bluuebunny/crossref_metadata_2025_split huggingface dataset:
LBMON231 Virilization Secondary To Androgen Producing Ovarian Serous Cystadenoma
Authors: De Guzman Vernon Joseph , Vargas-Jerez Julia , Zahra Tasneem 
Published: November 2022

Abstract

Background
Ovarian cystadenomas are classically considered as 'non-functional' tumors and among the most common benign ovarian neoplasms. Most of these tumors are asymptomatic and found incidentally on pelvic examination or with ultrasound. In rare circumstances these tumors may present as functional with secretions of excess androgens that subsequently produce virilizing features.

Clinical Case
A 59 year old Hispanic female G3P3(3003) presented to the clinic for receding hairline and facial hair for a duration of almost 2 years. Her medical history included total abdominal hysterectomy, due to fibroids, syphilis treated in Dominican Republic, Obesity, Vitamin D deficiency. On examination patient had hirsutism and significant hair growth on the abdomen, axilla, chest and extremities. The clitoris was enlarged, had frontal blading and increased abdominal circumference. Initial laboratory studies showed total testosterone was elevated [264 ng/mL] and free testosterone was high normal [4.2 pg/mL], DHEA-Sulfate normal [29.2 ug/mL], CA 125 unremarkable [5 U/mL]. Repeat labs were done showed elevated total testosterone and free testosterone [276 ng/mL and 4.7 pg/mL respectively] Normal levels of DHEA [87ng/dL] and DHEA-sulfate [ug/mL], 17-Hydroxyprogesterone [64 ng/mL], FSH normal [41.7 IU/L], LH normal [26.6 IU/L], morning cortisol level was normal [ 7.1 ug/mL] and a normal response to 1 mg dexamethasone suppression test. Transvaginal/Transabdominal ultrasound showed a left adnexa of 11.7×5.5×8.3 cm and simple cystic mass with no internal septations or nodularity and unremarkable right adnexa. Imaging by CAT scan showed a 9 cm left adnexal mass likely cystadenoma with unremarkable liver, spleen, pancreas and adrenals. Considering the laboratory, imaging findings and onset of symptoms the androgen production favors left adnexal cyst as the origin and not from the adrenals. Patient then underwent bilateral salphingoophorectomy without any complications and pathology reports revealed left serous cystadenoma. During her 2 week and 3 month post op follow up, patient reports no improvement of her hirsutism and virilization while repeat labs postoperatively showed normalization of total [15 ng/mL] and free testosterone [1.5 ng/mL].

Conclusion
In conclusion, we report a rare case of androgen producing ovarian serous cystadenoma with virilizing features. References: 1. Wasay Nizam, Shah A, Cornwell E., Naab, Tammey, Williams Mallory. Postmenopausal virilization secondary to large ovarian cystadenoma with stromal hyperthecosis. 2021.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBMON233 Hormonebayes: A Novel Bayesian Toolbox For Analysis Of Pulsatile Hormone Dynamics
Authors: Voliotis Margaritis , Abbara Ali , Prague Julia K , Veldhuis Johannes D , Dhilo Waljit S , Tsaneva-Atanasova Krasimira 
Published: November 2022

Abstract
The hypothalamus is the central regulator of reproductive hormone secretion. Pulsatile secretion of gonadotropin releasing hormone (GnRH) is fundamental to physiological stimulation of the pituitary gland to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Furthermore, GnRH pulsatility is altered in common reproductive disorders such as polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA). LH is measured routinely in clinical practice using an automated chemiluminescent immunoassay method and is the gold standard surrogate marker of GnRH. LH can be measured at frequent intervals (e. g., 10 minutely) to assess GnRH/LH pulsatility. However, this is rarely done in clinical practice because it is resource intensive, and there is no user-friendly and accessible method for computational analysis of the LH data available to clinicians. Here we present hormoneBayes, a novel open-access Bayesian framework that can be easily applied to reliably analyze serial LH measurements to assess LH pulsatility. The framework utilizes parsimonious models to simulate hypothalamic signals that drive LH dynamics, together with state-of-the-art (sequential) Monte-Carlo methods to infer key parameters and latent hypothalamic dynamics. We show that this method provides estimates for key pulse parameters including inter-pulse interval, secretion and clearance rates and identifies LH pulses in line with the current gold-standard deconvolution method. We show that these parameters can distinguish LH pulsatility in different clinical contexts including in reproductive health and disease in men and women (e. g., healthy men, healthy women before and after menopause, women with HA or PCOS). A further advantage of hormoneBayes is that our mathematical approach provides a quantified estimation of uncertainty. Our framework will complement methods enabling real-time in-vivo hormone monitoring and therefore has the potential to assist translation of personalized, data-driven, clinical care of patients presenting with conditions of reproductive hormone dysfunction.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBMON273 Not All Men Are Created Equal
Authors: van Rooyen Desmaré , Atkin Stephen L , Swart Amanda C 
Published: November 2022

