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Curr. Pers. MAPs 100
Research article
Curr. Pers. MAPs, 2019; 2(2): 100-112
Current Perspectives on Medicinal
and Aromatic Plants
An International Journal
ISSN: 2619-9645 | e-ISSN: 2667-5722
Bioapigyn® Ointment of Pelvic Muscle Tonus Versus Pelvic Floor Muscle
Training for the Treatment of Urinary Incontinence
Višnja OREŠČANIN1*, Štefica FINDRI GUŠTEK2, Ivan FISTONIĆ3, Damir HODŽIĆ4, Josip
VALETIĆ4, Josipa RODIĆ5
*1 OREŠČANIN Ltd., A. Jakšića 30, 10000 Zagreb, Croatia
2 Findri-Guštek Centre for gynecology, urology and occupational medicine, Ninska 5, Sesvete, Croatia
3 Obstetric/Gynecology & Menopause Clinic, Preradovićeva 10, 10000 Zagreb, Croatia
4 Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
5 Family medicine clinic, Vilima Korajca 19, 10000 Zagreb, Croatia
*Corresponding author : vorescan@gmail.com
Received : 08/08/2019
Accepted : 01/12/2019
Abstract
Objective/Purpose: The purpose of this work was the assessment of the clinical efficacy and safety of
Bioapigyn® vaginal ointment for pelvic muscle tonus compared to pelvic floor muscle training in alleviating
the symptoms of stress, urge and mixed urinary incontinence and vulvo-vaginal disorders in child-bearing
and menopausal & postmenopausal women. Materials and Methods: The experimental group consisted of
66 women was treated 28 days with Bioapigyn® ointment for pelvic muscle tonus (2.5 mL/day). The
control group also consisted of 66 participants was subjected to pelvic floor muscle training during 28 days
(five times a day). ICIQ-UI SF score, the residual urine volume, perineometry, the total score of vulvo-vaginal
symptoms and vaginal pH were determined before and after the treatment or training. Results: Following
the treatment with Bioapigyn® ointment ICIQ-UI-SF score decreased 54.9%, perineometry parameters
increased between 31.5 and 34.3%, residual urine decreased for 76.9% and vaginal pH for 14.2%. All
the symptoms of vulvo-vaginal disorders disappeared completely in all participants. The control group
showed no changes in vaginal pH or the improvement concerning the vulvo-vaginal complaints. ICIQ- UI-SF
score decreased for 4.3%, residual urine volume for 9.1% while perineometry parameters increased
between 4.3 and 8.3%. Conclusion/Discussion: Bioapigyn® vaginal ointment for pelvic muscle tonus
alleviate the symptoms of incontinence by tightening and firming of the smooth muscles of the pelvic floor
thanks to the ingredients with smooth muscles contraction/relaxation and astringent properties. Low pH,
high osmolarity, viscosity, greasiness and coating effect of the ointment eradicated vulvo-vaginal
complaints.
Key Words: Urinary Incontinence, Vulvo-Vaginal Disorders, Honey, Herbal Macerates
© CUPMAP. All rights reserved.
1. Introduction
Urinary incontinence (UI) is the complaint of
involuntary leakage of urine (Aoki et al.,
2018). It is a common chronic condition that
affects millions of persons around the world
(Minassian et al., 2008). Although UI tend to
increase with age it could affect people of all
ages. Urinary incontinence occurs when the
pressure within the bladder exceeds the total
urethral resistance and urine flows
involuntarily beyond the urinary sphincter
Oreščanin et al.
Research Article
Curr. Pers. MAPs 101
(Rovner and Wein, 2004; Aoki et al., 2018). It
occurs as a result of abnormalities of the
urethra or both that may result in either
overfunction or underfunction of the bladder
and/or urethra, resulting in the development
of urinary incontinence.
Chronic UI is classified into five types: stress,
urge, mixed, overflow and functional (Rovner
and Wein, 2004; Khandelwal and Kistler,
2013; Aoki et al., 2018).
Stress urinary incontinence (SUI) is defined
as the complaint of involuntary leakage
during effort or exertion, or on sneezing or
coughing (Luber, 2004; Khandelwal and
Kistler, 2013; Aoki et al., 2018). It is
characterized by loss of small amount of
urine during physical activity or intra-
abdominal pressure (coughing, sneezing
jumping, lifting, exercise).
Urge urinary incontinence (UUI) is
characterized by loss of urine preceded by a
sudden and severe desire to pass urine in
which patient typically loses urine on the way
to the toilet (Khandelwal and Kistler, 2013).
Unlike the physical changes associated with
stress urinary incontinence, UUI involves
physiological perturbations to bladder
function. There are three main etiologies
essential to the bladder that leads to urge
incontinence: detrusor over activity, poor
detrusor compliance and bladder
hypersensitivity (Rovner and Wein, 2004;
Khandelwal and Kistler, 2013; Aoki et al.,
2018; Radzimińska et al., 2018).
Mixed UI presents the combination of stress
and urge incontinence which is characterized
by involuntary leakage associated with
symptoms of urgency as well as loss of urine
with exertion, effort, sneezing, or coughing
(Rovner and Wein, 2004; Khandelwal and
Kistler, 2013; Radzimińska et al., 2018).
Although UI increases with age, its
prevalence varies widely. The median
prevalence of any type of UI in women based
on 35 studies (Minassian et al., 2003) was
27.6% (with a range of 4.8–58.4%).
