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Menopause (New York, N.Y.) Aug 2023Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). (Meta-Analysis)
Meta-Analysis
Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis.
IMPORTANCE
Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).
OBJECTIVE
The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.
EVIDENCE REVIEW
Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.
FINDINGS
A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.
CONCLUSIONS AND RELEVANCE
Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.
Topics: Female; Humans; Dyspareunia; Vagina; Hyperplasia; Bayes Theorem; Network Meta-Analysis; Vulva; Atrophy; Tamoxifen; Selective Estrogen Receptor Modulators; Vaginal Diseases; Endometrial Neoplasms
PubMed: 37369079
DOI: 10.1097/GME.0000000000002211 -
Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.Obstetrics and Gynecology Aug 2023To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN),... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention.
DATA SOURCES
We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022.
METHODS OF STUDY SELECTION
We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms.
TABULATION, INTEGRATION, AND RESULTS
Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration.
CONCLUSION
Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42022377982.
Topics: Female; Humans; Imiquimod; Antineoplastic Agents; Prospective Studies; Aminoquinolines; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms
PubMed: 37411024
DOI: 10.1097/AOG.0000000000005256 -
Medicina (Kaunas, Lithuania) Nov 2023: Signs and symptoms of vulvovaginitis, especially when recurrent, have a significant impact on a woman's quality of life. The aim of this study was to survey... (Observational Study)
Observational Study
Efficacy of a Novel Rigenase and Polyhexanide (Fitostimoline Septagel) Hydrogel Device for the Treatment of Vulvovaginitis Symptoms: Cross-Sectional Analysis of a National Survey and Prospective Observational Study.
: Signs and symptoms of vulvovaginitis, especially when recurrent, have a significant impact on a woman's quality of life. The aim of this study was to survey gynecologists about their habits regarding the treatments of the pathology and to evaluate the efficacy of a novel vaginal hydrogel composed of wheat extracts and polyhexanide aimed at reducing vulvovaginitis symptomatology. : A cross-sectional analysis of a national survey using 155 Italian gynecologists and a prospective, open-label, observational study were carried out in 75 outpatient clinics across Italy. Pre- and postmenopausal women with suspicion of vulvovaginitis due to at least four of the following symptoms (leucoxanthorrhea, bad odor from genitalia, vulvovaginal dryness, petechiae, burning, and pruritus) while waiting for microbiological swab analysis were included and treated with one hydrogel application every 3 days for 1 week. Primary endpoint was the complete resolution of symptomatology. : The pre-study survey reported that, for most clinicians, local or oral treatment (65.7% and 82.8%, respectively) with antibiotics or antifungals is used very often. Therefore, we proceeded to carry out an observational study. Overall, 615 (362 of fertile age and 253 in postmenopause) women were included in this study. At the 28th follow-up examination, complete resolution of symptomatology was achieved in 578/615 (94.1%; < 0.001) within 12.72 ± 6.55 and 13.22 ± 6.33 days for those of fertile age and in postmenopause, respectively ( = 0.342). All of the evaluated symptoms were significantly reduced after treatment ( = 0.001) without differences according to the patient's menopausal status. A slightly significant reduction in ( = 0.040) and ( = 0.049) was found after treatment. No patient reported side effects, adverse reactions, or discontinued therapy. : This pilot study showed that a hydrogel based on Rigenase (wheat extract) and polyhexanide could be a promising treatment for the relief of vulvovaginitis symptoms. However, these results are limited by the absence of a control group. Additional comparative and randomized controlled trials between the hydrogel and other non-antibiotic devices as well as local antibiotic therapy should be performed to increase the validity of the findings.
Topics: Female; Humans; Cross-Sectional Studies; Hydrogels; Prospective Studies; Pilot Projects; Quality of Life; Vulvovaginitis; Anti-Bacterial Agents
PubMed: 38004053
DOI: 10.3390/medicina59112004 -
Diagnostics (Basel, Switzerland) Jul 2023A range of conditions involving the vulvovaginal and anal area, and those associated with human papillomavirus (HPV) infection, which can manifest as benign,...
A range of conditions involving the vulvovaginal and anal area, and those associated with human papillomavirus (HPV) infection, which can manifest as benign, pre-neoplastic, or neoplastic lesions, can be grouped into lower genital tract diseases [...].
PubMed: 37568879
DOI: 10.3390/diagnostics13152515 -
Reproduction & Fertility Apr 2024Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains... (Review)
Review
ABSTRACT
Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions.
LAY SUMMARY
Manipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.
Topics: Female; Humans; Animals; Microbiota; Gastrointestinal Microbiome; Probiotics; Prebiotics; Reproduction
PubMed: 38513356
DOI: 10.1530/RAF-23-0060 -
Journal of Lower Genital Tract Disease Oct 2023Nonsclerotic lichen sclerosus (NSLS) refers to the clinicopathologic situation of examination findings consistent with lichen sclerosus (LS) but without dermal sclerosis... (Review)
Review
OBJECTIVE
Nonsclerotic lichen sclerosus (NSLS) refers to the clinicopathologic situation of examination findings consistent with lichen sclerosus (LS) but without dermal sclerosis on microscopy. This review aims to describe the features of NSLS and provide a classification framework.
