Steroid Levels Research Articles

Decreased Circulating Gonadotropin-Releasing Hormone Associated with Keratoconus.

Keratoconus (KC) is a corneal thinning dystrophy that leads to visual impairment. While the cause of KC remains poorly understood, changes in sex hormone levels have been correlated with KC development. This study investigated circulating gonadotropin-releasing hormone (GnRH) in control and KC subjects to determine if this master hormone regulator is linked to the KC pathology. Plasma and saliva were collected from KC subjects (n = 227 and n = 274, respectively) and non-KC controls (n = 58 and n = 101, respectively), in concert with patient demographics and clinical features. GnRH levels in both plasma and saliva were significantly lower in KC subjects compared to controls. This finding was retained in plasma when subjects were stratified based on age, sex, and KC severity. Control and KC corneal fibroblasts (HKCs) stimulated with recombinant GnRH protein in vitro revealed significantly increased luteinizing hormone receptor by HKCs and reduced expression of α-smooth muscle actin with treatment suggesting that GnRH may modulate hormonal and fibrotic responses in the KC corneal stroma. Further studies are needed to reveal the role of the hypothalamic-pituitary-gonadal axis in the onset and progression of KC and to explore this pathway as a novel therapeutic target.

Nur77 ameliorates cyclophosphamide-induced ovarian insufficiency in mice by inhibiting oxidative damage and cell senescence

Premature ovarian failure (POF) is among the primary causes of ovarian dysfunction that severely affects women’s physical and mental health. The main purpose of this study was to explore the expression level of Nerve growth factor-induced protein B (Nur77/NR4A1) in cyclophosphamide (CTX)-induced POF. We then tested whether Nur77 can exert a protective effect after CTX treatment and investigated the mechanism of Nur77’s role during ovarian injury. CTX promotes follicular atresia by inducing redox imbalance, apoptosis, and senescence, thereby causing direct toxicity to gonads. Additionally, CTX decreases ovarian reserve consumption by stimulating the excessive activation of primordial follicles. Nur77 can be stimulated by oxidative stress, DNA damage, metabolism, inflammation, etc. However, its relationship with POF remains unelucidated. We here found that Nur77 is expressed at low levels in POF ovaries. Therefore, Nur77 was identified as a regulator of ovarian injury and follicular development. According to the results, Nur77 overexpression alleviated redox imbalances, reduced cell senescence and apoptosis, and improved follicular reserve. Nur77 protects ovarian function by restoring disordered sex hormone levels and estrus cycles and promoting follicle growth and development at all levels. Moreover, the rapamycin protein kinase (AKT)/mammalian target of the rapamycin (mTOR) is a crucial regulator of the primordial follicle pool and follicular development. A relationship was observed between Nur77 and AKT through string and molecular docking. Experiments confirmed the involvement of the AKT/mTOR signaling pathway in the regulatory role of Nur77 in ovarian function. Thus, Nur77 is a critical target for POF prevention and treatment.

Thyroidectomy Induced Toxicity of Testis and Possible Amelioration by Chia (Salvia hispanica) Seeds Extract

Background: Thyroidectomy or thyroid surgery induces hypothyroidism and causes thyroid and testicular hormone deficiency. The current Study Aimed to examine the therapeutic effect of chia seeds extract against thyroidectomy-induced testicular toxicity, oxidative stress, DNA damage, proliferation in rats. Methods: 40 male rats were equally divided into 4 groups [Gp1, control ; Gp2, CSE ; Gp3, thyroidectomies rats; Gp4, treated thyroidectomies rats with chia seeds extract (Thy+CSE )]. Result: Following a thyroidectomy, significant reductions (P less than 0.05) were observed in The Levels of triiodothyronine (T3), thyroxine (T4), sexual hormones (Testosterone (tt), Follicle-Stimulating Hormone and Luteinizing Hormone And prolactin), count of sperm, index of morphology, vitality, progressive motility, total motility (PR+NP), Glutathione, Superoxide Dismutase, Glutathione S-Transferase and PCNA expressions compared to the control and CSE after three weeks. Additionally, thyroidectomy leads to significant (P less than 0.05) increases in the serum of thyrotropin (TSH), alanine transaminase, alkaline phosphatase, non-progressive sperms, immotile sperms, malondialdehyde, DNA damage and injury of testis and significant (P less than 0.05) decreases in blood. Thy+CSE treatment helped to modulate most of these changes and recover testicular injury when compared To The Control and CSE. Rats treated with CSE after thyroidectomy Showed gradual improvements in testicular functions, histology and spermatogenesis due to its beneficial affection in free radicals’ scavenger.

