Understanding Bacterial Vaginosis (BV) Symptoms and Treatment

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Summary

  • Bacterial vaginosis (BV) is a very common disruption of the vaginal microbiome, and the cause is unknown.
  • Untreated BV may increase your risk of pelvic inflammatory disease, infertility, and preterm birth, and make you more prone to getting a sexually transmitted infection.
  • BV is treated with antibiotics. While treatment is often successful, about 15-58% of women experience another episode of BV, something known as recurrent BV. There are things you can do to support your vaginal microbiome and stop BV from coming back.
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Bacterial vaginosis (BV) is an overgrowth of unfriendly bacteria.

In a typical healthy vaginal community, Lactobacillus are in charge. These protective bacteria like to dominate in numbers, and while they may be fine with other microbes hanging around, they rarely like to share space with unfriendly bacteria.

In bacterial vaginosis (BV), unfriendly bacteria such as Gardnerella vaginalis, Fannyhessea vaginae (also known as Atopobium vaginae), Prevotella, and others steal the microphone from Lactobacillus and use it to create a disrupted environment, with an increased pH [1]–[3].

Unfortunately, what causes BV is unknown. Some factors that may contribute to it are:

  • Having a vaginal community that is naturally low in Lactobacillus (CST 4)
  • Hormone changes
  • A high number of sexual partners
  • Smoking
  • Poor personal hygiene
  • Douching
  • Antibiotics [4]–[7]

Some scientists believe BV should be considered a sexually transmitted infection [8], but this is a controversial topic. Sharing microbes through sex can certainly alter your vaginal microbiome, but it’s not absolutely necessary to have sex to get BV.

If you have BV, you’re not alone

You may have had or currently have BV. Or maybe you have had it more than once. There’s nothing to be ashamed of because BV is one of the most common vaginal infections in women.

In fact, one in three women gets BV at some point in their lives and approximately 29% of women in the US have BV [9].

Common BV symptoms

One way to know if you have BV is to pay attention to your vaginal discharge. BV discharge is characterized by:

  • A fishy odor
  • Thin texture
  • Milky white or grayish color

Other common BV symptoms are:

  • A burning sensation in your vagina
  • Pain during sex or urination

A shocking fact is that 84% of women diagnosed with BV have no symptoms at all [10]. But not having any symptoms doesn’t mean you’re free from all the BV-associated complications.

These asymptomatic cases are more likely to be detected with molecular techniques such as metagenomic sequencing, the technology we use in Tiny Health microbiome tests.

How BV is diagnosed

BV is often diagnosed by the Amsel criteria [11]. If you have three out of four Amsel criteria, your clinical provider will diagnose you with BV. These criteria include:

  • A thin white-grayish vaginal discharge
  • A fishy smell
  • Clue cells (these are vaginal epithelial cells covered in bacteria) on microscopic examination
  • A pH higher than 4.5

A second way of diagnosing BV is by using the Nugent criteria. This involves putting a vaginal fluid sample into a microscope slide, staining it, and looking at it under a microscope [11]. The presence and numbers of different bacteria are then used to calculate a score and diagnose or rule out BV.

The problem is that this method is much more cumbersome and it usually requires sending your sample to a laboratory.

Finally, a third way of diagnosing BV is through molecular diagnostic techniques. These may be more expensive, but provide a better picture of the vaginal microbiome. Plus, this type of testing isn’t affected by the subjective interpretation of your provider. Our Vaginal Health Test can detect all the bacteria that are part of your vaginal microbiome at a very detailed level.

Changes in your vaginal microbiome during BV

One characteristic of BV is low levels of Lactobacillus [12]. There is, however, one particular species that doesn’t mind hanging out with the BV gang: Lactobacillus iners [13]. While this species is considered protective, it doesn’t protect as well as other Lactobacillus

Vaginal communities dominated by L. iners (CST 3) may be less stable and often transition to BV-like communities over time.

Gardnerella vaginalis is a key player in BV. While it’s usually present in small amounts in healthy vaginas [14], when its numbers increase, it pushes out protective Lactobacillus and creates a shield called a ‘biofilm’, which helps bacteria survive [15]–[17]. Other bacteria like Prevotella bivia and Fannyhessea vaginae join G. vaginalis to strengthen the biofilm and seek shelter within it [15]–[18].

