Comparative study between the efficacy and safety of topical sildenafil citrate solution and topical minoxidil 5%in the treatment of female pattern hair loss .

Comparative study between the efficacy and safety of topical sildenafil citrate solution and topical minoxidil 5%in the treatment of female pattern hair loss . | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative study between the efficacy and safety of topical sildenafil citrate solution and topical minoxidil 5%in the treatment of female pattern hair loss . Heba Abdo Mostafa, Hassan Abou Khodair Mohammed, Ibrahim Fouda This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2281439/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Female pattern hair loss (FPHL) is a nonscarring progressive thinning of hair with gradual decrease in it's number , especially in the frontal, central, and parietal scalp. the loss of terminal hairs in affected areas is usually incomplete and the frontal hairline is often spared. It is caused by follicular miniaturization, a process that gradually reduces the proportion of terminal to vellus hair . Aim of the work : to evaluate the efficacy and safety of topical sildenafil citrate 1 % solution in comparison with topical minoxidil 5% foam in the treatment of female pattern hair loss . Patients and methods: This exploratory pilot study included 30 female patients suffering from female pattern hair loss. Included patients were divided into 2 groups ; group1 : received 1% topical sildenafil citrate solution and group2 : received 5% topical minoxidil foam. Assessment of treatment response was done using trichoscopy. Results: In group 1 (treated with topical sildenafil 1%):There was a statistically significant increase in the vellus hair count in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant increase in the terminal hair count in the frontal region and vertex region after treatment as compared to before treatment. There was no statistically significant difference in the hair thickness in all the regions after treatment. , Group 2 (treated with topical minoxidil 5% ) there was a statistically significant increase in the Terminal hair count and hair thickness in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant decrease in the vellus hair count, but it was detected only in the frontal region. Conclusion: topical sildinafil 1% treatment proves to be a good alternative in the treatment of FPHL, although topical minoxidil 5% is still the first choice in FPHL treatment. FPHL Topical Minoxidil Sildenafil Introduction Female pattern hair loss (FPHL) is a nonscarring progressive thinning of hair with gradual decrease in it's number, especially in the frontal, central, and parietal scalp. The loss of terminal hairs in affected areas is usually incomplete and the frontal hairline is often spared. It is caused by follicular miniaturization, a process that gradually reduces the proportion of terminal to vellus hair [ 1 ]. Topical minoxidil is a hair growth stimulator that works by shortening the telogen process of the hair follicles, allowing them to reach the anagen phase prematurely. Minoxidil also prolongs the anagen phase by acting on the potassium channels of vascular smooth muscles and hair follicles, which increases the microcirculation near the hair follicles [ 2 ]. The molecular structure of sildenafil mimics that of cyclic guanosine monophosphate (cGMP), this similarity protects cGMP from degradation because sildenafil can bind to the catalytic site to act as a competitive inhibitor of cGMP-specific PDE-5, the enzyme that normally catalyzes the break down of vasodilatory cGMP[ 3 ]. Phosphodiestrase 5 is highly expressed in human dermal papilla cells (hDPCs) and human hair follicles (hHFs). Sildenafil enhances proliferation of hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and platelet- derived growth factor (PDGF) which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated extre cellular signal regulated kinase (ERK) and accelerates anagen induction by stimulating perifollicular vessel formation [ 4 ]. Patients And Methods This is an exploratory pilot study that was conducted at Al-Azhar University Hospitals' Dermatology, Venereology, and Andrology Department Outpatient Clinics (Damietta). The study included 30 cases with FPHL grade 1 and 2 Ludwig classification . Patients were randomly assigned into two groups: Group I : fifteen patients were subjected topical sildenafil citrate 1%solution ( Standard 1gm sildenafil dissolved in 100 ml ethanol solution to prepare 1% lotion). Twice daily application for 3 months, Group II : fifteen patients were subjected to minoxidil foam 5%(Hair back plus foam ,mina pharma) once daily for 3 months All patients were subjected to the following: full history taking , general examination, Dermatological and dermoscopic examination for grading of female pattern hair loss, Digital photographs were taken clinical & dermoscopic monthly and three months after treatment Assessment by Trichoscopy examination was performed with Derma Light Dl4. Hair loss regions including the vertex, frontal, temporal line and occipital regions were observed. At least 3-4 images were taken with a digital camera that was connected to the dermoscope with the same parameters. Degree of improvement was assessed in females according to the degree of improvement changes in Ludwig classifications . Also the degree of improvement was assessed by comparing the trichoscopic photos before and after treatment as regards hair density, number of terminal to vellus hair and hair thickness. Inclusion criteria: The study included 30 adult female patients between 18 and 45 years with grade 1 or 2 ludwig classification . Exclusion Criteria: Patients who were 45 years old, grade 3 FPHL Ludwig classification, who received systemic or topical treatment for FPHL in the last 6 months prior to the start of the study; who were Pregnant or lactating , who had hormonal disturbance like pco, who have any autoimmune disease, with known history of hypersensitivity to minoxidil or sildenafil, with other types of hair loss either cicatricial or non cicatricial and patients with aneamia, thyroid disease, and vit D deficiency.were excluded from the study Follow up: The follow up was conducted every month during treatment and for 3 months after the completion of treatment Ethical approval: The study was approved by an ethics committee of Damietta Faculty of Medicine IRB (00012367), Al-Azhar University, Egypt. An informed consent was obtained from all participants. Statistical analysis: Data analysis was