Higher FSH Level Is Associated With Increased Risk Of Incident Hip Fracture In Older Adults, Independent Of Sex Hormones.

Higher levels of FSH are associated with bone loss among women during the perimenopausal transition and among older men, independent of estradiol and testosterone levels, but whether higher FSH is an independent fracture risk factor is unknown. Determine whether baseline FSH level predicts subsequent hip fracture in older adults. Using a case-cohort design, we randomly sampled 295 participants stratified by sex from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort, including 25 participants with incident hip fracture within 10 years after baseline. We sampled an additional 230 sex-stratified participants with incident hip fracture. Serum FSH and sex hormone levels were measured at baseline. Robust weighted Cox proportional hazards models were used to determine the relationship between FSH and hip fracture risk. Incident hip fracture. As no interaction was identified between FSH and sex for the relationship with fracture, men and women were pooled for analysis. Higher levels of FSH were associated with a significantly increased risk of incident hip fracture in models adjusted for age and sex [hazard ratio (HR) 1.24 (95% CI 1.04-1.48, p=0.02)] and after further adjustment for estradiol, testosterone, and sex hormone binding globulin levels [HR 1.20 (95% CI 1.01-1.44, p=0.04) per sex-specific SD increase in FSH level]. Higher FSH is associated with increased risk of subsequent hip fracture. Our findings support a growing body of evidence for direct pleiotropic effects of FSH on bone, and for a role for FSH in aging and disability independent of sex hormone levels.

Vertebrate endocrine disruptors induce sex-reversal in blue mussels

Mollusks are the second most diverse animal phylum, yet little is known about their endocrinology or how they respond to endocrine disrupting compound (EDC) pollution. Characteristic effects of endocrine disruption are reproductive impairment, skewed sex ratios, development of opposite sex characteristics, and population decline. However, whether classical vertebrate EDCs, such as steroid hormone-like chemicals and inhibitors of steroidogenesis, exert effects on mollusks is controversial. In the blue mussel, Mytilus edulis, EDC exposure is correlated with feminized sex ratios in wild and laboratory mussels, but sex reversal has not been confirmed. Here, we describe a non-destructive qPCR assay to identify the sex of M. edulis allowing identification of males and females prior to experimentation. We exposed male mussels to 17α-ethinylestradiol and female mussels to ketoconazole, EDCs that mimic vertebrate steroid hormones or inhibit their biosynthesis. Both chemicals changed the sex of individual mussels, interfered with gonadal development, and disrupted gene expression of the sex differentiation pathway. Impacts from ketoconazole treatment, including changes in steroid levels, confirmed a role for steroidogenesis and steroid-like hormones in mollusk endocrinology. The present study expands the possibilities for laboratory and field monitoring of mollusk species and provides key insights into endocrine disruption and sexual differentiation in bivalves.

Associations of Co-Exposure to Polycyclic Aromatic Hydrocarbons and Heavy Metals with Sex Steroid Hormones among Children Aged 6–19 Years

Plain Language SummaryPolycyclic aromatic hydrocarbons (PAHs) and HMs are two classic groups of environmental endocrine-disrupting chemicals (EDCs). PAHs usually coexist with HMs and they may have a combined effect in affecting sex hormone levels in children. Sex steroid hormones have an important role in children’s growth and development which affects growth rate, central nervous system function, normal skeletal mineralization, and reproductive health. This study investigated the correlations between co-exposure to PAHs and HMs and levels of sex steroid hormones in children. Weighted multivariate linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to analyze the associations between co-exposure to PAHs and HMs and sex steroid hormone levels. We found that co-exposure to PAHs and HMs was associated with the levels of estradiol (E2), the testosterone (TT)/E2 ratio, free androgen index (FAI), and sex hormone-binding globulin (SHBG). Our analysis reveals that co-exposure to PAHs and HMs is hazardous to the reproductive health of children, and further mechanism and prospective studies are needed to provide additional substantial evidence.