Among 1700 French women employed in
academic hospital, 12.4% of them reported
SUI (Peyrat et al., 2002). The pregnancy,
particularly previous vaginal delivery and
hysterectomy represented the significant
risk factors. The prevalence of stress, urge,
mixed, and any UI among 2,875 adult women
were 23.7%, 9.9%, 14.5%, and 49.2%,
respectively (Minassian et al., 2008). The
obtained significant risk factors were age,
ethnic background, weight, parity and
hysterectomy.
Among 83,355 American nurses at the age
range from 37 to 54 years 43% of them
reported incontinence. Identified risk factors
were age, race/ethnicity, body mass index,
parity, smoking, type 2 diabetes mellitus, and
hysterectomy (Danforth et al., 2006).
Among 20,000 Chinese women in the age
range from 20 to 99 years the prevalence of
UI was 30.9%. Among them 18.9%, 2.6%, and
9.4% were diagnosed with SUI, UUI and
mixed incontinence, respectively (Zhu et al.,
2009). The authors identified age, vaginal
delivery, multiparty, alcohol consumption,
central obesity, constipation, chronic pelvic
pain, history of respiratory disease,
gynecological events, pelvic surgery, and
perimenopause and postmenopause status
as the significant risk factors. Buchsbaum et
al. (2002), estimated the prevalence of
urinary incontinence among a group of
nulliparous nuns which was app. 50%.
Among them 30% had stress incontinence,
24% had urge incontinence, 35% had mixed
incontinence, and 11% had urine loss
unrelated to stress and urge. Identified
covariates were BMI, multiple urinary tract
infections, and depression.
Higher prevalence of UI (Brown et al., 1999)
was obtained among postmenopausal
women (56%). Luber (2004), reported the
prevalence of SUI which ranged between 4%
and 35% depending on the country with age,
obesity, and smoking as the most significant
risk factors. Nygaard and Heit (2004),
Oreščanin et al.
Research Article
Curr. Pers. MAPs 102
reported that SUI occurs at least weekly in
one third of adult women.
A world wide survey conducted by McPhil
(2004), revealed the highest percentage of
women with SUI in UK (41%) and Canada
(42%) and the lowest percentage were
obtained in Spain (23%) while the mean
value for all considered countries was 32%.
Two-thirds of the symptomatic women were
younger than 50 years.
The treatment approaches depending on the
type of incontinence and its severity. The
most common treatment approaches are
various behavioral techniques, pelvic floor
muscle training (PFMT), electrical
stimulation, medical devices, medication,
surgical procedures, laser treatment
(Nygaard and Heit, 2004; Aoki et al., 2018).
Better results were obtained by surgical and
laser treatment. However, those methods
were associated with more risk compared to
the conventional treatment.
The purpose of this study was to assess the
efficacy and safety of Bioapigyn® vaginal
ointment for pelvic muscle tonus for the local
treatment of incontinence and vulvo-vaginal
disorders in adult female population in
comparison of pelvic floor muscle training
due to similar mode of action of those two
approaches.
2. Materials and Method
2.1. Study design
The study was designed as prospective,
randomized, controlled clinical trial. The
study protocol was approved by the Ethics
Committee of Findri Gustek Health Care
Center with EudraCT number 2019-001053-
23.
The investigator recruited the patients based
on their medical history, following the
predefined inclusion and exclusion criteria.
In total, 132 patients were included of 160
patients screened. After the informed
consent has been signed at Visit 1, Day 1 all
the patients completed International
Consultation on Incontinence Questionnaire -
Urinary Incontinence Short Form (ICIQ-UI
SF), and subjected to the measurement of
post voiding residual urine volume,
perineometry (maximal and average
pressure (mm Hg) and the mean duration of
the contractions), vaginal pH and self-
assessment of vulvo-vaginal complaints. The
questionnaire data and the clinical study
results were recorded in source data. The
patients were subjected to semi-quantitative
urine analysis and full gynaecological
examination in order to exclude other disease
and conditions.
Patients were included in the study only if
they meet all of the following criteria: stress,
urge or mixed urinary incontinence and
vulvo-vaginal disorders; history of vaginal
delivery; non-existence of other
gynecological problems; negative urine test;
no injuries and bleeding in the vaginal canal,
introitus and vestibule; in the investigator's
judgment, the patients should receive local
treatment only; signed informed consent. The
patients who met all the criteria were
divided into experimental and control group
by nurse based on the randomization code.
The patients of the experimental group were
given two tubes of Bioapigyn® vaginal
ointment for pelvic muscle tonus with an
applicator and instructions for use. Control
group was subjected to pelvic floor muscle
training and received training instructions.
66 patients were treated with Bioapigyn®
vaginal ointment for pelvic muscle tonus for
28 days. 2.5 mL of ointment was self-
administered by the patients once daily,
between 21:00 and 24:00 hours using
appropriate applicator. The second group
also consisted of 66 patients was scheduled
to the pelvic floor muscle training for 28 days
according to the instruction given by the
nurse. In short the patient mast contracts the
pelvic floor muscles, holding the contractions
for 10 seconds and then relaxes for 10
Oreščanin et al.
Research Article
Curr. Pers. MAPs 103
seconds. It must be repeated ten times five
times daily. The purpose of PFMT was to
improve the pelvic floor muscle function.
Follow-up period for both groups was from
Day 29 to Day 60.
