Clinical Research & Resources

Since 2003 our partners at Good Clean Love have worked with leading scientists and doctors to develop products that support sexual health and feminine hygiene – with low osmolality and mimicking a healthy vaginal pH – without harmful petrochemicals, parabens and synthetic fragrances. These scientifically-advanced products are being recommended by thousands of medical providers nationwide, for patients of all ages and at all stages of life, to improve their vaginal health and enhance their intimate relationships.

UN Global Consultation On Personal Lubricants

Non-toxic Lubricants For Vaginal And Rectal Intercourse: Anatomy And Physiology

Reviews evidence of epithelial damage and resulting instances of BV resulting from the use of higher osmolality personal lubricants during intercourse. (2016)

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Johns Hopkins University

Studies Raise Questions About Safety Of Personal Lubricants


Reports that isosmolar lubricants, such as agar-based Good Clean Love, did not damage cervical tissue samples or boost sexually transmitted infection rates. (2012)

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Backed By Clinical Studies: Promoting Conditions That Match Optimal Vaginal pH

Patented Bio-Match® products are formulated to provide women with healthier options for combating a variety of conditions and symptoms. Restore Moisturizing Vaginal Gel and BiopHresh Vaginal Probiotic Supplement support the growth of good lactobacilli. BioNude Ultra Sensitive Personal Lubricant is iso-osmotic; a characteristic shown to reduce epithelial damage during intercourse. Balance Moisturizing Personal Wash and Rebalance Feminine Wipes clean and are balanced to optimal pH levels. Try them in your clinic. Provide samples to your patients. They’ll thank you!

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A New Era of the Vaginal Microbiome: Advances Using Next‐Generation Sequencing
Jennifer M. Fettweis,  Myrna G. Serrano,  Philippe H. Girerd,  Kimberly K. Jefferson, and  Gregory A. Buck. Chemistry and Biodiversity (2012) 

Until recently, bacterial species that inhabit the human vagina have been primarily studied using organism‐centric approaches. Understanding how these bacterial species interact with each other and the host vaginal epithelium is essential for a more complete understanding of vaginal health. Molecular approaches have already led to the identification of uncultivated bacterial taxa associated with bacterial vaginosis. Here, we review recent studies of the vaginal microbiome and discuss how culture‐independent approaches, such as applications of next‐generation sequencing, are advancing the field and shifting our understanding of how vaginal health is defined. This work may lead to improved diagnostic tools and treatments for women who suffer from, or are at risk for, vaginal imbalances, pregnancy complications, and sexually acquired infections. These approaches may also transform our understanding of how host genetic factors, physiological conditions (e.g., menopause), and environmental exposures (e.g., smoking, antibiotic usage) influence the vaginal microbiome.

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Acute Exercise Improves Physical Sexual Arousal in Women Taking Antidepressants
Tierney A. Lorenz, and Cindy M. Meston. Annals of Behavioral Medicine (2012)

Background
Antidepressants can impair sexual arousal. Exercise increases genital arousal in healthy women, likely due to increasing sympathetic nervous system (SNS) activity.
Purpose
Test if exercise increases genital arousal in women taking antidepressants, including selective serotonin reuptake inhibitors (SSRIs), which suppress SNS activity, and selective serotonin and norepinephrine reuptake inhibitors (SNRIs), which suppress the SNS less.
Method
Women reporting antidepressant-related sexual arousal problems (N = 47) participated in three counterbalanced sessions where they watched an erotic film while we recorded genital and SNS arousal. In two sessions, women exercised for 20 min, either 5 or 15 min prior to the films.
Results
During the no-exercise condition, women taking SSRIs showed significantly less genital response than women taking SNRIs. Exercise prior to sexual stimuli increased genital arousal in both groups. Women reporting greater sexual dysfunction had larger increases in genital arousal post-exercise. For women taking SSRIs, genital arousal was linked to SNS activity.
Conclusions
Exercise may improve antidepressant-related genital arousal problems.

