10.5826/dpc.1303a139
Introduction: Female Pattern Hair Loss (FPHL) is considered the most common type of hair loss in females. Women with FPHL may suffer from psychological distress and defective social functioning. Patients with psychiatric and neurodegenerative disorders almost have a deficient brain and blood brain-derived neurotrophic factor levels (BDNF). This serum BDNF level may act as a diagnostic marker for negative psychological impact in FPHL patients.
Objectives: Evaluate the levels of serum BDNF in patients with FPHL and correlate its level to the severity of alopecia and the degree of psychological impact.
Methods:  Forty-six female patients with FPHL and 41 healthy age-matched female volunteers as a control were included in the study. Patients filled out a Dermatology Life Quality Index questionnaire. Both patients and controls filled Beck Depression Inventory, Beck Anxiety Inventory, and Perceived Stress Scale (PSS) questionnaires. Serum levels of BDNF were measured for all the participants using the ELISA technique.
Results: Patients with FPHL had significantly lower levels of BDNF and significantly higher Beck depression inventory score and PSS questionnaire scores. There is a significant negative correlation between serum levels of BDNF and Beck Depression Inventory, Beck Anxiety Inventory, and PSS questionnaire scores.
Conclusions: Patients with FPHL are at a high risk to develop chronic stress and depression. The serum level of BDNF is a good predictor for the assessment of chronic stress and depression in FPHL patients.
text/xml
2160-9381
2891
en
Basma HM Khatery
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
DLQI
Female Pattern Hair Loss and Negative Psychological Impact: Possible Role of Brain-derived Neurotrophic Factor (BDNF)
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-07-31
2022-10-05
2023-07-31
2023-08-24
e2023139
Dermatol Pract Concept
Introduction: Female Pattern Hair Loss (FPHL) is considered the most common type of hair loss in females. Women with FPHL may suffer from psychological distress and defective social functioning. Patients with psychiatric and neurodegenerative disorders almost have a deficient brain and blood brain-derived neurotrophic factor levels (BDNF). This serum BDNF level may act as a diagnostic marker for negative psychological impact in FPHL patients.
Objectives: Evaluate the levels of serum BDNF in patients with FPHL and correlate its level to the severity of alopecia and the degree of psychological impact.
Methods:  Forty-six female patients with FPHL and 41 healthy age-matched female volunteers as a control were included in the study. Patients filled out a Dermatology Life Quality Index questionnaire. Both patients and controls filled Beck Depression Inventory, Beck Anxiety Inventory, and Perceived Stress Scale (PSS) questionnaires. Serum levels of BDNF were measured for all the participants using the ELISA technique.
Results: Patients with FPHL had significantly lower levels of BDNF and significantly higher Beck depression inventory score and PSS questionnaire scores. There is a significant negative correlation between serum levels of BDNF and Beck Depression Inventory, Beck Anxiety Inventory, and PSS questionnaire scores.
Conclusions: Patients with FPHL are at a high risk to develop chronic stress and depression. The serum level of BDNF is a good predictor for the assessment of chronic stress and depression in FPHL patients.
Basma HM Khatery
2023/07/31
10.5826/dpc.1303a139
e2023139
Department of Dermatology, STDs, and Andrology, Faculty of Medicine Fayoum University, Faiyum, Egypt
2160-9381
DLQI
en
e2023139
Redler S, Messenger AG, Betz RC. Genetics and other factors in the aetiology of female pattern hair loss. Exp Dermatol. 2017;26(6):510-517. DOI: 10.1111/exd.13373. PMID: 28453904.
Female Pattern Hair Loss and Negative Psychological Impact: Possible Role of Brain-derived Neurotrophic Factor (BDNF)
https://dpcj.org/index.php/dpc/article/download/2891/2200
             Female Pattern Hair Loss and Negative
               Psychological Impact: Possible Role
          of Brain-derived Neurotrophic Factor (BDNF)
        Noha E Mohamed1, Mohamed R Soltan2, Sara A Galal3, Hassan Salem El Sayed4,
                         Hadir M Hassan1, Basma HM Khatery1


1 Department of Dermatology, STDs, and Andrology, Faculty of Medicine Fayoum University, Faiyum, Egypt
2 Psychiatry Department, Fayoum University, Faiyum, Egypt
3 Dermatology and Venereology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
4 Medical Biochemistry and Molecular Biology, Faculty of Medicine Fayoum University, Egypt The research was conducted in the outpatient
  clinic of the Department of Dermatology, STDs, and Andrology, Faculty of Medicine, Fayoum University



Key words: androgenetic alopecia, BDNF, psychological impact, DLQI
Citation: Mohamed NE, Soltan MR, Galal SA, El Sayed HS, Hassan HM, Khatery BHM. Female pattern hair loss and negative
psychological impact: possible role of brain-derived neurotrophic factor (BDNF). Dermatol Pract Concept. 2023;13(3):e2023139.
DOI: https://doi.org/10.5826/dpc.1303a139
Accepted: January 2, 2023; Published: July 2023
Copyright: ©2023 Mohamed et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Sara Ahmed Galal, Dermatology and Venereology Department, Faculty of Medicine for Girls, Al-Azhar University,
53, New Cairo, 3rd zone fifth, settlement, Cairo, Egypt Telephone number: 01008876877 Email address: drsaragalal@azhar.edu.eg




  ABSTRACT             Introduction: Female Pattern Hair Loss (FPHL) is considered the most common type of hair loss in
                       females. Women with FPHL may suffer from psychological distress and defective social functioning.
                       Patients with psychiatric and neurodegenerative disorders almost have a deficient brain and blood
                       brain-derived neurotrophic factor levels (BDNF). This serum BDNF level may act as a diagnostic
                       marker for negative psychological impact in FPHL patients.
                       Objectives: Evaluate the levels of serum BDNF in patients with FPHL and correlate its level to the
                       severity of alopecia and the degree of psychological impact.
                       Methods: Forty-six female patients with FPHL and 41 healthy age-matched female volunteers as a
                       control were included in the study. Patients filled out a Dermatology Life Quality Index questionnaire.
                       Both patients and controls filled Beck Depression Inventory, Beck Anxiety Inventory, and Perceived
                       Stress Scale (PSS) questionnaires. Serum levels of BDNF were measured for all the participants using
                       the ELISA technique.




