Search Results (56)

Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article

Sex steroid hormones and systemic iron metabolism are emerging as modulators of colorectal cancer (CRC) development and progression. However, information linking systemic factors to tumor characteristics and epithelial–mesenchymal transition (EMT) is limited, particularly in a sex-specific context. We measured serum levels of sex hormones [testosterone, estradiol, progesterone, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Carcinoembryonic antigen (CEA)] and iron-related biomarkers (iron, transferrin, ferritin, % transferrin saturation, ceruloplasmin, and the ceruloplasmin/transferrin ratio) in 82 CRC patients and 31 healthy controls. EMT-related proteins [mediator of ErbB2-driven cell motility 1 (MEMO1), E-cadherin, fibronectin, vimentin, and vinculin] were quantified by Western blotting in tumor and adjacent normal mucosa. Non-parametric tests and Spearman correlations were applied, stratified by sex and corrected for age and anemia where appropriate. Progesterone levels were significantly lower in male CRC patients (median 0.17 ng/mL vs. 0.20 ng/mL, p = 0.04) and higher in female patients (0.17 ng/mL vs. 0.10 ng/mL, p = 0.0077) compared with controls. The iron-related biomarkers indicated a pattern of iron deficiency, including in non-anemic patients, with reduced % transferrin saturation (p < 0.01) and an elevated ceruloplasmin/transferrin ratio (p = 0.02). Correlations were found between iron status, tumor stage, and hormonal levels. Progesterone correlated with EMT protein expression in healthy mucosa (e.g., fibronectin in females: ρ = 0.567, p = 0.014; vimentin in males: ρ = −0.446, p = 0.007), but not in tumor tissue. In the healthy mucosa of male patients, ceruloplasmin/transferrin correlated with MEMO1 (ρ = 0.419, p = 0.04), vinculin (ρ = 0.299, p = 0.041), and vimentin (ρ = 0.394, p = 0.07); transferrin levels inversely correlated with MEMO1 expression (ρ = −0.392, p = 0.032), and vimentin showed a positive correlation with serum iron (ρ = 0.350, p = 0.043). Furthermore, fibronectin expression inversely correlated with iron in the sole tumor tissue of female patients (ρ = −0.366, p = 0.040). These findings support the role of sex hormones and iron metabolism in CRC biology, suggesting that EMT might be accompanied by altered iron uptake and redox remodeling, which can enhance cellular motility and the metastatic potential. Full article

Background and Objectives: This study aimed to evaluate the impact of myoinositol (MYO) and α-lipoic acid (ALA) supplementation on hormonal and metabolic markers in women diagnosed with polycystic ovary syndrome (PCOS). Materials and Methods: A retrospective case–control study was conducted with 58 women aged between 18–40 years who met the Rotterdam criteria for PCOS. The case group (n = 29) received MYO (2000 mg/day) and ALA (400 mg/day) supplements, while the control group (n = 29) did not receive any treatment. Data on the subjects’ anthropometric measures, glycemic indices, sex hormones, and lipid profiles were collected. Results: The results demonstrated that, following three months of MYO + ALA supplementation, the case group exhibited steady body weight (p = 0.484) and BMI (p = 0.405), whereas the control group demonstrated a significant increase in both (p = 0.029; p = 0.026, respectively). A stratified analysis based on BMI, waist circumference, and waist-to-height ratio revealed that HbA1c (%) was significantly lower in the “normal” subgroup compared to the “risky” subgroup within the case group (p < 0.05). Although the mean HbA1c, insulin, and HOMA-IR values were comparable between the two groups, the LH/FSH ratio significantly increased in the control group (p = 0.010). No significant differences were observed in the lipid profiles between the two groups; however, LDL levels decreased significantly in the case group (p = 0.024). Across all classifications, the “normal” subgroup consistently exhibited lower HbA1c and TG/HDL ratios than the “risky” subgroup. Conclusions: Adding MYO + ALA supplementation to standard PCOS treatment may offer metabolic benefits, particularly in maintaining glycemic control, body weight, and BMI. Supplementation also reduces LDL. Full article

