnofsky scale. Being otherwise normal subjects, all patients, before the hemorrhoidal attack had a Karnofsky scale score of 100 as they were able to work and could be defi ned as normal subjects with no complaints. They did not show any signs indicative of a disease. During the hemorrhoidal attack, with severe signs/symptoms, the Karnofsky scale level may show – even temporarily for a few hours – a dramatic decrease, such as to scores in the range as low as 60–70. Severe (incapacitating) signs/symptoms due to hemorrhoidal attacks were arbitrarily defi ned as signs/symptoms capable of causing a tempo-rary decrease of at least 30% of the K-scale score for at least 6 h, or, at least a 20% decrease for a minimum of 24 h.

Table 1. Evaluation time plan

EVALUATION

INCLUSION

C1 C2 C4

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14TREATMENT FOLLOW-UPPERIOD

C = time points for evaluation of signs and symptoms.All subjects received the ‘best’ available standard treatment. The regimen for each of the four groups and the therapeutic program is shown in this summary table.A: Pycnogenol® (six times 50 mg tablets per day for four days, then three tablets per day for three days).B: Comparable placebo.C: Pycnogenol® cream/ointment in association with oral treatment.D: Oral Pycnogenol® in association with a sham cream (without Pycnogenol®).

Table 2. Signand symptoms

• ACUTE INTRAVASCULAR THROMBUS• ACUTE, SEVERE PERIANAL PAIN• PURPLE/BLACK, EDEMATOUS, TENSE SUB-CUTANEOUS � PERIANAL MASS• TENDERNESS• ISCHEMIA-NECROSIS OF THE OVERLYING SKIN BLEEDING• LOST WORKING DAYS• SOCIAL ROUTINE ALTERATIONS• IMPAIRMENT IN WALKING• IMPAIRMENT IN STANDING• IMPAIRMENT IN SITTING• IMPAIRMENT IN WORKING PERFORMANCE• EMBARASSMENT, SOCIAL WITHDRAWAL

Characteristics of individual signs/symptoms in patients with hemorrhoidal attacks and acute signs/symptoms. Each Signand symptom was measured on a four-point severity grading scale.


440 G. BELCARO ET AL.

Exclusion criteria. Patients requiring any other cardio-vascular treatment, or who had recently received surgery, were diagnosed with infections or tumors, or were severely handicapped were excluded from this study. No patient had indications for surgical treatment of hemorrhoids at the moment of inclusion or during the follow-up period. The need for surgery (bleeding, thrombosis, prolapse, pain not responding to medical treatment or other complications were all exclusion cri-teria). Portal hypertension was also an important exclu-sion criterion.

Blood tests. Blood pressure, heart rate and standard blood chemistry and rheology parameters were moni-tored. All values (excluding white cells count) were within normal ranges at inclusion. Fasting blood sugar, hemoglobin, kidney and liver function tests and electro-lytes were all within normal ranges at inclusion.

Diary. Lost working days, costs due to signs and symp-toms control (particularly to any drug treatment) and the occurrence of any complication or comparable recurrent attacks were recorded by all patients in a two-month diary.

Social quality of life parameters were evaluated with a social quality of life scale at day 7 and day 14.

Statistics. Considering the possible variability of results, measurements, and observations (within such a variable condition of acute hemorrhoids attacks) even in con-trolled, standardized conditions and inter-individual variations, we included at least 20 subjects in each of the study groups. A percentage of at least 25% female subjects were included in each group. A post-treatment or post-observation variation >5% in signs/symptoms was considered signifi cant (p < 0.05) to defi ne improve-

ment due to treatments or differences between groups.

The evaluation of signs/symptoms, even in standard-ized clinical/environmental and individual condi-tions cannot be considered regularly distributed statistically. Therefore non-parametric statistic tests (Mann- Whitney U-test and the analysis of the variance) among groups were used in the fi nal evaluation of treatment or follow-up-dependent statistical data. Data collection and elaboration and the fi nal statistical analysis were independently conducted by a separate group; the stat-isticians were not aware of the technical details of the study protocol.

RESULTS

The groups were comparable for age and gender (Table 4) and distribution regarding their clinical picture (Tables 5–7). No drop-outs occurred during the study and no side effects were recorded.

Variation in signs/symptoms

The most important and most frequently observed signs/symptoms assessed were acute intravascular thrombus, acute severe perianal pain, purple/black edematous and tense subcutaneous perianal mass, ten-derness, ischemia/necrosis of the overlying skin and bleeding. The scores progressively decreased in all groups (p < 0.05) during the two-week observational period. The decrease in signs/symptoms score was sig-nifi cantly higher in the Pycnogenol® groups as com-pared to the control group given placebo (p < 0.05)

Table 3. The Karnofsky Scale

(Subjects included into the study)

100 Able to work. Normal: no complaints; no evidence of disease. 90 Able to work. Able to carry on normal activity; minor symptoms. 80 Able to work. Normal activity with effort; some symptoms. 70 Independent; not able to work. Cares for themselves; unable to carry on normal

activity.

