1. Introduction
Vaginitis, an ailment affecting 75% of women globally at least once in their lifetime, is intrinsically linked to the delicate balance of the vaginal ecosystem and its pH levels. The vagina hosts a dynamic microbial environment, and disruptions can lead to pH imbalances, often resulting in vaginitis and necessitating medical intervention. Despite not being life-threatening, vaginitis causes significant discomfort and pain, impacting daily life. Bacterial vaginosis, trichomoniasis, and vulvovaginal candidiasis are the most prevalent forms of vaginitis. This review delves into the causes, diagnostic approaches, and symptoms of these vaginitis types, explores their connection to other diseases, addresses recurrent vaginitis and immune system interactions, and discusses effective treatments. Furthermore, we will examine the critical relationship between vaginal pH and the vaginal ecosystem, identify factors influencing vaginal pH, and introduce available vaginal pH self-testing products.
Keywords: vaginal pH, vaginitis, diagnosis, treatment
2. The Crucial Role of Normal Vaginal pH
Vaginal health is significantly determined by the vaginal pH value, which reflects the acidity or alkalinity within the vagina. Measured on the pH scale, where 7 is neutral, a healthy vaginal pH is moderately acidic, typically ranging from 3.8 to 5.0 [2, 3]. This acidity, lower than that of blood or interstitial fluids, is vital for protecting the vaginal mucosa from pathogenic organisms [4]. Factors such as overall health, age, hydration, diet, and sexual practices can influence vaginal pH. Notably, vaginal pH is age-dependent, with reproductive-age women generally having a pH between 4.0 and 4.5, while premenarchal and postmenopausal women may exhibit slightly higher values [12].
Maintaining this healthy vaginal pH is a complex interplay involving Lactobacillus acidophilus and other natural flora, estrogen, glycogen, and the dynamic balance between flora and potential pathogens [16]. Vaginal microorganisms, particularly Lactobacillus acidophilus, are key to this stability. Lactobacillus acidophilus ferments glycogen from vaginal mucosa decay into lactic acid, releasing hydrogen ions and creating an acidic environment (pH 4.0-4.5) [18]. This acidity acts as a protective barrier against harmful microbes, preventing infections. Imbalances in this ecosystem can lead to abnormal vaginal pH, indicating bacterial pathogens or menopausal status [19]. Elevated vaginal pH is also linked to bacterial vaginosis (BV) and preterm deliveries in pregnant women [20]. Monitoring vaginal pH, even through self-testing, is thus a proactive step in managing and preventing infections.
Factors Disrupting Vaginal pH Balance
Daily life factors can easily disrupt the normal vaginal pH, including unprotected sex, antibiotic use, vaginal douching, and menstrual cycle variations.
Unprotected sexual intercourse can lead to vaginal pH imbalance [21]. Semen, with a pH of around 8.0, is alkaline and can alter vaginal pH. It can stimulate bacterial growth, acting as a physiological buffer [22]. Unprotected sex can elevate vaginal pH significantly, persisting for 10-14 hours [23], reducing the vagina’s natural defense against infections.
Antibiotics, while crucial for treating bacterial infections [24], including vaginitis [24, 25], can also disrupt vaginal pH. They eliminate beneficial bacteria, such as lactobacilli, which are essential for maintaining vaginal acidity. Although necessary in severe cases, antibiotics can rapidly alter the vaginal microbiome within hours [26].
The vagina is self-cleaning and generally requires only external washing with water. Vaginal douching or excessive cleaning can disrupt the natural vaginal flora and pH balance. This disruption can lead to adverse effects like BV, pelvic inflammatory disease (PID), pregnancy complications, and even cervical cancer [27, 28, 29, 30]. The risks of vaginal douching outweigh any perceived benefits.
Menstrual cycles, regulated by endocrine factors [31], also influence vaginal pH. Menstrual blood, being slightly alkaline, can raise vaginal pH. Menstrual irregularities due to hormonal imbalances can further disrupt vaginal mucosa, affecting the microbial environment and increasing vaginitis risk [32]. While normal menstruation typically maintains a vaginal pH between 3.8 and 5.0 [3], menstrual cycle abnormalities, common in puberty, are associated with increased risk of abnormal pH and subsequent BV susceptibility [33].
