[Show abstract][Hide abstract]ABSTRACT: Vulvodynia, a common cause of dyspareunia, inflicts physical pain and emotional distress in 16% of women during their lifetime. Symptoms include burning, knife-like pain or pain on contact in the vulvar area for at least 3 months. The etiology of this condition is unclear, and acceptable diagnostic criteria are subjective. Treatment is empirical. A recent review reported success rates for medical treatments ranging from 13% to 67%. Few randomized treatment trials have been conducted. Two previous studies reported that vestibular tissues from women with localized provoked vulvodynia (LPV) when compared with healthy women showed a significant increase in vestibular mast cells, heparanase activity, and intraepithelial neuroproliferation. Data suggest that mast cell heparanase degrades and weakens the structural integrity of the vestibular stroma, resulting in penetration of nerve fibers through the epithelial basement membrane and vestibular hyperinnervation. Enoxaparin, a low-molecular-weight heparin (LMWH), is a strong inhibitor of heparanase activity. Some investigators have suggested that enoxaparin treatment may strengthen the vestibular stroma and prevent neuroproliferation in women with vulvodynia. This randomized, double-blind, placebo-controlled study evaluated the effectiveness of enoxaparin for treatment of LPV. Forty women (aged 19–39 years) with severe LPV were randomized to receive either enoxaparin (n = 20) or placebo (n = 20). Clinical pain scores and local vulvar sensitivity were compared before treatment, at the end of treatment, and at the end of the study 3 months later. The effect of treatment on the number of vestibular mast cells, heparanase quantification, and neuroproliferation was measured by comparing immunostaining of biopsied tissue taken from the most painful focus at the beginning of the study with those taken from a parallel vestibular site at the end of the study. There was a significantly greater reduction in vestibular sensitivity in the enoxaparin group than in the placebo group at the end of the study (29.6% vs 11.2%, respectively; P = 0.004). At the end of the study, 75% (15/20) of women in the treated group reported more than 20% pain reduction compared with 27.8% (5/18) in the placebo group (P = 0.004). Seven women in the enoxaparin group and 3 in the placebo group reported nearly painless intercourse at the end of the study. Among the women with improved sensitivity at the site parallel to the original biopsy site, a histologically documented reduction was found in the number of intraepithelial-free nerve fibers in the enoxaparin group. These findings show that enoxaparin treatment reduces neuroproliferation concomitant with a reduction in vestibular sensitivity and dyspareunia among patients with LPV.
Full-text Article · May 2013 · Obstetrical and Gynecological Survey
[Show abstract][Hide abstract]ABSTRACT: To estimate the effectiveness of enoxaparin-a low-molecular-weight heparin with antiheparanase properties-in treating localized provoked vulvodynia.
Forty women with severe localized provoked vulvodynia were randomly and blindly assigned to self-administer either 40 mg enoxaparin or saline subcutaneously for 90 days. Dyspareunia and local sensitivity were evaluated before, at the end, and 90 days after treatment. The most painful focus was biopsied at the beginning of the study and a parallel site at the end of study for mast cells, PGP 9.5 nerve fiber staining, and heparanase quantification.
The enoxaparin-treated women showed a greater reduction in vestibular sensitivity at the end of treatment and 3 months later (29.6% compared with 11.2%, P=.004). Seventy-five percent (15 of 20) of them reported more than 20% pain reduction compared with 27.8% (five of 18) in the placebo group (P=.004). Seven enoxaparin-treated women compared with three in the placebo group had almost painless intercourse at the end of the study. In women who had improvement of sensitivity at the site parallel to the original biopsy site, there was a histologically documented reduction in the number of intraepithelial-free nerve fibers in the enoxaparin group.
Enoxaparin reduced the vestibular sensitivity and dyspareunia, concomitant with a reduction in intraepithelial free nerve fibers, in women with localized provoked vulvodynia.