 

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Analysis of the Vaginal Microbiome by Next-Generation Sequencing and Evaluation of its Performance as a Clinical Diagnostic Tool in Vaginitis
Ki Ho Hong, Sung Kuk Hong, Sung Im Cho, Eunkyung Ra, Kyung Hee Han, Soon Beom Kang, Eui-Chong Kim, Sung Sup Park, and Moon-Woo Seong. Annals of Laboratory Mediciney (2016) 

Background: Next-generation sequencing (NGS) can detect many more microorganisms of a microbiome than traditional methods. This study aimed to analyze the vaginal microbiomes of Korean women by using NGS that included bacteria and other microorganisms. The NGS results were compared with the results of other assays, and NGS was evaluated for its feasibility for predicting vaginitis.

Methods: In total, 89 vaginal swab specimens were collected. Microscopic examinations of Gram staining and microbiological cultures were conducted on 67 specimens. NGS was performed with GS junior system on all of the vaginal specimens for the 16S rRNA, internal transcribed spacer (ITS), and Tvk genes to detect bacteria, fungi, and Trichomonas vaginalis. In addition, DNA probe assays of the Candida spp., Gardnerella vaginalis, and Trichomonas vaginalis were performed. Various predictors of diversity that were obtained from the NGS data were analyzed to predict vaginitis.

Results: ITS sequences were obtained in most of the specimens (56.2%). The compositions of the intermediate and vaginitis Nugent score groups were similar to each other but differed from the composition of the normal score group. The fraction of the Lactobacillus spp. showed the highest area under the curve value (0.8559) in ROC curve analysis. The NGS and DNA probe assay results showed good agreement (range, 86.2-89.7%).

Conclusions: Fungi as well as bacteria should be considered for the investigation of vaginal microbiome. The intermediate and vaginitis Nugent score groups were indistinguishable in NGS. NGS is a promising diagnostic tool of the vaginal microbiome and vaginitis, although some problems need to be resolved.

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Characterization of a Bacteriocin-Like Substance Produced by a Vaginal Lactobacillus salivarius Strain
Virginia S. Ocaña, Aída A. Pesce de Ruiz Holgado, and María Elena Nader-Macías. Applied and Environmental Microbiology (1999)

 

A novel bacteriocin-like substance produced by vaginal Lactobacillus salivarius subsp. salivarius CRL 1328 with activity against Enterococcus faecalis, Enterococcus faecium, and Neisseria gonorrhoeae was characterized. The highest level of production of this heat-resistant peptide or protein occurred during the late exponential phase. Its mode of action was shown to be bactericidal. L. salivarius subsp. salivarius CRL 1328 could be used for the design of a probiotic to prevent urogenital infections.

 

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Characterization of Commercially Available Vaginal Lubricants: A Safety Perspective
Ana Raquel Cunha, Rita M. Machado, Ana Palmeira-de-Oliveira, et al. (2012)

 

Twelve commercially available gel products were tested for pH value, pH buffering capacity, osmolality and cytotoxicity relevant to vaginal delivery. Obtained data were analyzed in light of the recent Advisory Note by the World Health Organization (WHO) for personal lubricants to be concomitantly used with condoms. Results showed that most products do not comply with pH and osmolality recommended standards, thus posing a potential hazard. Four products presented values of osmolality around three-times higher than the maximum acceptable limit of 1200 mOsm/kg. In vitro cell testing further identified substantial cytotoxicity even at 1:100 dilutions for three products, contrasting with no significant effect of up to at least a 1:5 dilution of a Universal Placebo gel. However, no direct correlation between these last results and pH or osmolality was found, thus suggesting that the individual toxicity of specific formulation components plays an important role in the outcome of a particular product.

 

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Characterization of the vaginal microflora in health and disease
Raluca Datcu. Danish Medical Journal (2014) 

BACKGROUND:

Bacterial vaginosis (BV) is an imbalance of the vaginal bacterial microbiota and its aetiology is still unknown. Our aims were to investigate the diagnostic potential of species/genus specific quantitative PCR (qPCR) for bacteria present in swabs and first-void urine (FVU) samples using Nugent's and Claeys' criteria and 454 sequencing of the vaginal microbiome as reference.