2.2. Description of investigational product
Bioapigyn® vaginal ointment for pelvic
muscle tonus is homogeneous, greasy,
viscous mass of characteristic herbal odor
and olive green color with pH of 4.93, density
of 0.9801 g/cm3 and viscosity of 20732 cP. It
consists of the following ingredients: honey;
beeswax (Cera flava); glycerol; oil extracts of
the plant species: areal parts of shepherd 's
purse (Capsella bursa-pastoris L.), nettle
leaves (Urtica diodica L.), oak bark (Quercus
robur L.), sage leaves (Salvia officinalis L.),
areal parts of yarrow (Achillea millefolium L.),
lady's mantle leaves and steam (Alchemilla
vulgaris L.), marigold flowers (Calendula
officinalis L.), cammomile flowers (Matricaria
chamomilla L.), plantain leaves (Plantago
major L.), olive leaves (Olea europaea L.);
essential oils: Australien tea tree (Melaleuca
alternifolia), thyme (Timus vulgaris ct.
thymol), oregano (Origanum vulgare).
Detailed description of the ointment
production was published previously
(Oreščanin et al., 2018).
2.3. Statistical analysis
Statistical analysis was performed using
STATISTICA 12.0 software package. The
required sample size was calculated by
Power analysis method. Considering the
medium effect size (0.35), the power goal of
80% and the Type I error significance level of
0.05, the required sample size is 66
participants per group, amounting to the
total of 132 participants. Frequencies and
percentages were calculated for each
categorical variable using frequency tables.
Potential differences between the groups of
categorical variable were determined using
2 Test. Basic statistical parameters were
determined for each continuous variable. The
Shapiro-Wilk W-Test was used to determine
the normality of distribution of continuous
variables, while Levene's Test was used for
homogeneity of variances. The t test was used
to determine the difference between mean
values of two groups with normally
distributed continuous variables, while the
analysis of variance and Newman-Keuls test
were used for the assessment of difference
among three and more groups. Before
carrying out the above-mentioned statistical
analyses of data, logarithmic transformation
was used to deal with the variables which
deviate from the normal distribution. To
determine the dependence of the dependent
variable on the chosen predictor variables,
multiple regression analysis was applied. The
p-value of less than 0.05 (p<0.05) will be
considered statistically significant in all
measurements.
3. Results
3.1. Description of the population
The control population ranged from 50 to 73
(56.8±6.2) years and experimental group
from 34 to 80 years (58.7±9.3). T-test
showed no significant difference (t=1.4;
p=0.153) between these two groups. There
was no significant difference (t=0.2; p=0.665)
in the number of childbirth between control
(2.1±0.9) and experimental group (2.0±1.1).
Both groups showed similar mean values and
standard deviations for body mass index
(26.3±4.8 for experimental and 25.7±4.1 for
the control group). There was no significant
difference between those two values (t=0.6;
p=0.434).
Among 66 participants of the experimental
group 20 of them are reproductive age
woman while 46 of them are either
menopausal or postmenopausal woman.
Similar distribution was also found in the
control group consisted of 28 reproductive
age participants and 38 of those of
menopausal & postmenopausal status.
According to the results of 2 test there was
no significant difference between the
Oreščanin et al.
Research Article
Curr. Pers. MAPs 104
percentages of either reproductive age or
menopausal & postmenopausal woman
between the experimental and control group.
3.2. Treatment efficiency of vulvo-vaginal
disorders
Table 1 presents the basic statistical
parameters and the results of t-test for the
symptoms of vulvo-vaginal disorders like
unpleasant odor, itching, burning, vaginal
discharge, vaginal dryness and dyspareunia
graded from 0 to 3 and total score of those
complaints in the control group subjected to
pelvic floor muscle training and experimental
group treated with Bioapigyn® ointment for
pelvic muscle tonus before and after the
training or treatment.
Table 1. Treatment efficiency of vulvo-vaginal disorders
Group
Stat.
parameter
Odor
Itching
Burning
Initial
Final
Initial
Final
Initial
Final
Control
X
0.4
0.4
1.3
1.3
1.5
1.5
SD
0.7
0.7
0.7
0.7
0.5
0.5
M
0.0
0.0
1.0
1.0
1.5
1.5
Min.
0
0
0
0
1
1
Max.
2
2
3
3
3
3
t-test
t=0; p=1.000
t=0; p=1.000
t=0; p=1.000
Experimental
X
0.5
0.0
1.3
0.0
0.0
1.2
SD
0.6
0.0
0.5
0.0
0.0
0.5
M
0.0
0.0
1.0
0.0
0.0
1.0
Min.
0
0
0
0
0
0
Max.
2
0
3
0
0
2
t-test
t=5.7;
p<0.0000*
t=20.3;
p<0.0000*
t=7.6;
p<0.0000*
Table 1. Continued.
Group
Stat.
parameter
Vaginal
discharge
Vaginal dryness
Dyspareunia
Total score
Initial
Final
Initial
Final
Initial
Final
Initial
Final
Control
X
1.4
1.4
1.0
1.0
1.2
1.2
6.7
6.7
SD
1.1
1.1
0.9
0.9
1.0
1.0
1.9
1.9
M
2.0
2.0
1.0
1.0
1.0
1.0
6.0
6.0
Min.
0
0
0
0
0
0
3
3
Max.
