Efficacy and safety of a new vaginal gel for the treatment of symptoms associated with vulvovaginal atrophy in postmenopausal women: A double-blind randomized placebo-controlled study.

OBJECTIVE: The aim of the present randomized placebo-controlled single-center study was to assess the efficacy and safety of a new vaginal gel (Meclon Idra - Alfasigma) in the treatment of vulvovaginal atrophy (VVA). The gel is composed of sea buckthorn (Hippophaë rhamnoides) oil, aloe vera, 18ß-glycyrrhetic acid, hyaluronic acid and glycogen. The study assessed whether the gel can reduce VVA symptoms (vaginal dryness, itching, burning sensation) and improve sexual function in postmenopausal women over 12 weeks. STUDY DESIGN: Postmenopausal women (n° = 60) reporting VVA symptoms were recruited and randomized in a 1:1 ratio to the gel or placebo. Active vaginal gel or placebo was applied for 14 days and then twice a week for 90 consecutive days. MAIN OUTCOME MEASURE: The Vaginal Health Index (VHI), including vaginal pH, was used to assess changes in objective signs, whereas the self-reported Female Sexual Function Index (FSFI) was used to investigate sexual function. RESULTS: Meclon Idra was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the VHI showing significant improvement at day 90 (P < .0001), and in reducing each VVA symptom (vaginal dryness, vaginal itching, burning sensation) at weeks 2 and 4, and the end of the study (P < .0001). The analysis of FSFI scores showed, after the end of treatment, an improvement of sexual function in the active-treatment group, with a statistically significant increase (P < 0.001) in all domains scores and total score (P < 0.001). CONCLUSIONS: The present single-center randomized clinical trial demonstrated the efficacy, tolerability and safety of 12-week treatment with a new vaginal gel in postmenopausal women with symptoms associated with VVA. Based on this trial, the gel seems to be a valid choice as a single, local agent for relieving VVA symptoms and improving sexual function, and to have good compliance. This trial is registered prospectively with the Clinical Trials Registry - India, number CTRI/2019/05/01911.

What is the role of dehydroepiandrosterone in gynecologic practice?

In small clinical trials, dehydroepiandrosterone (DHEA) has been found to relieve symptoms associated with postmenopausal conditions and infertility in women. DHEA may provide a cost-effective alternative to typical hormone therapies. Because of a lack of long-term and large-scale studies, only intravaginal DHEA supplementation is approved and recommended for treatment. Further investigation of DHEA supplementation is needed and encouraged to determine its safety and effectiveness.

Low-dose methotrexate-induced vulvar edema: A case report.

RATIONALE: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate. PATIENT CONCERNS: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp. DIAGNOSES: The patient was diagnosed based on clinical findings for MTX toxic reactions. INTERVENTIONS: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed. OUTCOMES: The vulvar edema and oral cavity ulceration and scalp ulceration healed. LESSONS: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.

Acute and sub acute toxicity study and randomized clinical trial of polyherbal coded drug candicure in the management of acute vulvo-vaginal candidiasis.

Vulvo-Vaginal Candidiasis is common gynecological disorder. Clinical trials are designed to evaluate the effect of medical intervention with allopathic and herbal medicine to treat vulvo-vaginal candidiasis. The toxicity index and the safety profile of test drug were assessed on animals' model. Toxicity study of polyherbal formulation was done in order to consider it safe before use. In acute toxicity study, a single dose of 2000 mg/kg was given to Swiss Albino mice and in sub-acute toxicity study three different doses were given to Wistar rats. Randomized Controlled Clinical Trials was conducted. Inclusion and exclusion criteria and informed consent from the patients were to be monitored. In acute toxicity study no morbidity and mortality noticed on single administration of dose 2000mg/kg/day. In sub -acute toxicity study no significant changes were observed in consumption of food and water, body weight, hematological parameters, Liver function test, renal function parameters and lipid profile. The statistical analysis showed C. albican was eradicated in 59 participants (78%) out of 75 participants by the use of Candicure (Test drug) and in 56 participants (74%) out of 75 participants by the use of Fluconazole therapy (Control drug). Chi-square test was applied and p-value was calculated 0.3101 which is greater than 0.05 showed that Candicure therapy and Fluconazole therapy is equally significant in eradication of C. albican. The acute and sub-acute toxicity study of polyherbal formulation on experimental animals is safe at a dose of 2000mg/kg/day. The clinical findings of randomized controlled trial revealed that the effect was almost comparable to control drug in eradicating the micro-organism.

