bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic PCOS Features Are Ameliorated by Mitochondrial Uncoupler BAM15 in a PCOS Mouse Model
Authors: Paris Valentina Rodriguez , Alexopoulos Stephanie J , Hu Ying , Shah Divya P , Aflatounian Ali , Edwards Melissa C , Bertoldo Michael , Kyle Hoehn L , Walters Kirsty A 
Published: May 2021

Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition characterized by endocrine, reproductive and metabolic dysfunction. At present, there is no cure for PCOS and current treatments are suboptimal. Obesity and adverse metabolic features are prevalent in women with PCOS, with weight loss having a beneficial effect on PCOS features. The use of dietary interventions aimed at weight loss have low long-term compliance in women suffering from PCOS. Recent data from animal studies has shown that a small molecule mitochondrial uncoupler, BAM15, is an effective method to pharmacologically treat obesity and metabolic diseases. Therefore, the aim of this study was to investigate the efficacy of BAM15 to ameliorate PCOS-traits in a hyperandrogenic PCOS mouse model. As expected, exposure of female mice to dihydrotestosterone (DHT) induced the PCOS metabolic features of increased body weight (P&lt;0.05), lean mass (P&lt;0.001), increased parametrial and mesenteric fat pad weights (both P&lt;0.05) and adipocyte hypertrophy (P&lt;0.05). Additionally, DHT-induced PCOS mice exhibited insulin resistance measured by HOMA-IR, increased cholesterol and fasting triglyceride levels and hepatic steatosis (all P&lt;0.05). In contrast, DHT-induced PCOS females treated with BAM15 displayed body weights which were comparable with controls, a significant decrease in parametrial and mesenteric fat depot weights (P&lt;0.05) and reduced adipocyte hypertrophy. Furthermore, BAM15 treatment decreased insulin resistance, cholesterol and fasting triglyceride levels, as well as the degree of hepatic steatosis observed in PCOS females, to levels comparable with controls. PCOS mice presented the reproductive PCOS traits of irregular cycles and ovulatory dysfunction, however BAM15 did not improve these PCOS traits. These findings demonstrate that the pharmacologic mitochondrial uncoupler BAM15 is able to ameliorate metabolic PCOS features in a hyperandrogenic PCOS mouse model. These data provide compelling evidence to support BAM15 as a potential innovative and viable therapeutic approach to manage metabolic traits associated with PCOS.
The Effects of Adiponectin on Infertile Women Undergoing IVF/ICSI Treatment and on Human Granulosa Cells
Authors: Qin Lixian , Sitticharoon Chantacha , Petyim Somsin , Keadkraichaiwat Issarawan , Sririwhitchai Rungnapa , Maikeaw Pailin , Churintaraphan Malika 
Published: May 2021

Abstract
Adiponectin, one of the most abundant adipocyte-secreted protein, has been involved in female reproductive regulation. This study aimed to 1) compare serum adiponectin levels in various phases of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment including Phase I (the beginning of gonadotropin stimulation), Phase II (around 8 days after gonadotropin stimulation), and Phase III (on the day of ovum pick-up) between success and unsuccess subjects; 2) compare follicular fluid (FF) adiponectin levels between success and unsuccess groups; 3) compare serum adiponectin levels among different phases of IVF/ICSI treatment in success and unsuccess groups; 4) compare the levels of adiponectin between serum and FF; and 5) investigate the effects of adiponectin on mRNA expressions of follicle stimulating hormone receptor (FSHR) and CYP19A1 (aromatase) in human granulosa-like tumor cell line (KGN) (n=3). In the human study, recruited participants (n=30) with age of 26-40 years were enrolled between April 2018 - May 2019. Blood samples were collected at Phases I, II, and III while FF samples were collected at Phase III. Adiponectin levels were comparable between success and unsuccess subjects in both serum (all phases) and FF (Phase III). Furthermore, serum adiponectin levels were comparable among Phase I, II, and III in success and unsuccess groups. In Phase III, serum adiponectin showed positive correlations with serum adiponectin in Phase I and II and serum FSH in Phase I. Interestingly, adiponectin levels in FF were significantly lower than serum at Phase III in unsuccessful pregnancies but were comparable in successful pregnancies. Moreover, FF adiponectin had a negative correlation with serum LH at Phase III in success subjects. In the KGN cell study, adiponectin had no effects on FSHR and CYP19A1 (aromatase) mRNA expression compared with control. In conclusion, high adiponectin levels in serum compared to FF might contribute to unsuccessful IVF/ICSI treatment.
