DHEAS Levels Research Articles

Yoga, Physical Therapy and Home Exercise Effects on Chronic Low Back Pain: Pain Perception, Function, Stress, and Quality of Life in a Randomized Trial.

Low back pain is a common health problem. In this study, we investigated the effects of yoga, physical therapy (PT), and home exercise (HE) on pain perception, function, stress, and quality of life in chronic low back pain (cLBP). We randomly assigned 54 participants to three distinct treatment groups: (a) a physical therapy group (PT) who received spinal stabilization exercises (SSE) combined with local heat and transcutaneous electrical stimulation; (b) a home exercise group (HE) who received SSE as part of the home program; and (c) a yoga group who received yoga exercises. The primary outcome measures were a Visual Analog Scale (VAS) for measuring pain, and the Oswestry Disability Index (ODI) to measure function. Secondary outcome measures were the Tampa Kinesiophobia Scale (TKS), Central Sensitization Inventory (CSI), pain sensitivity (L3 and deltoid R/L PPTs), Spielberger State-Trait Anxiety Inventory (STAI), plasma cortisol and DHEA-S levels, Transversus Abdominis (TrA) muscle activation, and the Nottingham Health Profile (NHP). Assessments were conducted before and after a six-week intervention period. All three groups demonstrated improvements in pain on the VAS, function on the ODI, pain sensitivity on the L3 and deltoid R/L PPTs, CSI, anxiety on the STAI, TrA muscle activation, and quality of life on the NHP (p < .05). The PT group exhibited a more pronounced improvement on the ODI score (p < .05) than the other groups. Cortisol levels only decreased in the PT group (p < .05). The exercises did not impact DHEA-S and NHP-S parameters. Thus, all interventions resulted in decreased stress, pain intensity, pain sensitivity, central sensitization, and improved function and quality of life; there was no singularly superior approach between interventions. These findings will aid in tailoring treatment programs for managing cLBP according to individual needs.

7135 Changes in 11-oxygenated androgens in healthy prepubertal children from ages 4, 6, to 8 years: a prospective cohort study

Abstract Disclosure: Y. Lee: None. K. Lee: None. J. Kim: None. Y. Lim: None. J.I. Kim: None. B. Kim: None. Y. Hong: None. J. Song: None. C. Shin: None. Y. Lee: None. Background: 11-oxygenated androgens (11-oxyandrogens) have been recognized for their important role in adrenarche or androgen excess conditions. However, the trajectory during childhood remains understudied. Herein, we examined the longitudinal changes in 11-oxyandrogens among healthy prepubertal children. Methods: In an ongoing prospective cohort study, 172 prepubertal children with available blood samples at the ages of 4, 6, and 8 years were included. Serum concentrations of 14 adrenal androgens and precursors, including dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), androstenedione (A4), testosterone (T), 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone (11OHT), and 11-ketotestosterone (11KT) were assessed using liquid chromatography-tandem mass spectrometry. Repeated measures ANOVA was used to analyze the changes in adrenal androgens across age groups. Linear mixed model analysis was used to evaluate factors associated with adrenal hormone levels during 4 to 8 years of age. Results: Among 172 prepubertal children (107 boys, 65 girls), 11OHA4 was the predominant 11-oxyandrogen, exceeding concentrations of DHEA or A4. Serum 11KT level was higher than testosterone level from 6 years of age. Across age 4, 6, and 8 years, 11-oxyandrogens showed an increasing trend. Trajectories of 11OHA4, 11KA4, and 11KT significantly differed by sex (p for interaction &amp;lt; 0.05). Serum levels of 11OHA4 and 11KT consistently increased from 4, 6, to 8 years in both sexes, while 11OHT increased during 6-8 years (p &amp;lt; 0.05 for all). Serum 11KA4 levels increased during 4-6 years in boys and 6-8 years in girls (p &amp;lt; 0.05 for all). Girls showed higher levels of 11OHA4, 11KA4 at 4 years, 11OHT at 6 years, and 11KT at 4 and 6 years. Regarding classic adrenal androgens, DHEA, DHEAS, and A4 also exhibited increases in different patterns between sexes (p for interaction &amp;lt; 0.05) during 4-8 years. Girls had higher serum DHEA and A4 levels at 4 and 6 years, and DHEAS levels at 4 years (p &amp;lt; 0.05 for all). In boys, lower gestational age, lower birth weight z-score, and higher body mass index (BMI) z-score were correlated with elevated levels of DHEA and DHEA-S. Additionally, a higher BMI z-score was associated with increased levels of A4, 11OHT, and 11KT (p &amp;lt; 0.05 for all, multivariable models). In girls, a higher BMI z-score was linked to elevated DHEA levels, while a higher birth weight z-score was associated with increased A4 levels (p &amp;lt; 0.05 for all, multivariable models). Conclusion: In prepubertal children, 11-oxyandrogens showed increasing patterns similar to classic androgens, with sex-differences. Some 11-oxyandrogens were more predominant than classic androgens. This study suggests the importance of 11-oxyandrogens as biomarkers for zona reticularis development and adrenarche in prepubertal children. Presentation: 6/3/2024

