Follicle-stimulating Hormone Research Articles

Safety assessment of three common food additives: the reproductive, oxidative and enzymatic perspective

This investigation was designed to evaluate the reproductive toxicity induced by potassium bromate (at doses of 50, 40, 30, 20, and 10 mg/kg), sodium benzoate (at doses of 5, 4, 3, 2, and 1 mg/kg), and caramel IV (at a dose of 200 mg/kg for 1, 2, 3, 4, and 5 weeks) in male albino mice through the assessments of sperm abnormality and sperm count. The concentrations of the three additives tested were chosen purposefully based on the acceptable daily intake of each of the additives by standard organizations. The level of Total Testosterone (TT), Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH), as well as the activities of catalase (CAT), superoxide dismutase (SOD), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), were also measured. The results obtained showed that all three tested food additives led to a statistically significant (p < 0.05) increase in abnormal sperm cells among exposed mice. The sperm abnormalities observed include folded sperm, amorphous heads, distal droplets, absent hooks, improper tail attachments, and looped tails. Furthermore, it was observed that only mice exposed to potassium bromate and caramel exhibited a statistically significant decrease in mean sperm count. Alterations in the levels and activities of TT, ALT, FSH, AST, LH, and ALP were also observed to be concentration-dependent in the exposed mice. The findings suggest that the reproductive toxicity and changes in enzyme activities in the treated mice are dependent on the concentration of potassium bromate and sodium benzoate, as well as the duration of exposure to caramel IV. These indicate that high consumption of foods or beverages containing potassium bromate, sodium benzoate, and caramel IV colourant may induce reproductive abnormalities in the consumers.

Variations in gut microbiota composition and reproductive hormone levels between laying and broody Muscovy ducks

High broodiness in Muscovy ducks impedes animal husbandry growth. The interaction between endocrine hormones and gut microbiota has been proven to play a crucial role in reproductive performance, and whether it can regulate the broody behavior of Muscovy ducks requires further research. Nine laying ducks (Laying group) and nine broody ducks (Broodiness group) were selected. Corresponding serum, ileum, and cecum chyme were collected for further research. The results showed that, compared to the laying group, the serum concentration of prolactin decreased, while the levels of Mullerian inhibiting substance, follicle-stimulating hormone, and follistatin increased in the broodiness group (P < 0.05). 16S rDNA sequencing showed that, the broodiness group exhibited lower abundance levels of Rothia, Streptococcus, and Lactobacillus, whereas the abundance of Turicibacter, Aliicoccus, and Facklamia was higher in the ileum compared to the laying group (P < 0.05). In the cecum, the broodiness group exhibits a significant reduction in the abundance of Butyricicoccus and unclassified_f_Rikenellaceae, while the abundance of Christensenellaceae_R-7_group, Ruminococcus_torques_group, Parabacteroides, norank_f_Oscillospiraceae, Cloacibacillus, Sellimonas, Shuttleworthia, norank_f_UCG-010, unclassified_f_Lachnospiraceae, Oscillospira, Synergistes, Family_XIII_AD3011_group and Eubacterium_nodatum_group is higher compared to the laying group. A Spearman correlation analysis reveals that both in the ileum and cecum, serum hormones exhibit significant correlations with the top 20 abundant intestinal microbial genera. Among these, serum follistatin has most entries of significant correlations with the detected microbial genera (P < 0.05). In conclusion, the broody behavior of Muscovy ducks can be modulated by the interaction between hormones and gut microbiota. Notably, the relationship between Follistatin and the composition of gut microbiota, specifically Firmicutes, is the most prominent.

Morning tiredness and insomnia symptoms are associated with increased blood pressure in midlife women

ObjectivesThe objective of this study was to investigate how blood pressure, sleep architecture, sleep-disordered breathing, body habitus, and levels of serum follicle-stimulating hormone are associated with symptoms of insomnia and sleep quality during menopausal transition. Methods64 healthy premenopausal women (aged 45–47 years) were recruited to the study. Data were collected at baseline and at 10-year follow-up during sleep laboratory and laboratory visits. A sleep questionnaire was used to evaluate sleep quality and insomnia symptoms. Data were analysed using multiple linear and logistic regression with a backward method. ResultsDuring the menopausal transition, a change in insomnia symptoms was associated with a change in morning systolic blood pressure (β = 0.114 (CI95% 0.023–0.205), p = 0.016). At follow-up, at the age of 56, a higher percentage of REM sleep was associated with a lower odds of restless sleep (OR = 0.842 (95 % CI 0.742–0.954), p = 0.007), while both higher systolic and diastolic evening blood pressure was associated with an increased odds of morning tiredness.OR = 1.047 (95 % CI 1.003–1.092), p = 0.034 and OR = 1.126 (95 % CI 1.018–1.245), p = 0.007, respectively. ConclusionsIn healthy midlife women, a change blood pressure is related to the development of insomnia symptoms during menopausal transition. In postmenopausal women, a high evening blood pressure may be associated with morning tiredness and a reduced amount of REM sleep may be perceived as restless sleep.

In vivo treatment with a non-aromatizable androgen rapidly alters the ovarian transcriptome of previtellogenic secondary growth coho salmon (Onchorhynchus kisutch).