Original Article | Dermatol Pract Concept. 2023;13(3):e2023139                                                                        1
                      Results: Patients with FPHL had significantly lower levels of BDNF and significantly higher Beck
                      depression inventory score and PSS questionnaire scores. There is a significant negative correlation
                      between serum levels of BDNF and Beck Depression Inventory, Beck Anxiety Inventory, and PSS ques-
                      tionnaire scores.
                      Conclusions: Patients with FPHL are at a high risk to develop chronic stress and depression. The
                      serum level of BDNF is a good predictor for the assessment of chronic stress and depression in FPHL
                      patients.




Introduction                                                        Therefore, we aimed to evaluate the levels of serum BDNF
                                                                 in patients with FPHL and correlate its level to both the de-
Female Pattern Hair Loss (FPHL) is a common cause of             gree of psychological impact and the severity of alopecia.
non-scarring alopecia in females manifested as, successive
loss of terminal hairs in the vertex and frontal areas of the
scalp. AGA is distinguished by follicular miniaturization
                                                                 Methods
which is characterized by a short anagen phase and increased     The present case-control study included 46 female patients
vellus hairs [1].                                                with FPHL and 41 age-matched healthy female volunteers.
    In general, alopecia is known to be associated with             The patients were recruited from the Dermatology, STDs,
many psychiatric comorbidities such as depression, anxiety,      and Andrology Department Clinic, during the period be-
personality disorders, and drug abuse. Moreover, patients        tween May 2021 to August 2021.
with alopecia have noticeably higher suicidal rates and get         All included individuals, or their families provided an in-
hospitalized for mental health diseases. Regarding specific      formed written agreement to be included in the study. This
types of hair loss, FPHL may be linked to many psychiatric       study was conducted according to the Declaration of Hel-
comorbidities, especially in patients with extensive scalp af-   sinki and the protocol approved by the ethics committee of
fection [2].                                                     Würzburg University and by the Institutional Review Board
    FPHL may lead to depression and decreased life quality,      of the Faculty of Medicine, Fayoum University (IRB number
poor self-esteem, and negative body image [3].                   IRB00003613) in January 2018. An informed written Arabic
    Brain-Derived Neurotrophic Factor (BDNF) is a member         consent form was signed by every participant in the presence
of the neurotrophins family which is known for its action        of one of the authors.
on the growth of central and peripheral nerves. Neurotro-
phins show a variety of immunomodulatory impacts on              Patients
non-neuronal cells especially mast cells, keratinocytes, and
                                                                 Female patients 15-50 years old complaining of AGA were
eosinophils [4].
                                                                 included in this study. Patients were diagnosed and classified
    BDNF controls human hair growth via tropomyo-
                                                                 according to Female Pattern Hair Loss Severity Index [7].
sin receptors (TrkB). BDNF markedly decreases hair shaft
                                                                    We exclude patients suffering from any systemic or cu-
elongation, promotes premature catagen, and decreases ke-
                                                                 taneous diseases other than FPHL. We also exclude patients
ratinocyte proliferation [5].
                                                                 with a past or present history of psychiatric illness or receiv-
    Panchaprateep et al postulated that BDNF may be essen-
                                                                 ing any regular psychotropic medication, antidepressants
tial in exerting the androgens impacts on hair follicles act-
                                                                 were also excluded. Pregnant and lactating women were ex-
ing as a negative regulatory factor. This study showed that
                                                                 cluded from the study.
balding scalp follicles produced 12-fold more BDNF than
the nonbalding scalp [6].
                                                                 Control
                                                                 Forty-one healthy female volunteers 15-50 years old were
                                                                 included in the study as a control.
Objectives
This study evaluates serum BDNF levels in patients with          Study Design
FPHL. We suggest that there may association between serum        All subjects were subjected to a Full history taking and clin-
BDNF levels and FPHL.                                            ical examination.




2                                                                    Original Article | Dermatol Pract Concept. 2023;13(3):e2023139
    The patients were diagnosed and classified according to               two tests. Logistic Regression analysis was used to detect the
FPHL Severity Index [7].                                                  most independent/ affecting factor for affecting cases. Linear
    Questionnaires to access the psychological state for all              Regression analysis was used to detect the most independent/
participants were done including Beck Depression Inven-                   affecting factor for affecting Serum BDNF.
tory, Beck Anxiety Inventory and Perceived Stress (PSS)
Scale [8-10].
    DLQI was done for the patient group only [11].
                                                                          Results
    The serum level of BDNF was measured for all subjects                 This case-control study included 87 females, 46 female pa-
using ELISA kits which were provided by biodiagnostic kits                tients suffering from FPHL, and 41 age-matched healthy fe-
(Sun red Biological Technology Company). Five ml of blood                 male subjects as a control. The participants were recruited
were collected from the antecubital vein by venipuncture and              from the Dermatology, STDs, and Andrology Department
left for 30 minutes at room temperature to allow clotting                 Clinic. The patients were diagnosed and classified according
and then centrifuged for 15 minutes at 3000 rpm. Serum was                to FPHL Severity Index.
separated, stored in an Eppendorf tube and kept at −20°C
until used for measurement of BDNF level.
                                                                          Patient Group
    Each female was subjected to full history, measurement
                                                                          Included 46 female patients, their ages ranged from 15 to 50
of serum level of BDNF using ELISA technique.
                                                                          years old with a Mean ± SD (29.85 ± 9.73) with a median
                                                                          (IQR) of 29.50 (22.0 - 38.0).
Statistical Analysis
Chi-square test was used for categorical variables, to compare
                                                                          Control Group
between different groups. Fisher Exact test or Monte Carlo
correction were used for correction for chi-square when                   Included 41 healthy females, their ages ranged from 20 – 51

more than 20% of the cells have expected count less than 5.               years with a Mean ± SD (26.44 ± 7.38) with median (IQR)