3
3
3
3
3
3
12
12
t-test
t=0; p=1.000
t=0; p=1.000
t=0; p=1.000
t=0; p=1.000
Experimental
X
0.5
0.0
2.0
0.0
0.0
2.0
7.6
0.0
SD
0.5
0.0
0.6
0.0
0.0
0.5
1.6
0.0
M
0.0
0.0
2.0
0.0
0.0
2.0
7.0
0.0
Min.
0
0
0
0
0
0
5
0
Max.
2
0
3
0
0
3
11
0
t-test
t=28.4;
p<0.0000*
t=31.4;
p<0.0000*
t=31.4;
p<0.0000*
t=38.6;
p<0.0000*
Oreščanin et al.
Research Article
Curr. Pers. MAPs 105
The total score of vulvo-vaginal complaints in
the control group ranged from 3 to 12
(6.7±1.9). The number of the symptoms at
baseline ranged from 3 to 5. The highest
mean values were obtained for burning,
vaginal discharge and itching. Expectedly,
following the four weeks of the training there
was no reduction in the number or severity of
the symptoms since there was no
concomitant treatment of vulvo-vaginal
disorders during the course of PFMT.
In the experimental group the total score of
vulvo-vaginal complaints ranged from 5 to 11
(7.6±1.6) at baseline. Quite opposite to the
control group, all the patients treated four
weeks with the Bioapigyn® ointment for
pelvic muscle tonus showed no symptoms of
vulvo-vaginal disorders following the
treatment. During the application of the
ointment and monitoring period none of the
patient experienced side-effects or new
symptoms of vulvo-vaginal disorders.
Table 1. Basic statistical parameters and the
results of t-test for the symptoms of vulvo-
vaginal disorders graded from 0 to 3 and total
score of the patients with incontinence and
vulvo-vaginal disorders in control (C) group
subjected to pelvic floor muscle training and
experimental (E) group treated with
Bioapigyn ointment for pelvic muscle tonus
before and after the treatment or training.
X̄ -mean; SD-standard deviation; M-median; *-
significantly different at p<0.05.
Vaginal pH value (Table 2) in the control
group at baseline ranged from 5 to 7
(5.8±0.6) and showed the same value
following the pelvic floor muscle training.
The experimental group showed similar
values at baseline ranging from 4.8 to 7.5
(6.0±0.7). Four weeks of the application of
Bioapigyn® ointment for pelvic muscle tonus
resulted in statistically significant (t=7.4;
p<0.0000) decrease of vaginal pH ranging
from 4.3 to 6.5 (5.2±0.6).
Table 2. Basic statistical parameters for
vaginal pH of the patients
Stat.
parameter
Control
Experimental
Initial
Final
Initial
Final
X
5.8
5.8
6.0
5.2
SD
0.6
0.6
0.7
0.6
M
5.8
5.8
6.0
5.0
Min.
5.0
5.0
4.8
4.3
Max.
7.0
7.0
7.5
6.5
t-test
t=0.0; p=1.0
t=7.4; p<0.0000*
Table 2. Basic statistical parameters for
vaginal pH of the patients with incontinence
and vulvo-vaginal disorders in control group
subjected to pelvic floor muscle training and
experimental group treated with Bioapigyn
ointment for pelvic muscle tonus before and
after the treatment or training. X̄ - mean; SD-
standard deviation; M-median; *-
significantly different at p<0.05.
3.3. The results of urinary incontinence
treatment
Based on the results of the total values of
International Consultation on Incontinence
Questionnaire - Urinary Incontinence Short
Form (ICIQ-UI SF) and additional
information obtained from the patients
when included in the study it was
determined that among 66 participants of
the experimental group 39 of them suffered
from stress UI, 17 from mixed UI and 10
from urge UI (Table 3).
Stress urinary incontinence also prevailed
in the control group with 45 of 66
participants. 11 of them had urge and 10
mixed urinary incontinence. Obtained
results were in agreement with previous
research confirming the highest incidence of
SUI, followed by mixed and UUI (Buchsbaum
et al., 2002; Minassian et al., 2008; Zhu et al.,
2009).
Oreščanin et al.
Research Article
Curr. Pers. MAPs 106
Table 3. Frequencies and percentages of the
subject of experimental and control group with
stress (SUI), urge (UUI) and mixed urinary
incontinence.
Type
of incontinence
Experimental
Control
N
%
N
%
SUI
39
59.1
45
68.2
UUI
10
15.2
11
16.7
Mixed
17
25.8
10
15.2
The severity of the symptoms in both
groups were determined at baseline and
after four weeks of the treatment or training
on the bases of the total value of ICIQ-UI SF
score and the results were presented in
Table 4. At baseline among 66
participants of the experimental group, 9 of
them experienced only mild symptoms, 29
moderate, 26 severe and 2 very severe
symptoms. Among the participants of the
control group 11 of them had slight, 27
moderate and 28 of them severe symptoms
of UI.
Following the treatment with Bioapigyn
ointment for pelvic muscle tonus, none of
the patients reported very severe symptoms
of incontinence while 18 of them (27.3%)
were completely dry. Complete
disappearance of the symptoms was
obtained in the patients with prevalently
stress urinary incontinence with initial
ICIQ-UI SF score ranging from 3 to 10.
The percentage of the patients with severe
symptoms decreased from 39.4% to only
6.1%. Those results were in line with the
previous research results following two
weeks of the application of Bioapigyn
ointment for pelvic muscle tonus (Orescanin
et al., 2018). After the treatment, 4.56% of
the patients were completely dry while very
severe symptoms decreased from 10.61%
to 0 and severe symptoms from 42.42% to
25.75%. Better results obtained in the
current study were the function of two times
longer treatment period.
