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Journal of Ethnopharmacology Aloe Vera; A new treatment for atrophic vaginitis, A Randomized Double-blinded Controlled Trial Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation

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Journal of Ethnopharmacology
Aloe Vera; A new treatment for atrophic vaginitis, A Randomized Double-blinded
Controlled Trial
--Manuscript Draft--
Manuscript Number: JETHNO-D-20-00812
Article Type: Research Paper
Keywords: Vaginal atrophy; Aloe Vera; Estrogen; Vaginal health index (VHI); maturity value
(MV); Menopause patients; Vaginal maturity index; Non hormonal treatment.
Corresponding Author: Alireza Salehi
Shiraz University of Medical Sciences
shiraz, Fars Iran, Islamic Republic of
First Author: Tahereh Poordast
Order of Authors: Tahereh Poordast
Lida Ghaedian
Leila Ghaedian
Fatemeh Sadat Najib
Seyed Jalal Hosseinimehr
Shohreh Alipour
Massood Hosseinzadeh
Hossein Molavi Vardanjani
Alireza Salehi
Abstract: Ethno pharmacological relevance
Vaginal atrophy is of the most common problems during menopause with significant
psychosocial and medical consequences. Estrogen as an approved therapy for vaginal
atrophy can be associated with adverse effects and several contraindications in
menopause patients. The aim is to compare the effect of Aloe Vera (AV) vaginal
cream with commercially available estrogen vaginal cream for management of vaginal
atrophy in menopause females.
Materials and Methods
This is a double-blinded randomized controlled trial on 66 menopause female with
complaints of vaginal atrophy symptoms. Subjects were randomly allocated in two
groups of 33 patients, named as estrogen and AV groups. Vaginal health index (VHI),
maturity value (MV), vaginal cytologic smear, transvaginal sonography (TVS) and
severity of symptoms related to vaginal atrophy were assessed before and after 6-
weeks of vaginal cream administration.
Results
Comparison of MV before and after treatment revealed that superficial cells were
significantly increased after administration of both vaginal cream (6.67 VS 54.33 in AV
group; 4.33 VS 59.67 in estrogen group). In addition, VHI (13.83 vs 20.13 in AV group;
13.97 vs 19.93 in estrogen group) and symptoms of vaginal atrophy (3.63 vs 1.10 in
AV group; 3.90 vs 0.66 in estrogen groups) were also significantly improved after
treatment in both groups. There was no significant difference between groups after
treatment except for fluid volume with a superiority in AV group (P-value= 0.004)
Conclusion
Aloe Vera vaginal cream can be as effective as estrogen vaginal cream in the
management of vaginal atrophy in menopause females.
Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation
Dear Editor-in-Chief
A.M. Viljoen
I am writing to submit our manuscript entitled, Aloe Vera; the new treatment of atrophic
vaginitis, A Randomized Double-blinded Controlled Trial" for consideration as Journal of
Ethnopharmacology as a research article.
In this double-blinded randomized controlled trial on 66 menopause female we want to compare
the effect of Aloe Vera vaginal cream with commercially available estrogen vaginal cream for
management of vaginal atrophy. Based on the study results, Aloe Vera vaginal cream can be as
effective as conventional estrogen vaginal cream in the management of vaginal atrophy in
menopause females.
Each of the authors confirms that this manuscript has not been previously published and is not
currently under consideration by any other journal. Additionally, all of the authors have
approved the contents of this paper and have agreed to the Journal of Ethnopharmacology
submission policies.
Each named author has substantially contributed to conducting the underlying research and
drafting this manuscript. Additionally, to the best of our knowledge, the named authors have no
conflict of interest, financial or otherwise.