Student t-test was used for normally distributed quantitative             26.0 (19.0 – 32.0). There was no statistically significant dif-

variables, to compare between two studied groups. Mann                    ference (P value ≤ 0.05) between both groups.

Whitney test was used for not normally distributed quanti-                   In the patient group 34 patients (73.9%) had positive

tative variables, to compare two studied groups. Spearman                 family history of FPHL, while in the control group only 6

coefficient was used to correlate between two distributed not             patients (14.9%) had positive family history.

normally quantitative variables.                                             Diet changes was reported in one patient (2.2%) in the

    Kruskal Wallis test was used for not normally distrib-                patient group, while 4 individuals (9.8%) in the control

uted quantitative variables, to compare between more than                 group have diet change (Table 1).

two studied groups. Receiver operating characteristic curve
(ROC) is generated by plotting sensitivity (TP) on Y axis ver-            Clinical Parameters of the Studied Groups
sus 1-specificity (FP) on X axis at different cut off values. The         In the patient group acne was reported in 11 patient (23.9%),
area under the ROC curve denotes the diagnostic performance               while only 1 individual (2.4%) in the control group have
of the test. Area more than 50% gives acceptable performance              acne. There was a high statistically significant difference re-
and area about 100% is the best performance for the test. The             garding presence of acne between the case and the control
ROC curve allows also a comparison of performance between                 groups (P value ≤ 0.05).




                                   Table 1. Clinical parameters of the studied group.
                                                      Cases (N = 46)            Control (N = 41)              χ2               P
 Family history of FPHL                                N            %             N          %
 Negative                                              12        26.1             35        85.4          30.669            <0.001
 Positive                                              34        73.9             6         14.9
 Diet changes                                          1            2.2           4          9.8           2.301            0.183
 Acne                                                  11        23.9             1          2.4           8.407            <0.05
 Hirsutism                                             8         17.4             4          9.8           1.063            >0.05
 Signs of virilization                                 0            0.0           0          0.0              –                –
 Menstrual irregularity                                11        23.9             5         12.2           1.983            >0.05



Original Article | Dermatol Pract Concept. 2023;13(3):e2023139                                                                         3
    Regarding Hirsutism of the studied patients 8 patient           (P <0.001) between serum BDNF and Beck Anxiety Score,
(17.4%) had Hirsutism, while in the control group Hirsut-           Beck Depression Score and a high statistically significant
ism was reported in 4 patient (9.8%). Signs of virilization         negative correlation (P < 0.001) regarding PSS (Table 6).
was not reported in patients and controls. There was no sta-
tistically significant difference regarding Hirsutism, the signs    Correlation Between FPHL Severity Index Score
of virilization and menstrual irregularity (Table 1).               and Different Parameters in Patient Group
                                                                    There were high statistically significant positive correlations
Local Examination of the Scalp                                      between FPHL Severity Index Score and age of patients, age
of the Studied Groups                                               of onset, duration of the FPHL and Sinclair Hair Density
Scalp itching and soreness were reported in 34.8%, and              Scale (P value ≤ 0.001) (Table 7).
10.9% of the patients while in 22% and 0% in the control               The univariate logistic regression analysis for the
group respectively with no statistically significant difference.    parameters affecting cases showed that there were sta-
    Scalp scaling was significantly statistically higher than       tistically significant relations (P value ≤ 0.05) regarding
the control group (P ≤ 0.05). There was a high statistically        presence of hormonal acne, presence of scaling, presence
significant difference (P = 0.001) regarding hair pull test, Sin-   of Hair Pull test, increasing in the Perceived Stress Scale,
clair hair shedding scale, Sinclair hair density scale, FPHL        increasing in the Beck Depression Score and increasing in
severity index scale and FPHL severity index score between          the Beck Depression Scale. There was high statistically sig-
the case group and the control group (Table 2).                     nificant relation (p value ≤ 0.001) regarding presence of
                                                                    family history of FPHL. The multivariate logistic regres-
Comparison Between the Two Studied Groups as                        sion analysis showed that there was a high statistically
Regards to the Psychological State                                  significant relation (P value ≤ 0.001) regarding presence
In the patient group PSS and Beck Depression was statisti-          of family history of FPHL. There was a statistically sig-
cally significantly higher than the control group (P ≤ 0.05),       nificant relation (P value ≤ 0.05) regarding Hair Pull test
while the Score Beck Depression Scale showed no statisti-           (Table 8).
cally significant difference.                                          The univariate logistic regression analysis for the pa-
    Regarding Beck Anxiety Score and Scale showed no sta-           rameters affecting serum level of BDNF in the case group
tistically significant difference between both groups (P value      (n = 46 vs. 41) showed that there were statistically signifi-
> 0.05) (Table 3).                                                  cant relations (P value ≤ 0.05) regarding duration of FPHL,
                                                                    increasing in Perceived Stress Scale, increasing in Beck Anx-
Analysis of the Dermatology Life Quality Index                      iety Score, increasing in Beck Anxiety Scale, increasing in
in the Patient Group                                                Beck Depression Score and increasing in Beck Depression
Only 2 cases (4.3%) had no effect on patient life, 9 cases          Scale. The multivariate Logistic regression analysis showed
(19.6%) with minor effect on patient’s life, 20 cases (43.5%)       that there was a statistically significant relation (P value
with moderate effect on patients life, 10 cases with very great     ≤ 0.05) regarding increasing in Beck Depression Score
impact on patient life and 5 cases (10.9%) with extreme im-         (Table 9).
pact on patient life respectively.


