Intramuscular Testosterone Research Articles

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

6590 Androgen Derived Hepatocellular Adenoma And Reinitiation Of Gender Affirming Hormone Therapy

Abstract Disclosure: A.L. McKenna: None. Y. Huang: None. L. Yang: None. N. Loo: None. C. Ritchie: None. A. Metcalfe: None. R. Nakhleh: None. M. Krishna: None. S. Thota-Kammili: None. J. Eleazer: None. A.Y. Chang: None. Hepatocellular adenomas (HCA) are uncommon, benign epithelial tumors of the liver. Risk factors include exogenous estrogen or androgen use, and genetic and metabolic syndromes. Management of HCA is delineated by sex assigned at birth; Observation is recommended in an HCA less than 5 cm in an individual assigned female at birth, while resection of an HCA in an individual assigned male at birth is recommended no matter the size due to risk of malignant transformation. What is not known is whether risk is different for individuals with gender incongruence on gender affirming hormone therapy (GAHT). There is limited data on the risk of HCA in this population. One case report of a transgender man who continued GAHT after diagnosis of an HCA though no follow-up information was available. We present follow-up on a transgender man assigned female at birth with multiple hemorrhagic HCA that was re-initiated on GAHT after stabilization of adenomas off GAHT. Unlike prior cases, the molecular profile showed ß-catenin negative, estrogen and androgen receptors positive. This is the first case report to our knowledge reporting detailed follow-up after restarting masculinizing GAHT after diagnosis of HCA. A 24-year-old transgender man presented to the emergency department with right upper quadrant pain. Initial labs were notable for ALT of 239 units per liter (U/L) and AST 165 U/L. Magnetic resonance imaging (MRI) of the abdomen and liver elastogram revealed multiple bilobar hepatic masses, the largest measuring 9.9 cm concerning for hemorrhagic HCA which was subsequently confirmed on liver biopsy. Immunostains were positive for estrogen and androgen receptors. The patient had no history of alcohol or illicit drug use, tattoos, or family history of liver disease. The patient had been treated with 100 mg of intramuscular testosterone cypionate weekly for the past six years for gender incongruence locally. No testosterone concentrations were available from prior to or during acute presentation. Discontinuation of hormone therapy was recommended along with conservative management with frequent MRI. Over the next 19 months, monitoring revealed improvement/resolution of the auto infarcting adenomas with the last MRI noting two stable HCA measuring 2.1 cm and 0.8 cm without new or enlarging liver lesions. Due to gender dysphoria off GAHT, reinitiation of hormone therapy with low dose AndroGel 1.62% topically was prescribed at 18 months after presentation. The patient has been monitored with labs monthly and plans to obtain MRI abdomen every three months. To date, the patient has tolerated reinitiation of therapy. This case demonstrates that patients on masculinizing GAHT who develop HCA can be conservatively managed and monitored based on pathology and that testosterone does not necessarily explain sex differences in the presentation/malignant transformation of HCA cisgender men as opposed to cisgender women. Presentation: 6/3/2024

6609 Central Serous Chorioretinopathy in the Eyes of the Beholder of Testosterone Depot Injection

Abstract Disclosure: H. Ni: None. D. Kankanamge: None. J. Jabbour: None. V.A. Preda: None. Background: Central serous chorioretinopathy (CSC) is a characterised by subretinal fluid accumulation causing detachment of the neurosensory retina and visual disturbance[1]. It has been postulated that increased focal choriocapillaris permeability results in leakage of interstial fluid into the subretinal space[1]. CSC is a rare side effect of testosterone therapy, the exact mechanism is unclear. Case : We present a 32-year-old male gym manager who has been self-administering anabolic steroids with testsoterone ethanoate IM injections every 14 days for body building. He reported left blurred vision for 8 weeks. He was normotensive and reported taking doxycycline and azithromycin for mycoplasma genitalia. There was no history of glucocorticoid exposure, smoking, alcohol use, gastoesophageal reflux disease, hypertension, shift work, sleep apnoea, nor other established risk factors for CSC. The visual acuity was OD 6/6 and OS 6/9 with intraocular pressures of 12mmHg on the right and 15mmg on the left. Fundoscopy revealed a left serous macular elevation involving the left fovea. A macular OCT confirmed the left acute central serous chorioretinopathy and right retinal pigment epithelial changes. The latter were suggestive of right CSC in the past. Discussion: Androgens have been associated with CSC in the literature. It has been hypothesised that exogenous testosterone may cause increased choriodal blood flow and permeability, promote atheroscleorsis, cause sodium retention and potentially interact with retinal pigment epithelium (RPE) via androgen receptors4. Intramuscular testosterone therapy causes fluctuation in plasma testosterone concentration (which is thought to be more relevant than absolute value of testosterone). Most cases (60%) of CSC resolve spontaneously, and appear to coincide with cessation of testosterone therapy5. Conclusion: Clinicans need to be alert to the use of testosterone and other anabolic steroids, prescribed or self administered, particularly in their patients with CSC or who have other risk factors for CSC, such as corticosteroids, smoking and hypertension.