(Excluded from this study) 60 Disabled; dependent. Requires occasional assistance; cares for most needs. 50 Moderately disabled; dependent. Requires considerable assistance and frequent

care. 40 Severely disabled; dependent. Requires special care and assistance. 30 Severely disabled. Hospitalized, death not imminent. 20 Very sick. Active supportive treatment needed. 10 Moribund. Fatal processes are rapidly progressing.

The Karnofsky scale was developed by Karnofsky, Abelmann, Craver and Burchenal in 1948. The 10-point Karnosky scale allows the rapid screening of a patient’s condition on a given day, without going through several, complex multiple-choice questions or sign/symptoms surveys more demanding for patients and staff. Before the hemorrhoidal attack, all included subjects had a K-scale of 100 and were able to work (Normal: no complaints; no evidence of disease). During the attack, with severe signs/symptoms the K-scale level dropped – even only for a few hours – with a dramatic decrease down to 60–70. Severe symptoms due to hemorrhoidal attacks were arbitrarily defi ned as signs/symptoms capable of causing a temporary decrease of at least 30% of K-scale score for at least 6 h, or, at least 20% for a minimum of 24 h.



Table 4. Details of patients

Groups Number Age M : F Time* hrs

A (Pycnogenol®) 20 49.3; 5.8 12 : 8 36; 2 B (controls, placebo) 21 48.9; 3 11 : 10 36.3; 2.2C (Pycnogenol® + local cream) 21 48.2; 7.1 11 : 10 37.2; 2.4D (Pycnogenol® + sham cream) 22 49.1; 5 13 : 9 38; 3Total 84 48.9;5.2 47 : 37 36.87; 2.4

* time from onset of acute episode (<48 h) until treatment started.

Table 5. Variation in signs/symptoms in patients with hemorrhoidal attacks (mean and SD)

Inclusion 7 days 14 days

Acute intravascular thrombus Pycnogenol® 2.1;1 0.6;0.2 0.2;0.1Control 2.3;0.5 1.9;0.2 1.7;0.2Sy + Loc Pycno 2.3;0.4 0.32;0.1 0.2;0.1Sy + ShLoc 2.1;1.1 0.5;0.2 0.2;0.1

Acute, severe perianal pain Pycnogenol® 3.2;1.3 0.8;0.3 0.3;0.1Control 3.4;0.2 2.2;0.2 1.9;0.4Sy + Loc Pycno 3.3;1 0.3;0.1 0.2;0.1Sy + ShLoc 3.2;1 0.7;0.2 0.2;0.1

Purple/black, edematous, tense subcutaneous perianal mass

Pycnogenol® 3.6;1.1 1.1;1 1.1;1Control 3.61;0.3 2.8;1 2.4;1Sy + Loc Pycno 3.6;1 0.5;0.3 0.4;0.1Sy + ShLoc 3.5;1.1 1.2;0.5 1;0.3

Tenderness Pycnogenol® 3.8;0.2 1.4;1 1.4;0.5Control 3.7;0.2 2.8;0.7 2.1;1Sy + Loc Pycno 3.7;0.1 1;1.1 1;0.5Sy + ShLoc 3.7;1.8 1.3;0.6 1.3;0.5

Ischemia-necrosis of the overlying skin Pycnogenol® 2.2;1 1;0.8 0.5;0.1Control 2.4;1.1 2.6;1 2;1.4Sy + Loc Pycno 2.2;0.8 0.5;0.2 0.3;0.1Sy + ShLoc 2.3;0.7 1;0.5 0.5;0.1

Bleeding Pycnogenol® 2.6;1 0;0 0;0Control 2.8;1 1.3;0.8 1;1Sy + Loc Pycno 2.7;0.7 0;0 0;0Sy + ShLoc 2.6;0.8 0;0 0;0

Signs/symptoms were measured on a 4-point severity grading scale (from 0 = absent to 4 = severe).Controls = Placebo.Sy = Systemic Pycnogenol®.ShLoc = Sham local treatment.