Recent evidence suggests that androgens are a potent driver of growth during late the primary stage of ovarian follicle development in teleosts. We have previously shown that the non-aromatizable androgen, 11-ketotestosterone (11-KT), both advances ovarian follicle growth in vivo and dramatically alters the primary growth ovarian transcriptome in coho salmon. Many of the transcriptomic changes pointed towards 11-KT driving process associated with the transition to a secondary growth phenotype. In the current study, we implanted previtellogenic early secondary growth coho salmon with cholesterol pellets containing 11-KT and performed RNA-Seq on ovarian tissue after 3 days in order to identify alterations to the ovarian transcriptome in early secondary growth. We identified 8,707 contiguous sequences (contigs) that were differentially expressed (DE) between control and 11-KT implanted fish and were able to collapse those to 3,853 gene-level IDs, more than a 3-fold more DE contigs than at the primary growth stage we reported previously. These contigs included genes encoding proteins involved in steroidogenesis, vitellogenin and lipid uptake, follicle stimulating hormone signaling, growth factor signaling, and structural proteins, suggesting androgens continue to promote previtellogenic secondary growth.

Estetrol Inhibits the Prostate Cancer Tumor Stimulators FSH and IGF-1

Background: The co-treatment of androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) with the fetal estrogen estetrol (E4) may further inhibit endocrine PCa tumor stimulators. We previously reported the suppression of follicle-stimulating hormone (FSH), total and free testosterone, and prostate-specific antigen by ADT+E4. Here, we provide more detailed data on FSH suppression by E4 and present new findings on the effect of ADT+E4 on insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study (the PCombi study) was conducted in advanced PCa patients treated with ADT. The study assessed the effect of E4 co-treatment with LHRH agonist ADT on tumor stimulators, including FSH and IGF-1. Patients starting ADT were randomized 2:1 to receive either 40 mg E4 (n = 41) or placebo (n = 21) for 24 weeks. Non-parametric analyses were performed on the per-protocol population (PP) and individual changes were visualized. Results: The PP included 57 patients (37 ADT+E4; 20 ADT+placebo). ADT+E4 almost completely suppressed FSH in all patients (98% versus 37%; p &lt; 0.0001). IGF-1 levels decreased by 41% with ADT+E4 versus an increase of 10% with ADT+placebo (p &lt; 0.0001). Conclusions: The almost complete suppression of the tumor stimulator FSH using ADT plus E4 observed in all individual patients in this study, along with the augmented suppression of IGF-1 versus an increase by ADT only, may be clinically relevant and suggest the enhanced anti-cancer treatment efficacy of E4 in addition to the previously reported additional suppression of total and free T and PSA.

Type 1 diabetes mellitus; ovarian reserve; anti-Müllerian hormone; ovarian function

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

Therapeutic Effects of Althaea officinalis L. and Metformin on Estradiol-Induced Polycystic Ovary Syndrome in Rats: Insights into The PI3K/AKT Pathway, Inflammation, and Oxidative Stress.

Polycystic ovary syndrome (PCOS) is one of the most important causes of infertility, irregular menstrual cycles, and anovulation in women. The current study aimed to investigate the therapeutic effects of Althaea officinalis L. (A. officinale) extract on PCOS in rats. In this experimental study, 70 rats in 7 groups (n=10/group) were studied for three weeks as follows; healthy control (HC), patient (PCOS), metformin (PCOS+MET), A. officinale treatment (PCOS+250 and 500 mg/kg A. officinale) and synergistic (PCOS+MET+250 and 500 mg/kg A. officinale) groups. Luteinizing hormone (LH), folliclestimulating hormone (FSH), progesterone (P) and testosterone (T) levels as well as inflammatory cytokines were measured. Total antioxidant capacity and lipid peroxidation levels were analyzed in ovarian tissue. The expression of GLUT-4, AKT, PI3K, PTEN genes and Ki-67 was assessed by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. A. officinale alone and especially in combination with MET moderated inflammatory and antioxidant parameters compared to the PCOS and MET groups. A. officinale in synergistic groups increased the apoptosis of granulosa cells by activating the PI3K/AKT pathway, resulting in a rise in the number of Ki-67 positive cells (P<0.05). Furthermore, following A. officinale treatment the LH/FSH rate decreased and FSH and P increased (P<0.05). Also, A. officinale extract could effectively normalize estrus cycle duration close to the normal group. The extract of A. officinale, in combination with metformin, can enhance the hypothalamic-pituitaryovary (HPO) axis with synergistic anti-inflammatory and antioxidant effects. Additionally, the extract showed apoptotic effect on cystic granulosa cells.

A Holistic View on Erectile Dysfunction: South African Medicinal Plants as Sustainable Alternative Therapies

Erectile dysfunction is a common problem affecting men worldwide, especially as they age. This condition is characterized by the inability to achieve or maintain an erection firm enough for sexual intercourse and may result from various factors, including vascular, neurogenic, hormonal, and psychological. Common first-line treatment options for the disease have relied on phosphodiesterase-5 inhibitors such as sildenafil (Viagra), which are costly, inaccessible, and sometimes result in adverse health effects. Consequently, there has been increasing interest in exploring medicinal plants as alternative remedies because of their easy access and affordability. In South Africa, 75 plant species with properties that affect testosterone levels, luteinizing hormone, and follicle-stimulating hormone are used as aphrodisiacs. Some plant extracts can increase blood testosterone concentrations and stimulate penile erection by maintaining nitric oxide levels. This paper presents current information about the possible utilization of South African medicinal plants as viable and readily available therapeutic alternatives for managing erectile dysfunction. In addition, it discusses in detail the various mechanisms of action of medicinal plants in managing the disease. The information on the efficacy of African medicinal plants in managing erectile dysfunction provided in this review will help increase awareness of the sustainable use of natural products. It may serve as a basis for including indigenous herbal remedies in the guidelines for erectile dysfunction management as potential treatment options in Africa.