Background/Objectives: Vitamin D deficiency is common in women with polycystic ovary syndrome (PCOS) and may be associated with metabolic and endocrine disorders as well as ovulatory dysfunction. Vitamin D supplementation may improve ovarian dysfunction and follicular development by effecting gene expression. The aim of the present study was to investigate the effects of vitamin D supplementation in women with PCOS through a prospective, randomized, two-phase, parallel design, placebo-controlled trial. Methods: We assessed the impact on ovarian morphology, cycle length, and ovulatory dysfunction. Transvaginal ultrasonography (TVUS) examinations and clinical laboratory assessments were conducted at the baseline, and again after 12 and 24 weeks. The participants received vitamin D (30,000 IU/week) or a placebo (without concurrent metformin use) for 12 weeks, supplemented with calcium, followed by an additional 12 weeks of vitamin D treatment. Results: The treatment resulted in improvements in ovarian morphology and regularity of menstrual cycles in more than half of the patients. Additionally, vitamin D3 was associated with a significant increase in the ovulation rate. A statistically significant reduction in mean testosterone levels was observed in the subgroup of patients with an LH/FSH ratio greater than 2. Conclusions: Our results suggest that vitamin D3 treatment could function as either a standalone or an adjunctive therapy in the management of PCOS. Full article

Background: As a complicated endocrine condition, polycystic ovarian syndrome affects around 20% of women who are of reproductive age. It is linked to an increased risk of endometrial cancer, cardiovascular diseases, mental illnesses, non-alcoholic fatty liver disease, metabolic syndrome, and Type 2 diabetes. Despite numerous genetic studies identifying several susceptibility loci, these only account for approximately 10% of the hereditary factors contributing to PCOS, leaving its etiology largely unknown. While genome-wide association studies (GWAS) have been conducted on various populations to identify SNPs linked to PCOS risk, no such study has been reported in Tabuk. Thus, this study aims to investigate the association of a glutathione S-transferase M1 (GSTM1) deletion, VEGF gene (I/D) insertion/deletion, and VEGF-2578 gene polymorphism with polycystic ovarian syndrome. Methodology: In this research study (case-control), we utilized the ARMS-PCR to determine and analyze the polymorphic variants of VEGF-2578 C/A (rs699947). We employed multiplex PCR for the GSTM1 deletion and MS-PCR (mutation specific PCR) for the vascular endothelial growth factor gene insertion/deletion. Results: The findings indicated statistically significant differences in various biochemical and endocrine serum biomarkers, including lipid profiles (cholesterol, HDL, and LDL), Type 2 diabetes markers (HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), free insulin fasting glucose), and hormone levels (testosterone, LH, progesterone and FSH) in PCOS patients. Specifically, regarding the GSTT1 genotype, individuals with the GSTT1-null genotype had an odds ratio (OR) of 4.16 and a relative risk (RR) of 2.14 compared to those with the GSTT1 genotype, with statistically significant differences (p = 0.0001). However, for the GSTM1 genotype, there was a statistically significant difference (p = 0.0002) in the OR and RR for the GSTM1-null genotype, which were 2.66 and 1.64, respectively. Protective effects were observed for individuals with either GSTT1 (+) GSTM1 (−) or GSTT1 (−) GSTM1 (+) genotypes, as well as for those with both null genotypes, yielding an OR of 0.41 and p < 0.003. The VEGF rs699947 C>A gene variation showed a statistically significant association between PCOS patients and controls (p < 0.020), with the A allele frequency higher among PCOS patients (0.42 vs. 0.30). Similarly, the VEGF rs4646994 I>D gene variation exhibited a statistically significant difference (p < 0.0034), with the D allele being more frequent in PCOS patients (0.52 vs. 0.35). The VEGF-A allele was strongly linked to PCOS susceptibility in the allelic model, exhibiting an OR of 1.62, RR of 1.27, and p < 0.007, while in the allelic comparison, the OR was 1.71, the RR was 1.32, and p < 0.004. Conclusions: This study concluded that null genotypes at rs4025935 and rs71748309, an insertion deletion at rs4646994, and the A allele of rs699947 were significantly associated with PCOS predisposition in our population and these could serve as potential loci for PCOS predisposition. To the best of our knowledge, it is the first study to highlight the association between these genetic variations and the predisposition of PCOS in our populations. Large-scale case-control studies in the future are required to confirm these results. Full article