The Hepatokine Adropin Is Regulated by Estrogen
Authors: Stokar Joshua , Gurt Irina , Yakubovsky Oran , Cohen-Kfir E Einav , Hallak Noa , Dresner-Pollak Rivka 
Published: May 2021

Abstract
Introduction: menopause is associated with weight gain, visceral adiposity and NAFLD. Rodent ovariectomy (OVX) is an accepted model for human menopause. Many OVX studies add high-fat diet or old-age to accentuate deranged phenotype. We have shown OVX alone induced weight gain and changes in liver transcriptome including downregulation of Enho, encoding for the hepatokine adropin (1). Here, we explore changes in VAT cytokine and adipokine genes, hepatic miRNA, and liver triglyceride content induced by OVX, in addition to estrogen’s role in regulation of adropin. Methods: 9-week-old C57BL/6J female mice underwent OVX or sham surgery. Groups of 10 mice were sacrificed at 6- and 12-weeks post-surgery and tissues harvested including mesenteric adipose tissue representing VAT. Liver TG was quantified using Cayman colorimetric assay. In-vitro studies performed in the murine hepatic cell-line, BNL1.ME. Adropin was measured using ELISA. Results: OVX induced adverse inflammatory cytokine & adipokine gene expression in VAT at 6-weeks post-surgery (Il18 1.1 p=0.01, Rares2 2.9, p=0.003, Retn 5.5, p=0.002) and 12-weeks post-surgery (Tnfa 2.3 p&lt;0.001, Cxcl5 1.9 p=0.04). In the liver, OVX induced an increase in TG content at 12 weeks post-surgery (realtive increase vs sham 2.0 p=0.05). Hepatic Enho expression showed a strong inverse coorelation with total body weight gain (r= -0.7 p&lt;0.001) and liver TG content (r=-0.4, p=0.04). In-vitro, estrogen induced an increase in Enho (relative mRNA change vs. growing medium 2.6, p=0.004); though protein level was unchanged, a trend for increased adropin was found in supernatant (relative change vs control 2.2 P=0.09). In-silico analysis of data from OVX mice treated with estrogen showed up-regulation of Enho (relative change vs vehicle, 6 p&lt;0.001). At 6-weeks post-surgery OVX induced changes in hepatic miRNA profile with 48 miRNAs differentially expressed vs SHAM (24 up & 24 down). Integrating data from same sample RNA-SEQ and miRNA-SEQ created a network of differently expressed miRNA with oppositely differently expressed known specific mRNA targets. mIR-29, a known regulator of Enho in liver, was not found to be correlated with Enho expression in this context. Conclusions: OVX alone is sufficient to induce adverse changes in VAT gene expression and liver TG. Hepatic adropin gene expression is regulated by estrogen and its downregulation was strongly correlated to phenotypes relevant to menopause induced metabolic dysfunction, weight gain and increased liver fat. Thus, adropin should be further explored as a novel therapeutic and/or biomarker for menopause induced metabolic dysfunction. (1) Stokar, J., Gurt, I., Cohen-Kfir, E., Yakubovsky, O., Hanna, A., Assayag, E., & Dresner-Pollak, R. (2019). RNA-Seq Analysis of Ovariectomy-Induced Changes in Mouse Liver Reveals New Targets for Menopause-Associated Metabolic Derangement. Journal of the Endocrine Society, 3(Supplement_1), SUN-033.
