Sex Hormone-binding Globulin Levels Research Articles

Metabolic Syndrome in Reproductive Age Women of Various Ethnic Groups. Neuroendocrine Status and Lipid Peroxidation System.

We analyzed the state of neuroendocrine regulation and LPO-antioxidant defense systems in reproductive age women with metabolic syndrome (MetS), representatives of the Russian and Buryat ethnic groups. Compared to the corresponding control groups, women from the Russian ethnic group with MetS had elevated levels of thyroid-stimulating hormone and free androgen index (FAI) and reduced levels of sex hormone-binding globulin, while women from the Buryat ethnic group had increased levels of prolactin and FAI. Changes in the LPO system in women of the Russian ethnic group with MetS consisted in an increase in the levels of substrates with double bonds, TBA-reactive substances, and fat-soluble vitamins. Buryat women with MetS had a higher content of primary oxidation products and reduced levels of glutathione. The results of the study indicate a hyperandrogenic shift in the neuroendocrine regulation system, as well as compensatory influences from different parts of the antioxidant defense system in women of reproductive age with MetS, depending on their ethnicity. These findings indicate the need for assessing and monitoring the levels of these metabolites in women with MetS, considering their ethnicity.

Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia

Objective: To investigate the correlations of cognitive function with serum levels of homocysteine (Hcy), sex hormone binding globulin (SHBG), and leptin in patients with schizophrenia. Methods: This was retrospective study. This study included 58 patients with schizophrenia (SCZ) as observation group and 60 clinically healthy individuals as control group admitted to Xiangshan County Hospital of Traditional Chinese Medicine Medical and Health Group Third Hospital from March 2022 to June 2023. Serum levels of Hcy, SHBG, and leptin in the two groups were measured, and Pearson correlation analysis was conducted to investigate the correlations between the Hcy, SHBG, and leptin levels and the psychiatric symptoms and cognitive function in the observation group. Results: The Hcy and SHBG levels in the observation group were significantly higher than those in the control group (p<0.05, respectively), and the leptin level was lower than that in the control group (p<0.05). The observation group scored significantly lower than the control group for each dimension of the MCCB (p<0.05, respectively). In the observation group, Hcy was positively correlated with negative symptoms and the PANSS total score (p<0.05, respectively) and was negatively correlated with scores for the leptin was negatively correlated with negative symptoms and the PANSS total score (p<0.05, respectively) and was positively correlated with scores for speed of processing (SOP), WMS-III, BVMT, and MSCEIT (p<0.05, respectively). Conclusions: Increased levels of Hcy and SHBG and decreased leptin are strongly associated with the occurrence of cognitive impairment in SCZ cases. Therefore, clinical observation and monitoring of these markers can help identify changes in patient conditions. doi: https://doi.org/10.12669/pjms.40.10.8923 How to cite this: Xu Y, Qian X, Zhang M, Liang M. Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia. Pak J Med Sci. 2024;40(10):2319-2323. doi: https://doi.org/10.12669/pjms.40.10.8923 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Associations of co-exposure to polycyclic aromatic hydrocarbons and heavy metals with sex steroid hormones among children aged 6-19 years.

Introduction Polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are endocrine-disrupting chemicals (EDCs) that may have a combined effect on sex hormone levels in children. This study investigated the correlations between co-exposure to PAHs and HMs and levels of sex steroid hormones in children. Methods We employed the data from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016, including 1,167 participants aged 6-19 years. Sex hormone indicators include testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), free androgen index (FAI), and the TT/E2 ratio. 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. Results Co-exposure to PAHs and HMs was associated with a 16.2% reduction [95%CI (-0.321, -0.004)] in SHBG level among prepubertal males and a 16% reduction [95%CI (-0.30, -0.03)] in E2 level among pubertal males by the weighted quantile sum (WQS) regression, and cadmium (Cd) and mercury (Hg) contributed the highest weight respectively. In the Bayesian kernel machine regression (BKMR) model, co-exposure to PAHs and HMs was positively associated with TT/ E2 in pubertal males and negatively correlated with FAI in pubertal females, and 1-hydroxypyrene (1-PYR) and Cd were the most important components respectively. Conclusions Co-exposure to PAHs and HMs was associated with sex hormone levels in children. These findings highlight the necessity for preventing the effects of these chemicals on sex hormones.

