Comparison of clinical outcomes and perinatal outcomes between natural cycle and hormone replacement therapy of frozen-thawed embryo transfer in patients with regular menstruation: a propensity score-matched analysis.

Purpose: To investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT). Methods: This study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method. Results: The NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model. Conclusion: This study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.

CRH upregulates supervillin through ERK and AKT pathways to promote bladder cancer cell migration.

Corticotropin-releasing hormone (CRH) has been well documented playing a role in the regulation of cellular processes, immune responses, and inflammatory processes that can influence the occurrence and development of tumors. Supervillin (SVIL) is a membrane-associated and actin-binding protein, which is actively involved in the proliferation, spread, and migration of cancer cells. This work investigated CRH's influence on bladder cancer cells' migration and relevant mechanisms. By using human bladder cancer cells T24 and RT4 in wound healing experiments and transwell assay, we found that the migration ability of the T24 cells was significantly increased after CRH treatment. In vivo experiments showed that CRH significantly promoted the metastases of T24 cells in cell line-derived xenograft (CDX) mouse model. Interestingly, downregulation of SVIL by SVIL-specifc small hairpin RNAs significantly reduced the promoting effect of CRH on bladder cancer cell migration. Furthermore, CRH significantly increased SVIL messenger RNA and protein expression in T24 cells, accompanied with AKT and ERK phosphorylation in T24 cells. Pretreatment with AKT inhibitor (MK2206) blocked the CRH-induced SVIL expression and ERK phosphorylation. Also, inhibition of ERK signaling pathway by U0126 significantly reduced the CRH-induced SVIL expression and AKT phosphorylation. It suggested that cross-talking between AKT and ERK pathways was involved in the effect of CRH on SVIL. Taken together, we demonstrated that CRH induced migration of bladder cancer cells, in which AKT and ERK pathways -SVIL played a key role.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism.

BACKGROUND: The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear. AIM: To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation. METHODS: A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH. RESULTS: MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones. CONCLUSION: MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Different Effects of Obesity and Fasting on the Expression of Type 3 Deiodinase and Thyroid Hormone Receptors in the Liver and Visceral Adipose Tissue of C57BL/6 Male Mice.

Introduction: Energy status can alter thyroid hormone signalling in different tissues. Little is known about the effect of fasting on the local thyroid hormone metabolism under high-fat diet (HFD)-induced obesity. We aimed to investigate the fasting effect on deiodinase type 3 (DIO3) and thyroid hormone receptors (TRs) expression in liver and visceral adipose tissue (VAT) of HFD-induced obese mice. Methods: The 30 male C57BL/6 mice were divided into three groups (n = 10/group): control (CON) group, obese (OB) group, and fasted obese (OBF) group. Materials: In a 14-week study, the expression levels of DIO3 and TRs in the liver and VAT of mice were measured by real-time polymerase chain reaction. Gene expression results were shown as fold changes defined by 2-ΔΔct. Comparison between groups was performed by using one-way-ANOVA or Kruskal-Wallis ANOVA test. Results: In the liver, there was a significantly lower expression of DIO3 and higher expression of TRs in obese fasted mice compared to obese mice. Compared to the lean mice, OBF mice had significantly lower expression of DIO3 and higher expression of TRß. In the VAT, mRNA expression of DIO3 was significantly increased in OBF and OB groups compared to the CON group. There were no significant differences in the mRNA expression of TRs between groups. Conclusion: Our findings suggest that fasting may be more effective in improving thyroid hormone metabolism in the liver rather than the VAT of obese mice.

Predischarge Peak Atrial Longitudinal Strain and Plasma N-terminal Pro-hormone Brain Natriuretic Peptide as a Predictor of Short-term Rehospitalization and Cardiovascular Mortality in Patients with Acute Heart Failure.