METHODS:

Self-collected swabs, vaginal smears and FVU were obtained from 177 women from Greenland (Study I and III) and physician-collected vaginal swabs and smears were obtained from 163 Swedish women (Study II). BV was diagnosed by Nugent's criteria in Study I and III and by Amsel's criteria in Study II. The vaginal swabs and FVU samples were analysed by qPCR for selected vaginal bacteria in all three studies and for four sexually transmitted infections (STIs) in Study I.

RESULTS:

Study I: STIs were common in women from Greenland and BV was found in 45% of these women but was not associated with individual STIs. In multivariate logistic analysis, Atopobium vaginae and Prevotella spp. were both independently associated with BV in swabs. BV could be subdivided into clusters dominated by a single or a few species together. Seven vaginal bacteria (A. vaginae, Prevotella spp. Gardnerella vaginalis, Bacterial vaginosis associated bacterium (BVAB) 2, Eggerthella-like bacterium, Leptotrichia amnionii and Megasphaera type 1) had areas under the receiver operating characteristic (ROC) curve > 85% in swabs, suggesting that they were good predictors of BV according to Nugent. Study II: For the majority of species/genera, the kappa values indicated fair to good agreement when their presence was determined by 454 pyrosequencing versus real-time PCR. The same seven vaginal bacteria as found in Study I, had areas under the ROC-curve > 85% in swabs from Swedish women, demonstrating a good diagnostic accuracy for BV according to Amsel. Study III: In a multivariate model, Megasphaera type 1 and Prevotella spp. remained significantly associated with BV in FVU samples. A linear regression analysis showed good agreement between bacterial load from swabs and FVU, but Prevotella spp. could be detected in high numbers in a few FVU samples without being present in swabs. After applying ROC curve analysis, the same seven vaginal bacteria as previously mentioned showed good prediction for BV according to Nugent in FVU. BV could be detected with comparable sensitivity in FVU and vaginal swabs.

CONCLUSION:

BV can be diagnosed by molecular methods performed either on swabs or urine but it is important to apply thresholds in order to improve the accuracy of the diagnosis. Furthers it was possible to identify clusters of BV dominated by single or paired bacteria, and these clusters could classify BV into subgroups, providing a more detailed understanding of the condition. Seven vaginal bacteria were highly accurate for BV diagnosis both in swabs and FVU. Finally a good agreement between Nugent and Claeys was found.

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Douching and endometritis: results from the PID evaluation and clinical health (PEACH) study.
Roberta Ness, David Soper, Robert L. Holley, Jeffrey Peipert, Hugh Randall, Richard Swet, Steven Sondheimer, Susan L. Hendrix, Sharon L. Hillier, Antonio Amortegui, Giuliana Trucco, and Debra Bass. Journal of the American Sexually Transmitted Diseases Association (2001) 

BACKGROUND:

Douching has been related to risk of pelvic inflammatory disease (PID).

GOAL:

To examine the association between douching and PID in a large, multicenter, clinical trial of PID after adjustment for race/ethnicity.

STUDY DESIGN:

Interviews were conducted with 654 women who had signs and symptoms of PID. Vaginal Gram stains and upper genital tract pathology/cultures were obtained from all the women. Women with evidence of plasma cell endometritis and/or gonococcal or chlamydial upper genital tract infections were compared with women who had neither endometritis nor upper genital tract infection.

RESULTS:

Women with endometritis or upper genital tract infection were more likely to have douched more than once a month or within 6 days of enrollment than women who never douched. These associations remained after adjustment for confounding factors, after analysis of black women only; and among women with normal or intermediate vaginal flora but not bacterial vaginosis.

CONCLUSION:

Among a predominantly black group of women with clinical PID, frequent and recent douching was associated with endometritis and upper genital tract infection.

