Secondary Sexual Characteristics Research Articles

A review on lipid and polymeric nano-based 17-β-estradiol delivery systems: advances and challenges

17β-estradiol (E2) is an endogenous steroid hormone pivotal for the development of female secondary sexual characteristics and the maintenance of the female reproductive system. Its roles extend beyond these physiological functions, as E2 is employed in hormone replacement therapy to alleviate symptoms associated with menopause. Furthermore, E2 exhibits therapeutic potential in the management of osteoporosis, breast cancer, and various neurological and cardiovascular conditions, partly due to its anti-inflammatory effects via modulation of the MAPK/NFκB signaling pathway. Notwithstanding, the hydrophobic nature of E2 significantly hinders the formulation of efficacious delivery systems for its clinical deployment. Recent advances have highlighted nano-based delivery systems for E2 as a promising solution to this solubility challenge. This review critically examines contemporary nano-delivery strategies for E2, particularly emphasizing lipid and polymeric nanoparticle-based systems. These nanostructures are designed to enhance stability, biocompatibility, controlled release, and targeted delivery of E2, yet the selectivity of E2 delivery for therapeutic purposes remains an ongoing challenge. The novelty of this review lies in its focus on the advances in nano-based E2 delivery systems over the past decade, a topic not extensively covered in prior literature. We present a comprehensive analysis of the encapsulation of E2 within polymeric and lipid nanoparticles, underscoring the untapped potential of these strategies. This review identifies a significant research gap, advocating for intensified experimental investigations that could pave the way for the translation of nano-based E2 therapies from bench to bedside.

Bassa statura non sindromica e ritardo puberale: non solo ritardo costituzionale di crescita e pubertà

A 14-year-old boy with suspected constitutional delay of growth and puberty (CDGP) presented with short stature, absence of secondary sex characteristics, bone age delayed by one year and family history of CDGP in his mother. The external genitalia were normal. Re-evaluated at the age of 17 years and 7 months (as he missed several visits), he presented with a short near-final height (bone age consistent with chronological age) below the target height, signs of progressed virilization, but insufficient testicular volume. The prevalence of nonsyndromic 46,XX testicular disorder is estimated at 1:20,000 males. In 80% of cases the condition is due to the presence of the SRY gene on the X chromosome, resulting from abnormal paternal meiosis. It is characterized by short stature, hypergonadotropic hypogonadism and sterility. The need for routine screening of gonadal cancer is still a matter of debate. Treatment of this condition consists of testos-terone replacement from the pubertal age. Psychological support should also be warranted since the communication of the diagnosis. The case suggests that non-syndromic 46,XX testicular disorder should be considered when evaluating a boy with hypogonadism and short stature, especially in patients with suspected CDGP who have progressive virilization and advancement of bone age, despite no increase in testicular volume.

Sexual Selection on Non-Ornamental Traits Is Underpinned by Evidence of Genetic Constraints on Sex-Biased Expression in Dusky Pipefish.

Species lacking distinct secondary sex characteristics, such as differences in size or morphology, are often thought to experience lower levels of sex-specific selection in comparison to highly sexually dimorphic organisms. However, monomorphism in classic visible traits could be a result of genetic or physiological constraints that prevent the sexes from reaching divergent fitness optima. Additionally, biochemical and molecular work have revealed a variety of less easily observed phenotypes that nonetheless exhibit profound dimorphism. Sex-specific selection could act on these more subtle, less visible, traits. We investigate sex-specific selection in the polygynandrous dusky pipefish (Syngnathus floridae), which lacks distinct secondary sexual characteristics such as size, colour and morphological dimorphism. Using experimental breeding populations, we revealed that although males and females have similar opportunities for sexual selection, only males experience significant sexual selection pressures on body size. We also investigated patterns of sex-biased and sex-specific gene expression in gonads, livers and gills, and tested whether genes with highly divergent expression patterns between the sexes are more likely to be tissue-specific, and therefore relieved of genetic constraints. Sex bias in gene expression was widespread, although the reproductive organs had the most sex-biased and sex-specific genes. Sex-specific selection on gene expression in gills was primarily related to immune response, whereas the liver and gonads had a wide variety of cellular processes, as well as reproductive proteins, showing sex-biased expression. These sex-biased genes showed higher organ-specificity in their expression patterns, suggesting that pleiotropic constraints might have historically impacted the evolution of sex-specific expression patterns. Altogether, we find evidence for ongoing and historical sex-specific selection in the dusky pipefish.