Efficacy and tolerability of a plant-based, multi-component cream (Ginetrox®) in vulvovaginal disorders of the genitourinary syndrome during menopause.

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a symptomatic condition including vaginal dryness, irritation, dyspareunia and recurrent urinary tract infections which affects 40-54% of post-menopausal women. Although several estrogen-based therapies are available, it is generally preferable to avoid hormonal therapy, particularly in women with mild symptoms or at risk for estrogen-responsive neoplasia. Therefore, the most common treatment options are over-the-counter vaginal creams for symptomatic relief. METHODS: Thirty-three postmenopausal women suffering from GSM were enrolled in this observational study. A multi-component cream (Ginetrox®, Indena, Milan, Italy) was applied on the vestibular area of the vagina for three months. The primary endpoints were: vaginal burning and/or pain, assessed by Visual Analog Scale and dyspareunia, assessed using the Marinoff Score. As a secondary endpoint, vestibular health was evaluated through a four-point scale. Side effects and adherence to treatment were also recorded. RESULTS: Statistically significant improvement was observed in pain scores and dyspareunia at the end of the treatment compared to baseline values. The vestibular health index significantly decreased after 3 months. Tolerability was acceptable. CONCLUSIONS: This preliminary study suggests that the plant-based, multi-component cream Ginetrox® could be effective and safe in counteracting menopause-related vaginal discomfort symptoms.

Intravenous zinc therapy for acquired zinc deficiency secondary to gastric bypass surgery: a case report.

Zinc deficiency may result from either a congenitally inherited defect of zinc absorption or is acquired secondarily from a variety of factors affecting dietary zinc intake, absorption, or loss. We report a case of acquired zinc deficiency secondary to gastric bypass surgery that resulted in vulvar cutaneous manifestations of delayed onset, with failure to clear after oral supplementation with zinc. The patient experienced improvement of symptoms only after administration of intravenous zinc supplementation. Upon review of the current literature, it is thought that the patient's original suboptimal response to oral supplementation and improvement after receiving intravenous zinc were related to the intentional surgical alteration and bypass of the absorptive capacity of the duodenum and jejunum. With the current prevalence of obesity and availability of surgical weight loss therapies, it is important to be mindful of the resulting nutritional deficiencies, their clinical manifestations, and factors affecting the efficacy of therapeutic approaches as seen in this case.

Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy.

OBJECTIVE: While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness. METHOD: Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo. RESULTS: Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 µg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant (p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo (p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects. CONCLUSION: The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing.

Efficacy of combination therapy of oral zinc sulfate with imiquimod, podophyllin or cryotherapy in the treatment of vulvar warts.

AIM: Zinc sulfate is beneficial in the treatment of epithelial warts. We conducted this study to compare the efficacy of combination therapy of oral zinc sulfate with conventional treatments in the treatment of vulvar warts. MATERIAL AND METHODS: This study was a randomized controlled trial. The sample size was 42 in each group. Women aged 20-50 years were placed by the block randomized method into six groups: the podophyllin-, imiquimod- and cryotherapy-treated groups, and another three groups receiving 8-week combination therapy of 400 mg oral zinc sulfate with one of the above-mentioned treatments. Data were analyzed using anova and Fischer's exact test with spss16. RESULTS: A total of 228 patients were recruited and completed the study in six treatment groups. No significant difference was observed in the response to treatment among these groups. Relapse after 6 months was significantly higher in the podophyllin-, imiquimod- and cryotherapy-treated patients compared to patients receiving these treatments in combination with oral zinc sulfate (P<0.05). CONCLUSIONS: Combined therapy of oral zinc sulfate with conventional treatments of vulvar warts appears to reduce the relapse rate.

Acute genital ulcers in nonsexually active young girls: case series, review of the literature, and evaluation and management recommendations.