Combination therapy of Sanjie Zhentong capsules for endometriosis: Impact on hormone regulation and serum expression of FOLR1 and MSLN.

Examining the impact of Sanjie Zhentong capsules on hormone levels and serum expression of folate receptor 1 (FOLR1) and Mesothelin (MSLN) in endometriosis patients. A cohort of 150 endometriosis patients admitted between June 2019 and June 2023 was divided into 2 groups based on Sanjie Zhentong intake, comprising 75 cases each. Comparative analyses encompassed uterine artery hemodynamic parameters, ultrasound (B-mode) findings, Visual Analog Scale scores, traditional Chinese medicine symptom scores, Endometriosis Health Profile-30 scores, and serum levels of FOLR1, MSLN, and sex hormones before and after treatment. Post-treatment, both groups exhibited increased peak systolic velocity compared to pretreatment, with the Sanjie Zhentong group showing a significantly higher increase (P < .05). Moreover, resistance index decreased in both groups post-treatment, with the Sanjie Zhentong group displaying a greater reduction (P < .05). Adnexal mass diameters, endometrial thickness, and uterine volume decreased post-treatment in both groups, with the Sanjie Zhentong group experiencing a more pronounced decrease (P < .05). Serum FOLR1, MSLN, and sex hormone levels also decreased post-treatment in both groups, with the Sanjie Zhentong group exhibiting a more significant decrease (P < .05). Additionally, pain scores, traditional Chinese medicine symptoms, and Endometriosis Health Profile-30 scores decreased post-treatment in both groups, with the Sanjie Zhentong group demonstrating a greater reduction (P < .05). Sanjie Zhentong capsules demonstrate efficacy in regulating sex hormones, reducing serum FOLR1 and MSLN expression, alleviating pain, shrinking adnexal masses, decreasing uterine size, and improving uterine artery blood flow in endometriosis patients.

Impact of polyethylene microplastics exposure on kallikrein-3 levels, steroidal-thyroidal hormones, and antioxidant status in murine model: protective potentials of naringin

The widespread presence of microplastics in the environment has raised significant concerns regarding their potential impact on human and animal health. Among various microplastic types, polyethylene microplastics (PE-MPs) are particularly prevalent due to the extensive use in packaging and consumer products. Exploring the uncharted therapeutic potentials of naringin, this study delves into its mitigating effects on disruptions in kallikrein-3 levels, steroidal-thyroidal hormone balance, and antioxidant defense triggered by PE-MPs exposure, paving the way for novel interventions in environmental toxin-induced endocrine and oxidative stress disorders. Male Wistar rats (n = 24) were randomly grouped into four: Control, PE-MPs (1.5 mg/kg), PE-MPs + NAR (1.5 mg/kg PE-MPs + 100 mg/kg NAR), and NAR (100 mg/kg). Hormonal and antioxidant parameters were assessed after 28 days of exposure. PE-MPs exposure caused a significant increase(p < 0.005) in the level of kallikrein-3 (KLK-3) while it significantly reduces the levels of testosterone (TST), luteinizing hormone, thyroid stimulating hormone (TSH) and Free-triiodothyronine (fT3) and Total cholesterol (TChol) concentration. PE-MPs exposure also disrupted significantly (p < 0.005) antioxidant profile by down-regulating the activities of glutathione-S-transferase, catalase (CAT), superoxide dismutase (SOD) and reducing levels of glutathione (GSH) and ascorbic acid (AA) while concentration of malondialdehyde (MDA) levels were increased relative to control. However, the mitigating potentials of naringin on disruptions in hormonal and antioxidant profiles caused by PE-MPs exposure were demonstrated, as NAR normalized KLK-3, steroid, and thyroid hormone levels, cholesterol concentration, and enhanced antioxidant defense. This suggests that NAR is a promising protective agent against endocrine and oxidative damage induced by environmental contaminants such as microplastics.

Multiple Benefits of Empagliflozin in PCOS: Evidence from a Preclinical Rat Model.

