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IF : 3.62 | IC Value 70.36
GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS X 371
Volume-5, Issue-7, July - 2016 • ISSN No 2277 - 8160
Original Research Paper Commerce Medical Science
Development And Testing of New Herbal Ointment for the
Treatment of Stress Urinary Incontinence-A Preliminary
Study
Oreščanin Višnja
OREŠČANIN Ltd., A. Jakšića 30, 10000 Zagreb, Croatia
Findri Guštek
Štefica
Findri-Guštek Centre for gynecology, urology and occupational
medicine, Ninska 5, Sesvete, Croatia
The purpose of this work was development, formulation and testing of new herbal ointment for the treatment of stress
urinary incontinence and its related symptoms. 50 women in the age range from 36 to 73 years were treated 8 weeks
with vaginal ointment (2 g/day) which consisted of the following ingredients: oil macerates of the plants Capsella
bursa-pastoris, Urtica diodica, Quercus robur, Quercus infectoria, Corylus avellana, Ocimum basilicum, Salvia officinalis, Achillea millefolium,
Calendula officinalis, Matricaria chamomilla, Hypericum perforatum, Alchemilla vulgaris, Thymus serpyllum, Plantago major, Symphytum
officinale; essential oils of the plants Melaleuca alternifolia, Cymbopogon martinii, Cinnamomum camphora ct. cineol, Eugenia caryophylata,
Thymus vulgaris ct. tymol, Origanum vulgare; honey; glycerin and Cera flava. The degree of incontinence and its impact on the quality of life
prior and after the therapy was assessed by the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form
(ICIQ-UI SF), where maximum score of 21 represents permanent incontinence and 0 no leakage of urine. Sexual gratification was assessed by the
Pelvic organ prolepses / urinary Incontinence / Sexual Questionnaire (PISQ-12). The variables with the highest, statistically significant influence
onto degree of incontinence and its impact on the quality of life were were Urine leak and related symptoms, Menopause, Frequent urinary
tract infections, Age and Number of childbirth. Significant improvement concerning both, incontinence (p<0.0001) and sexuality (p<0.0003)
was observed following two weeks of the application. In the end of the study the mean value of ICIQ-UI score decreased from 10.3±4.2 to 1.1±1.0
while PISQ-12 increased from 21.0±2.9 to 28.4±3.2. Following the eight weeks of the therapy 66% of the patients were completely dry, while other
34% exhibited only slight problems (ICIQ-UI score range 1-3). After only 7 days of the application the symptoms like burning, vaginal discharge,
vaginal dryness and painful sexual intercourse decreased significantly while in the end of the treatment disappeared completely.
ABSTRACT
KEYWORDS : herbal ointment, stress urinary incontinence, olive oil extracts, medicinal
plants, essential oils
INTRODUCTION
The International Continence Society Standardization of Terminolo-
gy of Lower Urinary Tract Dysfunction established clinical definition
of stress urinary incontinence (SUI) as the complaint of involuntary
leakage during effort or exertion, or on sneezing or coughing (Luber,
2004). Its prevalence ranged between 4% and 35% depending on the
country with age, obesity, and smoking as the most significant risk
factors (Luber, 2004). Nygaard and Heit, 2004 reported that SUI occurs
at least weekly in one third of adult women. Among 20,000 Chinese
women in the age range from 20 to 99 years the prevalence of SUI
was 18.9% (Zhu et al., 2009) and the significant risk factors are age,
vaginal delivery, multiparty, alcohol consumption, central obesity
constipation, chronic pelvic pain, history of respiratory disease, gyne-
cological events, pelvic surgery, and perimenopause and postmeno-
pause status. Among 1700 French women employed in academic
hospital, 12.4% of them reported SUI (Peyrat et al., 2002). The preg-
nancy, particularly previous vaginal delivery and hysterectomy rep-
resented the significant risk factors. The prevalence of SUI reported
by Minassian et al., 2008 among 2,875 adult women was 23.7%. 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. Iden-
tified risk factors were age, race/ethnicity, body mass index, parity,
smoking, type 2 diabetes mellitus, and hysterectomy (Danforth et
al., 2006). A world wide survey conducted by McPhil, 2004 reviled
the highest percentages of women with SUI in UK (41%) and Canada
(42%) and the lowest percentage was obtained in Spain (23%) while
the mean value for all tested countries was 32%. Two-thirds of the
symptomatic women were younger than 50. Higher prevalence of SUI
(Brown, et al., 1999) was obtained among postmenopausal women
(56%).
The most common treatment aproaches are pelvic floor muscle train-
ing pelvic floor muscle training, bladder training, vaginal devices, and
urethral inserts. Better results were obtained by surgical treatment.