Effect of hormone therapy on personality traits: preliminary evidence in older men and women.

Findings concerning the effects of hormone therapy (HT) on cognition and dementia are mixed, with some trials suggesting increased harm at older ages. Personality, like cognition, changes with dementia, but no clinical trials to date have examined the effects of HT on personality traits. This study aimed to determine the effects of HT on personality traits in older men and women. Secondary data analysis was performed from randomized, double-blind, placebo-controlled cross-over studies of menopausal HT in women and testosterone therapy (TT) in men. Participants were community-dwelling cognitively normal adults (mean age = 75.2 years), including 29 men and 22 women. Three months of hormone intervention (for women, 0.625 mg/day conjugated equine estrogen with or without 2.5 mg/day medroxyprogesterone acetate; for men, 200 mg intramuscular testosterone enanthate every 2 weeks) were crossed over with 3 months of identical placebo with a 3-month washout between intervention phases. The main outcome measure was neuroticism and conscientiousness personality domains and facets assessed with the Revised NEO Personality Inventory (NEO-PI-R) after the active and placebo intervention phases. In linear mixed-effect models, HT in women decreased conscientiousness (p < 0.01) and the conscientiousness facet of achievement striving (p < 0.01), and increased vulnerability, a facet of neuroticism (p < 0.05). Testosterone in men decreased conscientiousness (p < 0.05) and the conscientiousness facet of dutifulness (p < 0.05), and increased vulnerability (p < 0.05). In a preliminary study of healthy older adults, HT and TT formulations produced adverse changes in vulnerability and conscientiousness facets that parallel personality changes in dementia.

Persistent menstruation in transgender people using testosterone gender-affirming hormone therapy

Background The cessation of menstruation is a common and desired outcome of testosterone gender-affirming hormone therapy (GAHT), for trans and gender diverse (collectively referred to as trans) individuals recorded female at birth. This study aimed to (a) assess the prevalence and characteristics of menstruation before and after commencing testosterone GAHT, and (b) explore factors associated with persistent menstruation. Method Trans people using testosterone therapy for gender affirmation, aged ≥16 years and living in Australia completed an online cross-sectional survey between 28 August to 31 December 2020. Multivariable logistic regression analysis was applied to estimate the effect size of factors potentially contributing to the cessation or persistence of menstruation 6 months after starting testosterone therapy. Results There were 401 eligible respondents. Median age for commencement of testosterone GAHT was 23 years (IQR = 20, 28) and the median duration of testosterone therapy was 37 months (IQR = 19, 65). Intramuscular testosterone undecanoate injections were the most used formulation. Persistent menstruation >6 months after commencing testosterone GAHT was reported by 87 (22.8%) participants. The odds of reporting persistent menstruation >6 months after commencing testosterone were (a) higher in people using testosterone gels/creams compared to testosterone injections (OR = 11.3 [1.1, 118.2]), and (b) lower in individuals with a body mass index ≥30 kg/m2 versus <30 kg/m2 (OR = 0.5 [0.3, 0.99]). No association was found between persistent menstruation >6 months after commencing testosterone and (a) menstrual regularity prior to commencing testosterone GAHT, and (b) age at commencement of treatment. Conclusion Persistent menstruation >6 months after commencing testosterone GAHT may be impacted by body mass index and the mode of testosterone administration. This is important information for individuals considering testosterone GAHT as well as for clinicians advising on the benefits and drawbacks of different forms of testosterone administration as well as the likelihood of menstrual cessation.

Glucose ingestion does not lower testosterone concentrations in men on testosterone therapy.