performed by SPSS software, version 18 (SPSS Inc., PASW statistics for windows version 18. Chicago: SPSS Inc.). Qualitative data were described using number and percent. Quantitative data were described using median (minimum and maximum) for non-normally distributed data and mean± Standard deviation for normally distributed data after testing normality using Kolmogrov-Smirnov test. Significance of the obtained results was judged at the (0.05) level. Chi-Square , Fischer exact test , Monte Carlo tests were used to compare qualitative data between groups as appropriate Student t test was used to compare 2 independent groups for normally distributed data . Paired t test was used to compare 2 paired readings distributed data . The Spearman's rank-order correlation is used to determine the strength and direction of a linear relationship between two non-normally distributed continuous variables and / or ordinal variables. Results 30 cases with FPHL grade 1 and 2 Ludwig classification There were no statistically significant difference in the basic data in the two study groups including age, disease duration, percentage of cases with positive family history and degree of hair loss. There was a statistically significant increase in the Terminal hair count and hair thickness in the group treated with topical minoxidil 5% in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant decrease in the vellus hair count, but it was detected only in the frontal region. There was a statistically significant increase in the vellus hair count in the group treated with topical sildenafil 1% in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant increase in the terminal hair count in the frontal region and vertex region after treatment as compared to before treatment. There was no statistically significant difference in the hair thickness in all the regions after treatment. When comparing the results of the two drugs, minoxidil showed better results compared to sildenafil in terms of higher terminal hair count, thicker hair diameter and decreased number of vellus hair. The effects were more noticed in the frontal region and temporal region and less noticed in the vertex. Furthermore, there was higher degree of patients’ satisfaction in the minoxidil group compared to the sildenafil group, but it didn’t achieve a statistically significant difference. Table (1): Comparison of treatment response at the frontal region between the 2 groups . Topical Sildenafil 1% n=15 Topical Minoxidil 5% n=15 test of significance p- value Vellus hair count 11.33±7.49 -7.53±7.84 6.73 <0.001* Terminal hair count 15.53±8.18 26.87±11.79 3.06 0.005* Hair thickness (mm) 0.001±0.002 0.01±0.004 5.93 <0.001* Z : Mann Whitney test P value ≤0.05 is significant Table (2): Comparison of treatment response at the vertex between the 2 groups. Topical Sildenafil 1% n=15 Topical Minoxidil 5% n=15 test of significance p- value Vellus hair count 1.40±2.2 1.53±2.9 0.138 0.892 Terminal hair count 7.2±11.1 13.60±5.68 1.99 0.057 Hair thickness (mm) 0.002±0.004 0.009±0.007 3.41 0.002* Using Mann Whitney test P value ≤0.05 is significant Table (3): Comparison of treatment response at the temporal side between the 2 groups. . Mean ± SD test-value P value Group 1 (Sildenafil citrate solution 1 %) n=15 Group 2 (Minoxidil foam 5%) n=15 Vellous hair (VH) 3.80±5.40 -6.07±10.91 3.14 0.004* Terminal hair (TH) -1.3±5.84 13.67±6.45 6.67 <0.001* Hair thickness -0.002±0.004 0.009±0.010 3.99 <0.001* ª Using Mann Whitney test P value ≤0.05 is significant Discussion Female pattern hair loss is the most common hair loss disorder in women. Initial symptoms may develop during the teenage years [5]. FPHL is a complex polygenic disorder characterized clinically by diffuse hair thinning over the midfrontal scalp and increased hair shedding [6]. A number of agents have also been used in the treatment of female pattern hair loss including the androgen receptor antagonists spironolactone, cyproterone acetate, and flutamide as well as the 5 a reductase antagonist finasteride and dutasteride. These agents can be used either alone or in combination with topical minoxidil [7]. To the best of our knowledge this is the first study to compare the efficacy of topical sildenafil versus topical minoxidil in treatment of FPHL. The results were in accordance with Lucky et al. (2004) who included a total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. The results of the study showed that after 48 weeks of treatment, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group and the placebo group in terms of increase terminal hair count, decrease vellus hair count and increase hair growth/scalp coverage [8]. Blume-Peytavi et al. conducted a study to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The results showed that after 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS [9]. Choi and his colleagues investigated the expression of PDE5 in human dermal papilla cells (hDPCs) and human hair follicles (hHFs). The effects of sildenafil on hDPC proliferation were evaluated and the mRNA expression of growth factors and extracellular signal-regulated kinase (ERK) phosphorylation were investigated using real-time PCR and western blotting, respectively. Additionally, anagen induction and perifollicular vessel formation were evaluated using an in vivo mice model. The authors confirmed high expression of PDE5 in hDPCs and hHFs. Sildenafil enhances proliferation of hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and plateletderived growth factor (PDGF), which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice [4]. Stimulating blood flow in the human bald scalp promotes microcirculation in the surrounding HFs and can lead to promotion of hair growth and hypertrichosis. In addition, PDGF is also well known as a hair growth-promoting factor and is expressed in hDPCs and follicular keratinocytes [10]. . Phosphodiesterase inhibitors helps to increase cutaneous blood flow and this helps in promoting hair growth. As a support for this principal, Choi et al. (2018b) showed that cilostazol, a PDE3 inhibitor, promotes hair growth by stimulating hDPC proliferation, enhancing hair shaft elongation and acceleration of anagen induction in C57BL/6 mice [11]. The results of the current study agreed with a previous study by Al-Shabkhon et al. that was conducted in male patients with androgenic alopecia. The study included 30 male patients suffering from androgenic alopecia. Included patients were divided into 2 equal groups based on treatment received; one group received 1% topical sildenafil