Acute genital ulcers rarely occur in nonsexually active young girls. When present, they can cause significant physical and emotional distress for the patient and her parents, and prompt an evaluation for sexual abuse and sexually transmitted diseases. With this review, we aim to further characterize acute genital ulcers in nonsexually active young girls by reviewing the medical records of patients with this disorder and to offer an approach to the diagnosis, evaluation, and treatment of acute genital ulcers based on our understanding and knowledge of this condition. We retrospectively review our understanding and knowledge of acute genital ulcers in nonsexually active girls at a pediatric hospital. A review of the recent literature on acute genital ulcers and a multidisciplinary approach to the diagnosis, evaluation, and treatment of acute genital ulcers are also presented. Twelve patients presented with acute genital ulcers, 11 of which were hospitalized for evaluation and pain management. Extensive work-up failed to reveal a specific infectious or autoimmune etiology in all but one patient, who was diagnosed with acute mycoplasma pneumonia. Acute genital ulcers in nonsexually active young girls likely represent a form of idiopathic vulvar aphthosis. Evaluation of a first episode of acute genital ulcers with mild prodromal symptoms should be limited. Treatment consists primarily of supportive care and symptom relief.

Efficacy of aloe vera gel in the treatment of vulval lichen planus.

OBJECTIVE: To compare the efficacy of aloe vera gel and placebo in the topical management of vulval lichen planus. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. PLACE AND DURATION OF STUDY: Department of Dermatology, Isra University Hospital, Hyderabad, from January 2007 to January 2008. METHODOLOGY: Thirty-four female patients were randomized into two groups to receive aloe vera gel or placebo for local application for 8 weeks. Clinical data and treatment response was graded according to Thongprasom criteria. Z-test was used for comparing response between the groups. RESULTS: Thirty-four consecutive patients participated in the study. We found erosive and ulcerative lesions in 83% and 17%, respectively. The most common site of vulval lichen planus was the labia minora. Fourteen (82%) out of 17 patients treated with aloe vera had a good response i.e. clinically improved by at least 50% after 8 weeks of treatment, while one (5%) of 17 placebo-treated patients had a similar response (p < 0.001). Furthermore, one patient (5%) treated with aloe vera had a complete clinical remission. No side-effects were found in both groups. CONCLUSION: Aloe vera gel was a safe and effective treatment for patients with vulval lichen planus.

[Clinical observation on integrative Chinese and Western medicine in treating nontumorous vulval intraepithelial lesion].

OBJECTIVE: To assess the clinical effect of integrative Chinese and Western medicine in treating nontumorous vulval intraepithelial lesion (NIEL). METHODS: One hundred patients of NIEL, with their diagnosis confirmed by pathologic examination, were equally assigned to two groups randomly, the treatment group and the control group. The treatment group was treated by Chinese recipe consisting of herbs for nourishing Gan-Shen, it was decocted for 3 times, the foregoing two decoctions for oral intake, and the latter one (500 mL) for hip bathing 5-10 min every night before sleep. Besides, the self-formulated preparation Jingan oil (composed of aureomycin and glycerine, etc. ), was locally applied twice every day. The control group was treated only by local applying of Jingan oil and a 5-10 min hip bathing with warm water every night. The course for both groups was 2 months. Efficacy of the treatment was assessed at the end of the therapeutic course and after a 2-month follow-up, depending on the changes of local lesion degree, vulval symptoms as pain and itching, estrogen and progestin receptors in the lesion, and the scores of symptoms. RESULTS: The total clinical effective rate was 94% (47/50) in the treatment group and 66% (33/50) in the control group. The severity of local lesion degree, symptoms of pain and itching and the scores of symptoms were significantly improved in both groups, as compared with those before treatment (all P <0.01). However, comparison between groups showed that the improvement was better in the treatment group. The positive rates of estrogen and progestin receptors in the local lesions of the two groups showed insignificantly statistical difference. CONCLUSION: The integrative medical treatment can effectively alleviate the NIEL and improve the relevant clinical symptoms.

Vulvar lichen sclerosus : pathophysiology and treatment.

