The Impact of Serum Estradiol Levels on Vaginal pH and Candida Infections During Infertility Treatment

The Impact of Serum Estradiol Levels on Vaginal pH and Candida Infections During Infertility Treatment | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Impact of Serum Estradiol Levels on Vaginal pH and Candida Infections During Infertility Treatment Çağın Çakırgöz, Emine Çakırgöz, Dilara Kirmiç, Pınar Solmaz Hasdemir, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5294623/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 Purpose: This study aims to investigate the potential impact of serum estradiol levels on vaginal pH, flora, and susceptibility to Candida infections in patients undergoing infertility treatment. Methods: Clinical data and biochemical parameters were evaluated from 60 infertility patients aged 20–49. Blood serum estradiol levels were measured on the 2nd day of the menstrual cycle along with assessments of vaginal pH and mycological cultures. These procedures were repeated post-ovulation induction at peak estradiol levels. A comparative analysis of pre- and post-treatment samples from the same patients was conducted to determine the effect of increased estradiol on vaginal pH and Candida growth. Statistical analyses were performed using SPSS 22.0 software, with significance set at p < 0.05. Results: Post-treatment measurements indicated a significant increase in serum estradiol and vaginal pH compared to pre-treatment levels. Despite this, no significant correlation was found between estradiol levels and changes in vaginal pH, vulvovaginal symptoms, or culture growth. Similarly, vaginal pH levels did not significantly affect vulvovaginal symptoms or Candida culture growth. However, a significant relationship was identified between pre-treatment cultures and vulvovaginal symptoms, a correlation absent in post-treatment samples. Conclusion: The findings suggest that the substantial increase in serum estradiol levels during infertility treatment does not predispose patients to vaginal Candida infections via alterations in vaginal pH. There appears to be no additional risk of candidal infections associated with elevated estradiol during infertility treatments. Infertility Candida Estradiol Vaginal Flora Vaginitis Introduction A woman's life comprises various stages, such as childhood, puberty, reproductive age, menopause, and old age, each characterized by specific health issues. Reproductive health is a crucial aspect influencing all stages of a woman's life. According to the World Health Organization, 36% of the total disease burden in women is due to reproductive health issues [1]. The ages between 15 and 49, when women reach sexual maturity, are the periods with the highest frequency of reproductive health problems and peak reproductive system infections [2]. In our country, the prevalence of vaginal infections ranges from 37.1–65.6% [3]. Reproductive system infections predominantly arise from lower genital tract issues, including vaginitis and cervicitis [4]. Although vaginal infections do not have high mortality rates, they cause significant morbidity [5]. If untreated, they can lead to upper genital tract infections and long-term sequelae such as chronic pelvic pain, ectopic pregnancy, and infertility [6]. Reproductive system infections predominantly originate from lower genital tract issues such as vaginitis and cervicitis [7]. Though not highly fatal, vaginal infections contribute to significant morbidity [8]. Untreated vaginitis can ascend, leading to chronic pelvic pain, increased ectopic pregnancy rates, infertility, and tubo-ovarian abscesses [9]. Hence, addressing vaginitis is critical for mitigating future morbidities, and understanding predisposing factors is essential for effective treatment. Alterations in vaginal pH and associated microbiota disruptions can lead to vaginal infections [10]. The significance of these infections lies in their potential to cause chronic conditions, infertility, and cancer if untreated [11]. Symptoms include foul odor, itching, sensitivity, and pain, often leading to avoidance of sexual activity, physical fatigue, and increased susceptibility to sexually transmitted infections. These infections also impact body image, causing psychological issues, and result in economic, time, and productivity losses [12]. The human vagina hosts a diverse microbiota, predominantly Lactobacillus in healthy individuals. Disruptions in this ecosystem can lead to bacterial vaginosis, sexually transmitted infections, and vulvovaginal candidiasis. Factors such as menstruation, pregnancy, sexual activity, uncontrolled antibiotic use, and vaginal douching can alter the microbiota [13, 14]. Hormonal fluctuations during the menstrual cycle also impact the microbiota, with elevated vaginal pH reported in pathological conditions. Higher estradiol (E2) levels in young women due to pregnancy or hormonal contraceptives, and in postmenopausal women due to hormone replacement therapy, are linked to an increased risk of vaginal Candida [13, 14]. Estrogens are seen to affect the host defenses against Candida albicans by epithelial cells in the female genital tract [15]. Therefore, estrogen plays a vital role in the barrier and uptake functions of the vaginal epithelium, necessitating further comprehensive research. The vaginal flora is primarily aerobic, with Lactobacillus being the most frequently isolated microorganism in a healthy human vagina [16]. Lactobacillus produces lactic acid and hydrogen peroxide, preventing the overgrowth of other pathogenic bacteria [17]. Changes in environmental conditions can reduce the number of lactobacilli, allowing other bacteria to dominate and altering the vaginal microbiota [18]. The quantity of vaginal discharge can vary due to factors such as vaginal pH, age, hormonal status, sexual activity, menstrual cycle, estrogen levels, contraceptive methods used, medications, antibiotics, or surgical procedures performed on the patient [16, 19]. Methods Vaginal pH and Infections During the reproductive period, vaginal pH ranges from 3.8 to 4.5 [20]. In pediatric, adolescent, and menopausal periods, the pH value is greater than 4.5 [21]. Maintaining the normal pH range acts as a protective barrier against bacteria and fungi. In the newborn period, the vagina is acidic due to estrogen from the mother, but pH changes as maternal estrogen levels drop [22]. During the sexually active period, the glycogen-rich structure of the vaginal mucosa epithelium and the dominance of lactobacilli help maintain an acidic pH. In the postmenopausal period, estrogen decreases, lactobacilli disappear, the vaginal epithelium thins, and pH becomes alkaline, ranging from 6 to 8 [22]. This change increases the risk of bacterial infections [23]. Patients may present clinically with complaints such as severe vaginal discharge, itching, dyspareunia, dysuria, and foul odor [24]. Candidal Vaginosis Candidal vaginosis affects 75% of adult women at