Testosterone Levels Research Articles

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, & B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

8711 The Effect of Testosterone Therapy Upon Bone Remodelling in Testosterone Deficient APOE-/- Mice Fed a High Fat Diet

Abstract Disclosure: A. Williamson: None. L. Bateman: None. C. LeMaitre: None. T.H. Jones: None. N. Aberdein: None. D.M. Kelly: None. Introduction: Low testosterone can lead to bone loss in males, but the mechanisms are not fully characterised. This study investigates the effects of testosterone depletion, and subsequent testosterone treatment on parameters of bone remodeling in a murine model of cardiometabolic disease. Methods: At 8 weeks of age, high-fat diet-fed ApoE-/- mice were randomised into three groups: sham surgery + placebo treatment (control, n=9), orchidectomy + placebo treatment (n =8), and orchidectomy + testosterone treatment (n=10). 25 week old mice were sacrificed and tissues collected for analysis. Left tibiae were decalcified, paraffin embedded and sectioned prior to immunostaining of bone turnover markers including receptor activator of nuclear factor κB ligand (RANKL), Osteoprotegerin (OPG), runx2, Alkaline Phosphatase (ALP), adiponectin and marrow lipid content. Right tibiae underwent mechanical 3-point bend testing at 0.05mm/s using a CellScale Univert. Results: µCT demonstrated a significant decrease in trabecular bone volume, number, and bone mineral density (BMD) and increased trabecular thickness in orchidectomised mice compared to controls. These parameters returned to control levels in testosterone treated orchiectomised mice. No significant differences were observed in cortical bone. Lipid deposition within the bone marrow was significantly increased in testosterone deficient mice compared to testosterone replete mice. No significant differences in ALP immunopositivity were detected between groups, and runx2 was significantly decreased in orchiectomised mice treated with testosterone compared to controls. The ratio of RANKL/OPG immunopositivity was significantly increased in testosterone deficient mice compared to testosterone replete mice. 3-point bending demonstrated no significant differences in maximal force between groups despite a downward trend in orchiectomised groups compared to controls. Osteoclast number quantified from TRAP-stained sections was not different between groups. Discussion: Testosterone depletion accelerates trabecular bone loss, mediated by increased osteoclastogenesis via the RANKL/OPG pathway and increased bone marrow adiposity, an effect reversed by testosterone treatment. While this study highlights the benefits of testosterone upon trabecular bone health in male mice these changes may not alter fracture risk as 3-point-bend maximal force was not affected. Presentation: 6/2/2024

12333 46 XX/XY Chimerism - Positive NIPT And Post-natal Karyotype Is It Real?

Abstract Disclosure: K.L. Del Rosario: None. N. Sheriden: None. N. Vijayakanthi: None. Introduction: Non-Invasive Prenatal Testing(NIPT) using cell free fetal DNA in plasma of pregnant women has become a routine part of prenatal care in screening for fetal aneuploidies including sex chromosome abnormalities in most regions around the world. False positive results are increasingly imposing challenges in pre-natal as well as post-natal care. Case Discussion: We report a neonate born at 32+2 weeks gestation to a 42-year-old G2 P2 mother. Pregnancy was complicated by insulin dependent maternal type 2 diabetes mellitus, maternal chronic hypertension and a positive NIPT for high-risk monosomy X. Prenatal ultrasound showed male anatomy. Interestingly on physical exam after birth, the neonate had typical male external genitalia with bilateral normal male gonads. Chromosome analysis done immediately after birth revealed the presence of two cell lines: 40 of the 50 cells (80%) had a normal female 46 XX karyotype and 10 of the 50 cells (20%) had a normal male 46 XY karyotype. These findings could be due to reabsorbed twin, Klinefelter syndrome with two trisomy rescue events, maternal cell contamination or true chimerism. In addition, fluorescence in situ hybridization (FISH) analysis for X and Y probes revealed the presence of two cell lines. The first cell line (70% of the cells) had two hybridization signals for chromosome X and the second cell line (∼25% of the cells) had one hybridization signal for chromosome X and one for chromosome Y. Postnatal ultrasound showed normal testicles with no evidence of Mullerian structures. Newborn screening was negative for congenital adrenal hyperplasia (CAH). Genetics was consulted and recommended repeat chromosomal analysis, parental testing to determine sex chromosome segregation, and follow-up with pediatric endocrinology. Repeat cytogenetic testing at 2 weeks of life resulted in a normal male chromosome complement of 46,XY. Previous abnormal cytogenetics were thought to be due to maternal cell contamination. Further endocrine labs showed LH(1.16 uIU/ml) and testosterone levels ( 87 ng/dL), appropriate levels for age indicating normal Hypothalamic Pituitary Gonadal (HPG) axis and testicular Leydig cell function. Since the family was previously counseled regarding the concept of maternal cell contamination, they expressed understanding and were happy with the update of the normal karyotype result. Conclusion: False-positive results concerning for rare chimerism on NIPT can occur and should prompt a thorough history, physical exam, ultrasound studies and repeat testing to confirm its presence. Careful consideration should be taken when counseling family about the implications of these results, especially communication about gender assignment of the infant. Presentation: 6/3/2024