Serum BDNF in the Studied Groups                                    Conclusions
In the patient group serum level of BDNF was statistically          Neurotrophins including BDNF and their receptors have
significantly lower than the control group (P value < 0.05).        role in skin hemostasias and hair growth [12].
In patients mean ± SD was 0.85 ± 1.07, while in the controls           Botchkarev et al reviewed that stress may induced hair
was 1.07 ± 1.26 (Table 4).                                          loss, psoriasis, and other skin diseases. BDNF is a member of
    The cut off point for serum BDNF to discriminate pa-            a family of neurotrophins [13].
tients from control was ≤ 0.714. The sensitivity was 76.09             This study aimed to evaluate the levels of serum BDNF in
and the specificity was 56.10 (Table 5 and Figure 1).               patients with FPHL and correlate its level to the severity of
                                                                    alopecia and the degree of psychological impact.
Correlation Between Serum BDNF and Different                           Our study included (87) female subjects that were di-
Parameters in Patients Group                                        vided into two groups; Group A (case group): included 46
There were statistically significant positive correlations          female patients with FPHL while group B (control group):
(P ≤ 0.05) between serum BDNF and FPHL duration, while              included 41 age matched healthy female volunteers as con-
there was a statistically significant negative correlation          trol group.




4                                                                       Original Article | Dermatol Pract Concept. 2023;13(3):e2023139
                                  Table 2. Local examination of the studied groups.
                                            Cases (N = 46)                    Control (N = 41)
 Scalp
                                           N                 %                N                  %           χ2           P
 Itching                                   16              34.8               9                 22.0        1.743       >0.05
 Scaling                                   28              60.9              15                 36.6        5.114       <0.05
 Erythema                                   0               0.0               0                  0.0          –            –
 Soreness                                   5              10.9               0                  0.0        4.728         p
                                                                                                                        =0.057
 Hair Pull test
                                          No.                %               No.                 %           χ2           P
 Negative                                  29              63.0              38                 92.7       10.757       0.001
 Positive                                  17              37.0               3                  7.3
 Sinclair Hair Shedding Scale
                                          No.                %               No.                 %           χ2           P
 Bundle with 10 hairs                      27              58.7              41                 100        24.494       <0.001
 Bundle with 50 hairs                      17              37.0               0                  0.0
 Bundle with 100 hairs                      2               4.3               0                  0.0
 Sinclair Hair Density Scale
                                          No.                %               No.                 %           χ2           P
 1                                          6              13.0              41                 100.0      77.196*      <0.001
 2                                         32              69.6               0                  0.0
 3                                          8              17.4               0                  0.0
 Min.– Max.                             1.0– 3.0         1.0– 1.0        Min-Max.           1.0 – 3.0      123.0*       <0.001
 Mean ± SD.                            2.04±0.56          1.0±0.0        Mean±SD           2.04±0.56
 Median (IQR)                         2.(2.0-2.0)         1.0 (-)      Median (IQR)          2 (2-2)
 FPHL Severity Index
                                          No.                %               No.                 %           χ2           P
 FPHL unlikely                              0               0.0              41                 100.0       87.0        <0.001
 Early FPHL                                13              28.3               0                  0.0
 Established FPHL                          33              71.7               0                  0.0
 FPHL Severity Index Score
                                          No.                %               No.                 %           χ2           P
 Min. – Max.                            6.0-14.0          0.0-4.0        Min.-Max.         6.0 – 14.0        t=         <0.001
 Mean ± SD.                           11.09±2.53        0.78±0.91        Mean±SD          11.09±2.53       25.839
 Median (IQR)                         11(9.0-13)          1(0-1)       Median (IQR)         11(9-13)

FPHL = Female Pattern Hair Loss; IQR = interquartile range; SD = standard deviation.



     All female was subjected to full history, measurement of        no statistically significant difference regarding age between
serum level of BDNF and Questionnaires to access the psy-            the case and control groups as they were age matched.
chological state. Quality of life was accessed in the patient            There was a high statistically significant difference re-
group only.                                                          garding presence of acne between the case and the control
     The patients were diagnosed and classified according to         groups (P value ≤ 0.05).
FPHL Severity Index [7]. The cases age ranged from 15 to                 This is due to that Female Pattern Hair Loss and hor-
50 years with a mean of 29.85 ± 9.73, while the control age          monal acne can be due to androgen receptors hypersen-
ranged from 15 to 41 years with a mean of 26.44 ± 7.38. We           sitivity to circulating dihydrotestosterone or coexisted
selected this age group as androgen effects in addition to cos-      hyperandrogenic status such as virializing tumor, polycystic
metic concerns are marked during this age group. There was           ovarian syndrome, or those on oral contraceptive pills that



