Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 1 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 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. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 Introduction Female Pattern Hair Loss (FPHL) is a common cause of 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 which is characterized by a short anagen phase and increased vellus hairs [1]. In general, alopecia is known to be associated with many psychiatric comorbidities such as depression, anxiety, personality disorders, and drug abuse. Moreover, patients with alopecia have noticeably higher suicidal rates and get hospitalized for mental health diseases. Regarding specific types of hair loss, FPHL may be linked to many psychiatric comorbidities, especially in patients with extensive scalp af- fection [2]. FPHL may lead to depression and decreased life quality, poor self-esteem, and negative body image [3]. Brain-Derived Neurotrophic Factor (BDNF) is a member of the neurotrophins family which is known for its action on the growth of central and peripheral nerves. Neurotro- phins show a variety of immunomodulatory impacts on non-neuronal cells especially mast cells, keratinocytes, and eosinophils [4]. BDNF controls human hair growth via tropomyo- sin receptors (TrkB). BDNF markedly decreases hair shaft elongation, promotes premature catagen, and decreases ke- ratinocyte proliferation [5]. Panchaprateep et al postulated that BDNF may be essen- tial in exerting the androgens impacts on hair follicles act- ing as a negative regulatory factor. This study showed that balding scalp follicles produced 12-fold more BDNF than the nonbalding scalp [6]. Objectives This study evaluates serum BDNF levels in patients with FPHL. We suggest that there may association between serum BDNF levels and FPHL. Therefore, we aimed to evaluate the levels of serum BDNF in patients with FPHL and correlate its level to both the de- gree of psychological impact and the severity of alopecia. Methods The present case-control study included 46 female patients with FPHL and 41 age-matched healthy female volunteers. The patients were recruited from the Dermatology, STDs, and Andrology Department Clinic, during the period be- tween May 2021 to August 2021. All included individuals, or their families provided an in- formed written agreement to be included in the study. This study was conducted according to the Declaration of Hel- sinki and the protocol approved by the ethics committee of Würzburg University and by the Institutional Review Board of the Faculty of Medicine, Fayoum University (IRB number IRB00003613) in January 2018. An informed written Arabic consent form was signed by every participant in the presence of one of the authors. Patients Female patients 15-50 years old complaining of AGA were included in this study. Patients were diagnosed and classified according to Female Pattern Hair Loss Severity Index [7]. We exclude patients suffering from any systemic or cu- taneous diseases other than FPHL. We also exclude patients with a past or present history of psychiatric illness or receiv- ing any regular psychotropic medication, antidepressants were also excluded. Pregnant and lactating women were ex- cluded from the study. Control Forty-one healthy female volunteers 15-50 years old were included in the study as a control. Study Design All subjects were subjected to a Full history taking and clin- ical examination. 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. Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 3 The patients were diagnosed and classified according to FPHL Severity Index [7]. Questionnaires to access the psychological state for all participants were done including Beck Depression Inven- tory, Beck Anxiety Inventory and Perceived Stress (PSS) Scale [8-10]. DLQI was done for the patient group only [11]. The serum level of BDNF was measured for all subjects using ELISA kits which were provided by biodiagnostic kits (Sun red Biological Technology Company). Five ml of blood were collected from the antecubital vein by venipuncture and left for 30 minutes at room temperature to allow clotting and then centrifuged for 15 minutes at 3000 rpm. Serum was separated, stored in an Eppendorf tube and kept at −20°C until used for measurement of BDNF level. Each female was subjected to full history, measurement of serum level of BDNF using ELISA technique. Statistical Analysis Chi-square test was used for categorical variables, to compare between different groups. Fisher Exact test or Monte Carlo correction were used for correction for chi-square when more than 20% of the cells have expected count less than 5. Student t-test was used for normally distributed quantitative variables, to compare between two studied groups. Mann Whitney test was used for not normally distributed quanti- tative variables, to compare two studied groups. Spearman coefficient was used to correlate between two distributed not normally quantitative variables. Kruskal Wallis test was used for not normally distrib- uted quantitative variables, to compare between more than two studied groups. Receiver operating characteristic curve (ROC) is generated by plotting sensitivity (TP) on Y axis ver- sus 1-specificity (FP) on X axis at different cut off values. The