However, those methods were associated with more risk compared to
the conventional treatment (Nygaard and Heit, 2004).
The purpose of this work was development, formulation and testing
of new herbal ointment for the treatment of stress urinary inconti-
nence and its related symptoms as posible alternative to conventional
or surgical methods.
MATERIALS AND METHODS
Study Design
Among 437 patients in the age range from 18 to 78 reported to the
center during October 2015th, 184 had the symptoms of urinary in-
continence (UI). All the patients signed informed consent and com-
pleted three questioners. Among 184 incontinent patients, stress
urinary incontinence (SUI) was confirmed in 98 of them. Those pa-
tients were subjected to Pap test, cervical swabs for the presence
of aerobic bacteria, yeasts, Ureaplasma urealyticum, Chlamydia
trachomatis, Mycoplasma, and hrHPV DNA. The sample prepa-
ration and analysis was described in details in our previous work
(Findri Gustek et al., 2012). The patients with confirmed cervical le-
sions or bacterial/yeasts/viral infections were withdrawn from the
study and subjected to conventional treatment depending on the
diagnosis. The pregnant patients were also excluded. After all ex-
clusions the rest of the 50 patients represented our target group.
The patients were treated with herbal ointment (2 g/day) for eight
weeks. The ointment was inserted deep into vagina before bed-
time. The patients were advised to make daily notes about all the
changes occurred during the course of the therapy. The interview of
each patient was done twice a month. The degree of incontinence
and its impact on the quality of life prior and after the therapy was
assessed by the International Consultation on Incontinence Ques-
tionnaire - Urinary Incontinence Short Form (ICIQ-UI SF), where
maximum score of 21 represents permanent incontinence and 0 no
leakage of urine. The results of the ICIQ-UI SF may be divided into
the following four severity categories: slight (1-5), moderate (6-12),
severe (13-18) and very severe (19-21). Sexual gratification was as-
sessed by the Pelvic organ prolapses / urinary Incontinence / Sexual
Questionnaire (PISQ-12).
Preparation of the Ointment
For the production of the macerate the following plants were
used: Capsella bursa-pastoris (10%), Urtica diodica (10%),
Quercus robur (10%), Quercus infectoria (10%), Corylus avel-
lana (10%), Ocimum basilicum (10%), Salvia officinalis (10%),
Achillea millefolium (10%), Calendula officinalis (5%), Planta-
GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS X 372
Volume-5, Issue-7, July - 2016 • ISSN No 2277 - 8160 IF : 3.62 | IC Value 70.36
go major (5%), Matricaria chamomilla (2%), Hypericum perfo-
ratum (2%), Alchemilla vulgaris (2%), Thymus serpyllum (2%),
Symphytum officinale (2%). The macerate was prepared from
the dried plants obtained from herbal pharmacy and extra virgin
olive oil with solid/liquid ratio = 1:5. The plants were macerat-
ed 30 days on 500C and filtered. 80% of the macerate was mixed
with 4.3% of chestnut honey and 5% of glycerin and the mixture
was heated to 800C. 10% of melted Cera flava was added into
the mixture, homogenized and heated for additional 10 minutes
and allowed to cool to the room temperature. The essential oils
of Melaleuca alternifolia (0.2%), Cympobogon martini (0.1%),
Thymus vulgaris (0.1%), Eugenia caryophylata (0.1%), Cin-
namomum camphora (0.1%) and Origanum vulgare L (0.1%)
were added into cooled mixture, mixed thoroughly and packed.
Statistical Analysis
For statistical evaluation Statistica 11.0 software package was
employed. The description of the treated population was done
by basic statistics and frequency tables. Statistical significance
was set to p<0.05 in all the tests performed. The differences in
the percentage of each parameter between prior and after the
therapy were assessed by χ2 test. The influence of the predictor
variables on the degree of incontinence was tested by Multiple
regression method (Orescanin et al., 2015a).
RESULTS AND DISCUSSION
Description of the Population
The study group ranged from 36 to 73 years (54.68±10.89) with
the highest percentage of women (28%) ranging from 51 to 60
years. Equal distribution was obtained in the groups ranging
from 41 to 50 years and 61 to 70 years (20%) while the women
younger than 40 and older than 70 were represented with 18%
and 10%, respectively.
According to the education level, 60% of the patients finished sec-
ondary school, 16% primary school while 10%, 12% and 2% of them
had higher education, university diploma and PhD, respectively.
Postmenopausal women represented 64% of the population (Table
1). Among the tested population 88% of them had at least one child-
birth. The women with two childbirths prevailed (42%) followed by
three births (26%). 9 of 50 patients had one or two miscarriages and
11 (18%) of them had 1 to 3 induced abortions (22%).