and the other group received 5% topical minoxidil. Assessment of treatment response was done using trichoscopy. The results showed that sildenafil treated group showed statistically significant increase in VH and TH count at 18 cm point, 24 cm point after treatment compared to before treatment. While, temporal side showed statistically significant increase in VH only. minoxidil treated group showed statistically significant increase in TH count, T/V hair ratio and hair thickness at 18 cm point and temporal side after treatment compared to before treatment. VH count was significantly decreased after treatment compared to before treatment at 18 cm point. At 24 cm point, only TH was significantly increased after treatment compared to before treatment [12]. The authors showed better treatment results in the minoxidil group and higher patients’ satisfaction. The degree of difference in treatment response was better noticed in the temporal region followed by the frontal region and at last the vertex [12]. Despite the reported efficacy of minoxidil, one of its major disadvantages is that the treatment needs to be continued indefinitely. If treatment is stopped, clinical regression occurs within six months. The degree of alopecia will return to the level that would have occurred if there were no treatment [7]. Female pattern hair loss is the most common hair loss disorder in women. Initial symptoms may develop during the teenage years [5]. FPHL is a complex polygenic disorder characterized clinically by diffuse hair thinning over the midfrontal scalp and increased hair shedding [6]. A number of agents have also been used in the treatment of female pattern hair loss including the androgen receptor antagonists spironolactone, cyproterone acetate, and flutamide as well as the 5 a reductase antagonist finasteride and dutasteride. These agents can be used either alone or in combination with topical minoxidil [7]. To the best of our knowledge this is the first study to compare the efficacy of topical sildenafil versus topical minoxidil in treatment of FPHL. The results were in accordance with Lucky et al. (2004) who included a total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. The results of the study showed that after 48 weeks of treatment, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group and the placebo group in terms of increase terminal hair count, decrease vellus hair count and increase hair growth/scalp coverage [8]. Blume-Peytavi et al. conducted a study to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The results showed that after 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS [9]. Choi and his colleagues investigated the expression of PDE5 in human dermal papilla cells (hDPCs) and human hair follicles (hHFs). The effects of sildenafil on hDPC proliferation were evaluated and the mRNA expression of growth factors and extracellular signal-regulated kinase (ERK) phosphorylation were investigated using real-time PCR and western blotting, respectively. Additionally, anagen induction and perifollicular vessel formation were evaluated using an in vivo mice model. The authors confirmed high expression of PDE5 in hDPCs and hHFs. Sildenafil enhances proliferation of hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and plateletderived growth factor (PDGF), which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice [4]. Stimulating blood flow in the human bald scalp promotes microcirculation in the surrounding HFs and can lead to promotion of hair growth and hypertrichosis. In addition, PDGF is also well known as a hair growth-promoting factor and is expressed in hDPCs and follicular keratinocytes [10]. . Phosphodiesterase inhibitors helps to increase cutaneous blood flow and this helps in promoting hair growth. As a support for this principal, Choi et al. (2018b) showed that cilostazol, a PDE3 inhibitor, promotes hair growth by stimulating hDPC proliferation, enhancing hair shaft elongation and acceleration of anagen induction in C57BL/6 mice [11]. The results of the current study agreed with a previous study by Al-Shabkhon et al. that was conducted in male patients with androgenic alopecia. The study included 30 male patients suffering from androgenic alopecia. Included patients were divided into 2 equal groups based on treatment received; one group received 1% topical sildenafil and the other group received 5% topical minoxidil. Assessment of treatment response was done using trichoscopy. The results showed that sildenafil treated group showed statistically significant increase in VH and TH count at 18 cm point, 24 cm point after treatment compared to before treatment. While, temporal side showed statistically significant increase in VH only. minoxidil treated group showed statistically significant increase in TH count, T/V hair ratio and hair thickness at 18 cm point and temporal side after treatment compared to before treatment. VH count was significantly decreased after treatment compared to before treatment at 18 cm point. At 24 cm point, only TH was significantly increased after treatment compared to before treatment [12]. The authors showed better treatment results in the minoxidil group and higher patients’ satisfaction. The degree of difference in treatment response was better noticed in the temporal region followed by the frontal region and at last the vertex [12]. Despite the reported efficacy of minoxidil, one of its major disadvantages is that the treatment needs to be continued indefinitely. If treatment is stopped, clinical regression occurs within six months. The degree of alopecia will return to the level that would have occurred if there were no treatment [7]. Conclusion Topical application of sildenafil 1% proved to be beneficial in FPHL patients with minimal side effects while Topical minoxidil proved to be a gold standard in treatment of FPHL with high tolerability and satisfaction in treated patients. Declarations Conflict of interest: none to declare Funding resource: None References Bhat YJ, Saqib NU, Latif I, Hassan I. Female Pattern Hair Loss-An Update. Indian Dermatol Online J . 2020;11(4):493-501. Published 2020 Jul 13. Badri T, Nessel TA, Kumar D D. Minoxidil. [Updated 2021 Dec 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov . 2014;13(4):290-314. Choi HI, Kang BM, Jang J, Hwang ST, Kwon O. Novel effect of sildenafil on hair growth. Biochem Biophys Res Commun. 2018 Nov 2;505(3):685-91. Vujovic A, Del Marmol V. The female pattern hair loss: review of etiopathogenesis and diagnosis. Biomed Res Int . 