Original Article | Dermatol Pract Concept. 2023;13(3):e2023139                                                                   5
    Table 3. Comparison between the two studied groups according to stress, anxiety, and depression
                                               scales.
                                                                 Cases (N = 46)           Control (N = 41)           Test         P
 Perceived Stress Scale
    Min. – Max.                                                    13.0 – 39.0               10.0 – 35.0
    Mean ± SD.                                                    25.17 ± 5.96               21.27 ± 6.44           2.939        <0.05
    Median (IQR)                                                25.0 (22.0 – 29.0)        21.0 (16.0 – 27.0)
 Beck Anxiety Score
    Min. – Max.                                                    12.0 – 49.0               13.0 – 53.0
    Mean ± SD.                                                    28.83 ± 8.09               28.88 ± 9.18           0.028        >0.05
    Median (IQR)                                             27.50 (24.0 – 35.0)          26.0 (23.0 – 36.0)
 Beck Anxiety Scale
    Low anxiety                                                     6 (13%)                     5 (12.2%)
    Moderate anxiety                                               30 (65.2%)                24 (58.5%)             0.654        >0.05
    Potentially concerning level of anxiety                        10 (21.7%)                12 (29.3%)
 Beck Depression Score
    Min. – Max.                                                    1.0 – 36.0                   6.0 – 33.0
    Mean ± SD.                                                    20.39 ± 8.02               16.73 ± 6.29           2.347        <0.05
    Median (IQR)                                                19.0 (15.0 – 26.0)        16.0 (11.0 – 20.0)
 Beck Depression Scale
    Ups and downs are normal                                        3 (6.5%)                    6 (14.6%)
    Mild depression                                                11 (23.9%)                15 (36.6%)
    Border line depression                                         13 (28.3%)                11 (26.8%)
                                                                                                                    5.402        0.349
    Moderate depression                                            13 (28.3%)                   7 (17.1%)
    Severe depression                                              5 (10.9%)                    2 (4.9%)
    Extreme depression                                              1 (2.2%)                    0 (0.0%)

IQR = interquartile range; SD = standard deviation.




          Table 4. Comparison between the two studied groups regarding serum Brain-Derived
                                       Neurotrophic Factor.
       Serum BDNF                  Cases (N = 46)           Control (N = 41)           U- Mann Whitney                       P
 Min. – Max.                         0.31 – 7.68                 0.47 – 7.18
 Mean ± SD.                          0.85 ± 1.07                 1.07 ± 1.26                    688.50*                 <0.05*
 Median (IQR)                     0.65 (0.58 – 0.71)        0.73 (63.0 – 81.0)

BDNF = Brain-Derived Neurotrophic Factor; IQR = Inter quartile range; SD: Standard deviation.




    Table 5. Validity for serum Brain-Derived Neurotrophic Factor to discriminate patients (N = 46)
                                        from control (N = 41).
                           AUC          P              95% CI            Cut off      Sensitivity     Specificity     PPV        NPV
 Serum BDNF               0.635      0.030         0.517 – 0.753         ≤0.714          76.09            56.10       66.0       67.6

AUC = Area Under the Curve; BDNF = Brain-Derived Neurotrophic Factor; CI: confidence intervals; NPV = negative predictive value;
PPV = positive predictive value.




6                                                                         Original Article | Dermatol Pract Concept. 2023;13(3):e2023139
                                                                 contains progesterone with a high androgenic potential such
                                                                 as norethindrone [14].
                                                                    Bienenfeld and his colleagues stated that androgens are
                                                                 important in the incidence of FPHL and acne. They had es-
                                                                 sential but inadequate role in the development of, acne, and
                                                                 FPHL in women [15].
                                                                    Regarding hirsutism, the signs of virilization and Men-
                                                                 strual irregularity in our study there was no statistically
                                                                 significant difference regarding between the patient group
                                                                 and the control. Carmina and his colleagues suggest that
                                                                 FPHL may be evident in the absence of other signs of
                                                                 hyperandrogenism, as it may be related to many factors,
                                                                 including genetic influences, androgen sensitivity and lev-
                                                                 els, and perhaps inflammation in the scalp [3]. Scalp scal-
                                                                 ing was significantly statistically higher than the control
Figure 1. Receiver operating characteristic curve for serum
Brain-Derived Neurotrophic Factor to discriminate patients       group (p-value ≤ 0.05). This can be interpreted by that the
(N = 46) from control (N = 41).                                  hair follicle miniaturization and apoptosis occurring in
                                                                 FPHL are often associated with micro-inflammation. This
                                                                 micro-inflammation causes destruction of the erector pili
Table 6. Correlation between Serum BDNF and                      muscle and sebaceous gland hyperplasia. This led to an
 different parameters in cases group (N = 46).                   oily surface and scalp inflammation in form of seborrheic
          Serum BDNF vs.                       rs          P     dermatitis. Hence, FPHL usually coexists with seborrheic

 Age (years)                                 0.038       >0.05   dermatitis [16,17].
                                                                    In our study there was a statistically significantly higher
 Age of onset of FPHL                        -0.072      >0.05
                                                                 family history in the patient group (p value ≤ 0.001). Fam-
 Duration in years                           0.293       <0.05
                                                                 ily history is an important risk factor for an early onset
 Sinclair hair density scale                 0.036       >0.05
                                                                 FPHL [18]. Our findings were in accordance with Lukasik
 FPHL score                                  -0.050      >0.05
                                                                 and his colleagues who revealed that a positive history
 Perceived Stress Scale                      -0.336      0.001
                                                                 on the mother side is of great importance for FPHL inci-
 Beck Anxiety Score                          -0.336      <0.05   dence. Hair loss in more than one family member and in
 Beck Depression Score                       -0.328      <0.05   one grandparents may also indicate a higher risk of disease
 DLQI Score                                  0.228       >0.05   development [19].
                                                                    In the current study the Hair Pull test, Sinclair Hair Shed-
BDNF = Brain-Derived Neurotrophic Factor; DLQI = Dermatology
Life Quality Index; FPHL = Female Pattern Hair Loss.             ding Scale, Sinclair Hair Density Scale, FPHL Severity Index
                                                                 scale and FPHL Severity Index score were statistically signif-
                                                                 icant a higher in the patient group (P value ≤ 0.001).
  Table 7. Correlation between Female Pattern                       FPHL has a negative psychological effect on the patients.
  Hair Loss Severity Index Score and different                   It includes stress, depression and anxiety which are also im-
      parameters in cases group (N = 46).                        portant causes of telogen effluvium.
                                           FPHL score               Brenner and Oldoni in their study reported that telo-
                                         R                P      gen effluvium may be the initial symptom in patients with
                                                                 FPHL [20].
 Age (years)                           0.630           <0.001
                                                                    In the patient group the Perceived Stress Scale and Beck
 Age of onset of FPHL                  0.501           <0.001
                                                                 Depression was a statistically significantly higher than the
 Duration in years                     0.535           <0.001
                                                                 control group (P value ≤ 0.05).
 Sinclair Hair Density Scale           0.661           <0.001
                                                                    This may be due to that the low self-steam and negative
 Perceived Stress Scale                0.006           >0.05
                                                                 body image caused by FPHL lead to deep psychological im-
 Beck Anxiety Score                   -0.034           >0.05
                                                                 pact such as anxiety, stress and depression [3].
 Beck Depression Score                 0.117           >0.05        Our findings agree with Camacho and García-Hernández
 DLQI Score                           -0.008           >0.05     who found that AGA patients have personality changes in

