Treatment of Provoked Vulvodynia: A Systematic Review.

BACKGROUND: Treatment recommendations for provoked vulvodynia (PVD) are based on clinical experiences and there is a need for systematically summarizing the controlled trials in this field. AIM: To provide an overview of randomized controlled trials and non-randomized studies of intervention for PVD, and to assess the certainty of the scientific evidence, in order to advance treatment guidelines. DATA SOURCES: The search was conducted in CINAHL (EBSCO), Cochrane Library, Embase (Embase.com), Ovid MEDLINE, PsycINFO (EBSCO) and Scopus. Databases were searched from January 1, 1990 to January 29, 2021. STUDY ELIGIBILITY CRITERIA: Population: Premenopausal women with PVD. INTERVENTIONS: Pharmacological, surgical, psychosocial and physiotherapy, either alone or as combined/team-based interventions. CONTROL: No treatment, waiting-list, placebo or other defined treatment. OUTCOMES: Pain during intercourse, pain upon pressure or touch of the vaginal opening, sexual function/satisfaction, quality of life, psychological distress, adverse events and complications. STUDY DESIGN: Randomized controlled trials and non-randomized studies of interventions with a control group. STUDY APPRAISAL AND SYNTHESIS METHODS: 2 reviewers independently screened citations for eligibility and assessed relevant studies for risk of bias using established tools. The results from each intervention were summarized. Studies were synthesized using a narrative approach, as meta-analyses were not considered appropriate. For each outcome, we assessed the certainty of evidence using grading of recommendations assessment, development, and evaluation (GRADE). RESULTS: Most results of the evaluated studies in this systematic review were found to have very low certainty of evidence, which means that we are unable to draw any conclusions about effects of the interventions. Multimodal physiotherapy compared with lidocaine treatment was the only intervention with some evidential support (low certainty of evidence for significant treatment effects favoring physiotherapy). It was not possible to perform meta-analyses due to a heterogeneity in interventions and comparisons. In addition, there was a heterogeneity in outcome measures, which underlines the need to establish joint core outcome sets. CLINICAL IMPLICATIONS: Our result underscores the need of stringent trials and defined core outcome sets for PVD. STRENGTH AND LIMITATIONS: Standard procedures for systematic reviews and the Population Intervention Comparison Outcome model for clinical questions were used. The strict eligibility criteria resulted in limited number of studies which might have resulted in a loss of important information. CONCLUSION: This systematic review underlines the need for more methodologically stringent trials on interventions for PVD, particularly for multimodal treatments approaches. For future research, there is a demand for joint core outcome sets. Bohm-Starke N, Ramsay KW, Lytsy P, et al. Treatment of Provoked Vulvodynia: A Systematic Review. J Sex Med 2022;19:789-808.

Steroid receptor expression in vaginal epithelium of healthy fertile women and influences of hormonal contraceptive usage.

BACKGROUND: The objective of this study was to evaluate whether long-term usage of hormonal contraceptives modifies the steroid receptor expression in the human vaginal epithelium of healthy young women. METHODS: In a cross-sectional study, three groups of hormonal contraceptive users [combined oral contraceptives (COCs), levonorgestrel implants (LNG) and depot medroxyprogesterone acetate injections (DMPAs)] were compared to controls. Fifteen subjects (20-34 years) were enrolled to each group. Vaginal biopsies were collected at two occasions from each subject, and serum concentrations of E(2) and progesterone were measured. Monoclonal antibodies directed against progesterone receptors (PRs) and estrogen receptors (ERs) were used in immunohistochemistry on formalin-fixed tissue sections of vaginal mucosa. A program for immunohistomorphometric quantification was devised to estimate frequency of epithelial steroid receptor-expressing cells. RESULTS: Progesterone receptor expression was markedly down-regulated and significantly reduced in DMPA users compared to controls, COC and LNG users. In DMPA users, the ER expression was significantly elevated in the first compared to the second sample, and significantly elevated compared to LNG users. Estradiol concentration in serum was significantly reduced in hormonal contraceptive users compared to controls. CONCLUSIONS: Steroid receptor expression in human vaginal epithelium is altered by long-term use of DMPA compared to controls.

Colposcopic and histopathologic evaluation of women participating in population-based screening for human papillomavirus deoxyribonucleic acid persistence.

OBJECTIVE: Evaluation of colposcopic and histopathological findings in women screened for cervical human papillomavirus deoxyribonucleic acid persistence. STUDY DESIGN: A total of 12 527 women, aged 32 to 38 years old, attending the population-based cervical cancer screening program in Sweden were randomized 1:1 to mock testing or human papillomavirus deoxyribonucleic acid testing by general primer 5+/6+ polymerase chain reaction and subsequent typing. Human papillomavirus deoxyribonucleic acid-positive women with a normal Papanicolaou smear (n=341) and an equal number from the control group were human papillomavirus tested on average 19 months later. One hundred nineteen women with type-specific human papillomavirus persistence and 111 controls were referred to colposcopy, and 84.8% attended. RESULTS: Histopathology from colposcopically directed biopsies confirmed cervical intraepithelial neoplasia grade 2 or 3 in 28 of 100 of the women with human papillomavirus deoxyribonucleic acid persistence and in 2 of 95 among controls. CONCLUSION: Among women with normal Papanicolaou smear attending population-based screening, the positive predictive value of human papillomavirus deoxyribonucleic acid persistence for detection of biopsy-confirmed cervical intraepithelial neoplasia 2 or 3 was 29%.

Altered distribution of mannose-binding lectin alleles at exon I codon 54 in women with vulvar vestibulitis syndrome.

