bluuebunny/crossref_metadata_2025_split huggingface dataset:
7745 Hirsutism in young girls: Beyond PCOS
Authors: Mishra Ipsita , Baliarsinha A K 
Published: October 2024

Abstract
Disclosure: I. Mishra: None. A. Baliarsinha: None.
Hirsutism in young girls:Beyond PCOSAbstract: Hirsutism is excessive terminal hair that appears in a male pattern in women.Though obesity,insulin resistance and PCOS are common cause of hirsutism in young girls,suspicion of other etiologies must be made on a background of overlapping features.We describe 3 cases of young females presenting with hirsutism with varied etiologies. Case 1.16 year 11months old female presented with oligomenorrhea -3years,excessive hair growth over face -2 years.On examination,BMI was 25.2 kg/m2,Grade 2 acanthosis,A3P5B5,modified FG- 16/36,clitoral length-1.3cm and clitoral index - 70 mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 23.65 ng/ml,ONDST- 1.2 mcg/dl,LH - 1.49 IU/ml,FSH- 7.44IU/ml,serum testosterone- 70ng/dl,17OHP- 7.03 ng/ml,DHEAS- 553mcg/dl and post synacthen 17OHP- 36.89 ng/ml respectively.USG abdomen & pelvis was normal. HOMA-IR was 4.1.Diagnosis was LOCAH Case 2.19 year old female presented with hair growth in androgen dependent areas-5years, regular predictable menstrual cycles and was treated as a case of PCOS for 5 years with no changes in hair growth pattern.She was off therapy since 1 year prior presenting to us.On examination,BMI was 24 kg/m2, acanthosis absent,A3P5B5,modified FG- 18/36, clitoral length- 6 mm,clitoral index - 25mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 22.9 ng/ml,ONDST- 0.508 mcg/dl,LH - 5.98 IU/ml,FSH- 5.29 IU/ml, serum testosterone- 23.4 ng/dl,17OHP- 1.01 ng/ml and DHEAS- 298 mcg/dl respectivelyUSG Abdomen & pelvis;RO - 5.7cc,LO - 5.6 cc with B/L PCOM.Review TVS was normal.In view of discordant results DHT and luteal phase serum progesterone were done which were 80.5 pg/ml and 2.1ng/ml respectively.HOMA IR was 1.9.Diagnosis was IDIOPATHIC HIRSUTISM. Case 3.12 year old female child presented with excessive hair growth over face,chest,back and abdomen- 1yr,hoarseness of voice - 1 yr,onset of breast enlargement apprx 8 to 9yrs with non-attainment of menarche.On examination BMI was 30 kg/m2,Grade 3 acanthosis, A3P5B3,modified FG- 15/36,clitoral length- 2.8 cm & clitoral index - 120 mm2. Biochemical evaluation revealed normal thyroid function tests,LH - 15.3 IU/ml,FSH- 6 IU/ml,s.prolactin- 11.2 ng/ml,ONDST- 0.38 mcg/dl,DHEAS- 161 mcg/dl,serum testosterone- 140 ng/dl,17OHP- 3.9 ng/ml and post synacthen 17OHP- 4.10 ng/ml respectively.USG abdomen-s/o PCOS with normal adrenals. In view of discordant results short DAST was done which was Testosterone(ng/dl)baseline-125;4hr-91.1, DHEAS (mcg/dl) baseline-180;4hr-188 cortisol (mcg/dl) baseline-7.04;4hr-0.95.HOMA-IR was 5.4. Diagnosis was PCOS(OVARIAN THECOSIS).Varied presentations of hyperandrogenic disorders occurs in young females.A need to revise the diagnosis must be made if no response is obtained with initial drug regimes.
Presentation: 6/3/2024
8795 Impact of Retinoic Acid Receptor Alpha Conditional Knockout on Ovarian Follicle Development in the Mouse
Authors: Bogin Zlata , Keisker Abby , Urbanowski Audrey , White Carl , Kipp Jingjing Liu 
Published: October 2024

Abstract
Disclosure: Z. Bogin: None. A. Keisker: None. A. Urbanowski: None. C. White: None. J.L. Kipp: None.