Frequent gynecological problems were reported by 62% of the par-
ticipants (Table 1). Among them the problems like inflammation,
burning, vaginal discharge, unpleasant odor, vaginal dryness, painful
sexual intercourse, and frequent infections prevailed.
Frequent urinary tract infections persisted in 44% of the patients (Ta-
ble 1). Urine leakage, frequent urination, urine retention, dysuria, pain
and burning prevailed among incontinence symptoms.
ICIQ-UI SF score ranged from 3 to 16 (10.25±4.19). Among them
20% had slight problems, 40% of them reported moderate and
other 40% severe incontinence problems. According to the re-
sults of multiple regression analysis ICIQ-UI SF score showed
statistically significant correlation with selected predictor varia-
bles (R = 0.79; p<0.0027). Among the variables with the highest,
statistically significant correlations were Urine leak and related
symptoms (p=0.0015), Menopause (p=0.0123), Frequent uri-
nary tract infections (0.0382), Age (0.0418) and No. of childbirth
(0.0481).
Incontinence problems combined with the vaginal dryness and
painful intercourse had also significant impact on the sexual
gratification. PISQ-12 score before the therapy (Fig. 2) ranged
from 14 to 26 (21±2.91). The results of Multiple regression
analysis reviled significant correlation between predictor
variables and PISQ-12 score (R = 0.88; p<0.0381). ICIQ-UI SF
score (p=0.0021), Urine leak and related symptoms (p=0.0104),
Menopause (p=0.0372), Gynecological problems (p=0.0414) and
age (p=0.0448) had statistically significant contribution. Those
results confirmed that urinary incontinence had highly signifi-
cant impact on the quality of sex life.
Table 1. Frequencies tables for selected categorical vari-
able of the tested population
Variable Category N %
Menopause Yes 32 64
No 28 36
No. of childbirth
0 6 12
1 6 12
2 21 42
3 13 26
5 2 4
8 2 4
No. of miscarriages
0 41 82
1 3 6
2 6 12
No. of induced abortions
0 39 78
1 6 12
2 3 6
3 2 4
Gynecological problems No 31 62
Yes 19 38
Frequent urinary tract
infections
Yes 22 44
No 28 56
Urine leakage and other
symptoms
No 0 0
Yes 50 100
The Outcome of the Therapy
The first signs of the improvement in the case of incontinence ap-
peared after 7 days of the treatment with the herbal ointment. The
improvement was reflected in the lower number of urination during
the day and night, the possibility of complete emptying of the blad-
der half an hour after the application of the ointment, ability to retain
the urine much longer, lower volume and frequency of the escaped
urine during coughing, sneezing and physical activity and pleasant
feeling of vaginal lubrication.
As presented in Fig. 1 ICIQ-UI SF score decreased almost linearly dur-
ing the course of therapy with the value of 7.2±1.8 after two weeks,
4.3±1.5 after four weeks, 2.7±1.4 following the 6 weeks and finally
1.1±1.0 in the end of eight week. Significant difference was found
between the mean value of ICIQ-UI SF score before the therapy and
each follow up period since P value were in all cases <0.0001. In the
end of the therapy 66% of the patients were completely dry while in
other 34% of them only slight discomfort persisted with ICIQ-UI SF
score ranged from 1-3.
Figure 1. The results of International Consultation on In-
continence Questionnaire - Urinary Incontinence Short
Form (ICIQ-UI SF) prior and after each follow up peri-
od.*-statistically significant at p<0.05
Multiple regression analysis showed no obvious, statistically significant con-
tribution of the predictor variable to the outcome of the therapy expressed
as ICIQ-UI SF score (R=0.60; p=0.1571). None of the tested predictor varia-
ble showed statistically significant contribution.
PISQ-12 score was significantly higher for each follow up period (Fig. 2)
compared to the period before the therapy (p <0.0001) which pointed out
to the improvement in sexual gratification.
IF : 3.62 | IC Value 70.36
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Volume-5, Issue-7, July - 2016 • ISSN No 2277 - 8160
Figure 2. The results of Pelvic organ prolepses / urinary
Incontinence / Sexual Questionnaire (PISQ-12) prior and
after each follow up period.*-statistically significant at
p<0.05
The mean values increased from 23.2±3.0 after two weeks of the
therapy to 28.4±3.2 in the end of the treatment period. Linear regres-
sion showed excellent correlation between the ICIQ-UI SF and PISQ-
12 scores (R2=0.998; p<0.00001) during the course of the therapy
confirming once again a significant influence of incontinence on the
sexual gratification. The symptoms and problems like vaginal dryness,
inflammation, burning, vaginal discharge, painful intercourse, and
unpleasant odor disappeared completely in the end of the therapy.