Optimal polyandry in fruit flies.

The study of polyandry has received increasing scientific attention with an emphasis on the fitness benefits and costs that females derive from mating with multiple males. There are still gaps in our understanding of how polyandry affects female fitness, however, as many previous studies compared the fitness outcomes of a single mating vs. two or three matings and did not separate the consequences of multiple mating from the costs of sexual harassment. We therefore conducted controlled mating trials with female fruit flies (Drosophila melanogaster) that could mate at either low (every eight days), medium (every four days), or high (every other day) rates while controlling for exposure to harassment from males. We found that female lifetime fitness was highest under the high followed by the medium mating-rate conditions. Moreover, we did not detect reductions in lifespan as a consequence of higher rates of polyandry. Our results demonstrate that even at realistically high rates, polyandry can lead to net fitness benefits for females, which can have major implications for sexual selection. Specifically, we discuss the significance of our findings as they relate to competition and the evolution of secondary sex characteristics in females, and sperm competition amongst males.

Central Precocious Puberty During the COVID-19 Pandemic Period: A Systematic Review of Literature.

Central precocious puberty (CPP) is a condition where the hypothalamus-pituitary-gonadal axis is activated earlier than normal, leading to premature development of secondary sexual characteristics before eight years of age in girls and nine years of age in boys. The purpose of this study was to critically and systematically evaluate the literature regarding CPP rise during the COVID-19 pandemic. We searched PubMed and Google Scholar for relevant articles using the following MeSH terms: "COVID-19, "precocious puberty," "early puberty," "pediatric endocrinology," and "pandemic effects." We included studies calculating the risk of CPP before and during the COVID-19 pandemic. We excluded studies looking at patients with an identifiable cause for CPP or with peripheral precocious puberty. The primary outcome was the prevalence of central precocious puberty during the pandemic compared to the pre-pandemic period. We analyzed data regarding anthropometric, biochemical, and pelvic ultrasound data between the two groups. Overall, 16 studies with 2.175 subjects were included, of which 1.818 were diagnosed with CPP. There was a rise in the number of new diagnoses of CPP during the COVID-19 pandemic (985 subjects) compared with the pre-pandemic period (833 subjects). The mean age of diagnosis in the first group was 7.42 years versus 7.54 years in the second group. Notably, CPPduring the pandemic was associated with a higher body mass index (BMI) compared with the group of the pre-pandemic period (17.50 versus 17.08). The pandemic and lockdowns led to changes in lifestyle habits, social isolation, sleep disturbance, excess screen time, and increased stress levels. We hypothesize that these alterations influenced the increase in CPP frequency.

Adolescent and Young Adult Development in Transplant Recipients.

Solid organ transplantation (SOT) is the gold standard of therapy for individuals with end-organ dysfunction. Improved survival outcomes after SOT can help adolescent and young adult (AYA) recipients lead long and healthy life. However, successful SOT during adolescence and young adulthood is often complicated by the innate developmental challenges of this age group. The psychosocial tasks of adolescence include identity development, autonomous decision-making, establishing social networks, educational and vocational preparation, and navigating romantic relationships. These goals may be amplified or delayed for pediatric SOT recipients. Adolescence is also marked by rapid physical changes in linear growth and the development of secondary sexual characteristics. Yet AYA may experience physical and pubertal delays related to transplantation, as well as exaggerated body image dissatisfaction due to medication side effects. Strict adherence to medication and post-transplant regimens may interfere with adolescents' desire for normalcy and fitting in with peers. Healthcare providers should be aware that AYA value education and self-empowerment in transplant care. Transplant success needs to be defined by both medical and psychosocial outcomes, particularly when it relates to the vulnerable AYA population. Fortunately, investment from the patient, family, and care team can aid in transplant recovery and success. This article will identify the developmental challenges faced by AYA undergoing solid organ transplantation as well as strategies to engage positive outcomes.