Sexual dysfunction, influenced by hormonal imbalances, psychological factors, and chronic diseases, affects a significant portion of the population. Probiotics, known for their beneficial effects on gut microbiota, have emerged as potential therapeutic agents for improving sexual health. This systematic review evaluates the impact of probiotics on sexual function, hormonal regulation, and reproductive outcomes. A comprehensive search identified 3308 studies, with 12 meeting the inclusion criteria—comprising 10 randomized controlled trials (RCTs) and 2 in vivo and in vitro studies. Probiotic interventions were shown to significantly improve sexual function, particularly in women undergoing antidepressant therapy (p < 0.05). Significant improvements in Female Sexual Function Index (FSFI) scores were observed, with combined treatments such as Lactofem with Letrozole and Lactofem with selective serotonin reuptake inhibitors (SSRIs) demonstrating a 10% biochemical and clinical pregnancy rate compared to 0% in the control group (p = 0.05). Probiotic use was also associated with a 66% reduction in menopausal symptoms, increased sperm motility (36.08%), viability (46.79%), and morphology (36.47%). Probiotics also contributed to favorable hormonal changes, including a reduced luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio (from 3.0 to 2.5, p < 0.05) and increased testosterone levels. Regarding reproductive outcomes, probiotic use was associated with higher pregnancy rates in women undergoing fertility treatments and improvements in sperm motility, viability, and morphology in men. This review highlights the promising role of probiotics in addressing sexual dysfunction and reproductive health, suggesting their potential as adjunctive treatments for conditions such as depression and infertility. Further research is needed to better understand the underlying mechanisms of these beneficial effects. Full article

Background/Objectives: Hirsutism is excessive male-patterned hair in postpubertal women with multifactorial etiology and is an indicator of hyperandrogenism associated with polycystic ovary syndrome (PCOS). Indeed, it can be caused by the enhanced peripheral conversion of androgen precursors to testosterone, as in idiopathic hirsutism (IH). Moreover, hirsutism can be caused by hirsutism-related hyperandrogenic syndromes like non-classic congenital adrenal hyperplasia (NCAH) and idiopathic hyperandrogenism (IHA). Methods: In this study, we characterized a large cohort of Portuguese women referred for hirsutism and estimated the prevalence of PCOS, NCAH, IHA, and IH. The levels of androgens and gonadotropins and body mass index (BMI) were measured and compared with controls. The correlation between each variable was calculated. Results: In the cohort, we found a prevalence of PCOS of 56.2%, IH of 20.2%, IHA of 17.3%, and NCAH of 6.2%. Subjects with PCOS were the only ones showing a significant difference in BMI compared to the controls and had the lowest levels of sex hormone-binding globulin (SHBG). Those with NCAH were younger and more hirsute with higher levels of testosterone, among other androgens. Those with IH had lower luteinizing hormone (LH) and LH/follicle-stimulating hormone (FSH) ratios than those with PCOS. Those with IH had lower SHBG levels compared to the controls and a higher free androgen index (FAI). Those with IHA had higher androgens compared to those with IH, in particular, adrenal-derived androgens. Conclusions: The pathogenesis of hirsutism is complex, and the contributions of the pituitary gland, ovaries, adrenals, adipose tissue, and liver have to be ascertained to understand the clinical manifestations and delineate appropriate treatments. This study sheds new light on the fine hormonal regulation of these diseases. Full article

Background/Objectives: The hormonal aspect of undescended testes (UDTs) in prepubertal boys, i.e., after mini-puberty, is poorly understood. The aim of this study was to evaluate the hormonal function of UDTs before orchidopexy in prepubertal boys and its correlation with testicular parameters. Methods: The study included 90 prepubertal boys (0.9–8.8 years) with UDTs and 57 age-matched boys with testes in the scrotum (control). The testicular volume (TV), testicular atrophy index (TAI), and testicular growth potential (TGP) of the UDTs were assessed before orchidopexy and 18–24 months after. The analysis included FSH, LH, T, DHT, E2, Inh B, INSL3, and AMH levels. Results: The UDT group demonstrated a significantly higher FSH level and lower Inh B/FSH ratio than controls. Boys with UDTs aged under six years exhibited significantly higher FSH and LH levels and lower Inh B/FSH and T/LH ratios. The TV level of descended and undescended testes, both before and after surgery, was significantly positively related to T and DHT levels, but negatively with Inh B, INSL3 levels, Inh B/AMH, and Inh B/FSH. Conclusions: Hormonal evaluation of the hypothalamus–pituitary–testicular axis and Sertoli and Leydig cell function in prepubertal boys (after mini-puberty) may predict the further development and function of UDTs and may serve as a diagnostic tool in testicular descent disorder. Full article