least once in their lifetime, with 45% experiencing vulvovaginal candidiasis at least twice a year [25]. Candida albicans is responsible for 85–90% of cases [26]. It is characterized by a thick, white, curd-like discharge, dyspareunia, dysuria, vulvar itching, burning sensation in the vagina, and discomfort. Post-treatment with fluconazole and lifestyle changes are recommended [27]. Initially, topical hydrocortisone may be added to address irritation and itching [28]. Fluconazole is used in the treatment of candidal vaginitis [29]. The patient is given a single oral dose of fluconazole. If the patient has recurrent vulvovaginal candidiasis, a second dose of fluconazole is recommended one week later [28]. Treatment doses and durations vary depending on the severity of symptoms, the patient’s clinical status, and recurrence rates [29]. Oral antifungal therapy alone is not sufficient for the elimination of Candida. Patients should also be advised on dietary adjustments to eliminate refined carbohydrates that feed Candida, reducing the use of daily pads, avoiding vaginal douching that disrupts the flora, and wearing cotton underwear. The Effects of Estrogen on Vaginal Flora Various mechanisms have been developed to allow lactobacilli to dominate the flora again in postmenopausal women. Some of these mechanisms include the use of exogenous bacteria (probiotics), nutritional supplements (prebiotics), or a combination of both. The proportion of lactobacilli in the vaginal microbiota is important for protection against gynecological disorders and sexually transmitted infections [30,31]. However, this balance is disrupted post-menopause, leading to a decrease in lactobacilli. Studies have shown that changes in pH are not the main factor underlying the decrease in lactobacilli. Even if the vaginal environment is artificially acidified, the lactobacillus population cannot be maintained effectively [32]. One reason for this change in lactobacillus quantity may be the reduced estrogen production during menopause compared to levels in reproductive-aged women. This may affect the dynamics of the vaginal mucosa [33, 34]. Low doses of estrogen have been shown to restore acidic vaginal pH and induce glycogen production [35]. However, the direct effects of estrogens on lactobacilli were not well understood. Recent studies have reported that estradiol has direct effects on bacteria such as Agrobacterium tumefaciens, Pseudomonas aeruginosa, Prevotella intermedia [36], and Staphylococcus epidermidis [37]. However, the effects of estradiol on lactobacilli remain unclear. The Relationship Between Candidal Vaginosis and Estrogen Vaginal infections caused by Candida albicans are quite common today and are used as an important model in studying pathogenic mechanisms and immune responses. A study conducted on mice showed that intense Candida colonization not only leads to candidal vaginosis but also disrupts vaginal immune homeostasis, potentially resulting in bacterial superinfection. Estradiol is thought to exhibit immunomodulatory effects, particularly by suppressing cytokine production by epithelial and immune cells [38]. The effects of estradiol on Candida albicans were first studied by measuring filament formation and length. Following this, it was revealed that the localization of estradiol-binding protein 1 (Ebp1p) and the expression of CDR1 and CDR2 genes in Candida albicans are influenced by the host's estradiol levels [39]. Further research is needed to better understand the effects of estradiol on Candida albicans. Studies have shown that estrogens affect the defense mechanisms against Candida albicans in the female genital tract's epithelial cells. For example, primary uterine epithelial cells show a reduction in lipopolysaccharide-induced cytokines such as IL-6, IL-8, and macrophage migration inhibitory factor under the influence of estrogen. Additionally, estrogen has been found to reduce the expression of regulatory proteins like NF in these cells, which can lead to a decrease in the expression of cytokine genes such as IL-6, IL-8, IL-1α, IL-1β, and TNFα [40]. Therefore, it is believed that estrogen may play a significant role in the barrier and host defense functions of the vaginal epithelium. Estrogen also supports follicular development in the ovaries, increases tubal motility, promotes glandular and stromal proliferation in the endometrial tissue, induces NaCl crystallization in cervical mucus, acidifies vaginal pH, raises cervical pH, strengthens uterine contractions, and makes the myometrial tissue more sensitive to oxytocin. Study Description This descriptive study was designed with the participation of healthy women aged 18–49 who applied to the In Vitro Fertilization (IVF) Center at Manisa Celal Bayar University Hospital for infertility treatment. The study was conducted in accordance with the Helsinki Declaration revised in 2008, and received ethical approval from the Celal Bayar University Hospital Ethics Committee on 25.09.2023 (approval number 547). Informed consent was obtained from all participants. Selection of Patients Women aged 18–49 who applied to the IVF Center for infertility treatment were included in the study after being provided with the necessary information and giving written consent. Exclusion criteria included being under 18 or over 50, using intrauterine devices (IUDs), having acute infection signs, being menstruating, having abnormal bleeding, being pregnant or lactating, and being menopausal. Vaginal pH Measurement and Diagnosis of Vaginal Infections Vaginal pH measurements were performed on all eligible participants using a "Handheld Digital pH meter." "Sabouraud Dextrose Agar" culture medium was used to detect mycological pathogens in the vaginal mucosa. Collection of Blood Samples Blood samples were collected from all participants for E2 level testing. Routine blood tests were performed at the IVF Center, and additional tests for estradiol levels were included. Blood samples were analyzed at the hospital's biochemistry laboratory. Biochemical Measurements Estradiol levels were measured in all patients during the follicular phase of the menstrual cycle (days 2 or 3) and after treatment. Blood samples were analyzed using chemiluminescent methods. Statistical Analysis Data were analyzed using IBM SPSS 22.0 software. The Kolmogorov-Smirnov test was used to assess data distribution, and nonparametric analyses were conducted due to non-normal distribution. Descriptive tables and percentage distributions were created for socio-demographic data. The significance level was set at p < 0.05. Results The study included 60 participants. Data on age, vaginal pH, presence of vaginal symptoms, mycological culture results, and serum estradiol levels were analyzed. Correlation Analyses No statistically significant correlation was found between estradiol levels and vaginal pH measurements before and after ovulation induction treatment (p > 0.05). Logistic Regression Analysis No