Context: The postacute heart failure (AHF) rehospitalization rate is attributed to persistent hemodynamic congestion despite clinical improvement. Peak atrial longitudinal strain (PALS), utilizing speckle tracking echocardiography technology, shows potential in post-AHF prognosis. Meanwhile, N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) remains a known biomarker of intracardiac congestion. Aims: This study aimed to determine the relationship between predischarge PALS and NT-proBNP as predictors of major adverse cardiac event (MACE) in patients after AHF hospitalization. Settings and Design: This study is a prospective cohort study, conducted in Prof. Dr. I G.N.G Ngoerah Hospital, Bali, Indonesia. Subjects and Methods: The study included hospitalized AHF patients, collecting demographic data, comorbidities, therapies, and echocardiographic measures before discharge. Predischarge PALS and NT-proBNP were taken within 24 h before discharge. The main outcome was MACE, defined as rehospitalization and cardiovascular mortality within 90 days. Statistical Analysis Used: Comparative statistical analyses was done using independent t-test for continuous variables (Mann-Whitney U test for variables with abnormal distribution) and Chi-squared tests. Receiver operating characteristic (ROC) used in determining optimal threshold values of predischarge PALS and NT-proBNP as a predictor of MACE. Kaplan-Meier curves were employed to gauge event-free survival differences between these cohorts. Then, independent Cox regression was used to identify the predictors of MACE. Results: The study enrolled 67 patients with varying ejection fraction (EF) (16 - heart failure with preserved ejection fraction, 10 - heart failure with mildly reduced ejection fraction, and 41 - heart failure with reduced ejection fraction; mean age: 56.88 ± 14.57 years). Over the 90-day follow-up, 21 patients (31.3%) encountered MACE. Both PALS (area under the curve [AUC] 0.816) and NT-proBNP (AUC 0.856) before discharge served as predictors of MACE. There was no significant AUC difference between ROC curves (area difference: 0.039, P = 0.553). The regression model highlighted that PALS and NT-proBNP level before discharge acted as independent predictors of MACE, irrespective of EF, average E/e', or estimated predischarge pulmonary capillary wedge pressure. Conclusions: Predischarge PALS is comparable to NT-proBNP levels as independent predictors of short-term MACE after AHF hospitalization.

The risk of ovarian cancer in hormone replacement therapy users: a systematic review and meta-analysis.

Background: With the increasing use of hormone replacement therapy (HRT), there is a need to understand its impact on the occurrence of female malignant tumors. This systematic review and meta-analysis aimed to assess the risk of ovarian cancer associated with HRT and its related risk factors. Methods: PUBMED, OVID, Embase, Cochrane, and Web of Science were searched from 1980 to April 2022 to identify studies on the risk of ovarian cancer and hormone replacement therapy. The random-effects model was used to estimate the pooled risk of HRT in ovarian cancer, both in cohort studies and case-control studies. Additionally, the analysis examined the outcomes associated with different types of estrogen plus progesterone regimens. Meta-regression and sensitive analysis were performed to evaluate the heterogeneity. Results: 21 cohort studies (involving 15,313 cases and 4,564,785 participants) and 30 case-control studies (including 18,738 cases and 57,747 controls) were analyzed. The pooled risks of ovarian cancer for HRT users were 1.20 (95% confidence interval [CI] 1.01-1.44) from cohort studies and 1.13 (95%CI 1.04-1.22) from case-control studies. However, after restricting the study period to recent decades, the significant results indicating a higher risk disappeared in cohort studies conducted after 2010 and in case-control studies conducted after 2006. Furthermore, the continuous use of estrogen-progesterone replacement therapy (EPRT) was associated with a risk comparable to that of sequential use. Subgroup analysis showed that both estrogen replacement treatment (ERT) and EPRT had minor risks; The risk further increased with prolonged exposure time, particularly for durations exceeding 10 years. Additionally, serous ovarian cancer appeared to be more susceptible than other pathological types. Conclusion: The risk of ovarian cancer associated with HRT has been decreasing over time. However, ERT may increase this risk, particularly when used for an extended period. It is recommended that long-time users consider continuous EPRT as a safer alternative. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier CRD42022321279.

Formation mechanism and regulation analysis of trumpet leaf in Ginkgo biloba L.

Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes. Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses. Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba. Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.