Use of calculated free testosterone in men: advantages and limitations.

Due to technical requirements and high cost, equilibrium dialysis-free testosterone (T) measurements are not commonly available in clinical practice. Clinicians rely on calculated free T (cFT) as a proxy. This review discusses using free T as a second-line assessment, highlighting its relevance in preventing misdiagnosis and overtreatment of male hypogonadism. While there is consensus on measuring total T - comprising sex hormone-binding globulin (SHBG)-bound, albumin-bound, and free T - as a first step in diagnosing male hypogonadism, evidence confirms that aging and conditions like obesity influence both total T and SHBG levels. Furthermore, low free T has been associated with symptoms of androgen deficiency, even in men with normal total T. Clinicians should, however, be aware of limitations of free T calculations, particularly the lack of standardization. Recent developments include establishing age-stratified free T reference ranges measured by equilibrium dialysis. Free T remains a subject of longstanding controversy. Factors such as age and obesity can alter total T and SHBG levels. Free T serves as a second-line indicator of androgen exposure, taking SHBG fluctuations into account. Given that commonly used free T calculators only provide approximations of free T, there is a need to further standardize free T calculators.

Nonlinear association of sex hormone-binding globulin levels and chronic kidney disease, an analysis based on the National Health and Nutrition Examination Survey (NHANES) 2013–2016

Studies on the relationship between serum sex hormone-binding globulin (SHBG) levels and chronic kidney disease (CKD) remain limited and inconclusive. Therefore, this study aims to evaluate the effects of SHBG on CKD in a nationally representative population. We included a total of 7713 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Multivariate logistic regression models were utilized to evaluate the association between SHBG levels and CKD, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Additionally, we employed a restricted cubic-spline regression model to explore potential dose-response associations. Among the participants, 4030 (52.2%) were women, and CKD was observed in 13.50% (1043/7713). After adjusting for various variables, SHBG levels were found to be associated with the risk of CKD (OR: 1.24; 95% CI: 1.11–1.38), indicating a 24% higher risk of CKD for SHBG levels (log2-transformed). A comparison between the highest quartile (Q4) and the lowest quartile (Q1) of SHBG levels revealed an OR of 1.51 (95% CI: 1.17–1.95) for CKD prevalence. Notably, while the association between SHBG and the risk of CKD disappeared when SHBG levels were <46.1 nmol/l, it existed when SHBG levels exceeded 46.1 nmol/l. Taken together, these findings indicate nonlinear correlations between serum SHBG levels and CKD, with the inflection point occurring at approximately 46.1 nmol/l, which suggest that SHBG levels could serve as a useful marker for assessing CKD risk, with potential applications in early detection and management strategies.

Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.

Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits. The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences. Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound. The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovulation, the use of pulsatile GnRH treatment seems to be equally effective in both groups. Similar to FHA-non-PCOM patients, pulsatile GnRH therapy would be more efficient than exogenous gonadotropins in FHA-PCOM patients. Women with FHA-PCOM present a special sub-population of FHA patients. The diagnostic pitfall of FHA-PCOM should be emphasized in clinical guidelines about FHA and PCOS. The fact that almost half of the women with FHA have an ovarian follicle excess (i.e. PCOM) in face of low gonadotropin serum levels suggests that the intra-ovarian regulation of folliculogenesis is subject to individual variations, for unknown reasons, either genetic or epigenetic. Further studies are needed to investigate this hypothesis. Not applicable.

9224 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p&amp;lt;0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p&amp;lt;0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. Presentation: 6/3/2024

6961 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p&amp;lt;0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p&amp;lt;0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. Presentation: 6/3/2024

9224 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p&amp;lt;0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p&amp;lt;0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. Presentation: 6/3/2024

6961 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p&amp;lt;0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p&amp;lt;0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. Presentation: 6/3/2024