7802 A Review of 21 Cases of Kallmann Syndrome

Abstract Disclosure: T. Kashima: None. M. Ishimaru: None. E. Tanimoto: None. S. Fukui: None. C. Nakamura: None. N. Ujita: None. H. Miyagi: None. M. Igarashi: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. Kallmann syndrome is the most common form of hypogonadotropic hypogonadism. The incidence is estimated to be 1 in 10,000 birth boys and 1 in 50,000 birth girls. The goals of treatment for childhood puberty are to induce the progression of secondary sexual characteristics close to physiological sexual maturity, to improve psychosocial problems caused by delayed puberty, and to achieve fertility. Methods.Twenty-one patients (fifteen males and six females) with a diagnosis of Kallmann syndrome who visited our Department between August 2004 and November 2023 were included in the study. The electronic medical records were reviewed retrospectively. Results.The median age at first visit was 15 years and 11 months (13 years and 3 months to 17 years and 7 months). The chief complained were secondary sexual characteristics not yet developed, olfactory disturbance, amenorrhea, decreased growth rate, and micropenis. Three adults had symptoms of Kallmann's syndrome and were seen for close examination. 6 had a history of hearing loss. Family history included 2 cases of hypogonadotropic hypogonadism and a sibling with Sjogren-Larsson syndrome. 9 cases had genetic testing, including KAL1, KAL2, FGF8, IL17D, 1 case each, and 2 gene variants of CHD2.At the time of initial examination, the median testicular volume in males was 1.0 mL (1.0-3.0 ml). Five of the six female patients had no breast enlargement.Endocrine examination revealed that the mean basic LH and LHRH test peak values were 0.25 and 3.40 mIU/mL, respectively; the mean basic FSH and peak FSH values were 0.91 and 4.47 mIU/m, respectively; the mean testosterone level in males was 0.09 ng/mL; and the mean estradiol level in females was 5.58 pg/mL.For the 20 patients, excluding children, gonadotropins (HCG+rFSH) for men and estrogen patches for women were both started at low doses and titrated up to Kaufman therapy in women. Median age at initiation of treatment was 16 years and 5 months (14 years and 1 month to 18 years and 6 months). Bone density increased after the start of treatment. One patient diagnosed with micropenis in infancy was treated with testosterone for micropenis at 2 years and 5 months. Two male patients had a baby with their partners. Discussion.The age of diagnosis (age of first examination) is considerably older than the average age of onset of secondary sexual characteristics, so it is necessary to educate the public so that patients can be examined earlier. The patient's fertility was partially confirmed, and a smooth transition to adult/reproductive medical care can be expected through earlier intervention. Presentation: 6/1/2024

7128 Efficacy and Safety of Leuprolide Acetate 3M Depot in Chinese Children with Central Precocious Puberty: Interim Analysis of Multicenter, Single-Arm, Prospective Study