Table 6. Social scale

7 days 14 days

Social routine alterations Pycnogenol® 2.2;1 1;0.4Control 3.4;0.5 2;1.1Sy + Loc Pycnogenol® 2;1.1 0.4;0.1Sy + ShLoc 2.2;1.1 1;0.3

Impairment in walking Pycnogenol® 2;2 1;0.4Control 3.3;0.6 2;1.1Sy + Loc Pycnogenol® 1.2;1 0.6;0.2Sy + ShLoc 2;1.1 1;0.5

Impairment in standing Pycnogenol® 2.2;1 0.4;0.1Control 3.4;0.3 1.3;1Sy + Loc Pycnogenol® 2;0.5 0.2;0.1Sy + ShLoc 2.3;1.1 0.5;0.1

Impairment in working performance

Pycnogenol® 2.5;0.3 1.1;0.5Control 3.4;1.4 2.2;2Sy + Loc Pycnogenol® 0.3;0.1 0.2;0.1Sy + ShLoc 2.6;1 1;0.7

Embarrassment, social withdrawal

Pycnogenol® 3.1;1 1.1;0.4Control 3.7;0.3 2;1.1Sy + Loc Pycnogenol® 2;1 0.8;0.4Sy + ShLoc 3;1.2 1;0.4

Variations in quality of life parameters: SOCIAL SCALE (results are evaluated for the observation period, at 7 and 14 days).



showing the effi cacy of Pycnogenol® in relieving signs and symptoms of acute external hemorrhoids.

Considering the differences within the three Pycno-genol® groups, the scores were more signifi cantly decreased in the combined local + systemic treatment group (considering scores of each sign and symptom). This observation indicated a signifi cantly faster and better improvement in treatment groups using Pycno-genol® with an important added benefi t of topically applied Pycnogenol®. The results obtained with the sham cream in the group given oral Pycnogenol® were statistically comparable to those obtained in the group exclusively taking oral Pycnogenol®.

Considering hemorrhoidal bleedings, this complica-tion was completely absent in all three Pycnogenol® groups after day 7 and day 14 while it was still observed in controls (placebo) at the two weeks of follow-up.

Quality of life parameters

Table 6 shows the variations in quality of life parame-ters recorded at the two weeks follow-up. Those param-eters included social routine alterations, impairment in walking, impairment in standing, impairment in sitting, impaired working performance and embarrassment or social withdrawal. The ‘social quality of life scale’ results were evaluated at day 7 and day 14. The most important and most frequently observed social impairment prob-lems also progressively decreased – in parallel with hemorrhoidal signs and symptoms in all groups (p < 0.05) during the two weeks. However, the improvement in the social quality of life score was signifi cantly better

in the three Pycnogenol® treatment groups in compari-son with placebo controls (p < 0.021).

Statistical analysis of data from the three Pycno-genol® treatment groups shows signifi cantly decreased score values for each item (p < 0.05) in the group with combined local and systemic treatment. The results in the sham-cream-treated group combined with oral Pyc-nogenol® were comparable to those obtained in the oral Pycnogenol® only group.

These results confi rmed a signifi cantly faster and better improvement on social functions by Pycnogenol® with important added benefi t by the combination with topical Pycnogenol®.

Peak pain time

The duration of peak pain patients suffered was on average 17.8 h (SD 6) in the oral Pycnogenol® group (Table 7) in comparison with 23.6 h (SD 5) in controls (this difference was statistically signifi cant; p < 0.05). The peak-pain duration (16 h; SD 2) was signifi cantly lower in the combined, oral + topical Pycnogenol® treatment group (p < 0.05) as compared to controls. Moreover, this duration was also signifi cantly shorter (p < 0.05) compared to Pycnogenol® oral treatment only. Results in the sham-cream group combined with oral Pycnogenol® were comparable to the group using oral Pycnogenol® only treatment.

Costs and lost working days

Table 8 details the costs and lost working days (LWD) recorded by the patients in the four groups. Also the number of any recurrence or complication (within four weeks following the follow-up) is indicated.

There was a decreased number of working days (if 100% is the value recorded in controls); the Pycno-genol® group averaged 67.4% or less with a minimum of 63% in the combined oral and topical Pycnogenol® treatment (p < 0.05). Also the treatment costs (being 100% the value observed in controls) was signifi cantly decreased (p < 0.05) in the Pycnogenol® groups (down to 33% in the combined oral and topical Pycnogenol® treatment group).

Considering events such as recurrence of attacks or complications within the month following the follow-up period there was a signifi cant (p < 0.05) decrease in

Table 7. Occurrence and duration of pain

Treatment Peak-pain duration

Pycnogenol® 17.8; 6 hControl 23.6; 5 hSy + Loc Pycnogenol® 16; 2 hSy + ShLoc 17 h

HOURS WITH PEAK PAIN: is the evaluation from time 0 (beginning of severe signs/symptoms) to the end of severe, incapacitating pain requiring treatment and rest/immobility or severely altering social functions.