2014;2014:767628. Sinclair R. Hair shedding in women: how much is too much?. Br J Dermatol . 2015;173(3):846-48. Sinclair RD. Female pattern hair loss: a pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone. Int J Dermatol . 2018;57(1):104-9. Lucky AW, Piacquadio DJ, Ditre CM, et al. A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss. J Am Acad Dermatol. 2004;50(4):541-53. Blume-Peytavi U, Hillmann K, Dietz E, Canfield D, Garcia Bartels N. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women. J Am Acad Dermatol . 2011;65(6):1126-34.e2. Pyriochou A, Zhou Z, Koika V, et al. The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway. J Cell Physiol . 2007;211(1):197-204. Choi HI, Kim DY, Choi SJ, et al. The effect of cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, on human hair growth with the dual promoting mechanisms. J Dermatol Sci . 2018;91(1):60-68. Ali Abdulkareem Al-Shabkhon, Adel Ahmed Halim Emam, Ahmed Abd Elfattah Afify, Comparative study between the efficacy of topical sildenafil and topical minoxidil in the treatment of male androgenic alopecia, QJM: An International Journal of Medicine , Volume 114, Issue Supplement_1, October 2021, hcab093.007. Additional Declarations No competing interests reported. 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The loss of terminal hairs in affected areas is usually incomplete and the frontal hairline is often spared. It is caused by follicular miniaturization, a process that gradually reduces the proportion of terminal to vellus hair [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTopical minoxidil is a hair growth stimulator that works by shortening the telogen process of the hair follicles, allowing them to reach the anagen phase prematurely. Minoxidil also prolongs the anagen phase by acting on the potassium channels of vascular smooth muscles and hair follicles, which increases the microcirculation near the hair follicles [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe molecular structure of sildenafil mimics that of cyclic guanosine monophosphate (cGMP), this similarity protects cGMP from degradation because sildenafil can bind to the catalytic site to act as a competitive inhibitor of cGMP-specific PDE-5, the enzyme that normally catalyzes the break down of vasodilatory cGMP[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePhosphodiestrase 5 is highly expressed in human dermal papilla cells (hDPCs) and human hair follicles (hHFs). Sildenafil enhances proliferation of hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and platelet- derived growth factor (PDGF) which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated extre cellular signal regulated kinase (ERK) and accelerates anagen induction by stimulating perifollicular vessel formation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e"},{"header":"Patients And Methods","content":"\u003cp\u003e\u0026nbsp;This is \u003cstrong\u003ean exploratory pilot study that was\u0026nbsp;\u003c/strong\u003econducted at Al-Azhar University Hospitals\u0026apos; Dermatology, Venereology, and Andrology Department Outpatient Clinics (Damietta).\u003c/p\u003e\n\u003cp\u003eThe study included 30 cases with FPHL grade 1 and 2 Ludwig \u0026nbsp; classification . Patients were randomly assigned into two groups: \u003cstrong\u003eGroup I\u003c/strong\u003e: fifteen patients were subjected topical sildenafil citrate 1%solution (\u0026nbsp;Standard 1gm sildenafil dissolved in 100 ml ethanol solution to prepare 1% lotion). Twice daily application for 3 months, \u003cstrong\u003eGroup II\u003c/strong\u003e: fifteen patients were subjected to minoxidil foam 5%(Hair back plus foam ,mina pharma) once daily for 3 months\u003c/p\u003e\n\u003cp\u003eAll patients were subjected to the following: full history taking , general examination, Dermatological and dermoscopic examination for grading of female pattern hair loss, Digital photographs were taken clinical \u0026amp; dermoscopic monthly and three months after treatment Assessment by Trichoscopy examination was performed with Derma Light Dl4. \u0026nbsp; Hair loss regions including the vertex, frontal, temporal line and occipital regions were observed. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt least 3-4 images were taken with a digital camera that was connected to the dermoscope with the same parameters.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Degree of improvement was assessed in females according to the degree of improvement changes in Ludwig classifications . \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlso the degree of improvement was assessed by comparing the trichoscopic photos before and after treatment as regards hair density, number of terminal \u0026nbsp;to \u0026nbsp; vellus hair and hair thickness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion criteria:\u0026nbsp;\u003c/strong\u003eThe study included 30 adult female patients between 18 and 45 years with grade 1 or 2 ludwig classification .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria:\u0026nbsp;\u003c/strong\u003ePatients who were \u0026lt;18 and \u0026gt;45 years old, grade 3 FPHL Ludwig classification, who received systemic or topical treatment for FPHL in the last 6 months prior to the start of the study;\u0026nbsp;who were \u0026nbsp; Pregnant or lactating , who had \u0026nbsp; hormonal disturbance like pco, who have any autoimmune disease,\u0026nbsp;with known history of\u0026nbsp; hypersensitivity to minoxidil or sildenafil, \u0026nbsp;with other types of hair loss either cicatricial or non cicatricial and patients with aneamia, thyroid disease, and vit D deficiency.were excluded from the study\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow up:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe follow up was conducted every month \u0026nbsp;during treatment and for 3 months after the completion of treatment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u0026nbsp;\u003c/strong\u003eThe study was approved by an ethics committee of Damietta Faculty of Medicine IRB (00012367), Al-Azhar University, Egypt. An informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis:\u003c/strong\u003e Data analysis was performed by SPSS software, version 18 (SPSS Inc., PASW statistics for windows version 18. Chicago: SPSS Inc.). Qualitative data were described using number and percent. Quantitative data were described using median (minimum and maximum) for non-normally distributed data and mean\u0026plusmn; Standard deviation for normally distributed data after testing normality using Kolmogrov-Smirnov test. Significance of the obtained results was judged at the (0.05) level.