7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma

Abstract Disclosure: R.C. Attah: None. I. Sirisena: None. Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref &amp;lt;30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref &amp;lt;1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg &amp;lt;205 pg/mL), normetanephrine 244.1 (ref &amp;lt;210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (&amp;gt;4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases. Presentation: 6/1/2024

6768 A Rare Presentation of Primary Adrenal Insufficiency with Hypertension &amp; Hypokalemia

Abstract Disclosure: A.M. San Hernandez: None. R. Alshantti: None. G. Espinoza Mercado: None. J.L. San Hernandez: None. Introduction: Adrenal Insufficiency is caused by the failure of the adrenal cortex to produce glucocorticoids +/- mineralocorticoids. This can be due to a defect in the adrenal cortex, or in the hypothalamic pituitary axis. The clinical manifestations are usually non-specific, ranging from mild vague symptoms to life threatening crisis. Therefore, diagnosis requires a high level of suspicion by providers. Unusual presentations of primary adrenal insufficiency (PAI) with hypertension and hypokalemia have been rarely described in the literature. We present a rare case of PAI with hypertension and hypokalemia. Case Presentation: A 68 years old female with a medical history of rheumatoid arthritis, hypothyroidism on Levothyroxine, chronic transaminitis, and bicytopenia presented to the hospital with a 6 weeks history of generalized weakness, loss of appetite, weight loss, and dizziness. Patient denied any diuretic or steroid use within the last 2 years. On arrival, she was afebrile, hypertensive (168/84mmHg), with normal oxygenation and pulse. Physical examination was unremarkable with normal volume status. Initial laboratory results showed low sodium 116 mEq/L, low serum osmolality 247 MEQ/kg, normal potassium 3.6 mEq/L, Creatinine 0.3 mg/dL &amp; BUN 9 mg/dL. She was initially started on IVF normal saline. Further workup revealed normal TSH &amp; FT4 levels. Urine study showed urine osmolality (477 MOSM/KG), &amp; urine sodium (127 mEq/L). Given these findings, SIADH was suspected and fluid restriction was started. Sodium level continued to be low with minimal improvement to 120 mEq/L, potassium levels also dropped (3.3-3.2 mEq/L), requiring daily replacement. BP remained elevated ranging from 150s to 160s systolic and 80s to 90s diastolic. Hypertension was controlled with her home medication Amlodipine. Although atypical presentation with hypertension &amp; hypokalemia, the diagnosis of adrenal insufficiency was considered. Laboratory evaluation showed low morning cortisol 5.2 ug/dL, with album level 3.5 g/dL. Cosyntropin stimulation test showed 1.3 ug/dL (at baseline), 9.9 (30 min post administration), and 14.4 (1 hour post administration); results confirming PAI. ACTH, Renin, Aldosterone, &amp; DHEAS levels were normal. CT adrenal was normal. Patient was started on hydrocortisone; some of her symptoms &amp; Na level improved. Further investigation of the etiology of PAI and possible hyperaldosteronism is pending outpatient follow up. Conclusion: Adrenal insufficiency is a life threatening condition with serious consequences if diagnosis is missed. It manifests by a wide spectrum of symptoms and signs, some can be masked by the presence of other comorbid conditions leading to atypical presentations. Our case highlights the importance of maintaining a high level of suspicion of adrenal insufficiency in patients with atypical presentation, including those with hypertension &amp; hypokalemia. Presentation: 6/3/2024

Endocrine Characteristics and Obstetric Outcomes of PCOS Patients with Successful IVF and Non-IVF Pregnancies.