statistically significant relationship was found between estradiol levels and symptoms or culture results before and after treatment (p > 0.05). However, vaginal pH values were statistically significant in explaining the culture results, with higher pH values associated with increased culture positivity (p < 0.05). Paired Sample T-Test Statistically significant differences were found between pre- and post-treatment pH and estradiol levels (p < 0.05). Discussion The vaginal pH of women of reproductive age ranges from 3.8 to 4.5 [41]. Lactobacillus is the most frequently isolated microorganism in the vagina and influences vaginal pH by producing lactic acid [42]. Menopause leads to increased vaginal pH due to decreased estrogen levels [43]. Factors such as menstruation, pregnancy, sexual activity, antibiotic use, uncontrolled diabetes, humid and warm environments, and vaginal douching can alter the microbiota [44]. Increased estradiol levels have been associated with a higher risk of vaginal Candida infections [44]. Our study examined the impact of estradiol on vaginal pH and fungal infections. Our results showed that vaginal pH was not predictive of vaginal symptoms or fungal culture results. Although estradiol and vaginal pH levels significantly increased after treatment, no significant relationship was found between these factors and symptoms or culture results. Estrogen has been shown to lower vaginal pH and increase cervical pH [45]. However, the specific estrogen levels required to achieve these effects are not well understood. Our study did not find a significant relationship between estradiol levels and vaginal pH or mycological culture results. Future studies with larger sample sizes are needed to clarify these relationships and explore the potential use of estradiol levels as a diagnostic tool for vaginal Candida infections. Understanding the physiological mechanisms behind estrogen's impact on vaginal pH and microbiota could improve clinical diagnosis and treatment options. A study has shown that vaginal pH can be a simple and cost-effective tool for providing information about the health and cellular morphology of the vaginal epithelium in clinical settings and for predicting vulvovaginal symptoms [45]. However, our results indicated that vaginal pH did not significantly affect the prediction of vaginal symptoms or the growth in fungal cultures. Another study in the literature found that using vaginal pH measurement as a screening tool is useful and inexpensive. It was noted that a vaginal pH of 4.5 is consistent with premenopausal serum estradiol levels and the absence of bacterial pathogens. Higher vaginal pH levels between 5.0 and 6.5 were associated with the proliferation of bacterial pathogens or decreased serum estradiol levels. In patients with high pH, a vaginal culture should confirm the diagnosis. If bacterial pathogens are absent, a vaginal pH between 6.0 and 7.5 can be a strong indicator of menopause [46]. In our study, ovulation induction was performed in infertile patients. Serum estradiol levels before treatment were found to be lower than after treatment. Similarly, as serum estradiol levels increased, vaginal pH also increased. Despite the increase in vaginal pH and estradiol levels post-treatment, there was no significant correlation between these changes and patients' symptoms or fungal culture growth. Another study in the literature indicated that while rising estrogen levels before ovulation increased vaginal pH, this increase did not lead to vaginal infections [47]. In our study, we observed that both estradiol and vaginal pH values significantly increased after gonadotropic agents were administered for ovulation induction. Despite the increase in vaginal pH and estradiol, there was no observed increase in candidal infections or vulvovaginal symptoms. A study found that when patients had symptoms, mycological cultures were taken, and vaginal pH was measured. Patients were then treated with fluconazole. After the symptoms subsided and the treatment ended, cultures and vaginal pH were re-evaluated. It was observed that vaginal pH increased in the diseased vagina and returned to normal after treatment and symptom resolution [48]. In our study, although vaginal pH and serum estradiol levels significantly increased post-treatment, there was no significant relationship between these changes and patients' symptoms or fungal culture growth. It has been demonstrated that estrogen decreases vaginal pH and increases cervical pH [45]. However, the exact serum levels of estrogen required to achieve this effect, or why some women have different vaginal pH levels despite the presence of estrogen, and why some women experience more frequent vulvovaginal candidiasis, remain unclear. In our study, we found no significant difference in estradiol's effect on vaginal pH between pre- and post-treatment serum levels. Our literature review did not find any comprehensive studies examining the relationship between serum estradiol levels, mycological culture results, and vulvovaginal symptoms. Our aim was to investigate whether there is a significant relationship between serum estradiol levels and these parameters, potentially leading to new studies. However, the statistical analysis results from our study indicated no significant difference in patients' symptoms or fungal culture growth when comparing pre- and post-treatment estradiol levels. These findings suggest that although ovulation induction significantly increases estradiol levels and vaginal pH, it does not predispose patients to candidal infections, implying that our treatments do not increase the risk of such infections. In another study, samples were taken from patients with vulvovaginal symptoms, and a significant relationship was found between symptoms and fungal growth [48]. In our study, there was a significant relationship between pre-treatment cultures and vulvovaginal symptoms, but no significant relationship was found between post-treatment cultures and symptoms. The reason for not finding the significant relationship post-treatment may be due to the medications increasing vaginal pH, causing asymptomatic but still present fungal growth in cultures. Another reason for not finding significant results in our study could be the limited number of patients. The percentage of patients with fungal growth in cultures was low in the general patient population. If the number of patients with fungal growth had been higher, we might have found significant relationships among the parameters we examined. Conclusion In conclusion, while estradiol and vaginal pH levels increased significantly after ovulation induction treatment, there was no significant association with vaginal symptoms or fungal culture results. These findings suggest that the hormonal treatments used in infertility therapy do not increase the risk of vaginal infections, providing reassurance for clinical practice. Further studies are needed to explore the physiological