Additionally, several other bacteria can be linked to BV, including Megasphaera, Dialister, Mobiluncus, Sneathia amnii, Sneathia sanguinegens, Porphyromonas, Aerococcus, UBA629 sp005465875 (also known as Candidatus Lachnocurva vaginae), Eggerthella, and Peptoniphilus [3], [19].

BV and its associated complications

Untreated BV may increase your risk of other vaginal, urinary, and sexually transmitted infections. It may also contribute to the development of inflammatory conditions that can threaten fertility or lead to pregnancy complications [20], [21].

Having BV may increase your risk of:

  • Pelvic inflammatory disease (PID). BV could make you about three times more likely to develop asymptomatic PID [22].
  • Infertility. High levels of G. vaginalis or F. vaginae could decrease your chances of getting pregnant after in vitro fertilization [23].
  • Recurrent implantation failure (RIF). Gardnerella, Fannyhessea, and Prevotella are high in women that experience RIF [24].
  • Preterm birth (PTB). Compared to healthy women, pregnant women diagnosed with BV are about twice as likely to experience PTB [25], [26]. Also, having BV-associated bacteria such as Gardnerella, Prevotella, Fannyhessea, Sneathia, and Megasphaera may significantly increase the risk of PTB [27]–[35].
  • Viral sexually transmitted infections. Compared to women with a negative diagnosis, women diagnosed with BV are 1.6-2.6 times more likely to be infected with Human immunodeficiency virus (HIV), Human papillomavirus (HPV), or Herpes simplex virus 2 (HSV-2) [36]–[38].
  • Bacterial sexually transmitted infections. Compared to women with a negative diagnosis, women diagnosed with BV are 1.4-2.0 times more likely to get chlamydia, gonorrhea, or trichomoniasis [39], [40].

That’s a pretty long list of complications. The good news is that BV can be treated and there are things you can do to prevent it from coming back.

BV treatment

BV is treated with antibiotics. If you suspect you may have BV, it’s very important to always get a diagnosis from your provider, never do antibiotics on your own. This is especially relevant if you are pregnant or breastfeeding. Depending on your pregnancy trimester, some antibiotics for BV may be harmful for your baby. Your provider will help you choose the appropriate treatment.

These are the most common antibiotics used to treat BV:

  • Metronidazole (Flagyl, Metrogel-Vaginal, others). Comes as a pill to take orally or as a topical gel that you apply into your vagina. 
  • Clindamycin (Cleocin, Clindesse, others). Comes as a cream that you apply into your vagina. 
  • Tinidazole (Tindamax). Comes as a pill to take orally.

The bad news? BV-associated bacteria build such a strong biofilm that they are not easy to get rid of with antibiotics. 

Depending on the country, 15-58% of women experience recurrent BV [41]–[43]. This occurs when symptoms are alleviated by antibiotics but return soon after the treatment is finished, and this can happen more than one time [13], [14]. This may also happen because bacteria like F. vaginae can be resistant to antibiotics like metronidazole [44].

Another thing to consider is that, while antibiotics for BV are intended to eliminate BV-associated bacteria, they can also impact other beneficial bacteria like Lactobacillus. Because of this, an alternative treatment may be a good idea.

Alternative treatments for BV include:

  • Vaginal Lactobacillus probiotics. These can be used together with antibiotic treatment to increase success and replenish Lactobacillus levels [45], [46]. You may also want to try probiotics alone, especially if you experience recurrent BV that doesn’t fully improve with antibiotic treatment. Some clinical trials in non-pregnant women have shown that probiotics can be effective in treating BV [47], [48].

  • Vaginal Lactobacillus suppositories. There are several studies showing that these are effective at restoring Lactobacillus levels, and may help reduce the episodes of BV [49]–[54]. If you’re pregnant, ask your provider before trying vaginal suppositories. Some brands may contain boric acid, which should not be used during pregnancy.

  • Vaginal vitamin C tablets. One of the characteristics of BV is a higher vaginal pH. Vaginal vitamin C tablets have a special formulation that slowly releases vitamin C in your vaginal canal. This helps lower the pH, which inhibits the growth of unfriendly species and supports beneficial Lactobacillus [55]–[59]. These tablets can be used along with a Lactobacillus probiotic to help with colonization. Some Lactobacillus suppositories contain vitamin C (also known as ascorbic acid).