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eChi-Square , Fischer exact test , Monte Carlo tests were used to compare qualitative data between groups as appropriate\u003c/li\u003e\n \u003cli\u003eStudent t test was used to compare 2 independent groups for normally distributed data .\u003c/li\u003e\n \u003cli\u003ePaired t test was used to compare 2 paired readings distributed data .\u003c/li\u003e\n \u003cli\u003eThe Spearman\u0026apos;s rank-order correlation is used to determine the strength and direction of a linear relationship between two non-normally distributed continuous variables and / or ordinal variables.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Results ","content":"\u003cp\u003e30 cases with FPHL grade 1 and 2 Ludwig classification There were no statistically significant difference in the basic data in the two study groups including age, disease duration, percentage of cases with positive family history and degree of hair loss.\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant increase in the Terminal hair count and hair thickness in the group treated with topical minoxidil 5% in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant decrease in the vellus hair count, but it was detected only in the frontal region.\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant increase in the vellus hair count in the group treated with topical sildenafil 1% in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant increase in the terminal hair count in the frontal region and vertex region after treatment as compared to before treatment. There was no statistically significant difference in the hair thickness in all the regions after treatment.\u003c/p\u003e\n\u003cp\u003eWhen comparing the results of the two drugs, minoxidil showed better results compared to sildenafil in terms of higher terminal hair count, thicker hair diameter and decreased number of vellus hair. The effects were more noticed in the frontal region and temporal region and less noticed in the vertex. Furthermore, there was higher degree of patients\u0026rsquo; satisfaction in the minoxidil group compared to the sildenafil group, but it didn\u0026rsquo;t achieve a statistically significant difference.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (1): Comparison of treatment response at the frontal region between the 2 groups\u003c/strong\u003e.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"653\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.898928024502297%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.61102603369066%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTopical Sildenafil 1%\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.124042879019907%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTopical Minoxidil 5%\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.367534456355283%\"\u003e\n \u003cp\u003e\u003cstrong\u003etest of significance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.998468606431853%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep- value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.898928024502297%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVellus hair count\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.61102603369066%\"\u003e\n \u003cp\u003e11.33\u0026plusmn;7.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.124042879019907%\"\u003e\n \u003cp\u003e-7.53\u0026plusmn;7.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.367534456355283%\"\u003e\n \u003cp\u003e6.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.998468606431853%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.898928024502297%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTerminal hair count\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.61102603369066%\"\u003e\n \u003cp\u003e15.53\u0026plusmn;8.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.124042879019907%\"\u003e\n \u003cp\u003e26.87\u0026plusmn;11.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.367534456355283%\"\u003e\n \u003cp\u003e3.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.998468606431853%\"\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.898928024502297%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHair thickness (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.61102603369066%\"\u003e\n \u003cp\u003e0.001\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.124042879019907%\"\u003e\n \u003cp\u003e0.01\u0026plusmn;0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.367534456355283%\"\u003e\n \u003cp\u003e5.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.998468606431853%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eZ :\u003cem\u003e\u0026nbsp;Mann Whitney test P value \u0026le;0.05 is significant\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (2): Comparison of treatment response at the vertex between the 2 groups.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"627\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTopical Sildenafil 1%\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTopical Minoxidil 5%\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e\u003cstrong\u003etest of significance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep- value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVellus hair count\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e1.40\u0026plusmn;2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e1.53\u0026plusmn;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e0.892\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTerminal hair count\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e7.2\u0026plusmn;11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e13.60\u0026plusmn;5.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHair thickness (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e0.002\u0026plusmn;0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e0.009\u0026plusmn;0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.095693779904305%\"\u003e\n \u003cp\u003e3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.936204146730464%\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eUsing Mann Whitney test P value \u0026le;0.05 is significant\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3):\u0026nbsp;\u003c/strong\u003eComparison of treatment response at the temporal side between the 2 groups. .