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

Comparison of clinical, hormonal, pathological and treatment outcomes of ectopic Cushing's syndrome by sex: results of a multicenter study.

To compare clinical and hormonal data, neuroendocrine neoplasia (NEN) localization, treatment, and survival outcomes in ectopic Cushing's syndrome (ECS) by sex. Eleven experienced centers from our country participated in this retrospective study. The clinical and hormonal features, tumor imaging, pathological results, treatment modalities, and disease courses of the patients were evaluated. 28 female and 26 male patients with ECS were compared. The mean age at diagnosis, clinical characteristics, and hormonal evaluation results were similar. However, insulin-requiring diabetes mellitus (p = 0.04) and osteoporosis with fractures were more common in males (p = 0.03). While more patients with increased DHEA-S levels than the upper limit of normal were found to be higher in females, central hypothyroidism were higher in males (p = 0.02). At the diagnosis, 36 NENs (68% of females and 69% of males) were localized. Small cell lung carcinoma was higher in males (p = 0.02), and the frequency of other NENs was not different. Curative surgery was performed on 61% of females and 46% of males. Tumor size, Ki-67 labeling index, positive ACTH immunostaining, local lymph node and distant metastasis rates were similar in both sexes. In the follow-up, the tumor became visible in 7 of 10 females and 4 of 8 males after medical treatment and/or bilateral adrenalectomy. The remission rates (65% of females, 62% of males) and NEN-related death rates (14% of females, 30% of males) were similar. While ECS has a similar disease course in many aspects in males and females, hyperglycemia and osteoporosis are more severe in males.

Efficacy and safety of systemic spironolactone for acne in female patients in Sulaymaniyah teaching center of dermatology

Background and objectives: Acne vulgaris is a common disease in which hormone plays a role in its pathogenesis. Spironolactone, an androgen receptor blocker is used to treat acne. This study aims to evaluate the efficacy and safety of systemic spironolactone for acne in female patients in our local area. Methods: Open-label therapeutic trial study performed in the Sulaymaniyah teaching center of dermatology between 1/2/2022 - 1/9/2022, on a total of 47 patients aged 12-38 years old. Patients were divided into two groups in regard to age. Hormonal profile was assessed for all the patients. The 4-grade European classification system was used to classify the acne severity. Spironolactone 100 mg once daily at morning was given to them with follow up monthly for 3 months. Clinical response of the drug was assessed through a decrease in the number of the lesions. Signs and symptoms of the side effects were checked monthly. Results: In a total of 47 patients, 22 patients were ? 25 years and 25 patients were &gt;25 years. A significant difference was recorded in the response rate among the patients' ages and hormonal status of them as 83.3%, 61.1% and 50% of the complete response was in those who were &gt;25 years old and had abnormal testosterone and DHEA-s levels respectively. 100% of non-responder patients were below 25 years old with normal hormonal levels. 55.32% of the patients had no side-effect and menstrual irregularity was the most commonly reported side effect. Conclusion: Spironolactone is statistically considered an effective and safe line for the treatment of acne vulgaris particularly for acne in female over 25 with abnormal hormonal levels.

Endocrine-disrupting effects of bisphenol-A, thiamethoxam, and fipronil in hormone-naïve transmen compared to cis-women.