Adult Onset Isolated Hypogonadotropic Hypogonadism- a Cause of Secondary Amenorrhea
Authors: Patel Shailendra B , Yada Srujana Kamala 
Published: May 2021

Abstract
A 23-year-old African American female was referred for secondary amenorrhea evaluation. She attained menarche at 12 years and had regular menses. At 18 years, she used OCPs for few months, and used plan B, after which her menses stopped. She had hot flashes and sweating. She was placed on progesterone, but never had withdrawal bleeding. Review of systems was positive for intentional weight loss after her menses stopped, hair loss and nipple discharge. She denied any loss of sensation of smell. She has a PMH of asthma, anxiety and OSA. Family history was not significant for any fertility issues. She smoked cannabis after menses stopped. On physical examination, vitals were stable, BMI of 35 kg/meter2, well-developed secondary sexual characteristics, no thyromegaly, acne or hirsutism. Upon work up, CBC, CMP were normal, Urine pregnancy test was negative, gonadotropins were undetectable (FSH- &lt;0.7mIU/ml, LH- &lt;0.2mIU/ml), anti-mullerian hormone was 3.82ng/ml (WNL), Estradiol was also absent (&lt;15pg/ml), with a low Total testosterone (11ng/dl), TSH was 1.17uIU/ml, Free T4 was 1.1ng/dl, ACTH was 9.58pg/ml, Cortisol was 14.8mcg/dl, and Prolactin was 1.5ng/ml. MRI brain was normal with normal pituitary gland, no focal lesion visualized. Pelvic ultrasound showed ovaries 5.9mL and 4.6mL with multiple follicles present bilaterally. Diagnosis of adult-onset isolated hypogonadotropic hypogonadism (IHH) was made. Patient was started on estradiol patches and progesterone. IHH is a genetic disorder of defective production or action of GnRH. IHH when associated with anosmia is called Kallmann syndrome. It was first described by German American geneticist Joseph Kallmann in 1944. GnRH is a decapeptide, produced in arcuate nucleus and pre-optic nucleus of hypothalamus. GnRH stimulates anterior pituitary to secrete FSH and LH. IHH is caused due to impaired migration of GnRH neurons to brain during embryogenesis. It is inherited as autosomal or X-linked dominant or recessive. Gene mutations associated are ANOS-1, FGFR, PROK-2. It is rare in females. IHH has a broad spectrum of clinical presentation from complete absence of sexual development to partial completion of puberty. It presents with microphallus, cryptorchidism, cleft lip/palate, syndactyly, renal aplasia. In childhood presents with anosmia, hearing deficits, dental agenesis, mirror movements, short stature. During puberty, absent pubertal growth spurt, amenorrhea, lack of virilization, no secondary sexual characteristics, infertility. In partial forms, known as Adult onset or acquired form of IHH, patients have slight testicular growth, thelarche, menarche. Goals of treatment are- pubertal induction, maintenance of sexual maturation and restoration of fertility. In females, pre-puberty only estrogen is given, after puberty both estrogen and progesterone are used, for fertility, pulsatile gonadotropins or GnRH analogues are used.
To Be or Not to Be: Pregnant or Not
Authors: Patel Bijal , Kamalimotlagh Sharifeh , Patel Nilesh , Pinsker Richard W 
Published: May 2021

Abstract
Background: Beta Human chorionic gonadotropin (β-hCG) is used for diagnosing pregnancy. Differential diagnosis for elevated β-hCG includes false positive test due to antibody interference, gestational trophoblastic disease (GTD), pituitary production of β-hCG or non-gestational malignancies including hepatic, neuroendocrine, breast, ovarian, pancreatic, cervical, and gastric cancers. We are presenting a case of a menopausal woman noted to have persistently positive serum pregnancy test.
Case: 42-year-old female (G3 P2 A1) with a history of thyroid nodules and hypothyroidism was referred to endocrinology clinic for persistently positive serum pregnancy test without being pregnant. Last C-section delivery was 13 yrs ago. Last menstrual period was more than one year ago. Prior to that, her menstruation had always been irregular. Patient denied any spotting, pelvic discomfort/pain or weight loss in last few months. Seven months ago, POCT urine UCG test was done as per radiology protocol prior to CT abdomen for flank pain, and came back positive. Serum β-hCG was mildly positive at 4.3 (0.0 - 2.4 mIU/ml). Pelvic ultrasound did not show presence of a gestational sac. Repeat serum β-hCG level a week later was 3.8 mIU/ml. Patient was told she had early miscarriage. However, about 6 months later, PCP repeated serum β-hCG level and was elevated at 6.2 mIU/ml and thus patient was referred to endocrinology. Further work up showed FSH 61.3 (post-menopausal: 13.1-86.5 mIU/ml), prolactin 12.6 (3.0-18.6 ng/mL), TSH 9.41(0.47 - 4.70 uIU/ml) and estradiol level &lt;15 pg/ml. β-hCG by dilution was ordered but was cancelled by lab for unknown reason. Patient was then also seen by OB-GYN who advised patient that she is menopausal and started her on estrogen-progesterone (E/P) therapy. About 4 weeks after starting E/P therapy, urine UCG came back negative. Hyper- glycosylated hCG (H-hCG) was not elevated. Patient was explained that false positive pregnancy test was due to pituitary production of β-hCG.