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Effects of Feminine Hygiene Products on the Vaginal Mucosal Biome
Bisiayo Fashemi, Mary L. Delaney M.A., Andrew B. Onderdonk Ph.D. & Raina N. Fichorova M.D., Ph.D. Microbial Ecology in Health and Disease (2013)

 

This study evaluates in-vitro their effects on Lactobacillus crispatus, which is dominant in the normal vaginal microbiota and helps maintain a healthy mucosal barrier essential for normal reproductive function and prevention of sexually transmitted infections and gynecologic cancer. Some OTC vaginal products may be harmful to L. crispatus and alter the vaginal immune environment. Illustrated through these results, L. crispatus is essential in the preservation of the function of vaginal epithelial cells in the presence of some feminine hygiene products.

 

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Evidence for a curvilinear relationship between sympathetic nervous system activation and women's physiological sexual arousal
Tierney K. Lorenz, Christopher B. Harte, Lisa D. Hamilton, and Cindy M. Meston. Psychophysiology (2011)

 

There is increasing evidence that women's physiological sexual arousal is facilitated by moderate sympathetic nervous system (SNS) activation. Literature also suggests that the level of SNS activation may play a role in the degree to which SNS activity affects sexual arousal. We provide the first empirical examination of a possible curvilinear relationship between SNS activity and women's genital arousal using a direct measure of SNS activation in 52 sexually functional women. The relationship between heart rate variability (HRV), a specific and sensitive marker of SNS activation, and vaginal pulse amplitude (VPA), a measure of genital arousal, was analyzed. Moderate increases in SNS activity were associated with higher genital arousal, while very low or very high SNS activation was associated with lower genital arousal. These findings imply that there is an optimal level of SNS activation for women's physiological sexual arousal.

 

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Hyperosmolar Sexual Lubricant Causes Epithelial Damage in the Distal Colon: Potential Implication for HIV Transmission
Edward J. Fuchs, Linda A. Lee, Michael S. Torbenson, et al. The Journal of Infectious Diseases (2007)

 

Many sexual lubricants are hyperosmolar. Hyperosmolar enemas induce epithelial damage, and enema use has been associated with an increased risk of HIV infection. To inform the development of rectal microbicide formulation, we evaluated the effects of hyperosmolar gels on the rectal mucosa. Rectally applied hyperosmolar gels induce greater epithelial denudation and luminal secretion than iso-osmolar gels. Because denudation plausibly increases the risk of HIV transmission, hyperosmolar gels make poor rectal microbicide formulations, and hyperosmolar sexual lubricants may increase susceptibility to HIV infection.

 

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Interactions Between Inflammation and Female Sexual Desire and Arousal Function
Tierney K. Lorenz. Current Sexual Health Controls (2019) 

Purpose of Review
To describe the current state of research on interactions between inflammation and female sexual function.
Recent Findings
Inflammation may interfere with female sexual desire and arousal via direct (neural) and indirect (endocrine, vascular, social/behavioral) pathways. There are significant sex differences in the effect of inflammation on sexual function, arising from different evolutionary selection pressures on the regulation of reproduction. A variety of inflammation-related conditions are associated with the risk of female sexual dysfunction, including cardiovascular disease, metabolic syndrome, and chronic pain.
Summary
Clinical implications include the need for routine assessment for sexual dysfunction in patients with inflammation-related conditions, the potential for anti-inflammatory diets to improve sexual desire and arousal function, and consideration of chronic inflammation as moderator of sexual effects of hormonal treatments. Although the evidence points to a role for inflammation in the development and maintenance of female sexual dysfunction, the precise nature of these associations remains unclear.

 

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Interaction of menstrual cycle phase and sexual activity predicts mucosal and systemic humoral immunity in healthy women
Tierney K. Lorenz, Gregory E. Demas, and Julia R. Heiman. Physiology & Behavior (2015) 