INCIDENCE, SOCIODEMOGRAPHIC, AND CLINICAL CHARACTERISTICS OF ANOVULATORY INFERTILITY AMONG WOMEN PRESENTING TO A SECONDARY CARE HOSPITAL OF NORTH INDIA

Objectives: The objective of the study was to assess the incidence and factors associated with anovulatory infertility among reproductive-age women. Methods: The study was an observational cross-sectional study conducted in the Department of Obstetrics and Gynecology of a secondary care hospital of Prayagraj, Uttar Pradesh over a period of 20 months, from October 2020 to May 2022. A consecutive sampling method was used to recruit a total of 100 women presenting with a complaint of inability to conceive even after regular intercourse over the past 1 year into the present research. Based on the detailed physical and clinical examination as well as laboratory findings, the final diagnosis of the cause and the nature of the infertility (primary/secondary) were established. Results: Among the 100 patients, 22 were found to have anovulatory infertility. The mean age was 28.68±3.71 years. Majority (50%) belonged to the upper socioeconomic class the mean weight of patients was 55.91±5.66 kg and the mean body mass index was 22.85±2.21 kg/m2. Majority presented with normal menstruation, followed by oligomenorrhoea (45.5%). 81.8% of the participants had hirsutism. The mean follicle-stimulating hormone of patients was 6.30±1.87 IU/mL, the mean luteinizing hormone was 6.04±1.83 IU/mL, mean estradiol was 45.00±6.50 pg/mL, mean anti-mullerian hormone was 6.94±2.13 ng/mL, mean total cholesterol was 76.21±16.86 ng/dL, mean thyroid stimulating hormone was 2.63±0.98 mIU/L and mean prolactin was 15.94±4.94 ng/mL. About 86.4% had primary infertility, the most common cause being polycystic ovarian syndrome (PCOS, 63.6%). This was followed by hyperprolactinemia (13.6%) and hypothyroidism (9.2%). Secondary anovulation associated with obesity was identified in 13.6% of the patients. Conclusion: The incidence of anovulatory infertility was 22%, with the majority being primary infertility due to PCOS, followed by hyperprolactinemia, and hypothyroidism.

Correlation between abdominal visceral fat and the risk of endometrial cancer in patients with polycystic ovary syndrome

Objective: To explore the correlation between abdominal fat and the occurrence risk of endometrial cancer (EC) in patients with polycystic ovary syndrome (PCOS). Methods: The clinical information of 120 PCOS patients receiving treatment in our hospital from March 2019 to April 2022 were included in this study. Patients were divided into two groups, endometrial cancer (EC, n=35) and normal group (NM, n=85). Statistical analysis included t-test, c2-test, and Pearson's correlation coefficient. We analysed the data using logistic regression. The predictive accuracy and discriminative ability of the prediction model were assessed by the area under the receiver operating characteristic (ROC) curve (AUC) and calibration curves. Results: The incidence rate of EC in women with PCOS is 10.91% (12/110). Significant differences were found in waist circumference, hypertension, diabetes, hyperlipidemia, body mass index (BMI), waist-hip ratio (WHR), insulin resistance index (HOMA-IR), visceral fat area (VFA) oestrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), estradiol (E2), and luteinizing hormone (LH) between the two groups (P&lt;0.05). No statistical difference was found in age, hip circumference, menopause, use of intrauterine device, progesterone (P) and follicle-stimulating hormone (FSH) between the groups (P&gt;0.05). Multivariate logistic regression analysis showed that BMI, HOMA-IR, VFA and HER2 were independent influencing factors of EC in PCOS patients (P&lt;0.05). The AUC of BMI, HOMA-IR, VFA, HER2 were 0.878 (95%CI: 0.810~0.946), 0.831 (95%CI: 0.751~0.911), 0.816 (95%CI: 0.704~0.929) and 0.737 (95%CI: 0.634,0.840), respectively. The model had more diagnostic effectiveness (AUC=0.973). Conclusions: In PCOS disease, high-level BMI, HOMA-IR, VFA, and positive HER2 show an increased risk in the incidence of EC. These findings suggest that BMI, HOMA-IR, VFA, and HER2 are potential markers for Risk assessment of EC. HER2: Human epidermal growth factor receptor-2, E2: estradiol, P: progesterone, LH: Luteinizing hormone, FSH: Follicle-stimulating hormone. Keywords: Polycystic ovary syndrome; Abdominal visceral fat; Endometrial cancer; Occurrence risk.