Current evidence suggests that the etiology of gender dysphoria (GD) is multifactorial: this, however, remains unclear. Endocrine-disrupting chemicals (EDCs) are one of the etiological hypotheses. In this study, we aimed to evaluate the urinary levels of bisphenol A (BPA), thiamethoxam, and fipronil in hormone-naïve transmen compared with case-matched cis-women as well as the relation between sex hormone levels and EDCs. Drug-naïve transmen diagnosed with GD and who were referred from the psychiatry outpatient clinic to the outpatient clinic of the Department of Endocrinology, Marmara University Hospital, were included in the study. These individuals were assessed for eligibility; 38 drug-naïve transmen and 22 cis-women were recruited as the control group. After anthropometric evaluation laboratory tests for FSH, LH, total testosterone, and estradiol were carried out, spot urine samples were collected to evaluate the urine metabolic excretion of BPA, thiamethoxam, and fipronil. We found that androgens, total testosterone, androstenedione, and DHEAS levels were significantly higher in transmen than in cis-women. Thiamethoxam was considerably higher in cis-women than in transmen, whereas fipronil and BPA levels were similar in both groups. A negative correlation was found between thiamethoxam and testosterone and between thiamethoxam and BPA levels. The available data suggest that the EDCs that we are most exposed to in our lives are not the only factor in GD development. Even transmen who have not taken hormone replacement have high testosterone levels; however, the mechanism has not as yet been elucidated. The challenge is to determine whether this is a factor leading to GD or a condition that develops in common with GD.

The human fecal endocannabinoidome mediator profile is mainly defined by the fecal microbiota and diet.

The endocannabinoid system and its extension, the endocannabinoidome (eCBome), are involved in numerous biological processes, notably energy homeostasis, across virtually all tissues. While the circulating eCBome mediator profile is associated with dietary intakes and metabolic status, an important knowledge gap resides in the identification of the precise determinants of these mediators in the gut lumen. We aimed at establishing the profile of eCBome mediators in human feces and investigating their association with circulating eCBome mediators, dietary intakes, metabolic status and gut microbiota composition. N-acyl-ethanolamines (NAEs) and 2-monoacyl-glycerols (2-MAGs) were profiled by LC-MS/MS in plasma and feces of a cross-sectional cohort (n = 195) and a short term dietary intervention trials (n = 21) with comprehensive dietary intakes and gut microbiota measures. Six NAEs and seven 2-MAGs were identified in fecal samples, but some, especially omega-3 derived mediators, were undetectable in the majority of samples. Fecal NAEs, and to a lower extent 2-MAGs, were positively albeit weakly correlated with the circulating levels of eCBome mediators. Fecal 2-AG, PEA and DHEA levels were positively associated with visceral adiposity and with some parameters of the metabolic profile. Dietary intakes of foods rich in fibers were associated with lower fecal levels of several eCBome mediators, while intakes of unsaturated fatty acids were associated with fecal 2-OG and 2-LG. Interestingly, gut microbiota diversity and composition were a strong correlate of the fecal eCBome profile. The fecal eCBome profile is associated with gut microbiota composition and dietary intakes, more than with the circulating profile. These results strengthen the hypothesis of an interrelation between the gut microbiome and eCBome signaling involved in the regulation of numerous host biological processes.

Iraqi Women with Hirsutism, Clinical and Biochemical Characteristics: Retrospective Study

This clinical research aimed to assess the frequency of different some clinical and biochemical features of hirsitusm among Iraqi women retrospectively. Methods: This study is a descriptive cohort study included 100 Hirsutism -affected females. A retrospective analysis of patient assessed using the recently approved diagnostic guidelines for hyper androgenic women with hirsutism Clinical features, family history and hormone levels results were analyzed. Results: At our presentation, the mean age of the 100 Hirsitusm-affected females was 26.9 years ranged of (13-42) years. The mean of BMI (kg/m2) for all patients was 27.38 (Overweight), 55% of women had oligomenorrhea ,3 % had amenorrhea and 42% had none. Associated features were highly Significant (P≤0.01), highly percentage was 39% acne, the low percentage was 6% Alopecia and Acne while 47% of them were none. About 90% of all patients had TSH&gt;0.5(U/mL) while 10 % had TSH &lt;=0.5(U/mL). The mean total serum testosterone level and free testosterone were 0.598 in 72%, 27.69 in 83% of the patients respectively. The mean serum prolactin level was 24.82 but the mean serum DHEA-S (µg/dL) were 328.62 in all patients. A family history was found in 40% of the patients. conclusion: In the current study the clinical characteristics of Hirsitusm was more common in women with a high Body Mass Index nearly a half of them. The most Associated features in hirsute women was Acne and Alopecia. Also more than half of them had oligomenorrhea. While a Biochemical Characteristics study revealed that 90% of hirsute women had hypothyroidism, There is a 37% increase in DHEAS levels, a 72% increase in total testosterone, and a 35% increase in prolactin. The prolactin and total serum testosterone level elevation were not severe. About 40% of the patients had a family history.

Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake.

Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. In this trial, 97 out of 100 randomized participants (mean age: 64.65±4.84years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3months of intervention, significant improvements in waist circumference (83.48±10.22 vs. 82.5±9.88 vs. 82.37±9.42cm, P for trend=0.046), 6-min walking distance (525.65±58.46 vs. 534.47±51.87 vs. 552.02±57.66m, P for trend=0.001), five-time sit-to-stand time (7.63±1.63 vs. 6.81±1.8 vs. 6.4±1.42s, P for trend <0.001), grip strength (26.74±6.54 vs. 27.53±6.99 vs. 28.52±7.09kg, P for trend <0.001), and MNA score (26.8±2.14 vs. 27.73±1.74 vs. 27.55±1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32±49.84 vs. 101.36±42.58 vs. 93.43±41.49mg/dL, P for trend=0.023), increased HDL-C (60.04±16.21 vs. 60±17.37 vs. 62.55±18.27mg/dL, P for trend=0.02), and DHEA-S levels (97.11±54.39 vs. 103.39±56.75 vs. 106.83±60.56μg/dL, P for trend=0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88±5811.68 vs. 11508.97±7151.08 vs. 11220.80±7190.71pg/mL, P for trend=0.016) in controls. The intervention group showed greater improvements in 6min walking distance (β=0.71, 95% CI: 6.88 to 40.79, P=0.006), five-time sit-to-stand test (β=-0.87, 95% CI: -1.59 to -0.15, P=0.017), MNA score (β=0.96, 95% CI: 0.20 to 1.71, P=0.013), serum triglycerides (β=-15.01, 95% CI: -27.83 to -2.20, P=0.022), LDL-C (β=-9.23, 95% CI: -16.98 to -1.47, P=0.020), and DHEA-S levels (β=9.98, 95% CI: 0.45 to 19.51, P=0.04) than controls. Protein-enriched soup with weekly exercise over 12weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

Metformin modulates corticosteroids hormones in adrenals cells promoting Mycobacterium tuberculosis elimination in human macrophages

Research suggests that both tuberculosis (TB) and type 2 diabetes mellitus (T2DM) have an immuno-endocrine imbalance characterized by dysregulated proinflammatory molecules and hormone levels (high cortisol/DHEA ratio), impeding an effective immune response against Mycobacterium tuberculosis (Mtb) driven by cytokines, antimicrobial peptides (AMPs), and androgens like DHEA. Insulin, sulfonylurea derivatives, and metformin are commonly used glucose-lowering drugs in patients suffering from TB and T2DM. For this comorbidity, metformin is an attractive target to restore the immunoendocrine mechanisms dysregulated against Mtb. This study aimed to assess whether metformin influences cortisol and DHEA synthesis in adrenal cells and if these hormones influence the expression of proinflammatory cytokines and AMPs in Mtb-infected macrophages. Our results suggest that metformin may enhance DHEA synthesis while maintaining cortisol homeostasis. In addition, supernatants from metformin-treated adrenal cells decreased mycobacterial loads in macrophages, which related to rising proinflammatory cytokines and AMP expression (HBD-2 and 3). Intriguingly, we find that HBD-3 and LL-37 can modulate steroid synthesis in adrenal cells with diminished levels of cortisol and DHEA, highlighting the importance of crosstalk communication between adrenal hormones and these effectors of innate immunity. We suggest that metformin's effects can promote innate immunity against Mtb straight or through modulation of corticosteroid hormones.