Several studies have documented shifts in humoral immune parameters (e.g., immunoglobulins) across the menstrual cycle in healthy women. It is thought that these shifts may reflect dynamic balancing between reproduction and pathogen defense, as certain aspects of humoral immunity may disrupt conception and may be temporarily downregulated at ovulation. If so, one could expect maximal cycle-related shifts of humoral immunity in individuals invested in reproduction – that is, women who are currently sexually active – and less pronounced shifts in women who are not reproductively active (i.e., abstinent). We investigated the interaction of sexual activity, menstrual cycle phase, and humoral immunity in a sample of 32 healthy premenopausal women (15 sexually active, 17 abstinent). Participants provided saliva samples during their menses, follicular phase, ovulation (as indicated by urine test for LH surge), and luteal phase, from which IgA was assayed. Participants also provided blood samples at menses and ovulation, from which IgG was assayed. Sexually active participants provided records of their frequency of sexual activity as well as condom use. At ovulation, sexually active women had higher IgG than abstinent women (d = 0.77), with women reporting regular condom use showing larger effects (d = 0.63) than women reporting no condom use (d = 0.11). Frequency of sexual activity predicted changes in IgA (Cohen's f2 = 0.25), with women reporting high frequency of sexual activity showing a decrease in IgA at ovulation, while women reporting low frequency or no sexual activity showing an increase in IgA at ovulation. Taken together, these findings support the hypothesis that shifts in humoral immunity across the menstrual cycle are associated with reproductive effort, and could contribute to the mechanisms by which women's physiology navigates tradeoffs between reproduction and immunity.

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Intravaginal practices, vaginal flora disturbances, and acquisition of sexually transmitted diseases in Zimbabwean women.
J. H. H. M. van de Wijgert, P. R. Mason, L. Gwanzura, M. T. Mbizvo, Z. M. Chirenje,V. Iliff, S. Shiboski, and N. S. Padian. The Journal of Infectious Diseases (2000) 

One hundred sixty-nine Zimbabwean women were studied to determine whether the use of intravaginal practices (cleaning with the fingers, wiping the vagina, and inserting traditional substances) are associated with disturbances of vaginal flora and acquisition of sexually transmitted diseases (STDs). Subjects were interviewed and received counseling and a pelvic examination at enrollment, 1 month, and 6 months, and vaginal specimens were collected at enrollment and at 6 months. Users were more likely than nonusers to have vaginal flora disturbances but were not more likely to acquire an STD (relative risk [RR], 2.15; P = .188). Certain vaginal flora disturbances were associated with increased STD incidence and HIV prevalence. The absence of lactobacilli from the vaginal flora was associated with being positive for human immunodeficiency virus in baseline (odds ratio [OR], 0.24; P = .001) and 6-month transition multivariate models (OR, 0.39; P = .025). The presence of clue cells at baseline was associated with a higher incidence of STDs (RR, 1.94; P = .025).

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Is Wetter Better? An Evaluation of Over-the-Counter Personal Lubricants for Safety and Anti-HIV-1 Activity
Charlene S. Dezzutti, Elizabeth R. Brown, Bernard Moncla, et al. International DOI Foundation (2012)

 

Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm.

 

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Is there a protective role for vaginal flora?
Jack D. Sobel. Current Infectious Disease Reports (1999)

The notion of a protective vaginal flora is relatively new. Resident flora manifest colonization resistance to prevent or reduce the likelihood of exogenous microorganisms, viruses, bacteria, yeast, or parasites becoming established in the lower genital tract of women following sexual (HIV, Neisseria gonorrhoeae, Escherichia coli, Candida albicans, Trichomonas vaginalis) or nonsexual (uropathogenic E. coli) transmission. The concept of preserving or reestablishing protective flora has been hastened by several factors, including the potential widespread use of vaginal microbicides, the increased heterosexual spread of HIV, and the imminent availability of exogenous Lactobacillus species probiotic therapy.

 
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Menopause and the vaginal microbiome
Alicia L .Muhleisenab, and Melissa M. Herbst-Kralovetz. Maturitas (2016) 

For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis.

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Microbiome in Parturition and Preterm Birth
Indira U. Mysorekar,and Bin Cao. The Journal of Infectious Diseases (2014) 

Preterm parturition is a one of the most significant global maternal-child health problem. In recent years, there has been an explosion in reports on a role for microbiomes (i.e., a microbial biomass) on a plethora of physiologic and pathologic human conditions. This review aims to describe our current understanding of the microbiome and its impact on parturition, with particular emphasis on preterm birth. We will focus on the roles of vaginal and oral mucosal microbiomes in premature parturition and describe the state-of-the-art methodologies used in microbiome studies. Next, we will present new studies on a potential microbiome in the placenta and how it may affect pregnancy outcomes. Finally, we will propose that host genetic factors can perturb the normal “pregnancy microbiome” and trigger adverse pregnancy outcomes.