mechanisms and potential diagnostic applications of estradiol levels in vaginal health. Declarations a. Ethics approval The study was approved by the Manisa Celal Bayar University Animal Experiments Local Ethics Committee (approval number: 25.09.2023/547). Procedures were conducted in accordance with the ethical standards of the institution and the national research committee. b. Consent for publication All authors have reviewed the manuscript and give their consent for publication. c. Availability of data and material All data generated or analysed during this study are included in this published article. d. Competing interests The authors declare that they have no competing interests. e. Funding This research was conducted without any financial support or external funding. g. Acknowledgements The authors have no acknowledgements to declare. References Görgel EB, Çakıroğlu PF. Menopoz döneminde kadın. Ankara: Ankara Üniversitesi Basımevi; 2007: 1-15. Şen S, Er Güneri S. Öğrenci Hemşirelerin Genital Hijyen Uygulamaları ve Farkındalıkları. CBU-SBED. 2020;7(2):96-101. Ünsal A, Özyazıcıoğlu N, Sezgin S. DOĞU KARADENİZDEKİ BİR BELDE VE ONA BAĞLI DOKUZ KÖYDE YAŞAYAN BİREYLERİN GENİTAL HİJYEN DAVRANIŞLARI. Anadolu Hemşirelik ve Sağlık Bilimleri Dergisi. 2010;13(2):12-9. World Health Organization. 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Diagn Microbiol Infect Dis. 2020;97(2):115024. DOI: 10.1016/j.diagmicrobio.2020.115024 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5294623","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":368565415,"identity":"49b16e2e-14dc-47cd-b58b-71c036900ae2","order_by":0,"name":"Çağın Çakırgöz","email":"","orcid":"","institution":"Saruhanlı State Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Çağın","middleName":"","lastName":"Çakırgöz","suffix":""},{"id":368565416,"identity":"e62d9308-a205-42bd-9543-5dc8f2c9d976","order_by":1,"name":"Emine Çakırgöz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIiWNgGAWjYDCCAyDCAESwQdj8ICKhgBQtkg0gLQaEtDBAtICBAcIQ7IDv9gHGRzcK7sjxtx9LPFzxy8be+PzqxA8PDBjk+cUOYNUieS6B2TjH4JmxxJm0AwfP9qUxm914u1kC6DDDmbMTsGoxOMPAJp1jcDhxA0N6w8HGnsNsZjfObgBpSTC4jVML+2+glvoN/M/BWniMZ5zd/IOAFjZmoJYEAwmgwxp+HJYw4O/dhtcWyTOMzSCHGc648SzhYGNDmoHEDd5tFkATcPqF7wzzwc85fw7L8/enGX9s+GNjz99/dvPNHxU28vzS2LUwMDA2ILHbgIQEWKUEDuUY4A8Q8x8gVvUoGAWjYBSMEAAATQZmKEwMpa4AAAAASUVORK5CYII=","orcid":"","institution":"Manisa Celal Bayar University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Emine","middleName":"","lastName":"Çakırgöz","suffix":""},{"id":368565417,"identity":"88c864d3-2edc-4835-86e8-64584214fd4e","order_by":2,"name":"Dilara Kirmiç","email":"","orcid":"","institution":"Aliağa State Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dilara","middleName":"","lastName":"Kirmiç","suffix":""},{"id":368565420,"identity":"c94fba50-0f54-4fd6-b1b9-2676a7356254","order_by":3,"name":"Pınar Solmaz Hasdemir","email":"","orcid":"","institution":"Manisa Celal Bayar University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pınar","middleName":"Solmaz","lastName":"Hasdemir","suffix":""},{"id":368565421,"identity":"a4266b70-ae75-4827-b6d1-fa41a87c9b42","order_by":4,"name":"Kenan Değerli","email":"","orcid":"","institution":"Manisa Celal Bayar University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kenan","middleName":"","lastName":"Değerli","suffix":""}],"badges":[],"createdAt":"2024-10-19 12:53:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5294623/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5294623/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72104386,"identity":"7057a70a-3c08-4448-a139-68d93b59222c","added_by":"auto","created_at":"2024-12-22 14:01:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":410694,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5294623/v1/0afe99a6-293f-4242-95db-c55f0168843c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Impact of Serum Estradiol Levels on Vaginal pH and Candida Infections During Infertility Treatment","fulltext":[{"header":"Introduction","content":"\u003cp\u003eA woman's life comprises various stages, such as childhood, puberty, reproductive age, menopause, and old age, each characterized by specific health issues. Reproductive health is a crucial aspect influencing all stages of a woman's life. According to the World Health Organization, 36% of the total disease burden in women is due to reproductive health issues [1].\u003c/p\u003e \u003cp\u003eThe ages between 15 and 49, when women reach sexual maturity, are the periods with the highest frequency of reproductive health problems and peak reproductive system infections [2]. In our country, the prevalence of vaginal infections ranges from 37.1\u0026ndash;65.6% [3]. Reproductive system infections predominantly arise from lower genital tract issues, including vaginitis and cervicitis [4]. Although vaginal infections do not have high mortality rates, they cause significant morbidity [5]. If untreated, they can lead to upper genital tract infections and long-term sequelae such as chronic pelvic pain, ectopic pregnancy, and infertility [6].\u003c/p\u003e \u003cp\u003eReproductive system infections predominantly originate from lower genital tract issues such as vaginitis and cervicitis [7]. Though not highly fatal, vaginal infections contribute to significant morbidity [8]. Untreated vaginitis can ascend, leading to chronic pelvic pain, increased ectopic pregnancy rates, infertility, and tubo-ovarian abscesses [9]. Hence, addressing vaginitis is critical for mitigating future morbidities, and understanding predisposing factors is essential for effective treatment.\u003c/p\u003e \u003cp\u003eAlterations in vaginal pH and associated microbiota disruptions can lead to vaginal infections [10]. The significance of these infections lies in their potential to cause chronic conditions, infertility, and cancer if untreated [11]. Symptoms include foul odor, itching, sensitivity, and pain, often leading to avoidance of sexual activity, physical fatigue, and increased susceptibility to sexually transmitted infections. These infections also impact body image, causing psychological issues, and result in economic, time, and productivity losses [12].\u003c/p\u003e \u003cp\u003eThe human vagina hosts a diverse microbiota, predominantly Lactobacillus in healthy individuals. Disruptions in this ecosystem can lead to bacterial vaginosis, sexually transmitted infections, and vulvovaginal candidiasis. Factors such as menstruation, pregnancy, sexual activity, uncontrolled antibiotic use, and vaginal douching can alter the microbiota [13, 14]. Hormonal fluctuations during the menstrual cycle also impact the microbiota, with elevated vaginal pH reported in pathological conditions. Higher estradiol (E2) levels in young women due to pregnancy or hormonal contraceptives, and in postmenopausal women due to hormone replacement therapy, are linked to an increased risk of vaginal Candida [13, 14].