Subclinical Hypothyroidism in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Background: The association between subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) has been reported in several studies, but it is not well-recognized. The aim of this study was to evaluate the prevalence of SCH in women with PCOS.Methods: An extensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library databases. All articles published before May 2018 was considered for eligibility. No language restrictions were implemented. The prevalence of SCH in PCOS was calculated by the meta-analysis to produce an odds ratio (OR) with 95% confidence interval (CI).Results: A total of 6 studies including 692 PCOS patients and 540 controls were eligible for the meta-analysis. The combined odds ratio (OR) of SCH risk for women with PCOS compared with controls was 2.87 (95% CI = 1.82–9.92; P < 0.000001). The OR increased to 3.59 when limiting thyroid stimulating hormone (TSH) cut-off to ≥4 mIU/L.Conclusions: Women with PCOS are more likely to develop SCH

The causal association between smoking initiation, alcohol and coffee consumption, and women’s reproductive health: A two-sample Mendelian randomization analysis

Objective: A number of epidemiological studies have demonstrated that smoking initiation and alcohol and coffee consumption were closely related to women’s reproductive health. However, there was still insufficient evidence supporting their direct causality effect.Methods: We utilized two-sample Mendelian randomization (TSMR) analysis with summary datasets from genome-wide association study (GWAS) to investigate the causal relationship between smoking initiation, alcohol and coffee consumption, and women’s reproductive health-related traits. Exposure genetic instruments were used as variants significantly related to traits. The inverse-variance weighted (IVW) method was used as the main analysis approach, and we also performed MR-PRESSO, MR-Egger, weighted median, and weighted mode to supplement the sensitivity test. Then, the horizontal pleiotropy was detected by using MRE intercept and MR-PRESSO methods, and the heterogeneity was assessed using Cochran’s Q statistics.Results: We found evidence that smoking women showed a significant inverse causal association with the sex hormone-binding globulin (SHBG) levels (corrected β = −0.033, p = 9.05E-06) and age at menopause (corrected β = −0.477, p = 6.60E-09) and a potential positive correlation with the total testosterone (TT) levels (corrected β = 0.033, p = 1.01E-02). In addition, there was suggestive evidence for the alcohol drinking effect on the elevated TT levels (corrected β = 0.117, p = 5.93E-03) and earlier age at menopause (corrected β = −0.502, p = 4.14E-02) among women, while coffee consumption might decrease the female SHBG levels (corrected β = −0.034, p = 1.33E-03).Conclusion: Our findings suggested that smoking in women significantly decreased their SHBG concentration, promoted earlier menopause, and possibly reduced the TT levels. Alcohol drinking had a potential effect on female higher TT levels and earlier menopause, while coffee consumption might lead to lower female SHBG levels

Elevated follicular cortisone level is a negative predictor of clinical pregnancy in women undergoing fresh embryo transfer

Background: Although numerous studies have investigated the potential correlation between follicular fluid (FF) steroid concentrations and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes, few have accounted for the effect of controlled ovarian hyperstimulation regimes on FF steroid concentrations. Objective: To comprehensively compare follicular steroid concentrations between women stimulated with gonadotropin-releasing hormone agonist (GnRHa) and antagonist (GnRHant) protocols and to explore the associations between FF steroid concentrations and IVF/ICSI outcomes. Methods: A total of 295 infertile women undergoing IVF/ICSI from January 2018 to May 2020 were enrolled. Eighty-four and 211 women received GnRHa and GnRHant protocols, respectively. Seventeen steroids in FF were quantified by liquid chromatography tandem mass spectrometry (LC–MS/MS), and the correlation of follicular steroids with clinical pregnancy was explored. Results: Follicular steroid concentrations were similar between the GnRHa and GnRHant groups. Follicular cortisone levels were adversely associated with clinical pregnancy in fresh embryo transfers. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.639 (95% confidence interval = 0.527–0.751, p = 0.025) for predicting non-pregnancy, with an optimal cutoff value of 15.81 ng/mL (sensitivity = 33.3%, specificity = 94.1%). Women with FF cortisone concentrations ≥15.81 ng/mL were fifty times less likely to achieve clinical pregnancy in fresh embryo transfers than those with FF cortisone levels below this threshold (adjusted OR = 0.019, 95% confidence interval = 0.002–0.207, p = 0.001) after adjusting for age, body mass index, baseline serum progesterone levels, serum levels of luteinizing hormone, estradiol and progesterone on human chorionic gonadotropin day, ovarian stimulation protocols, and the number of transferred embryos. Conclusions: There was no significant difference in intrafollicular steroid levels between GnRHa and GnRHant protocols, and intrafollicular cortisone level ≥15.81 ng/mL was found to be a strong negative predictor of clinical pregnancy in fresh embryo transfers with high specificity