3. Common Types of Vaginitis
Vaginitis is a prevalent condition among women of all ages, with most experiencing it at least once [34]. It arises from pathogen introduction or vaginal environment changes that favor pathogen proliferation and alter vaginal flora. Symptoms like discharge, odor, itching, irritation, and burning [35] cause discomfort and potential vaginal complications, often linked to abnormal vaginal flora [12]. Vulvovaginal complaints are a frequent reason for seeking medical advice [36]. The primary causes of vaginitis are bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis [16].
Bacterial vaginosis accounts for 40-50% of vaginitis cases, vulvovaginal candidiasis for 20-25%, and trichomoniasis for 15-20%. Non-infectious causes, such as irritation, allergies, and atrophic or inflammatory vaginitis, are less common, representing 5-10% of cases [14]. Table 1 summarizes symptoms, signs, risks, and pH values associated with different vaginitis types. Diagnosing vaginitis based on symptoms alone is challenging. Notably, women with vulvovaginal candidiasis can present with a normal or acidic vaginal pH [14]. Misdiagnosis can lead to ineffective treatment and complications like pelvic inflammatory disease [37, 38].
Bacterial vaginosis, the most common vaginitis, results from an imbalance where anaerobic bacteria overgrow and protective Lactobacillus diminishes [39]. Organisms like Gardnerella vaginalis, Mobiluncus species, Mycoplasma hominis, and Peptostreptococcus species are implicated [40]. Diagnosis relies on Amsel criteria and Gram staining [41]. A “fishy” odor, produced by amines from anaerobic bacteria, is a characteristic symptom [42, 43]. BV can lead to pelvic inflammatory disease (PID) and tubal infertility [44, 45]. Studies show a higher prevalence of BV in infertile women compared to fertile women (45.5% vs. 15.4%), and in patients with unexplained infertility (37.4%) and polycystic ovarian disease (PCOD) (60.1%) [48]. Treating BV may improve pregnancy rates in infertile women [49].
Vulvovaginal candidiasis, the second most common vaginal infection [14], affects approximately 50% of women at least once, constituting over 25% of infectious vaginitis cases [50]. While various Candida species exist, Candida albicans is responsible for 80-90% of infections [51]. Symptoms include itching, vaginal soreness, dyspareunia, and increased discharge [43], often with a normal vaginal pH. Treatment typically involves vaginal imidazole or triazole antifungals or oral fluconazole [52]. Vulvovaginal candidiasis can be categorized as simple or complex based on clinical presentation, microbiology, host factors, and treatment response [53], with treatment classifications detailed in Table 2.
Trichomoniasis, the third most common vaginitis, is caused by the protozoan Trichomonas vaginalis, a motile organism with flagella [2]. It is the most prevalent non-viral sexually transmitted infection, particularly among individuals with multiple partners [54], affecting 30-80% of male partners of infected women [55]. Symptoms are often nonspecific, including increased discharge, irritation, and itching [54], and diagnosis can be challenging as 20-50% of women are asymptomatic [34, 56]. Microscopic diagnosis is more reliable, and other indicators include a positive odor test and vaginal pH greater than 5.4 [43]. Trichomoniasis is linked to increased HIV transmission rates [57]. Due to its sexual transmission and high recurrence, the CDC recommends retesting 3 months post-treatment [53].
3.1. Effective Treatments for Vaginitis
Effective management of vaginitis requires accurate diagnosis and appropriate treatment. For bacterial vaginosis, standard treatment is metronidazole (Flagyl) (500 mg twice daily for 7 days) [53]. Alternatives include metronidazole gel (Metrogel) (one applicator (5g) daily for 5 days) or clindamycin 2% cream (one applicator (5g) at bedtime for 7 days). Clindamycin cream is preferred for metronidazole allergies or intolerance. Cochrane reviews indicate comparable efficacy between clindamycin and metronidazole, with 91-92% clinical cure rates after 2-3 weeks [58]. In 2018, the FDA approved single-dose oral secnidazole (Solosec) for BV [59], with trials showing similar efficacy to metronidazole [60]. Contrary to previous beliefs, antibiotic treatment for BV during pregnancy does not prevent preterm birth [61]. Treatment primarily aims to relieve symptoms, though recurrence is common, necessitating extended treatment for frequent relapses.