6629 Pure Androgen Secreting Adrenal Adenoma In A Premenopausal Woman

Abstract Disclosure: S. Syed: None. Background: Pure androgen secreting adrenal adenomas are extremely rare; most of the reported cases occur in post-menopausal women, with significant virilization of acute onset and are usually malignant. Here we present a case of an androgen secreting adrenal adenoma found in a young female with regular menstrual cycles and hirsutism. Clinical Case: A 27-year-old female with no significant past medical history was referred to Endocrinology clinic for evaluation of elevated testosterone level noted on a routine OBGYN exam. Patient had miscarriage six months prior to initial endocrine clinic visit. She had a routine follow up visit with her gynecologist after miscarriage and noted to have mild male pattern hair growth on her chin, worse after stopping birth control pills two years ago. Patient had menarche at 14 years of age and had regular menstrual cycle until started birth control pills. The skin examination revealed coarse male pattern hair on chin. Scattered acne was present on back. No signs of hypercortisolism were present. Labs done at time of initial consultation showed unremarkable comprehensive metabolic panel, thyroid and gonadotropic hormones. Testosterone was elevated at 122ng/dl (0-75ng/dl). Pelvic ultrasound done in the year prior showed normal uterus and adnexal structures. Further work up showed elevated DHEAS 781 µg/dL (18-391 µg/dL) and normal 17 OH progesterone and androstenedione levels. MRI abdomen with and without contrast done at outside facility showed a 4 cm x 3.3 cm x 4.1 cm well-circumscribed round shaped, mildly heterogeneously enhancing mass arising from right adrenal gland, with restricting diffusion, no signal dropout in out-of-phase imaging. Normal ovaries were noted. Given the large size of lesion, adrenalectomy was recommended. Patient underwent laparoscopic right adrenalectomy. The histologic features on pathology specimen were consistent with an adrenal cortical adenoma. No evidence of malignancy was seen (based on modified Weiss criteria). 3 weeks post op labs showed Testosterone level reduced to 19 ng/dl (0-75ng/dl) and DHEAS 138 ug/dl (18-391 µg/dL). Patient is recovering from recent childbirth. Conclusion: In adults, pure androgen secreting adrenal tumors are extremely rare. Diagnosis of malignancy is made with histopathological examination and Weiss score calculation. Our patient has unique presentation of having mild hirsutism in setting of regular menstrual cycles with no other symptoms of virilization and is noted to have unexpectedly large adrenal adenoma. Given the size of adenoma, there was concern for adrenal cortical carcinoma, however histological examination was consistent with a benign lesion. Presentation: 6/1/2024

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

7709 Ovotesticular Difference of Sex Development: Prognostic Evaluation, Sex Assignment, and Ethics

Abstract Disclosure: X. Xu: None. Y. Lin: None. B. Shivanna: None. A. Lee: None. J.C. Hakim: None. D.G. Mann: None. L.M. Noll: None. P. Georgiadis: None. S.K. Gunn: None. L.P. Karaviti: None. Background: Our case provides the identification and management of a newborn baby with ovotesticular syndrome, which was formerly known as true hermaphroditism. The term was classically derived from Greek mythology in which the deity 'Hermaphroditus', merging with the nymph Salamis, embodied both male and female attributes. The term 'true hermaphroditism' is now avoided due to its stigmatizing connotations. Ovotesticular difference of sex development (DSD) is an exceedingly rare condition, occurring in fewer than 1 in 20,000 births. This condition involves the coexistence of functional ovarian and testicular tissue within one individual, presenting a challenge in sex assignment due to unpredictable gender development. Clinical Case: This is a single case of the presence of ovarian and testicular differentiation on one side and a transitional zone of mixed pattern. Prenatal genetic testing consistent 46,XX karyotype. Initial ultrasound at the outside hospital revealed a uterus and right testicle. The baby exhibited Prader stage 4 genitalia, with a palpable gonad in the right labioscrotal area and the left gonad not palpable. Prophylactic hydrocortisone was started due to concerns regarding NR5A1/SF1 mutation. Further evaluations, including genetic tests, hormonal assessments, urinalysis and kidney ultrasound for the WT1 mutation, and scrotal and pelvic ultrasounds, were conducted. The high-dose ACTH stimulation test ruled out adrenal insufficiency. The testosterone level was in the male range, and the HCG stimulation test further confirmed functioning Leydig cells. The postnatal karyotype was 46,XX, and chromosome microarray analysis showed no abnormalities. Our approach to this case was multidisciplinary, including our endocrine experts, urologist, gynecologist, ethicist, and psychologist. We discussed the fluidity of sex assignment and addressed the degree of virilization, nature of the gonadal tissue, and emphasized the necessity of regular clinical follow-up. Our main concern was to educate the parents and protect the choices of the child. In this case, the child assumed a male sex assignment, as a result of the decision-making process between our team and the parents. In this context we did emphasize the fluidity of sex assignment. Clinical Lesson: Long-term outcomes for ovotesticular DSD remain understudied. Existing reports highlight varying rates of gender dysphoria, sexual function, and psychological well-being. Our approach to managing ovotesticular DSD involved a framework emphasizing ethical considerations and parental involvement. We advocated for and practiced a shared decision-making model involving healthcare providers, parents, and ultimately the patient. Presentation: 6/3/2024