Sex steroid hormones: an overlooked yet fundamental factor in oral homeostasis in humans.

Sex steroid hormones (SSH) are extremely versatile molecules with a myriad of physiological functions. Next to their well-known role in sexual development and reproduction, SSH play active roles in practically every tissue in the human body, including the oral cavity. It has long been demonstrated that periodontal tissues express SSH receptors and therefore are responsive to the presence of SSH. Interestingly, SSH not only interact with the periodontal tissues but also with other tissues in the oral cavity such as dental enamel, pulp, cementum, oral mucosa, and salivary glands. Questions concerning the possible physiological functions of these receptors and their role in maintenance of oral health, remain unanswered. The purpose of this scoping review was to gather and summarize all the available evidence on the role of SSH in physiological processes in the oral cavity in humans. Two comprehensive literature searches were performed. References were screened and selected based on title, abstract and full text according to our inclusion criteria. Both searches yielded 18,992 results of which 73 were included. Results were divided into four categories: (1) Periodontium; (2) Dental structure; (3) Mucosa; and (4) Salivary glands. The interaction of these tissues with progestagens, androgens and estrogens are summarized. Sex steroid hormones are an overlooked yet fundamental factor in oral homeostasis. They play important roles in the development and function of the periodontium, dental structure, mucosa and salivary glands. Dentists and healthcare providers should consider these hormonal factors when assessing and treating oral health conditions.

The Relationship Between Anemia and Parathyroid Hormone Levels in Patients With Kidney Failure Undergoing Hemodialysis Treatment in Georgia.

INTRODUCTION: Chronic kidney disease (CKD) and its associated complications, such as anemia and secondary hyperparathyroidism (SHPT), pose significant challenges to global healthcare systems. This study explores the demographic and clinical characteristics of 284 kidney failure (KF) patients undergoing hemodialysis, in an effort to shed light on the possible association between anemia and SHPT. A proven connection between the two could theoretically influence the management plans for CKD patients, with the hopes of achieving lower morbidity and/or mortality in this patient group. METHODS: A retrospective, cross-sectional, real-world data analytical study was conducted at a hemodialysis center in Tbilisi, Georgia, encompassing a sample size of n = 284 patients on maintenance hemodialysis. The data analyzed was extracted from patients' medical records. RESULTS: According to our results, the prevalence of anemia was strikingly high at 82.04%, underlining its substantial burden within this patient population. Our analysis revealed a notable systemic association between anemia and SHPT, particularly when considering hemodialysis vintage. However, our final analysis model revealed no statistically significant association between anemia and intact parathyroid hormone (iPTH) levels.  Conclusion: Our study revealed a significant systemic relationship between anemia and SHPT when hemodialysis duration was considered, despite initial analyses showing no direct association. Future research should focus on longitudinal and multi-center studies to better understand this relationship, aiming to enhance the care and management of CKD patients on hemodialysis.

Bone mineral density: comparison between women under hormone replacement therapy with Turner syndrome or idiopathic premature ovarian insufficiency.

CONTEXT: Turner syndrome (TS) is characterized by short stature and premature ovarian insufficiency (POI). The main long-term complication of POI is osteoporosis, which can be prevented by hormone replacement therapy (HRT). OBJECTIVE: The objective of our study was to compare initial bone mineral density (BMD) and progression between TS and idiopathic POI patients under HRT. METHODS: A single-center retrospective study was conducted between 1998 and 2018. All women had undergone at least two bone densitometry assessments at least 2 years apart. RESULTS: 68 TS patients and 67 idiopathic POI patients were included. Mean age at initial assessment was 27 years (IQR, 21-35.5 years) in TS patients and 31.5 years (IQR, 23-37 years) in idiopathic POI patients (p=0.1). Lumbar and femoral neck BMD were lower in the TS group than in the idiopathic POI group (respectively 0.89g/cm² versus 0.95g/cm², p=0.03; 0.70g/cm² versus 0.77g/cm², p<0.0001). Mosaic karyotype was associated with better BMD in TS patients while history of growth hormone treatment had no impact on BMD. Over time, a significant gain in vertebral BMD was observed in TS patients versus a loss of BMD in idiopathic POI patients (p=0.0009). CONCLUSION: TS patients had a lower BMD at baseline than idiopathic POI patients, at both spinal and femoral levels. Over time, on HRT, a significant gain in vertebral BMD was observed in patients with TS, compared with a loss of BMD in patients with idiopathic POI. We hypothesized that earlier initiation and longer duration of HRT played an important role in this finding. Long-term prospective follow-up to assess the incidence of fractures in TS would be useful.

Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer.

Background: The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT. Methods: The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (µg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age. Results: In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m2 (n=46), ≥23 and <25 kg/m2 (n=30), and ≥25 kg/m2 (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 µg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011). Conclusion: The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Evaluation of Oxidative Stress, Thyroid Hormones, Trace Elements and Some Biochemical Markers in Goats Naturally Infected with Theileria ovis.

BACKGROUND: Theileriosis is a tick-borne disease caused by protozoon species in the Theileria genus of the Theileriidae family. The biochemical changes induced by infection are considered to be an important understanding of the pathophysiology of caprine theileriosis. In this study, it was aimed to determine oxidative stress, thyroid hormones, trace elements, and biochemical parameters in theileriosis infection. MATERIALS AND METHODS: A sample of 14 goat was used for this purpose, of which 7 were healthy and 7 were infected with Theileria ovis. Theileria infection was diagnosed from the polymerase chain reaction (PCR). Sera from blood samples was tested for total antioxidant capacity (TAC), total oxidant capacity (TOC), oxidative stress index (OSI), alanine aminotransferase (ALT), aspartate transaminase (AST), gamma glutamyl transferase (GGT), total protein, albumin, triglyceride, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), urea, blood urea nitrogen (BUN), creatinine, triiodothyronine (T3), thyroxine (T4), copper (Cu), zinc (Zn), cobalt (Co), manganese (Mn), selenium (Se), iron (Fe). RESULT: TOC, OSI, AST, ALT and GGT values were higher in the patient group than in the healthy group (P < 0.05). On the other hand, there were decreases in TAC, T3, T4, total protein, albumin, creatinine, Cu, Zn, Se, and Co values (P < 0.05). However, there was not found to be a statistical difference between the healthy and patient groups in terms of triglyceride, cholesterol, HDL, LDL, urea, BUN, Mn, and Fe values (P > 0.05). CONCLUSIONS: It can be stated that oxidative stress is a complication of caprine theileriosis and it may be accompanied with hypothyroidism and deficits in trace minerals.

SIADH as a Rare Complication of Foramen Magnum Stenosis in an Infant With Achondroplasia.

Achondroplasia is the most common skeletal dysplasia and is associated with serious complications such as foramen magnum stenosis (FMS). This case report describes an infant with achondroplasia who presented with a syndrome of inappropriate antidiuretic hormone secretion (SIADH), secondary to significant FMS and myelocompression. A 2-month-old boy with prenatally diagnosed achondroplasia was referred due to disordered breathing and altered consciousness. On admission, apathy, hypotonus, and hypothermia with typical features of achondroplasia were noticed. Laboratory investigations revealed severe hyponatremia and hypochloridaemia with normal glucose and urea levels. The diagnosis of SIADH was made based on low serum osmolality in the presence of high urine osmolality, along with an elevated copeptin level. An emergency computerized tomography showed a high-grade stenosis at the cranio-cervical junction; subsequent magnetic resonance imaging demonstrated myelocompression. The patient underwent decompression surgery the next day; serum osmolality increased after the operation. Spontaneous breathing after extubation was sufficient whereas tetraplegia persisted despite intensive physiotherapy. Clinicians should be aware of SIADH as a presenting sign of FMS in children with achondroplasia. Further discussion is warranted regarding improving parental education and timing of screening recommendations.

Is intraoperative parathyroid monitoring during minimally invasive parathyroidectomy still justified?