Table 4. Frequencies and percentages of the subject of experimental (E) and control (C) group
before and after the treatment or training based on the severity of the symptoms of urinary
incontinence.
Severity
Initial
Final
E
C
E
C
N
%
N
%
N
%
N
%
Non (0)
0
0
0
0
18
27.3
2
3.0
Slight (1-5)
9
13.6
11
16.7
22
33.3
13
19.7
Moderate (6-12)
29
43.9
27
40.9
22
33.3
26
39.4
Severe (13-18)
26
39.4
28
42.4
4
6.1
25
37.9
Very severe (19-21)
2
3.0
0
0
0
0
0
0
Some improvement was also obtained in the
control group subjected to PFMT. Two
patients were completely dry, 13 of them
experienced slight, 26 moderate and 25
severe symptoms. Similar to the
experimental group complete
disappearance of the symptoms was
obtained in the patients with stress urinary
incontinence with initial ICIQ-UI SF score of
3. When comparing the treatment with
Bioapigyn ointment for pelvic muscle
tonus with PFMT applied for the same time-
period the ointment treatment was found
superior compared to PFMT. The total ICIQ-
UI-SF score in the control group (Table 5) at
baseline ranged from 3 to 18 (10.8±4.3).
Slight decrease was obtained following the
training to 9.7±4.6. However, this decrease
was not statistically significant (t=1.4;
p=0.1770). In the previous study (Oreščanin
Oreščanin et al.
Research Article
Curr. Pers. MAPs 107
et al., 2018), following the six months of
PFMT the mean value of ICIQ-UI SF score
slightly decreased from 8.34±4.21 to
7.92±4.71, which was not statistically
significant.
In the experimental group the
initial values of ICIQ-UI-SF score ranged
from 3 to 21 (11±4.5). Those values
decreased significantly following the
treatment (t=7.87; p<0.0000) with the
range from 0 to 17 while mean values
and standard deviation decreased to
4.9±4.5.
Table 5. Basic statistical parameters for
total ICIQ-UI-SF score of the patients with
incontinence and vulvo-vaginal disorders in
control group subjected to pelvic floor
muscle training and experimental group
treated with Bioapigyn ointment for pelvic
muscle tonus before and after the treatment
or training. X- mean; SD-standard
deviation; M-median; *- significantly
different at p<0.05
Stat.
parameter
Control
Experimental
Initial
Final
Initial
Final
X
10.8
9.7
11.0
4.9
SD
4.3
4.6
4.5
4.3
M
10.5
9.5
12.0
5.0
Min.
3.0
0.0
3.0
0.0
Max.
18.0
18.0
21.0
17.0
t-test
t=1.4; p=0.1770
t=7.87; p<0.0000*
The results of perineometry and post voiding
residual urine volume before and following
the training or treatment with the ointment
were presented in Table 6.
In the control group the initial values of the
maximum pressure ranged from 0 to 32
(18.5±10.9), the average pressure from 0 to
30 (15.1±9.7) and duration of pressure from
0 to 32 (15.5±10.9). Following the PFMT all
three parameters increased slightly and
reached the mean values and standard
deviations of 19.3±11.4, 16.0±10.3 and
16.8±11.5 for maximum, average and
duration of pressure, respectively. Based on
the results of t-test none of these values
showed statistically significant increase
compared to the initial values. In the
experimental group the initial values of the
maximum pressure ranged from 0 to 28
(11.0±9.0), the average pressure from 0 to 24
(8.1±7.5) and duration of pressure from 0 to
32 (9.4±9.9). Following the treatment with
Bioapigyn® ointment all three parameters
increased and reached the mean values and
standard deviations of 14.6±9.8, 10.7±8.4
and 12.7±10.4 for maximum, average and
duration of pressure, respectively.
Based on the results of t-test all three
parameters showed statistically significant
increase compared to the initial values. Those
results confirmed that Bioapigyn® ointment
for pelvic muscle tonus increased
significantly the pelvic muscle strength
following four weeks of the application.
Previous study (Oreščanin et al., 2018) also
showed increase in the pelvic muscle
strength parameters. However, due to two
times shorter treatment period this increase
was not statistically significant. The initial
values of post voiding residual urine (Table
6) in the control group ranged from 0 to 30
mL (11.2±8.9 mL) and showed slight but not
significant (p=0.5042) decrease to 10.1±8.4
mL (range 0 to 27.7 mL).
On the contrary, the experimental group
showed statistically significant decrease
(t=4.1; p<0.0000) of the volume of residual
urine from 6.9±10.1 mL (range 0 to 61.3 mL)
to 1.6±2.3 mL (range from 0 to 10.5 mL)
which could be explained by increase of
pelvic floor muscle performance increasing
intravesical pressure high enough to enable
empting the bladder almost completely. Only
two weeks of the treatment with Bioapigyn®
ointment (Orescanin et al., 2018) reduced
significantly (p=0.0002) post voiding
residual urine volume from 8.73±11.18 to
2.78±5.93 mL.
Oreščanin et al.