  • Essential oil suppositories. If you are not pregnant, essential oil suppositories are another alternative that may help relieve BV symptoms. However, it’s important to mention that these have only been tested in laboratory experiments. If you choose to use them, always do so with the guidance of your provider. Dr. Aviva Romm also shares her go-to homemade suppository essential oil blend for addressing BV.

When shopping for a vaginal probiotic or suppository, you may want to look for high-performing and well-researched vaginal strains. When you take a Tiny Health vaginal test we recommend products whose strains have been proven to be effective in clinical trials.

Reduce the risk of BV

Luckily, there are things you can do to support your vaginal microbiome and reduce the risk of developing BV. A few include:

  • Eating fermented foods such as yogurt, kefir, and pickles 
  • Wearing cotton underwear and loose fitting clothes
  • Consuming probiotics
  • Avoiding douching or using harsh soaps or wipes
  • Wiping from front to back when using the bathroom

Following these measures is especially important if you have a certain vaginal microbiome type called Community State Type (CST) 4, which features low levels of Lactobacillus. Don’t know what type of vaginal community you have?

Our Tiny Health vaginal test can help you identify yours and provide a detailed report with personalized tips to optimize your vaginal health.

References

[1] S. Srinivasan et al., “More than meets the eye: associations of vaginal bacteria with gram stain morphotypes using molecular phylogenetic analysis,” PloS One, vol. 8, no. 10, p. e78633, 2013, doi: 10.1371/journal.pone.0078633..

[2] S. Srinivasan et al., “Metabolic signatures of bacterial vaginosis,” mBio, vol. 6, no. 2, pp. e00204-15, Apr. 2015, doi: 10.1128/mBio.00204-15.

[3] C. A. Muzny et al., “Identification of Key Bacteria Involved in the Induction of Incident Bacterial Vaginosis: A Prospective Study,” J. Infect. Dis., vol. 218, no. 6, pp. 966–978, Aug. 2018, doi: 10.1093/infdis/jiy243.

[4] C. R. Kenyon and R. Colebunders, “Strong association between the prevalence of bacterial vaginosis and male point-concurrency,” Eur. J. Obstet. Gynecol. Reprod. Biol., vol. 172, pp. 93–96, Jan. 2014, doi: 10.1016/j.ejogrb.2013.10.011.

[5] C. R. Kenyon, J. Buyze, M. Klebanoff, and R. M. Brotman, “Association between bacterial vaginosis and partner concurrency: a longitudinal study,” Sex. Transm. Infect., vol. 94, no. 1, pp. 75–77, Feb. 2018, doi: 10.1136/sextrans-2016-052652.

[6] M. A. Klebanoff et al., “Personal hygienic behaviors and bacterial vaginosis,” Sex. Transm. Dis., vol. 37, no. 2, pp. 94–99, Feb. 2010, doi: 10.1097/OLQ.0b013e3181bc063c.

[7] R. M. Brotman et al., “Association between cigarette smoking and the vaginal microbiota: a pilot study,” BMC Infect. Dis., vol. 14, p. 471, Aug. 2014, doi: 10.1186/1471-2334-14-471.

[8] L. A. Vodstrcil, C. A. Muzny, E. L. Plummer, J. D. Sobel, and C. S. Bradshaw, “Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment,” BMC Med., vol. 19, no. 1, p. 194, Sep. 2021, doi: 10.1186/s12916-021-02077-3.

[9] E. H. Koumans et al., “The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health,” Sex. Transm. Dis., vol. 34, no. 11, pp. 864–869, Nov. 2007, doi: 10.1097/OLQ.0b013e318074e565.

[10] K. Peebles, J. Velloza, J. E. Balkus, R. S. McClelland, and R. V. Barnabas, “High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis,” Sex. Transm. Dis., vol. 46, no. 5, pp. 304–311, May 2019, doi: 10.1097/OLQ.0000000000000972.

[11] H. Verstraelen and R. Verhelst, “Bacterial vaginosis: an update on diagnosis and treatment,” Expert Rev. Anti Infect. Ther., vol. 7, no. 9, pp. 1109–1124, Nov. 2009, doi: 10.1586/eri.09.87.