This study evaluated the effects of kaempferol (KAE), and vitamin E (VE) on the performance, reproductive hormones, and the composition of the cecum and uterus microbiota in late-laying hens. A total of 192 49-week-old Jinghong No. 1 laying hens were randomly divided into four groups, with six replicates in each group and eight laying hens in each replicate, pre-reared for one week and formally tested for ten weeks. The CON group was fed basal diets, the VE group, the KAE group, and the KAE + VE group were fed a basal diet to which was added 0.2 g/kg VE, 0.4 g/kg KAE, and 0.2 g/kg VE + 0.4 g/kg KAE, respectively. The results are as follows. Compared to the CON group, the VE group, the KAE group, and the KAE + VE group significantly increased the egg production rate, average daily egg weight and significantly decreased the feed-to-egg ratio. The VE + KAE group significantly improved the Haugh unit. The VE group, the KAE group, and the KAE + VE group considerably enhanced the eggshell strength, eggshell relative weight, eggshell thickness, yolk color, and relative yolk weight. The serum E₂ and LH levels of the KAE group and the KAE + VE group and the serum FSH levels of the KAE + VE group were significantly higher. In the ovary, the KAE group and the KAE + VE group’s ESR1 gene expression levels were significantly higher, and the KAE + VE group’s FSHR gene expression levels were markedly higher. In the uterus, the KAE group and the KAE + VE group’s ESR1 gene expression levels were dramatically higher, and the KAE + VE group’s ESR2 and FSHR gene expression levels were significantly higher. 16S rRNA gene sequencing revealed a significant aggregation of cecum and uterus colonies in the Beta diversity PCoA. In the cecum, Firmicutes, Bacteroidetes, and WPS-2 were the dominant phylums. In the uterus, the Firmicutes, Proteobacteria, and Bacteroidetes were the dominant phylums. The KAE + VE group’s F/B was significantly higher at the phylum level than in the CON group and the VE group. In summary, the addition of VE and KAE to the diet can improve the production performance of late-laying hens, increase the content of reproductive hormones, and stabilize the cecal and uterus microbiota, which may be related to the hormone and microbiota linkage of the gut–uterus axis. Full article

Background: Prolactin levels have been shown to influence metabolic outcomes, including insulin resistance. Metformin is known to be beneficial in polycystic ovary syndrome (PCOS) patients. PCOS women might react differently to metformin treatment depending on their baseline prolactin levels. Methods: In this retrospective study, the homeostasis model assessment for insulin resistance (HOMA-IR), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, and total testosterone and sex hormone-binding globulin (SHBG) were measured in 75 obese/overweight women with PCOS and insulin resistance before initiation of metformin treatment and after 6–8 months. Results: At baseline, HOMA-IR was inversely correlated to SHBG (r = −0.408; p < 0.001) and prolactin (r = −0.402; p < 0.001). After 6–8 months of metformin treatment, the LH:FSH ratio and the HOMA-IR declined significantly (p < 0.05). A significant positive correlation could be shown between basal prolactin and the difference in the HOMA-IR (r = 0.233; p = 0.044). Women with lower baseline prolactin (≤14.9 ng/mL) revealed a sharper decline in HOMA-IR (−0.8, IQR −1.0; −0.5 vs. −0.6, IQR −0.8; −0.3; p = 0.049) as well as an increase in prolactin at follow-up (1.6 ng/mL, IQR −0.2;3.8 vs. −1.3, IQR −4.6;3.2; p = 0.003) compared to patients with a baseline prolactin > 14.9 ng/mL. Conclusions: In overweight/obese, insulin-resistant PCOS women, lower baseline prolactin levels are associated with higher baseline HOMA-IR levels as well as with a better response to metformin treatment. More data are necessary to prove these observations in larger populations. Full article