7269 Interim Analysis of Gonadotropin-Releasing Hormone Agonist (GnRHa) Treatment in Children with Central Precocious Puberty: Focus on FMV Urinary LH Levels and Clinical Outcomes

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) refers to early activation of the hypothalamic–pituitary–gonadal (HPG) axis in children. There is an urgent need to understand the treatment pattern and clinical outcomes among children suffering from CPP. Studies have reported that first morning voided (FMV) urinary Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) have substantial association with CPP tested in GnRH stimulation test and can be useful in diagnosis and management of CPP in children. Gonadotropin-releasing hormone agonists (GnRHa) such as Leuprolide acetate (LA) are the recommended treatment for children suffering from CPP. The current study aimed to provide the information on level of LH and FSH in FMV urine when CPP diagnosis at baseline and the present results may also revealed trend of FMV-LH and FMV-FSH change during LA intervention in children with CPP. Here we present interim results from this study. Methods: This is an open-label, multicentre, single arm, prospective study that enrolled 31 subjects with CPP. Individuals were administered LA depot 11.25 mg, subcutaneously every 12 weeks. The study comprises a screening period; a 6-month treatment period: 24 weeks; and a post-treatment follow-up period: 12 weeks. The FMV urinary LH and FSH were diagnosed by Clopper-Pearson method with a 95% confidence interval. Results: Due to the data collection time point for the interim analysis, only 8 female subjects reached the 12-week visit time point and had a 12-week visit for FMV urinary Gn testing. Therefore, for this interim analysis, only FMV Gn decline at week 12 of the 8 subjects who had a 12-week visit will be presented. At baseline, the mean value of FMV urinary LH and FSH is 0.58 IU/L and 2.27 IU/L respectively. The FMV Gn urinary LH was demonstrated a decrease in 87.5% (95% CI: 47.35,99.68) of the children after LA intervention. Additionally, urinary FSH value of FMV urinary Gn was found to decrease in 75.00% of the children (95% CI: 34.91,96.81) compared to baseline FSH value. Conclusion: The present study reveals a decreasing trend in FMV Gn urinary LH and FSH levels in CPP children treated with LA during interim analysis. LA was shown to be safe and effective in ameliorating the level of LH and FSH in children suffering from CPP. From the study, it can be concluded that urinary LH and FSH may act as a potential biomarker for diagnosis and management of CPP. Presentation: 6/3/2024

8734 Absent FSH Signaling Rescues Spatial and Recognition Memory Impairments in Female 3xTg Mice

Abstract Disclosure: S. Sims: None. F. Sen: None. F. Sultana: None. A. Liu: None. V. Laurencin: None. A. Gumerova: None. O. Barak: None. S. Rojekar: None. A.R. Pallapati: None. L. Cullen: None. R. Chen: None. K. Goosens: None. V. Ryu: None. T. Yuen: None. M. Zaidi: None. T. Frolinger: None. F. Korkmaz: None. Alzheimer’s disease (AD) is a major progressive neurodegenerative disorder of the aging population, accounting for more than 60-80% of dementia cases. High serum level of the pituitary gonadotropin, follicle-stimulating hormone (FSH), is strongly associated with the onset of AD. We recently showed that FSH activates hippocampal Fshr to drive AD–like pathology and cognitive impairment in AD mice, that FSH blockade in these mice abrogates the AD-like phenotype by inhibiting the neuronal C/EBPβ–δ-secretase pathway, and that FSH and ApoE4, the most prevalent genetic risk factor of AD, jointly trigger AD-like pathogenesis by activating C/EBPβ-δ-secretase signaling. To further confirm the role of FSH in AD cognitive decline, we used female 3xTg;Fshr+/+, 3xTg;Fshr+/– and 3xTg;Fshr–/– mice that underwent sham surgery or ovariectomy (OVX) at 8 weeks of age. Sham-operated 3xTg;Fshr–/– mice were implanted with 17β-estradiol pellets to normalize E2 levels. Morris Water Maze (MWM) and Novel object recognition (NOR) tests were perform in these mice to assess spatial and recognition memory, respectively. 3xTg;Fshr+/+ mice displayed impaired spatial memory at 5-month of age in the MWM test. This impairment, in both the learning and retrieval phases, is significantly ameliorated in 3xTg;Fshr–/– mice and to a lesser extent in 3xTg;Fshr+/– mice, suggesting that Fshr expression has a negative impact on memory. At 5 and 10 months of age, sham-operated 3xTg;Fshr–/– mice show better memory performance in the MWM test during the learning phase when compared to their wild-type littermates, suggesting a rescue of spatial memory and progression with age. However, this rescue was not seen when mice were ovariectomized. At 5 months of age, sham-operated 3xTg;Fshr–/– mice displayed better memory retrieval compared with 3xTg;Fshr+/+ mice. This effect was not observed when the mice were 10-month-old, suggesting that the beneficial effect of the absence of FSH signaling on memory consolidation could be masked by disease severity and older age. OVX 3xTg;Fshr+/+, 3xTg;Fshr+/– mice displayed a decline in memory consolidation at 10-months of age compared with 5-month of age, while the 3xTg;Fshr–/– mice showed a significantly slower decline. Using the NOR test, we found impaired recognition memory in 10-month-old sham-operated or OVX 3xTg;Fshr+/+ and 3xTg;Fshr+/– mice; this effect was prevented in OVX 3xTg;Fshr–/– mice. Finally, 3xTg;Fshr–/– mice displayed lower Aβ40 and Aβ42 levels in the brain (ELISA). Altogether, our results confirm a protective effect of absent Fshr signaling on spatial learning, consolidation, memory retrieval, recognition memory and reduction of brain Aβ40 and Aβ42. Presentation: 6/1/2024

12559 Objective Versus Subjective Measures Of Reproductive Development And Psychological Well-Being In Peri-Menarcheal Adolescents: A Pilot Study