Table 8. Treatment costs and lost working days

Lost working days Treatment costs (*) Recurrent attack of complications (after follow-up)

Pycnogenol® 3; 1 (65%) 225; 49 (57.8%) 5%Controls 4.6; 1.2 (100%) 389.5; 87 (100%) 18%Sy + Loc Pycnogenol® 2.9; 1 (63%) 129; 68 (33%) 3%Sy + ShLoc 3.1; 1.1 (67.4%) 221; 71 (56.8%) 6%

Lost working days recorded by the patients in the four groups. Also the number of any recurrent attack or complication (within the four weeks after the follow-up) is indicated. There was a decreased number of working days (if 100% is the value recorded in controls the Pycnogenol® group averaged 67.4% or less with a minimum of 63% in the combined treatment. Also the treatment cost (being 100% the value observed in controls) was signifi cantly decreased in the Pycnogenol® groups (down to 33% in the combined treatment group). Considering recurrence or complications within the months after the follow-up period there was a signifi cant (p < 0.05) decrease in occurrence of events in the Pycnogenol® groups in comparison with a 18% recorded incidence in controls.The lowest incidence was observed in the combined treatment group.



the occurrence of events in the Pycnogenol® groups in comparison with an 18% recorded incidence in controls.

The lowest incidence was observed in the com-bined oral + topical Pycnogenol® treatment group (p < 0.05).

DISCUSSION

Pycnogenol® has been extensively researched for benefi ts related to venous insuffi ciency by us and other groups. Other fl avonoids commonly used for treatment of symp-toms related to venous insuffi ciency have also been tested in patients with hemorrhoids. A recently published meta-analysis of these studies concluded that fl avonoids may decrease bleedings, pain and itching, though the overall benefi cial effects of fl avonoids for treatment of hemor-rhoids were questioned (Alonso-Coello et al., 2006).

The study we present here is the fi rst controlled clini-cal investigation of Pycnogenol® for treatment of hem-orrhoids. We wanted to fi nd out if Pycnogenol® would be helpful for acute hemorrhoids which would reveal the effi cacy more compellingly than management of persist-ing hemorrhoids. Pycnogenol® did signifi cantly improve all symptoms we investigated and particularly the com-plete control of bleedings was surprising. However, in view of the acute problems, we chose to apply a very high daily dosage of 300 mg Pycnogenol® for four days, which was then lowered to 150 mg for the following three days. In most clinical trials with Pycnogenol®, including those we have carried out previously, a daily dosage of 100 to 150 mg was employed (Belcaro et al., 2005; 2006; Cesarone et al., 2006a; Grimm et al., 2006).

In studies for venous insuffi ciency, Pycnogenol® was demonstrated to be superior to other bioactive fl avo-noid species, such as horsechestnut seed extract Veno-stasin, Troxerutin and Dafl on (Koch, 2002; Riccione et al., 2004; Cesarone et al., 2006b). This may explain the good effi cacy we found with Pycnogenol® for the treat-ment of acute hemorrhoids. Unlike other fl avonoid species, Pycnogenol® signifi cantly improves endothelial function which could contribute to the decreased isch-

emia and intravascular thrombus found in our study (Nishioka et al., 2007). We previously found that Pyc-nogenol® is very effective for prevention of thrombosis (Belcaro et al., 2004).

Our study showed that applying Pycnogenol® locally to acute hemorrhoids exerts a more potent effect for improving symptoms than using systemic Pycnogenol® alone. Typically, topical application of active ingredi-ents will ensure higher concentrations in the treated body region. In view of the high amounts of orally taken Pycnogenol® this cannot be the only explanation for the dramatic improvement of symptoms when additional topical Pycnogenol® was utilized. Pycnogenol® does have bacteriostatic activity and topically applied Pycno-genol® was shown in pharmacologic studies to acceler-ate the healing of wounds (Blazsò et al., 2004; Torras et al., 2005). Such activities, particularly the antimicro-bial activity, may only be achievable with topically applied Pycnogenol®. In our clinical experience with Pycnogenol® we previously found a faster healing of ulcers in diabetes and chronic insuffi ciency patients when topical Pycnogenol® was added to the oral regimen (Belcaro et al., 2005; 2006).

In conclusion, Pycnogenol® treatment signifi cantly reduced the intensity and duration of pain and bleeding in acute hemorrhoidal episodes. With Pycnogenol® the number of procedures and hospital admissions caused by severe signs/symptoms was decreased. Furthermore, the costs of treatment were lowered by reducing the number of possible complications and the number of lost working days. This study indicates that Pycnogenol® (both in oral and topical forms) represents an effective way for controlling the common, disabling problem of acute hemorrhoidal attacks. Pycnogenol® should be effective for the management of hemorrhoids and the prevention of future acute outbreaks.

Finally, the importance of the quality of social life of patients with hemorrhoids shouldn’t be underestimated. This is one aspect which was particularly appreciated by the hemorrhoid patients in our study. Additional studies which are currently in progress will investigate the effi -cacy of chronic use of Pycnogenol® for preventing new attacks and in the management of hemorrhoids.

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Pycnogenol® treatment of acute hemorrhoidal episodes