Full-text Article · Sep 2012 · Obstetrics and Gynecology
[Show abstract][Hide abstract]ABSTRACT: Unlabelled:
Topical application of the calcium antagonist nifedipine has demonstrated effectiveness in treating chronic anal fissure, without adverse effects. Like chronic anal fissure, vulvodynia is associated with muscle hypertonicity and an inflammatory infiltrate. We conducted a double-blind placebo-controlled study to investigate the effectiveness of 2 concentrations of topical nifedipine cream in the treatment of vulvodynia. Thirty participants were alternately assigned to 3 topical treatment groups: .2% nifedipine, .4% nifedipine, and placebo. All administered the cream to the vestibule 4 times daily for 6 weeks. For all 3 treatment groups, mean pain intensity on vestibular touch, assessed by the Q-tipped cotton test, pain from speculum insertion, and reports of pain during sexual intercourse was reduced at post-treatment compared with pre-treatment. These improvements remained at 3 months' follow-up. The effectiveness of nifedipine in treating vulvodynia did not exceed that of placebo.
The topical application of both nifedipine and a placebo reduced pain in women with vulvodynia. This study highlights the need for controlled trials of treatments for vulvodynia and raises doubts about studies conducted without comparison to placebo.
Full-text Article · Dec 2010 · The journal of pain: official journal of the American Pain Society
[Show abstract][Hide abstract]ABSTRACT: The cause of vestibulitis, currently known as vestibulodynia, is still an enigma. Among those attempting to decipher the puzzle, Israeli researchers are well represented. This article reviews the developments in terminology, etiology, treatment, and research directions, with an emphasis on the role of IsraeLi research. Forty-four articles, covering a range of aspects of vestibulodynia, are testimony to the commendable contribution of Israeli research to the understanding of this disease. For example, the finding of mast cell proLiferation and degranulation, enhanced heparanase expression, and the resultant increase and penetration of nerve fibers into the epithelial emanates from Israel. Furthermore, an Israeli first proposed the new name, vestibulodynia. Implemented in the 1980s, immediately after its initiation in the United States, surgical treatment and research in Israel is at the forefront in the world. Israeli teams investigating the effectiveness of surgical treatment conclude that perineoplasty is more successful than any other treatment. Nonetheless, with 57% complete response, and 89% improvement, surgery does not cure all those suffering from vestibulodynia.
[Show abstract][Hide abstract]ABSTRACT: We compared a novel vaginal tablet consisting of 100 mg of clotrimazole and 100 mg of metronidazole ('Clo-Met') to a 100-mg clotrimazole tablet in the treatment of vaginitis.
A multicenter, double-blind, randomized controlled study. Women with vaginal discharge and diagnosed as suffering from vaginitis caused by Trichomonas vaginalis, bacterial vaginosis or Candida albicans, or any combination of the three, and who had not received treatment for vaginitis during the previous month, were studied.
165 patients were enrolled into the study--84 into the combined therapy group, and 81 into the clotrimazole group. In women with Candida vaginitis, Clo-Met was more effective than clotrimazole treatment (p < 0.012 and p < 0.05, respectively).
A combination vaginal tablet consisting of clotrimazole and metronidazole is therapeutically effective in candidal vaginitis. The effectiveness of Clo-Met on bacterial vaginosis, T. vaginalis infection as well as on vaginal infections due to a combination of these microorganisms should be studied further.