Polycystic ovary syndrome (PCOS) is the most common complex endocrinological condition of women that is associated with infertility and metabolic disorders during the reproductive period. Recently, a great deal of research has focused on the etiopathogenesis of this disorder and the modulation of therapeutic approaches. There are still many controversies in the choice of therapy, and metformin is one of the most commonly used agents in the treatment of PCOS. Considering the link between metabolic disorders and PCOS, glycemic status is crucial in these patients, and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) represent a potentially promising new therapeutic approach. These drugs have been shown to improve glucose metabolism, reduce adipose tissue, decrease oxidative stress, and protect the cardiovascular system. These data prompted us to investigate the effects of empagliflozin (EMPA) in a PCOS rat model and compare them with the effects of metformin. We confirmed that EMPA positively affects somatometric parameters, glucose and lipid metabolism, and the levels of sex hormones, as well as reduces oxidative stress and improves ovarian function and morphology. Administration of EMPA at doses of 5 mg/kg, 15 mg/kg, and 45 mg/kg during a 4-week treatment period improved, as induced by estradiol valerate and a high-fat diet, the metabolic and reproductive statuses in a PCOS rat model. The best effects, which were comparable to the effects of metformin, were achieved in groups receiving the middle and highest applied doses of EMPA. These results may prompt further clinical research on the use of EMPA in patients with PCOS.

Effect of climatic factors on sexual maturity Labeo rohita fish

&lt;p&gt;This study examined the varying levels of thyroxine hormone impact (at doses of 2, 10, and 50 µg g-1 BW) as an environmentally responsive hormone on the fatty acid and sexual steroid profiles in male Labeo rohita fish. Each treatment group comprised six male fish with an average weight of 5.4 ± 0.58 kg. Blood samples were collected from male rohu fish pre-and post-injection, as well as following sperm retrieval from the caudal peduncle. Biotechnical parameters were evaluated post-fertilization. Among male breeders, the pituitary treatment and the 50 µg g-1 BW thyroxine treatment exhibited the highest levels of estradiol, testosterone, 17-alpha hydroxyprogesterone, cortisol, LH, as well as testicular protein and fat content. Whereas the lowest levels were observed in the LHRH recipient and control groups (p &amp;lt; 0.05). Moreover, the saturated fatty acids C16:0 and C18:0, monounsaturated fatty acids C18:1n9c and C24:1n9, along with polyunsaturated fatty acids C20:3n6 and C22:6n3 in male breeders, were found to be the predominant fatty acids in the testes under hormonal treatment. The pituitary treatment and the 50 µg g-1 BW thyroxine treatment demonstrated a greater total percentage of testicular fatty acids compared to other interventions (p &amp;lt; 0.05). These findings emphasize the heightened efficacy of pituitary hormone and subsequent thyroxine hormone administration at a dose of 50 µg g-1 BW, relative to lower thyroxine doses and LHRH. The aforementioned treatment can increase the levels of sex hormones that are important for sexual responsiveness, emphasizing their pivotal role in facilitating successful artificial reproduction in male Rohu breeders.&lt;/p&gt;

Sex-specific Genetic Determinants of Right Ventricular Structure and Function.

While sex differences in right heart phenotypes have been observed, the molecular drivers remain unknown. To provide biological insights into sex differences in the structure and function of the right ventricle (RV) using common genetic variation. RV phenotypes were obtained from cardiac magnetic resonance imaging in 18,156 women and 16,171 men from the UK Biobank. Observational analyses and sex-stratified genome-wide association studies were performed. Candidate female-specific loci were evaluated against invasively measured cardiac performance in 479 female patients with idiopathic or heritable pulmonary arterial hypertension (PAH), recruited to the UK NIHR BioResource Rare Diseases study. Sex was associated with differences in RV volumes and ejection fraction in models adjusting for left heart counterparts, blood pressure, lung function and sex hormone levels. Six genome-wide significant loci (13%) revealed heterogeneity of allelic effects between women and men, and significant sex-by-genotype interaction. These included two sex-specific candidate loci present in women only: a locus for RV ejection fraction in BMPR1A and a locus for RV end-systolic volume near DMRT2. Epigenetic data in RV tissue indicate that variation at the BMPR1A locus likely alters transcriptional regulation. In female patients with PAH, a variant located in the promoter of BMPR1A was significantly associated with cardiac index (effect size 0.16 l/min/m2), despite similar RV afterload. BMPR1A has emerged as a biologically plausible candidate gene for female-specific genetic determination of RV function, showing associations with cardiac performance under chronically increased afterload in female patients with PAH.