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) due to early activation of the hypothalamic-pituitary-gonadal axis leads to early puberty. CPP has a negative impact on adult height. Leuprolide acetate (LA), a gonadotropin-releasing hormone agonist (GnRHa) is the standard treatment for CPP. As CPP requires prolonged treatment, a 3-month (3M) depot formulation would increase patient compliance and reduce the injection burden. This interim analysis presents the effect of LA 3M depot on the gonadotropic axis and assesses safety in children with CPP. Methods: In this open-label, multicenter, single-arm, and prospective study, 31 children with CPP were included. Key inclusion criteria were the appearance of secondary sexual characteristics below the age of eight years in girls and nine years in boys with a confirmed diagnosis of CPP. Children treated with prior GnRHa and/or having underlying medical conditions were excluded. Eligible children were treated with LA 11.25 mg subcutaneously every 12 weeks. The primary endpoint of this interim analysis was the proportion of children achieving inhibition of peak LH defined as peak LH ≤ 3.0 IU/L in the GnRH stimulation test at weeks 24. The secondary endpoint was safety analysis in the children receiving at least one dose of LA 3M depot. Results: At baseline, 30 girls and one boy were enrolled. The median (95% CI) chronological age (CA) of the girls was 8.0 (7.0, 9.0) years and the boy was 10 years old. Girls had a median height of 136.95 (131.5, 139.7) cm, weight of 30 (27, 34) kg, and BMI of 16.4 (15.1, 17.9) kg/m2. Baseline bone (BA) age was 11 (10, 11) years, and BA/CA was 1.24 (1.2, 1.3). Boy’s characteristics at baseline differed in CA (10 years), height (144 cm), and BMI (17.4 kg/m2) from girls of this cohort. Due to the data collection time points for the interim analysis, 8 out of the 31 enrolled subjects had a visit at week 24, and 30 subjects reached the week 12 visit time point and had a visit at week 12. The percentage of children achieving inhibition of peak LH (≤ 3.0 IU/L) in the GnRH stimulation test at week 12 was 100 (88.4, 100) %. At week 24, all of them achieved inhibition of LH in the GnRH stimulation test 100 (63, 100) %. Decreases in BA/CA from baseline at weeks 12 and 24 are 93 (77.9, 99.2) % and 50 (15.7, 84.3) % respectively. No progression of the Tanner stage was observed in 96.7 (82.8, 99.9) % and 100 (63, 100) % at weeks 12 and 24. At the data cut-off, 4 (13.33%) patients experienced a total of 5 treatment-emergent adverse events (TEAEs) in the safety population of 30 subjects. No grade ≥3 AE or serious AE was reported. The incidence of injection site reaction was 3.33%. Conclusion: LA at 11.25mg/3M depot effectively suppresses the gonadotropic axis at weeks 12 and 24, normalizing growth and reversibly slowing the early onset of puberty in children with CPP. LA in a 3-month injecting frequency is a safe and convenient treatment option to improve patient compliance. Presentation: 6/3/2024

8129 A Case of Pituitary Stalk Interruption Syndrome Presenting With Panhypopituitarism

Abstract Disclosure: A. Salvat: None. M. Sevilla: None. Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital abnormality characterized by the classic triad of a thinned or interrupted pituitary stalk, an ectopic or absent neurohypophysis, and a hypoplastic or absent anterior pituitary gland. Clinical manifestations vary and can include neonatal hypoglycemia, short stature, cryptorchidism, and delayed puberty. Symptoms can present at birth or later in life with variable degrees of hormone deficiency. Clinical case: A 25-year-old male with hypothyroidism (on levothyroxine since age 13) presented for evaluation of hypogonadotropic hypogonadism. At birth, he was diagnosed with bilateral cryptorchidism and had frequent hypoglycemic episodes. During his childhood and early teenage years, his growth paralleled of his peers. However, at age 18, he experienced a growth spurt with unusually long arms and legs. He never developed secondary sexual characteristics. Physical examination showed blood pressure of 109/62 mmHg, height 193 cm, weight 76 kg, Tanner stage 1 pubic hair, microphallus, and nonpalpable testicles. The initial labs were consistent with panhypopituitarism: FSH 0.14 mIU/mL (0.95–11.95 mIU/mL), luteinizing hormone <0.09 mIU/mL (0.57–12.07 mIU/mL), total testosterone <4 ng/dL (240–871 ng/dL), prolactin 30.31 ng/dL (3.46–19.40 ng/dL), AM cortisol <1 ug/dL (3.7–19.4 ug/dL), ACTH 14 pg/mL (6–50 pg/mL ), cortisol levels 60 minutes after consyntropin stimulation test of 3.6 ug/dL (3.7–19.4 ug/dL), IFG-1 <16 ng/mL (63–373 ng/mL), TSH 7.24 uIU/mL (0.35–4.94 uIU/mL), free T4 0.53 ng/dL (0.70–1.48 ng/dL). Karyotype 46, XY, inv (9) (p12q13). The whole exome sequencing testing was negative. Pituitary magnetic resonance imaging showed hypoplasia of the anterior pituitary gland, ectopic location of the posterior pituitary gland at the expected base of the pituitary infundibulum anterior to the mammary bodies, and hypoplastic or absent pituitary infundibulum, findings suggestive of pituitary stalk interruption syndrome. Scrotal ultrasound showed no testicular or epididymal tissue within the scrotum. DEXA scan showed osteoporosis associated with a long history of non-treated testosterone deficiency. The levothyroxine was adjusted, and the patient was started on intramuscular testosterone, calcium, and vitamin D to manage the hypogonadism and improve the bone mineral density. Conclusion: Diagnosis of PSIS is often delayed due to its variable presentation and age of onset. Although this condition is considered rare, it should be in the differential diagnosis of patients presenting with panhypopituitarism. Early identification of deficient hormones, as well as prompt initialization of hormone replacement therapy, is essential to prevent serious complications associated with these deficiencies, such as adrenal crisis, osteoporosis, diminished quality of life, delayed puberty, and infertility. Presentation: 6/3/2024