8162 A Unique Presentation of Ovarian Steroid Cell Tumor Causing Hyperandrogenism in a Postmenopausal Woman

Abstract Disclosure: A. Rehan: None. M. Pandey: None. I. Goyal: None. E. Punni: None. N. Shakir: None. Background:­­­ Steroid cell tumors of the ovary are a rare entity, constituting less than 0.1% of all ovarian tumors. These tumors can present with diverse endocrine and paraneoplastic effects, including androgen excess and polycythemia. Hyperandrogenism in females can lead to hirsutism, virilization, alopecia, menstrual irregularities, acne, and emotional changes, with complications including hyperlipidemia and insulin resistance. There are various causes of androgen excess in a female including polycystic ovary syndrome (PCOS), androgen-secreting tumors, Cushing’s syndrome, and congenital adrenal hyperplasia. In a postmenopausal woman displaying signs of androgen excess, one must consider androgen-secreting tumors, and even the rare ovarian steroid cell tumor as a possible cause. Clinical Case: A 62-year-old female with type 2 diabetes mellites, obstructive sleep apnea, anxiety and depression initially presented to her primary care provider with fatigue, light-headedness, and weight loss. Initial blood work done revealed a hemoglobin greater than 20 g/dL (NR 12-16) and hematocrit greater than 60% (NR 36-48), requiring several sessions of phlebotomy. Symptoms persisted and she was finally referred to a hematologist who noted physical exam findings of hirsutism and virilization, including temporal hair loss and excess facial/body hair growth. Other concerning signs included clitoromegaly, decrease in chest size, and deepening voice. Menopause had occurred at age 50, and the patient did not have any issues with fertility during her reproductive years. Biochemical evaluation revealed testosterone level of greater than 1500 ng/dL (NR 19-82) with normal sex hormone binding globulin level, DHEA-S 652 ug/dL (NR 29-220), appropriately suppressed FSH/ LH, and normal salivary cortisol levels. Tumor markers showed normal CEA, and alpha fetoprotein but elevated CA 125 to 80.5 U/ml (NR &amp;lt; 38.1). Pelvic ultrasound demonstrated a 12 cm heterogeneously echoic, vascular right adnexal mass concerning for ovarian malignancy. Pelvic MRI showed a 9.8 cm right sided cystic and solid adnexal mass. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, peritoneal biopsies, and omentectomy. Pathology revealed a stage IA steroid cell tumor measuring 11.4 cm. After resection, the patient reported improvement in facial hair and fatigue. Labs showed normalization of hemoglobin, hematocrit, and testosterone levels. Conclusion: This rare case highlights the importance of considering steroid cell tumor as a cause of polycythemia with hyperandrogenism. Timely diagnosis and intervention play a critical role in preventing irreversible virilization, mitigating malignant risks, and, in certain instances, preserving fertility. Generally, the prognosis is favorable, and symptom and lab normalization is often achieved through surgical resection. Presentation: 6/2/2024

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

8039 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

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

8039 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

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

7896 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

Investigating the Genetic Association of 40 Biochemical Indicators with Parkinson's Disease.

The mechanisms of Parkinson's disease (PD) are not fully understood, which hinders the development of effective therapies. Research indicates that lower levels of biochemical indicators like bilirubin, vitamin D, and cholesterol may elevate the risk of PD. However, clinical studies on abnormal levels of biochemical indicators in PD patients' circulation are inconsistent, leading to ongoing debate about their association with PD. Here, we investigate the genetic correlation between 40 biochemical indicators and PD using a bidirectional two-sample Mendelian randomization (MR) approach to uncover potential causal relationships. Data from genome-wide association studies (GWAS) were utilized, with genetic variations from specific lineages serving as instrumental variables (IVs). The methodology followed the STROBE-MR checklist and adhered to the three principal assumptions of MR. Statistical analyses employed methods including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Biochemical indicators including albumin, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) showed significant associations with PD risk. Elevated levels of albumin (OR = 1.246, 95% CI 1.006-1.542, P = 0.043) and SHBG (OR = 1.239, 95% CI 1.065-1.439, P = 0.005) were linked to higher PD risk. Conversely, increased CRP levels (OR = 0.663, 95% CI 0.517-0.851; P = 0.001) could potentially lower PD risk. The robustness of the results was confirmed through various MR analysis techniques, including assessments of directional pleiotropy and heterogeneity using MR-Egger intercept and MR-PRESSO methods. This study systematically reveals, for the first time at the genetic level, the relationship between 40 biochemical indicators and PD risk. Our research verifies the role of inflammation in PD and provides new genetic evidence, further advancing the understanding of PD pathogenesis. The study shows a positive correlation between albumin and SHBG with PD risk and a negative correlation between CRP and PD risk. This study identifies for the first time that SHBG may be involved in the onset of PD and potentially worsen disease progression.