Research Article
Curr. Pers. MAPs 108
Table 6. Basic statistical parameters and the results of t-test for the perineometry and residual
urine volume of the patients with incontinence and vulvo-vaginal disorders in control (C) group
subjected to pelvic floor muscle training and experimental (E) group treated with Bioapigyn®
ointment for pelvic muscle tonus before and after the treatment or training. X- mean; SD-
standard deviation; M-median; *-significantly different at p<0.05
Group
Stat.
parameter
Max. pressure
(mm Hg)
Average pressure
(mm Hg)
Duration of
pressure (s)
Residual
urine (mL)
Initial
Final
Initial
Final
Initial
Final
Initial
Final
Control
X
18.5
19.3
15.1
16.0
15.5
16.8
11.2
10.1
SD
10.9
11.4
9.7
10.3
10.9
11.5
8.9
8.4
M
21.0
22.0
15.5
16.5
14.5
15.5
9.7
9.3
Min.
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
Max.
32.0
33.0
30.0
30.0
32.0
34.0
30.3
27.7
t-test
t=0.4; p=0.6851
t=0.5; p=0.5489
t=0.7;p=0.5113
t=0.7;p=0.5042
Experimental
X
11.0
14.6
8.1
10.7
9.4
12.7
6.9
1.6
SD
9.0
9.8
7.5
8.4
9.2
10.4
10.1
2.3
M
11.0
14.5
7.0
9.0
7.0
8.5
3.0
0.7
Min.
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
Max.
28.0
32.0
24.0
28.0
32.0
37.0
61.3
10.5
t-test
t=2.21;p=0.0286*
t=2.04; p=0.0475*
t=2.09;t=0.0407*
t=4.1; p<0.0000*
Table 7. The results of multiple regression analysis testing for the influence of selected
predictor variables on the initial values of ICIQ-UI-SF score, perineometry (maximum and
average pressure and duration of pressure) and post voiding residual urine. *-significantly
different at p<0.05
Predictor
variable
ICIQ-UI-SF
Maximum
pressure
Average
pressure
Duration of
pressure
Residual
urine
volume
β
p
β
p
β
p
β
p
β
p
Age
0.45
0.0041*
0.49
0.0000*
0.46
0.0000*
0.38
0.0000*
0.19
0.0929
Menopause
0.56
0.0000*
0.27
0.0054*
0.28
0.0036*
0.44
0.0000*
0.32
0.0064*
No of birth
0.10
0.1879
0.00
0.9696
0.01
0.9327
0.02
0.6795
0.04
0.5954
BMI
0.13
0.0742
0.01
0.8944
0.03
0.6686
0.04
0.5337
0.02
0.7644
R=0.63;
p<0.0000*
R=0.70;
p<0.0000*
R=0.70;
p<0.0000*
R=0.76;
p<0.0000*
R=0.48;
p<0.0000*
Oreščanin et al.
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Curr. Pers. MAPs 109
The influence of predictor variables (age,
menopausal status, BMI and number of child-
birth) on the initial values of the incontinence
parameters of the total tested population
was assessed by Multiple regression analysis
(Table 7).
Multiple regression analysis confirmed, good
to very good (R ranged from 0.48 to 0.76),
statistically significant (p<0.05) influence of
the predictor variables (Table 7) on the initial
values of ICIQ-UI-SF score, perineometry and
post voiding residual urine. Based on the
results of beta coefficients and their
significance level it seems that among four
predictor variables only menopausal status
and age exhibited statistically significant
contribution. In the case of residual urine
content the menopausal status was the only
significant predictor variable.
Those results were in line with the previous
research identifying age and menopause as
the significant predictor of incontinence
(Luber, 2004; Danforth et al., 2006;
Minassian et al., 2008; Zhu et al., 2009). Those
authors also identified obesity as significant
predictor, however, our results failed to show
any significant contribution. The reason for
that lies in the fact that the population from
the current study had an ideal or slightly
elevated BMI.
According to the results of multiple
regression it seems that menopausal status is
the variable with the highest influence on all
assessed incontinence parameters. ICIQ-UI-
SF score and post-voiding residual urine
volume were significantly higher in
menopausal & postmenopausal participants
compared to child-bearing age participants.
On the contrary, all three perineometry
parameters that determine pelvic floor
muscle strength were significantly lower in
menopausal & postmenopausal woman
compared to those of child- bearing age.
3.4. Quantification of the difference in the
treatment efficiency between the
experimental and control group
The results t-test showed significant
difference for perineometry parameters and
residual urine volume at baseline.
Consequently, the direct comparison of the
efficiency between the treatment and
training was not possible. Since direct
comparison of the mean values of selected
variables wouldn’t be appropriate approach
due to differences in the initial values in two
tested groups the percentage of the changes
(decrease or increase) of the mean value of
each variable following the treatment was
calculated for both groups and the
differences between the percentages were
tested by 2 test (Table 8).
There was no decrease of the total score of
vulvo-vaginal disorders and vaginal pH in the
control group. ICIQ-UI-SF score decreased
9.8%, perineometry parameters increased
between 4.3 and 8.3% while residual urine
volume decreased for 9.1%. Better results for
perineometry parameters were obtained
following six months PFMT (Oreščanin et al.,
2018) with increase ranging between 7.3 and
26.4%.
The experimental group showed better
results for all tested variables compared to
PFMT group. The application of the ointment
resulted in 100% decrease of vulvo-vaginal
disorders, 14.2% decrease in vaginal pH,
76.9% decrease in residual urine volume and
54.9% decrease in the mean value of ICIQ-UI-
SF score. In the same time, perineometry
parameters determining pelvic muscle
strength increased between 31.5 and 34.3%.