[12] X. Chen, Y. Lu, T. Chen, and R. Li, “The Female Vaginal Microbiome in Health and Bacterial Vaginosis,” Front. Cell. Infect. Microbiol., vol. 11, p. 631972, 2021, doi: 10.3389/fcimb.2021.631972.

[13] J. Ravel et al., “Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis,” Microbiome, vol. 1, no. 1, p. 29, Dec. 2013, doi: 10.1186/2049-2618-1-29.

[14] S. Srinivasan et al., “Temporal variability of human vaginal bacteria and relationship with bacterial vaginosis,” PloS One, vol. 5, no. 4, p. e10197, Apr. 2010, doi: 10.1371/journal.pone.0010197.

[15] L. Hardy et al., “A fruitful alliance: the synergy between Atopobium vaginae and Gardnerella vaginalis in bacterial vaginosis-associated biofilm,” Sex. Transm. Infect., vol. 92, no. 7, pp. 487–491, Nov. 2016, doi: 10.1136/sextrans-2015-052475.

[16] A. Swidsinski et al., “Adherent biofilms in bacterial vaginosis,” Obstet. Gynecol., vol. 106, no. 5 Pt 1, pp. 1013–1023, Nov. 2005, doi: 10.1097/01.AOG.0000183594.45524.d2.

[17] J. Castro, A. S. Rosca, C. A. Muzny, and N. Cerca, “Atopobium vaginae and Prevotella bivia Are Able to Incorporate and Influence Gene Expression in a Pre-Formed Gardnerella vaginalis Biofilm,” Pathog. Basel Switz., vol. 10, no. 2, p. 247, Feb. 2021, doi: 10.3390/pathogens10020247.

[18] C. A. Muzny, P. Łaniewski, J. R. Schwebke, and M. M. Herbst-Kralovetz, “Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis,” Curr. Opin. Infect. Dis., vol. 33, no. 1, pp. 59–65, Feb. 2020, doi: 10.1097/QCO.0000000000000620.

[19] M. Zozaya-Hinchliffe, R. Lillis, D. H. Martin, and M. J. Ferris, “Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis,” J. Clin. Microbiol., vol. 48, no. 5, pp. 1812–1819, May 2010, doi: 10.1128/JCM.00851-09.

[20] J. H. H. M. van de Wijgert, “The vaginal microbiome and sexually transmitted infections are interlinked: Consequences for treatment and prevention,” PLoS Med., vol. 14, no. 12, p. e1002478, Dec. 2017, doi: 10.1371/journal.pmed.1002478.

[21] J. Ravel, I. Moreno, and C. Simón, “Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease,” Am. J. Obstet. Gynecol., vol. 224, no. 3, pp. 251–257, Mar. 2021, doi: 10.1016/j.ajog.2020.10.019.

[22] H. C. Wiesenfeld et al., “Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease,” Obstet. Gynecol., vol. 100, no. 3, pp. 456–463, Sep. 2002, doi: 10.1016/s0029-7844(02)02118-x.

[23] T. Haahr, J. S. Jensen, L. Thomsen, L. Duus, K. Rygaard, and P. Humaidan, “Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients,” Hum. Reprod. Oxf. Engl., vol. 31, no. 4, pp. 795–803, Apr. 2016, doi: 10.1093/humrep/dew026.

[24] M. Fu, X. Zhang, Y. Liang, S. Lin, W. Qian, and S. Fan, “Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure,” mBio, vol. 11, no. 3, pp. e03242-19, Jun. 2020, doi: 10.1128/mBio.03242-19.

[25] J. A. Svare, H. Schmidt, B. B. Hansen, and G. Lose, “Bacterial vaginosis in a cohort of Danish pregnant women: prevalence and relationship with preterm delivery, low birthweight and perinatal infections,” BJOG Int. J. Obstet. Gynaecol., vol. 113, no. 12, pp. 1419–1425, Dec. 2006, doi: 10.1111/j.1471-0528.2006.01087.x.

[26] B. Guerra et al., “Pregnancy outcome after early detection of bacterial vaginosis,” Eur. J. Obstet. Gynecol. Reprod. Biol., vol. 128, no. 1–2, pp. 40–45, Oct. 2006, doi: 10.1016/j.ejogrb.2005.12.024.

[27] D. B. DiGiulio et al., “Temporal and spatial variation of the human microbiota during pregnancy,” Proc. Natl. Acad. Sci., vol. 112, no. 35, pp. 11060–11065, Sep. 2015, doi: 10.1073/pnas.1502875112.