7838 Improvement of Cognition and Memory Scores in Transgender Individuals Within One Year of Initiating Gender-Affirming Hormone Therapy

Abstract Disclosure: C.M. Godar: None. S.C. De La Torre: None. O. Bonsu: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: The use of gender-affirming hormone therapy (GAHT) in transgender individuals is known to provide many beneficial health effects to reduce gender dysphoria, reduce depressive symptoms, and increase overall quality of life. Cognitive function and memory ability are known to be influenced by sex hormone levels in studies of hormone replacement therapy in post-menopausal women, but studies of GAHT’s effects on cognition and memory in transgender patients have been scarcely reported. We discuss a study of cognitive testing in transgender individuals before and after 12 months of gender-affirming feminizing or masculinizing hormone therapy using a validated cognitive assessment tool. Methods: A prospective study of 32 transgender patients aged 18-45 years was approved by IRB at an academic medical center. The Wechsler Memory Scale 4th edition (WMS®-IV, Pearson) was administered to 19 transgender females and 13 transgender males prior to initiation of GAHT and again after one year of GAHT use. Mean scores were analyzed and reported for five categories of cognitive and memory function: auditory memory (AMI), visual memory (VMI), visual working memory (VWMI), immediate memory (IMI), and delayed memory (DMI). Mean scores for baseline and 12-month data were analyzed for total population and male and female subgroups. Results: Baseline mean WMS-IV values for the total study population were: AMI 105 points, VMI 78 points, VWMI 107 points, IMI 88 points, DMI 91 points. Mean values after 12 months of GAHT were: AMI 120 points, VMI 81 points, VWMI 110 points, IMI 99 points, DMI 102 points. Mean percent change from baseline to 12 months was as follows: AMI 13.4%, VMI 8.9%, VWMI 2.6%, IMI 12.8%, DMI 13%. Similar patterns were noted for both gender subgroups. Discussion: It is well-known that transgender individuals are subject to higher rates of depression, anxiety, and suicidality compared to the general population. Decreased cognitive function and memory are known effects of untreated depression. Our study demonstrated that treatment of gender dysphoria with GAHT provided a tangible cognitive and memory benefit. The long-term impact of GAHT on cognition and memory is not known and deserves additional study. Limitations of this study included the absence of a cis-gender control group and inability to stratify data based on age, which may provide additional significance. Presentation: 6/2/2024

The senolytic drug ABT-263 accelerates ovarian aging in older female mice

Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility.

7838 Improvement of Cognition and Memory Scores in Transgender Individuals Within One Year of Initiating Gender-Affirming Hormone Therapy

Abstract Disclosure: C.M. Godar: None. S.C. De La Torre: None. O. Bonsu: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: The use of gender-affirming hormone therapy (GAHT) in transgender individuals is known to provide many beneficial health effects to reduce gender dysphoria, reduce depressive symptoms, and increase overall quality of life. Cognitive function and memory ability are known to be influenced by sex hormone levels in studies of hormone replacement therapy in post-menopausal women, but studies of GAHT’s effects on cognition and memory in transgender patients have been scarcely reported. We discuss a study of cognitive testing in transgender individuals before and after 12 months of gender-affirming feminizing or masculinizing hormone therapy using a validated cognitive assessment tool. Methods: A prospective study of 32 transgender patients aged 18-45 years was approved by IRB at an academic medical center. The Wechsler Memory Scale 4th edition (WMS®-IV, Pearson) was administered to 19 transgender females and 13 transgender males prior to initiation of GAHT and again after one year of GAHT use. Mean scores were analyzed and reported for five categories of cognitive and memory function: auditory memory (AMI), visual memory (VMI), visual working memory (VWMI), immediate memory (IMI), and delayed memory (DMI). Mean scores for baseline and 12-month data were analyzed for total population and male and female subgroups. Results: Baseline mean WMS-IV values for the total study population were: AMI 105 points, VMI 78 points, VWMI 107 points, IMI 88 points, DMI 91 points. Mean values after 12 months of GAHT were: AMI 120 points, VMI 81 points, VWMI 110 points, IMI 99 points, DMI 102 points. Mean percent change from baseline to 12 months was as follows: AMI 13.4%, VMI 8.9%, VWMI 2.6%, IMI 12.8%, DMI 13%. Similar patterns were noted for both gender subgroups. Discussion: It is well-known that transgender individuals are subject to higher rates of depression, anxiety, and suicidality compared to the general population. Decreased cognitive function and memory are known effects of untreated depression. Our study demonstrated that treatment of gender dysphoria with GAHT provided a tangible cognitive and memory benefit. The long-term impact of GAHT on cognition and memory is not known and deserves additional study. Limitations of this study included the absence of a cis-gender control group and inability to stratify data based on age, which may provide additional significance. Presentation: 6/2/2024