According to the results of 2 test the
differences between two groups were
statistically significant for all tested
parameters.
Current results for the experimental group
were significantly better compared to the
previous study (Oreščanin et al., 2018)
lasting only two weeks which resulted in
Oreščanin et al.
Research Article
Curr. Pers. MAPs 110
30.7% decrease of the mean value of ICIQ-UI
score, 68.2% decrease of residual urine
volume, 11.3% decrease of vaginal pH and
between 25.3 and 31.7% increase of
perineometry parameters. However, two
weeks of the treatment were long enough for
complete disappearance of vulvo-vaginal
complaints.
Table 8. The percentage of decrease of the Total score of vulvo-vaginal disorders, vaginal pH,
residual urine volume and ICIQ-UI-SF score and increase of perineometry parameters in the
control and experimental group compared to initial value and the results of 2 between control
and experimental group. *-significantly different at p<0.05
Variable
Control
Experimental
2
P
Total score-vulvo-vaginal disorders
0.0
100.0
128.0
<0.0001*
Vaginal pH
0.0
14.2
8.1
0.0045*
ICIQ-UI-SF score
9.8
54.9
28.6
<0.0001*
Maximum pressure (mm Hg)
4.3
33.1
16.2
0.0001*
Average pressure (mm Hg)
6.3
31.5
12.1
0.0005*
Duration of pressure (s)
8.3
34.3
11.8
0.0006*
Residual urine (mL)
9.1
76.9
59.2
<0.0001*
3.5. Clinical efficiency and treatment rating
by the patients
Following the treatment with Bioapigyn®
ointment for pelvic muscle tonus 25.8% of
the participant of the experimental and 3% of
the control subjects were completely dry
which was recorded as clinical cure. Clinical
improvement was found in 74.2%
participants of the experimental and 97% of
the control group.
Both approaches have received good ratings
by the patients. Treatment with Bioapigyn
ointment showed a significantly better rating
(4.9±0.3) compared to PFMT (4.4.±0.6)
which was expected due to better
performance of the ointment compared to
PFMT.
3.6. Clinical safety
At Visit II the respondents using medical
device are asked by the principal investigator
if they experienced any side effects or
adverse reaction after the first application of
the ointment as well as throughout the
course of the study. Furthermore, a complete
gynaecological examination was performed
to determine the possible occurrence of
adverse reactions (irritation of the vulvo-
vaginal area, allergic reaction), worsening of
the existing or the occurrence of new
symptoms. Patients were asked to describe in
their own words the feeling after the
application of the ointment.
Patients described a slight feeling of
tightening and contraction in the vaginal
area. After 20 to 30 minutes following the
application of the ointment, they were able to
empty the bladder completely. Patients with
vaginal dryness and accompanying
symptoms (itching, burning, and pain) after a
week of administration experienced a
comfortable feeling of vaginal moisture
whiles the symptoms of itching and burning
has disappeared. None of the patients
reported severe burning or itching in the
vulva-vaginal area, nor the appearance of an
allergic reaction or the exacerbation of the
existing symptoms or the appearance of new
symptoms. The gynaecologic examination did
not show any signs of irritation or worsening
Oreščanin et al.
Research Article
Curr. Pers. MAPs 111
of the vulvo-vaginal disorders. Just opposite,
the examination confirmed the recovery of
the vaginal mucosa in menopausal and
postmenopausal women. There was no
increase of vaginal pH in none of the subjects.
On the contrary in majority of women vaginal
pH was reduced significantly and only in few
of them remained the same. All the patients
confirmed that they could keep the urine
significantly longer, the number of urination
during the night decreased, patients could
empty the bladder better compared to the
baseline. The measurement of the
perineometry parameters confirmed slight to
significant enhancement of the pelvic floor
muscle strength in all participants. In all
patients who had residual urine at the first
visit, its volume was reduced at the second
visit. Based on the above facts obtained from
the patients or by direct examination and
measurement it is possible to conclude that
the medical device does not cause any
adverse effects and is safe for vaginal
administration in the dose of 2.5 mL per day
for up to 28 days.
4.Discussion and Conclusions
Conducted study confirmed the efficiency of
Bioapigyn® vaginal ointment for pelvic
muscle tonus in alleviating urinary
incontinence in women. The ointment
decreased the total value of ICIQ-UI-SF score
in all 66 subjects. This significant
improvement was the consequence of the
strengthening of the pelvic floor muscles
which was quantitatively confirmed by
increasing in the values of perineometry
parameters (maximum pressure, average
pressure, duration of the pressure) and
reducing the volume of post voiding residual
urine.
Consequently, this study has confirmed that
the main mode of action of the ointment is
physico-mechanical by causing the
contraction and relaxation of the smooth
muscles of the pelvic floor similar to PFMT or
electrical stimulation. However, compared to
the PFMT conducted during the same time
period the ointment showed significantly
better results considering all measured
parameters.
Although, there are no published data on
human studies considering the influence of a
single ingredient on the contraction of
smooth muscles, the in vitro results or those
obtained on the animal model have
confirmed that the plants Capsella bursa-
pastoris and Urtica diodice (Grosso, 2011; Al-
Snafi, 2015) induce smooth muscle
contraction/relaxation activity. Moreover,
smooth muscle contraction could be caused
by the astringent property of the plants such
as Quercus robur, Achillea millefolium, Salvia
officinalis, Olea europaea, Plantago major.