Oral calorie intake causes an acute and transient decline in serum testosterone concentrations. It is not known whether this decline occurs in men on testosterone therapy. In this study, we evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy. This is a secondary analysis of samples previously collected from a study of hypogonadal men with type 2 diabetes who received testosterone therapy. Study participants (n = 14) ingested 75 grams of oral glucose, and blood samples were collected over 2 h. The test was repeated after 23 weeks of intramuscular testosterone therapy. The mean age and body mass index of study volunteers were 53 ± 8 years and 38 ± 7 kg/m2, respectively. Following glucose intake, testosterone concentrations fell significantly prior to testosterone therapy (week 0, p = 0.04). The nadir of testosterone concentration was at 1 h, followed by recovery to baseline by 2 h. In contrast, there was no change in testosterone concentrations at week 23. The change in serum testosterone concentrations at 60 min was significantly more at week 0 than week 23 (-11 ± 10% vs 0 ± 16%, p = 0.05). We conclude that oral glucose intake has no impact on testosterone concentrations in men on testosterone therapy. Endocrinology societies should consider clarifying in their recommendations that fasting testosterone concentrations are required for the diagnosis of hypogonadism, but not for monitoring testosterone therapy.

Prostate-specific antigen (PSA) levels in men with Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a rare genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioral challenges, cognitive dysfunction, and hormone deficiencies. Hypogonadism is common but knowledge on potential side effects of testosterone replacement is limited, in particular, the long-term effects on behavior and PSA. Patients and methodsRetrospective case studies of seven men, median age 46 years, with genetically verified PWS, testosterone treated hypogonadism and available PSA values were included. Long-term follow-up of PSA was accessible in four patients. Medical records were reviewed for adverse effects. ResultsFive men were treated with intramuscular testosterone undecanoate, two had no hypogonadism. Median PSA was 0.68 μg/L (0.23–1.3), median testosterone 15 nmol/L. After a median time of 17 years of testosterone replacement median PSA was 0.75 μg/L (range 0.46–1.4). Testosterone replacement was well tolerated, and no major behavioral changes were reported. Five were treated with growth hormone for >20 years. ConclusionLevels of PSA were low. Long-term treatment with testosterone was working well and did not result in any clinically meaningful increase in PSA. Our results indicate that testosterone replacement is neither associated with serious adverse events regarding changes in behavior or effect on PSA. However, larger studies are needed to confirm our results.

522 Testosterone Supplementation in Patients with Burn Hypermetabolism

Abstract Introduction After major burn injuries, patients experience a hypermetabolic response that leads to hyperdynamic circulatory, physiologic, catabolic, and immune system responses. Many transdisciplinary approaches have been tested to mitigate this postburn hypermetabolic syndrome such as comprehensive burn rehabilitation, nutritional support, monitoring, and pharmacological interventions. Oxandrolone, a synthetic analog of testosterone, has been shown to have higher anabolic properties and minimal androgenic effects and studied intensely in burn care. In 2023, the FDA asked all manufacturers of oxandrolone to cease production and subsequently removed the drug from market on June 28, 2023. Our study examines the cost and operationalization of an intramuscular (IM) testosterone protocol as an alternative in male burn patients with ≥20% total body surface area (TBSA). Methods A cost analysis was conducted using the National Drug Codes (NDC) and commercially available benchmarking data. The cost of oxandrolone and testosterone were included in our analysis. Following a thorough literature review, a protocol was developed for adult male patients with &amp;gt;20% TBSA burn injuries. Patients undergoing gender affirming hormone therapy, untreated obstructive sleep apnea, or hormonal blockers for cancer were excluded from the protocol. Results The protocol begins with total serum testosterone levels at the time of admission and weekly thereafter for male patients with ≥20% TBSA injury. Once a testosterone level &amp;lt; 150 ng/dL is detected, supplementation of testosterone with 200 mg IM once weekly for two weeks is started. Weekly evaluations include total body weight, metabolic panels, and nutritional panels. Cost comparison between oxandrolone and testosterone show an equivalent unit cost of $8.62 versus $8.38, respectively. Conclusions Drug shortages and supply chain challenges are becoming more common in burn care. We hypothesize testosterone to be both a clinically effective and cost-effective alternative to oxandrolone in the setting of burn hypermetabolism in male patients with major burns. Currently, burn experts are working with endocrinologists to assess pharmacologic alternatives for female patients and have obtained IRB-approval to evaluate both safety and efficacy of testosterone supplementation in the setting of burn hypermetabolism. Applicability of Research to Practice This study evaluates the safety and efficacy of testosterone supplementation as an alternative to oxandrolone in the setting of burn hypermetabolism. This study helps provide guidance to other burn centers in filling the gap in therapy that now exists in the pharmacologic management of hypermetabolic syndrome in patients with severe burns.