Sincerely,
Alireza Salehi
Corresponding Author
Research Center for Traditional Medicine and History of Medicine, Shiraz Medical School, Shiraz University
of Medical Sciences, Shiraz, Iran
Tel: 0098-71-32337589
Fax: 0098-71-32338476
Email: salehialireza45@yahoo.com
Cover Letter
Graphical Abstract Click here to download Graphical Abstract Graphical Abstract.tif
Title Page:
Aloe Vera; A new treatment for atrophic vaginitis, A Randomized Double-
blinded Controlled Trial
Tahereh Poordast1,2, Lida Ghaedian1, Leila Ghaedian3, Fatemeh Sadat Najib1,2, Seyed Jalal
Hosseinimehr8 , Shohreh Alipour4, Massood Hosseinzadeh5, Hossein Molavi Vardanjani6,
Alireza Salehi7*,
1 Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences,
Shiraz, Iran
2 Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Obstetrics and Gynecology, Kosar Hospital, Shiraz, Iran
4 Department of Quality Control, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz,
Iran
5 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
6 MPH Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
7 Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical
Sciences, Shiraz, Iran
8 Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center,
Mazandaran University of Medical Sciences, Sari, Iran
*Corresponding Author:
Alireza Salehi, MD, MPH, PhD of Epidemiology
Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical
Sciences, Shiraz, Iran
Tel: 0098-71-32337589
Fax: 0098-71-32338476
Email: salehialireza45@yahoo.com
https://orcid.org/0000-0003-2750-8499
Abbreviations:
VHI, Vaginal health index; MV, Maturity value; TVS, Transvaginal Sonography; GU,
genitourinary; HTN, Hypertension.
Manuscript File
Aloe Vera; the new treatment of atrophic vaginitis, ARandomized Double-blinded
Controlled Trial
Abstract
Ethno pharmacological relevance
Vaginal atrophy is of the most common problems during menopause with significant
psychosocial and medical consequences. Estrogen as an approved therapy for vaginal atrophy
can be associated with adverse effects and several contraindications in menopause patients. The
aim is to compare the effect of Aloe Vera (AV) vaginal cream with commercially available
estrogen vaginal cream for management of vaginal atrophy in menopause females.
Materials and Methods
This is a double-blinded randomized controlled trial on 66 menopause female with complaints of
vaginal atrophy symptoms. Subjects were randomly allocated in two groups of 33 patients,
named as estrogen and AV groups. Vaginal health index (VHI), maturity value (MV), vaginal
cytologic smear, transvaginal sonography (TVS) and severity of symptoms related to vaginal
atrophy were assessed before and after 6-weeks of vaginal cream administration.
Results
Comparison of MV before and after treatment revealed that superficial cells were significantly
increased after administration of both vaginal cream (6.67 VS 54.33 in AV group; 4.33 VS 59.67
in estrogen group). In addition, VHI (13.83 vs 20.13 in AV group; 13.97 vs 19.93 in estrogen
group) and symptoms of vaginal atrophy (3.63 vs 1.10 in AV group; 3.90 vs 0.66 in estrogen
groups) were also significantly improved after treatment in both groups. There was no significant
difference between groups after treatment except for fluid volume with a superiority in AV
group (P-value= 0.004)
Conclusion
Aloe Vera vaginal cream can be as effective as estrogen vaginal cream in the management of
vaginal atrophy in menopause females.
Keywords: Vaginal atrophy; Aloe Vera; Estrogen; Vaginal health index (VHI); maturity value
(MV); Menopause patients; Vaginal maturity index; Non hormonal treatment.
1. Introduction
According to North American Menopause Society, 40% of post-menopausal women may present
by symptoms of vaginal atrophy which include dryness, vulvar pruritus, discharge, burning and
dyspareunia (Griesser et al., 2012; Pickar, 2013). Moreover, susceptibility to genitourinary (GU)
infection increases in such patients which may be related to decrease in lactic acid as a result of
alteration of bacterial flora of GU and , thus, amplification in PH levels(Palacios, 2009). The
high prevalence of genitourinary atrophy, who seek for medication therapy and its effects on
quality of life ensures the necessity of introducing better management strategies for such
complications of GU aging process(Palacios, 2009). Estrogen depletion receptors which can be
found in vulva, the vagina and the pelvic floor muscles, is considered as the main cause of
genitourinary symptoms of menopause females. However, these receptors do not disappear
completely and the remnant ones are sensitive to exogenous estrogen consumption (Chen et al.,
1999; Gebhart et al., 2001). Estrogen-containing compounds can enhance estrogen receptor
amount even, in some case to its pre-menopausal counts. This can ultimately lead to epithelial
proliferation, vascularization and vaginal secretion (Cavallini et al., 2008). Thus, estrogen
compounds take more attention as a treatment for post-menopausal vaginal atrophy by addition
in the aging population(Castelo-Branco et al., 2005).