7883 Atypical Presentation of Macroprolactinoma: Discordantly Low Serum Prolactin and Therapeutic Challenges

Abstract Disclosure: S. Hossain: None. M.S. Hossain: None. B. Gautam: None. S.C. Kumar: None. H. Liao: None. D.S. Rosenthal: None. Introduction: Pituitary tumors are categorized as microadenomas (<1 cm) and macroadenomas (>1 cm) with prolactinomas being one of the most common causes. The mean prevalence of prolactinomas is 10 per 100,000 in men and 30 per 100,000 in women. Serum prolactin levels corresponds to the size of the prolactinoma and any discrepancy should be treated with caution as that may indicate co-existence of pluripotent cells. We present a patient who presented with visual field defect and headaches, found to have a pituitary macroadenoma with discordantly low serum prolactin level compared to the size of adenoma, prompting a change in the treatment course. Case Presentation: A 42 year old male with no past medical history was seen as an endocrinology consult requested by neurosurgery for frequent headaches and visual problems for 1 year. Vital signs were normal, with negative orthostatic drop of blood pressure. He had prominent bitemporal hemianopsia confirmed by formal visual field testing by Ophthalmology. No galactorrhea or features suggestive of acromegaly or hyperthyroidism. He complained of erectile dysfunction but appeared to have normal male secondary sexual characteristics. MRI of brain showed a suprasellar mass measuring 3.8 x 2.6 x 2.2 cm with mass effect on the optic chiasm, hypothalamus with extension and infiltration into the right cavernous sinus. Lab results showed elevated prolactin of 1343.5 ng/ml confirmed by serial dilution, low serum testosterone level of 134 ng/dl and inappropriately normal FSH and LH. Complete blood counts, comprehensive metabolic panel, TFT, ACTH, cortisol and IGF-1 were normal. Patient was started on bromocriptine and he noticed improvement in his field of vision and acuity within one week of starting therapy. He continued to show sustained improvement in vision and resolution of his headaches at the one-month mark. MRI 2 months from starting bromocriptine showed modest reduction in size of the tumor to 2.1 x 2.3 x 2.4 cm with continued mass effect on the optic chiasm. Prolactin level decreased to 69.3 ng/ml. Therefore, although there was some improvement in visual fields, surgical resection was recommended to alleviate the mass effect on the optic chiasm. Conclusion: Our case highlights the significance of identifying discrepancies between the size of a prolactinoma and serum prolactin levels. Expected prolactin level from a prolactinoma similar in size to our case would be >3000 ng/ml when ours was 1343.5ng/ml. Despite undergoing treatment and lowering of prolactin levels our patient's pituitary adenoma did not significantly reduce in size after two months of treatment with bromocriptine and the mass continued to exert pressure on the optic chiasm. This suggests possible presence of pluripotent cells in addition to prolactin-producing cells within the tumor. The recommended course of action was surgical resection of the mass. Presentation: 6/1/2024