Effect of Pre-operative Parenteral Testosterone on Penile Dimensions and Vascularity in Proximal Hypospadias: A Prospective Observational Study.

Severe or proximal hypospadias is associated with inadequate local tissue and small phallus size. Pre-operative androgens have been used to increase phallus size, but there are very few studies on its role in proximal hypospadias. This study aimed to assess the effects of pre-operative intramuscular (IM) testosterone on proximal penile hypospadias in terms of penile morphology and tissue characteristics of penile skin. This prospective observational study was conducted on 27 patients of proximal hypospadias over a period from June 2017 to July 2018. The patients were sequentially enrolled into two groups: Group A and Group B. Group A patients received IM testosterone before surgery, whereas Group B patients were operated without pre-operative testosterone. Outcomes were analysed in terms of change in penile dimensions and effect on vascularity of penile skin. Pre-operative IM testosterone in Group A caused a significant increase in stretched penile length from a mean of 3.058 cm (±0.691) to 3.9 cm (±0.875) ( P = 0.002), penile circumference from a mean of 4.142 cm (±0.772) to 4.667 cm (±1.174) ( P = 0.029) and glans width from a mean of 1.225 cm (±0.245) to 1.750 cm (±0.571) ( P = 0.002). There was higher microvessel density in the preputial skin of Group A (mean: 12.212 [±4.745] blood vessels/high-power field [HPF]) compared to Group B (8.867 [±3.258] blood vessels/HPF) ( P = 0.043). Pre-operative testosterone in proximal hypospadias causes significant changes in penile dimensions and tissue characteristics. Improvement in penile dimensions leads to ease in operability and better tissue handling. However, more studies with large sample size are required to establish the beneficial effects of pre-operative hormone stimulation on urethroplasty.

P-40 A rare cause of male infertility: 46, XX testicular disorder of sex development

Abstract Introduction 46, XX testicular disorder of sex development (DSD) is a rare condition with an estimated incidence of 1 per 20,000 individuals. The clinical spectrum ranges from ambiguous genitalia that is usually diagnosed at birth, to male infertility that is diagnosed in the adult years. However, the diagnosis of 46, XX DSD in an individual presenting with infertility may be challenging due to occult clinical findings. A thorough physical examination as well as clinical suspicion is required for diagnosis. Clinical Case A 22-year-old male presented to the urology clinic for infertility despite at least 3 years of regular unprotected intercourse. On physical examination, his testicles were palpable bilaterally in the scrotum with small volumes. Laboratory results revealed hypergonadotropic hypogonadism and his spermiogram revealed azoospermia. Abdominopelvic ultrosonagraphy (US) was reported normal except abdominal situs inversus. Tumor markers for a probable testicular tumor were negative. He was referred to medical genetic department. His family history was unremarkable except for parental consanguineouty. The chromosomal analyze revealed a 46, XX karyotype, and fluorescence in situ hybridization (FISH) disclosed that the SRY gene locus was translocated to the X chromosome: 46,x,der(x) t(x;Y) (sry+); SRY + AZF a,b,c microdeletion. The patient was consulted to the endocrinology department for further evaluation of hypogonadism. On physical exam, he had eunuchoid habitus with incomplete virilization, bilateral and symmetric gynecomastia. The height, and body mass index of the patient was 165 cm, and 29.2 kg/m2, respectively. The testicles were bilaterally palpable in the scrotum, with a volume of 4 mL each. His luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone levels were 14 mUI/mL (laboratory reference: 1.5–9 mUI/mL), 42 mUI/mL (1.4–18 mUI/mL), and 140 ng/dl (197-700 ng/dL), respectively. The bone age matched his chronological age. Bone densitometry revealed osteopenia. A direct X-ray of the thorax showed thoracic situs inversus, he diagnosed with situs inversus totalis. Detailed genetic analyses could not be done concerning this diagnosis due to financial constraints. He had no history of lung infections that ruled out Kartagener's syndrome. Treatment was started with monthly intramuscular testosterone injections of 250 mg/ml. The patient and his family received genetic counseling, including advice that assisted reproduction will not work owing to AZFabc deletion. Conclusion 46, XX DSD is an uncommon genetic disorder that is rarely identified during the evaluation of male infertility. Clinical suspicion and a comprehensive physical exam are keys for diagnosis. Genetic analysis is essential for definitive diagnosis. A multidisciplinary is required for treatment and follow-up. Psychological support and genetic counseling are also critical for the management of these patients.