However, estrogen might be associated with some complications in postmenopausal women,
leading to reduced compliance in routine use of estrogen cream (JUDD et al.,
1983).Furthermore, long-term estrogen therapy can increase the chance of breast cancer and
endometrial thickness(Cummings, 1991). It can also aggravate or induce hypertension in post-
menopausal women(Mashchak and Lobo, 1985). Hence, an estrogen alternative is needed for
management of patients who might suffer from complication of estrogen creams. Although many
compounds have been studied for this purpose, recommendation of a compound with similar or
higher efficacy compared to estrogen is still controversial.
Aloe barbadensis miller, known as Aloe Vera (AV) can increase collagen content of the wound.
The botanical name of Aloe vera is Aloe barbadensis miller and belongs to Asphodelaceae
(Liliaceae) family. It grows mainly in the dry regions, originated from North Africa. The plant
has triangular, fleshy leaves with serrated edges, yellow tubular flowers and fruits that contain
numerous seeds. AV contains 75 potentially active constituents: vitamins, enzymes, minerals,
sugars, lignin, saponins, salicylic acids and amino acids (Atherton, 1997). An increased synthesis
of hyaluronic acid and dermatan sulfate in the granulation tissue of a healing wound has been
also reported (Chithra et al., 1998).AV also shows antimicrobial activity by rupturing bacterial
cell walls (Athiban et al., 2012; Ndhlala et al., 2009). AV also has antioxidant effect through free
radical- and superoxide radical-scavenging activities (Anilakumar et al., 2010) and anti-
inflammatory activities via inhibition of the cyclooxygenase pathway and reduces prostaglandin
E2 production from arachidonic acid (Hutter et al., 1996).
non-hormonal therapies seem to be a suitable alternative. Due to acceptable efficacy and
different vaginal moisturizers are presented commercially as over-the-counter and commonly
prepared by synthetic ingredients. Some commercially available products contains natural
extracts or juices which known as Emerita®, Yes®, and Hyalo GY ® contains aloe vera leaf juice.
(Sinha and Ewies, 2013). All mentioned products could regulate patients' vaginal pH and
osmolarity similar to healthy adult ranges (Edwards and Panay, 2016). Based on indian
traditional ethnomedical system Ayurveda, Aloe vera is categorized as ayurvedic herb due to it
emmenagogues properties. Emmenagogues herbs may stimulate pelvic area and uterus blood
flow or may stimulate menstruation. They also can stimulate menstrual flow in hormonal
disorders or conditions like oligomenorrhea in which menstruation is absent (Silver, 2007).
It also serve as a moisturizing and anti-aging agent (West and Zhu, 2003). Considering the well-
known dominant wound healing and anti-inflammatory effect combined with less likely or weak
estrogenic effect (especially in form of low dose topical gel), it can be hypothesized that this
compound can be effective in vaginal atrophy therapy with no or less complication as compared
to pure estrogenic compounds. Considering the lack of a non-hormonal commercial product in
our country drug list, and according to mentioned healing and anti-inflammatory properties of
AV, we decided to prepare and investigate AV cream versus estrogen vaginal cream efficacy, on
vaginal atrophy symptoms in menopausal women.
2. Materials and Methods
Aloe vera powder was purchased from Barijessence, Phytopharmaceutical Company, Iran while
all essential analysis were performed by the Company. This company presented analysis
documents to authorized national office that approved it for human applications. The main
components of aloe vera powder are polysaccharides (pectins, cellulose, hemicellulose,
glucomannan, acemannan and mannose derivatives) that previously identified in literature (Bozzi
et al., 2007). Liquid white paraffin, stearyl alcohol, cetyl alcohol, white soft paraffin, and
propylene glycol, sodium lauryl sulfate, and methylparaben were purchased from Merck
(Germany).This is arandomized double-blinded controlled trial on menopause females. Patients
were selected from an outpatient gynecologic clinic affiliated to Shiraz University of medical
sciences. The study is approved by the ethic committee of Shiraz University of Medical Sciences
and Iranian registry of clinical trials (IRCT20190405043170N1). Written informed consent was
filled and signed by all of the patients. Patient allocation was preformed after the informed
consent taking.
2.1 Patient selection and study design
We randomly allocated 66 patients into two groups named control group (conventional treatment
i.e. estrogen cream) and intervention group (Aloe Vera cream) with an allocation ratio of 1:1.