Lichen sclerosus is a chronic disorder of the skin and mucosal surfaces, and is most commonly seen on the female genital skin. It also occurs on other areas of the body. Any age group may be affected, although it is seen more often in elderly women. The exact cause of lichen sclerosus is unknown. There have been reports of family members with lichen sclerosus; thus it may have a genetic link. There is also the possibility of an autoimmune connection. Currently, ultra-potent topical corticosteroids are the medical treatment of choice. Other treatments that have been utilized for this condition include testosterone, progesterone, tacrolimus, surgery, and phototherapy. Surgery should be reserved for symptomatic patients who fail to respond to multiple medical treatments, as there is a high recurrence rate following surgery. The risk of developing squamous cell carcinoma of the vulva approaches 5% in women with vulvar lichen sclerosus, and therefore close surveillance by the healthcare provider and patient is needed. This review discusses the history, clinical features, pathophysiology, and treatment of lichen sclerosus of the vulva, as well as pregnancy issues and sexual function in patients with this condition. In addition, problems specific to children with lichen sclerosus are reviewed.

Vulvar dysesthesia (vulvodynia). A follow-up study.

OBJECTIVE: To assess long-term outcome in women treated for vulvar dysesthesia (vulvodynia). STUDY DESIGN: Cross-sectional survey via mailed questionnaires of women with vulvar dysesthesia treated at the University of Michigan. Questionnaires addressed symptom characteristics and their predictors, pregnancy response and treatments used. Analysis included t tests, nonparametric tests and multivariate analyses to assess associations between the degree of improvement (in the amount of pain experienced) since diagnosis and potential predictors of that outcome. RESULTS: Of 234 questionnaires mailed, 104 were completed. Based on a 7-point pain scale (0-6, with 6 indicating excruciating pain), the level of pain at the time of the survey (1.6 +/- 1.3) was significantly lower than that at the time of diagnosis (4.5 +/- 1.5) (P < .0001). Of the 104 women, 56.8% reported > 50% improvement in their pain since diagnosis, and the pain had worsened in 1.9%. Greater improvement was noted with higher pain levels at baseline and with a shorter time since onset. The majority of women who had been pregnant since developing vulvar pain reported improvement (30%) or no change (40%) in symptoms during and after pregnancy. Treatments (nonrandom) rated as most effective included antidepressants (used for pain control) and anticonvulsant medications, biofeedback and counseling. CONCLUSION: Most women with vulvar dysesthesia reported markedly less pain at follow-up, although few reported a "cure." Pregnancy was not associated with worsening of vulvar symptoms for most women. Controlled clinical trials will be needed to elucidate treatments that are most effective.

[Incidence and management of condylomata acuminata by French general physicians]. / Incidence et prise en charge des condylomes acuminés externes en médecine générale.

OBJECTIVES: Condylomata acuminata (or genital warts) are sexually transmitted diseases caused by human papillomavirus. Until now, there has been no available epidemiologic data about this disease in France. We conducted a prospective study among French general practitioners (GPs) to estimate the incidence of consultations for external condylomata acuminata in general practice. We also assessed the management of patients with external condylomata acuminata by French GP's. DESIGN: A panel of French general practitioners, members of the Sentinel network, had to fill-in prospectively a questionnaire for each patient with condylomata acuminata diagnosed between July and November 2000. RESULTS: The annual number of consultations for external condylomata acuminata with French GP's was estimated at 23,000 (CI (95 p. 100) 21,000-25,000) including 15,000 new cases (CI (95 p. 100) 13,000-17,000). Taking into account the estimations we made at the same time in office-based private dermatologists, we estimated the annual incidence of external condylomata acuminata in France at 107/100 000 inhabitants. The management of patients with external condylomata acuminata by French GP's was in accordance with the European guidelines in 54 to 78 p. 100 of cases. French GP's mostly prescribed chemical treatment. DISCUSSION: A proportion of cases of condylomata acuminata may have not been diagnosed. Similarly, some lesions may have been wrongly diagnosed as condylomata acuminata, but these proportions of false positive and false negative remain unknown. The incidence of external condylomata acuminata in France is similar to those estimated in others developed countries.

Pure versus complicated vulvar vestibulitis: a randomized trial of fluconazole treatment.