DLQI = Dermatology Life Quality Index; FPHL = Female Pattern     general and that Depression was higher in female 55% with
Hair Loss.                                                       AGA [21].



Original Article | Dermatol Pract Concept. 2023;13(3):e2023139                                                                7
    Table 8. Univariate and multivariate Logistic regression analysis for the parameters affecting cases
                                           (N = 46 versus. 41).
                                                                                                        #
                                                             Univariate                                     Multivariate
                                                    P               OR (95%CI)                  P                 OR (95%CI)
 Age (years)                                       0.075       1.047 (0.995 – 1.101)
 Presence of diet changes                          0.165       0.206 (0.022 – 1.919)
 Presence of hirsutism                             0.309       1.947 (0.540 – 7.023)
 Presence of hormonal acne                         0.018      12.571 (1.544 –102.33)           0.165        8.642 (0.412 – 181.091)
 Presence of menstrual irregularity                0.166       2.263 (0.713 – 7.182)
 Scalp
     Presence of itching                           0.190       1.896 (0.729 – 4.936)
     Presence of scaling                           0.025       2.696 (1.131 – 6.427)           0.898         0.879 (0.121 – 6.377)
 Presence of family history of FPHL              <0.001       16.528 (5.570 –49.046)         <0.001         27.072(5.532 –132.498)
 Presence of Hair Pull test                        0.003      7.425 (1.985 – 27.771)           0.023         7.677 (1.319 – 44.696)
 Increasing in Sinclair Hair Shedding              0.189       0.664 (0.360 – 1.223)
 Scale
 Increasing in Sinclair Hair Density Scale         0.999                  –
 Increasing in FPHL score                          0.990                  –
 Increasing in Perceived Stress Scale              0.006       1.108 (1.029 – 1.192)           0.197         1.082 (0.960 – 1.221)
 Increasing in Beck Anxiety Score                  0.977       0.999 (0.951 – 1.050)
 Increasing in Beck Anxiety Scale                  0.518       0.793 (0.393 – 1.602)
 Increasing in Beck Depression Score               0.026       1.074 (1.009 – 1.144)           0.270         0.915 (0.781 – 1.071)
 Increasing in Beck Depression Scale               0.023       1.577 (1.066 – 2.332)           0.103         2.229 (0.851 – 5.838)
 Increasing in Serum BDNF                          0.625       0.911 (0.627 – 1.324)

BDNF = Brain-Derived Neurotrophic Factor; CI = Confidence interval; FPHL = Female Pattern Hair Loss; LL = Lower limit; OR = odds
ratio; UL = Upper Limit.




     Regarding to quality of life most patient had impaired            FPHL acts as a source of depression and chronic stress
Dermatology Life Quality Index.                                     which leads to decrease in circulating BDNF concentration
     This may be caused by psychosocial problems in patients        in case group [2].
with FPHL, due to low self-esteem, altered self-image leading          On the contrary, Pancrateep and his colleagues found
to depression, and less frequent positive social engagements.       that in late male androgenic alopecia, mesenchymal dermal
     Patients with AGA usually do alter their behavior peculiarly   papillae cells of the balding scalp follicles produced about
due to hair loss. Some patients use diverse haircuts or wash        12-fold more BDNF than those from the nonbalding scalp.
their hair more frequent in order to gain more volume [22].         They stated that the BDNF may be essential in mediating the
Our study agrees with Shilpashree and his colleagues who            impact of androgens on the hair follicles, acting as a negative
found that most patients of FPHL suffer from moderate to            regulatory factor [6].
severe psychosocial impact [23].                                       This may be due to local production of BDNF by fibro-
     In our study the patient group serum level of BDNF             blasts in the skin and T-lymphocytes may also produce neu-
was statistically significantly lower than the control group        rotrophies in the skin [12].
(P value < 0.05).                                                      In our study, there was statistically significant negative
     This can be interpreted by the relation between BDNF           correlation regarding serum BDNF with Perceived Stress
levels and major depressive disorders, anxiety related disor-       Scale, Beck Anxiety Score and Beck Depression Score respec-
ders, response to stressful events, and neurodevelopmental          tively (P value ≤ 0.05).
disorders. Most of these studies showed decreased BDNF                 Various studies have studied the link between BDNF
                                         12
levels with these psychiatric disorders.                            levels and psychological disorders like major depression,