12539 Estrogen Type In Contraceptives Matters: Effects On Spatial Memory And Anxiety-Like Behaviors In A Female Rat Model

Abstract Disclosure: A.P. Hegwood: None. S. Kujawa: None. A.V. Prakapenka: None. According to U.S. Centers for Disease Control &amp; Prevention, ∼12% of the U.S. population uses combined oral contraceptives (COCs). Behavioral side effects are common factors in COC discontinuation. Management of COC-related side effects primarily centers around altering the synthetic ethinyl estradiol (EE) dose, the predominant estrogen in COCs. Estradiol valerate (EV) is a recently introduced natural estrogen alternative to EE. EE-containing COCs, such as EE/dienogest (DNG), were found to decrease free steroid hormone serum levels compared to EV-containing COCs, such as EV/DNG. In women and in female rodent models, steroid hormones (e.g., 17-ß estradiol (E2), testosterone) dose-dependently modulate spatial memory and anxiety-related behaviors. We hypothesized that in a rat model of hormonal contraceptive use, EE/DNG differentially modulates spatial memory and anxiety-like behaviors compared to EV/DNG, corresponding to circulating steroid hormone levels. Thirty-six young-adult (3-4-months-old) female rats were randomly assigned to EE/DNG (0.13µg EE and 8.6µg DNG per day), EV/DNG (8.6µg EV and 8.6µg DNG per day), or vehicle treatment (propylene glycol) continuously administered by subcutaneous osmotic pump. At four weeks of treatment, rats were tested on the delayed spontaneous alternation (dSA) task to evaluate spatial memory and the elevated plus maze (EPM) to evaluate anxiety-like behavior. Following EPM, serum was collected and analyzed for E2, progesterone, androstenedione, and testosterone levels using liquid chromatography-mass spectrometry and corticosterone levels using radioimmunoassay. Spontaneous alternation behaviors were similar across all three groups on the dSA. However, EE/DNG increased use of an egocentric navigational strategy, the use of consecutive turns, on the dSA compared to vehicle and EV/DNG. Egocentric strategy is likely mediated by the striatal memory system, engagement of which is elevated with stress and anxiety. Of note, EE/DNG decreased time spent in the open arms of the EPM compared to vehicle and EV/DNG, indicating increased anxiety-like behaviors with EE/DNG. Both EE/DNG and EV/DNG decreased androstenedione, testosterone, and E2 circulating levels compared to vehicle. Steroid hormone serum levels did not differ between EE/DNG and EV/DNG; 58% of EE/DNG serum samples were undetermined/below threshold for E2 levels, limiting statistical analysis. Altogether, we found that, compared to vehicle and the natural EV, the synthetic EE component in hormonal contraceptives elevates anxiety-like behaviors in female rats, an effect that corresponds to increased use of an egocentric navigational strategy on a spatial memory task. Our findings support the notion that estrogen type matters for behavioral outcomes associated with contraceptive use, identifying estrogen type as a possible tool for management of COC-related side effects. Presentation: 6/1/2024