area under the ROC curve denotes the diagnostic performance of the test. Area more than 50% gives acceptable performance and area about 100% is the best performance for the test. The ROC curve allows also a comparison of performance between two tests. Logistic Regression analysis was used to detect the most independent/ affecting factor for affecting cases. Linear Regression analysis was used to detect the most independent/ affecting factor for affecting Serum BDNF. Results This case-control study included 87 females, 46 female pa- tients suffering from FPHL, and 41 age-matched healthy fe- male subjects as a control. The participants were recruited from the Dermatology, STDs, and Andrology Department Clinic. The patients were diagnosed and classified according to FPHL Severity Index. Patient Group Included 46 female patients, their ages ranged from 15 to 50 years old with a Mean ± SD (29.85 ± 9.73) with a median (IQR) of 29.50 (22.0 - 38.0). Control Group Included 41 healthy females, their ages ranged from 20 – 51 years with a Mean ± SD (26.44 ± 7.38) with median (IQR) 26.0 (19.0 – 32.0). There was no statistically significant dif- ference (P value ≤ 0.05) between both groups. In the patient group 34 patients (73.9%) had positive family history of FPHL, while in the control group only 6 patients (14.9%) had positive family history. Diet changes was reported in one patient (2.2%) in the patient group, while 4 individuals (9.8%) in the control group have diet change (Table 1). Clinical Parameters of the Studied Groups In the patient group acne was reported in 11 patient (23.9%), while only 1 individual (2.4%) in the control group have acne. There was a high statistically significant difference re- garding presence of acne between the case and the control 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 4 Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 (P <0.001) between serum BDNF and Beck Anxiety Score, Beck Depression Score and a high statistically significant negative correlation (P < 0.001) regarding PSS (Table 6). Correlation Between FPHL Severity Index Score and Different Parameters in Patient Group There were high statistically significant positive correlations between FPHL Severity Index Score and age of patients, age of onset, duration of the FPHL and Sinclair Hair Density Scale (P value ≤ 0.001) (Table 7). The univariate logistic regression analysis for the parameters affecting cases showed that there were sta- tistically significant relations (P value ≤ 0.05) regarding presence of hormonal acne, presence of scaling, presence of Hair Pull test, increasing in the Perceived Stress Scale, increasing in the Beck Depression Score and increasing in the Beck Depression Scale. There was high statistically sig- nificant relation (p value ≤ 0.001) regarding presence of family history of FPHL. The multivariate logistic regres- sion analysis showed that there was a high statistically significant relation (P value ≤ 0.001) regarding presence of family history of FPHL. There was a statistically sig- nificant relation (P value ≤ 0.05) regarding Hair Pull test (Table 8). The univariate logistic regression analysis for the pa- rameters affecting serum level of BDNF in the case group (n = 46 vs. 41) showed that there were statistically signifi- cant relations (P value ≤ 0.05) regarding duration of FPHL, increasing in Perceived Stress Scale, increasing in Beck Anx- iety Score, increasing in Beck Anxiety Scale, increasing in Beck Depression Score and increasing in Beck Depression Scale. The multivariate Logistic regression analysis showed that there was a statistically significant relation (P value ≤ 0.05) regarding increasing in Beck Depression Score (Table 9). Conclusions Neurotrophins including BDNF and their receptors have role in skin hemostasias and hair growth [12]. Botchkarev et al reviewed that stress may induced hair loss, psoriasis, and other skin diseases. BDNF is a member of a family of neurotrophins [13]. This study aimed to 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. Our study included (87) female subjects that were di- vided into two groups; Group A (case group): included 46 female patients with FPHL while group B (control group): included 41 age matched healthy female volunteers as con- trol group. Regarding Hirsutism of the studied patients 8 patient (17.4%) had Hirsutism, while in the control group Hirsut- ism was reported in 4 patient (9.8%). Signs of virilization was not reported in patients and controls. There was no sta- tistically significant difference regarding Hirsutism, the signs of virilization and menstrual irregularity (Table 1). Local Examination of the Scalp of the Studied Groups Scalp itching and soreness were reported in 34.8%, and 10.9% of the patients while in 22% and 0% in the control group respectively with no statistically significant difference. Scalp scaling was significantly statistically higher than the control group (P ≤ 0.05). There was a high statistically significant difference (P = 0.001) regarding hair pull test, Sin- clair hair shedding scale, Sinclair hair density scale, FPHL severity index scale and FPHL severity index score between the case group and the control group (Table 2). Comparison Between the Two Studied Groups as Regards to the Psychological State In the patient