The ovaries are the primary endocrine and reproductive organs in females. The ovarian follicle is the basic structural and functional unit of the ovary. When there is abnormal development in ovarian follicles, infertility and reproductive diseases such as polycystic ovarian syndrome (PCOS), premature ovarian failure (POF), and ovarian cancers may occur. Retinoic acid (RA), a biologically active derivative of vitamin A, is a signaling molecule that plays a vital role in various physiological processes, including embryonic development, tissue differentiation, and reproduction. We have shown that RA stimulates granulosa cell proliferation through a cell signaling cascade involving Retinoic Acid Receptors (RARs), which have three isoforms alpha, beta, and gamma. In this study, we characterized a new retinoic acid receptor alpha conditional knockout (RARA cKO) mouse model with RARA deleted in granulosa cells during embryonic development. The body weight and uterus weight of the RARA cKO mice were decreased at week 7 but returned to normal at week 15 and 12 months. The animals were either sub-fertile or infertile with phenotypic evidence of POF. In addition, a variety of ovarian pathologies were observed, including the presence of hemosiderin, increased cyst formation, and abnormal follicle counts. Overall, this study provides evidence of the involvement of retinoic acid signaling, mediated by RARA, in ovarian development and fertility. This study will help to better understand the prevention and treatment of ovarian diseases.
Presentation: 6/2/2024
8331 Melatonin is associated with higher placental weight and higher birth weight
Authors: Kampmann Ulla , Lauritzen Esben S , Knorr Sine , Bjerre Mette , Goodyear Laurie J , Middelbeek Roeland , Kusuyama Joji , Fuglsang Jens , Ovesen Per , Møller Magnus 
Published: October 2024

Abstract
Disclosure: U. Kampmann: Grant Recipient; Self; Novo Nordisk, Ulla Kampmann. Speaker; Self; Merck, Novo Nordisk. E.S. Lauritzen: None. S. Knorr: None. M. Bjerre: None. L.J. Goodyear: None. R. Middelbeek: None. J. Kusuyama: None. J. Fuglsang: None. P. Ovesen: Grant Recipient; Self; Novo Nordisk. M. Møller: None.
Background and aim: Melatonin is both a neuroendocrine hormone which regulates circadian rhythm and an antioxidant. Melatonin is primarily produced in the pineal gland but also in the placenta and the role of melatonin in pregnancy is emerging. We examined melatonin levels during pregnancy and performed correlations with placental weight, birth weight and birth weight Z-score as markers of placental function. Material and methods: Blood samples were obtained in each trimester of pregnancy from a cohort of 400 pregnant women, followed at a Danish University Hospital. Data on pre-gestational BMI, smoking status, placental weight, birth weight and Z-score were collected. Melatonin, and biomarkers of oxidative stress: SOD3, CD 163 and CRP were measured on blood samples collected in the morning. Correlations were calculated using mixed models. Results: We included 372 healthy, singleton pregnancies. Melatonin levels increased significantly throughout pregnancy from 17.0 pg/mL (95% CI: 14.1 - 19.9) and 18.8 pg/mL (95% CI: 15.8 - 21.8) in the 1st and 2nd trimester, respectively, to 45.9 pg/mL (95% CI: 40.8 - 51.0) in the 3rd trimester. There was a significant positive correlation between the antioxidant enzyme SOD3 and melatonin throughout pregnancy with a coefficient of 0.15 (95% CI: 0.13 - 0.17) and there was a significant positive association between placental weight and melatonin (coefficient: 0.014 (95% CI: 0.000 - 0.028)) and Z-score and melatonin levels (coefficient: 1.95 (95% CI: 0.13 - 3.79)). This was however not significant when adjusting for smoking and pre-pregnancy BMI. Conclusion: The current study is to date, the largest study that have performed longitudinal measures of melatonin throughout pregnancy. Melatonin levels increase significantly during pregnancy and indicate that placenta is a major source of melatonin, that plays a protective role against oxidative stress in pregnancy.