COM33 suppresses carboplatin-induced epithelial-mesenchymal transition via inhibition of Twist1 in ovarian cancer

Despite favorable responses to platinum-based chemotherapy in ovarian cancer (OC), chemoresistance is still a major cause of treatment failure. Hence, we develop a novel synthetic agent, COM33, to relieve the chemoresistance caused by carboplatin. The anti-cancerous effects of the combination of COM33 and carboplatin on OC are evaluated by cell viability, wound healing, and transwell invasion assays. A mechanistic investigation is carried out by using RNA-Seq analysis and then verified by western blot analysis and immunofluorescence microscopy. The safety and efficacy in vivo are evaluated using SKOV3 tumor-bearing nude mice. Results show that the co-administration of COM33 enhances the inhibitory effects of carboplatin on cancer cell viability, migration, and invasion in vitro and tumor growth in vivo. Furthermore, COM33 suppresses the carboplatin-induced epithelial-mesenchymal transition (EMT) by inhibiting the ERK signaling pathway. Additionally, we show that Twist1, the effector of the ERK signaling pathway, participates in carboplatin-induced EMT and is also inhibited by COM33. Our data show that the combination of carboplatin with COM33 is beneficial for chemotherapy against OC, which may be a potential novel anti-tumor strategy

LncRNA SNHG5 adversely governs follicular growth in PCOS via miR-92a-3p/CDKN1C axis

Summary: Small nucleolar RNA host genes (SNHGs) have been implicated in various biological processes, yet their involvement in polycystic ovary syndrome (PCOS) remains elusive. Specifically, SNHG5, a long non-coding RNA implicated in several human cancers, shows elevated expression in granulosa cells (GCs) of PCOS women and induces PCOS-like features when overexpressed in mice. In vitro, SNHG5 inhibits GC proliferation and induces apoptosis and cell-cycle arrest at G0/G1 phase, with RNA-seq indicating its impact on DNA replication and repair pathways. Mechanistically, SNHG5 acts as a competing endogenous RNA by binding to miR-92a-3p, leading to increased expression of target gene CDKN1C, which further suppresses GC proliferation and promotes apoptosis. These findings elucidate the crucial role of SNHG5 in the pathogenesis of PCOS and suggest a potential therapeutic target for this condition. Additional investigations such as large-scale clinical studies and functional assays are warranted to validate and expand upon these findings

Association between the prevalence of hyperuricemia and reproductive hormones in polycystic ovary syndrome

Abstract Background The prevalecne of hyperuricemia in polycystic ovary syndrome (PCOS) is still uncertain. We aimed to investigate the prevalence of hyperuricemia in PCOS and to determine the influence of reproductive hormones on uric acid concentration. Methods This retrospective cross-sectional study was performed at a large reproductive medicine center. Between March 2007 and October 2016, a total of 1,183 women with PCOS and 10,772 women without PCOS were included. PCOS was diagnosed according to the Rotterdam criteria. Anthropometric parameters, blood pressure, uric acid, reproductive hormones, glucose and lipids were measured in all subjects. Results The serum uric acid (SUA) level was higher in women with PCOS than in women without PCOS. The prevalence of hyperuricemia in women with PCOS (25.48%) was significantly higher than that in women without PCOS (8.74%). Analysis stratified for age and body mass index (BMI) showed that both the SUA level and the prevalence of hyperuricemia were higher in women with PCOS of different age and BMI groups than in women without PCOS. After adjusting for age, BMI and estimated glomerular filtration rate (eGFR), logistic regression analysis revealed that the luteinizing/follicle-stimulating hormone (LH/FSH) ratio (odds ratio (OR) = 1.20, 95% CI = 1.01–1.43) and testosterone level (OR = 1.56, 95% CI = 1.27–1.90) were positively associated with the prevalence of hyperuricemia in females with PCOS. Conclusions The serum uric acid (SUA) level and the prevalence of hyperuricemia markedly increased in women with PCOS. The testosterone level was positively associated with the SUA level and the prevalence of hyperuricemia in females with PCOS

Alternative splicing of the androgen receptor in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and a leading cause of female subfertility. The mechanism underlying the pathophysiology of PCOS remains to be illustrated. Here, we identify two alternative splice variants (ASVs) of the androgen receptor (AR), insertion and deletion isoforms, in granulosa cells (GCs) in ∼62% of patients with PCOS. AR ASVs are strongly associated with remarkable hyperandrogenism and abnormalities in folliculogenesis, and are absent from all control subjects without PCOS. Alternative splicing dramatically alters genome-wide AR recruitment and androgen-induced expression of genes related to androgen metabolism and folliculogenesis in human GCs. These findings establish alternative splicing of AR in GCs as the major pathogenic mechanism for hyperandrogenism and abnormal folliculogenesis in PCOS