Gynecological examination also confirmed significant improvement in
the appearance of vaginal mucosa in postmenopausal women follow-
ing the therapy.
Significant improvement following the therapy could be explained by
the composition of the ointment containing the plants like Capsel-
la bursa-pastoris and Urtica diodica that induced contraction of
smooth muscles (Al-Snafi, 2015; Grosso et al., 2011; Broncano et al.,
1987), and consequently, enhanced both bladder and uterine muscle
tonus significantly.
The bioactive components extracted from the plants with confirmed
uterotonic activity (Matricaria chamomilla, Calendula officinalis,
Plantago major, Symphytum officinale, Capsella bursa pastoris,
and Hypericum perforatum) also contributed to the improvement of
uterine muscle tonus (Shipochliev, 1981).
Besides, the tannins rich plants with well known astringent activity
like Quercus robur, Quercus infectoria, Corylus avellana, Ocimum
basilicum had also positive effect on vaginal mucosa trough their
strong wound healing, anti-inflammatory and antioxidative poten-
tial (EMA, 2009; Ahmad et al., 2011; Oliveira et al., 2007; Dubey and
Pathak, 2015).
Beneficial effects of the oil extracts of the plants Salvia officinalis,
Achillea millefolium Calendula officinalis, Plantago major, Mat-
ricaria chamomilla, Hypericum perforatum, Alchemilla vulgaris,
Thymus serpyllum and Symphytum officinale onto vaginal muco-
sa was described in details in our previous papers (Orescanin et al.,
2015a, Orescanin et al., 2015a, Orescanin and Findri Gustek, 2015c).
In short, the selected plants act in the formulation as free radical
scavenging, metal chelating, and reactive oxygen quenching agents,
thus protecting vaginal mucosa from the damage caused by highly
reactive species present in intracellular space. The main wound heal-
ing and anti-inflammatory mechanism could be explained by inter-
action of bioactive components of the extracts with host membrane
signaling pathways that promote the synthesis of collagen fibers and
anti-inflammatory proteins trough numerous cascade reactions. Con-
sequently, it results with wound closure and re-epithelization of the
damaged area and decrease of inflammatory changes of the vaginal
mucosa. Another anti-inflammatory mechanism could be explained
by the inhibition of host membrane signaling pathways, and conse-
quently the inhibition of the synthesis of pro-inflammatory mediators.
Furthermore, the above mentioned plants macerate in the combina-
tion with essential oils of Melaleuca alternifolia, Thymus vulgaris,
Cymbopogon martinii, Origanum vulgare, Cinnamomum campho-
ra and Eugenia caryophyllata showed a strong antibacterial, antifun-
gal and antiviral activity against wide range of genital pathogens. So,
they maintain the healthy balance of very complex vaginal flora by
preventing uncontrolled growth of the pathogens that can cause in-
fection and also serve as natural preservatives in the ointment (Ores-
canin and Findri Gustek, 2015c).
Honey with its antimicrobial, prebiotic and probiotic activity provides
healthy balance of the vaginal flora by preventing the transition of
the vaginal flora from comensal to pathogenic form. It encourages
the development of normal vaginal flora and establishes normal acid-
ic pH of the vagina (Orescanin and Findri Gustek, 2015c).
Cera flava was used in the ointment formulation as supporting ma-
terial and also as the component which forms protective layer on the
genital tract membranes and prevent irritations while glycerol was
used in the ointment formulation as moisturizer (Orescanin and Findri
Gustek, 2015c).
CONCLUSIONS
The prevalence of stress urinary incontinence among the women re-
ported to the center was 22.4%. The most frequent symptoms/con-
ditions prior to the therapy were: frequent urination (up to 30 times
per day), inability to sustain urine, urine retention, frequent bladder
infections, vaginal dryness, painful intercourse, loss of sexual desire.
The variables with the highest, statistically significant influence onto
degree of incontinence and its impact on the quality of life were were
Urine leak and related symptoms, Menopause, Frequent urinary tract
infections, Age and No. of childbirth. Significant improvement con-
cerning both, incontinence (P < 0.0001) and sexuality (P < 0.0003)
was observed following two weeks of the application. In the end of
the study the mean value of ICIQ-UI score decreased over 9 times
while PISQ-12 increased for app. 1.4 times. In the end of the therapy
66% of females had no leakage of urine, while other 34% exhibited
only slight symptoms (mean ICIQ-UI score = 1.1; range 1-3). After
only 7 days of the application the symptoms like burning, vaginal dis-
charge, vaginal dryness and painful sexual intercourse decreased sig-
nificantly while in the end of the treatment disappeared completely.
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