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Antiprogestins in gynecological diseases.

ABSTRACT: Antiprogestins constitute a group of compounds, developed since the early 1980s, that bind progesterone receptors with different affinities. The first clinical uses for antiprogestins were in reproductive medicine, e.g., menstrual regulation, emergency contraception, and termination of early pregnancies. These initial applications, however, belied the capacity for these compounds to interfere with cell growth. Within the context of gynecological diseases, antiprogestins can block the growth of and kill gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. They can also interrupt the excessive growth of cells giving rise to benign gynecological diseases such as endometriosis and leiomyomata (uterine fibroids). In this article, we present a review of the literature providing support for the antigrowth activity that antiprogestins impose on cells in various gynecological diseases. We also provide a summary of the cellular and molecular mechanisms reported for these compounds that lead to cell growth inhibition and death. The preclinical knowledge gained during the past few years provides robust evidence to encourage the use of antiprogestins in order to alleviate the burden of gynecological diseases, either as monotherapies or as adjuvants of other therapies with the perspective of allowing for long-term treatments with tolerable side effects. The key to the clinical success of antiprogestins in this field probably lies in selecting those patients who will benefit from this therapy. This can be achieved by defining the genetic makeup required - within each particular gynecological disease - for attaining an objective response to antiprogestin-driven growth inhibition therapy.Free Spanish abstractA Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/1/15/suppl/DC1.

SUBMITTER: Goyeneche AA

PROVIDER: S-EPMC4247796 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundGynecological diseases have been taken attention and studied worldwide. Although, no recent studies have delineated the magnitude of gynecological diseases among Chinese women. This study aims to evaluate the current situation of menstruation and gynecological diseases prevalence among Chinese women.MethodsA cross-sectional study was conducted at a hospital affiliated with Nanjing medical university in Nanjing, China between September 2021 and February 2022. A sample size of 977 women aged 18-52 years participated in a face-to-face interview questionnaire. Logistic regression was performed to determine whether pubertal timing and menstrual characteristics were associated with gynecological diseases.ResultsThe most prevalent gynecological disease was dysmenorrhea (45.96%), followed by polycystic ovary syndrome, PCOS (19.04%), uterine fibroids (14.23%), spontaneous abortion (13.20%), trouble conceiving (12.59%), ovarian dysfunction (11.16%) and endometriosis (4.09%). In the adjusted model, heavy bleeding with large clots was associated with an increased risk of dysmenorrhea (odds ratio, OR = 5.01, 95% Confidence interval, CI 2.26, 11.10; p = 0.000), while history of precocious puberty diagnosis was associated with a reduced risk of dysmenorrhea (OR = 0.50, 95%CI: 0.26, 0.94; p = 0.031). Regular menstrual cycle in the past 12 months and regular menstrual periods were associated with decreased risk of PCOS (OR = 0.44, 95%CI 0.30, 0.65; p = 0.000) and (OR = 0.52, 95%CI 0.36, 0.74; p = 0.000), respectively. Histories of early thelarche, early menarche, and precocious puberty diagnosis were associated with increased risk of ovarian dysfunction (OR = 1.96, 95%CI 1.25, 3.08, p = 0.004), (OR = 2.26, 95%CI 1.24, 4.13; p = 0.008) and (OR = 2.79, 95%CI 1.36, 5.74; p = 0.005), respectively. Heavy bleeding and heavy bleeding with large clots were associated with endometriosis (OR = 4.92, 95%CI 1.50, 16.15, p = 0.009) and (OR = 5.67, 95%CI 1.42, 22.56; p = 0.014), respectively.ConclusionsThe prevalence of gynecological diseases is increasing among Chinese women and pubertal timing and menstrual characteristics may be associated with some gynecological diseases, specifically dysmenorrhea, PCOS, ovarian dysfunction, and endometriosis.

Project description:BackgroundIncreasing number of studies have demonstrated certain patterns of microbial changes in gynecological diseases; however, the interaction between them remains unclear. To evaluate the consistency or specificity across multiple studies on different gynecological diseases and microbial alterations at different sites of the body (gut and genital tract), we conducted a systematic review and meta-analysis.MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Library up to December 5, 2022(PROSPERO: CRD42023400205). Eligible studies focused on gynecological diseases in adult women, applied next-generation sequencing on microbiome, and reported outcomes including alpha or beta diversity or relative abundance. The random-effects model on standardized mean difference (SMD) was conducted using the inverse-variance method for alpha diversity indices.ResultsOf 3327 unique articles, 87 eligible studies were included. Significant decreases were found in gut microbiome of patients versus controls (observed species SMD=-0.35; 95%CI, -0.62 to -0.09; Shannon index SMD=-0.23; 95%CI, -0.40 to -0.06), whereas significant increases were observed in vaginal microbiome (Chao1 SMD = 1.15; 95%CI, 0.74 to 1.56; Shannon index SMD = 0.51; 95%CI, 0.16 to 0.86). Most studies of different diagnostic categories showed no significant differences in beta diversity. Disease specificity was observed, but almost all the changes were only replicated in three studies, except for the increased Aerococcus in bacterial vaginosis (BV). Patients with major gynecological diseases shared the enrichment of Prevotella and depletion of Lactobacillus, and an overlap in microbes was implied between BV, cervical intraepithelial neoplasia, and cervical cancer.ConclusionsThese findings demonstrated an association between alterations in gut and genital microbiota and gynecological diseases. The most observed results were shared alterations across diseases rather than disease-specific alterations. Therefore, further investigation is required to identify specific biomarkers for diagnosis and treatment in the future.

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Antiprogestins in gynecological diseases.

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