\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"611\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"18.790849673202615%\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"41.1764705882353%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMean \u0026plusmn; SD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"20.098039215686274%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003etest-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"19.934640522875817%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"51.39442231075697%\"\u003e\n \u003cp\u003eGroup 1\u003c/p\u003e\n \u003cp\u003e(Sildenafil citrate solution 1 %)\u003c/p\u003e\n \u003cp\u003en=15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"48.60557768924303%\"\u003e\n \u003cp\u003eGroup 2\u003c/p\u003e\n \u003cp\u003e(Minoxidil foam 5%)\u003c/p\u003e\n \u003cp\u003en=15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.821603927986907%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVellous hair (VH)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.112929623567922%\"\u003e\n \u003cp\u003e3.80\u0026plusmn;5.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.967266775777414%\"\u003e\n \u003cp\u003e-6.07\u0026plusmn;10.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.130932896890343%\"\u003e\n \u003cp\u003e3.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.967266775777414%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.821603927986907%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTerminal hair (TH)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.112929623567922%\"\u003e\n \u003cp\u003e-1.3\u0026plusmn;5.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.967266775777414%\"\u003e\n \u003cp\u003e13.67\u0026plusmn;6.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.130932896890343%\"\u003e\n \u003cp\u003e6.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.967266775777414%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.821603927986907%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHair thickness\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.112929623567922%\"\u003e\n \u003cp\u003e-0.002\u0026plusmn;0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.967266775777414%\"\u003e\n \u003cp\u003e0.009\u0026plusmn;0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.130932896890343%\"\u003e\n \u003cp\u003e3.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.967266775777414%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003e\u0026ordf;\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eUsing Mann Whitney test P value \u0026le;0.05 is significant\u0026nbsp;\u003c/em\u003e\u003c/p\u003e"},{"header":"Discussion ","content":"\u003cp\u003eFemale pattern hair loss is the most common hair loss disorder in women. Initial symptoms may develop during the teenage years\u0026nbsp;\u003cstrong\u003e[5].\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFPHL is a complex polygenic disorder characterized clinically by diffuse hair thinning over the midfrontal scalp and increased hair shedding\u003cstrong\u003e[6].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA number of agents have also been used in the treatment of female pattern hair loss including the androgen receptor antagonists spironolactone, cyproterone acetate, and flutamide as well as the 5 a reductase antagonist finasteride and dutasteride. These agents can be used either alone or in combination with topical minoxidil\u0026nbsp;\u003cstrong\u003e[7].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge this is the first study to compare the efficacy of topical sildenafil versus topical minoxidil in treatment of FPHL.\u003c/p\u003e\n\u003cp\u003eThe results were in accordance with Lucky et al. (2004) who included a total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. The results of the study showed that after 48 weeks of treatment, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group and the placebo group in terms of increase terminal hair count, decrease vellus hair count and increase hair growth/scalp coverage\u003cstrong\u003e[8].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBlume-Peytavi et al. conducted a study to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The results showed that after 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants\u0026apos; agreement with \u0026quot;the treatment does not interfere with styling my hair\u0026quot; (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS\u003cstrong\u003e[9].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChoi and his colleagues investigated the expression of PDE5 in human dermal papilla cells (hDPCs) and human hair follicles (hHFs). The effects of sildenafil on hDPC proliferation were evaluated and the mRNA expression of growth factors and extracellular signal-regulated kinase (ERK) phosphorylation were investigated using real-time PCR and western blotting, respectively. Additionally, anagen induction and perifollicular vessel formation were evaluated using an in vivo mice model. The authors confirmed high expression of PDE5 in hDPCs and hHFs. Sildenafil enhances proliferation of hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and plateletderived growth factor (PDGF), which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice\u003cstrong\u003e[4].\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStimulating blood flow in the human bald scalp promotes microcirculation in the surrounding HFs and can lead to promotion of hair growth and hypertrichosis. \u0026nbsp; In addition, PDGF is also well known as a hair growth-promoting factor and is expressed in hDPCs and follicular keratinocytes\u003cstrong\u003e[10].\u003c/strong\u003e. Phosphodiesterase \u0026nbsp;inhibitors helps to increase cutaneous blood flow and this helps in promoting hair growth.\u003c/p\u003e\n\u003cp\u003eAs a support for this principal, Choi et al. (2018b) showed that cilostazol, a PDE3 inhibitor, promotes hair growth by stimulating hDPC proliferation, enhancing hair shaft elongation and acceleration of anagen induction in C57BL/6 mice\u003cstrong\u003e[11].