Abstract Disclosure: K.C. McCormick: None. M.E. Lujan: None. J. Chang: None. L. Ipp: None. A. Alladeen: None. H. Lamar: None. J. Mendle: None. H. Vanden Brink: None. Introduction: Risk of psychopathology emerges during the pubertal and peri-menarcheal years; however objective physiological measures of maturation often differ from adolescents’ own reports of their development. Understanding how psychological symptoms emerge in relation to both objective and subjective evaluations of reproductive development can provide critical insights into mental health risk and variability in psychological symptom severity during the pre-menarcheal and early post-menarcheal years. Methods: 52 females 9-15 years old (n=16 pre-menarcheal, n=36 &amp;lt;2 years post-menarche) underwent a non-fasting blood draw for reproductive hormones (estradiol, anti-mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH)), anthropometry, detailed reproductive and menstrual history, and a series of surveys to evaluate depression (CES-DC), anxiety (MASC), perceptions of pubertal-related change (POPS), and transdiagnostic psychological processes (rumination, emotional clarity) which can contribute to, and are risk factors for, psychopathology. Whether psychological symptoms are associated with objective measures (menarche, gynecological age, reproductive hormone concentrations) versus subjective measures (self-reported tanner stage, severity of dysmenorrhea) were contrasted using t-tests and Pearson Correlation Coefficient analyses (JMP Pro (v17)). Results: The majority of participants (26/36 post-menarcheal and 11/16 pre-menarcheal) exceeded the standard cut-off of 15 for depressive symptoms, consistent with research on mental health symptomatology in this cohort of youth. POPS scores were higher (39±10.9) in post-menarcheal versus pre-menarcheal (31±12.6) adolescents indicating post-menarcheal adolescents reported more puberty-linked change in their lives (Pttest=0.04). Lower emotional clarity was associated with higher AMH concentrations (r= -0.27, p=0.0944). Depressive symptoms tended to be greater (27+14.8) in those with moderate dysmenorrhea versus mild/no dysmenorrhea (19±11.1, Pttest=0.08). Depression (r=0.30, p=0.032) and anxiety symptoms (r=0.32, p=0.027), and rumination (r=0.30, p=0.033) were associated with higher self-reported Tanner scores; POPS was trending (r=0.25, p=0.0776). Neither estradiol nor FSH were associated with any measures of psychological well-being. Conclusion: Both objective measures of reproductive development and adolescent self-reports may help providers assess individual vulnerability to internalizing psychopathology, such as depression and anxiety. Additionally, given population level increases in depressive symptoms in adolescents, researchers should avoid utilizing simple cutoffs for depression and anxiety, which lack specificity and overlook critical variability which can further elucidate mental and physical health dynamics. Presentation: 6/2/2024

6615 Clinical features and genetic etiology of primary ovarian insufficiency in 46,XX children

Abstract Disclosure: F. Wang: None. X. Yin: None. X. Lan: None. P. Li: None. Purpose: The clinical features of primary ovarian insufficiency in 46,XX children were analyzed, the pathogenic genes of POI were screened, and the genetic etiology of primary ovarian insufficiency in children 46,XX was clarified. Method: The clinical data of 46,XX POI patients were collected, including uterine and ovarian ultrasound, serum follicle-stimulating hormone (FSH), estrogen, anti-mullerian hormone (AMH), chromosomal karyotype analysis, adrenal and thyroid function, and immune function. Whole exome sequencing (WES) and CNV were used to screen POI candidate genes. Novel mutations such as MCM8 gene were used to verify cell function. HE staining, immunohistochemistry, cell fluorescence, and Tunnel method were used to observe the changes in ovarian tissue structure. Construction overexpression plasmids of Mutant MCM8 gene in Hela cells. Result: 1. Clinical features of 46,XX POI: The age of onset of the children was 11.9∼16.1 years old. In addition to POI, the clinical phenotype showed height growth retardation. Among them, 4 cases were short stature, 3 cases were growth hormone deficiency, and 5 cases were backward in bone age. All of them showed elevated FSH (&amp;gt;25 IU/L), and 7 cases had low serum AMH (&amp;lt;0.5 ng/ml). 2.The Screening of POI candidate genes and pathogenicity analysis: 5 of the 10 children carried the mutations of the pathogenic genes with POI, that is, 2 cases (sisters of the same family) carried two novel heterozygous mutations of MCM8 gene, one infant carried two novel heterozygous mutations of CYP19A1 gene, and one case with delayed puberty carried one homozygous mutation of ZSW1M7 gene. 3.The MCM8 mutant were functionally validated: The sisters carried two novel mutations, namely p.C242R and p.S445*. The elder sister (the proband) showed POI, short stature and tumor susceptibility, while the younger sister showed a trend of gradual increase in FSH level and ovarian decline. The follicles of the proband disappeared and fibrous tissue proliferation, the MCM8 expression was lower, and the positive rate of cell apoptosis was higher than normal control. The downregulation of Bax and Capase3 expression in mutant MCM8 of Hela cell was delayed compared with wild type, indicating the persistence of apoptosis. Conclusion: 1. The clinical characteristics of 46,XX POI in children are ovarian hypoplasia, often combined with height growth retardation, biochemical manifestations of hypergonadotropic hypogonadism, decreased serum AMH, and karyotype 46,XX. 2.46,XX POI genetic etiology analysis found that five known POI-related pathogenic genes, namely CYP19A1, MCM8, and ZSW1M7, in which five novel mutations were identified.3.Mutant MCM8 promotes ovarian apoptosis by activating the Bcl-2/Bax/Caspase 3 pathway. Keywords: Primary ovarian insufficiency, short stature, apoptosis Presentation: 6/3/2024