Article · Sep 2008 · Gynecologic and Obstetric Investigation
[Show abstract][Hide abstract]ABSTRACT: Recently, we have shown that vestibular hyperinnervation and the presence of 8 or more mast cells in a 10 x 10 microscopic field can be used as diagnostic criteria in localized vulvodynia (vulvar vestibulitis). We have also documented that degranulation of mast cells occurs in these cases. The present study further examines the characteristics of vestibular hyperinnervation and mast cell function in localized vulvodynia to elucidate if the 2 processes-hyperinnervation and mast cell increase and degranulation-are related. We examined vestibular tissue from 7 women aged 18 to 48 with severe localized vulvodynia and from 7 healthy control women. Parallel sections were stained by Giemsa and then immunostained for CD117 and heparanase. Nerve fibers that expressed protein gene product 9.5 were examined. Tissues from women with localized vulvodynia documented a significant increase in vestibular mast cells, subepithelial heparanase activity, and intraepithelial hyperinnervation compared with healthy women. This is the first documentation of heparanase activity in localized vulvodynia. Heparanase, which is degranulated from mast cells, is capable of degrading the vestibular stroma and epithelial basement membrane, thus permitting stromal proliferation and intraepithelial extension of nerve fibers, as seen in the present study. The hyperinnervation has been thought to cause the vestibular hyperesthesia distinctive of localized vulvodynia.
Article · Feb 2008 · International Journal of Gynecological Pathology
[Show abstract][Hide abstract]ABSTRACT: Developing the vaccine against human papillomavirus (HPV) types 6, 11, 16 and 18 which cause a variety of lesions, in particular cervical cancer, is regarded as a scientific breakthrough and received the FDA and CDC approval. Cervical cancer is the leading cause of death from cancer in women in developing countries. About 490,000 women develop cervical cancer yearly and 230,000 women die yearly of this disease. The vaccine includes a virus-like-particle (VLP) without the genetic core, which could have caused a malignant transformation. The present review describes how HPV causes cancer and how the vaccine has been developed. The large scale studies that have examined the vaccine depicted that it is well received, leads to a high antibody level, and prevents a chronic HPV infection and the diseases that are associated with it. However, several new questions arose, such as: at what age to administer the vaccine and whether it is possible to vaccinate those who had already been infected; for how long the immunity acquired by the vaccine lasts and is it effective in those whose immune system is depressed. Although best results will be achieved if the vaccine is administered to girls prior to sexual intercourse, vaccination at a later age may also be valuable. Previous exposure to the vaccine is not a contraindication to administration of the quadrivalent vaccine and it is not necessary to examine if it has occurred. Cervical cancer screening policy should continue for a few more years.
[Show abstract][Hide abstract]ABSTRACT: Unlabelled:
Recurrences of cervical intraepithelial neoplasia (CIN) as well as invasive cervical carcinoma have been reported to arise following ablative or excisional treatment for cervical intraepithelial neoplasia. This review utilizes MEDLINE and National Library of Medicine's PubMed review of the various screening tools used in follow-up protocols for women treated by loop excision for CIN. Cervical cytology, colposcopy, endocervical curettage and HPV typing have been advocated for use as tools for follow up. Involvement of the surgical margins and the presence of HPV-DNA are associated with higher risks of recurrence and should be taken into consideration. The psychological impact of undergoing colposcopy may affect compliance with follow-up visits and should be dealt with appropriately.
After completion of this article, the reader should be able to list the various tools that can be used for the surveillance of patients after treatment for CIN, to compare the advantages and disadvantages of each surveillance method, and summarize methods to improve compliance with follow-up.
Article · Oct 2004 · Obstetrical and Gynecological Survey
[Show abstract][Hide abstract]ABSTRACT: Large loop excision of the transformation zone (LLETZ) is regarded as the treatment of choice in cases of Cervical Intraepithelial Neoplasia (CIN). Since the method is easy to learn and the equipment is inexpensive, many gynecologists now perform it in the clinic. Concern has been raised regarding the use of this procedure with insufficient indication by physicians who have not been adequately trained in performing LLETZ.
This article aims to verify whether the indications for LLETZ in Israel are similar to those accepted in the updated literature and to discuss the need for licensure to perform LLETZ. Licensure would limit the use of LLETZ only to professionals specifically trained to conduct this procedure.
A questionnaire was sent to gynecologists, heads of obstetrics and gynecology departments as well as managers of public and private hospitals, regarding LLETZ performed in 2001. Topics covered in the questionnaire included: the number of LLETZ procedures performed, the patient's age, pre- and post-operative histopathological diagnosis, complications, follow-up and recurrence rate. The physicians were asked to complete separate questionnaires for each of the clinics in which he or she worked.