Vulvovaginal candidiasis treatment options include topical and oral antifungals [62], aimed at symptom relief. Topical azoles and single-dose oral fluconazole (Diflucan) (150 mg) are CDC-recommended first-line treatments [53]. Common topical medications are clotrimazole, miconazole, terconazole, and butoconazole, typically used for 3-7 days. Oral fluconazole is favored over ketoconazole due to fewer side effects [63]. Treatment strategies differ for simple and complicated Candida vaginitis, with complicated cases requiring more aggressive approaches. Recurrent vaginal candidiasis, often Candida albicans-related, benefits from intensive fluconazole treatment (150 mg every three days for three doses) and maintenance therapy (150 mg weekly for 6 months) to relieve symptoms for up to a year [64].
Trichomonas vaginalis is a globally prevalent sexually transmitted parasite, causing trichomoniasis, and can also infect the male prostate and urethra [65]. Treatments primarily involve oral or parenteral 5-nitroimidazole drugs. In the US, FDA-approved options are metronidazole and tinidazole [66]. Single-dose or extended nitroimidazole regimens cure about 90% of cases [67].
Gastrointestinal discomfort is a common, usually mild, side effect of metronidazole, but can be severe at high doses for refractory trichomoniasis [68]. Tinidazole, another nitroimidazole, has a lower therapeutic dose and milder side effects [69]. Vaginal nitroimidazole cream has a lower cure rate (<50%). Combined oral and vaginal treatment shows better efficacy than oral treatment alone [67, 70]. Concurrent treatment of sexual partners and abstinence until both are symptom-free post-treatment are advised.
Oral lactic acid bacteria administration shows promise in altering vaginal microbiota. Studies using L. fermentum 57A, L. plantarum 57B, and L. gasseri 57C daily for 60 days improved Nugent scores and reduced vaginal pH [71]. Lactobacillus acidophilus, Lactobacillus rhamnosus GR-1, and Lactobacillus fermentum RC-14 at ≥108 CFU/day also show therapeutic effects [72]. Maintaining balanced intestinal bacteria may positively influence vaginal microbiota. Lactobacillus supplements can support a weakly acidic vaginal environment, reduce urogenital infections, and establish a protective barrier.
3.2. Recurrent Vaginal Candidiasis and Immune System Dynamics
Recurrent vaginal candidiasis is a common concern [73]. Despite effective initial treatments, relapse is frequent post-therapy. Temporary suppression of cell-mediated immunity can contribute to recurrence [74]. Lymphocytes in women with recurrent candidiasis often show reduced proliferative response to Candida albicans, potentially due to increased prostaglandin E2 production by macrophages [75], inhibiting interleukin 2 and lymphocyte proliferation. Impaired lymphocyte response facilitates Candida albicans proliferation and infection.
Recurrent vaginal candidiasis may stem from antibiotic resistance, with symptoms worsening in cases of four or more annual episodes [76]. While long-term fluconazole maintenance can manage relapses, prolonged use is challenging [64] and may lead to drug resistance, shifts in Candida species, and increased non-communicable diseases.
Wozniak et al. (2005) highlighted cell-mediated immunity (CMI) as the primary defense against most Candida infections, though not against systemic or local Candida infections. Immunomodulation in vaginal tissues suggests suppression of protective Th1 responses. Research explores immunotherapy and gene therapy to enhance protection against vaginal candidiasis in mouse models [77]. Adenomyosis may enable vaginal tissue tropism, making immunotherapy applicable for vaginal diseases requiring local immune response control. However, cytokine immunotherapy and adenovirus gene therapy have not yet significantly improved protection against vaginal candidiasis [78].
Bernalis et al. (2015) used animal models to characterize mucosal immunity mechanisms against Candida albicans, focusing on innate and adaptive immunity interactions [76]. Their findings indicate that Th1 protective immunity can induce both cell-mediated (CMI) and antibody (Abs)-mediated immunity. Active intravaginal immunization with aspartyl proteases, specifically recombinant proteins like virions and secreted aspartyl protease 2 (Sap2) (PEV7), may prevent vaginal Candida albicans infections, suggesting potential for a recurrent vaginal candidiasis vaccine. Combining these insights may pave the way for immunotherapy-based vaccines to alleviate recurrent vaginitis.