Presentation: 6/1/2024
8509 Molecular and Reproductive Assessment in Ames strain under or not Hormonal Replacement
Authors: Azevedo B V , Trigueiro N , Marques J M , Yariwake V , Tamashiro L , Cruz R , Veras M M , Carvalho L 
Published: October 2024

Abstract
Disclosure: B.V. Azevedo: None. N. Trigueiro: None. J.M. Marques: None. V. Yariwake: None. L. Tamashiro: None. R. Cruz: None. M.M. Veras: None. L. Carvalho: None.
Introduction: The Ames lineage, a mouse model with a mutation in the Prop1 gene, exhibits GH, TSH, and PRL deficiencies along with low levels of gonadotropins. This has prompted an investigation into aging and reproductive restoration after hormone replacement reported in the literature. Aims: The present study aims to analyze the pathophysiologic mechanisms in the reproductive system and fertility restoration. Methods: This is a prospective study approved by the ethical committee for animal use at the University of Sao Paulo Medical School. An isogenic Ames lineage was categorized into four groups: 1) Ames wild-type mice, 2) untreated Ames dwarf mice with sexual maturity, 3) untreated Ames dwarf mice without sexual maturity, and 4) Ames dwarf mice under hormonal treatment. Male Ames dwarf mice received treatment with levothyroxine and human recombinant GH, starting at 30 days postnatal (dp) for 40 days, followed by weekly applications until 90 dp. At the time of euthanasia, a set of analyses were conducted on animals from each group to characterize sexual maturation, fertility, and tissue collection for reproductive parameter analyses, such as seminiferous tubule morphology by histology, testicular weight, gonadosomatic index, and spermogram analysis. Additionally, pituitary RNAseq was performed using the poly-A tail capture method with the Illumina stranded mRNA prep kit and sequenced on the NextSeq 2000. Results: Treated dwarf mice exhibited fertility restoration, an increase in testicular volume with an improvement of testicular function, and complete spermatogenesis. Untreated Ames dwarf mice were infertile, but those that reached sexual maturity without hormonal replacement showed improvements in reproductive parameters, such as enhanced testicular development, maturation of some seminiferous tubules, increased testicular weight, and improvement in the spermogram compared to immature Ames dwarf mice. Transcriptome analyses revealed distinct patterns of all Ames dwarf mice groups and the wild-type. It was observed a decrease in Fshb expression in the group without sexual maturation compared to the wild-type group. Additionally, Prl and Slc6a12 were upregulated in the spontaneously sexually mature Ames dwarf compared to the non-restored Ames dwarf mice. Conclusion: GH and levothyroxine treatment in the Ames lineage are effective in restoring fertility and improving reproductive parameters in male Ames dwarf mice. However, sexually mature Ames dwarf mice without treatment presented improvements in reproductive and molecular parameters despite remaining infertile. These findings provide valuable insights into the complex interaction among hormonal replacement, modulating mechanisms, and sexual maturity.
Presentation: 6/2/2024
8354 OVARIAN HYPERTHECOSIS: AN UNCOMMON CAUSE OF HYPERANDROGENISM IN A POSTMENOPAUSAL WOMAN
Authors: de Griné Severino Mariana , Silva Francisca Pinho , Lopes Marta Vaz , Doutel Delfim , Nunes Carla , Alexandre Maria Inês , Bugalho Maria Joao 
Published: October 2024

Abstract
Disclosure: M.D. Severino: None. F.P. Silva: None. M.V. Lopes: None. C. Nunes: None. M.I. Alexandre: None. M.J. Bugalho: None.