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

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

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

8309 Injectable Estradiol Dosing Regimens; A Retrospective Review of Hormone Therapy for Gender-Diverse Adults Assigned Male at Birth

Abstract Disclosure: M. Kanin: None. M. Slack: None. R. Patel: None. K. Chen: None. N. Jackson: None. K. Williams: None. S. Grock: None. Introduction: Many gender incongruent individuals assigned male at birth (AMAB) seek hormone therapy to achieve physical and emotional changes. Hormone therapy typically includes estradiol, with or without an anti-androgen. However, limited data with relatively weak justifications support the currently recommended regimens. In particular, dosing schedules for injectable estradiol can vary considerably. UCSF guidelines recommend initiating estradiol valerate at 5 mg parenterally weekly or estradiol cypionate 2 mg weekly. Endocrine Society Guidelines recommend estradiol valerate or cypionate parenterally 5-30 mg every 2 weeks or 2-10 mg weekly. Our clinical observations led to the concern that current guideline-based dosing of injectable estradiol can result in supratherapeutic estradiol levels. Thus, we designed a retrospective cohort study to evaluate injectable estradiol dosing requirements for gender diverse individuals at our institution. Hypothesis: We hypothesize that low dose estradiol injections can lead to therapeutic estradiol levels (100-200 pg/mL) and suppressed testosterone (<50 ng/dL). Design: We performed a retrospective cohort study of gender diverse individuals AMAB aged 18-89 who were newly prescribed injectable estradiol by a single clinic from January 2017 to March 2023. Exclusion criteria included history of orchiectomy or estradiol use within the previous six months. Patients were identified using structured query language to extract data from our institution’s electronic health record system. A total 33 patients were identified, 29 of whom were eligible for inclusion. Data was collected for 15 months after estradiol initiation. Results: All individuals were prescribed estradiol valerate except for 1 who was prescribed estradiol cypionate. Estradiol dose ranged from 2.5 to 10 mg weekly and an average initial dose of 4.26 mg weekly. Mean initial estradiol level obtained while on treatment for at least 30 days was 349.8 pg/mL, which is supratherapeutic. Mean initial testosterone level was 25.3 ng/dL, which is suppressed. Mean estradiol dose at completion of data collection was 3.68 mg with a mean final estradiol level of 245.2 pg/mL. Testosterone levels reached less than 50 ng/dL for everyone in the sample with a mean final testosterone of 23.3ng/dL despite significant reductions in estradiol dose (change=-0.58 mg per week, p=0.001) Conclusion: Our study demonstrates lower dosages of estradiol can be used to achieve therapeutic estradiol levels in gender incongruent patients seeking estrogen therapy. Using lower dosages can avoid supratherapeutic estradiol levels and the associated risks. Further prospective studies are needed with the aim to reevaluate current guideline dosing recommendations for injectable estradiol. Presentation: 6/2/2024