3.3. Vaginal pH in Infection Diagnosis
Normal vaginal pH ranges from 3.8 to 5.0, but it can be altered by vaginitis, particularly due to changes in the vaginal ecosystem from topical treatments or unprotected sex. Thus, vaginal pH measurement is a useful screening tool for vaginitis. Anaerobic bacteria replacing normal lactobacilli elevates vaginal pH above 4.5 in bacterial vaginosis. Trichomonas infections often result in pH > 5.4. Candida vaginitis typically presents with normal vaginal pH, although elevated values have been reported [13, 36]. Hanna et al. (1985) found vaginal microbial status changes at pH 5.0-5.5 or 6.0-7.5, supporting the correlation between increased vaginal pH and infection [79].
Thinkhamrop et al. (1997) assessed vaginitis in gynecology outpatients using medical history, physical and vaginal exams, microbiological specimens, and pH measurements [80]. Their results showed that vaginal fluid pH testing combined with clinical symptoms is more reliable for vaginitis screening than pH testing alone. pH testing alone showed higher sensitivity for BV diagnosis compared to other vaginitis types, with an overall sensitivity of about 50% for infectious vaginitis, increasing to 73% for BV specifically, and only 22% for fungal vaginitis. Combining pH testing with clinical diagnosis improves sensitivity to 67.5%.
Factors like unprotected sex, antibiotics, douching, and menstrual cycle changes can also alter vaginal pH. pH testing alone has a reported vaginitis diagnostic sensitivity of 66% [81]. Combining pH tests with clinical symptoms for BV screening increases sensitivity to 81.3% (95% CI: 69.2-89.5) (Table 3). The higher sensitivity for BV is attributed to bacterial overgrowth reducing lactobacilli and their acidic secretions, thus increasing pH. Vaginal pH tests are clinically valuable for BV detection. While limited in sensitivity alone, they are convenient for self-monitoring, especially with vaginitis symptoms.
4. Vaginal pH Self-Test Products
For women experiencing symptoms like itching, odor, or abnormal discharge, vaginal pH self-testing can be beneficial. However, the FDA cautions that these tests do not diagnose HIV, chlamydia, herpes, gonorrhea, syphilis, or group B streptococcus [82]. Clinicians already utilize vaginal pH testing for vaginitis diagnosis [8, 19]. Self-testing empowers women to manage aspects of their health. These self-test tools are recommended for rapid, simple, and effective early screening.
The Hygeia Touch Self-Testing Kit for Vaginal Infection [83] employs a vaginal applicator with a bromocresol green pH indicator. This FDA-registered device uses a pH test paper on a biocompatible stick. Inserted vaginally to collect a sample, it rests for 1 minute to react. Colorimetric results indicate pH level, aiding in distinguishing Candida albicans, bacteria, or trichomonas infections.
The Biosynex Exacto 3 vaginal infection test [84] offers 90% reliability and accuracy, providing immediate, easy-to-interpret, color-coded results for preliminary vaginal infection diagnosis. Table 4 summarizes other commercially available vaginitis self-diagnostic devices.
The Hygeia Touch kit stands out with its double-layer protection, preventing test paper detachment and direct skin contact, and an elastic baffle for safe insertion depth. Medical-grade plastic ensures comfort and safety. These devices aid in disease course monitoring and appropriate OTC antifungal selection, FDA-approved since 1990. They empower self-care, promote vaginal health awareness, and facilitate vaginal pH and overall health maintenance.
5. Conclusion
Vaginal health is a critical aspect of women’s overall well-being, with vaginal pH playing a pivotal role. pH is valuable in diagnosing, monitoring, and managing vaginitis-related conditions. We have outlined factors affecting vaginal pH, various vaginitis types, symptoms, risks, and treatments. Recurrent vaginitis is linked to immune system factors. Vaginal pH self-test products are useful for monitoring pH and detecting vaginitis, especially alongside other diagnostic methods. These tools serve as point-of-care tests in clinics and convenient self-tests at home, promoting vaginal health awareness and proactive care.
Acknowledgments
This study was supported by grants from the Ministry of Science and Technology, Taiwan (109-2222-E-182A-002).