Discussion: We propose considering following aspects when approaching a case of elevated β-hCG in absence of pregnancy. 1) Hook effect can mask very high level of β-hCG, repeating test after dilution will rule out hook effect. 2) Many case studies have shown pituitary production of β-hCG in perimenopausal women. Perimenopausal women 41-55 years of age with mildly elevated serum β-hCG levels (5.0-14.0 mIU/ml) and concomitant FSH level over 45.0 mIU/ml are likely to have pituitary production of β-hCG(1). If we can suppress β-hCG with two weeks of E/P therapy, this supports pituitary production of β-hCG. 3) If above testing is equivocal then one can consider checking H-hCG which is predominately secreted by the more invasive cytotrophoblastic cells, and supports diagnosis of GTD.
References: 1) Gronowski AM, et al. Use of serum FSH to identify perimenopausal women with pituitary hCG. Clinical Chemistry. 2008. 54:4. 652-6.
A Retrospective Analysis of Progestogen Use in Transgender Women
Authors: Chang Julia J , Zhang Phoebe , Ariel Danit 
Published: May 2021

Abstract
Background: Many transgender women seek progestogens as part of their feminizing gender-affirming hormone treatment (GAHT), particularly to address breast development, body composition, mood stabilization, and changes in sexual desire and sleep. However, there are few studies that evaluate the role of progestogen use in feminizing GAHT. Reasons for initiating and continuing progestogen therapy have been mostly anecdotal to date, dependent on patient preference and provider practice style, and data about effects remain scarce.
Objective: To characterize progestogen use patterns in transgender women at one academic center; identify reasons for initiation and continuation of its use; and determine perceived related benefits and adverse events.
Methods: Retrospective analysis of transgender women prescribed feminizing GAHT at Stanford Health Care (SHC) between 2014-2020. Those using either combination estrogen + micronized progesterone or combination estrogen + medroxyprogesterone acetate (MPA) were included in our sample. Twenty-five consecutive charts were reviewed in detail for patterns of progestogen use, reasons for initiation and continuation, and its perceived effects.
Results: 410 transgender women sought care at SHC between 2014-2020. Ninety-six patients (23%) were prescribed micronized progesterone and 15 patients (4%) MPA at some point in their care, in addition to estrogen use. Of the 25 patient charts reviewed in detail (median age 30 years, IQR 25-42), 32% (n = 8) had clear documentation in the medical record of why progestogen was started and 25% (n = 6) included a description of the patient’s perceived effects with progestogen therapy. The most common reason to start progestogen was improved breast development (20%, n = 5). Three individuals reported improved nipple/breast growth. Median duration of progestogen use was 34.4 months (IQR 22.3-47.4) with 22 out of 25 patients still on progestogen therapy at time of chart review. Median duration of estrogen use prior to initiation of progestogen use was 14.2 months (IQR 7.1-35.8). No cardiovascular or thromboembolic events were noted in the reviewed patients on progestogen therapy.
Discussion: Over one in four transgender women seeking feminizing GAHT received a form of progestogen therapy as part of their overall GAHT. Most patients on progestogens lack documentation of why it was started or whether the patient seems to benefit from its addition. Given the continued paucity of data supporting or against progestogen use in feminizing GAHT, gender-affirming hormone providers may benefit from further education on how to counsel patients about progestogen use and how to assess for potential progestogen-associated effects over time. Finally, more consistent documentation in the electronic medical record will allow for more definitive conclusions regarding the benefits and risks of progestogen therapy in the future.