Background/Objective: Infertility affects an estimated 40–50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment. Methods: A single-center retrospective cohort study was conducted. Data spanning from 2012 to 2019 were compiled from patients with PCOS who visited the Gynecologic Endocrinology Unit and the Infertility Unit at the Department of Obstetrics and Gynecology, University of Debrecen. Patients diagnosed with PCOS who had had at least one successful delivery beyond the 23rd gestational week at the department were eligible for inclusion in the study. Results: Fifteen percent of the 206 pregnancies leading to successful deliveries of 232 newborns in our cohort conceived with IVF. A one year increase in the maternal age increased the odds of being in the IVF group by 22% (OR: 1.222, 95% confidence interval, CI: 1.11–1.35, p < 0.001). Baseline DHEAS and androstenedione levels were significantly lower in the IVF group as compared to the non-IVF group: 1 μmol/L increase in the DHEAS level decreased the odds of being in the IVF group by 18% (OR: 0.82, 95% CI: 0.66–1.01, p = 0.06), and 1 μg/L increase in the serum androstenedione concentration decreased the same odds by 42% (OR: 0.58, 95% CI: 0.33–1.02, p = 0.056). DHEAS levels <6.5 μmol/L had an OR 3.86 (95% CI 1.10–13.50, p = 0.04) and LH/FSH ratio <1.3 had an OR 3.58 (95% CI 1.18–10.81, p = 0.03) for being in the IVF group. The birth weight (3069 ± 683 g vs. 3362 ± 638 g, p = 0.02) and the gestational age (37.23 ± 2.55 vs. 38.54 ± 2.28 weeks, p = 0.004) were significantly lower in the IVF group, but in the singleton subgroups, no significant differences could be found. Birth weight percentiles showed no significant difference in either subgroup. In the IVF group, both preterm delivery (29% vs. 8.3%, OR 4.53, 95% CI 1.75–11.70, p = 0.002; singleton subgroup: 17.4% vs. 6.3%, OR 3.12, 95% CI 0.89–10.92, p = 0.07) and cesarean section (71% vs. 43.2%, OR 3.22, 95% CI 1.40–7.40, p = 0.006; singleton subgroup: 65.2% vs. 42.4%, OR 2.55, 95% CI 1.02–6.35, p = 0.04) were more frequent than in the non-IVF group. Gestational diabetes and preeclampsia were not significantly different in the IVF and non-IVF groups. Conclusions: In PCOS patients with successful pregnancies, those who conceive with IVF seem to be different in their baseline hormone levels and symptoms from the non-IVF group. Adverse obstetric outcomes are more common in the IVF group, and some of these differences persist when adjusting for singleton pregnancies and maternal age, too. Full article

Highly purified human menopausal gonadotropin (HP-hMG [Menopur^®, Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur^® and two of Menogon^® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid^® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel^® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid^®) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20–30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9–1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18–47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20–30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG. Full article

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5–18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226 Full article

Juvenile angiofibroma (JA) is a rare, sex-specific, and highly vascularized nasal tumor that almost exclusively affects male adolescents, but its etiology has been controversial. The G protein-coupled hormone receptor LHCGR [luteinizing hormone (LH)/choriogonadotropin (hCG) receptor] represents a promising new candidate for elucidating the underlying mechanisms of sex specificity, pubertal manifestation, and JA progression. We used highly sensitive RNAscope technology, together with immunohistochemistry, to investigate the cellular expression, localization, and distribution of LHCGR in tissue samples from JA patients. Our results provide evidence for LHCGR expression in subsets of cells throughout JA tissue sections, with the majority of LHCGR⁺ cells located in close vicinity to blood vessels, rendering them susceptible to endocrine LH/hCG signaling, but LHCGR⁺ cells were also detected in fibrocollagenous stroma. A majority of LHCGR⁺ cells located near the vascular lumen co-expressed the neural crest stem cell marker CD271. These results are intriguing as both LH and hCG are produced in a time- and sex-dependent manner, and are known to be capable of inducing cell proliferation and angiogenesis. Our results give rise to a new model that suggests endocrine mechanisms involving LHCGR and its ligands, together with autocrine and paracrine signaling, in JA vascularization and cell proliferation. Full article

Polycystic ovary syndrome (PCOS) is an endocrine disease commonly associated with metabolic disorders in females. Leonurine hydrochloride (Leo) plays an important role in regulating immunity, tumours, uterine smooth muscle, and ovarian function. However, the effect of Leo on PCOS has not been reported. Here, we used dehydroepiandrosterone to establish a mouse model of PCOS, and some mice were then treated with Leo by gavage. We found that Leo could improve the irregular oestros cycle of PCOS mice, reverse the significantly greater serum testosterone (T) and luteinising hormone (LH) levels, significantly reduce the follicle-stimulating hormone (FSH) level, and significantly increase the LH/FSH ratio of PCOS mice. Leo could also change the phenomenon of ovaries in PCOS mice presented with cystic follicular multiplication and a lacking corpus luteum. Transcriptome analysis identified 177 differentially expressed genes related to follicular development between the model and Leo groups. Notably, the cAMP signalling pathway, neuroactive ligand-receptor interactions, the calcium signalling pathway, the ovarian steroidogenesis pathway, and the Lhcgr, Star, Cyp11a, Hsd17b7, Camk2b, Calml4, and Phkg1 genes may be most related to improvements in hormone levels and the numbers of ovarian cystic follicles and corpora lutea in PCOS mice treated by Leo, which provides a reference for further study of the mechanism of Leo. Full article