Erythrocytosis Is Rare With Exogenous Testosterone in Gender-Affirming Hormone Therapy.

Studies have found a variable incidence of erythrocytosis among people using testosterone as part of gender-affirming hormone therapy (GAHT). To examine the effect of using exogenous testosterone as GAHT on hematocrit in a large North American cohort. We conducted a cross-sectional analysis of testosterone and hematocrit laboratory values in 6670 patients who were prescribed testosterone through Plume, a national provider of GAHT. The prevalence of erythrocytosis, the mean hematocrit at predetermined testosterone thresholds and with varying routes of testosterone administration were assessed. Among 6670 individuals, 560 (8.4%) had a hematocrit ≥50%, 182 ≥ 52% (2.7%), and 60 ≥ 54% (0.9%). There was significant variation (P < .001) in hematocrit between different clinically relevant testosterone thresholds (T < 50 vs T 50-299 vs T 300-999 vs T ≥ 1000 ng/dL) and when comparing serum testosterone in increments of 50 ng/dL within the target range for males (300-1000 ng/dL) (P < .001). Mean hematocrit ranged from 41.84% (T < 50 ng/dL) to 45.68% (T 900-949 ng/dL). Patients on intramuscular testosterone had a higher mean hematocrit than those on transdermal testosterone (44.96% vs 43.41%, P < .001). Both route of administration (P < .001) and testosterone level (P < .001) had statistically significant associations with hematocrit when controlling for each other. While the magnitude of change in hematocrit with serum level and route of administration of testosterone was statistically significant, the absolute levels were within the normal range, unlikely to be clinically meaningful. These findings, along with the low prevalence of erythrocytosis, should help allay concerns about the use of testosterone as GAHT.

A prospective comparison study of subcutaneous and intramuscular testosterone injections in transgender male adolescents.

This prospective study compares testosterone injection type and effects on biochemical changes, clinical effects, and quality of life amongst transgender and gender diverse (TGD) adolescents assigned female at birth (AFAB) over the first 6months of subcutaneous (SQ) vs. intramuscular (IM) testosterone injections as part of their gender affirming care. Subjects were testosterone-naïve transgender adolescents, AFAB, ages 14-18 years old. Subjects were either randomized to injection type or selected a preferred injection type. At enrollment, subjects completed baseline labs and PedsQL™ quality of life questionnaire. At 3month and 6month follow up, subjects completed peak and trough testosterone levels, PedsQL™, masculinizing effects, and medication experience questionnaires. Twenty-six subjects participated with a median age 15.5 years. By 6-month follow up, trough testosterone levels were comparable between the two groups. Peak testosterone levels were higher in the IM group at 3-month follow up. Mild adverse effects were rare (12 %, all in SQ subjects) and limited to skin reaction only. Self-reported masculinization effects and quality of life were not statistically different between injection groups. A total of 92 % of participants was self-injecting by 3-month follow up. In this prospective study, clinical and biochemical effects are similar between SQ and IM testosterone injections for transgender adolescents. Subjects expressed preference for both injection types. Both SQ and IM injection modalities are safe and effective for TGD youth initiating testosterone and both options should be offered to patients.