8                                                                         Original Article | Dermatol Pract Concept. 2023;13(3):e2023139
   Table 9. Univariate and multivariate linear regression analysis for the parameters affecting serum
                                   BDNF in cases group (N = 46).
                                                                                                          #
                                                                 Univariate                                   Multivariate
                                                        P               B (95%CI)                 P                 B (95%CI)
 Age (years)                                          0.383      0.014 (-0.019 – 0.048)
 Presence of diet changes                             0.976      0.033 (-2.173 – 2.240)
 Presence of hirsutism                                0.575      -0.237 (-1.083 – 0.608)
 Presence of hormonal acne                            0.504      -0.251 (-1.001 – 0.499)
 Presence of menstrual irregularity                   0.478      -0.266 (-1.016 – 0.484)
 Scalp
   Presence of itching                                0.723      -0.119 (-0.794 – 0.555)
   Presence of scaling                                0.108      -0.521 (-1.161 – 0.119)
 Age of onset of FPHL                                 0.968      -0.001 (-0.040 – 0.038)
 Duration of FPHL in years                            0.009        0.117 (0.031 – 0.204)       0.362          0.030 (-0.036 – 0.096)
 Presence of family history of FPHL                   0.643      0.169 (-0.562 – 0.900)
 Presence of Hair Pull test                           0.275      -0.361 (-1.018 – 0.297)
 Increasing in Sinclair Hair Shedding Scale           0.252      -0.315 (-0.863 – 0.232)
 Increasing in Sinclair Hair Density Scale            0.957      0.016 (-0.569 – 0.601)
 Increasing in FPHL score                             0.983      0.001 (-0.127 – 0.130)
 Increasing in Perceived Stress Scale                 0.010      -0.068 (-0.118 – -0.017)      0.872          0.003 (-0.038 – 0.044)
 Increasing in Beck Anxiety Score                     0.005      -.059 (-0.099 – -0.019)       0.080          -0.039 (-0.082 – 0.005)
 Increasing in Beck Anxiety Scale                     0.011      -0.675 (-1.187 – -0.163)      0.948          -0.017 (-0.554 – 0.519)
 Increasing in Beck Depression Score                  0.009      -.080 (-0.140 – -0.021)       0.011       -0.044 (-0.078 – -0.011)
 Increasing in DLQI                                   0.561      -0.019 (-0.084 – 0.046)
 Increasing in Beck Depression Scale                  0.024      -0.301 (-0.560 – -0.042)      0.738          -0.038 (-0.267 – 0.191)

B = Unstandardized Coefficients; BDNF = Brain-Derived Neurotrophic Factor; CI = Confidence interval; DLQI = Dermatology Life Quality
Index; FPHL = Female Pattern Hair Loss; LL = Lower limit; UL = Upper Limit.




anxiety-related disorders, chronic stress, and neurodevel-            a significant association between decreased serum BDNF
opmental disorders. The vast majority have reported that              levels and FPHL. BDNF may be an etiologic factor in its
the development of the psychiatric diseases is associated             progression.
with deficient BDNF levels. Furthermore, other studies have
demonstrated that sufficient effective treatment improves the         Limitations of this Study
BDNF level of such patients [24].
    In this study there were high statistically significant cor-      Was the lack of estimation of the tissue BDNF level in the
relations between FPHL Score and age of patients, age of              balding scalp. Further studies are needed to investigate
onset of FPHL, FPHL duration and Sinclair Hair Density                BDNF in both serum and skin.
Scale (P value ≤ 0.001). This may be related that woman
with advancing age, there is gradually declines female sex
                                                                      References
hormones (progesterone and estrogen) and this may explain
the unopposed increase of the negative impact of androgens             1. Tamashunas NL, Bergfeld WF. Male and female pattern hair loss:
                                                                          Treatable and worth treating. Cleve Clin J Med. 2021;88(3):
effect on the hair follicles [25].
                                                                          173-182. DOI: 10.3949/ccjm.88a.20014. PMID: 33648970.
    Patients suffering from FPHL have a high risk to develop
                                                                       2. Davis DS, Callender VD. Review of quality of life studies in
chronic stress, anxiety and depression. The serum level of                women with alopecia. Int J Womens Dermatol. 2018;4(1):18-22.
BDNF acts as a good predictor for assessment of negative                  DOI: 10.1016/j.ijwd.2017.11.007. PMID: 29872671. PMCID:
psychological affection in such patients. We suggest that                 PMC5986111.