Development of Repository From a Pediatric Gender Clinic
Authors: Gortakowski Michele , Gordner Chelsea C 
Published: May 2021

Abstract
Objectives: With the publication of updated guidelines for care of transgender and gender non-conforming individuals, there has been an increase in the presence of gender diversity in both mainstream media and medical literature. Several gaps currently exist in medical knowledge regarding long term effects of gender-affirming therapies. There is a lack of standardization in study design, patient sampling, and outcome measures, and most studies are retrospective. Here we describe the creation of both a retrospective and prospective repository of patients who presented to the Massachusetts Medical School-Baystate Medical Center (UMass-Baystate) pediatric gender program.
Methods: Baystate Medical Center is located in western MA and is a tertiary referral center. A pediatric gender clinic was created in 2014. A repository containing both retrospective and prospective data was approved by the UMass-Baystate IRB to include patients ages 2 to 24 years of age who presented to our gender clinic. Retrospective data was obtained using the McKesson billing database. Sociodemographic, clinical and behavioral health data were collected. We are consenting individuals as they present to the clinic for the prospective component. Those that have consented fill out a survey at each visit. The repository has been approved to follow outcome data for 25 years.
Results: To date, we have 218 individuals in the repository, 75 of which are in the prospective component. Age of presentation ranged from 6 yrs to 24 yrs with an average age of 15 yrs. 62% identified as transmale, 31% as transfemale and the remainder as gender fluid or other. 75% have been prescribed gender affirming hormone therapy (56% GnRH agonist therapy, 20% estrogen, 58% testosterone). Of those being followed prospectively, 76% identified as white, 19% Hispanic. 79% were satisfied or very satisfied with their care.
Conclusions: Here we describe the demographic and clinical characteristics of patients that have presented to our gender clinic since 2014. The creation of our gender repository will allow us to assess sociodemographic, clinical and behavioral health outcomes of treatment, including metabolic parameters, bone health, and mental health outcomes in our pediatric population. Future projects include assessment of the change in cardiovascular risk in individuals on gender-affirming hormone therapy.
Patient and Parent Reported Psychosocial Concerns in Children and Adolescents With Turner syndrome
Authors: Fimmel Fiona , Clary Lauren E , Shankar Roopa Kanakatti 
Published: May 2021

Abstract
Background: Pediatric patients with Turner syndrome (TS) are reported to have a higher incidence of anxiety, depression and social isolation but there is minimal data on self-reported measures. Methods: We utilized the validated PROMIS (Patient Reported Outcomes Measurement Information System) question bank to develop 4-question short forms to assess patient and parent self-reported scores in the domains of depression, anxiety, and peer relationships in our TS cohort. Completed PROMIS short forms from TS patients seen in the multidisciplinary TS clinic between 1/1/2019 and 6/1/2020 were retrospectively analyzed. Clinical data were also abstracted from medical records and correlated with the measures of depression, anxiety, and peer relationships. Descriptive analyses of the T-scores were completed using a non-parametric Wilcoxon rank-sum test and the dyad results were analyzed for agreement between parent and patient reporting. Results: Data from 26 patients (mean age 13y, range 4.6-20.6y) were included in the analysis: 3.9% were clinically referred for depression/anxiety after psychology assessment, 15% had developmental delays and 15% had an individualized education plan. Nearly 77% had short stature (&lt;5%ile), 58% had received growth hormone and 54% were on estrogen therapy. Median scores were not statistically different from population norms for patient (N=22) or parent (N=25) reports in the 3 domains and did not vary by age, estrogen supplementation or stature. Internal reliability of the questionnaires measured by overall Cronbach alpha for each domain were acceptable (0.73-0.93). While parent and patient reported anxiety scores were correlated (R=.452, p=.040.), the depression and peer relationship scores were not correlated. Parent-reported peer relationship scores were negatively correlated with patient-reported anxiety (R=-0.46, p=0.04) and parent reported anxiety (R=-0.43, p=0.04) scores. Parent perceived depression and anxiety measures were also correlated (R=0.77, p&lt; 0.001) as were patient reported scores in these domains (R=0.6, p=0.003). Conclusions: In contrast to existing literature in TS indicating a higher incidence of psychosocial concerns, the patient and parent self-reported scores on depression, anxiety and peer relationship were not statistically different from the population normative data, and parent and patient perceived scores were not correlated in all domains. While the small number of patients in this pilot study may be insufficiently powered to detect a small difference in scores in these domains, the data underscores the need to develop a TS-specific validated psychosocial questionnaire that more adequately assesses the psychosocial concerns in this population.