6874 A Rare Case Of Hereditary 1,25 (OH)2D Resistant Rickets

Abstract Disclosure: G. Umarji: None. F. Thelmo: None. S.A. Jabbour: None. Vitamin D-dependent rickets type 2A (VDDR2A) also known as hereditary 1,25 (OH)2D resistant rickets is due to biallelic loss-of-function mutations in the gene encoding vitamin D receptor on chromosome 12q13.11, thus, it represents a true form of tissue resistance to vitamin D. It is a scarce form of rickets with approximately only 120 cases reported. A 37-year-old male was referred to endocrinology by neurosurgery for evaluation of metabolic bone disease. Seven years ago, he was in a car accident which resulted in a lumbar spine injury causing radiculopathy and severe low back pain leading to lumbar spine decompression/fusion. However, he suffered from nonunion of bones and had to undergo another surgery a year later with recurrent postoperative nonunion of bones. During the operation, the surgeon noticed that his spine seemed demineralized. He had a history of multiple minor fractures in childhood, decreased hearing in left ear for two years, fragile teeth for many years, and some hair loss since age 30. Physical exam showed a height of 1.82 m, weight 89.3 kg with body mass index of 26 kg/m2, broken teeth, no leg bowing and normal stance. Laboratory results showed normal renal function, thyroid function tests and testosterone level, corrected calcium 8.3 mg/dL (8.7-10.2), 25-OH-vitamin D 54 ng/mL (30-100), phosphorus 2.8 mg/dL (2.8-4.1), intact parathyroid hormone 65 pg/mL (15-65), bone-specific alkaline phosphatase 21 mcg/L (4-27), 24-hour urine calcium 156 mg/day (100-300), 24-hour urine phosphorus 1,752 mg/day (390-1,425), FGF-23: 93 RU/mL (44-215) and 1,25 (OH)2D 92 pg/mL (24-81.5). Dual absorptiometry of the lumbar spine and hip showed osteopenia with Z scores of -2.2 and -1.2 respectively. Genetic testing for metabolic bone disease panel showed heterozygous mutation in VDR gene at nucleotide position c.146+9dup associated with autosomal recessive VDDR2A. We present a very rare form of vitamin D resistant rickets. As many patients with VDDR2A are unable to respond to any form of vitamin D, it is suggested that VDDR2 be more appropriately described as hereditary 1,25 (OH)2D resistant rickets (HVDRR), hereditary resistance to 1,25 (OH)2D, or even pseudovitamin D-deficiency type IIA (PDDR IIA). Clinical features include severe rickets, bone pain, hypotonia, dental caries and alopecia. Biochemical features include hypocalcemia, hypophosphatemia, normal to elevated alkaline phosphatase, normal 25(OH)D and importantly, elevated 1,25-(OH)2D levels. Management is with high doses of calcium and vitamin D therapy. While rare, this disease highlights the need for a comprehensive evaluation of metabolic bone diseases and a thorough understanding of calcium and vitamin D metabolism. Presentation: 6/2/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in < 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone < 2.6 ng/dL; Total testosterone: < 10ng/dL; and Free androgen index < 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

7202 CPP with Rapid Pubertal Progression in a 9-Year-Old Boy with Hypothalamic Teratoma

Abstract Disclosure: R. Robilliard: None. G. Tung: None. K. Svokos: None. R. Lulla: None. J.Q. Quintos: None. Background: Central Precocious Puberty (CPP) in males is rare, with incidence of 0.01-2/10,000. The most common identifiable cause of CPP in young children is hypothalamic hamartoma. No case hypothalamic teratoma has been reported to cause CPP in males. Clinical Case: At the age of 10-years and 5-months, a boy presented to the pediatric endocrinology with signs of precocious puberty including facial hair development, voice deepening, and increased growth velocity that began at 9 years old. There was no significant past medical history and he denied headache, blurry vision, or diplopia. Physical examination showed height of 140.4 cm (47%), Tanner 4 genitalia, Tanner 3 pubic hair, and testicular volumes of 15 cc (left) and 12-15cc (right). Bone age (BA) determined by radiography was 13.5 years with a predicted adult height (PAH) of 63 inches. The mid-parental target height was 67 +/- 4 inches. Evaluation including TSH, glucose, serum and CSF β-HCG, DHEA, CSF AFP was normal. Serum LH was 2.9 IU/L and testosterone level was 109 ng/dl, consistent with CPP. MRI of the pituitary showed a small, heterogeneous and fat-containing lesion extending inferiorly from the tuber cinereum consistent with teratoma. Treatment included GnRH agonist Lupron (30mg) every 3 months. Laboratory evaluation 8 months after initial presentation showed suppressed LH of 0.9 IU/L and FSH 0.5 mIU/mL, and testosterone of 57 ng/dL. Repeat radiography for BA one year after GnRHa suppression showed BA of 14 years at CA of 11 years 6 months and PAH of 64.4 inches. Growth velocity slowed to 5.3 cm/year. At the most recent follow-up visit at CA of 12 years, height was 151.5 cm (61%), growth velocity 6.3 cm/year (74% for age), Tanner 5 penis and pubic hair, left testicular volume of 15-20cc and right testicular volume of 15 cc. Most recent radiographic BA is14 years, and PAH is 65.9 inches. Given response to GnRH agonist injections every 3 months, the absence of CNS symptoms referable to the teratoma and no change in MR imaging, no surgical intervention is recommended. Conclusion: This is the first case of a hypothalamic teratoma reported in a male associated with CPP. Despite this rare cause, the patient has responded to standard treatment with GnRH agonist therapy alone. Presentation: 6/1/2024