CYP21A2 Intron 2 Genetic Variants Might Be Associated with the Clinical Characteristics of Women with PCOS.

Pathogenic variants in the CYP21A2 gene are related to the classic and non-classic forms of congenital adrenal hyperplasia (CAH). However, the role of CAH carrier status in the clinical presentation of polycystic ovarian syndrome (PCOS) is still unclear. Moreover, the possible associations of different CYP21A2 gene polymorphisms with metabolic and reproductive abnormalities in PCOS have not been investigated. Therefore, the present study aims to examine the prevalence of the most common CYP21A2 pathogenic variant IVS2-13A/C>G (c.293-13A/C>G) in Eastern European women with PCOS and to evaluate the associations between common intron 2 genetic polymorphisms and the clinical symptoms of the patients. Sixty consecutively recruited women with PCOS were genotyped for the CYP21A2 intron 2 IVS2-13A/C>G genetic variant. Additionally, CYP21A2 intron 2 polymorphic variants rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) were tested and described. The clinical and hormonal characteristics were compared in women with PCOS and with polymorphic and wild-type genotypes. The heterozygous CYP21A2 pathogenic variant IVS2-13A/C>G was found in one of the investigated PCOS patients (1.67%) with a non-hyperandrogenic type of PCOS. The presence of the rs6453 (c.293-44G>T) T-allele was associated with increased levels of DHEAS (15.18 vs. 9.14 µmol/L, p = 0.003) compared to the wild-type genotype in the investigated group. The rs6451 (c.293-67C>A/G) minor alleles were associated with an earlier age of menarche in the patients (12.0 vs. 13.0 years, p = 0.007). The polymorphic rs369651496 minor 6G allele was related to a better lipid profile in the women with PCOS, while the rs6474 variant modulated the blood pressure of the patients. The presence of CYP21A2 genetic minor alleles of rs6467 (IVS2-13A/C, c.293-13A/C), rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) might modulate the adrenal androgens, age of menarche, and metabolic features in women with PCOS. Further studies on 21-hydroxylase genetic variants (pathogenic and polymorphisms) in different ethnic groups might help reveal the influence of adrenal steroidogenesis on PCOS development, clinical manifestations, and lifelong cardiovascular risks.

P-616 Impact of Dehydroepiandrosterone sulfate and Free Androgen Index on pregnancy and neonatal outcomes in PCOS patients

Abstract Study question What were the effects of free androgen, DHEAS on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS ? Summary answer PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). What is known already Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by different source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear. Study design, size, duration A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 μmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy. Participants/materials, setting, methods This retrospective cohort study included 1647 PCOS patients. The diagnosis of PCOS was based on the Rotterdam criteria.Exclusion criteria included patients with congenital adrenal hyperplasia, androgen-secreting masses, oocyte donation cycles, and PGT cycles. Main results and the role of chance Higher FAI levels (&amp;gt;6.4) were associated with decrease in clinical pregnancy rate (PR) (58.91% vs. 51.47%, p = 0.064), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011), cumulative pregnancy rate (CPR) (p = 0.032), and cumulative live birth rate (p = 0.032). When DHEAS levels exceeded 9.5 μmol/L, there was a significant decrease in clinical PR (60.33% vs. 49.55%, P = 0.008), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (p = 0.031) and cumulative live birth rate (CLBR) (p = 0.031). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (45.95%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 58.10%, while an elevation in DHEAS alone is associated with a pregnancy rate of 61.44%, both of which are lower than when neither FAI nor DHEAS are elevated(62.73%). The live birth rates exhibit a similar trend(30.00%vs40.00%vs41.83%vs44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR. Limitations, reasons for caution Firstly, the data used to develop the model were obtained from a single center with a relatively small sample size. Secondly, the patients included in this study were predominantly of slim physique with a lower proportion of obesity. Wider implications of the findings Both adrenal-derived DHEAS and ovarian-derived FAI are responsible to the unfavorable pregnancy outcomes in lean PCOS women. Trial registration number 2020B1212060029