6693 Hypopituitarism in Pregnancy

Abstract Disclosure: N.A. Mcheik: None. H. Howarth: None. Background: Hypopituitarism in pregnancy requires careful management to ensure both maternal and fetal well-being. Disruptions of the pituitary gland in pregnancy can be due to adenomas, pituitary infarction, autoimmune disease, trauma, etc. Complications of hypopituitarism in pregnancy stem from inadequate production of thyroid stimulating hormone, growth hormone, gonadotropins and cortisol. Hormone replacement therapy will be necessary in such cases. For instance, patients in late pregnancy may require an increased dose of hydrocortisone due to the rise of corticosteroid-binding globulin. Patients may need increased doses of glucocorticoid therapy during labor given the major surgical stress. Antenatal care should include close follow up with endocrinologists and obstetricians and regular assessment of maternal hormone levels and fetal growth. Case: We present a case of a 37-year-old female G3P0020 at 24 weeks who presented with complaint of constant headache for 6 days. Associated with photophobia, intermittent blurry vision, nausea, and vomiting. She was admitted and given 1 g Magnesium bolus as well as Robaxin and Tylenol for headache without relief. Given persistence of symptoms and non-focal neurologic exam, MRI brain was completed that showed an enlarged pituitary gland with blood products. MRI pituitary showed an approximately 1.3 x 1.2 x 1.8 cm hemorrhagic lesion on the right side of pituitary gland with fluid level, most in keeping with hemorrhagic pituitary apoplexy. Thyroid function studies were consistent with central hypothyroidism with a low TSH 0.05, low Ft4 0.5, and normal Ft3 2.4. Luteinizing hormone was 0.1 mIU/mL (&amp;lt;1.5 normal in pregnancy), follicle stimulating hormone was &amp;lt;0.5 mIU/mL (&amp;lt;0.1 normal in pregnancy), estradiol &amp;gt;5000 pg/mL (1278-7192 normal in pregnancy), and prolactin 254 ng/mL (80-400 normal in pregnancy). IGF-1 was normal at 148 ng/ml. Morning cortisol was low at 1.8 ug/dL and ACTH was 9 pg/mL (low normal). Cortrosyn stimulation test at 60 minutes was normal at 17.7 ug/dL, however, given clinical improvement on steroids, the clinical picture is consistent with central hypoadrenalism. For treatment, she was started on IV hydrocortisone 50 mg every 8 hours and oral levothyroxine 100 mcg daily. The patient was discharged home on oral hydrocortisone 20 mg daily in the morning and 10 mg daily in the afternoon with close follow up. Conclusion: Ultimately, the management of hypopituitarism in pregnancy requires a personalized approach to hormone replacement and obstetric care and this is done through multidisciplinary care involving endocrinologists and obstetricians to optimize outcomes for both the mother and the baby. Presentation: 6/1/2024

6693 Hypopituitarism in Pregnancy

Abstract Disclosure: N.A. Mcheik: None. H. Howarth: None. Background: Hypopituitarism in pregnancy requires careful management to ensure both maternal and fetal well-being. Disruptions of the pituitary gland in pregnancy can be due to adenomas, pituitary infarction, autoimmune disease, trauma, etc. Complications of hypopituitarism in pregnancy stem from inadequate production of thyroid stimulating hormone, growth hormone, gonadotropins and cortisol. Hormone replacement therapy will be necessary in such cases. For instance, patients in late pregnancy may require an increased dose of hydrocortisone due to the rise of corticosteroid-binding globulin. Patients may need increased doses of glucocorticoid therapy during labor given the major surgical stress. Antenatal care should include close follow up with endocrinologists and obstetricians and regular assessment of maternal hormone levels and fetal growth. Case: We present a case of a 37-year-old female G3P0020 at 24 weeks who presented with complaint of constant headache for 6 days. Associated with photophobia, intermittent blurry vision, nausea, and vomiting. She was admitted and given 1 g Magnesium bolus as well as Robaxin and Tylenol for headache without relief. Given persistence of symptoms and non-focal neurologic exam, MRI brain was completed that showed an enlarged pituitary gland with blood products. MRI pituitary showed an approximately 1.3 x 1.2 x 1.8 cm hemorrhagic lesion on the right side of pituitary gland with fluid level, most in keeping with hemorrhagic pituitary apoplexy. Thyroid function studies were consistent with central hypothyroidism with a low TSH 0.05, low Ft4 0.5, and normal Ft3 2.4. Luteinizing hormone was 0.1 mIU/mL (&amp;lt;1.5 normal in pregnancy), follicle stimulating hormone was &amp;lt;0.5 mIU/mL (&amp;lt;0.1 normal in pregnancy), estradiol &amp;gt;5000 pg/mL (1278-7192 normal in pregnancy), and prolactin 254 ng/mL (80-400 normal in pregnancy). IGF-1 was normal at 148 ng/ml. Morning cortisol was low at 1.8 ug/dL and ACTH was 9 pg/mL (low normal). Cortrosyn stimulation test at 60 minutes was normal at 17.7 ug/dL, however, given clinical improvement on steroids, the clinical picture is consistent with central hypoadrenalism. For treatment, she was started on IV hydrocortisone 50 mg every 8 hours and oral levothyroxine 100 mcg daily. The patient was discharged home on oral hydrocortisone 20 mg daily in the morning and 10 mg daily in the afternoon with close follow up. Conclusion: Ultimately, the management of hypopituitarism in pregnancy requires a personalized approach to hormone replacement and obstetric care and this is done through multidisciplinary care involving endocrinologists and obstetricians to optimize outcomes for both the mother and the baby. Presentation: 6/1/2024