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of the current study agreed with a previous study by Al-Shabkhon et al. that was conducted in male patients with androgenic alopecia. The study included 30 male patients suffering from androgenic alopecia. Included patients were divided into 2 equal groups based on treatment received; one group received 1% topical sildenafil and the other group received 5% topical minoxidil. Assessment of treatment response was done using trichoscopy. The results showed that sildenafil treated group showed statistically significant increase in VH and TH count at 18\u0026thinsp;cm point, 24\u0026thinsp;cm point after treatment compared to before treatment. While, temporal side showed statistically significant increase in VH only. minoxidil treated group showed statistically significant increase in TH count, T/V hair ratio and hair thickness at 18\u0026thinsp;cm point and temporal side after treatment compared to before treatment. VH count was significantly decreased after treatment compared to before treatment at 18\u0026thinsp;cm point. At 24\u0026thinsp;cm point, only TH was significantly increased after treatment compared to before treatment\u003cstrong\u003e[12].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors showed better treatment results in the minoxidil group and higher patients\u0026rsquo; satisfaction. The degree of difference in treatment response was better noticed in the temporal region followed by the frontal region and at last the vertex\u003cstrong\u003e[12].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDespite the reported efficacy of minoxidil, one of its major disadvantages is that the treatment needs to be continued indefinitely. If treatment is stopped, clinical regression occurs within six months. The degree of alopecia will return to the level that would have occurred if there were no treatment\u003cstrong\u003e[7].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFemale pattern hair loss is the most common hair loss disorder in women. Initial symptoms may develop during the teenage years\u0026nbsp;\u003cstrong\u003e[5].\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFPHL is a complex polygenic disorder characterized clinically by diffuse hair thinning over the midfrontal scalp and increased hair shedding\u003cstrong\u003e[6].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA number of agents have also been used in the treatment of female pattern hair loss including the androgen receptor antagonists spironolactone, cyproterone acetate, and flutamide as well as the 5 a reductase antagonist finasteride and dutasteride. These agents can be used either alone or in combination with topical minoxidil\u0026nbsp;\u003cstrong\u003e[7].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge this is the first study to compare the efficacy of topical sildenafil versus topical minoxidil in treatment of FPHL.\u003c/p\u003e\n\u003cp\u003eThe results were in accordance with Lucky et al. (2004) who included a total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. The results of the study showed that after 48 weeks of treatment, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group and the placebo group in terms of increase terminal hair count, decrease vellus hair count and increase hair growth/scalp coverage\u003cstrong\u003e[8].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBlume-Peytavi et al. conducted a study to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The results showed that after 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants\u0026apos; agreement with \u0026quot;the treatment does not interfere with styling my hair\u0026quot; (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS\u003cstrong\u003e[9].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChoi and his colleagues investigated the expression of PDE5 in human dermal papilla cells (hDPCs) and human hair follicles (hHFs). The effects of sildenafil on hDPC proliferation were evaluated and the mRNA expression of growth factors and extracellular signal-regulated kinase (ERK) phosphorylation were investigated using real-time PCR and western blotting, respectively. Additionally, anagen induction and perifollicular vessel formation were evaluated using an in vivo mice model. The authors confirmed high expression of PDE5 in hDPCs and hHFs. Sildenafil enhances proliferation of hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and plateletderived growth factor (PDGF), which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice\u003cstrong\u003e[4].\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStimulating blood flow in the human bald scalp promotes microcirculation in the surrounding HFs and can lead to promotion of hair growth and hypertrichosis. \u0026nbsp; In addition, PDGF is also well known as a hair growth-promoting factor and is expressed in hDPCs and follicular keratinocytes\u003cstrong\u003e[10].\u003c/strong\u003e. Phosphodiesterase \u0026nbsp;inhibitors helps to increase cutaneous blood flow and this helps in promoting hair growth.\u003c/p\u003e\n\u003cp\u003eAs a support for this principal, Choi et al. (2018b) showed that cilostazol, a PDE3 inhibitor, promotes hair growth by stimulating hDPC proliferation, enhancing hair shaft elongation and acceleration of anagen induction in C57BL/6 mice\u003cstrong\u003e[11].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of the current study agreed with a previous study by Al-Shabkhon et al. that was conducted in male patients with androgenic alopecia. The study included 30 male patients suffering from androgenic alopecia. Included patients were divided into 2 equal groups based on treatment received; one group received 1% topical sildenafil and the other group received 5% topical minoxidil. Assessment of treatment response was done using trichoscopy. The results showed that sildenafil treated group showed statistically significant increase in VH and TH count at 18\u0026thinsp;cm point, 24\u0026thinsp;cm point after treatment compared to before treatment. While, temporal side showed statistically significant increase in VH only. minoxidil treated group showed statistically significant increase in TH count, T/V hair ratio and hair thickness at 18\u0026thinsp;cm point and temporal side after treatment compared to before treatment. VH count was significantly decreased after treatment compared to before treatment at 18\u0026thinsp;cm point. At 24\u0026thinsp;cm point, only TH was significantly increased after treatment compared to before treatment\u003cstrong\u003e[12].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors showed better treatment results in the minoxidil group and higher patients\u0026rsquo; satisfaction. The degree of difference in treatment response was better noticed in the temporal region followed by the frontal region and at last the vertex\u003cstrong\u003e[12].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDespite the reported efficacy of minoxidil, one of its major disadvantages is that the treatment needs to be continued indefinitely. If treatment is stopped, clinical regression occurs within six months. The degree of alopecia will return to the level that would have occurred if there were no treatment\u003cstrong\u003e[7].