Sample size calculation was done assuming a type I error of 0.05, a statistical power of 80
percent, and a rate of 20% additional improvement in the AV group compared with the control
group.
Postmenopausal womenwith following inclusion criteria were included: 1) non-hysterectomized;
2) postmenopausal with2 or moreyears since final menstrual cycle; 3) age > 40 years; and 4)
presence of urogenital symptoms (vaginal dryness,pruritus,dyspareunia, burning or dysuria).
Patients with following criteriawere excluded from the study. 1) using exogenous sexhormones
during 6 months before starting study; 2) recent corticosteroid use; 3) vaginal infection; 4)
vaginalabnormality; 5) vaginal bleeding with unknown origin; 6) known or suspected history of
hormone-dependenttumor; 7) Breast carcinoma; 8) acute thromboembolic disorder associated
with estrogen use; and 9)any seriousdisease or chronic condition such as hepatic disorder,
inflammatory disease, autoimmune disease or moderate to severe HTN.
2.2 Randomization and blinding
Random allocation was done based on a table of random numbers. Sixty cream tubes with same
appearance including 33 estrogen cream and 33 AV cream were administered randomly to the
patients. The patients and the physician administered the cream were blinded to the cream group.
In addition, the pathologist and the statistics were also blinded to the patients’ group.
2.3 Baseline Measurements
Demographic data including Age, Age of menopause, Time after menopause, Job, Economic
status, Educational level was collected at the study baseline. Participants were examined by a
GYN/OB specialist for evaluation of signs and symptoms of atrophic vaginitis, taking vaginal
cytologic smear for evaluation of maturity value (MV) and transvaginal sonography of
endometrial thickness. GYN/OB specialist filled the baseline section of the study data collection
form for each patient. Vaginal cytologic smear samples were examined by pathologist and data
items were filled.
2.4 Intervention
Patients were trained and prescribed to use vaginal cream 5 mg per night for first 2 weeks and
then 3 nights per week for the next 4 weeks. Patients were asked not to use other vaginal cream
or hormonal medication during therapy.
2.5 Aloe vera cream preparation
Preparation of aloe cream Liquid white paraffin, stearyl alcohol, cetyl alcohol and white soft
paraffin were mixed and heated to the boiling point as the oil phase. AV powder
(Barijessence,Phytopharmaceutical Company, Iran) mixed with deionized water was added to a
mixture of propylene glycol, sodium lauryl sulfate, and methylparaben. The mixture was heated
as the aqueous phase. These two separate phases were mixed continuously while being
cooled(Eshghi et al., 2010; Khorasani et al., 2009).Thus, after cooling, the uniform cream that
was produced was placed in an aluminum package similar to a conjugated estrogen tube,
weighing 50 g. The cream contained AV gel powder 2%. Our experimental research and
formulations were carried out in sterile conditions under the supervision of the pharmaceutic
group at the School of Pharmacy, Shiraz. The final creams were tested for any probable
contamination.
Commercial vaginal Estrogen cream:conjugated estrogen 0.625 vaginal cream Manufactured by
ALDO-UNION, S.A. (Barcelona Spain)
2.6 Study outcomes
For evaluation of vaginal atrophy symptoms, a questionnaire about the severity of dyspareunia,
vaginal dryness, vaginal/vulvar pruritus, vaginal burning or urinary complaint was given to
patients to score the severity of each symptom on the basis of 5 grade scaling. Sum of each
symptom grade considered as total vaginal atrophy symptom score.
Signs of vaginal atrophy was assessed, based on the Gloria Bachmann Vaginal HealthIndex
(VHI) by spaculum examination, consisting of 5 measures: elasticity fluid volume, PH, epithelial
integrityand moisture. Each parameter is graded from 1 to 5 (worst to best condition) and a total
score< 15 willbe considered as atrophic.
Maturity value was also assessed by a cytopathologist who was alsoblinded to patient group. The
maturity value is an inexpensive means to evaluate hormonalinfluences in women. The MV may
be collected from vaginal, conjunctival, urethral, and buccal mucosalsurfaces.The index is read
from left to right and refers to the percentage of parabasal, intermediate, andsuperficial
squamous cells appearing on a smear, with the total of all three values equaling 100%. A shift to
the left indicates an increase in the parabasal or intermediate cells, while a shift to the
rightdenotes an increase in the superficial or intermediate cells.