Abstract

Background
Clinical assessment of androgens in the diagnosis of androgen excess, hypogonadism, androgen replacement or suppressive therapy and in anti-doping practices is generally limited to a few C19 steroids. More accurate evaluations may be gained with comprehensive steroid analysis. The aim of this study was to determine all major circulating adrenal and gonadal steroids together with the adrenal C11-oxy C19 steroids.

Methods
Serum androgens, mineralocorticoids, glucocorticoids, progesterones and C11-oxy steroids were determined in 71 healthy men, 18-35yrs, using ultra-performance convergence-chromatography tandem mass spectrometry. Data was analysed using GraphPad Prism Version 9.3.1.

Results
Profiles and inter-individual steroid concentrations differed considerably. Testosterone (25.2 nM) was detected in all subjects while dehydroepiandrosterone (DHEA) was undetectable in 18% of the subjects. Comparing subjects with DHEA, 11.14 (3.178-52.73) nM and those without DHEA identified steroids differing significantly (p≤0. 001; q values ≤5%): 11-OHA4 (4. 0 ±0.3 vs 1.6±0.3 nM), 16-hydroxyprogesterone (0.7±0. 07 vs 0.3 ±0.1 nM), corticosterone (15.5±1.8 vs 3.8±1.1 nM), 11-dehydrocorticosterone (4.5±0.3 vs 2±0.5nM), cortisol, (357±21.2 vs 157.9±29.3 nM) and cortisone (57.9±2.4 vs 35.3 ±5.4 nM). Dihydrotestosterone (∼4.3 nM) and 11-hydroxytestosterone (∼0.5 nM) were detected at comparable concentrations, however, at a frequency of 25% and &gt;90%, respectively (in both groups). 11-ketotestosterone levels were also comparable but below the limit of accurate quantification while present in ∼50% of the subjects. Epitestosterone levels were comparable (0.2±0. 02 vs 0.1±0. 03 nM), but higher in younger subjects 18-25 yrs (p&lt;0. 05).

Conclusions
Analysis of gonadal and adrenal steroids indicate greater circulating steroid heterogeneity than previously thought. Data shows that the often-disregarded adrenal C11-oxy C19 steroids contributed to 16% of the androgen profile. Furthermore, given that the C19 steroids were 1.8-fold lower in men without measurable DHEA, the functional oxyandrogens, 11-ketotestosterone and 11-hydroxytestosterone, would be of particular physiological importance due to their androgenic activity. Absence of measurable DHEA showed an overall modulated adrenal steroidogenic flux in these men, evident in the attenuated glucocorticoid production. Data underscores the modulatory role of cytochrome P450 11β-hydroxylase in these individuals, potentially impacting on diagnostic testing and evaluation.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP089 Effects Of Low-dose Oral Micronised Progesterone On Sleep, Psychological Distress And Breast Development In Transgender Individuals Undergoing Feminising Hormone Therapy: A Prospective Controlled Study
Authors: Nolan Brendan J , Frydman Aviva S , Leemaqz Shalem Y , Carroll Meg , Grossmann Mathis , Zajac Jeffrey D , Cheung Ada S 
Published: November 2022

Abstract

Objective
The role of micronised progesterone in hormone regimens for transgender individuals undergoing feminising hormone therapy remains uncertain. We aimed to determine the effect of oral micronised progesterone (progesterone) on sleep quality, psychological distress and breast development in transgender individuals undergoing feminising hormone therapy. Design: Prospective case-control study. Twenty-three transgender individuals on stable estradiol treatment newly commencing 100mg oral progesterone (n=23) and controls continuing standard care (n=19) were assessed over 3 months.

Methods
Pittsburgh Sleep Quality Index (PSQI), Kessler psychological distress scale (K10), and Tanner stage to assess breast development were assessed at 0 and 3 months. Non-parametric ANCOVA were used to compare differences between groups.

Results
Compared with controls over 3 months, there was no difference in PSQI (P=0.35), K10 (P=0.64) or Tanner stage (P=0.42). There was no significant difference in the proportion of individuals with clinically significant improvement in PSQI (25% vs. 22%, P=0.84). One individual had a significant deterioration in psychological distress that improved following cessation of progesterone.