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The mycobiota: interactions between commensal fungi and the host immune system
David M. Underhill, and Iliyan D. Iliev. Nature Reviews Immunology (2014) 

The body is host to a wide variety of microbial communities from which the immune system protects us and that are important for the normal development of the immune system and for the maintenance of healthy tissues and physiological processes. Investigators have mostly focused on the bacterial members of these communities, but fungi are increasingly being recognized to have a role in defining these communities and to interact with immune cells. In this Review, we discuss what is currently known about the makeup of fungal communities in the body and the features of the immune system that are particularly important for interacting with fungi at these sites.

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Obstetric and Gynecological Diseases and Complications Resulting from Vaginal Dysbacteriosis
Stefan M. Kovachev. Microbial Ecology (2014) 

Accurate knowledge of the composition and ecology of vaginal microbial environment of a healthy woman is necessary for the understanding of normal flora and how to reduce the risk for diseases. Vagina and its microflora form a balanced ecosystem in which dominated bacteria are vaginal lactobacilli. There are dynamic changes in this ecosystem having structure and composition depending on many factors. The term dysbacteriosis defines any movement outside the normal range for the given biotope of obligate and/or facultative microflora. Such a change in the quantity and quality of the respective microbial balance is fraught with danger and requires correction and recovery. The purpose of this overview is to examine obstetric and gynecological diseases that can cause vaginal impaired microbial balance. Vaginal dysbacteriosis is a cause, predecessor, and often also consequence of vaginal infections. In essence, any vaginal infection can be seen as dysbacteriosis, developed to the most severe extent. Here, there is a dominant microorganism other than lactic acid bacteria in the vagina (clinically manifested or not, respectively), depletion of defense mechanisms of the vagina associated with the shift of lactobacilli from their dominant role in the vaginal balance, decrease in their number and species diversity, and a resulting change in the healthy status of the vagina. Vaginal dysbacteriosis can be found in pathogenetic mechanism, whereby many obstetric and gynecological diseases develop. Most of these diseases lead directly to increased maternal and infant morbidity and mortality, so it is important to understand the reasons for them and the arrangements for their prevention.

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Partnered sexual activity moderates menstrual cycle–related changes in inflammation markers in healthy women: an exploratory observational study
Tierney Lorenz, Gregory E.Demas, and Julia R.Heiman. Fertility and Sterility (2017)

 

OBJECTIVE:

To examine differences in inflammation markers in sexually active versus abstinent women and observe changes in inflammation markers across the menstrual cycle. Cycle-related immune fluctuations may have evolved to reduce interference with conception. If so, reproductively active (i.e., sexually active) women should show the most variability in cytokine expression.
DESIGN:
Participants provided serum samples at menses and ovulation (from which cytokines were assayed) and saliva samples at menses and during follicular, ovulation, and luteal phases (from which C-reactive protein [CRP] was assayed). Participants self-reported intercourse frequency during the study.
SETTING:
Academic research laboratory.
PATIENT(S):
Thirty-two healthy, naturally cycling premenopausal women (sexually active, n = 15; abstinent, n = 17).
INTERVENTION(S):
Observational study.
MAIN OUTCOME MEASURE(S):
Levels of proinflammatory cytokines (interleukin-6 [IL-6], interferon γ [IFN-γ], tumor necrosis factor-α [TNF-α]), an anti-inflammatory cytokine (interleukin-4 [IL-4]), and a marker of total inflammation (CRP).
RESULT(S):
Sexually active women had higher levels of all of the immune markers measured, including both pro- and anti-inflammatory cytokines, than abstinent women. Relative to sexually active women, abstinent women had less change across the menstrual cycle in levels of CRP. Among sexually active women, higher intercourse frequency predicted greater midcycle decreases in CRP, IL-6, and IFN-γ and midcycle increases in IL-4.
CONCLUSION(S):
Sexual activity may stimulate a complex interaction between pro- and anti-inflammatory cytokines that subsequently drives midcycle declines in inflammation.