The completed questionnaires comprised of 625 LLETZ procedures in eight public and three private colposcopy clinics. The ages of the women ranged from 18 to 70 years old, with 49% in the 18 to 34 age range. Most women (416) who underwent the LLETZ procedure had CIN grades 2 or 3. However, 128 women with CIN 1 were also treated. Among this group, 50% were confirmed CIN 1 according to the surgical specimen but 43 women had normal epithelium, 20 (15.6%) had high grade CIN (2-3) and one had invasive cancer. The most common post-operative short and long-term complication was heavy bleeding. Involvement of the surgical specimen borders was found in one fifth of the cases.
The finding that about half of the women who underwent LLETZ were below the age of 35 years is of particular significance since the health insurance agencies in Israel only cover a pap smear screening test for women between the ages 35-54, once every three years. Therefore, there is an indication to start screening from the age 18. Similar to other countries in the world, the main indication to perform LLETZ in Israel is CIN 2-3. However, performing LLETZ for CIN 1 in many cases, and administering general anesthesia in certain centers, calls for the introduction of licensure for performing LLETZ. Involvement of the margins of the specimen in the neoplastic process in one fifth of the patients was similar to that reported in the literature. The various centers in Israel have different approaches as to the required surveillance period for women following LLETZ. It is suggested that women with involvement of the surgical specimen margins by CIN should be under medical surveillance at colposcopy clinics for a period of at least eight years.
[Show abstract][Hide abstract]ABSTRACT: To determine the DNA sequence of polymerase chain reaction (PCR) products obtained from surgical specimens of patients with severe vulvar vestibulitis, in order to identify and type the human papillomavirus (HPV)-DNA associated with vulvar vestibulitis.
Fifty three women, referred for dyspareunia and diagnosed as having severe vestibulitis, underwent perineoplasty operation consisting of surgical removal of the sensitive vestibule. PCR analysis using L1 HPV primer was performed, and DNA sequencing of the samples that were found to contain HPV-DNA was undertaken, using the dideoxy chain termination method.
Using PCR, HPV-DNA was detected in 31 of 53 tissue specimens (58%). DNA sequencing of 12 HPV-positive PCR products revealed extensive homology to human Alu consensus sequence, albeit not to any known HPV sequence.
The presence of interspersed, repetitive-DNA sequence Alu, which is known to be the preferred site for HPV integration into human genome, in the PCR product reinforces previous observations, suggesting that HPV may have a role in the pathogenesis of vulvar vestibulitis. It further implies a possible integration of the HPV into human DNA in these cases.
Article · May 2000 · European Journal of Obstetrics & Gynecology and Reproductive Biology
[Show abstract][Hide abstract]ABSTRACT: To consider the omission of several diagnostic steps from the management of patients with high-grade squamous intraepithelial lesion (SIL) by analyzing the role of each step on the choice of treatment.
Each diagnostic procedure was correlated to the treatment and outcome in 87 women with high-grade SIL. Treatments considered were large loop excision of the transformation zone (LLETZ) cold knife conization, and CO2 laser vaporization.
Unsatisfactory colposcopy (P< or =0.01) and positive endocervical curettage (ECC) specimen (P< or =0.01) were essential for choice of treatment. CIN2 diagnoses of the preoperative cervical biopsy were rediagnosed as CIN3 based on the surgical specimen in 57% of the cases. The margins of 33 and 23% of surgical specimens removed by LLETZ or knife conization, respectively, displayed CIN involvement. Forty and 47% of these patients, respectively, later developed recurrent CIN.
Omission of colposcopy and ECC could have resulted in sub-optimal treatment in many cases. Excision by LLETZ or knife conization is recommended for cases of CIN2 and CIN3. Follow up is imperative for patients with involvement of the margins.