SAT396 Transgender Care From The VA Perspective

Abstract Disclosure: P.R. Nayak: None. Background: Medically necessary care for transgender and gender non-conforming veterans was officially mandated in 2011 by the Veterans Health Administration. However, access to care can be difficult and tortuous to navigate. Additionally, the healthcare disparities experienced by transgender veterans extend beyond medical therapy; mental health services, appropriate sexual health education, and population specific needs and screenings are often inadequate. In 2019, providers and staff at our VA medical center formed a multi-disciplinary team to provide coordinated and whole health focused gender-affirming care for this unique population. The team consists of an endocrinologist, mental health providers, social workers, clinical pharmacist, speech therapist, primary care provider, and a prosthetic representative.Case: A 32 year old transmale veteran with depression and bipolar disorder met with our social worker after expressing his desire to continue his transition. He had come out to his community and presented as male for over a year. He was referred to the endocrinologist who recommended egg harvesting prior to starting hormone replacement therapy per veteran's desire for biologic children. A social worker coordinated his consultation with a reproductive endocrinologist for the procedure. Simultaneously, a prosthetics representative helped veteran obtain a chest binder and a stand-to-pee device. Upon completion of egg harvesting, he started testosterone therapy, titrated to therapeutic levels.A year after starting hormones, he pursued top surgery and completed this locally. Due to ongoing menstrual bleeding on intramuscular testosterone, he was referred to ob-gyn and subsequently underwent hysterectomy and left oophorectomy. Post hysterectomy, he and his partner began experiencing relationship problems. They were referred to the sex therapist to work on their physical intimacy and sexuality. Three years on hormone therapy, veteran reported difficulty with the voice variations, though his voice had deepened to his liking far earlier in his medical transition. He started working with a speech therapist for voice masculinization with improvement noted at follow up. Conclusion: A multi-disciplinary approach to gender-affirming care is beneficial in providing patients with the care they deserve in a timely, respectful and coordinated manner. Our patient experienced a smoother and supportive transition due to the team of providers who were able to provide gender appropriate care across several disciplines during each phase of his transition. Without a team approach, this population often face several hurdles and delays to their transition. Since 2019, we have served over 50 transgender and gender non-confirming veterans in their transition. While not all have met their transition goals, most have benefited from the support and guidance of our team. Presentation: Saturday, June 17, 2023

FRI439 Spermatogenesis Induction For Hypogonadotrophic Hypogonadism In An Australian Tertiary Hospital Andrology Service

Abstract Disclosure: S. Sarlos: None. M. Herath: None. I. Sim: None. R. Upreti: None. R.I. McLachlan: None. C.A. Allan: None. Infertility affects 8-12% of couples with male factors contributing to 50% and solely responsible in 20-30% of cases. Male infertility due to hypogonadotrophic hypogonadism (HH) is amenable to medical treatment. We report a series of 23 men treated for infertility from HH (congenital n=13, acquired n=10) with a median age of 33 years. Causes included panhypopituitarism (n=11) [empty sella (n=2), adenoma (n=3), craniopharyngioma (n=1), pituitary hypoplasia (n=3), CHARGE syndrome (n=1), cranial radiotherapy (n=1)], Kallmann syndrome (n=1), thalassaemia major (n=1) and idiopathic (n=10). Urinary or recombinant human chorionic gonadotrophin (hCG) as an LH substitute was used based on established protocols. Commencing doses were 1500 IU or 62.5mcg s/cut twice weekly respectively and titrated to achieve normal serum total testosterone. Recombinant FSH was added after 6 months for persisting azoospermia. Wherever possible, men previously treated with long-acting injectable testosterone undecanoate were transitioned to transdermal testosterone for a minimum of 6 months prior to initiation of gonadotrophin therapy. There was wide variability in time to first appearance of sperm (median 16 months, range 4 - 42). In androgen treatment-naive men with acquired HH in adulthood (n=9), sperm was detected at a median 8 months (range 3 - 21 months) and for 4 men, hCG monotherapy was sufficient. For men with congenital causes of HH (n=13), time to first sperm detection was longer (median 17 months, range 12 - 42) and all required addition of FSH. In men previously treated with intramuscular testosterone (n=8), the median time to sperm appearance was 17 months (range 12-24) as compared to 13 months (5-42) in men treated with transdermal testosterone (n=6). To date, 11 of the 16 men actively seeking fertility have had children, with 7 requiring assisted reproduction. Gonadotrophin therapy is an effective fertility treatment for most men with HH. Clinicians can anticipate a longer time to spermatogenesis in men pre-treated with intramuscular androgens and those with congenital HH. Couples often move to assisted reproductive therapy, likely due to considerations such as semen quality, co-existing female factors and/or desire for prompt conception. Presentation: Friday, June 16, 2023

SAT395 Gender Dysphoria In A Patient With Ovotesticular Disorder Of Sex Development