 

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Pathogenesis of abnormal vaginal bacterial flora
Gilbert G. G. Donders, Eugene Bosmans, Alfons Dekeersmaecker, Annie Vereecken, Ben Van Bulck, and Bernard Spitz. American Journal of Obstetrics and Gynecology (2000) 

Objective: This study was undertaken to determine the relationships between microscopy findings on wet mounts, such as lactobacillary grade or vaginal leukocytosis, and results of vaginal culture, lactate and succinate content of the vagina, and levels of selected cytokines. Study Design: In a population of 631 unselected women seeking treatment at an obstetrics and gynecology outpatient clinic, vaginal fluid was obtained by wooden Ayre spatula for wet mounting and pH measurement, by high vaginal swab for culture, and by standardized vaginal rinsing with 2 mL 0.9% sodium chloride solution for measurements of lactate, succinate, interleukin 1β, interleukin 8, leukemia inhibitory factor, and interleukin 1 receptor antagonist concentrations. Lactate and succinate levels were measured by gas-liquid chromatography and the cytokine concentrations were measured by specific immunoassays. Both univariate analysis (Student t test, Welch test, χ2 test, and Fisher exact test) and multivariate regression analysis (Cox analysis) were used. Results: Increasing disturbance of the lactobacillary flora (lactobacillary grades I, IIa, IIb, and III) was highly correlated with the presence of Gardnerella vaginalis, Trichomonas vaginalis, enterococci, group B streptococci, and Escherichia coli. Vaginal pH and interleukin 8 and interleukin 1β concentrations increased linearly with increasing lactobacillary grade, whereas lactate concentrations and the presence of epithelial cell lysis decreased. A similar pattern of associations with increasing leukocyte count was clear, but in addition there was an increase in leukemia inhibitory factor concentration. Multivariate analysis of vaginal leukocytosis, lactobacillary grades, and the presence of positive vaginal culture results showed that interleukin 1β concentration was most closely related to the lactobacillary grade, leukemia inhibitory factor concentration was most closely related to the lactobacillary grade and positive culture results, interleukin 8 concentration was most closely related to positive culture results, and interleukin 1 receptor antagonist concentration was most closely related to vaginal leukocytosis and positive culture results. The concentration ratio of interleukin 1β to interleukin 1 receptor antagonist remained stable, except when vaginal leukocytosis increased. In its most severe form, with >10 leukocytes per epithelial cell present, a decompensation of the vaginal flora with a collapse in interleukin 1β and interleukin 1 receptor antagonist concentrations was seen, but there was a concurrent sharp increase in leukemia inhibitory factor concentration. This pattern was completely different from the course of the cytokine concentrations associated with a lactobacillary grade increase. Conclusion: Both disturbed lactobacillary grade and the presence of increasing vaginal leukocytosis were correlated with lactobacillary substrate (lactate) concentration, pH, and the concentrations of a variety of cytokines. There was a remarkably linear increase in these cytokines as either leukocytosis or lactobacillary grade became more severe. In circumstances in which leukocytosis was extreme, however, interleukin 1β was no longer produced but leukemia inhibitory factor concentrations increased. We speculate that in extreme inflammation the body tries to limit the damage that can be done by exaggerated cytokine production. (Am J Obstet Gynecol 2000;182:872-8.)