\u003c/p\u003e \u003cp\u003eEstrogens are seen to affect the host defenses against Candida albicans by epithelial cells in the female genital tract [15]. Therefore, estrogen plays a vital role in the barrier and uptake functions of the vaginal epithelium, necessitating further comprehensive research.\u003c/p\u003e \u003cp\u003eThe vaginal flora is primarily aerobic, with Lactobacillus being the most frequently isolated microorganism in a healthy human vagina [16]. Lactobacillus produces lactic acid and hydrogen peroxide, preventing the overgrowth of other pathogenic bacteria [17]. Changes in environmental conditions can reduce the number of lactobacilli, allowing other bacteria to dominate and altering the vaginal microbiota [18]. The quantity of vaginal discharge can vary due to factors such as vaginal pH, age, hormonal status, sexual activity, menstrual cycle, estrogen levels, contraceptive methods used, medications, antibiotics, or surgical procedures performed on the patient [16, 19].\u003c/p\u003e"},{"header":"Methods","content":"\n\u003ch3\u003eVaginal pH and Infections\u003c/h3\u003e\n\u003cp\u003eDuring the reproductive period, vaginal pH ranges from 3.8 to 4.5 [20]. In pediatric, adolescent, and menopausal periods, the pH value is greater than 4.5 [21]. Maintaining the normal pH range acts as a protective barrier against bacteria and fungi. In the newborn period, the vagina is acidic due to estrogen from the mother, but pH changes as maternal estrogen levels drop [22].\u003c/p\u003e \u003cp\u003eDuring the sexually active period, the glycogen-rich structure of the vaginal mucosa epithelium and the dominance of lactobacilli help maintain an acidic pH. In the postmenopausal period, estrogen decreases, lactobacilli disappear, the vaginal epithelium thins, and pH becomes alkaline, ranging from 6 to 8 [22]. This change increases the risk of bacterial infections [23]. Patients may present clinically with complaints such as severe vaginal discharge, itching, dyspareunia, dysuria, and foul odor [24].\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCandidal Vaginosis\u003c/h2\u003e \u003cp\u003eCandidal vaginosis affects 75% of adult women at least once in their lifetime, with 45% experiencing vulvovaginal candidiasis at least twice a year [25]. Candida albicans is responsible for 85\u0026ndash;90% of cases [26]. It is characterized by a thick, white, curd-like discharge, dyspareunia, dysuria, vulvar itching, burning sensation in the vagina, and discomfort. Post-treatment with fluconazole and lifestyle changes are recommended [27]. Initially, topical hydrocortisone may be added to address irritation and itching [28]. Fluconazole is used in the treatment of candidal vaginitis [29]. The patient is given a single oral dose of fluconazole. If the patient has recurrent vulvovaginal candidiasis, a second dose of fluconazole is recommended one week later [28]. Treatment doses and durations vary depending on the severity of symptoms, the patient\u0026rsquo;s clinical status, and recurrence rates [29]. Oral antifungal therapy alone is not sufficient for the elimination of Candida. Patients should also be advised on dietary adjustments to eliminate refined carbohydrates that feed Candida, reducing the use of daily pads, avoiding vaginal douching that disrupts the flora, and wearing cotton underwear.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eThe Effects of Estrogen on Vaginal Flora\u003c/h3\u003e\n\u003cp\u003eVarious mechanisms have been developed to allow lactobacilli to dominate the flora again in postmenopausal women. Some of these mechanisms include the use of exogenous bacteria (probiotics), nutritional supplements (prebiotics), or a combination of both. The proportion of lactobacilli in the vaginal microbiota is important for protection against gynecological disorders and sexually transmitted infections [30,31]. However, this balance is disrupted post-menopause, leading to a decrease in lactobacilli.\u003c/p\u003e \u003cp\u003eStudies have shown that changes in pH are not the main factor underlying the decrease in lactobacilli. Even if the vaginal environment is artificially acidified, the lactobacillus population cannot be maintained effectively [32]. One reason for this change in lactobacillus quantity may be the reduced estrogen production during menopause compared to levels in reproductive-aged women. This may affect the dynamics of the vaginal mucosa [33, 34]. Low doses of estrogen have been shown to restore acidic vaginal pH and induce glycogen production [35]. However, the direct effects of estrogens on lactobacilli were not well understood. Recent studies have reported that estradiol has direct effects on bacteria such as Agrobacterium tumefaciens, Pseudomonas aeruginosa, Prevotella intermedia [36], and Staphylococcus epidermidis [37]. However, the effects of estradiol on lactobacilli remain unclear.\u003c/p\u003e\n\u003ch3\u003eThe Relationship Between Candidal Vaginosis and Estrogen\u003c/h3\u003e\n\u003cp\u003eVaginal infections caused by Candida albicans are quite common today and are used as an important model in studying pathogenic mechanisms and immune responses. A study conducted on mice showed that intense Candida colonization not only leads to candidal vaginosis but also disrupts vaginal immune homeostasis, potentially resulting in bacterial superinfection. Estradiol is thought to exhibit immunomodulatory effects, particularly by suppressing cytokine production by epithelial and immune cells [38].\u003c/p\u003e \u003cp\u003eThe effects of estradiol on Candida albicans were first studied by measuring filament formation and length. Following this, it was revealed that the localization of estradiol-binding protein 1 (Ebp1p) and the expression of CDR1 and CDR2 genes in Candida albicans are influenced by the host's estradiol levels [39]. Further research is needed to better understand the effects of estradiol on Candida albicans. Studies have shown that estrogens affect the defense mechanisms against Candida albicans in the female genital tract's epithelial cells. For example, primary uterine epithelial cells show a reduction in lipopolysaccharide-induced cytokines such as IL-6, IL-8, and macrophage migration inhibitory factor under the influence of estrogen. Additionally, estrogen has been found to reduce the expression of regulatory proteins like NF in these cells, which can lead to a decrease in the expression of cytokine genes such as IL-6, IL-8, IL-1α, IL-1β, and TNFα [40]. Therefore, it is believed that estrogen may play a significant role in the barrier and host defense functions of the vaginal epithelium.\u003c/p\u003e \u003cp\u003eEstrogen also supports follicular development in the ovaries, increases tubal motility, promotes glandular and stromal proliferation in the endometrial tissue, induces NaCl crystallization in cervical mucus, acidifies vaginal pH, raises cervical pH, strengthens uterine contractions, and makes the myometrial tissue more sensitive to oxytocin.