Article · Aug 1999 · European Journal of Obstetrics & Gynecology and Reproductive Biology
[Show abstract][Hide abstract]ABSTRACT: To examine whether vestibulitis has a physical or a psychosexual etiology.
MEDLINE was searched to retrieve publications dating from January 1981 through June 1998 that evaluated the outcomes of surgical treatment and the psychosexual theory of the origin of vestibulitis. INTEGRATION: Articles were analyzed for methods of subject selection and surgery, surgical outcome, and length of follow-up.
A significant decrease in symptoms (complete responses + partial responses) was reported by 89% of 646 women who had perineoplasty for vulvar vestibulitis. Complete resolution of dyspareunia with surgical treatment was reported in 72% of 512 women whose cases were reviewed in studies in which complete responses and partial responses were evaluated separately. Women with vestibulitis did not differ from the normal population with respect to marital satisfaction, psychologic distress, or psychopathology. A suggestion that childhood sexual abuse caused vestibulitis has not been confirmed. The findings of somatization and shyness might be explained as results rather than causes of vulvar vestibulitis.
We do not agree that vestibulitis is a psychosexual problem and one that should not be treated surgically. A high rate of success can be achieved with proper surgical treatment.
[Show abstract][Hide abstract]ABSTRACT: Objective: To examine whether vestibulitis has a physical or a psychosexual etiology. Data Sources: MEDLINE was searched to retrieve publications dating from January 1981 through June 1998 that evaluated the outcomes of surgical treatment and the psychosexual theory of the origin of vestibulitis. Integration: Articles were analyzed for methods of subject selection and surgery, surgical outcome, and length of follow-up. Results: A significant decrease in symptoms (complete responses + partial responses) was reported by 89% of 646 women who had perineoplasty for vulvar vestibulitis. Complete resolution of dyspareunia with surgical treatment was reported in 72% of 512 women whose cases were reviewed in studies in which complete responses and partial responses were evaluated separately. Women with vestibulitis did not differ from the normal population with respect to marital satisfaction, psychologic distress, or psychopathology. A suggestion that childhood sexual abuse caused vestibulitis has not been confirmed. The findings of somatization and shyness might be explained as results rather than causes of vulvar vestibulitis. Conclusion: We do not agree that vestibulitis is a psychosexual problem and one that should not be treated surgically. A high rate of success can be achieved with proper surgical treatment.
Full-text Article · May 1999 · Obstetrics and Gynecology
[Show abstract][Hide abstract]ABSTRACT: A continuing challenge in the management of women with vulvar vestibulitis is the patient who has not responded to surgical treatment. The main reason for persistent dyspareunia is failure to excise the sensitive periurethral tissue in the primary operation. In other cases, the Bartholin's glands may be the source of the pain. A low oxalate diet, the administration of interferon, and biofeedback training of the lower pelvic muscles-treatments that are used as a first-choice approach for vulvar vestibulitis, may all work in the postoperative patient. The management of a patient with residual vestibulitis should be conservative, and only when medical measures fail, do we consider additional surgical methods such as Bartholin's gland resection or repeat perineoplasty.
Article · Feb 1998 · Obstetrical and Gynecological Survey
[Show abstract][Hide abstract]ABSTRACT: Our purpose was to recognize special features of women with both vestibulitis and constant vulvar pain (vestibulodynia) and to determine whether vestibulodynia is a separate disease entity or a subset of vestibulitis.
Ninety-one women with severe vulvar vestibulitis underwent perineoplasty by a single surgeon during 1992 to 1995. Twenty-five (27%) of them who had vestibulodynia were compared with 66 (73%) who had dyspareunia alone. With univariate and then multivariate analysis, the two groups were compared with regard to demographic, social, and medical variables, the presence of human papillomavirus deoxyribonucleic acid, physical findings in the vestibule, and surgical outcome.