Abstract Disclosure: T. Moreno: None. P. Rodrigues: None. S. Ribeiro: None. D.M. Carvalho: None. Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare condition characterized by the presence of both ovarian and testicular tissue in the gonads. Management and sex designation of these patients depend on several factors and an underlying potential for gender dysphoria should be acknowledged.Clinical Case: A 12-month-old patient from Guinea-Bissau, born from consanguineous parents, was referred to Pediatric Surgery due to atypical genitalia. Karyotype was 46,XX and SRY gene analysis was negative. Genitoscopy showed absence of a vagina and a uterus was not found on magnetic resonance imaging. An exploratory laparotomy and biopsy of the gonads was performed. The pathology report confirmed the presence of gonadal ovarian and testicular tissue, establishing the diagnosis of OT-DSD. Surgical removal of both gonads and clitoroplasty was performed and a female sex designation was attributed. Endocrinology follow-up was started at the age of 8 and the first physical examination revealed weight 48.6 kg (&amp;gt; P97), height 135.5 cm (P90–97); Tanner stage I (P1A1M0) and a blind vagina with normal clitoris size. Blood tests showed FSH 12.53 mUI/L, LH 1.07 mUI/L, estradiol 5.8 pg/mL and total testosterone 0.04 ng/mL. Reconstructive surgery for a neovagina was performed at 13-years-old and, two years later, the patient was started on hormone replacement therapy with transdermic estradiol. At the age of 16, the patient manifested gender dysphoria issues, decided to stop estradiol and was referred for psychiatric evaluation. Two years later, intramuscular testosterone enanthate was initiated but treatment was stopped after a six-month trial, as the patient claims to identify as male but is not interested in seeking hormone treatment at this point.Conclusion: OT-DSD is an uncommon condition, raising issues of gender assignment that are dependent on factors such as age at diagnosis, phenotype, internal structures and reproductive potential. Scarce data exists on long-term outcomes in OT-DSD, including the frequency of gender dysphoria in these patients. Gender identity is an important factor to consider on long-term follow-up of OT-DSD patients. Presentation: Saturday, June 17, 2023

Clonal hematopoiesis of indeterminate potential (CHIP) and association with response to bipolar androgen therapy (BAT).

e17048 Background: CHIP, the expansion of hematopoietic cells carrying acquired somatic alterations associated with hematologic malignancies, is associated with increased inflammation, risk of heart disease, and poor outcomes. BAT, where testosterone levels are therapeutically manipulated between castrate levels to supraphysiologic levels, has been shown to be an effective therapy for some men with castration resistant prostate cancer. Clinical predictors of response are not established. We hypothesized that CHIP, would be negatively associated with clinical outcomes. Methods: Baseline peripheral blood from participants on the RESTORE Cohort C (NCT02090114) were analyzed for the presence of CHIP. Patients in this cohort had castration resistant prostate cancer with progressive disease after treatment with ADT alone. All participants were treated with 400mg of intramuscular testosterone cypionate every 28 days. Peripheral blood mononuclear cells were analyzed for the presence of CHIP using targeted next generation sequencing focused on 49 genes most commonly mutated in CHIP and myeloid malignancies. Given patients had metastatic and non-metastatic CRPC, progression free survival was determined based on the time to the start of the next therapy. Results: CHIP was present in 6 of 29 patients at baseline (21%) with one patient having 2 clones (Table). Median age of patients CHIP+ was 73 compared to age of 68 in the CHIP- group (p = 0.16). Median PSA was higher in the CHIP+ group (median 15, IQR 1-56) compared to the CHIP- group (median 3.5, IQR 1-57). 67% of the CHIP+ group and 57% of the CHIP- group had baseline Gleason scores of &gt; = 8. The CHIP+ group had a median PFS of 8.8 months compared to 13.3 months in the CHIP- group (HR 3.3 95%CI 1.2, 9.1; p = 0.02). This remained significant after adjusting for age. There was no difference in overall survival (HR = 2.5 95% CI 0.5,2.9; p = 0.3). Conclusions: Among men treated with BAT as first line treatment for CRPC after ADT alone, CHIP was associated with a decreased progression free survival. Larger studies are needed to understand the impact of CHIP in larger cohorts of men treated with BAT and other therapies for prostate cancer.[Table: see text]

(300) Impact of Intranasal Testosterone versus Intramuscular Testosterone cypionate on Hematocrit of Hypogonadal Men: Data from an ongoing Phase IV, Open-label, Randomized Clinical Trial.