\u003c/strong\u003e\u003c/p\u003e"},{"header":"Conclusion ","content":"\u003cp\u003eTopical application of sildenafil 1% proved to be beneficial in FPHL patients with minimal side effects \u0026nbsp;while Topical minoxidil proved to be a gold standard in treatment of FPHL with high tolerability and satisfaction in treated patients. \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e none to declare\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding resource:\u003c/strong\u003e None\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBhat YJ, Saqib NU, Latif I, Hassan I. Female Pattern Hair Loss-An Update. \u003cem\u003eIndian Dermatol Online J\u003c/em\u003e. 2020;11(4):493-501. Published 2020 Jul 13.\u003c/li\u003e\n \u003cli\u003eBadri T, Nessel TA, Kumar D D. Minoxidil. [Updated 2021 Dec 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.\u003c/li\u003e\n \u003cli\u003eMaurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Advances in targeting cyclic nucleotide phosphodiesterases. \u003cem\u003eNat Rev Drug Discov\u003c/em\u003e. 2014;13(4):290-314.\u003c/li\u003e\n \u003cli\u003eChoi HI, Kang BM, Jang J, Hwang ST, Kwon O. Novel effect of sildenafil on hair growth. Biochem Biophys Res Commun. 2018 Nov 2;505(3):685-91.\u003c/li\u003e\n \u003cli\u003eVujovic A, Del Marmol V. The female pattern hair loss: review of etiopathogenesis and diagnosis. \u003cem\u003eBiomed Res Int\u003c/em\u003e. 2014;2014:767628.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Sinclair R. Hair shedding in women: how much is too much?. \u003cem\u003eBr J Dermatol\u003c/em\u003e. 2015;173(3):846-48.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Sinclair RD. Female pattern hair loss: a pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone. \u003cem\u003eInt J Dermatol\u003c/em\u003e. 2018;57(1):104-9.\u003c/li\u003e\n \u003cli\u003eLucky AW, Piacquadio DJ, Ditre CM, et al. A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss. J Am Acad Dermatol. 2004;50(4):541-53.\u003c/li\u003e\n \u003cli\u003eBlume-Peytavi U, Hillmann K, Dietz E, Canfield D, Garcia Bartels N. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women. \u003cem\u003eJ Am Acad Dermatol\u003c/em\u003e. 2011;65(6):1126-34.e2.\u003c/li\u003e\n \u003cli\u003ePyriochou A, Zhou Z, Koika V, et al. The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway. \u003cem\u003eJ Cell Physiol\u003c/em\u003e. 2007;211(1):197-204.\u003c/li\u003e\n \u003cli\u003eChoi HI, Kim DY, Choi SJ, et al. The effect of cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, on human hair growth with the dual promoting mechanisms. \u003cem\u003eJ Dermatol Sci\u003c/em\u003e. 2018;91(1):60-68.\u003c/li\u003e\n \u003cli\u003eAli Abdulkareem Al-Shabkhon, Adel Ahmed Halim Emam, Ahmed Abd Elfattah Afify, Comparative study between the efficacy of topical sildenafil and topical minoxidil in the treatment of male androgenic alopecia, \u003cem\u003eQJM: An International Journal of Medicine\u003c/em\u003e, Volume 114, Issue Supplement_1, October 2021, hcab093.007.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"FPHL, Topical, Minoxidil, Sildenafil","lastPublishedDoi":"10.21203/rs.3.rs-2281439/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2281439/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003eBackground\u003c/u\u003e: Female pattern hair loss (FPHL) is a nonscarring progressive thinning of hair with gradual decrease in it's number , especially in the frontal, central, and parietal scalp. the loss of terminal hairs in affected areas is usually incomplete and the frontal hairline is often spared. It is caused by follicular miniaturization, a process that gradually reduces the proportion of terminal to vellus hair\u003cstrong\u003e \u003c/strong\u003e\u003cu\u003e.\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAim of the work\u003c/u\u003e: to evaluate the efficacy and safety of topical sildenafil citrate 1 % solution in comparison with topical minoxidil 5% foam in the treatment of female pattern hair loss .\u003c/p\u003e\n\u003cp\u003e\u003cu\u003ePatients and methods:\u003c/u\u003e This exploratory pilot study included 30 female patients suffering from female pattern hair loss. Included patients were divided into 2 groups ; \u003cstrong\u003egroup1\u003c/strong\u003e: received 1% topical sildenafil citrate solution and \u003cstrong\u003egroup2\u003c/strong\u003e: received 5% topical minoxidil foam. Assessment of treatment response was done using trichoscopy.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eResults:\u003c/u\u003e \u0026nbsp;In \u003cstrong\u003egroup 1\u003c/strong\u003e(treated with topical sildenafil 1%):There was a statistically significant increase in the vellus hair count in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant increase in the terminal hair count in the frontal region and vertex region after treatment as compared to before treatment. There was no statistically significant difference in the hair thickness in all the regions after treatment. , \u0026nbsp;\u003cstrong\u003eGroup 2\u003c/strong\u003e(treated with topical minoxidil 5% ) there was a statistically significant increase in the Terminal hair count and hair thickness in the frontal region, vertex and temporal side after treatment as compared to before treatment. Also, there was statistically significant decrease in the vellus hair count, but it was detected only in the frontal region.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConclusion:\u003c/u\u003e topical sildinafil 1% treatment proves to be a good alternative in the treatment of FPHL, although topical minoxidil 5% is still the first choice in FPHL treatment.\u003c/p\u003e","manuscriptTitle":"Comparative study between the efficacy and safety of topical sildenafil citrate solution and topical minoxidil 5%in the treatment of female pattern hair loss .","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-18 14:39:57","doi":"10.21203/rs.3.rs-2281439/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fa34ddd0-61d6-4ad5-ae0a-a084dcbe377d","owner":[],"postedDate":"November 18th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-11-21T17:44:10+00:00","versionOfRecord":[],"versionCreatedAt":"2022-11-18 14:39:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2281439","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2281439","identity":"rs-2281439","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}