\u003c/p\u003e\n\u003ch3\u003eStudy Description\u003c/h3\u003e\n\u003cp\u003eThis descriptive study was designed with the participation of healthy women aged 18\u0026ndash;49 who applied to the In Vitro Fertilization (IVF) Center at Manisa Celal Bayar University Hospital for infertility treatment. The study was conducted in accordance with the Helsinki Declaration revised in 2008, and received ethical approval from the Celal Bayar University Hospital Ethics Committee on 25.09.2023 (approval number 547). Informed consent was obtained from all participants.\u003c/p\u003e\n\u003ch3\u003eSelection of Patients\u003c/h3\u003e\n\u003cp\u003e Women aged 18\u0026ndash;49 who applied to the IVF Center for infertility treatment were included in the study after being provided with the necessary information and giving written consent. Exclusion criteria included being under 18 or over 50, using intrauterine devices (IUDs), having acute infection signs, being menstruating, having abnormal bleeding, being pregnant or lactating, and being menopausal.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eVaginal pH Measurement and Diagnosis of Vaginal Infections\u003c/h2\u003e \u003cp\u003e Vaginal pH measurements were performed on all eligible participants using a \"Handheld Digital pH meter.\" \"Sabouraud Dextrose Agar\" culture medium was used to detect mycological pathogens in the vaginal mucosa.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCollection of Blood Samples\u003c/h3\u003e\n\u003cp\u003eBlood samples were collected from all participants for E2 level testing. Routine blood tests were performed at the IVF Center, and additional tests for estradiol levels were included. Blood samples were analyzed at the hospital's biochemistry laboratory.\u003c/p\u003e\n\u003ch3\u003eBiochemical Measurements\u003c/h3\u003e\n\u003cp\u003eEstradiol levels were measured in all patients during the follicular phase of the menstrual cycle (days 2 or 3) and after treatment. Blood samples were analyzed using chemiluminescent methods.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using IBM SPSS 22.0 software. The Kolmogorov-Smirnov test was used to assess data distribution, and nonparametric analyses were conducted due to non-normal distribution. Descriptive tables and percentage distributions were created for socio-demographic data. The significance level was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 60 participants. Data on age, vaginal pH, presence of vaginal symptoms, mycological culture results, and serum estradiol levels were analyzed.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation Analyses\u003c/h2\u003e \u003cp\u003eNo statistically significant correlation was found between estradiol levels and vaginal pH measurements before and after ovulation induction treatment (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLogistic Regression Analysis\u003c/h2\u003e \u003cp\u003eNo statistically significant relationship was found between estradiol levels and symptoms or culture results before and after treatment (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, vaginal pH values were statistically significant in explaining the culture results, with higher pH values associated with increased culture positivity (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePaired Sample T-Test\u003c/h2\u003e \u003cp\u003eStatistically significant differences were found between pre- and post-treatment pH and estradiol levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe vaginal pH of women of reproductive age ranges from 3.8 to 4.5 [41]. Lactobacillus is the most frequently isolated microorganism in the vagina and influences vaginal pH by producing lactic acid [42]. Menopause leads to increased vaginal pH due to decreased estrogen levels [43]. Factors such as menstruation, pregnancy, sexual activity, antibiotic use, uncontrolled diabetes, humid and warm environments, and vaginal douching can alter the microbiota [44]. Increased estradiol levels have been associated with a higher risk of vaginal Candida infections [44]. Our study examined the impact of estradiol on vaginal pH and fungal infections.\u003c/p\u003e \u003cp\u003eOur results showed that vaginal pH was not predictive of vaginal symptoms or fungal culture results. Although estradiol and vaginal pH levels significantly increased after treatment, no significant relationship was found between these factors and symptoms or culture results.\u003c/p\u003e \u003cp\u003eEstrogen has been shown to lower vaginal pH and increase cervical pH [45]. However, the specific estrogen levels required to achieve these effects are not well understood. Our study did not find a significant relationship between estradiol levels and vaginal pH or mycological culture results. Future studies with larger sample sizes are needed to clarify these relationships and explore the potential use of estradiol levels as a diagnostic tool for vaginal Candida infections. Understanding the physiological mechanisms behind estrogen's impact on vaginal pH and microbiota could improve clinical diagnosis and treatment options.\u003c/p\u003e \u003cp\u003eA study has shown that vaginal pH can be a simple and cost-effective tool for providing information about the health and cellular morphology of the vaginal epithelium in clinical settings and for predicting vulvovaginal symptoms [45]. However, our results indicated that vaginal pH did not significantly affect the prediction of vaginal symptoms or the growth in fungal cultures.\u003c/p\u003e \u003cp\u003eAnother study in the literature found that using vaginal pH measurement as a screening tool is useful and inexpensive. It was noted that a vaginal pH of 4.5 is consistent with premenopausal serum estradiol levels and the absence of bacterial pathogens. Higher vaginal pH levels between 5.0 and 6.5 were associated with the proliferation of bacterial pathogens or decreased serum estradiol levels. In patients with high pH, a vaginal culture should confirm the diagnosis. If bacterial pathogens are absent, a vaginal pH between 6.0 and 7.5 can be a strong indicator of menopause [46]. In our study, ovulation induction was performed in infertile patients. Serum estradiol levels before treatment were found to be lower than after treatment. Similarly, as serum estradiol levels increased, vaginal pH also increased. Despite the increase in vaginal pH and estradiol levels post-treatment, there was no significant correlation between these changes and patients' symptoms or fungal culture growth.\u003c/p\u003e \u003cp\u003eAnother study in the literature indicated that while rising estrogen levels before ovulation increased vaginal pH, this increase did not lead to vaginal infections [47]. In our study, we observed that both estradiol and vaginal pH values significantly increased after gonadotropic agents were administered for ovulation induction. Despite the increase in vaginal pH and estradiol, there was no observed increase in candidal infections or vulvovaginal symptoms.