Conclusions
Low-dose progesterone was not associated with changes in sleep quality, psychological distress, or breast development over three months follow-up, though there was significant inter-individual variability. Larger, placebo-controlled trials are required to further evaluate different doses of progesterone in feminising hormone therapy regimens.
Presentation: No date and time listed
ODP403 Diversity of Estrogen-Responsive Genes in Endometriotic Lesions
Authors: Izawa Masao , Taniguchi Fuminori 
Published: November 2022

Abstract

Background
Endometriosis has been accepted as an estrogen-dependent disease for more than two decades. So far, estrogen modulators that targeting estrogen depletion in endometriotic lesions have been expected as the first option of treatments to improve the symptoms associated with endometriosis. However, the limits of treatment are becoming apparent.

Objective
As the background of limits, we hypothesized the heterogeneity of genetic and/or epigenetic environments in endometriotic lesions (1). To test our hypothesis, we examined the expression profile of estrogen-responsive genes using endometriotic stromal cells as a model. Patients: Institutional Review Boards approved this project. We obtained informed consent from all patients. The chocolate cyst lining in the ovaries of patients with endometriosis was the source of endometriotic tissue. As a control, the eutopic endometrial tissues were obtained from uteri of premenopausal women who had uterine leiomyoma.

Methods
Stromal cells were prepared from endometriotic and endometrial tissues. ESR1 and ESR2 expression were evaluated using RT-PCR (2). For RNA-seq analysis of estrogen-responsive genes, total cellular RNAs from endometriotic cells treated with or without 10nM estradiol for 8hr were prepared. Following the quality control (concentration&gt;50ng/ul, RIN&gt;9), RNA samples were used for polyA+ selected library preparation and the strand-specific RNA-seq (NovaSeq, DNBSEQ-G400, 20M paired- end (PE) reads and 2×150bp PE/sample). Estrogen-responsive genes were extracted using RNA-seq bioinformatics analysis. Genes with adjusted p-values &lt; 0. 05 and absolute log2 fold changes &gt; 1 were extracted as estrogen-responsive genes (DESeq2 BP). Principal component analysis (PCA) was used to visualize sample-to-sample distances. Differential gene GO enrichment analysis was performed (GOseq. v1.34.1).

Results
1) wild type ERα mRNA expression in endometriotic cells was one-tenth of that in endometrial cells. wild type ERβ1 and the splice variant ERβ2 mRNAs were expressed in endometriotic cells at a comparable level of the ERα. 2) PCA suggested the presence of at least two cell types in endometriotic cells. 3) Cluster analysis of gene expression suggested the presence of 2 cell types: endometriotic cells with or without GATA6 expression (3). 4) Estrogen-responsive genes were significantly different among the cells examined. 4) Differential gene GO enrichment analysis suggested the diversity of gene expression profiles depending on the cells.

Conclusion
In the hope of overcoming the limits of endocrine-targeted therapy in endometriosis, we examined the estrogen-responsive genes in endometriotic cells. The finding suggests the diversity of estrogen-responsive genes in endometriotic lesions. References(1) Fertil Steril (2019) 111: 327–39. (2) Reprod Sci (2016) 23: 871-6. (3) Am J Reprod Immunol (2019) 81: e13078.
Presentation: No date and time listed
ODP405 Effects of Gonadotrope-Specific Knockout of Creb on HPG Axis Function in Mice
Authors: Hausken Krist , Quinn Alyssa , Kim Han , Boehm Ulrich , Carroll Rona , Kaiser Ursula 
Published: November 2022

Abstract

Background and Objective
Reproduction is regulated by FSH and LH, which are synthesized and secreted by pituitary gonadotropes in response to pulsatile hypothalamic GnRH in a frequency dependent manner. Low and high GnRH pulse frequencies preferentially increase Fshb and Lhb expression, respectively, mediated by preferential coupling to Gαs-PKA-Creb and Gαq-PKC-MAPK-AP1 signaling cascades in vitro. The mouse Fshb proximal promoter contains a half-AP1/half-CRE recognition motif that binds Creb in vitro, and mutation of this half-CRE results in loss of preferential GnRH stimulation of Fshb at low pulse frequencies in immortalized gonadotrope LβT2 cells. Therefore, the purpose of this study was to identify the direct role of Creb on gonadotropin regulation in vivo. We hypothesized that gonadotrope-specific deletion of Creb would influence pubertal timing and/or fertility due to reduced Fshb expression.