Original Article | Dermatol Pract Concept. 2023;13(3):e2023139                                                                          9
 3. Carmina E, Azziz R, Bergfeld W, et al. Female Pattern Hair Loss            pathophysiologic, and therapeutic review. Int J Women Der-
    and Androgen Excess: A Report From the Multidisciplinary An-               matol. 2018;4(4):203-211. DOI: 10.1016/j.ijwd.2018.05.001.
    drogen Excess and PCOS Committee. J Clin Endocrinol Metab.                 PMID: 30627618. PMCID: PMC6322157.
    2019;104(7):2875-2891. DOI: 10.1210/jc.2018-02548. PMID:             15.   Bienenfeld A, Azarchi S, Lo Sicco K, Marchbein S, Shapiro J,
    30785992.                                                                  Nagler AR. Androgens in women: Androgen-mediated
 4. Kashyap MP, Roberts C, Waseem M, Tyagi P. Drug Targets in                  skin disease and patient evaluation. J Am Acad Dermatol.
    Neurotrophin Signaling in the Central and Peripheral Nervous               2019;80(6):1497-1506. DOI: 10.1016/j.jaad.2018.08.062.
    System. Mol Neurobiol. 2018;55(8):6939-6955. DOI: 10.1007                  PMID: 30312644.
    /s12035-018-0885-3. PMID: 29372544. PMCID: PMC7444275.               16.   Pekmezci E, Dundar C, Turkoglu M. Proprietary Herbal Extract
 5. Peters EM, Hansen MG, Overall RW, et al. Control of human                  Downregulates the Gene Expression of IL-1α in HaCaT Cells:
    hair growth by neurotrophins: brain-derived neurotrophic fac-              Possible Implications Against Nonscarring Alopecia. Med Arch.
    tor inhibits hair shaft elongation, induces catagen, and stimu-            2018;72(2):136-140. DOI: 10.5455/medarh.2018.72.136-140.
    lates follicular transforming growth factor beta2 expression.              PMID: 30302033. PMCID: PMC6126931.
    J Invest Dermatol. 2005;124(4):675-685. DOI: 10.1111/j.0022-         17.   Ramos PM, Brianezi G, Martins AC, da Silva MG, Marques ME,
    202X.2005.23648.x. PMID: 15816823.                                         Miot HA. Apoptosis in follicles of individuals with female
 6. Panchaprateep R, Korkij W, Asawanonda P. Brain-derived                     pattern hair loss is associated with perifollicular microinflam-
    nerve factor and neurotrophins in androgenetic alopecia.                   mation. Int J Cosmet Sci. 2016;38(6):651-654. DOI: 10.1111
    Br J Dermatol. 2011;165(5):997-1002. DOI: 10.1111/j.1365                   /ics.12341. PMID: 27163333
    -2133.2011.10514.x. PMID: 21729031.                                  18.   Zhang X, Caulloo S, Zhao Y, Zhang B, Cai Z, Yang J. Female
 7. Harries M, Tosti A, Bergfeld W, et al. Towards a consensus on              pattern hair loss: clinico-laboratory findings and trichoscopy de-
    how to diagnose and quantify female pattern hair loss - The                pending on disease severity. Int J Trichology. 2012;4(1):23-28.
    ‘Female Pattern Hair Loss Severity Index (FPHL-SI)’. J Eur                 DOI: 10.4103/0974-7753.96082. PMID: 22628986. PMCID:
    Acad Dermatol Venereol. 2016;30(4):667-676. DOI: 10.1111                   PMC3358934.
    /jdv.13455. PMID: 26676524.                                          19. Łukasik A, Kozicka K, Kłosowicz A, Jaworek A, Wojas-Pelc A.
 8. García-Batista ZE, Guerra-Peña K, Cano-Vindel A,                         The role of family history and its influence on the onset
    Herrera-Martínez SX, Medrano LA. Validity and reliabil-                  time in female pattern hair loss. Postepy Dermatol Alergol.
    ity of the Beck Depression Inventory (BDI-II) in general and             2021;38(5):815-818. DOI: 10.5114/ada.2020.100745. PMID:
    hospital population of Dominican Republic. PLoS One.                     34849129. PMCID: PMC8610059.
    2018;13(6):e0199750. DOI: 10.1371/journal.pone.0199750.              20. Brenner FM, Oldoni C. Telogen effluvium x female pattern hair
    PMID: 29958268. PMCID: PMC6025862.                                       loss: is there correlation? An Bras Dermatol. 2019;94(4):486-
 9. Kaviani H, Mousavi AS. Psychometric Properties of the Persian            487. DOI: 10.1590/abd1806-4841.20198427. PMID: 31644631.
    Version of Beck Anxiety Inventory (BAI). Tehran University               PMCID: PMC7007028.
    Medical Journal. 2008;66(2),136-140.                                 21. Camacho FM, García-Hernández M. Psychological features
10. Cohen S, Kamarck T, Mermelstein R. Perceived stress scale.               of androgenetic alopecia. J Eur Acad Dermatol Venereol.
    J Health Soc Behav. 1983;24(4):385-396. PMID: 6668417.                   2002;16(5):476-480. DOI: 10.1046/j.1468-3083.2002.00475.x.
11. Shikiar R, Harding G, Leahy M, Lennox RD. Minimal important              PMID: 12428841.
    difference (MID) of the Dermatology Life Quality Index (DLQI):       22. Chan L, Cook DK. Female pattern hair loss. Aust J Gen Pract.
    results from patients with chronic idiopathic urticaria. Health          2018;47(7):459-464. DOI: 10.31128/AJGP-02-18-4498. PMID:
    Qual Life Outcomes. 2005;3:36. DOI: 10.1186/1477-7525-3-                 30114864.
    36. PMID: 1590721.; PMCID: PMC1180464.                               23. Shilpashree P, Syrti Clarify, Ak Jaiswal, Shashidhar T. Impact of
12. Yanik ME, Erfan G, Albayrak Y, Aydin M, Kulac M, Kuloglu M.              female pattern hair loss on the quality of life of patients J Pak
    Reduced serum brain-derived neurotrophic factor in patients              Assoc Dermatol. 2016;26(4):347-352.
    with first onset vitiligo. Neuropsychiatr Dis Treat. 2014;10:2361-   24. Autry AE, Monteggia LM. Brain-derived neurotrophic factor
    2367. DOI: 10.2147/NDT.S74826. PMID: 25540586. PMCID:                    and neuropsychiatric disorders. Pharmacol Rev. 2012;64(2):238-
    PMC4270357.                                                              528. DOI: 10.1124/pr.111.005108. PMID: 22407616. PMCID:
13. Botchkarev VA, Yaar M, Peters EM, et al. Neurotrophins in skin           PMC3310485.
    biology and pathology. J Invest Dermatol. 2006;126(8):1719-          25. Redler S, Messenger AG, Betz RC. Genetics and other fac-
    1727. DOI: 10.1038/sj.jid.5700270. PMID: 16845411.                       tors in the aetiology of female pattern hair loss. Exp Derma-
14. Fabbrocini G, Cantelli M, Masarà A, Annunziata MC,                       tol. 2017;26(6):510-517. DOI: 10.1111/exd.13373. PMID:
    Marasca C, Cacciapuoti S. Female pattern hair loss: A clinical,          28453904.




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