Smooth muscle contraction/relaxation
stimulated by the ointment ingredients
resulted in the tightening and firming of the
smooth muscles of the pelvic floor and
consequently, reduced the symptoms of
incontinence significantly especially in
perimenopausal and menopausal women
(Oreščanin and Findri Gustek, 2016,
Oreščanin et al., 2018).
Besides, product is also indicated for
alleviations of vulvo-vaginal disorders that
are often associated with incontinence in
perimenopausal and menopausal women.
Disappearance of all vulvo-vaginal disorders
could be explained physical parameters like
low pH, high osmolarity, high viscosity and
greasiness, emollient as well as low water
activity of Bioapigyn® ointment for pelvic
muscle tonus leading to eradication of the
symptoms of vulvo-vaginal disorders due to:
the creation of unfavourable conditions for
the growth, adhesion and multiplication of
the pathogens; the creation of the protective
coating on the vaginal mucosa, enabling its
recovery and preventing further irritation;
alleviation of the vaginal dryness due to the
presence of the humectants; preventing pain
during sexual intercourse due to its
lubricating and coating effect.
Oreščanin et al.
Research Article
Curr. Pers. MAPs 112
Conflict of Interest
The authors have declared that they have no
conflict of interest.
References
1. Al-Snafi, A.E., 2015. The chemical constituents and
pharmacological effects of Capsella bursa-
pastoris-A review. International Journal of
Pharmacology and toxicology, 5(2), 76-81.
2. Aoki, Y., Brown, H.W., Brubaker, L., Cornu, J.N.,
Daly, J.O., Cartwright, R., 2018. Urinary
incontinence in women, Nature Reviews Disease
Primers, 3, 17042. doi:10.1038/nrdp.2017.42.
3. Brown, J.S., Grady, D., Ouslander, J.G., Herzog, A.R.,
Varner, R.E., Posner, S.F., 1999. Prevalence of
Urinary Incontinence and Associated Risk Factors
in Postmenopausal Women. Obstetrics &
Gynecology, 94(1), 66–70.
4. Buchsbaum, G.M., Chin, M., Glantz, C., Guzick, D.,
2002. Prevalence of Urinary Incontinence and
Associated Risk Factors in a Cohort of Nuns.
Obstetrics & Gynecology, 100(2), 226–229.
5. Danforth, K.N., Townsend, M.K., Lifford, K., Curhan,
G.C., Resnick, N.M., Grodstein, F., 2006. Risk factors
for urinary incontinence among middle-aged
women. American Journal of Obstetrics and
Gynecology, 194, 339–345.
6. Grosso, C., Vinholes, J., Silva, L.R., Guedes de
PinhoI, P., Gonçalves, R.F., Valentão P., JägerII A.K.,
Andrade P.B., 2011. Chemical composition and
biological screening of Capsella bursa-pastoris.
Brazilian Journal of Pharmacognosy, 21(4), 635-
644.
7. Khandelwal, C., Kistler, C., 2013. Diagnosis of
Urinary Incontinence. American Family Physician,
87(8),543-550.
8. Luber, K. M., 2004. The Definition, Prevalence, and
Risk Factors for Stress Urinary Incontinence.
Reviews in urology, 6(3), 3-9.
9. McPhil, J. H., 2004. The prevalence of stress
urinary incontinence in women. Nursing time,
100(20), p.70.
10. Minassian, V.A., Drutz, H.P., Al-Badr, A., 2003.
Urinary incontinence as worldwide problem.
International Journal of Gynecology and
Obstetrics, 82, 327–338.
11. Minassian, V.A., Stewart, W.F., Wood, G.C., 2008.
Urinary Incontinence in Women: Variation in
Prevalence Estimates and Risk Factors. Obstetrics
& Gynecology, 111(2), 324-331.
12. Nygaard, IE., Heit, M., 2004. Stress Urinary
Incontinence. Obstetrics & Gynecology, 104(3),
607-620.
13. Oreščanin, V., Findri Guštek, Š. Fistonić, I., Rodić,
J., 2018. Efficacy of bioapigyn® ointment for
pelvic muscle tonus in the treatment of stress
urinary incontinence and vulvo-vagnal disorders.
IJRDO - Journal of Health Sciences And Nursing,
3(10), 13- 25.
14. Oreščanin, V., Findri Guštek, Š., 2016.
Development and Testing of New Herbal Ointment
for the Treatment of Stress Urinary Incontinence-
A Preliminary Study. Global Journal For Research
Analysis, 5(7), 371-374.
15. Peyrat, L., Haillot, O., Bruyere, F., Boutin, J.M.,
Bertrand, P., Lanson, Y., 2002. Prevalence and risk
factors of urinary incontinence in young and
middle-aged women. BJU International, 89(1), 61–
66.
16. Radzimińska, A., Strączyńska, A., Weber-Rajek, M.,
Styczyńska, H., Strojek, K., Piekorz. Z., 2018. The
impact of pelvic floor muscle training on the
quality of life of women with urinary
incontinence: a systematic literature review.
Clinical Interventions in Aging, 13, 957–965.
17. Rovner, S.E., Wein, J.A., 2004. Treatment Options
for Stress Urinary Incontinence. Reviews in
urology, 6 (Suppl 3), S29–S47.
18. Zhu, L., Lang, J., Liu, C., Han, S., Huang, J., Li, X.,
2009. The epidemiological study of women with
urinary incontinence and risk factors for stress
urinary incontinence in China. Menopause, 16(4),
831-836.