group PSS and Beck Depression was statisti- cally significantly higher than the control group (P ≤ 0.05), while the Score Beck Depression Scale showed no statisti- cally significant difference. Regarding Beck Anxiety Score and Scale showed no sta- tistically significant difference between both groups (P value > 0.05) (Table 3). Analysis of the Dermatology Life Quality Index in the Patient Group Only 2 cases (4.3%) had no effect on patient life, 9 cases (19.6%) with minor effect on patient’s life, 20 cases (43.5%) with moderate effect on patients life, 10 cases with very great impact on patient life and 5 cases (10.9%) with extreme im- pact on patient life respectively. Serum BDNF in the Studied Groups In the patient group serum level of BDNF was statistically significantly lower than the control group (P value < 0.05). In patients mean ± SD was 0.85 ± 1.07, while in the controls was 1.07 ± 1.26 (Table 4). The cut off point for serum BDNF to discriminate pa- tients from control was ≤ 0.714. The sensitivity was 76.09 and the specificity was 56.10 (Table 5 and Figure 1). Correlation Between Serum BDNF and Different Parameters in Patients Group There were statistically significant positive correlations (P ≤ 0.05) between serum BDNF and FPHL duration, while there was a statistically significant negative correlation Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 5 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= 25.839 <0.001 Mean ± SD. 11.09±2.53 0.78±0.91 Mean±SD 11.09±2.53 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 serum level of BDNF and Questionnaires to access the psy- chological state. Quality of life was accessed in the patient group only. The patients were diagnosed and classified according to FPHL Severity Index [7]. The cases age ranged from 15 to 50 years with a mean of 29.85 ± 9.73, while the control age ranged from 15 to 41 years with a mean of 26.44 ± 7.38. We selected this age group as androgen effects in addition to cos- metic concerns are marked during this age group. There was no statistically significant difference regarding age between the case and control groups as they were age matched. There was a high statistically significant difference re- garding presence of acne between the case and the control groups (P value ≤ 0.05). This is due to that Female Pattern Hair Loss and hor- monal acne can be due to androgen receptors hypersen- sitivity to circulating dihydrotestosterone or coexisted hyperandrogenic status such as virializing tumor, polycystic ovarian syndrome, or those on oral contraceptive pills that 6 Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 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. 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 2.939 <0.05 Mean ± SD. 25.17 ± 5.96 21.27 ± 6.44 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 0.028 >0.05 Mean ± SD. 28.83 ± 8.09 28.88 ± 9.18 Median (IQR) 27.50 (24.0 – 35.0) 26.0 (23.0 – 36.0) Beck Anxiety Scale Low anxiety 6 (13%) 5 (12.2%) 0.654 >0.05 Moderate anxiety 30 (65.2%) 24 (58.5%) Potentially concerning level of anxiety 10 (21.7%) 12 (29.3%) Beck Depression Score Min. – Max. 1.0 – 36.0 6.0 – 33.0 2.347 <0.05 Mean ± SD. 20.39 ± 8.02 16.73 ± 6.29 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%) 5.402 0.349 Mild depression 11 (23.9%) 15 (36.6%) Border line depression 13 (28.3%) 11 (26.8%) 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 – 7.18 688.50* <0.05*Mean ± SD. 0.85 ± 1.07 1.07 ± 1.26 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. Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 7 Figure 1. Receiver operating characteristic curve for serum Brain-Derived Neurotrophic Factor to discriminate patients (N = 46) from control (N = 41). Table 6. Correlation between Serum BDNF and different parameters in cases group (N = 46). Serum BDNF vs. rs P Age (years) 0.038 >0.05 Age of onset of FPHL -0.072 >0.05 Duration in years 0.293 <0.05 Sinclair hair density scale 0.036 >0.05 FPHL score -0.050 >0.05 Perceived Stress Scale -0.336 0.001 Beck Anxiety Score -0.336 <0.05 Beck Depression Score -0.328 <0.05 DLQI Score 0.228 >0.05 BDNF = Brain-Derived Neurotrophic Factor; DLQI = Dermatology Life Quality Index; FPHL = Female Pattern Hair Loss. Table 7. Correlation between Female Pattern Hair Loss Severity Index Score and different parameters in cases group (N = 46). FPHL score R P Age (years) 0.630 <0.001 Age of onset of FPHL 0.501 <0.001 Duration in years 0.535 <0.001 Sinclair Hair Density Scale 0.661 <0.001 Perceived Stress Scale 0.006 >0.05 Beck Anxiety Score -0.034 >0.05 Beck Depression Score 0.117 >0.05 DLQI Score -0.008 >0.05 DLQI = Dermatology Life Quality Index; FPHL = Female Pattern Hair Loss. 