Author Contributions
Conceptualization, Y.-P.L., W.-C.C., C.-M.C. and C.-J.S.; investigation, Y.-P.L., W.-C.C., C.-M.C. and C.-J.S.; writing—original draft preparation, Y.-P.L. and W.-C.C.; writing—review and editing, Y.-P.L., W.-C.C., C.-M.C. and C.-J.S.; visualization, Y.-P.L.; supervision, C.-J.S.; project administration, C.-J.S. All authors have read and agreed to the published version of the manuscript.
Funding
This study is partially funded from Taiwan’s Ministry of Science and Technology (MOST 109-2622-E-007-009-CC3, MOST 109-2222-E-182A-002 & MOST 110-2221-E-007-073-MY2).
Conflicts of Interest
The authors declare no conflict of interest.
Footnotes
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
(References are the same as in the original article and are not included here for brevity, but would be present in a complete article).
Table 1. Symptoms and signs of vaginitis (Information from [12,13,14,15,16,17]).
| Diagnosis | Etiology | Symptoms | Signs | Risks | pH Value |
|---|---|---|---|---|---|
| Bacterial vaginosis | Anaerobic bacteria (Prevotella, Mobiluncus, Gardnerella vaginalis, Ureaplasma, Mycoplasma) | Fishy odor; malodorous; homogenous; clear, white, or gray discharge that may worsen after intercourse; pelvic discomfort may be present. | No inflammation. | Increased risk of HIV, gonorrhea, chlamydia, and herpes infections. | greater than 4.5 |
| Vulvovaginal candidiasis | Candida albicans, Candida krusei, Candida glabrata | No odor; white, thick, cheesy, or curdy discharge; vulvar itching or burning. | Signs of inflammation;Vulvar erythema and edema. | vulvodynia | 4.0 |
| Trichomoniasis | Trichomonas vaginalis | Green or yellow, frothy discharge; foul odor; pain with sexual intercourse, vaginal soreness, dysuria. | Signs of inflammation, “strawberry cervix”; Vestibular erythema may be present. | Increased risk of HIV infectionIncreased risk of preterm labor.Should be screened for other sexually transmitted infections. | 5.0~6.0 |
Table 2. Treatment for the most common vaginitis (Information from [13,14,15,36]).
| Treatment |
|---|
| Initial Regimen |
| Bacterial vaginosis |
| Vulvovaginal candidiasis |
| Trichomoniasis |
Table 3. Diagnostic performance of vaginal fluid pH and other tests in screening for vaginitis 1–3 and for BV 4–6 (Information from [80]).
| Test | Sensitivity(95% C.I.) | Specificity(95% C.I.) | Accuracy(95%C.I.) |
|---|---|---|---|
| pH screen for vaginitis | 49.7%(42.6–56.9) | 75.5%(69.0–81.0) | 63.0%(58.1–67.7) |
| pH + clinical symptoms and signs to screen for vaginitis | 67.5%(60.4–73.9) | 62.0%(55.0–68.6) | 64.7%(59.8–69.4) |
| Clinical symptoms and signs to screen for vaginitis | 38.6%(31.9–45.7) | 77.7%(71.5–82.9) | 59.0%(54.1–63.7) |
| pH screen for BV vaginitis | 73.4%(60.7–83.3) | 70.1%(64.9–74.8) | 70.6%(65.9–75.0) |
| pH + clinical symptoms and signs to screen for BV vaginitis | 81.3%(69.2–89.5) | 53.1%(47.6–58.5) | 57.5%(52.6–62.4) |
| Clinical symptoms and signs to screen for BV vaginitis | 39.1%(27.4–52.1) | 71.5%(66.5–76.1) | 66.6%(61.9–71.1) |
Table 4. Summary of commercially available vaginal self-test products.
| Brand | Hygeia Touch | Biosynex | FloriSense | Monistat |
|---|---|---|---|---|
| Appearance | ||||
| Accuracy | 88% | 90% | 92% | 92% |
| Test/pack | 1 | 3 | 2 | 2 |
| Advantage | Optimized safety and ease of use with double-layer structure. | Quantity advantage with 3 tests per box. | High reliability with over 90% accuracy and easy-to-read results. | Specifically effective for diagnosing yeast-based vaginal infections. |
