Uterine leiomyoma is found in ~50–80% of women of a reproductive age and is the most common reason for hysterectomy. Recently, posttranscriptional gene silencing by microRNAs (miRs) has been reported as a mechanism for regulating gene expression stability in the pathogenesis of uterine leiomyomas. In this study, miR microarray analysis of leiomyomas and paired myometrial tissue revealed numerous aberrantly expressed miRs, including miR-150. In functional assays, transfection with miR-150 mimic resulted in decreased migration and fibrosis, implying an inhibition of leiomyoma growth. To identify the target genes of miR-150 in leiomyoma, gene set analysis and network analysis were performed. To overcome the limitations of in silico analysis, changes in expression levels of hallmark genes in leiomyoma after transfection with a miR-150 mimic were also evaluated using qRT-PCR. As a result, the Akt/p27^Kip1 pathway was presumed to be one of the target pathways of miR-150. After transfecting cultured leiomyoma cells with the miR-150 mimic, expression levels of its target gene Akt decreased, whereas those of p27^Kip1 increased significantly. Our results suggest that miR-150 affects the cell cycle regulation in uterine leiomyoma through the Akt/p27^Kip1 pathway.

Objectives: Formononetin is one of the phytoestrogens that functions like a selective estrogen receptor modulator (SERM). In this study, we evaluated the effects of formononetin on endometriosis progression in vitro and in vivo. Materials and methods: After pathological confirmation, 10 eutopic and ectopic endometria were collected from patients with endometriosis. Ten eutopic endometria samples were collected from patients who did not have endometriosis. To determine the cytotoxic dose and therapeutic dose of formononetin, the concentration of 70% of the cells that survived after formononetin administration was estimated using a Cell counting kit-8 (CCK 8) assay. Western blot analysis was used to determine the relative expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 in the eutopic endometria without endometriosis, eutopic endometria with endometriosis, and ectopic endometria with endometriosis as the formononetin concentration was increased. We confirmed the effect of formononetin on apoptosis and migration in endometriosis using fluorescence-activated cell sorting (FACS) and wound healing assays, respectively. A mouse model of endometriosis was prepared using a non-surgical method, as previously described. The mice were intraperitoneally administered formononetin for four weeks after dividing them into control, low-dose formononetin (40 mg/kg/day) treatment, and high-dose (80 mg/kg/day) formononetin treatment groups. All the mice were euthanized after formononetin treatment. Endometriotic lesions were retrieved and confirmed using hematoxylin and eosin (H&E) staining. Immunohistochemical (IHC) staining of p27 was performed. Results: We set the maximum concentration of formononetin administration to 80 μM through the CCK8 assay. Based on formononetin concentration, the expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 proteins were measured using Western blot analysis (N = 4 per group). The expression level of pERK, p27, and pSTAT3 in eutopic endometrium with endometriosis tended to decrease with increasing formononetin concentration, and a significant decrease was noted at 80 μM. The expression of p27 in ectopic endometrium with endometriosis was also significantly decreased at 80 μM of formononetin. FACS analysis revealed that formononetin did not significantly affect apoptosis. In the wound healing assay, formononetin treatment revealed a more significant decrease in the proliferation of the eutopic endometrium in patients with endometriosis than in the eutopic endometrium without endometriosis. Relative expression of sex hormone receptors decreased with increasing formononetin doses. Although no significant differences were observed in the ER, PR-A, ERβ/ERα, and PR-B/PR-A, significant down-regulation of PR-B expression was noted after formononetin treatment at 80 μM. In the in vivo study, endometriotic lesions in the formononetin-treated group significantly decreased compared to those in the control group. The relative expression of p27 using IHC was highest in the control group and lowest in the high-dose formononetin treatment group. Conclusions: Formononetin treatment was shown to inhibit the proliferation of eutopic and ectopic endometria in patients with endometriosis through the regulation of p27, pSTAT3, and PR-B. In an endometriosis mouse model, formononetin treatment significantly reduced the number of endometriotic lesions with decreased p27 expression. The results of this study suggest that formononetin may be used as a non-hormonal treatment option for endometriosis.

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX–TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 μM of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.

Background: Primary dysmenorrhea is a common gynecologic condition that frequently requires pharmacologic treatment. Pelubiprofen, a 2-arylpropionic acid-derived prodrug with relatively selective cyclooxygenase-2 inhibitory activity, has demonstrated analgesic efficacy in acute pain conditions. Methods: This multicenter, randomized, double-blind, placebo-controlled, crossover phase 3 trial randomized 120 women aged 19–44 years with primary dysmenorrhea to one of two treatment sequences over two menstrual cycles. Pelubiprofen at 45 mg or a matching placebo was administered at the onset of moderate or severe menstrual pain. The co-primary endpoints were time-weighted sums of the total pain relief (TOTPAR-8) and pain intensity difference (SPID-8) during the first 8 h after dosing. Results: Of 120 randomized women, 115 comprised the modified intention-to-treat population and 116 comprised the safety population. Pelubiprofen demonstrated significantly greater analgesic efficacy than placebo, with least-squares mean TOTPAR-8 values of 22.17 versus 15.50 and SPID-8 values of 10.00 versus 6.17 (both p < 0.0001). Significant between-treatment differences were also observed at 12 h (TOTPAR-12 and SPID-12). Treatment-emergent adverse events occurred in 9/113 (8.0%) pelubiprofen treatment periods and 10/112 (8.9%) placebo treatment periods; all events were mild to moderate, and the only serious adverse event occurred during a placebo treatment period and was judged to be unrelated to study treatment. Conclusions: Pelubiprofen at 45 mg provided superior short-term analgesic efficacy compared with placebo and was generally well tolerated in women with primary dysmenorrhea.

Background/Objectives: We aimed to characterize age-related clinicopathologic features, preoperative risk stratification, surgical management, and menstrual and reproductive outcomes of surgically managed ovarian and adnexal masses in children and adolescents. Methods: This retrospective study included 77 patients (aged 6–18 years) treated at a tertiary center between 2010 and 2020. Patients were grouped by age (6–12, 13–15, 16–18 years). Results: Abdominal pain (63.6%) was the most common presentation, and laparoscopic surgery was performed in 72.7% of cases. Overall, 84.4% of masses were non-malignant, with mature cystic teratoma being the most common (39.0%). Twelve patients (15.6%) had borderline or malignant tumors. Cyst diameter peaked in the 13–15 year group (p = 0.04), while torsion (9.1%) occurred exclusively in patients aged ≤15 years (p < 0.01). Preoperative O-RADS accurately stratified risk: all borderline or malignant tumors were O-RADS 4–5, whereas 84.6% of non-malignant lesions were O-RADS 2–3. Elevated CA-125 and AFP correlated well with epithelial and malignant germ cell tumors, respectively. Ovary-sparing surgery (OSS) was achieved in 11 of 12 patients with borderline or malignant tumors; after a median 4.2-year follow-up, 11 were alive without disease, and 10 had resumed menstruation. Conclusions: Most pediatric and adolescent adnexal masses are non-malignant. Age influences mass size and torsion risk. Preoperative O-RADS combined with tumor markers effectively aids risk stratification. Fertility preservation is feasible and safe for nearly all patients, supporting conservative surgical planning when intervention is necessary.