2.7 Follow up measurements
One week after completion of the treatment period (6-week), patients were examined by
OB/GYN and data items on VHI, MV and TVS were assessed. Vaginal cytologic smear and
sonography were done.According to symptoms of vaginal atrophy before and after treatment,
and incidence of any complication treatment satisfaction were examined. Treatment satisfaction
was evaluatedsubjectively using a single question 5-point Likert scale (very satisfied, satisfied,
uncertain, dissatisfied andvery dissatisfied).
2.8 Statistical analysis
Forcomparison of categorical variables and quantitative variables between the two group’s chi-
square andindependent t-test were used, respectively. For comparison of variables before and
after therapy, Wilcoxon and paired t-test were used. Multivariate repeated measures analysis of
variance was also applied. P-value<0.05 was considered significant.All data was analyzed by
SPSS software (SPSS Statistics for Windows, version 18.0).
3. Results
Finally, 60 patients with 30 cases in each group, completed the 6- week’s therapeutic course and
included in the study analysis(Figure 1).
Fig 1. The study flow diagram
Excluded (n=154)
Not meeting inclusion criteria (n=142)
Declined to participate (n=10)
Other reasons (n=2)
Analysed (n=30)
Excluded from analysis (give reasons) (n=0)
Lost to follow-up (give reasons) (n=0)
Discontinued intervention (give reasons) (n= 3)
2 due to sever vaginal burning sensation
1 due to spotting
Allocated to Conventional cream (n=33)
Received allocated intervention (n=33)
Did not receive allocated intervention (give
reasons) (n=0)
Lost to follow-up (give reasons) (n=3)
2 due to distance from the study setting
1 due to hip fracture
Discontinued intervention (give reasons) (n=0)
Allocated to AV cream (n=33)
Received allocated intervention (n=33)
Did not receive allocated intervention (give
reasons) (n=0)
Analysed (n=30)
Excluded from analysis (give reasons) (n=0)
Allocation
Analysis
Follow-Up
Randomized (n=66)
Enrollment
Comparison of baseline features between the two groups showed no significant difference,
except for economic status, which was in a higher level in AV group (P=0.026; table 1).
Table 1. Comparison of demographic characteristics of patients between the AV and estrogen groups.
Variable
AV
Estrogen
p- value
Age
59.6±8.29
61.2±10.28
.51
Time from menopause
11.13±6.62
12.73±7.04
.368
parity
4.1±1.99
4.3±1.97
.697
Education
Under-diploma
20(66.7)
20(66.7)
.99
Diploma
7(23.3)
7(23.3)
Academic
3(10)
3(10)
Occupation
House keeper
26(86.7)
20(90)
.99
Retired
4(13.3)
3(10)
Economy
Low
6(20)
16(53.3)
.026
Intermediate
16(53.3)
10(33.3)
High
8(26.7)
4(13.3)
Marital status
Married
19(63.3)
18(60)
.791
Single,widow, separated
11(36.7)
12(40)
Intercourse
No
11(36.7)
8(26.7)
.231
< 5/months
11(36.7)
18(60)
5/months
8(26.7)
4(13.3)
Both groups have similar rate of vaginal atrophy-related symptoms before therapy(3.63 vs
3.90; p-value= 0.663) Additionally, Gloria Bachman index was not statistically different between
the two groups(P-value=0.766). As shown in table 2, separate comparison of each part of this
index also showed no significant difference between estrogen and AV groups.
Table 2. Comparison of vaginal atrophy symptoms, VHI and MV before and after treatment in each
group.