OBJECTIVE: To examine the effectiveness of a 6-month treatment consisting of a weekly oral dose of 150 mg fluconazole for women with vestibulitis, and to explore the causes of treatment failure. METHODS: Forty women with vestibulitis were randomized to either of two treatment groups. One group received a 6-month low oxalate diet with calcium citrate complement, as a placebo, and the second group the same diet and calcium citrate with the addition of a weekly oral tablet of 150 mg fluconazole. The women were examined 3 months after completing treatment, for response to therapy. RESULTS: The addition of intensive 6-month fluconazole treatment did not lead to an outcome better than that attained by maintaining a low oxalate diet with calcium citrate supplementation. The satisfactory response rate was 15 and 30%, respectively. The presence of 'complicated vestibulitis', candidiasis concomitant with vestibulitis, decreases the satisfactory response rate regardless of the type of treatment administered (odds ratio 19.9, 95% CI 1.6, 250). CONCLUSION: Prolonged oral fluconazole is an ineffective treatment of vestibulitis, whether pure or complicated by concomitant vulvovaginal candidiasis. The coexistence of candidiasis and vestibulitis - complicated vestibulitis - might represent a subset of vestibulitis that is resistant to the currently available medical therapy.

[Cetyltrimethylammonium naproxenate as vaginal lavage in the therapy of vulvovaginal dystrophies in the postmenopause]. / Il naprossenato di cetiltrimetilammonio lavanda vaginale nella terapia delle distrofie vulvo-vaginali in post-menopausa.

A peculiar aspect of the postmenopausal period is atrophy of the lower genital tract, vagina and vulva. This is due to estrogen deficiency and is accompanied by vaginal pH elevation, lower number of lactobacilli and increased incidence of aspecific vulvovaginitis. We tested a new vaginal douche with an antibacterial-anti-inflammatory (non antibiotic-nonsteroidal) principle, cetyltrimethylammonium naproxenate 0.223% as an adjunct to classical estrogen topical replacement therapy. We treated 34 menopausal patients (mean age 67 yrs) in a double parallel controlled (15 A only estrogen topical therapy vs 19 B topical estrogen plus cetyltrimethylammonium naproxenate douches uid) study for 30 days. A significant reduction of symptoms was obtained in both groups although a faster reduction has been seen in the group treated with both drugs (= B). In conclusion a better replacement of physiological pH with reappearance of lactobacilli, a selective action on vaginal pathogens, a faster symptom remission and an higher psychophysical welfare can be attributed to the vaginal douche used in adjunct to classical estrogen topical therapy.

New therapies for the treatment of genital warts.

The treatment of genital warts with cytodestructive agents such as podophyllin and trichloroacetic acid continues to impose a heavy burden on the workload of genitourinary medicine clinics. Consequently clinics are now looking to new, economical treatments that will improve the management of patients with genital warts. The most promising of these new agents is podophyllotoxin, which is now available in pharmaceutically pure form tailored for the home treatment of external genital warts in males and females.

Superficial laser vulvectomy. IV. Extended laser vaporization and adjunctive 5-fluorouracil therapy of human papillomavirus-associated vulvar disease.

Although most human papillomavirus infections can be managed satisfactorily by office methods, extensive, refractory, and dysplastic vulvar disease poses frustrating problems. This observational cohort study evaluated the efficacy of extended laser ablation (vaporization of both clinically apparent and adjacent subclinical changes) among 160 women drawn from 1000 referrals between 1982-1987. During the final 2 years, the protocol incorporated two different 5-fluorouracil (5-FU) regimens: routine once-weekly applications as prophylaxis against postoperative recurrence, and twice-weekly dosing to avoid further laser surgery among patients with early but diffuse failures. One hundred seven patients (66.9%) were controlled by a single operation. Subsequent therapy for the remaining 53 women involved 44 additional superficial photovaporizations, 38 courses of therapeutic 5-FU, four deep laser destructions with skin grafting, and six trials of systemic alpha-interferon. Eventually, 158 patients (98.7%) entered stable clinical remission. Adjuvant 5-FU improved success rates among the 76 women with two or more adverse prognostic factors (87.5 versus 55.8%; P less than .01) but had no prophylactic value in the other 84 women. In contrast, the therapeutic 5-FU regimen was generally effective, avoiding the need for further surgery in 22 (57.9%) of 38 inevitable failures, compared with only four successes (10.3%) among 39 historic controls managed with caustic agents (chi 2 = 19.5; P less than .001). Improvements in laser technology had no impact upon outcome, but more sophisticated heat containment strategies reduced postoperative pain, healing time, and morbidity. Given adequate technique and an appropriate indication, we find extended laser ablation to be an excellent primary control method. However, the availability of an effective adjuvant regimen would be a valuable complement.