8679 Case: The Sexual, Physical and Psychological Effects of Post-Finasteride Syndrome

Abstract Disclosure: E.M. Lonergan: None. S.M. Maher: None. I. Yaseen: None. D.B. O'Shea: None. Post-finasteride syndrome (PFS) is an increasingly recognised disorder with a myriad of physical and neuropsychiatric symptoms persisting for greater than three months in a small proportion of patients treated with Finasteride. We present the case of a 45-year-old male who was taking oral Finasteride for hair loss. He first presented to endocrinology services having stopped Finasteride after twenty years reporting new onset reduced libido, penile shrinkage, fatigue, new food intolerances and agitated depression which was the predominant symptom in this case. He described the emergence of gynaecomastia, which was evident on examination, as well as muscle atrophy. Biochemistry was unremarkable including testosterone 24.6 nmol/L (8.6-29.0), oestradiol 100 pmol/L (50 – 159), LH 7.1 IU/L (1.7-8.6), FSH 16.8 IU/L (1.5-12.4), urinary free cortisol 177 nmol/24h (12-486) and urinary steroid profile. The patient was offered a trial of IM testosterone for 3 months followed by a course of hCG which he declined after discussing with patients online via a PFS patient forum citing anecdotal pseudo immune downregulation in this cohort. GLP-1 receptor agonist therapy was considered as a second-line treatment option. The patient expressed a preference for hydrocortisone treatment after conducting online research which has not been commenced due to a lack of evidence. The inhibition of 5-alpha-reductase in Finasteride-treated patients has been documented to cause reversible sexual dysfunction. However, with increasing case reports of PFS, it was included in the list of Rare and Genetic Diseases of the NIH in 2015. The syndrome encompasses symptoms and signs seen in our case, as well as erectile dysfunction, decreased ejaculatory volume, infertility, Peyronie’s disease, testicular pain, dry skin, memory problems and insomnia. Suicidal ideation was included in the product label as per FDA mandate in 2022. The literature is largely inconclusive regarding the underlying aetiology, duration, and severity of the disorder. A large retrospective study revealed 0.8% of patients developed sexual dysfunction with persistence in 33% of these cases after drug suspension, the main independent risk factor being drug treatment for longer than 7 months. Neuropsychiatric symptoms are likely related to the presence of 5-alpha-reductase isoforms in the brain with resulting alterations in CSF and plasma neuroactive steroid levels and metabolites. Evidence-based treatment options for PFS are limited. PFS is a rare but debilitating syndrome to which a subset of patients appears to be predisposed, but of which the pathophysiology is poorly understood. Further studies in this regard, as well as an exploration of effective treatment options are required. Presentation: 6/1/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

7985 Insights into the Menopausal Transition: A Comparative Analysis of Hypothalamic Reproductive Aging in Women and a Mouse Model of Menopause

Abstract Disclosure: J.C. Bloom: None. S.A. Pereira: None. E. Torres Jimenez: None. D.C. Page: None. V.M. Navarro: None. Menopause onset is the major determinant of reproductive lifespan in women and is characterized by the decline in estrogen production from the ovary. While much of our current understanding of the menopause transition in humans comes from a series of observational longitudinal studies initiated in the 1980s and 1990s, the mechanisms by which reproductive aging impacts healthy brain aging remains a profoundly under-studied aspect of women’s health. The hypothalamus, a hub of homeostatic and temperature regulation, is highly sensitive to changes in sex steroid levels. Recently, activation of the neurokinin 3 receptor (NK3R) by neurokinin B (NKB) has been linked to the onset of vasomotor symptoms (VMS) during menopausal transition. NKB is secreted by hypothalamic Kisspeptin, NKB, Dynorphin (KNDy) neurons in response to decreasing estradiol levels. Here, we present a comparative study of the expression trajectories of the KNDy genes (KISS1, TAC3, PDYN, respectively) and NK3R (TACR3) in hypothalamic samples of humans across menopause and a mouse model of peri- and post-menopause (short- and long-term ovariectomy (OVX), respectively). RNA-sequencing data of human and mouse hypothalamic samples revealed a high correlation in the expression profile of the KNDy/NK3R genes between both species. Further investigation has revealed a highly conserved pool of genes in human and mouse hypothalami that correlate with TACR3 upon decline of circulating sex steroids. Thus, by examining conserved gene expression patterns across this critical reproductive period, we have been able to identify novel candidate targets involved in menopausal transition which may serve to better elucidate the biology of menopause-associated conditions affecting the brain, such as VMS and cognitive decline. Presentation: 6/2/2024

7985 Insights into the Menopausal Transition: A Comparative Analysis of Hypothalamic Reproductive Aging in Women and a Mouse Model of Menopause