8661 A case of post-menopausal female with virilization due to Sertoli-Leydig cell ovarian tumor recurring in contralateral ovary 8 years later

Abstract Disclosure: M.S. Maharaul: None. J.L. Miller: None. Introduction: Sertoli-Leydig cell tumors (SLCTs) are rare androgen-secreting tumors of the ovaries, accounting for less than 0.5% of all ovarian tumors. Their incidence peaks in the second to third decade of life. New onset of severe hyperandrogenism with virilization in postmenopausal women is exceedingly rare, and the three most frequent causes are ovarian tumors, ovarian hyperthecosis and adrenal androgen producing tumors. We report one such case of ovarian androgen producing tumor which was further complicated by recurrence in the contralateral ovary. Case: A 66-year-old woman presented for evaluation of hyperandrogenism. Physical examination revealed evidence of virilization and clitoromegaly. Laboratory workup was remarkable for total serum testosterone level of 367 ng/dL with normal dehydroepiandrosterone sulfate and cortisol levels. A computerized scan of abdomen did not show any adrenal masses. Transvaginal ultrasound revealed uterine myomas but did not show any ovarian pathology. She underwent selective vein catheterization of her adrenal glands as well as ovaries and was noted to have right ovary secreting 3,982 ng/dL of testosterone whereas all other samples had total testosterone levels < 200 ng/dL. She underwent right salpingo-oophorectomy. Histopathologic examination revealed a 2.2 cm well differentiated Sertoli-Leydig cell tumor confined to the ovary; the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 18 ng/dL. 8 years later, she returns with recurrent symptoms of hyperandrogenism. Repeat workup revealed a total testosterone level of 662 ng/dL. A computerized scan of abdomen and transvaginal ultrasound revealed an unremarkable uterus and left ovary. Magnetic resonance imaging of the pelvis was done that showed a 1.2 cm enhancing mass in the left ovary. She then underwent left salpingo-oophorectomy and supracervical hysterectomy. Histopathologic examination revealed a 1.5 cm Sertoli-Leydig-cell tumor of the left ovary, the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 24 ng/dL and she felt significant improvement in her symptoms. Conclusion: We present an interesting case of virilization in a post-menopausal female due to Sertoli-Leydig cell tumor that resolved after unilateral oophorectomy but recurred 8 years later in the contralateral ovary with resolution after completion oophorectomy. Presentation: 6/2/2024

8162 A Unique Presentation of Ovarian Steroid Cell Tumor Causing Hyperandrogenism in a Postmenopausal Woman

Abstract Disclosure: A. Rehan: None. M. Pandey: None. I. Goyal: None. E. Punni: None. N. Shakir: None. Background:­­­ Steroid cell tumors of the ovary are a rare entity, constituting less than 0.1% of all ovarian tumors. These tumors can present with diverse endocrine and paraneoplastic effects, including androgen excess and polycythemia. Hyperandrogenism in females can lead to hirsutism, virilization, alopecia, menstrual irregularities, acne, and emotional changes, with complications including hyperlipidemia and insulin resistance. There are various causes of androgen excess in a female including polycystic ovary syndrome (PCOS), androgen-secreting tumors, Cushing’s syndrome, and congenital adrenal hyperplasia. In a postmenopausal woman displaying signs of androgen excess, one must consider androgen-secreting tumors, and even the rare ovarian steroid cell tumor as a possible cause. Clinical Case: A 62-year-old female with type 2 diabetes mellites, obstructive sleep apnea, anxiety and depression initially presented to her primary care provider with fatigue, light-headedness, and weight loss. Initial blood work done revealed a hemoglobin greater than 20 g/dL (NR 12-16) and hematocrit greater than 60% (NR 36-48), requiring several sessions of phlebotomy. Symptoms persisted and she was finally referred to a hematologist who noted physical exam findings of hirsutism and virilization, including temporal hair loss and excess facial/body hair growth. Other concerning signs included clitoromegaly, decrease in chest size, and deepening voice. Menopause had occurred at age 50, and the patient did not have any issues with fertility during her reproductive years. Biochemical evaluation revealed testosterone level of greater than 1500 ng/dL (NR 19-82) with normal sex hormone binding globulin level, DHEA-S 652 ug/dL (NR 29-220), appropriately suppressed FSH/ LH, and normal salivary cortisol levels. Tumor markers showed normal CEA, and alpha fetoprotein but elevated CA 125 to 80.5 U/ml (NR < 38.1). Pelvic ultrasound demonstrated a 12 cm heterogeneously echoic, vascular right adnexal mass concerning for ovarian malignancy. Pelvic MRI showed a 9.8 cm right sided cystic and solid adnexal mass. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, peritoneal biopsies, and omentectomy. Pathology revealed a stage IA steroid cell tumor measuring 11.4 cm. After resection, the patient reported improvement in facial hair and fatigue. Labs showed normalization of hemoglobin, hematocrit, and testosterone levels. Conclusion: This rare case highlights the importance of considering steroid cell tumor as a cause of polycythemia with hyperandrogenism. Timely diagnosis and intervention play a critical role in preventing irreversible virilization, mitigating malignant risks, and, in certain instances, preserving fertility. Generally, the prognosis is favorable, and symptom and lab normalization is often achieved through surgical resection. Presentation: 6/2/2024