[28] B. J. Callahan et al., “Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women,” Proc. Natl. Acad. Sci. U. S. A., vol. 114, no. 37, pp. 9966–9971, Sep. 2017, doi: 10.1073/pnas.1705899114.

[29] A. C. Freitas, A. Bocking, J. E. Hill, D. M. Money, and VOGUE Research Group, “Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth,” Microbiome, vol. 6, no. 1, p. 117, Jun. 2018, doi: 10.1186/s40168-018-0502-8.

[30] K. Hočevar et al., “Vaginal Microbiome Signature Is Associated With Spontaneous Preterm Delivery,” Front. Med., vol. 6, p. 201, 2019, doi: 10.3389/fmed.2019.00201.

[31] R. G. Brown et al., “Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes,” Transl. Res. J. Lab. Clin. Med., vol. 207, pp. 30–43, May 2019, doi: 10.1016/j.trsl.2018.12.005.

[32] J. M. Fettweis et al., “The vaginal microbiome and preterm birth,” Nat. Med., vol. 25, no. 6, pp. 1012–1021, Jun. 2019, doi: 10.1038/s41591-019-0450-2.

[33] M. A. Elovitz et al., “Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery,” Nat. Commun., vol. 10, no. 1, p. 1305, Mar. 2019, doi: 10.1038/s41467-019-09285-9.

[34] N. Tabatabaei et al., “Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study,” BJOG Int. J. Obstet. Gynaecol., vol. 126, no. 3, pp. 349–358, Feb. 2019, doi: 10.1111/1471-0528.15299.

[35] C. Feehily et al., “Shotgun sequencing of the vaginal microbiome reveals both a species and functional potential signature of preterm birth,” NPJ Biofilms Microbiomes, vol. 6, no. 1, p. 50, Nov. 2020, doi: 10.1038/s41522-020-00162-8.

[36] J. Atashili, C. Poole, P. M. Ndumbe, A. A. Adimora, and J. S. Smith, “Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies,” AIDS Lond. Engl., vol. 22, no. 12, pp. 1493–1501, Jul. 2008, doi: 10.1097/QAD.0b013e3283021a37.

[37] Y. Liang, M. Chen, L. Qin, B. Wan, and H. Wang, “A meta-analysis of the relationship between vaginal microecology, human papillomavirus infection and cervical intraepithelial neoplasia,” Infect. Agent. Cancer, vol. 14, p. 29, 2019, doi: 10.1186/s13027-019-0243-8.

[38] M. F. Gallo et al., “Risk factors for incident herpes simplex type 2 virus infection among women attending a sexually transmitted disease clinic,” Sex. Transm. Dis., vol. 35, no. 7, pp. 679–685, Jul. 2008, doi: 10.1097/OLQ.0b013e31816fcaf8.

[39] R. M. Brotman et al., “Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection,” J. Infect. Dis., vol. 202, no. 12, pp. 1907–1915, Dec. 2010, doi: 10.1086/657320.

[40] J. E. Balkus et al., “Bacterial vaginosis and the risk of trichomonas vaginalis acquisition among HIV-1-negative women,” Sex. Transm. Dis., vol. 41, no. 2, pp. 123–128, Feb. 2014, doi: 10.1097/OLQ.0000000000000075.

[41] J. Wilson, “Managing recurrent bacterial vaginosis,” Sex. Transm. Infect., vol. 80, no. 1, pp. 8–11, Feb. 2004, doi: 10.1136/sti.2002.002733.

[42] R. L. Cook, V. Redondo-Lopez, C. Schmitt, C. Meriwether, and J. D. Sobel, “Clinical, microbiological, and biochemical factors in recurrent bacterial vaginosis,” J. Clin. Microbiol., vol. 30, no. 4, pp. 870–877, Apr. 1992, doi: 10.1128/jcm.30.4.870-877.1992.

[43] C. S. Bradshaw et al., “High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence,” J. Infect. Dis., vol. 193, no. 11, pp. 1478–1486, Jun. 2006, doi: 10.1086/503780.

[44] E. De Backer et al., “Antibiotic susceptibility of Atopobium vaginae,” BMC Infect. Dis., vol. 6, p. 51, Mar. 2006, doi: 10.1186/1471-2334-6-51.