Folliculogenesis and steroidogenesis alterations after chronic exposure to a human-relevant mixture of environmental toxicants spare the ovarian reserve in the rabbit model

BackgroundIndustrial progress has led to the omnipresence of chemicals in the environment of the general population, including reproductive-aged and pregnant women. The reproductive function of females is a well-known target of endocrine-disrupting chemicals. This function holds biological processes that are decisive for the fertility of women themselves and for the health of future generations. However, insufficient research has evaluated the risk of combined mixtures on this function. This study aimed to assess the direct impacts of a realistic exposure to eight combined environmental toxicants on the critical process of folliculogenesis.MethodsFemale rabbits were exposed daily and orally to either a mixture of eight environmental toxicants (F group) or the solvent mixture (NE group, control) from 2 to 19 weeks of age. The doses were computed from previous toxicokinetic data to reproduce steady-state serum concentrations in rabbits in the range of those encountered in pregnant women. Ovarian function was evaluated through macroscopic and histological analysis of the ovaries, serum hormonal assays and analysis of the expression of steroidogenic enzymes. Cellular dynamics in the ovary were further investigated with Ki67 staining and TUNEL assays.ResultsF rabbits grew similarly as NE rabbits but exhibited higher total and high-density lipoprotein (HDL) cholesterol levels in adulthood. They also presented a significantly elevated serum testosterone concentrations, while estradiol, progesterone, AMH and DHEA levels remained unaffected. The measurement of gonadotropins, androstenedione, pregnenolone and estrone levels yielded values below the limit of quantification. Among the 7 steroidogenic enzymes tested, an isolated higher expression of Cyp19a1 was measured in F rabbits ovaries. Those ovaries presented a significantly greater density/number of antral and atretic follicles and larger antral follicles without any changes in cellular proliferation or DNA fragmentation. No difference was found regarding the count of other follicle stages notably the primordial stage, the corpora lutea or AMH serum levels.ConclusionFolliculogenesis and steroidogenesis seem to be subtly altered by exposure to a human-like mixture of environmental toxicants. The antral follicle growth appears promoted by the mixture of chemicals both in their number and size, potentially explaining the increase in atretic antral follicles. Reassuringly, the ovarian reserve estimated through primordial follicles number/density and AMH is spared from any alteration. The consequences of these changes on fertility and progeny health have yet to be investigated.

The association between female sexual function and metabolic features of the polycystic ovary syndrome in Turkish women of reproductive age

Objective To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age. Method This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls. Results Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls. Conclusion PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.

Hypogonadism as a consequence of craniopharyngioma in female patients: comparison of childhood and adult onset and effects of estrogen replacement therapy.

(1) to compare clinical, biochemical features in female patients with hypoestrogenism due to childhood- and adult-onset CP; (2) to reveal effects of estrogen replacement therapy in female patients with childhood-onset CP. Thirty-seven women that received specific treatment for CP in the period from 1980 to 2019 were recruited: 21 with childhood-onset and 16 with adult-onset CP. Clinical and hormonal characteristics were evaluated. Seventeen-beta-estradiol 2 mg and dydrogesterone 10 mg in sequential regiment was used in 18 childhood-onset cases. Mean follow-up was 31 months. Amenorrheic women with childhood- and adult-onset CP presented with the same complaints except for lack of genital hair and breast hypoplasia, which were common in patients with childhood-onset CP. BMI was lower in childhood-onset CP group, as was the proportion of overweight patients. They had more favorable lipid profile. The levels of estradiol, testosterone and DHEA-S were low and did not differ. Uterine and ovary volumes were reduced in all patients, but the decline was noticeable in the childhood-onset group. Mineral bone density of lumbar vertebrae was diminished in childhood-onset group. Estrogen therapy in these patients led to clinical improvement: increase in BMD in lumbar spine without negative changes in BMI and/or lipid profile. Study showed that women with childhood-onset CP had less negative metabolic changes. However, they have more pronounced breast and uterus hypoplasia and lower BMD in lumbar spine. The estrogen replacement therapy led to clinical improvement and BMD increase in lumbar spine without increase of BMI and/or lipid profile changes.