12539 Estrogen Type In Contraceptives Matters: Effects On Spatial Memory And Anxiety-Like Behaviors In A Female Rat Model

Abstract Disclosure: A.P. Hegwood: None. S. Kujawa: None. A.V. Prakapenka: None. According to U.S. Centers for Disease Control & Prevention, ∼12% of the U.S. population uses combined oral contraceptives (COCs). Behavioral side effects are common factors in COC discontinuation. Management of COC-related side effects primarily centers around altering the synthetic ethinyl estradiol (EE) dose, the predominant estrogen in COCs. Estradiol valerate (EV) is a recently introduced natural estrogen alternative to EE. EE-containing COCs, such as EE/dienogest (DNG), were found to decrease free steroid hormone serum levels compared to EV-containing COCs, such as EV/DNG. In women and in female rodent models, steroid hormones (e.g., 17-ß estradiol (E2), testosterone) dose-dependently modulate spatial memory and anxiety-related behaviors. We hypothesized that in a rat model of hormonal contraceptive use, EE/DNG differentially modulates spatial memory and anxiety-like behaviors compared to EV/DNG, corresponding to circulating steroid hormone levels. Thirty-six young-adult (3-4-months-old) female rats were randomly assigned to EE/DNG (0.13µg EE and 8.6µg DNG per day), EV/DNG (8.6µg EV and 8.6µg DNG per day), or vehicle treatment (propylene glycol) continuously administered by subcutaneous osmotic pump. At four weeks of treatment, rats were tested on the delayed spontaneous alternation (dSA) task to evaluate spatial memory and the elevated plus maze (EPM) to evaluate anxiety-like behavior. Following EPM, serum was collected and analyzed for E2, progesterone, androstenedione, and testosterone levels using liquid chromatography-mass spectrometry and corticosterone levels using radioimmunoassay. Spontaneous alternation behaviors were similar across all three groups on the dSA. However, EE/DNG increased use of an egocentric navigational strategy, the use of consecutive turns, on the dSA compared to vehicle and EV/DNG. Egocentric strategy is likely mediated by the striatal memory system, engagement of which is elevated with stress and anxiety. Of note, EE/DNG decreased time spent in the open arms of the EPM compared to vehicle and EV/DNG, indicating increased anxiety-like behaviors with EE/DNG. Both EE/DNG and EV/DNG decreased androstenedione, testosterone, and E2 circulating levels compared to vehicle. Steroid hormone serum levels did not differ between EE/DNG and EV/DNG; 58% of EE/DNG serum samples were undetermined/below threshold for E2 levels, limiting statistical analysis. Altogether, we found that, compared to vehicle and the natural EV, the synthetic EE component in hormonal contraceptives elevates anxiety-like behaviors in female rats, an effect that corresponds to increased use of an egocentric navigational strategy on a spatial memory task. Our findings support the notion that estrogen type matters for behavioral outcomes associated with contraceptive use, identifying estrogen type as a possible tool for management of COC-related side effects. Presentation: 6/1/2024