8380 Pituitary Stalk Interruption Syndrome, A Rare Cause of Panhypopituitarism

Abstract Disclosure: F. Abdulkarim: None. E. Alshdifat: None. P. Henriquez Feliz: None. J. Vargas-Jerez: None. T. Zahra: None. Pituitary Stalk Interruption Syndrome, A Rare Cause of Panhypopituitarism Faridat Abdulkarim, MD. Esra’a Alshdifat, MD. Pamela Henriquez Feliz, MD. Julia Vargas- Jerez, MD. and Tasneem Zahra, MD. Introduction: Pituitary stalk interruption syndrome (PSIS) is a rare congenital pituitary anatomical abnormality with reported incidence of 0.5 per 100,000 live births. It is characterized by the triad of thin or interrupted pituitary stalk, absent or ectopic posterior lobe and hypoplastic or aplastic anterior lobe seen on MRI. The anterior pituitary function is usually impaired however the posterior pituitary is usually intact and normal. We report a case of a Now 34-year-old Female who presented to the endocrine clinic with underdeveloped sexual characteristics. MRI done was consistent with PSIS. This is the second case of PSIS we report from our Institution. Case Presentation: A Now 34-year -old Hispanic American Female presented to our endocrine clinic with underdeveloped secondary sexual characteristics. She had panhypopituitarism, including Growth hormone deficiency and was treated with growth hormone from early childhood until age 13-14 years. She re-presented to our clinic at the age of 28 years after being lost to follow up for many years. On physical examination, she was 175cm tall, weighed 89.4kg and BMI 29.1kg/m2Patient has pre-pubertal breast, tanner stage 1, no axillary hair, small external genitalia with scanty pubic hair. Hormonal analysis revealed Estradiol <5 pg/mL (low), FSH 0.4 IU/L (low), LH <0.3 IU/L (low), Progesterone 0.1ng/mL (Low), Testosterone <2.5 ng/dL (8.4- 48.1ng/dl) Prolactin 22.3ng/mL (3.4-24.1 ng/ml), TSH 0.88uIU/mL (0.27-4.20), Free T4 0.5ng/dl (0.9-1.8) , ACTH 7.7pg/mL (7.2-63.3), Baseline AM Cortisol 0.7ug/dL (6.0-18.4) and 5.5 ug/dL after Cosyntropin test, IGF-1 17ng/mL (83-280). Urinalysis revealed normal specific gravity. Chromosome analysis with Normal Karyotype 46XX. Pelvic US revealed Markedly diminutive uterus and ovaries. MRI of the pituitary was highly suggestive of PSIS. She is currently being treated with levothyroxine and hydrocortisone Conclusion: PSIS is a rare congenital abnormality. Fortunately has good prognosis, however if left undiagnosed/untreated has high mortality mainly from Adrenal insufficiency and Myxedema coma. The patient discussed above, has underdeveloped sexual characteristics and primary amenorrheaLaboratory finding consistent with Panhypopituitarism with Normal prolactin which is the case in most patient with PSIS. Imaging revealed atrophic uterus and ovaries, and MRI revealed Findings which are highly suggestive of PSISShe previously had problems with outpatient clinic visits and medication compliance. However, she is currently compliant with hormonal replacement therapy which is the mainstay of treatment. Presentation: 6/3/2024

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

Primary and Secondary Sexual Characteristics of Kuhli Loach (Pangio kuhlii)

Kuhli loach (Pangio kuhlii) a popular ornamental freshwater fish species with economic potential, originating from Sumatra, Kalimantan, Java, and Malaysia. The kuhli loach's appeal lies in its vibrant colors and distinctive eel-like body. This study aims to explores the sexual primary and secondary characteristics of the kuhli loach. Conducted at Universitas Airlangga in Banyuwangi, Indonesia, the study involved a thorough analysis of 50 kuhli loaches, evenly split between males and females. Morphological observations revealed significant differences (p < 0.05), such as the elongated body and expanded abdominal region in females, suggesting adaptations for reproduction. Internal examinations, including peritoneal dissections and histological analysis, unveiled distinct stages of spermatogenesis in males and ovarian development in females, providing insights into the reproductive cycle. Meristic and morphometric analyses identified noteworthy differences in pectoral fin rays, suggesting potential roles in reproductive behavior, while other traits exhibited similarity between genders. This study contributes to the understanding of kuhli loach ecology and reproductive biology, highlighting the importance of addressing sustainability concerns arising from the continuous exploitation of wild populations. This study serves as a foundational step towards advancing reproductive improvement in fish and supports the conservation of this unique ornamental fish species, with implications for aquaculture practices and economic considerations.