The vestibulodynia and vestibulitis groups differed in age (30.5 +/- 10.6 years vs 24.7 +/- 6.2 years respectively), as well as in marital status (married, 44% vs 18%, respectively), nonuse of contraception (20% vs 1%, respectively), presence of human papillomavirus deoxyribonucleic acid in the vestibule (80% vs 48%, respectively), and failure of surgical treatment (incomplete response rate, 64% vs 2%, respectively). With multivariate analysis, patients with human papillomavirus deoxyribonucleic acid present in the vestibule have an odds ratio of 5.44 (95% confidence interval, 1.45 to 20.33) of belonging to the group with vestibulodynia, whereas dysuria and age have odds ratios of 3.70 (95% confidence interval 1.09 to 12.55) and 1.14 (95% confidence interval 1.04 to 1.24), respectively.
Vestibulodynia is a unique syndrome in that it affects women who are older than those who have vestibulitis alone and it is associated with human papillomavirus deoxyribonucleic acid, dysuria, and a higher surgical failure rate than that for vestibulitis.
Article · Jan 1998 · American Journal of Obstetrics and Gynecology
[Show abstract][Hide abstract]ABSTRACT: To assess the efficacy of a novel glycosylated mammalian cell derived recombinant human interferon-beta (r-hIFN-beta-1a) in the intralesional treatment of genital condylomata acuminata. The study was randomized, double-blind and placebo-controlled. Patients (n=60) with up to 8 distinct condylomata acuminata were randomized to receive either one million international units (IU) of r-hIFN-beta-1a or placebo intralesionally into each lesion, 3 times a week, for a total of 9 occasions. Biopsies were taken from each patient before enrolment to allow human papillomavirus (HPV) testing, and patients were tested for the development of anti-IFN-beta antibodies. Efficacy was assessed by measuring the complete response rate 3 months after treatment. The complete response rate was not significantly better with r-hIFN-beta-1a than with placebo. However, after 3 months, 73.3% of patients treated with r-hIFN-beta-1a had experienced at least a partial response to treatment, compared with 33.3% of placebo-treated patients. At 19 days and 6 weeks, r-hIFN-beta-1a produced a significantly larger reduction in the area of condylomata. Lesions with detectable HPV6 or 11 showed a trend towards a better response rate to treatment with r-hIFN-beta-1a than lesions where no HPV DNA was detected. The treatment was well tolerated. In the 5 patients who developed non-neutralizing anti-IFN-beta antibodies, therapeutic efficacy was not compromised. Intralesional r-hIFN-beta-1a was effective in the reduction of the size of genital condylomata acuminata.
Article · Nov 1997 · International Journal of STD & AIDS
[Show abstract][Hide abstract]ABSTRACT: To evaluate positional hydrostatic effects on blood pressure determination during pregnancy.
We studied 30 normotensive, pregnant women at 34-41 weeks of gestation. Blood pressures were taken in the sitting, left lateral, right lateral and supine positions with a two-minute stabilization period between positions. The bisacromial diameter was measured. Multivariate analysis of variance for repeated measures was used to evaluate the affect of position on blood pressure.
Mean systolic pressure in the right arm was 2.6 mm Hg greater than that in the left arm (P < .05). There was no difference between the arms in diastolic blood pressure. Immediate blood pressure in the lower arm was no greater than in the higher arm in lateral positions, and there were no other significant positional effects. Observed blood pressures were significantly different than those theoretically expected on the basis of hydrostatic effects (P < .0001).
Positional effects on blood pressure in the lateral positions do not appear immediately (within two minutes), indicating that hydrostatic pressure does not account for these changes. The well-documented blood pressure reduction from longer duration in the lateral position does not appear to be an artifact of hydrostatic effect. Repositioning pregnant women in the supine position to have the cuff at the level of the heart is unnecessary and often undesirable when fetal perfusion is an important consideration. We suggest that American Heart Association blood pressure guidelines stating that all measurements be taken with the cuff at the level of the heart to avoid hydrostatic pressure change be revised for pregnancy.
Article · Jul 1997 · The Journal of reproductive medicine