7102 Pituitary Apoplexy with Eventual Complete Tumour Involution

Abstract Disclosure: A. Ng: None. R. Lai: None. Pituitary apoplexy is an endocrinological emergency resulting from infarction or haemorrhage of the pituitary gland. We present a case of pituitary apoplexy from a non-functioning pituitary macroadenoma, complicated by pituitary insufficiency and subsequent tumour involution. An 80-year-old gentleman presented to the Emergency Department with sudden severe headaches and persistent vomiting and admitted for further evaluation. Computed tomography (CT) imaging of the brain showed a prominent pituitary gland and magnetic resonance imaging (MRI) confirmed a large sellar hyperintense lesion containing blood and proteinaceous material. It measured 1.6 cm by 1.2 cm by 1 cm and indented the optic chiasm. CT angiography did not reveal any aneurysms or intracranial haemorrhage. There were no neurological or visual field deficits at presentation. There was no indication for surgery upon neurosurgical consultation. Initial evaluation of the pituitary axis was consistent with central hypocortisolism (cortisol 75 nmol/L, adrenocorticotropic hormone 1.4 pmol/L [reference range (RR) 1.6-13.9]) and hypoprolactinaemia (prolactin 56 mIU/L, RR 73-351). Luteinising hormone levels were < 1 IU/L (RR 1-9); follicle stimulating hormone levels were 3 IU/L (RR 1-19) and testosterone levels were < 1 nmol/L (RR 5 to 30) as the patient was on androgen deprivation therapy for prostate cancer. Hydrocortisone was started and he was monitored for development of frank diabetes insipidus. He did not require regular desmopressin. He later developed anti-diuretic hormone mediated hyponatraemia (serum sodium nadir of 125 mmol/L, serum osmolality 275 mmol/kg, urine osmolality 390 mmol/kg) that was managed with fluid restriction and solute loading. He also developed central hypothyroidism on day 19 of admission (free thyroxine 11 pmol/L, thyroid stimulating hormone 0.49 mIU/L, RR 0.45-4.5) and oral levothyroxine was started. He was discharged with oral hydrocortisone and levothyroxine replacement. A repeat MRI of the pituitary 2 months later showed complete resolution of the mass and resolution of the mass effects. He was kept on oral hydrocortisone and levothyroxine replacement with regular follow-up.Most pituitary macroadenomas are non-functional, and can present with complications of apoplexy, mass effects or hormonal disturbances. However, the natural history of non-functional macroadenomas is not well known as most are operated on. Spontaneous regression of the tumour can rarely occur, notably in the setting of apoplexy and lymphocytic hypophysitis. Recovery of the pituitary axis may also accompany tumour regression. As spontaneous remission of pituitary macroadenomas may occur, close observation of tumours without visual field defects or significant mass effects may be an alternative to surgery. Presentation: 6/1/2024 12:15:00 PM

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in < 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone < 2.6 ng/dL; Total testosterone: < 10ng/dL; and Free androgen index < 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

5048 A Rare Cause of Hyperandrogenism in Postmenopausal Women: Ovarian Stromal Hyperplasia

Abstract Disclosure: S. Mark: None. M.H. Shanik: None. I.J. Romao: None. Ovarian stromal hyperplasia (OSH) is a rare cause of hyperandrogenism. It is a non-neoplastic proliferation of ovarian stromal cells that leads to the overproduction of testosterone. This case report highlights that OSH should be considered in patients who present with hyperandrogenism.A 49-year-old postmenopausal woman with a past medical history of polycystic ovary syndrome, type 2 diabetes and obesity complained of unwanted hair growth. On the physical exam her BMI was 51. She had an obese body habitus, hirsutism of her chin, chest and back and acanthosis nigricans on her neck. Blood work showed a total testosterone of 203 (2-45 ng/dL) and free testosterone 29 (0.1-6.pg/dL). FSH, LH, DHEAS, estradiol, SHBG and 17 hydroxyprogesterone (17 OHP) were in the normal range. She completed a 1 mg dexamethasone suppression test that was normal. She took spironolactone for hirsutism with minimal relief. Pelvic ultrasound was limited due to body habitus. CT of the abdomen and pelvis showed no adrenal or ovarian masses. The patient had a family history of pancreatic, ovarian, and breast cancer. Given her symptoms and her family history, the patient underwent genetic testing that was negative. She underwent bilateral salpingo-oophorectomy. Pathology revealed bilateral ovarian stromal hyperplasia. After surgery, her total testosterone normalized to 18 ng/dL and free testosterone was 1.6ng/dL with improvement in hair distribution. The patient continued to struggle with her weight and diabetes management.OSH is a non-malignant proliferation of ovarian stromal cells which leads to overproduction of testosterone. It occurs more in postmenopausal women and rarely in women of reproductive age. There is approximately 1 case of OSH in every 1000 cases of hirsutism. Clinical features include obesity, insulin resistance, acanthosis nigricans, acne, and hirsutism. Testosterone levels are usually greater than 150 ng/dL. Differential diagnosis includes PCOS, Cushing’s disease, adrenal or ovarian tumor and non-classic adrenal hyperplasia. Transvaginal ultrasound can be used to assess the ovaries for tumors or increase in size. If negative a pelvic MRI or CT can be done for further assessment. The gold standard for diagnosis would be histological evaluation following bilateral oophorectomy which is curative. Pathology usually shows stromal hyperplasia that is nodular or diffuse. Alternative treatment options include GNRH agonist therapy in patients who are not surgical candidates. Complications of this condition include insulin resistance, acanthosis nigricans and diabetes mellitus. After treatment hyperandrogenism skin changes improve. It is important that clinicians consider OSH as a cause of hyperandrogenism to ensure timely diagnosis and treatment. Presentation: 6/2/2024