Methods and Results
Gonadotrope-specific Creb knockout (Creb1 fx/fx / Gnrhr GRIC/+; Creb KO) and control (Creb1 fx/fx) mice were generated by Cre-Lox recombination and markers for pubertal onset were evaluated. We observed no differences in body weights of Creb KO and littermate control mice in either females or males from postnatal day (PND) 21 to 3 months of age (n=9/genotype/sex). The age of vaginal opening, a marker of puberty onset in female mice, was not significantly different between female Creb KO (PND 28.4±0.5; n=21) and littermate control (PND 29.5±0.6; n=17) mice. Similarly, the age of first estrus, determined by vaginal lavage and cytology, was not significantly different between Creb KO mice (PND 37.6±1.9; n=9) and littermate controls (PND 36.6±2.2; n=8). Estrous cyclicity was normal over a three-week period in Creb KO and control mice, which spent similar amounts of time in diestrus/metestrus, proestrus, or estrus. Male Creb KO mice tended to show preputial separation at a younger age (PND 28.8±0.3; n=19) compared to littermate control (PND 29.6±0.3; n=22) mice, but the difference did not reach statistical significance (p=0. 06).

Conclusions
Deletion of Creb from pituitary gonadotropes did not affect the timing of pubertal onset in female mice, but we did observe a trend for male Creb KO mice to have advanced puberty, as measured by preputial separation. Normal pubertal timing does not preclude potential effects of Creb-mediated gonadotropin regulation on folliculogenesis, spermatogenesis, or fertility (including litter size), for which studies are ongoing.
Presentation: No date and time listed
ODP406 Effects of hormone replacement therapy on memory cognitive function in postmenopausal women: a systematic review and meta-analysis
Authors: Chen Yan , Chen Lin , Yao Jin , Chen Prof Gang 
Published: November 2022

Abstract

Objective
To investigate the effect of hormone replacement therapy (HRT) on memory cognitive function in postmenopausal women.

Methods
PubMed, Cochrane, Embase, Chinese Biomedical Literature Database (CBM)and web of ClinicalTrials.gov were systematically searched for randomized controlled trials comparing the effect of HRT on memory function in postmenopausal women to Placebo. The primary outcome of interest is memory cognitive function (measured by tests used in the study). We assessed pooled data by using random-effects model.

Results
Ten studies with 2818 participants were finally eligible for inclusion in the analysis. Compared with placebo, HRT showed no significant differences on logical memory including both immediate (weighted mean difference [WMD] 0.34, 95% CI: -0.73, 1.40) and delayed(0.99, 95% CI: -0.51, 2.48) recall in postmenopausal women, also no differences on short-delay (-0. 00, 95% CI: -0.37, 0.37) or long-delay (-0.19, 95% CI: -0.69, 0.31) recall of California Verbal Learning Test, but yielded an a mean reduction in digit span forward of -0.20 (95%CI: -0.36,-0. 03), with no significant difference in digit span total scores (-0.67, 95% CI: -1.58, 0.24) or backward (-0.10, 95%CI: -0.26, 0. 05). In women within 5 years of menopause, HRT still shows no harmful or beneficial effects on immediate (WMD 0.45, 95% CI: -0.75, 1.65) or delayed recall (WMD 1. 03, 95% CI: -0.93, 3. 00) of logical memory, but no detrimental effects on digit span forward (WMD -0.11, 95% CI: -0.72, 0.50).

Conclusion
This review suggests that HRT do not improve verbal memory in postmenopausal women, may even impair some domains of short-term memory. HRT may thus not be a potential therapeutic strategy to prevent memory decline in postmenopausal women.
Presentation: No date and time listed
ODP407 Effects of Leptin and Ghrelin on Ovarian Steroidogenesis and Involvement of BMP Action in Rat Granulosa Cells.
Authors: Nakano Yasuhiro , Kashino Chiaki , Hasegawa Toru , Iwata Nahoko , Soejima Yoshiaki , Suyama Atsuhito , Yamamoto Koichiro , Otsuka Fumio 
Published: November 2022