Introduction: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. With parathyroidectomy, a cure rate of over 95% at initial surgery is reported. Localization of the abnormal parathyroid gland is critical for the operation to be successful. The aim of this study is to analyze data of patients with single gland disease (SGD) and positive concordant localization imaging undergoing minimally invasive parathyroidectomy (MIP) and intraoperative parathyroid hormone monitoring (IOPTH) to evaluate if IOPTH is still justified in patients with localized SGD. Methods: A retrospective database analysis of all minimally invasive operations with IOPTH for PHPT and positive concordant localization in ultrasound (US) and 99mTc-sestamibi scintigraphy (MIBI) between 2016-2021. When both US and MIBI were negative, patients underwent either choline or methionine PET-CT. The patients were also analyzed a second time without applying IOPTH. Results: In total, 198 patients were included in the study. The sensitivity of US, MIBI and PET-CT was 96%, 94% and 100%, respectively. Positive predictive value was 88%, 89% and 94% with US, MIBI and PET-CT, respectively. IOPTH was true positive in 185 (93.4%) patients. In 13 (6.6%) patients, no adequate IOPTH decline was observed after localizing and extirpating the assumed enlarged parathyroid gland. Without IOPTH, the cure rate decreased from 195 (98.5%) to 182 (92%) patients and the rate of persisting disease increased from 2 (1.0%) to 15 (7.5%) patients. Conclusion: Discontinuing IOPTH significantly increases the persistence rate by a factor of 7.5 in patients with concordantly localized adenoma. Therefore, IOPTH appears to remain necessary even for this group of patients.

A review of complex hormone regulation in thyroid cancer: novel insights beyond the hypothalamus-pituitary-thyroid axis.

Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations.

BMI z-score as a prognostic factor for height velocity in children treated with recombinant human growth hormone due to idiopathic growth hormone deficiency.

PURPOSE: Growth hormone deficiency (GHD) causes growth disturbances during childhood. The most recommended treatment of GHD is the administration of recombinant human growth hormone (rhGH). Recent studies have proved that well-nourished GHD children respond better to rhGH therapy compared to undernourished individuals. The aim of this study was to analyze nutritional status along with height velocity in GHD children during the first two years of rhGH therapy, and to estimate the optimal BMI z-score range in which these children achieve the best growth results. METHODS: This retrospective analysis included 80 prepubertal idiopathic GHD children treated with rhGH. Anthropometric data were obtained from medical records made at an initial visit and then follow-up visits after 12 and 24 months of treatment. The body mass index (BMI) was calculated and standardized into z-score, basing on Cole's LMS method. Then, the BMI z-score was analyzed in relation to the parameters of growth response. RESULTS: The higher the BMI z-score at treatment entry, the greater the increase in height during the first twelve months of rhGH therapy. BMI z-score ≥0 noted at the beginning of each year of the treatment are associated with significantly better growth increments throughout the first and the second years of the therapy. CONCLUSION: Prepubertal idiopathic GHD children with BMI z-score below 0 would probably benefit from the improvement of their nutritional status prior to the rhGH treatment beginning. It seems that increasing BMI z-score to obtain values between 0 and 1 would be optimal for the growth process.

Incidence of High Risk and Malignant Pathological Findings in Transgender and Gender Diverse Individuals Undergoing Gender-Affirming Mastectomy.

BACKGROUND: Concrete, data-driven guidelines for breast cancer screening among the transgender and gender diverse (TGD) population is lacking. The present study evaluates possible associations of gender-affirming hormone therapy (GAHT) on incidental breast pathology findings in trans-masculine patients to inform decision making about breast cancer screening. PATIENTS AND METHODS: This was a retrospective cohort study of patients who had gender-affirming mastectomy or breast reduction at a single center from July 2019 to February 2024. A total of 865 patients met the inclusion criteria. Gender-affirming testosterone therapy and length of exposure were evaluated to seek differences in post-operative pathology findings. RESULTS: The median age at the time of surgery was 27 years [interquartile range (IQR) 21-30]. Most participants identified as female to male (658, 75.6%). A significant portion of the participants (688, 79.2%) were undergoing testosterone therapy at the time of surgery, with the median duration of testosterone use prior to surgery being 14 months (IQR 4-29). High risk or malignant findings were noted in pathology results for 12 of 1730 breasts (0.7%). Ordered logistic regression found that duration of testosterone therapy was not associated with increasing severity of incidental breast pathology. Additionally, patients under 25 years of age were 70% less likely to have any incidental finding on pathological evaluation than older patients [odds ratio (OR) 0.3, p < 0.01, confidence interval (CI) 0.18-0.50]. CONCLUSIONS: The present study found that patients undergoing GAHT should not be screened for breast cancer with increased frequency compared with cis-gender women. Additionally, it may be appropriate for trans women under the age of 25 with normal breast cancer risk to forego pathological breast tissue examination.