8309 Injectable Estradiol Dosing Regimens; A Retrospective Review of Hormone Therapy for Gender-Diverse Adults Assigned Male at Birth

Abstract Disclosure: M. Kanin: None. M. Slack: None. R. Patel: None. K. Chen: None. N. Jackson: None. K. Williams: None. S. Grock: None. Introduction: Many gender incongruent individuals assigned male at birth (AMAB) seek hormone therapy to achieve physical and emotional changes. Hormone therapy typically includes estradiol, with or without an anti-androgen. However, limited data with relatively weak justifications support the currently recommended regimens. In particular, dosing schedules for injectable estradiol can vary considerably. UCSF guidelines recommend initiating estradiol valerate at 5 mg parenterally weekly or estradiol cypionate 2 mg weekly. Endocrine Society Guidelines recommend estradiol valerate or cypionate parenterally 5-30 mg every 2 weeks or 2-10 mg weekly. Our clinical observations led to the concern that current guideline-based dosing of injectable estradiol can result in supratherapeutic estradiol levels. Thus, we designed a retrospective cohort study to evaluate injectable estradiol dosing requirements for gender diverse individuals at our institution. Hypothesis: We hypothesize that low dose estradiol injections can lead to therapeutic estradiol levels (100-200 pg/mL) and suppressed testosterone (<50 ng/dL). Design: We performed a retrospective cohort study of gender diverse individuals AMAB aged 18-89 who were newly prescribed injectable estradiol by a single clinic from January 2017 to March 2023. Exclusion criteria included history of orchiectomy or estradiol use within the previous six months. Patients were identified using structured query language to extract data from our institution’s electronic health record system. A total 33 patients were identified, 29 of whom were eligible for inclusion. Data was collected for 15 months after estradiol initiation. Results: All individuals were prescribed estradiol valerate except for 1 who was prescribed estradiol cypionate. Estradiol dose ranged from 2.5 to 10 mg weekly and an average initial dose of 4.26 mg weekly. Mean initial estradiol level obtained while on treatment for at least 30 days was 349.8 pg/mL, which is supratherapeutic. Mean initial testosterone level was 25.3 ng/dL, which is suppressed. Mean estradiol dose at completion of data collection was 3.68 mg with a mean final estradiol level of 245.2 pg/mL. Testosterone levels reached less than 50 ng/dL for everyone in the sample with a mean final testosterone of 23.3ng/dL despite significant reductions in estradiol dose (change=-0.58 mg per week, p=0.001) Conclusion: Our study demonstrates lower dosages of estradiol can be used to achieve therapeutic estradiol levels in gender incongruent patients seeking estrogen therapy. Using lower dosages can avoid supratherapeutic estradiol levels and the associated risks. Further prospective studies are needed with the aim to reevaluate current guideline dosing recommendations for injectable estradiol. Presentation: 6/2/2024

7467 Supplement Use Among Transgender Patients: Case Reports and Literature Review

Abstract Disclosure: H. Cunningham: None. Q. Jones: None. C. Kelley: None. The barriers to initiating gender affirming medical treatment are innumerable and increasing in the wake of wide-sweeping anti-trans legislation, leading many transgender individuals to utilize more accessible means of transitioning. We provide examples of patient-initiated supplement use at a gender medicine clinic in the Southeast. We describe a 60-year-old transgender woman who was unable to establish care due to lack of affirming providers in her region and insurance approval delays. She began taking Pueraria mirifica, along with saw palmetto and fenugreek, for feminization. Subsequently, her breast size increased from an A to B cup, and she noticed fat redistribution to her hips. When finally seen one year later, labs demonstrated suppressed luteinizing and follicle stimulating hormones and increased sex hormone binding globulin, with an associated decrease in estradiol and testosterone levels. Cessation of supplements resulted in lab normalization. Our second case describes masculinizing effects, including voice deepening, experienced by a transgender man using a supplement that contained "orchic extract.” Supplements used for gender affirmation can also have more adverse effects, including polycythemia in the setting of trenbolone, an illicit steroidogenic performance enhancing supplement used for masculinization by some patients assigned female at birth. Patients without access to gender affirming hormones through a medical provider, or who do not feel comfortable accessing health care, may be more likely to use supplements purchased online without a prescription. Considering this, we must create more safe spaces for gender affirming care and ask all transgender patients about supplement use. Providers should consider supplement use as a possible explanation for unexpected lab results. The literature on supplement use for gender-affirming effects is sparse; this presentation provides a summary of and contributes to the current literature on this topic. Presentation: 6/2/2024