Estrogen
AV
Variable
P-value**
P-
value*
P value$
Post
Pre
P
value$
Post
Pre
.325
.9
<0.001
.13±.35
.93±.91
<0.001
.23±.43
.97±1.13
dyspareunia
Vaginal
atrophy
symptoms
.203
.057
<0.001
.13±.35
1.37±.61
<0.001
.27±.45
1.07±.58
Vaginal
dryness
.087
.99
<0.001
.07±.25
.53±.63
0.001
.13±.35
.53±.57
Pruritus
vulvae
.358
.736
<0.001
.1±.31
.7±.7
0.001
.07±.25
.53±.78
Vaginal
burning
.091
0.069
0.043
.23±.57
.37±.67
0.043
.40±.67
.53±.9
Urinary
complaint
0.103
0.663
<0.001
0.66±1.02
3.90±2.41
<0.001
1.10±0.99
3.63±2.29
Total
symptom
0.337
0.727
<0.001
4.17±0.79
1.87±0.73
<0.001
3.97±0.81
1.93±0.74
PH
VHI
0.004
0.073
<0.001
3.73±0.52
2.63±0.49
<0.001
4.13±0.51
2.4±0.49
Fluid
volume
0.384
0.523
<0.001
4.33±0.66
3.27±0.52
<0.001
4.47±0.5
3.17±0.7
Epithelial
integrity
0.142
0.43
<0.001
3.73±0.69
2.63±0.81
<0.001
3.5±0.51
2.77±0.43
Moisture
0.475
0.99
<0.001
3.97±0.67
3.57±0.858
<0.001
4.07±0.37
3.57±0.50
Elasticity
0.633
0.766
<0.001
19.93±1.57
13.97±1.93
<0.001
20.13±1.66
13.83±1.48
VHI
0.278
0.183
<0.001
59.67±17.12
4.33±5.04
<0.001
54.33±20.46
6.67±8.02
Superficial
cells
MV
0.711
0.838
0.630
32.67±13.11
31.33±13.83
0.837
31.33±8.02
30.67±11.12
Intermediate
cells
0.07
0.866
<0.001
8±8.05
64.33±15.24
<0.001
14.33±16.95
63.67±15.2
Parabasal
cells
0.542
0.785
<0.001
20±9.01
76±11.99
<0.001
22.0±10.72
70.0±17.22
MV
0.151
-
2.86±0.98
-
2.53±0.76
-
Endometrial thickness
$P-value for comparison of before vs after measures;* P-value for comparison of before measures in AV and
estrogen groups; **P-value for comparison of after measures in AV and estrogen groups.
Comparisons of different measured parameters before and after treatment are shown in
table 2. In both groups, rate of vaginal atrophy symptoms was significantly decreased after
treatment (P-value <0.001 in both groups). Vaginal health index was also significantly improved
in all measures (P-value<0.001 in both groups).
As shown in table 2, none of Vaginal atrophy symptoms, VHI, or MV was significantly
different between the two groups after treatment.
Although all patients in both groups were satisfied or very satisfied of using both creams,
patients in estrogen group reported higher degree of satisfaction (3.0 vs 3.4; P= 0.002).
In AV group, two patients complain of increased vaginal discharge after treatment,
however, no abnormal finding was detected in vaginal cytologic smear or physical examination.
In estrogen group, 6 patients reported vaginal burning early after use of vaginal cream which
gradually improved with continuation of therapy.
4. Discussion
This study shows that AV cream can improve signs and symptoms of vaginal atrophy in
menopause patients with similar efficacy as compared to estrogen cream. In addition,
insignificant rare complications in both groups, indicates that AV cream can be used as a good
alternative choice when estrogen cream is not indicated.
Several studies were conducted in order to investigate the effects of estrogen compounds and
derivatives on post-menopausal vaginal atrophy. In a study conducted by Smith et.al,it was
detected that a vaginal silicone ring which release low doses of estradiol continuously can be
effective and safe in vaginal atrophy treatment(Smith et al., 1993). In another survey, performed
by Griesser et.al, using estradiol passeries can be sufficient for local treatment of vaginal
atrophy(Griesser et al., 2012).Lima et.al, concluded that isoflavine which is a phytoestrogen
compound as a vaginal gel form, can improve vaginal atrophy symptoms as well as increase cell
maturation values(Lima et al., 2013).Moreover, local estrogen therapy is also introduced as a
well-tolerated and useful therapy for vaginal atrophy treatment and it is preferable to systemic
estrogen therapy when the only goal of treatment is vaginal atrophy(Reiter, 2013). However,
some studies revealed that patients show low compliance in using local estrogen therapy, and
estrogen tablets are more preferable for them(Minkin et al., 2013).Another survey done by
Mattssone et.al, was also manifested that women mostly prefer small estrogen tablet medication
to local compounds(Mattsson et al., 2013).Another study, by Cummings et al, was detected that
long-term estrogen therapy can increase the chance of breast cancer up to about 30%(Cummings,
1991). Mashchok et al, also, suggested that estrogen replacement therapy can aggravate or, even,
induce hypertension in post-menopausal women (Mashchak and Lobo, 1985). It can also
increase endometrial thickness after long-term therapy(Goldstein et al., 2000). As it can be seen,
estrogen therapy, besides its all benefits, can have several complications for women thus, an
estrogen subsides seems to be needed for replacing this kind of medication therapy.