OBJECTIVES: Mannose-binding lectin (MBL) is active in the innate immune defense against microorganisms. In this study, we determined whether vulvar vestibulitis syndrome, a disorder of unknown etiology, was associated with an altered distribution of MBL alleles. STUDY DESIGN: Buccal swabs were obtained from women with vulvar vestibulitis syndrome in New York (62) and from 2 cities in Sweden (60), as well as control women in New York (48) and Sweden (51). DNA was tested for a single nucleotide polymorphism at codon 54 in exon I by polymerase chain reaction, endonuclease digestion, and gel electrophoresis. Blood samples were also obtained from the New York women and tested by ELISA for plasma MBL concentrations. The relationships between genotype, allele frequencies, blood MBL levels, and diagnosis were analyzed by Fisher exact test and one-way analysis of variance. RESULTS: The variant MBL allele, MBL*B, was detected in 35.5% and 26.7% of vulvar vestibulitis patients from New York and Sweden, respectively. Only 12.5% of New York controls (P=.007) and 9.8% of Swedish controls (P=.01) were MBL*2-positive. All women, with one exception, who were positive for MBL*B were MBL*A/MBL*B heterozygotes. Women who carried MBL*B had almost a 10-fold reduction in median plasma MBL concentrations (278 ng/mL), as opposed to women who were MBL*A homozygotes (1980 ng/mL) (P < .0001). CONCLUSION: MBL*B carriage and reduced plasma MBL levels are more common in women with vulvar vestibulitis syndrome than in control patients, and may contribute to symptomatology in a subset of patients.

Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium.

OBJECTIVE: To determine whether use of steroid hormone contraceptives modifies immune defense parameters of the vaginal epithelium in humans. METHODS: Vaginal biopsies were collected during the follicular and luteal phases in regularly menstruating women (controls) and in women using combined oral contraceptives, depot-medroxyprogesterone acetate injections, or levonorgestrel implants. Fifteen healthy women (aged 20-34 years) were enrolled in each group. Biopsies were analyzed in a blinded manner. Epithelial thickness was estimated by morphometry. Immune cells were analyzed by immunomorphometry with cell-type-specific monoclonal antibodies. RESULTS: The epithelium of controls harbored 241+/-35 leukocytes (CD45+ cells) per mm2 (mean+/-1 standard error of the mean), and the thickness was 261+/-16 microm. T lymphocytes (CD3+) dominated, and cytotoxic or suppressor T cells (CD8+) were more frequent than T helper cells (CD4:CD8 ratio: 0.7+/- 0.1). Macrophages (CD68+) constituted the second-largest population, followed by Langerhans cells (CD1a+). B cells, natural killer cells, monocytes, and granulocytes were generally absent. There were no significant differences between the follicular and luteal phases. The epithelium was significantly thicker in all three groups that used hormonal contraceptive (333+/-9 microm) compared with controls, and it exhibited superficial hyperplasia. The frequency of intraepithelial leukocytes (CD45+) was increased in depot-medroxyprogesterone acetate (P<.001) and levonorgestrel implant users (P<.04). In depot-medroxyprogesterone acetate users, this was explained by an increased frequency of the CD8+ T lymphocyte subset. CONCLUSION: Hormonal contraceptives induce hyperplasia of the vaginal epithelium. The significant changes in the intraepithelial leukocyte population in depot-medroxyprogesterone acetate and levonorgestrel implant users most probably reflect altered local immune capacity.

[Dyspareunia in women is common, particularly in younger women. Pain history and the women's age provide valuable clues for diagnosis]. / Samlagssmärta hos kvinnor vanligt, inte minst hos yngre. Smärtanamnes och kvinnans ålder ger god vägledning för diagnos.

Very little is known about the causes of dyspareunia. The aim of this study was to investigate the diagnoses in a non-patient population of women after a short interview and a careful pelvic examination, and to analyze the predictive value of age and different pain characteristics according to Bayesian analysis and Bayes' Theorem. Sixty-four women with severe and prolonged dyspareunia were recruited from the Swedish national screening program for cervical cancer. It was shown that the diagnoses varied with age, and that age and various pain characteristics were very good predictors of the different diagnoses. The study concludes that diagnosing the most common types of severe dyspareunia is fairly easy and that extensive examinations are not generally required.

Prevalence and incidence of prolonged and severe dyspareunia in women: results from a population study.

AIMS: The principle aim of this study was to investigate the prevalence and incidence of prolonged (>/= 6 months) and severe dyspareunia in a non-patient population of women, and to explore the rate of recovery as well as the inclination to seek medical care. Another aim was to compare the use of oral contraceptives among women who had ever had dyspareunia and those who had not. METHODS: A total of 3,017 women aged 20-60 participating in a screening program for cervical cancer answered a questionnaire about possible painful coitus. RESULTS: The prevalence was 9.3% for the whole group and 13% for women aged 20-29 and 6.5% for the women aged 50-60, with a risk ratio of 2.0 (95% CI 1.4-2.8) for the youngest age group compared with the oldest. The incidence risk ratio was 9.3 (95% CI 2.8-30.9) for the youngest age group compared with the oldest. Using age-specific incidence rates, a rising incidence of dyspareunia in young women was demonstrated. Of the women who had ever had prolonged and severe dyspareunia 28% had consulted a physician for their symptoms; 20% recovered after treatment, while 31% recovered spontaneously. No differences were found in the use of oral contraceptives between the women who had had dyspareunia and those who had not. CONCLUSIONS: Prolonged and severe dyspareunia is a great health problem among all women and especially young women, for whom a rising incidence of dyspareunia is suggested and discussed. Surprisingly few women have consulted a physician, raising the question of why this is the case and what can be done about it.