Mayer-Rokitansky-Küster-Hauser Syndrome: A Case of Primary Amenorrhoea and Diagnostic Approach

Background: Amenorrhoea, defined as the absence of menstruation, can be classified into primary and secondary types. Primary amenorrhoea is diagnosed when menstruation has not occurred by age 15 or within three years of breast development. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare cause of primary amenorrhoea characterized by uterovaginal aplasia in women with a normal 46, XX karyotype and secondary sexual characteristics. This case report discusses a 15-year-old girl diagnosed with MRKH syndrome after a thorough diagnostic workup. Methods: A detailed diagnostic evaluation was conducted, including physical examination, imaging (ultrasonography and MRI), hormonal testing, and chromosomal analysis. The patient presented with primary amenorrhoea and no family history of related conditions. Ultrasound and MRI confirmed the absence of a uterus and non-visualization of the ovaries. Hormonal tests were within normal ranges, and chromosomal analysis revealed a 46, XX karyotype. Results: The diagnostic workup confirmed an atrophic uterus with small bilateral ovaries and no functional endometrial tissue. Mayer-Rokitansky-Küster-Hauser syndrome was diagnosed. The patient was counseled regarding surgical options, including neovaginoplasty, to create a functional vaginal canal for sexual intercourse. Conclusion: MRKH syndrome, though rare, is an important consideration in cases of primary amenorrhoea. Timely diagnosis through imaging and chromosomal analysis is crucial for appropriate management. Psychological counseling and surgical options such as neovaginoplasty can significantly improve the quality of life for affected individuals, particularly regarding sexual health and reproductive possibilities. Addressing the psychological burden associated with infertility is also critical to patient care.

Smart City Aquaculture: AI-Driven Fry Sorting and Identification Model

The development of smart agriculture has become a critical issue for the future of smart cities, with large-scale management of aquaculture posing numerous challenges. Particularly in the fish farming industry, producing single-sex fingerlings (especially male fingerlings) is crucial for enhancing rearing efficiency and could even provide key support in addressing future global food demands. However, traditional methods of manually selecting the gender of broodfish rely heavily on experienced technicians, are labor-intensive and time-consuming, and present significant bottlenecks in improving production efficiency, thus limiting the capacity and sustainable development potential of fish farms. In response to this situation, this study has developed an intelligent identification system based on the You Only Look Once (YOLO) artificial intelligence (AI) model, specifically designed for analyzing secondary sexual characteristics and gender screening in farmed fish. Through this system, farmers can quickly photograph the fish’s cloaca using a mobile phone, and AI technology is then used to perform real-time gender identification. The study involved two phases of training with different sample sets: in the first phase, the AI model was trained on a single batch of images with varying parameter conditions. In the second phase, additional sample data were introduced to improve generalization. The results of the study show that the system achieved an identification accuracy of over 95% even in complex farming environments, significantly reducing the labor costs and physical strain associated with traditional screening operations and greatly improving the production efficiency of breeding facilities. This research not only has the potential to overcome existing technological bottlenecks but also may become an essential tool for smart aquaculture. As the system continues to be refined, it is expected to be applicable across the entire life cycle management of fish, including gender screening during the growth phase, thereby enabling a more efficient production and management model. This not only provides an opportunity for technological upgrades in the aquaculture industry but also promotes the sustainable development of aquaculture. The smart aquaculture solution proposed in this study demonstrates the immense potential of applying AI technology to the aquaculture industry and offers strong support for global food security and the construction of smart cities.

Swyer Syndrome: Clinical Case of Gonadal Dysgenesis in a 15-year-old Girl

Swyer syndrome is a rare genetic disorder in which gonadal dysgenesis and karyotype 46, XY are observed. In the postnatal and prepubescent period, this disease has no clinical manifestations and is asymptomatic, which makes diagnosis difficult. The first signs of the syndrome appear in puberty in the form of underdevelopment of secondary sexual characteristics. This review presents the criteria based on which such a diagnosis as Swyer syndrome can be made. The main diagnostic methods are highlighted, the possibilities of both surgical treatment of patients and drug treatment due to hormone replacement therapy are considered. Verification of the syndrome contributes to a more thorough examination, which will allow you to determine management tactics and avoid complications from other organs and systems.

