The Translational Role of miRNA in Polycystic Ovary Syndrome: From Bench to Bedside—A Systematic Literature Review

MicroRNAs (miRNAs) are small, non-coding RNAs that are essential for the regulation of post-transcriptional gene expression during tissue development and differentiation. They are involved in the regulation of manifold metabolic and hormonal processes and, within the female reproductive tract, in oocyte maturation and folliculogenesis. Altered miRNA levels have been observed in oncological and inflammatory diseases, diabetes or polycystic ovary syndrome (PCOS). Therefore, miRNAs are proving to be promising potential biomarkers. In women with PCOS, circulating miRNAs can be obtained from whole blood, serum, plasma, urine, and follicular fluid. Our systematic review summarizes data from 2010–2021 on miRNA expression in granulosa and theca cells; the relationship between miRNAs, hormonal changes, glucose and lipid metabolism in women with PCOS; and the potential role of altered miRNAs in fertility (oocyte quality) in PCOS. Furthermore, we discuss miRNAs as a potential therapeutic target in PCOS and as a diagnostic marker for PCOS

Urinary Metabolites Reveal Hyperinsulinemia and Insulin Resistance in Polycystic Ovarian Syndrome (PCOS)

The identification of insulin resistance and hyperinsulinemia in polycystic ovary syndrome (PCOS) is not a minor issue. The homeostasis model assessment of insulin resistance index (HOMA) is the most used index of IR (Insulin Resistance), validated in overweight and obese patients but not in normal-weight PCOS subjects, who can still present with increased insulin secretion by an oral glucose tolerance test [OGTT]. The evaluation of insulin secretion and resistance represents a still unresolved problem. The aim of this study is to identify a possible yet noninvasive method to properly evaluate the insulin metabolism in young non-diabetic subjects. Girls aged 14–22 years, afferent to the center of Gynecological Diseases in Childhood and Adolescence of Cagliari (Italy), were screened for PCOS. A total of 42 subjects comprised the study group. Hormonal assays, OGTT, transabdominal (TA) or transvaginal (TV) US, and urine collection for 1H-NMR analysis were assayed in the early follicular phase. A 1H-NMR coupled multivariate statistical analysis was performed. The OPLS model indicated that the NMR profile of urine had a good fit and prediction ability for the AUC OGTT with R2 = 0.813. Metabolomics can be a promising tool to the potential identification of biomarkers of an exaggerated insulin response to OGTT and can encourage substantial progress for a more accurate and early diagnosis in PCOS

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Failure of the homeostatic model assessment calculation score for detecting metabolic deterioration in young patients with polycystic ovary syndrome

OBJECTIVE: To verify whether the homeostatic model assessment (HOMA) test is a suitable method for the identification of metabolic deterioration in normal-weight patients affected by polycystic ovary syndrome (PCOS). DESIGN: Prospective clinical study. SETTING: Academic clinic and research environment in Cagliari, Italy. PATIENT(S): Forty-nine PCOS normal-weight adolescent subjects, and 50 eumenorrheic, normal-weight, nonhirsute controls matched for age and body mass index (BMI). INTERVENTION(S): History and physical examination, oral glucose tolerance test (OGTT) and blood sampling, ultrasound. MAIN OUTCOME MEASURE(S): The HOMA score and integrated secretory area under the curve of insulin values (I-AUC) during the OGTT were calculated. RESULT(S): Normal insulin sensitivity was defined as upper control 95th percentile by HOMA values <65.6, I-AUC at 180 minutes <16,921, and I-AUC at 120 minutes <11,817. When applying the calculated I-AUC cutoff, 27 PCOS patients were classified as normoinsulinemic and 22 as hyperinsulinemic, whereas using the calculated HOMA cutoff, only 9 PCOS patients could be classified as insulin resistant (IR). Thirteen of the 40 non-IR PCOS patients presented with hyperinsulinemia; fasting glucose and insulin levels and HOMA scores were not sufficient to identify these subjects. Thus, the HOMA test displayed a low sensitivity (41%) and specificity (100%) in the diagnosis of the metabolic disorder disclosed by I-AUC. Moreover, analysis of I-AUC after 120 and 180 minutes revealed how the shorter evaluation period did not suffice for identification of all hyperinsulinemic subjects, implying an unrecognized condition in 11 of 22 subjects. CONCLUSION(S): In young, normal-weight patients with PCOS, the prevalence of hyperinsulinemia is not detectable by HOMA studies. The prevalence of IR was 18% according to HOMA evaluation, whereas hyperinsulinemia was found in 44% of subjects examined by I-AUC. Normal-weight, young PCOS patients should undergo a 3-hour OGTT to detect early metabolic abnormalities