Abstract Disclosure: J.C. Bloom: None. S.A. Pereira: None. E. Torres Jimenez: None. D.C. Page: None. V.M. Navarro: None. Menopause onset is the major determinant of reproductive lifespan in women and is characterized by the decline in estrogen production from the ovary. While much of our current understanding of the menopause transition in humans comes from a series of observational longitudinal studies initiated in the 1980s and 1990s, the mechanisms by which reproductive aging impacts healthy brain aging remains a profoundly under-studied aspect of women’s health. The hypothalamus, a hub of homeostatic and temperature regulation, is highly sensitive to changes in sex steroid levels. Recently, activation of the neurokinin 3 receptor (NK3R) by neurokinin B (NKB) has been linked to the onset of vasomotor symptoms (VMS) during menopausal transition. NKB is secreted by hypothalamic Kisspeptin, NKB, Dynorphin (KNDy) neurons in response to decreasing estradiol levels. Here, we present a comparative study of the expression trajectories of the KNDy genes (KISS1, TAC3, PDYN, respectively) and NK3R (TACR3) in hypothalamic samples of humans across menopause and a mouse model of peri- and post-menopause (short- and long-term ovariectomy (OVX), respectively). RNA-sequencing data of human and mouse hypothalamic samples revealed a high correlation in the expression profile of the KNDy/NK3R genes between both species. Further investigation has revealed a highly conserved pool of genes in human and mouse hypothalami that correlate with TACR3 upon decline of circulating sex steroids. Thus, by examining conserved gene expression patterns across this critical reproductive period, we have been able to identify novel candidate targets involved in menopausal transition which may serve to better elucidate the biology of menopause-associated conditions affecting the brain, such as VMS and cognitive decline. Presentation: 6/2/2024

7561 Maternal Sucrose Consumption During Gestation Alone Does Not Affect Glucocorticoids and Aldosterone in the Fetal Brain and Blood of Rats

Abstract Disclosure: M.M. Jung: None. D.R. Seib: None. M. Idrissi: None. H.W. Chen: None. K.K. Soma: None. Sucrose (table sugar) is a common added sugar in foods and beverages. Sucrose intake is high worldwide, yet little is known about how sucrose affects the brain and hormones. We designed an isocaloric, macro/micro-nutrient matched control diet (1% kcal sucrose) and high-sucrose diet (26% kcal sucrose) paradigm where the two diets only differ in kcal from sucrose. In this paradigm, maternal high-sucrose diet intake alters glucocorticoids (GCs) which are steroid hormones that regulate numerous physiological processes including the stress response. 16 wk of maternal sucrose intake (10 wk before mating, 3 wk during gestation, and 3 wk during lactation) increases blood and brain corticosterone levels in adult female offspring. Moreover, 13 wk of maternal sucrose intake (10 wk before mating and 3 wk during gestation) increases 11-deoxycorticosterone (DOC, corticosterone precursor) and 11-dehydrocorticosterone (DHC, corticosterone metabolite) in maternal serum, and increases aldosterone in fetal blood and brain at embryonic day 19.5 (E19.5). These results suggest that long-term maternal sucrose intake is a stressor that alters GC and aldosterone signalling. It is unclear whether a maternal high-sucrose diet only during gestation alters fetal steroid levels, or whether long-term sucrose consumption before mating is necessary. Here, we investigate the effects of maternal sucrose intake during gestation only on GCs and aldosterone in the fetal blood and brain. We hypothesize that maternal sucrose intake only during gestation will alter GC and aldosterone signaling in the fetus. We predict that maternal sucrose consumption during gestation alone will increase GC and aldosterone levels in the fetal blood and brain. Female Long-Evans rats were fed either a high-sucrose diet or a control diet starting E0.5 (day of mating confirmation) (n=15/diet). On E19.5, we collected fetal brain and blood and microdissected the regions of the fetal brain that are sensitive to GCs and aldosterone: nucleus accumbens, amygdala, hypothalamus, ventral hippocampus, and ventral tegmental area. We measured a panel of 15 steroids including GCs and aldosterone in the fetal brain (0.8-1.6 mg/region) and blood (5 µL) using liquid chromatography-tandem mass spectrometry, the gold standard for steroid quantification. Maternal high-sucrose diet intake during gestation alone did not alter maternal food intake, maternal body mass, or litter size, but increased the percentage of male offspring per litter. Maternal sucrose intake did not alter DOC, corticosterone, or DHC levels in the fetal blood and brain regions. Aldosterone was not detected in the fetal blood and brain. These results suggest that maternal sucrose intake during gestation alone does not alter GC and aldosterone levels in the developing fetus and that a longer duration of maternal sucrose intake is needed to alter offspring endocrine physiology. Presentation: 6/1/2024