\u003c/p\u003e \u003cp\u003eA study found that when patients had symptoms, mycological cultures were taken, and vaginal pH was measured. Patients were then treated with fluconazole. After the symptoms subsided and the treatment ended, cultures and vaginal pH were re-evaluated. It was observed that vaginal pH increased in the diseased vagina and returned to normal after treatment and symptom resolution [48]. In our study, although vaginal pH and serum estradiol levels significantly increased post-treatment, there was no significant relationship between these changes and patients' symptoms or fungal culture growth.\u003c/p\u003e \u003cp\u003eIt has been demonstrated that estrogen decreases vaginal pH and increases cervical pH [45]. However, the exact serum levels of estrogen required to achieve this effect, or why some women have different vaginal pH levels despite the presence of estrogen, and why some women experience more frequent vulvovaginal candidiasis, remain unclear. In our study, we found no significant difference in estradiol's effect on vaginal pH between pre- and post-treatment serum levels.\u003c/p\u003e \u003cp\u003eOur literature review did not find any comprehensive studies examining the relationship between serum estradiol levels, mycological culture results, and vulvovaginal symptoms. Our aim was to investigate whether there is a significant relationship between serum estradiol levels and these parameters, potentially leading to new studies. However, the statistical analysis results from our study indicated no significant difference in patients' symptoms or fungal culture growth when comparing pre- and post-treatment estradiol levels. These findings suggest that although ovulation induction significantly increases estradiol levels and vaginal pH, it does not predispose patients to candidal infections, implying that our treatments do not increase the risk of such infections.\u003c/p\u003e \u003cp\u003eIn another study, samples were taken from patients with vulvovaginal symptoms, and a significant relationship was found between symptoms and fungal growth [48]. In our study, there was a significant relationship between pre-treatment cultures and vulvovaginal symptoms, but no significant relationship was found between post-treatment cultures and symptoms. The reason for not finding the significant relationship post-treatment may be due to the medications increasing vaginal pH, causing asymptomatic but still present fungal growth in cultures.\u003c/p\u003e \u003cp\u003eAnother reason for not finding significant results in our study could be the limited number of patients. The percentage of patients with fungal growth in cultures was low in the general patient population. If the number of patients with fungal growth had been higher, we might have found significant relationships among the parameters we examined.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, while estradiol and vaginal pH levels increased significantly after ovulation induction treatment, there was no significant association with vaginal symptoms or fungal culture results. These findings suggest that the hormonal treatments used in infertility therapy do not increase the risk of vaginal infections, providing reassurance for clinical practice. Further studies are needed to explore the physiological mechanisms and potential diagnostic applications of estradiol levels in vaginal health.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003ea. Ethics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Manisa Celal Bayar University Animal Experiments Local Ethics Committee (approval number: 25.09.2023/547). Procedures were conducted in accordance with the ethical standards of the institution and the national research committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb. Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have reviewed the manuscript and give their consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ec. Availability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ed. Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ee. Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was conducted without any financial support or external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eg. Acknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no acknowledgements to declare.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eG\u0026ouml;rgel EB, \u0026Ccedil;akıroğlu PF. Menopoz d\u0026ouml;neminde kadın. Ankara: Ankara \u0026Uuml;niversitesi Basımevi; 2007: 1-15.\u003c/li\u003e\n\u003cli\u003eŞen S, Er G\u0026uuml;neri S. \u0026Ouml;ğrenci Hemşirelerin Genital Hijyen Uygulamaları ve Farkındalıkları. CBU-SBED. 2020;7(2):96-101.\u003c/li\u003e\n\u003cli\u003e\u0026Uuml;nsal A, \u0026Ouml;zyazıcıoğlu N, Sezgin S. DOĞU KARADENİZDEKİ BİR BELDE VE ONA BAĞLI DOKUZ K\u0026Ouml;YDE YAŞAYAN BİREYLERİN GENİTAL HİJYEN DAVRANIŞLARI. Anadolu Hemşirelik ve Sağlık Bilimleri Dergisi. 2010;13(2):12-9.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Report on the Regional Reproductive Health Strategy Workshop, South East Asia Region. City: World Health Organization; 1995.\u003c/li\u003e\n\u003cli\u003ePalas P, Kara\u0026ccedil;am Z. KADINLARIN TUTUKEVİNDE BULUNMALARININ GENİTAL HİJYEN UYGULAMALARINA ETKİSİ. Anadolu Hemşirelik ve Sağlık Bilimleri Dergisi. 2013;16(1):27-35.\u003c/li\u003e\n\u003cli\u003eCang\u0026ouml;l E, Toku\u0026ccedil; B. Jinekoloji polikliniğine başvuran kadınlarda genital enfeksiyon sıklığı ve genital hijyen davranışları. Florence Nightingale Hemşirelik Dergisi. 2013;21(2):85-91.\u003c/li\u003e\n\u003cli\u003eRabiu KA, Adewunmi AA, Akinlusi FM, Akinola OI. Female reproductive tract infections: understandings and care seeking behaviour among women of reproductive age in Lagos, Nigeria. BMC Womens Health. 2010;10:8. 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J Ayub Med Coll Abbottabad. 2009;21(2):90-3.\u003c/li\u003e\n\u003cli\u003eDurğut S, Yağmur Y. Mikrobiyotanın kadın ve \u0026ccedil;ocuk sağlığına etkisi. Ege \u0026Uuml;niversitesi Hemşirelik Fak\u0026uuml;ltesi Dergisi. 2020;36(3):207-16.\u003c/li\u003e\n\u003cli\u003eAcarkan T. Vajinal flora bozukluğu ve vajinit. Bilimsel Tamamlayıcı Tıp Reg\u0026uuml;lasyon ve N\u0026ouml;ral Terapi Dergisi. 2016;10(2):8-12.\u003c/li\u003e\n\u003cli\u003eKarako\u0026ccedil; H, \u0026Ouml;zerdoğan N, U\u0026ccedil;tu AK. Menopozla ilgili genito\u0026uuml;riner sendrom. JGON. 2017;14(3):122-6.\u003c/li\u003e\n\u003cli\u003eŞahin NN. Bakteriyel Vajinoz: Yaygınlığı, Tanısı ve İnfeksiyonu Etkileyen Fakt\u0026ouml;rler. Hacettepe \u0026Uuml;niversitesi Tıp Fak\u0026uuml;ltesi, Halk Sağlığı Anabilim Dalı, Ankara, Flora. 2000; 5(1): 67-73.\u003c/li\u003e\n\u003cli\u003eBagnall P, Rizzolo D. Bacterial vaginosis: a practical review. 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İstanbul: Nobel Tıp Kitabevleri, Nobel Matbaacılık; 2006.\u003c/li\u003e\n\u003cli\u003eO'Hanlon DE, Moench TR, Cone RA. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One. 2013;8(11). DOI: https://doi.org/10.1371/journal.pone.0080074\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"31\"\u003e\n\u003cli\u003eCone RA. Vaginal microbiota and sexually transmitted infections that may influence transmission of cell-associated HIV. J Infect Dis. 2014;210(Suppl 3):616-621. DOI: https://doi.org/10.1093/infdis/jiu459\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"32\"\u003e\n\u003cli\u003eBuggio L, Somigliana E, Borghi A, Vercellini P. Probiotics and vaginal microecology: fact or fancy? BMC Womens Health. 2019;19:72. DOI: 10.1186/s12905-019-0723-4.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"33\"\u003e\n\u003cli\u003eFarage MA, Maibach HI. Morphology and physiological changes of genital skin and mucosa. Curr Probl Dermatol. 2011;40:9-19. DOI: https://doi.org/10.1159/000321042\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"34\"\u003e\n\u003cli\u003eFarage M, Maibach H. Lifetime changes in the vulva and vagina. Arch Gynecol Obstet. 2006;273(4):195-202. DOI: https://doi.org/10.1007/s00404-005-0079-x\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"35\"\u003e\n\u003cli\u003eShen J, Song N, Williams CJ, Brown CJ, Yan Z, Xu C, et al. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep. 2016;6:24380. DOI: https://doi.org/10.1038/srep24380\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"36\"\u003e\n\u003cli\u003eFteita D, K\u0026ouml;n\u0026ouml;nen E, S\u0026ouml;derling E, G\u0026uuml;rsoy UK. Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the \u003cem\u003ePrevotella intermedia\u003c/em\u003e group bacteria. Anaerobe. 2014;27:7-13. DOI: https://doi.org/10.1016/j.anaerobe.2014.02.003\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"37\"\u003e\n\u003cli\u003eWang X, Zhou YC, Huang YC, Zou TN, L\u0026uuml; ZY, Chen Y, et al. Estradiol stimulates the growth and biofilm formation of clinical Staphylococcus epidermidis. Zhonghua Yi Xue Za Zhi. 2016 Oct 18;96(38):3083-9. Chinese. DOI: https://doi.org/10.3760/cma.j.issn.0376-2491.2016.38.010\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"38\"\u003e\n\u003cli\u003eEr DK, Uzuner H, Gen\u0026ccedil; S, Ke\u0026ccedil;eli S. Germ T\u0026uuml;p Testinin M\u0026uuml;eller Hinton Agar Ve Serumda Karşılaştırılması. KOU Sag Bil Derg. 2015;1(1):30-4. DOI: https://doi.org/10.30934/kusbed.349545\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"39\"\u003e\n\u003cli\u003eKurakado S, Kurogane R, Sugita T. 17\u0026beta;-Estradiol inhibits estrogen binding protein-mediated hypha formation in Candida albicans. Microb Pathog. 2017;109:151-155. DOI: 10.1016/j.micpath.2017.05.038\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"40\"\u003e\n\u003cli\u003eSert \u0026Uuml;Y, Bozkurt N. Human microbiota and its effects on gynecological diseases. Jinekoloji - Obstetrik ve Neonatoloji Tıp Dergisi. 2019;16(4):244-249.\u003c/li\u003e\n\u003cli\u003eGodha K, Tucker KM, Biehl C, Archer DF, Mirkin S. Human vaginal pH and microbiota: an update. Gynecol Endocrinol. 2017;34(6):451-455. DOI: 10.1080/09513590.2017.1407753\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"42\"\u003e\n\u003cli\u003eLinhares IM, Summers PR, Larsen B, Giraldo PC, Witkin SS. Contemporary perspectives on vaginal pH and lactobacilli. Am J Obstet Gynecol. 2011;204(2):120.e121-125. DOI: 10.1016/j.ajog.2010.07.010\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"43\"\u003e\n\u003cli\u003eMirmonsef P, Modur S, Burgad D, Gilbert D, Golub ET, French AL, McCotter K, Landay AL, Spear GT. 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DOI: 10.1016/s0002-9378(97)70345-4\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"47\"\u003e\n\u003cli\u003eLin YP, Chen WC, Cheng CM, Shen CJ. Vaginal pH value for clinical diagnosis and treatment of common vaginitis. Diagnostics. 2021;11(11):1996 DOI: 10.3390/diagnostics11111996\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"48\"\u003e\n\u003cli\u003eDonders GG, Grinceviciene S, Ruban K, Bellen G. Vaginal pH and microbiota during fluconazole maintenance treatment for recurrent vulvovaginal candidosis (RVVC). Diagn Microbiol Infect Dis. 2020;97(2):115024. DOI: 10.1016/j.diagmicrobio.2020.115024\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":"Infertility, Candida, Estradiol, Vaginal Flora, Vaginitis","lastPublishedDoi":"10.21203/rs.3.rs-5294623/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5294623/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e \u003cp\u003eThis study aims to investigate the potential impact of serum estradiol levels on vaginal pH, flora, and susceptibility to Candida infections in patients undergoing infertility treatment.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eClinical data and biochemical parameters were evaluated from 60 infertility patients aged 20\u0026ndash;49. Blood serum estradiol levels were measured on the 2nd day of the menstrual cycle along with assessments of vaginal pH and mycological cultures. These procedures were repeated post-ovulation induction at peak estradiol levels. A comparative analysis of pre- and post-treatment samples from the same patients was conducted to determine the effect of increased estradiol on vaginal pH and Candida growth. Statistical analyses were performed using SPSS 22.0 software, with significance set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003ePost-treatment measurements indicated a significant increase in serum estradiol and vaginal pH compared to pre-treatment levels. Despite this, no significant correlation was found between estradiol levels and changes in vaginal pH, vulvovaginal symptoms, or culture growth. Similarly, vaginal pH levels did not significantly affect vulvovaginal symptoms or Candida culture growth. However, a significant relationship was identified between pre-treatment cultures and vulvovaginal symptoms, a correlation absent in post-treatment samples.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eThe findings suggest that the substantial increase in serum estradiol levels during infertility treatment does not predispose patients to vaginal Candida infections via alterations in vaginal pH. There appears to be no additional risk of candidal infections associated with elevated estradiol during infertility treatments.\u003c/p\u003e","manuscriptTitle":"The Impact of Serum Estradiol Levels on Vaginal pH and Candida Infections During Infertility Treatment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-02 11:04:33","doi":"10.21203/rs.3.rs-5294623/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":"b9b0b198-bc1f-45b6-a1c3-036097d6133c","owner":[],"postedDate":"November 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-22T13:53:36+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-02 11:04:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5294623","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5294623","identity":"rs-5294623","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}