Very low dose of flutamide in the treatment of hyperandrogenism

Hyperandrogenism is a condition affecting 5–10% of adolescents. The aim of this study was to evaluate the efficacy of very low dose of flutamide in the treatment of hyperandrogenism in adolescence. One hundred and fifty-eight patients, presenting severe acne and/or hirsutism, received 62.5 mg/day of flutamide + ethinylestradiol + gestodene for 18 months. The patients were subjected to assessments of hepatic enzymes levels. Thirty subjects treated with drospirenone + ethinylestradiol represented the control group. After 18 months of treatment, it was obtained a decrease of hirsutism (−39.9%), an almost recovery of acne (98% of patients) with better results of those obtained in control group. Only one case of light hypertransaminasemia was recorded, regressed spontaneously. Very low dose of flutamide was successful and safe and in the treatment of hyperandrogenism in adolescence

Hirsutism and hyperandrogenism associated with hyperreactio luteinalis in a singleton pregnancy: a case report.

The incidence of hyperandrogenism during pregnancy is low, although the incidence of some of the ovarian diseases that can cause it is higher. Hyperreactio luteinalis is a rare benign condition that may mimic ovarian and trophoblastic malignancies. A 23-year-old woman at 20 weeks’ gestational age presenting with severe hirsutism and ovarian masses was treated conservatively and subsequently gave birth to a healthy female neonate. Final diagnosis was hyperreactio luteinalis. Conservative management with close monitoring of patients with hyperreactio luteinalis represents the best approach in such rare cases. Counseling should be provided to reassure the patient as to the transient effects of hyperandrogenism on the mother and the fetus

The quantitative insulin sensitivity check index is not able to detect early metabolic alterations in young patients with polycystic ovarian syndrome

Objective. To verify whether QUICKY is a suitable method for the identification of metabolic deterioration in normal weight patients affected by polycystic ovarian syndrome (PCOS). Design. Prospective clinical study. Patient(s). Seventy-nine PCOS normal weight adolescent subjects, 50 eumenorrheic, normal weight, non-hirsute controls matched for age and BMI. Method(s). Quantitative insulin sensitivity check index (QUICKY) and integrated secretory area under the curve of insulin values (I-AUC) during oral glucose tolerance test were calculated. Result(s). Seventy-nine PCOS and 50 controls were studied. Normal insulin sensitivity was defined as upper control 95th percentile by QUICKY values <0.31, I-AUC at 180 min < 16,645. When applying the calculated I-AUC cut-off, 41 PCOS were classified as normoinsulinemic and 38 as hyperinsulinemic, whereas using the calculated QUICKY cut-off, only 19 PCOS could be classified as insulin resistant (IR). Fifteen out of the 60 non-IR PCOS presented hyperinsulinemia; fasting glucose and insulin levels and QUICKY were not sufficient to identify these subjects. Thus, QUICKY displayed a low sensitivity (44%) and specificity (91%) in the diagnosis of the metabolic disorder disclosed by I-AUC. Conclusions. In young normal weight patients with PCOS the prevalence of early alterations of insulin metabolism are not detectable by QUICKY studies