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 group (p-value ≤ 0.05). This can be interpreted by that the hair follicle miniaturization and apoptosis occurring in FPHL are often associated with micro-inflammation. This micro-inflammation causes destruction of the erector pili muscle and sebaceous gland hyperplasia. This led to an oily surface and scalp inflammation in form of seborrheic dermatitis. Hence, FPHL usually coexists with seborrheic dermatitis [16,17]. In our study there was a statistically significantly higher family history in the patient group (p value ≤ 0.001). Fam- ily history is an important risk factor for an early onset FPHL [18]. Our findings were in accordance with Lukasik and his colleagues who revealed that a positive history on the mother side is of great importance for FPHL inci- dence. Hair loss in more than one family member and in one grandparents may also indicate a higher risk of disease development [19]. In the current study the Hair Pull test, Sinclair Hair Shed- 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). FPHL has a negative psychological effect on the patients. It includes stress, depression and anxiety which are also im- portant causes of telogen effluvium. Brenner and Oldoni in their study reported that telo- gen effluvium may be the initial symptom in patients with FPHL [20]. In the patient group the Perceived Stress Scale and Beck Depression was a statistically significantly higher than the control group (P value ≤ 0.05). This may be due to that the low self-steam and negative body image caused by FPHL lead to deep psychological im- pact such as anxiety, stress and depression [3]. Our findings agree with Camacho and García-Hernández who found that AGA patients have personality changes in general and that Depression was higher in female 55% with AGA [21]. 8 Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 FPHL acts as a source of depression and chronic stress which leads to decrease in circulating BDNF concentration in case group [2]. On the contrary, Pancrateep and his colleagues found that in late male androgenic alopecia, mesenchymal dermal papillae cells of the balding scalp follicles produced about 12-fold more BDNF than those from the nonbalding scalp. They stated that the BDNF may be essential in mediating the impact of androgens on the hair follicles, acting as a negative regulatory factor [6]. This may be due to local production of BDNF by fibro- blasts in the skin and T-lymphocytes may also produce neu- rotrophies in the skin [12]. In our study, there was statistically significant negative correlation regarding serum BDNF with Perceived Stress Scale, Beck Anxiety Score and Beck Depression Score respec- tively (P value ≤ 0.05). Various studies have studied the link between BDNF levels and psychological disorders like major depression, Regarding to quality of life most patient had impaired Dermatology Life Quality Index. This may be caused by psychosocial problems in patients with FPHL, due to low self-esteem, altered self-image leading to depression, and less frequent positive social engagements. Patients with AGA usually do alter their behavior peculiarly due to hair loss. Some patients use diverse haircuts or wash their hair more frequent in order to gain more volume [22]. Our study agrees with Shilpashree and his colleagues who found that most patients of FPHL suffer from moderate to severe psychosocial impact [23]. In our study the patient group serum level of BDNF was statistically significantly lower than the control group (P value < 0.05). This can be interpreted by the relation between BDNF levels and major depressive disorders, anxiety related disor- ders, response to stressful events, and neurodevelopmental disorders. Most of these studies showed decreased BDNF levels with these psychiatric disorders.12 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 Scale 0.189 0.664 (0.360 – 1.223) 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. Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 9 a significant association between decreased serum BDNF levels and FPHL. BDNF may be an etiologic factor in its progression. Limitations of this Study Was the lack of estimation of the tissue BDNF level in the balding scalp. Further studies are needed to investigate BDNF in both serum and skin. References 1. Tamashunas NL, Bergfeld WF. Male and female pattern hair loss: Treatable and worth treating. Cleve Clin J Med. 2021;88(3): 173-182. DOI: 10.3949/ccjm.88a.20014. PMID: 33648970. 2. Davis DS, Callender VD. Review of quality of life studies in women with alopecia. Int J Womens Dermatol. 2018;4(1):18-22. DOI: 10.1016/j.ijwd.2017.11.007. PMID: 29872671. PMCID: PMC5986111. anxiety-related disorders, chronic stress, and neurodevel- opmental disorders. The vast majority have reported that the development of the psychiatric diseases is associated with deficient BDNF levels. Furthermore, other studies have demonstrated that sufficient effective treatment improves the BDNF level of such patients [24]. In this study there were high statistically significant cor- relations between FPHL Score and age of patients, age of onset of FPHL, FPHL duration and Sinclair Hair Density Scale (P value ≤ 0.001). This may be related that woman with advancing age, there is gradually declines female sex hormones (progesterone and estrogen) and this may explain the unopposed increase of the negative impact of androgens effect on the hair follicles [25]. Patients suffering from FPHL have a high risk to develop chronic stress, anxiety and depression. The serum level of BDNF acts as a good predictor for assessment of negative psychological affection in such patients. We suggest that 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. 10 Original Article | Dermatol Pract Concept. 2023;13(3):e2023139 pathophysiologic, and therapeutic review. 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