Are Young People with Turner Syndrome Who Have Undergone Treatment with Growth and Sex Hormones at Higher Risk of Metabolic Syndrome and Its Complications?

Metabolic syndrome (MetS), characterized by visceral obesity, glucose abnormalities, hypertension and dyslipidemia, poses a significant risk of diabetes and cardiovascular disease. Turner syndrome (TS), resulting from X chromosome abnormalities, carries health complications. Despite growing evidence of an increased risk of MetS in women with TS, its prevalence and risk factors remain under investigation. These considerations are further complicated by the varying timing and dosages of treatment with growth hormone and sex hormones. We conducted a cross-sectional study comparing 44 individuals with TS with 52 age-matched control subjects. Growth hormone treatment in the study group was administered for varying lengths of time, depending on clinical response. We collected anthropometric, metabolic, endocrine and body composition data. Statistical analyses included logistic regression. Baseline characteristics, including age, BMI and height, were comparable between the TS and control groups. Hormonally, individuals with TS showed lower levels of testosterone, DHEA-S, and cortisol, as well as elevated FSH. Lipid profiles indicated an atherogenic profile, and the body composition analysis showed increased visceral adipose tissue in those with TS. Other metabolic abnormalities were common in individuals with TS too, including hypertension and impaired fasting glucose levels. The risk of MetS components was assessed in subgroups according to karyotypes: monosomy 45X0 vs. other mosaic karyotypes. Logistic regression analysis showed a significant association between increased visceral adipose tissue in subjects with TS. Those with metabolic complications tended to have less muscle strength compared to those without these complications in both the study and control groups. This study highlights the unique metabolic and cardiovascular risk profile of individuals with TS, characterized by atherogenic lipids, higher levels of visceral adipose tissue and increased metabolic abnormalities. These findings underscore the importance of monitoring metabolic health in individuals with TS, regardless of age, BMI or karyotype, and suggest the potential benefits of lifestyle modification, building more muscle strength, and weight control strategies. Further research is needed to better understand and address the metabolic challenges faced by women with TS.

Physician and Adolescent Hirsutism Score Ratings and Their Concordance to Androgen Levels [ID 2683618

INTRODUCTION: Hirsutism affects 5–15% of reproductive-aged women. The gold standard for quantifying hirsutism is the modified Ferriman–Gallwey (mFG) score. This study explores whether adolescent and physician ratings of hirsutism using the mFG score, correlate with androgen levels in the setting of confounders like depilation. METHODS: Hispanic adolescent females with irregular menstruation and suspected polycystic ovary syndrome (PCOS) were recruited from obstetrics and gynecology clinics at TTUHSC El Paso between September 2021 and May 2023. Patients completed an intake questionnaire, completed PCOS laboratory testing, and rated their hair growth using the mFG visual scoring method. Providers used same the methods for rating hirsutism during the same visit. We estimated Lin’s concordance correlation and Bland–Altman agreement between patient and provider mFG ratings. Linear regression explored factors affecting score changes. Statistical analysis was done by STATA 17.0. RESULTS: Forty females participated in this study. The average age at enrollment was 16.19 with a mean (SD) mFG score of 10.55 (5.95) (physicians) and 18.29 (5.78) (adolescents). Adolescents reported higher mean mFG scores than physicians. There is a low level of agreement between the two groups (−7.95; 95% CI: −23.02, 7.12). Specifically, physicians underrated hirsutism scores for arm hair. Using unadjusted linear regression, DHEAS and 17-hydroxyprogesterone levels demonstrate the hormonal influence on hirsutism. CONCLUSION: Preliminary findings indicate discordance between physicians’ and patients’ mFG scores, possibly influenced by examination precision and patient perception. Physician-scored mFG, and evaluation of androgen levels, may serve as precise hirsutism markers for Hispanic adolescents.

Impact of dehydroepiandrosterone sulfate and free androgen index on pregnancy and neonatal outcomes in PCOS patients

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear.MethodsA retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy.ResultsHigher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR.ConclusionIn conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.