Introduction: Severe hirsutism in postmenopausal women demands a careful clinical evaluation to exclude a malignant cause, such as adrenal or ovarian androgen-secreting tumors. Ovarian hyperthecosis is an uncommon and benign cause of hyperandrogenism and, consequently, hirsutism. It is caused by persistent testosterone synthesis due to proliferation of ovarian stromal cells and nests of luteinized theca cells. It occurs more often in postmenopausal women, as aromatization of testosterone to estradiol decreases due to the loss of granulosa cells. It is also frequently associated with obesity and insulin resistance. Clinical case: We present the case of a 61-year-old woman, with a history of hypertension and dyslipidemia, referred to Endocrinology Clinic due to a year long history of hirsutism, most severe on her face, chest, and abdomen. She also mentioned slight clitoromegaly. She had no other virilization symptoms such as acne, male-pattern alopecia, voice deepening or mammary atrophy. Her menarche occurred at the age of 14 and she had regular menses until menopause, at the age of 51. She had a BMI of 32 kg/m2 and an uncharacteristic phenotype. At observation, she had a mild hirsutism (Ferriman-Gallwey score of 9). This contrasted with the biochemical findings of severe androgenism - total testosterone of 366 ng/dL (reference values [RV] for women between 5-48) with free testosterone 7.8 pg/mL and SHBG 74 nmol/L (RV 32-128), resulting in a Free Androgen Index of 17,16 (RV &lt;6.6). DHEAS, androstenedione, 17-hydroxyprogesterone and prolactin were normal, and gonadotropins were in the menopausal range. Blood tests also showed hyperinsulinemia and pre-diabetes with HbA1c 6,2%. She denied exposure to steroids in the form of new medication, supplements, or creams/gels (including second-hand exposure through her partner) and she had no exposure to other drugs with androgenic effect. Abdominal and pelvic CT scan, as well as transvaginal ultrasound, showed no adrenal or ovarian lesions. An ovarian cause was deemed the most likely and laparoscopic diagnostic bilateral salpingo-oophorectomy was performed. Gross pathology revealed ovaries of regular size, while histology showed bilateral ovarian stromal hyperthecosis. Testosterone levels returned to normal one month after surgery (14,2 ng/dL). Conclusion: Benign, ovarian causes of hyperandrogenism are uncommon in postmenopausal women, requiring a high index of suspicion. The diagnosis is difficult, and laparoscopic bilateral salpingo-oophorectomy is essential as both a diagnostic and therapeutic tool.
Presentation: 6/2/2024
7019 Persistently Elevated Estradiol Levels in a Transgender Male; An Unexpected Pregnancy
Authors: Kanin Maralee , Grock Shira , Agrawal Nupur 
Published: October 2024

Abstract
Disclosure: M. Kanin: None. S. Grock: None. N. Agrawal: None.
Background: Testosterone is the backbone of gender-affirming hormone therapy (GAHT) for transmasculine and non-binary individuals assigned female at birth (AFAB). While testosterone can affect fertility, it should not be used as contraception and is contraindicated in pregnancy. It is important to counsel patients on fertility preservation, pregnancy, and contraceptive options prior to testosterone initiation. However, the Endocrine Society Guidelines and World Professional Association for Transgender Health Standards of Care provide minimal guidance on reproductive health and contraceptive options. Case Description: An 18-year-old individual AFAB on GAHT with testosterone was referred to endocrinology for elevated estradiol levels. On presentation, the patient denied vaginal bleeding or breast tenderness. The date of last menstrual period was reported as two years prior. There was no significant past medical or surgical history. Medications included subcutaneous testosterone cypionate 20 mg weekly. Physical exam was notable for elevated BMI 42.6kg/m², mild facial hair and central adiposity. Hormone analysis revealed testosterone of 172 ng/dL (adult male: 200-1000) and estradiol 27,322 pg/mL (mid-cycle Female: 80-400). Estradiol by mass spectrometry obtained due to concern for immunoassay interference resulted at &gt; 10,000 pg/mL. FSH &lt;0.1 mIU/mL, LH&lt;0.1 mIU/mL, DHEA-S 2,460 ng/mL (adult female: 400-3600), androstenedione 1.85 ng/mL (0.260 - 2.140), prolactin 328 ng/mL (3 -23.1). CT abdomen and pelvis and pituitary MRI were ordered to assess for ovarian, adrenal and/or pituitary tumor. Later that day additional laboratory tests revealed alpha fetoprotein 126 ng/mL (0 -6.7), progesterone 100.2 ng/mL (luteal phase: 3.0-25.0), beta-hCG 32,571 mIU/ml, inhibin B&lt;10, inhibin A 500.1pg/ml (luteal phase: 40-80) and CA-125 19 U/mL (0 - 35). Given the elevated beta-hcg the patient was asked if they were having sex in a way that could result in pregnancy to which they answered affirmatively. CT and MRI were cancelled, and abdominal ultrasound was obtained which revealed a single living intrauterine pregnancy with estimated gestational age 35 weeks 2 days. Testosterone was stopped and they subsequently delivered a healthy baby girl. Conclusion: Gender diverse patients on testosterone can experience unplanned pregnancy. As testosterone is contraindicated in pregnancy, counseling on reproductive health and contraception is needed. A pregnancy test should be considered prior to initiating hormones for appropriate individuals. It is important to be aware that Individuals AFAB may not desire estrogen containing birth control and placement of intrauterine devices can be dysphoric. Further investigation into how contraceptive options may affect outcomes for individuals on GAHT is needed to minimize barriers to care and to enable patients to make well informed decisions.