7467 Supplement Use Among Transgender Patients: Case Reports and Literature Review

Abstract Disclosure: H. Cunningham: None. Q. Jones: None. C. Kelley: None. The barriers to initiating gender affirming medical treatment are innumerable and increasing in the wake of wide-sweeping anti-trans legislation, leading many transgender individuals to utilize more accessible means of transitioning. We provide examples of patient-initiated supplement use at a gender medicine clinic in the Southeast. We describe a 60-year-old transgender woman who was unable to establish care due to lack of affirming providers in her region and insurance approval delays. She began taking Pueraria mirifica, along with saw palmetto and fenugreek, for feminization. Subsequently, her breast size increased from an A to B cup, and she noticed fat redistribution to her hips. When finally seen one year later, labs demonstrated suppressed luteinizing and follicle stimulating hormones and increased sex hormone binding globulin, with an associated decrease in estradiol and testosterone levels. Cessation of supplements resulted in lab normalization. Our second case describes masculinizing effects, including voice deepening, experienced by a transgender man using a supplement that contained "orchic extract.” Supplements used for gender affirmation can also have more adverse effects, including polycythemia in the setting of trenbolone, an illicit steroidogenic performance enhancing supplement used for masculinization by some patients assigned female at birth. Patients without access to gender affirming hormones through a medical provider, or who do not feel comfortable accessing health care, may be more likely to use supplements purchased online without a prescription. Considering this, we must create more safe spaces for gender affirming care and ask all transgender patients about supplement use. Providers should consider supplement use as a possible explanation for unexpected lab results. The literature on supplement use for gender-affirming effects is sparse; this presentation provides a summary of and contributes to the current literature on this topic. Presentation: 6/2/2024

7975 TLR4 Signaling Modulates Reproductive and Metabolic Outcomes in a Mouse Model of Polycystic Ovary Syndrome

Abstract Disclosure: K.D. Wiggins: None. Z. Del Mundo: None. J.A. Ayala Angulo: None. M. Lopez: None. C. Garcia: None. C. Nguyen: None. J. De La Torre: None. A. Saba: None. D. Trinh: None. D. Nicholas: None. Polycystic Ovarian Syndrome (PCOS), characterized by disruptions in both reproductive and metabolic functions, is associated with abnormal immune system activity and chronic inflammation. Although the precise mechanistic drivers of chronic inflammation in PCOS are not fully elucidated, elevated serum levels of lipopolysaccharide (LPS) have been observed. We propose that Toll-like receptor 4 (TLR4) signaling, influenced by dysregulated LPS levels, is a central driver of chronic inflammation affecting both reproductive and metabolic pathways. To investigate this hypothesis, we subcutaneously implanted a nonsteroidal aromatase inhibitor, Letrozole (LET), in pubertal TLR4 knockout mice (TLR4KO) and C57BL/6J (wild type) mice. Our five-week LET treatment revealed that TLR4KO mice successfully entered all phases of the estrous cycle, with normalized Luteinizing Hormone (LH) and increased Follicle Stimulating Hormone (FSH) levels. These findings highlight TLR4's role in shaping cycling patterns and regulating fundamental hormonal pathways vital for reproductive health. Despite the genetic manipulation of the inflammatory pathway leading to a reduction in overall body weight gain, it had no discernible impact on the overall body composition of fat and lean mass. Additionally, our study found that dysregulation of blood glucose levels over time was independent of reduced body weight. TLR4KO mice demonstrated inefficient glucose clearance compared to wild-type mice, hinting at potential increases in insulin resistance, imbalances in adipose tissue inflammation, or possible alterations in the gut microbiota. Our study underscores the significance of disrupting the pro-inflammatory TLR4 pathway in shaping the reproductive and metabolic phenotypes in Letrozole-induced PCOS. The investigation into TLR4 becomes pivotal for comprehending the role of chronic inflammation in PCOS development or progression, offering valuable insights into potential therapeutic targets. Presentation: 6/2/2024

7394 Testicular Function in Young Adults with Growth Hormone (GH) Deficiency Previously Treated with GH: Comparison with Normal Controls