Why do oestrogens matter: systematic review and meta-analysis assessing GnRH antagonists, considering add-back therapy, for endometriosis-associated pain.

Gonadotrophin-releasing hormone (GnRH) antagonists have been demonstrated to reduce endometriosis-associated pain. Because of the hypo-oestrogenic state they induce, however, higher dosages of GnRH antagonists are not recommended for used long term. This unwanted effect may be eliminated by so-called add-back therapy (ABT). This review was conducted to assess the safety and efficacy of GnRH antagonists, with or without add-back hormonal replacement therapy. Out of the 345 studies selected through the initial search, seven randomized controlled trials were included, comparing different oral GnRH antagonists at varying dosages, from a minimum of 50 mg to a maximum of 200 mg once or twice daily. Women treated with the lowest dose of GnRH antagonists had significantly greater mean pain score reductions from baseline throughout treatment compared with those treated with placebo (odds ratio [OR] -13.12, 95% CI -17.35 to -8.89 and OR -3.08, 95% CI -4.39 to -1.76 for dysmenorrhoea and non-menstrual pelvic pain, respectively). Compatible with the dose-response effect, a positive correlation was found between response rates and adverse event rates. While GnRH antagonists offer an advantage in terms of pain reduction for endometriosis, the more recent literature suggests using GnRH antagonists with ABT, which, while mitigating the hypo-oestrogenic effects of GnRH antagonists, maintain their efficacy, while allowing their long-term use.

[Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on metabolomics].

In this study, a mouse model of premature ovarian failure(POF) was constructed by injecting D-galactose(200 mg·kg~(-1)) into the back of the neck for 6 weeks. The mice were randomly divided into a normal group(group N), a model group(group M), and a Qiwei Guibao Granules group(group A, 12.87 g·kg~(-1)). Starting from the 11th day of modeling, group A was treated with Qiwei Guibao Granules by gavage for 32 days, while group M and group N were given equal volume of saline. Metabolomics analysis was used to explore the mechanism of action of Qiwei Guibao Granules in the treatment of POF. The results showed that compared with group N, the group M exhibited decreased wet weight of bilateral ovaries, increased levels of LH and FSH in serum, and significantly decreased levels of E_2 and PROG. After treatment with Qiwei Guibao Granules, compared with the group M, the group A showed a significant increase in the wet weight of bilateral ovaries, a significant decrease in the levels of FSH and LH in serum, and a significant increase in the level of E_2. Metabolomics analysis revealed 55 differential metabolites identified between group N and group M(14 upregulated and 41 downregulated compared with group N) and 82 differential metabolites identified between group M and group A(56 upregulated and 26 downregulated compared with group M), with 5 metabolites showing consistent changes between the group N vs group M. After excluding these 5 metabolites, 77 metabolites that changed after intervention with Qiwei Guibao Granules were focused on. These mainly involved histidine metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism. Among them, carnosine, 1-methyl-L-histidine, imidazoleacetic acid, choline, L-threonine, beta-hydroxypyruvic acid, phosphatidylcholine, and glycerol-3-phosphate were the major differential metabolites in these three metabolic pathways. Therefore, Qiwei Guibao Granules may exert therapeutic effects on POF mice by regulating amino acid metabolism and lipid metabolism in the mouse body.