METHODS
The International Society of the Study of Vulvovaginal Diseases tasked the Difficult Pathologic Diagnoses Committee with development of consensus documents for conditions with problematic histopathology. The Difficult Pathologic Diagnoses Committee reviewed the literature on NSLS and formulated descriptions and diagnostic criteria, then approved by the International Society of the Study of Vulvovaginal Diseases membership.
RESULTS
Nonsclerotic LS may be categorized into 4 histopathologic subtypes: lichenoid dermatitis, hypertrophic lichenoid dermatitis, dermal fibrosis without acanthosis, and dermal fibrosis with acanthosis. Each has a pathologic differential diagnosis of 1 or more entities, so clinical correlation is required for final diagnosis of LS. There is no evidence to support a reliable association between absent sclerosis and clinical appearance, duration, or oncogenic potential of LS.
CONCLUSIONS
Pathologists and clinicians should be familiar with the concept of NSLS and its implications for patient management. Use of the term "early LS" to indicate a lack of sclerosis in presumed LS should be abandoned. Clinical correlation is required to confirm LS from among the differential diagnoses.
Topics: Female; Humans; Lichen Sclerosus et Atrophicus; Sclerosis; Vaginal Diseases; Dermatitis; Fibrosis
PubMed: 37467474
DOI: 10.1097/LGT.0000000000000760 -
International Journal of Women's Health 2024Vulvar vaginal atrophy is a common condition affecting postmenopausal women, significantly impacting their quality of life. Fortunately, various treatment options are... (Review)
Review
Vulvar vaginal atrophy is a common condition affecting postmenopausal women, significantly impacting their quality of life. Fortunately, various treatment options are available, ranging from hormonal to non-hormonal therapies. Ospemifene has emerged as a promising non-hormonal alternative for managing vulvar vaginal atrophy. Its targeted approach, unique mechanism of action, favorable safety profile particularly for breast tissue, and efficacy make it a valuable option for women seeking relief from symptoms such as vaginal pain, dryness and dyspareunia and cannot receive estrogen supplementations. This is particularly the case for breast cancer survivors or women with a significant family history of estrogen-dependent cancers. Hence, tailored treatment plans, considering individual preferences and health circumstances, are essential in optimizing outcomes and improving the overall well-being of affected individuals.
PubMed: 38855356
DOI: 10.2147/IJWH.S431520 -
Clinical Obstetrics and Gynecology Mar 2024The impact of bothersome vulvovaginal symptoms related to hypoestrogenism on quality of life (QOL) has been evaluated in large international surveys and qualitative...
The impact of bothersome vulvovaginal symptoms related to hypoestrogenism on quality of life (QOL) has been evaluated in large international surveys and qualitative studies of vulvovaginal atrophy, most of which were completed before the introduction of the term genitourinary syndrome of menopause (GSM) and focus primarily on vulvovaginal atrophy. The QOL domain most affected in these studies is sexual function, although women also report impacts on self-confidence, self-esteem, sleep, and general enjoyment of life. Health-related QOL measures are available that evaluate the impact of some symptoms associated with GSM on QOL; new measures are in development that assess the full range of symptoms associated with GSM.
Topics: Female; Humans; Vagina; Quality of Life; Vulva; Genital Diseases, Female; Atrophy; Menopause
PubMed: 37972951
DOI: 10.1097/GRF.0000000000000836 -
Clinical Obstetrics and Gynecology Mar 2024Genitourinary syndrome of menopause is a common, under-reported, and undertreated chronic progressive condition requiring long-term treatment. Hypoestrogenism in the...
Genitourinary syndrome of menopause is a common, under-reported, and undertreated chronic progressive condition requiring long-term treatment. Hypoestrogenism in the urogenital tissues is associated with bothersome dyspareunia, vulvovaginal symptoms, overactive bladder, and frequent urinary tract infections. Vaginal hormone therapies, including vaginal estrogen and intravaginal dehydroepiandrostenedione, are safe and effective and improve symptoms and clinical findings. Systemic hormone therapy treats vulvovaginal atrophy less effectively than vaginal hormone therapies with increased stress and urge urinary incontinence. Oral ospemifene effectively treats vaginal dryness and dyspareunia. Clinicians need to ask about symptoms of genitourinary syndrome of menopause, confirm the diagnosis, and suggest appropriate treatment options.
Topics: Female; Humans; Dyspareunia; Vulva; Menopause; Vagina; Hormones; Atrophy
PubMed: 38032827
DOI: 10.1097/GRF.0000000000000835 -
American Journal of Clinical Dermatology Sep 2023Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with...
BACKGROUND
Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144).
OBJECTIVES
The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials.
METHODS
The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to < 12 and 12 to < 18 years) and bodyweight (< 25 kg, 25 to < 50 kg, and ≥ 50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125).
RESULTS
A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to < 12 years subgroup and 12 to < 18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the < 25 kg, 25 kg to < 50 kg, and ≥ 50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (< 12 years: 11.8/100 PY; ≥ 12 years: 42.4/100 PY) and bodyweight (< 25 kg: 22.8/100 PY; 25 kg to < 50 kg: 19.0/100 PY; ≥ 50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab.
CONCLUSIONS
Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients.
GOV IDENTIFIER
NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023.
Topics: Adolescent; Child; Humans; Antibodies, Monoclonal; Double-Blind Method; Etanercept; Psoriasis; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Clinical Trials, Phase III as Topic
PubMed: 37341961
DOI: 10.1007/s40257-023-00782-8