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Surface characteristics of lactobacilli isolated from human vagina
Virginia Ocaña, Elena Bru, Aída A. P. De Ruiz Holgado, and María Elena Fatima Nader-Macías. The Journal of General and Applied Microbiology (1999)

 

In the present paper, the taxonomic classification of 134 lactobacilli isolates from vaginal samples of 200 women of Tucumán, Argentina, is reported. They were clustered in three metabolic groups of the genus Lactobacillus, most belonging to the obligately homofermentative group (56%), mainly represented by Lactobacillus delbrueckii subsp. delbrueckii and L. acidophilus. In the facultatively heterofermentative group (24%), the dominant species were L. paracasei subsp. paracasei and L. agilis, and in the obligately heterofermentative group (20%), L. brevis was the dominant species. All strains were studied for surface characteristics and adhesion-predicting properties. A correlation between the methods employed for hydrophobicity testing of the different isolates (Microbial Adhesion to Hydrocarbons and Salt Aggregation Test) is reported. Most strains were highly hydrophobic. Their hemagglutination capability with human erythrocytes was also tested, which was positive only for a few strains. Some isolates were self-aggregating. From our results, strains that shared the properties assayed were selected for further testing of some other desirable characteristics, such as antagonistic substance production, adhesion to biological substrates, and appropriate technological properties, to suggest the elaboration of a probiotic for the vaginal tract.

 

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Vaginal Microbiota
Werner Mendling. Microbiota of the Human Body (2016) 

The knowledge about the normal and abnormal vaginal microbiome has changed over the last years. Culturing techniques are not suitable any more for determination of a normal or abnormal vaginal microbiota. Non culture-based modern technologies revealed a complex and dynamic system mainly dominated by lactobacilli.

The normal and the abnormal vaginal microbiota are complex ecosystems of more than 200 bacterial species influenced by genes, ethnic background and environmental and behavioral factors. Several species of lactobacilli per individuum dominate the healthy vagina. They support a defense system together with antibacterial substances, cytokines, defensins and others against dysbiosis, infections and care for an normal pregnancy without preterm birth.

The numbers of Lactobacillus (L.) iners increase in the case of dysbiosis.

Bacterial vaginosis (BV) – associated bacteria (BVAB), Atopobium vaginae and Clostridiales and one or two of four Gardnerella vaginalis – strains develop in different mixtures and numbers polymicrobial biofilms on the vaginal epithelium, which are not dissolved by antibiotic therapies according to guidelines and, thus, provoke recurrences.

Aerobic vaginitis seems to be an immunological disorder of the vagina with influence on the microbiota, which is here dominated by aerobic bacteria (Streptococcus agalactiae, Escherichia coli). Their role in AV is unknown.

Vaginal or oral application of lactobacilli is obviously able to improve therapeutic results of BV and dysbiosis.

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The vaginal mycobiome: A contemporary perspective on fungi in women's health and diseases
David H. Martin, and Jeanne M. Marrazzo. The Journal of Infectious Diseases (2016) 

This article summarizes the highlights of the expert technical consultation on bacterial vaginosis (BV), sponsored by the National Institute of Allergy and Infectious Disease and held in Washington, DC, on 8–9 April 2015. Many issues touched on in this article are discussed in much greater detail in the 6 preceding articles in this supplement to The Journal of Infectious Diseases. There was a consensus among the meeting attendees concerning the most important research issues in the field: the pathogenesis of the syndrome, way to optimize treatment, and the relative roles of sexual transmission and endogenous infection in BV epidemiology. This article concludes with a listing of BV and genitourinary tract research priorities that were discussed and agreed on by attendees. The most important of these included better characterization of vaginal microbiome community state subtypes, application of advanced “-omic” technologies to improve understanding of BV pathogenesis, further investigation of the relationships between the male and female genitourinary tract microbiomes, and the development of new drugs for BV treatment.

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Women's Perceptions About Lubricant Use and Vaginal Wetness During Sexual Activities
Kristen N. Jozkowski PhD, Debby Herbenick PhD, MPH, Vanessa Schick PhD, et al. International Society For Sexual Medicine (2012)

 

Exogenous lubricant use in the United States is common among women; however, there is little empirical research describing women's perceptions of lubricants, lubricant use, and vaginal wetness or dryness during penile‐vaginal intercourse or other sexual behaviors. Findings suggest that women generally feel positively about lubricants and lubricant use and prefer vaginal‐penile intercourse to feel more wet. Such insights into women's perceptions of lubricants and lubricant use can be helpful to medical and other health professionals as well as sexual health educators, who routinely make recommendations to women about ways to incorporate products, such as lubricants, into their sexual activities.

 

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