Sirtuin 1-mediated autophagy regulates testosterone synthesis in Leydig cells of piglets

Testosterone is secreted by Leydig cells (LCs), which play an important physiological role in preserving male secondary sex characteristics, protecting male reproductive function, and establishing the blood-testis barrier. Studies have shown that autophagy is particularly active in LCs; however, its involvement in testosterone synthesis in porcine LCs has not been fully explored. Therefore, this experiment aimed to investigate the influence of autophagy on testosterone secretion in porcine LCs and its potential regulatory mechanism. Our results demonstrated that both testicular autophagy and serum testosterone levels increased in piglets during postnatal development from 4 to 18 weeks. In addition, autophagy was found to degrade the Na+/H+ exchange regulatory factor 2 (NHERF2), leading to the up-regulation of scavenger receptor class B type 1 (SRB1). This process resulted in increased cholesterol intake and enhanced testosterone production. The observable level of sirtuin 1 (SIRT1) was directly proportional to the level of autophagy. In vitro investigations have shown that SIRT1 can affect the level of autophagy, cholesterol uptake as well as testosterone release. In conclusion, testosterone synthesis during pig development is regulated by SIRT1. SIRT1 mediates the degradation of NHERF2 through autophagy, thereby weakening its negative regulatory effect on the high-density lipoprotein receptor SRB1 in Leydig cells. This process increases cholesterol uptake and enhances testosterone synthesis.

Vaginal Agenesis: Diagnosis on Ultrasound and Management of a Case at the Gabriel Toure University Hospital in Bamako (Mali)

Vaginal malformations can be diagnosed by ultrasound in a large number of cases. The prevalence of uterovaginal aplasia usually reported in the literature is 1/4000 to 1/10,000. Objectives: We tell you about the difficulties of diagnosis with ultrasound, the difficulties of managing our case of vaginal aplasia. Observation: This was a 20-year-old patient saleswoman, single. History of the disease: was marked by cyclic pelvic headache for 6 months with primary amenorrhea. She has no particular medical-surgical history. On physical examination: Secondary sexual characteristics were developed. On inspection of the vulva, normal pubic hair was noted. Examination of the vulva showed the labia majora and labia minora present and normal-looking. A hymen could not be identified and there was no visible vaginal opening. Faced with this clinical and paraclinical symptomatology, we made the diagnosis of vaginal agenesis. The ultrasound showed a uterus measuring about 92x71x62 mm, its parenchyma is homogeneous, its contours are regular. The presence in the uterine cavity at the corporeofundic level of a homogeneous echogenic collection of about 66.5 cc (69x35 mm). Note the congenital malformation of the cervix with agenesis). The Surgical Procedure Performed is vaginoplasty. Conclusion: Ultrasound of uterine malformation is difficult and requires some experience from the sonographer.

Clinical phenotype and molecular genetic analysis of seven children with CHARGE syndrome

To explore the clinical phenotype and genetic etiology for seven children with CHARGE syndrome (CS). Clinical data of seven children with CS diagnosed between March 2020 and December 2022 at the Children's Hospital Affiliated to Zhengzhou University were analyzed. Genomic DNA was extracted from peripheral blood samples from the children and their parents, and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. The ages of the children had ranged from 1 day after birth to 12 years old, and all of them had shown growth retardation. The reasons for their admission had included postnatal breathing, swallowing and feeding difficulties in five cases. One child was found to have abnormal external genitalia in conjunct with hearing impairment, whilst another child had shown no secondary sexual characteristics during puberty. All of the children were found to harbor CHD7 gene variants, which included 3 nonsense variants, 2 frameshifting variants and 2 missense variants, i.e., c.6292C>T (p.R2098*), c.2754G>A (p.W918*), c.469C>T (p.R157*), c.3308T>A (p.V1103D), c.7111delC (p.Q2371Kfs), c.6023delA (p.D2008Vfs) and c.3565C>T (p.R1189C). All of the variants were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3308T>A (p.V1103D) and c.3565C>T (p.R1189C) variants were rated as likely pathogenic (PS2+PM2_Supporting+PP3), whilst the remainders were rated as pathogenic (PVS1+PS2+PM2_Supporting). There is strong clinical and genetic heterogeneity in CS. Early genetic testing may facilitate accurate diagnosis. The detection of novel variants has expanded the phenotypic spectrum of CS and the mutational spectrum of the CHD7 gene.