Abstract
Leptin and ghrelin are the two major hormones which regulate food intake and energy balance. They have also been reported to have pleiotropic functions, including the modulation of ovarian function via the hypothalamic-pituitary-ovarian system or in a direct manner to the ovaries. Blood leptin levels increase over the menstrual cycle and peak at the time of the luteinizing hormone (LH) surge. Leptin secreted from adipocytes acts on the hypothalamus and pituitary gland to stimulate the secretion of GnRH and gonadotropins. In the ovaries, high levels of leptin inhibit follicle-stimulating hormone (FSH)-induced steroid secretion and follicular development. Ghrelin, secreted by the stomach, has been reported to modulate GnRH secretion in the hypothalamus and to affect FSH and LH secretion, as well as steroidogenesis in the ovaries. Knockout of these hormones leads to impaired fertility. However, the mechanism of the direct effects of leptin and ghrelin on the ovaries has not been well elucidated. In the present study, we investigated the effects of leptin and ghrelin on the ovarian steroidogenesis using primary culture of rat granulosa cells, by focusing on the ovarian bone morphogenetic protein (BMP) system, which plays an important role in follicular development and steroidogenesis and acts as a luteinizing inhibitor. The results showed that treatment with leptin (1 to 300 ng/mL) did not affect either estradiol (E2) or progesterone (P4) production, but enhanced FSH-induced P4 production at low concentrations (10 ng/mL). On the other hand, treatment with ghrelin (1 to 300 nM) did not affect E2 and P4 production, but enhanced FSH-induced P4 production in a concentration-responsive manner. The mRNA levels of the follicular steroid synthases (StAR, P450scc, 3βHSD, 20αHSD) were examined. Leptin treatment enhanced 3βHSD mRNA levels. Both leptin treatment and ghrelin treatment decreased FSH-induced 20αHSD mRNA levels. However, both treatments decreased FSH-induced cAMP production. In addition, leptin treatment tended to suppress the transcriptional activity of Id-1 induced by BMP-6. Collectively, these results indicate that both leptin and ghrelin enhance FSH-induced P4 production by suppressing BMP signaling in rat granulosa cells. It was thus suggested that leptin and ghrelin which regulate food intake and energy balance can also act as endogenous regulators for the modulation of P4 synthesis and luteinizing process by ovarian follicles.
Presentation: No date and time listed
ODP411 Frequency of hyperandrogenism in Mexican adult women with type 1 diabetes mellitus: a pilot study.
Authors: García-Sãenz Manuel , Ramírez-Rentería Claudia , Ferreira-Hermosillo Aldo , López-Juãrez Nitzia G , Lobaton-Ginsberg Miry 
Published: November 2022

Abstract

Background
Hyperandrogenism has been described with different frequencies in populations of women and adolescents with type 1 diabetes (T1D). Ethnic differences account for variation in genetic causes as well as clinical and metabolic parameters for diagnosis. We aimed to evaluate clinical, laboratory and imaging tests of a sample of adult women with T1D in order to calculate a valid sample size for further studies in our population, which presents a high prevalence of metabolic syndrome.

Materials and methods
we included the first patients from a group of 55 women with T1D between the ages of 18 and 45. Blood samples were performed in the early follicular phase and ultrasound in the follicular phase. Ferriman-Gallwey score was evaluated by two independent trained observers. We excluded patients with hysterectomy or oophorectomy or continuous use of hormonal contraceptives in the last 3 months or previous cosmetic treatments. Non-parametric tests were calculated using SPSS v 21. 0 with a p&lt;0. 05. Results are expressed in medians and interquartile ranges (IQR) or percentages.

Results
27 women had full workup, their median age was 32 years (IQR 25-40), the age of diagnostic of T1D was 13.5 years (IQR 10-20), 55.5% had a BMI &gt;25 kg/m2, HbA1c was 8.6% (IQR 7.3-10) and used 0.83 UI insulin/kg/day (IQR 0.62-1. 06). Using the Rotterdam criteria 40.7% had PCOS, and 33.3% by stricter criteria based in hyperandrogenemia (AE-PCOS and NIH). A Ferriman-Gallwey score of 9 or higher was agreed in 40.7% of the cases with a inter-observer kappa of 77% (p&lt;0. 001), 22.8% had elevated total testosterone, and 14.8% had DHEA-S above the upper limit of normal for age, the 55.6% had ultrasonographic criteria for PCOM. We eliminated 4 cases with 17-OHP progesterone of &gt; 2. 0ng/mL, and 1 with undiagnosed primary ovarian insufficiency. A sample size of 41 is needed to achieve a power of 80% in this setting. Insulin doses were higher in patients with SOP compared with other patients (1. 06IU/kg/day in patients with PCOS and 0.73IU/kg/day in patients without PCOS, p=0. 013, IC -0.59; -0. 07).

Discussion and conclusions
Our population shows a high frequency of hyperandrogenism, which affects the patients reproductive capabilities, but also may be related to adverse metabolic outcomes. Hyperandrogenism may be related to PCOS, but also to undiagnosed comorbidities, which require further endocrine evaluation. More awareness is needed in the diagnosis of these conditions in our population.
Presentation: No date and time listed