The AV plant has been known and used for centuries for its health, beauty, medicinal and skin
care properties(Davis, 1997). AV is known as the healing plant. AV gel increased collagen
content and composition in the wound and increased the degree of collagen cross linking, leading
to acceleration of wound contraction. An increased synthesis of hyaluronic acid and dermatan
sulfate in a healing wound following oral or topical treatment hasalso been reported (Chithra et
al., 1998). The reduction of vaginal atrophy symptoms in AV group in our study can be also
explained by these healing properties of AV. AV also shows antimicrobial activity by rupturing
bacterial cell walls (Ndhlala et al., 2009). An important study in support of the anti-inflammatory
activity of AV in rats with induced peptic ulcer has shown that the mean ulcer index of the
control group was 50 ± 3.5, whereas the mean ulcer index of the AV treated group was 20 ± 1.79
and the mean ulcer index of the standard omeprazole-treated group was 10 ± 1.96(Borra et al.,
2011).
Our study also revealed significant improvement in cytologic and clinical indices of vaginal
atrophy after AV administration. Another study in support of AV reported that sucralfate and AV
treatment in the ulcer groups showed reduced gastric inflammation, enhanced epithelial cell
proliferation, elongated gastric glands, and reduced ulcer sizes (Eamlamnam et al., 2006).
We also found that AV can increase percent of superficial epithelial cells in vaginal mucosa of
postmenopausal women with vaginal atrophy symptoms. Rajar et.al, was shown that AV gels can
be effective on lichen planus which is a chronic inflammatory disease of mucosal surfaces (Rajar
et al., 2008). It also serves as a moisturizing and anti-aging agent. Mucopolysaccharides help in
binding moisture into the skin. Its moisturizing effects has also been studied in treatment of dry
skin associated with occupational exposure where AV gel gloves improved the skin integrity,
decreased appearance of fine wrinkle and erythema(West and Zhu, 2003). Our study also showed
that fluid volume and moisture of vaginal mucosa were significantly increased after treatment
with AV.
AV has a controversial effect on estrogen level, as well. AV gel specifically suppress breast
cancer cell proliferation by targeting estrogen receptor(Huang et al., 2013). There are also studies
suggesting the therapeutic effect of AV on endometriosis and PCO patients that indicates
possible low dose estrogenic effect for AV(Bostanci et al., 2016). It is assumed that this is the
inhibitory effect of AV on estrogen receptor that lead to increase in estrogen levels by gonads via
a negative feedback mechanism. However, the estrogenic effect of AV can be more controversial
in postmenopausal women while in this group, there is no functioning gonads to produce
estrogen in response to estrogen receptor inhibition by AV. Therefore, it seems that the healing,
anti-inflammatory and moisturizing properties of AV, which are mentioned before, are the
responsible mechanism for improving vaginal atrophy symptoms in our patients. Thus, AV gel
can be safely recommended for treatment of vaginal atrophy in patients with estrogen
contraindication.
As the study was a pilot RCT in the field, it has a limitation in sample size. This may be the most
major study consideration in the interpretation of the results.
5. Conclusion:
This study showed that AV can be safely used as a treatment option in vaginal atrophy in
menopause patients. However, further studies with higher statistical power are still required to
investigate the effect of this compound in patients who cannot tolerate estrogen.
Acknowledgement
The present article was extracted from a thesis written by Lida Ghaedian and was financially
supported by Shiraz University of Medical Sciences, Shiraz, Iran (grants No.4666). The authors
would like to thank the Center for Development of Clinical Research of Namazi Hospital for
their contribution to the statistical analysis.
Conflict of Interest statement:
Each named author has substantially contributed to conducting the underlying research and
drafting this manuscript. Additionally, to the best of our knowledge, the named authors haveno
conflict of interest, financial or otherwise.
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