[45] R. C. R. Martinez et al., “Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial,” Can. J. Microbiol., vol. 55, no. 2, pp. 133–138, Feb. 2009, doi: 10.1139/w08-102.

[46] K. Anukam et al., “Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial,” Microbes Infect., vol. 8, no. 6, pp. 1450–1454, May 2006, doi: 10.1016/j.micinf.2006.01.003.

[47] G. Vujic, A. Jajac Knez, V. Despot Stefanovic, and V. Kuzmic Vrbanovic, “Efficacy of orally applied probiotic capsules for bacterial vaginosis and other vaginal infections: a double-blind, randomized, placebo-controlled study,” Eur. J. Obstet. Gynecol. Reprod. Biol., vol. 168, no. 1, pp. 75–79, May 2013, doi: 10.1016/j.ejogrb.2012.12.031.

[48] K. C. Anukam, E. Osazuwa, G. I. Osemene, F. Ehigiagbe, A. W. Bruce, and G. Reid, “Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis,” Microbes Infect., vol. 8, no. 12–13, pp. 2772–2776, Oct. 2006, doi: 10.1016/j.micinf.2006.08.008.

[49] J. M. Bohbot, E. Daraï, F. Bretelle, G. Brami, C. Daniel, and J. M. Cardot, “Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence,” J. Gynecol. Obstet. Hum. Reprod., vol. 47, no. 2, pp. 81–86, Feb. 2018, doi: 10.1016/j.jogoh.2017.11.005.

[50] C. R. Cohen et al., “Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis,” N. Engl. J. Med., vol. 382, no. 20, pp. 1906–1915, May 2020, doi: 10.1056/NEJMoa1915254.

[51] A. Tomusiak et al., “Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial,” Drug Des. Devel. Ther., vol. 9, pp. 5345–5354, 2015, doi: 10.2147/DDDT.S89214.

[52] F. Vicariotto, L. Mogna, and M. Del Piano, “Effectiveness of the two microorganisms Lactobacillus fermentum LF15 and Lactobacillus plantarum LP01, formulated in slow-release vaginal tablets, in women affected by bacterial vaginosis: a pilot study,” J. Clin. Gastroenterol., vol. 48 Suppl 1, pp. S106-112, 2014, doi: 10.1097/MCG.0000000000000226.

[53] M. C. Verdenelli et al., “Impact of Probiotic SYNBIO(®) Administered by Vaginal Suppositories in Promoting Vaginal Health of Apparently Healthy Women,” Curr. Microbiol., vol. 73, no. 4, pp. 483–490, Oct. 2016, doi: 10.1007/s00284-016-1085-x.

[54] A. E. Stapleton et al., “Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection,” Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am., vol. 52, no. 10, pp. 1212–1217, May 2011, doi: 10.1093/cid/cir183.

[55] A. Zahra, G. Fateme, and A. MohamadReza, “Comparison of the effectiveness of vitamin C vaginal tablet with metronidazole vaginal gel in the treatment of bacterial vaginosis,” Afr. J. Pharm. Pharmacol., vol. 4, no. 7, pp. 484–489, Jul. 2010, doi: 10.5897/AJPP.9000083.

[56] E. E. Petersen, M. Genet, M. Caserini, and R. Palmieri, “Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial,” Arzneimittelforschung., vol. 61, no. 4, pp. 260–265, 2011, doi: 10.1055/s-0031-1296197.

[57] E. E. Petersen and P. Magnani, “Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study,” Eur. J. Obstet. Gynecol. Reprod. Biol., vol. 117, no. 1, pp. 70–75, Nov. 2004, doi: 10.1016/j.ejogrb.2004.02.032.

[58] F. Polatti, M. Rampino, P. Magnani, and P. Mascarucci, “Vaginal pH-lowering effect of locally applied vitamin C in subjects with high vaginal pH,” Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol., vol. 22, no. 4, pp. 230–234, Apr. 2006, doi: 10.1080/09513590600647441.

[59] V. N. Krasnopolsky et al., “Efficacy of vitamin C vaginal tablets as prophylaxis for recurrent bacterial vaginosis: a randomised, double-blind, placebo-controlled clinical trial,” J. Clin. Med. Res., vol. 5, no. 4, pp. 309–315, Aug. 2013, doi: 10.4021/jocmr1489w.