Presentation: 6/2/2024
7980 Physical Activity Attenuates the Association of Early Adolescent Adiposity with Later PCOS
Authors: Whooten R , Rifas-Shiman S , Perng W , Chavarro J , Oken E , Hivert M F 
Published: October 2024

Abstract
Disclosure: R. Whooten: None. S. Rifas-Shiman: None. W. Perng: None. J. Chavarro: None. E. Oken: None. M. Hivert: None.
Purpose: Adiposity is a risk factor for polycystic ovary syndrome (PCOS). Limited knowledge exists regarding modifiable behaviors, such as physical activity, during early-life may mitigate the association of adiposity with PCOS risk. We aimed to assess how moderate-vigorous physical activity (MVPA) may impact the association of adiposity in early adolescence with later report of adolescent PCOS. Methods: Within the Project Viva prospective cohort, we used multivariable logistic regression to assess the association of body mass index z-score (BMIz) at early adolescence (mean age 13.1 years) with mid-late adolescent PCOS (self-reported diagnosis or oligo-anovulation with clinical/biochemical hyperandrogenism at mean age 17.7 years). We stratified our analyses by actigraphy-assessed MVPA during early adolescence (≥30 versus &lt;30 minutes/day). In multivariable models, we adjusted for maternal education and PCOS; and child race and ethnicity, dietary behaviors, actigraphy-assessed sleep duration, and self-reported screentime; and season of actigraphy assessment. Results: Among 341 female adolescents, n=47 (14%) met criteria for PCOS at mid-late adolescence. At early adolescence, mean (SD) BMIz was 0.32 (1.10) units and n=110 (32%) had ≥30 minutes/day MVPA. There was no difference in MVPA ≥30 minutes/day among those with versus without later PCOS (30% vs 33%, p=0.70). In unadjusted analyses, there was an association of early adolescent BMIz with mid-late adolescent PCOS (OR=1.93, 95%CI 1.39, 2.69 per unit increase in BMIz). In stratified analyses, the association of early adolescent adiposity with later PCOS was stronger in those with MVPA &lt;30 minutes/day (OR=2.07, 95%CI 1.37, 3.11) than in those with MVPA ≥30 minutes/day (OR=1.72, 95%CI 0.97, 3.06). These findings persisted after adjusting for all covariates (overall: OR=1.72 95%CI 1.15, 2.56; MVPA &lt;30 min/day: OR=2.01 95%CI 1.17, 3.45; MVPA ≥30 minutes/day: OR=1.36 95%CI 0.64, 2.91), however p-values for interaction terms were non-significant. Conclusion: Our findings suggest that maintaining ≥30 minutes MVPA daily during early adolescence may attenuate the association of adiposity with risk of PCOS by late adolescence. This has implications for the importance of promoting physical activity among at-risk individuals.
Presentation: 6/2/2024
9221 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study
Authors: Yahyavi Sam Kafai , Selmer Christian , Torp-Pedersen Christian , Juul Anders , Jensen Martin Blomberg 
Published: October 2024

Abstract
Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility.
BACKGROUND AND OBJECTIVE: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects &gt; 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women.
Presentation: 6/3/2024