Abstract Disclosure: R. Cannarella: None. A. Crafa: None. S. Sapienza: None. M.M. Caruso: None. A.E. Calogero: None. Background: We have previously reported that treatment with recombinant human growth hormone (rhGH) can influence testicular growth and puberty onset in children with GH deficiency (GHD), and suggested GH as a determinant of testicular growth in childhood (doi: 10.3389/fendo.2021.619895). Limited evidence is available on testicular function in post-pubertal GHD patients. Objective: This prospective controlled study was undertaken to evaluate testicular function in young GHD adults previously undergone to GH treatment. Patients and Methods: Post-pubertal patients with non-syndromic GHD (&amp;gt;18 years), in whom GH therapy was discontinued after reaching the therapeutic goal, were required to have a complete evaluation of testicular function. Those who agreed were enrolled in our study. Age-matched healthy men older than 18 years served as controls. Exclusion criteria were: the presence of varicocele, urogenital infections, cryptorchidism, hypospadias, hypogonadism, testicular trauma or torsion, and other congenital or acquired disorders capable of interfering with testicular function. The study outcomes were: serum gonadotropins and total testosterone (TT), conventional sperm parameters, and testicular volume (TV) measured by ultrasound examination. Between-group analysis was performed using the Student’s t-test for independent samples or the Mann-Whitney test, for normally or non-normally distributed variables, respectively. Data were reported as mean±standard deviation for non-skewed data and median (interquartile range) for skewed data. Results: 26 patients with GHD and 25 age-matched controls (18.8±3.3 years vs. 20.1±3.6 years; p=0.18) were enrolled. Patients and controls did not differ for serum luteinizing hormone [2.6 (1.5-4.9) IU/L vs. 3.5 (2.8-4.8) IU/L); p=0.2], follicle-stimulating hormone [3.4 (2.2-4.3) IU/L vs. 3.1 (2.3-4.3) IU/L); p=1.0], and TT [5.7 (4.7-6.8) ng/dL vs. 6.0 (5.1-7.4) ng/dL); p=0.4] levels. At semen analysis, GHD patients had lower semen volume (2.1±1.4 mL vs. 3.5±1.5 mL; p=0.002), total sperm count [135.0 miL/ejaculate (54.3-229.0) vs. 231.3 miL/ejaculate (124.8-285.0); p=0.03], progressive motility [25.5% (15.0-34.0%) vs. 32.0% (30.0-36.5); p=0.02], and total motility [56.0% (49.0-62.0) vs. 66.5% (62.5-70.0); p=0.0001] compared to controls. No difference was found in sperm concentration [73.0 miL/mL (45.0-92.0) vs. 68.0 miL/mL (39.0-90.0); p=1.0] and normal morphology [8.5% (7.0-12.0) % vs. 10.0% (7.5-14.0); p=0.3]. Importantly, GHD patients had lower right (13.3±3.4 mL vs. 16.9±4.1 mL; p=0.001) and left (12.5±3.4 mL vs. 16.3±3.8 mL; p=0.0005) TV. Conclusion: This study provides the first evidence of lower TV and slightly worse semen parameters in patients with GHD compared to healthy controls. Serum GH levels during growth may be important for achieving normal testicular volume and spermatogenesis in adulthood. Presentation: 6/2/2024

9277 Testicular Function in Young Adults with Growth Hormone (GH) Deficiency Previously Treated with GH: Comparison with Normal Controls

Abstract Disclosure: R. Cannarella: None. A. Crafa: None. S. Sapienza: None. M.M. Caruso: None. A.E. Calogero: None. Background: We have previously reported that treatment with recombinant human growth hormone (rhGH) can influence testicular growth and puberty onset in children with GH deficiency (GHD), and suggested GH as a determinant of testicular growth in childhood (doi: 10.3389/fendo.2021.619895). Limited evidence is available on testicular function in post-pubertal GHD patients. Objective: This prospective controlled study was undertaken to evaluate testicular function in young GHD adults previously undergone to GH treatment. Patients and Methods: Post-pubertal patients with non-syndromic GHD (&amp;gt;18 years), in whom GH therapy was discontinued after reaching the therapeutic goal, were required to have a complete evaluation of testicular function. Those who agreed were enrolled in our study. Age-matched healthy men older than 18 years served as controls. Exclusion criteria were: the presence of varicocele, urogenital infections, cryptorchidism, hypospadias, hypogonadism, testicular trauma or torsion, and other congenital or acquired disorders capable of interfering with testicular function. The study outcomes were: serum gonadotropins and total testosterone (TT), conventional sperm parameters, and testicular volume (TV) measured by ultrasound examination. Between-group analysis was performed using the Student’s t-test for independent samples or the Mann-Whitney test, for normally or non-normally distributed variables, respectively. Data were reported as mean±standard deviation for non-skewed data and median (interquartile range) for skewed data. Results: 26 patients with GHD and 25 age-matched controls (18.8±3.3 years vs. 20.1±3.6 years; p=0.18) were enrolled. Patients and controls did not differ for serum luteinizing hormone [2.6 (1.5-4.9) IU/L vs. 3.5 (2.8-4.8) IU/L); p=0.2], follicle-stimulating hormone [3.4 (2.2-4.3) IU/L vs. 3.1 (2.3-4.3) IU/L); p=1.0], and TT [5.7 (4.7-6.8) ng/dL vs. 6.0 (5.1-7.4) ng/dL); p=0.4] levels. At semen analysis, GHD patients had lower semen volume (2.1±1.4 mL vs. 3.5±1.5 mL; p=0.002), total sperm count [135.0 miL/ejaculate (54.3-229.0) vs. 231.3 miL/ejaculate (124.8-285.0); p=0.03], progressive motility [25.5% (15.0-34.0%) vs. 32.0% (30.0-36.5); p=0.02], and total motility [56.0% (49.0-62.0) vs. 66.5% (62.5-70.0); p=0.0001] compared to controls. No difference was found in sperm concentration [73.0 miL/mL (45.0-92.0) vs. 68.0 miL/mL (39.0-90.0); p=1.0] and normal morphology [8.5% (7.0-12.0) % vs. 10.0% (7.5-14.0); p=0.3]. Importantly, GHD patients had lower right (13.3±3.4 mL vs. 16.9±4.1 mL; p=0.001) and left (12.5±3.4 mL vs. 16.3±3.8 mL; p=0.0005) TV. Conclusion: This study provides the first evidence of lower TV and slightly worse semen parameters in patients with GHD compared to healthy controls. Serum GH levels during growth may be important for achieving normal testicular volume and spermatogenesis in adulthood. Presentation: 6/2/2024