Abstract Introduction The potential increase in hematocrit and subsequent risk of polycythemia has been regarded as one of the most worrisome adverse effects of testosterone therapy (TT). Recent evidence has shown that the modality of delivery and half-life of each formulation may affect the incidence of these side effects. Therefore, we hypothesized that longer-acting intramuscular testosterone would increase hematocrit to a higher degree than the shorter-acting nasal formulations that can more closely mimic normal physiology. Objective To compare the effects of Intranasal Testosterone (NT) and Intramuscular Testosterone (TC) on hematocrit and serum testosterone levels in testosterone deficient men over 4 months. Methods This Phase IV, randomized, open-label clinical trial was performed on 39 symptomatic, testosterone deficient (TD) men with at least two serum testosterone levels below 300 ng/dL drawn before 10AM. Men were randomized (1:1) to receive either nasal gel three times per day (5.5mg per nostril) and intramuscular TC (200mg) once every two weeks. The primary outcomes were changes in Hematocrit and serum T before and after four months. Secondary outcomes were changes in estradiol (E), PSA and 17-OHP. Data analysis was performed using two-sample and single-sample T tests (Microsoft Excel v.16.60). Results A total of 39 men with testosterone deficiency were randomized to receive either NT (n=15) or TC (n=24). The median participant age was 46 years old with a mean serum T of 237.1 ng/dL and hematocrit of 43.3%. Prevalence of participants who screened positive for OSA on STOP-BANG questionnaire for NT and TC group were 67% and 71%, respectively. Compared to their respective baselines, men in both groups saw significantly increased serum testosterone levels (p 52%) after 4 months was 0% in NT group and 4.2% in TC. Those taking TC saw increases in E (p=0.003) and decreases in 17-OHP (p&amp;lt;0.001) at follow-up, where NT saw no changes. Neither regimen significantly impacted PSA at follow-up. Conclusions Both Intranasal and Intramuscular testosterone regimens are effective in treating hypogonadal men. However, short-acting nasal T does not appear to impact hematocrit levels especially when compared to testosterone cypionate. Those who are at increased risk of developing polycythemia or want to avoid changes in their E or 17-OHP levels may benefit from short-acting T formulations. Disclosure Yes, this is sponsored by industry/sponsor: Acerus Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals

(032) Direct-to-Consumer Telemedicine Companies Offering Gender Affirming Hormone Therapy

Abstract Introduction As direct-to-consumer telemedicine (DTCT) companies increase virtual services for gender affirming medical therapy, examination of platform practices is essential to ensure the field’s standard of care is being met and cost-effective care is being offered. This is especially important considering the reduced access to care and potentially increased vulnerability of the gender-diverse population. Objective We aimed to describe the gender care services offered by DTCT companies for gender affirming medical therapy and to compare them to the current standards of care. We also compared the associated costs of each platform with those that may be encountered for similar care at a tertiary care center. Methods Google was queried in March 2022 to identify DTCT platforms offering gender affirming medical therapy. Platforms based outside the US were excluded. Websites were reviewed for information regarding the transgender affirming medical therapy and associated costs. Using a single institution’s online cost estimator, pay-per-service costs for similar care was estimated at a tertiary care center for a patient without insurance, with private insurance, and with Medicaid. The estimated costs for the first year of therapy with either oral estradiol or intramuscular testosterone were calculated and compared between each platform and the tertiary center. Services provided by DTCT platforms were also compared to those recommended by the World Professional Associated for Transgender Health (WPATH) Standards of Care, Version 7.1. Results Six transgender care DTCT platforms were identified: Folx, True U Clinic, QueerDoc, Queer Med, Trans Clinique, and Plume. All platforms offered gender affirming hormone therapy and several other gender care services (Table 1). All platforms utilized an Informed Consent Model for gender affirming therapy. None of the platforms offered mental or behavioral health services. Laboratory assessments for treatment monitoring were recommended at least quarterly upon treatment initiation, and typically reduced in frequency with ongoing care. Several platforms offered monthly membership payment plans ranging from $59 - $139/month and varying in service inclusion, while other platforms offered pay-per-service plans. The estimated first-year cost for initiation of hormone therapy via the DTCT platforms without insurance ranged from $1,022 to $1,428 for oral estradiol therapy and $1,184 to $1,668 for intramuscular testosterone therapy. In comparison, estimated first-year costs for estrogen and testosterone therapy at the tertiary center without insurance were $1,184 and $1,216, respectively (Figure 1). Estimated first-year costs were lower for a patient at the tertiary center with private insurance or Medicaid. Conclusions DTCT companies offer virtual care for gender affirming medical therapy for transgender, non-binary, and intersex people. Platforms utilized an Informed Consent Model and regular follow up with laboratory assessment, practices which appear to be consistent with the guidelines presented by WPATH. For patients without insurance, the first-year costs of gender affirming hormones are similar through DTCT platforms and a tertiary care center. There is a likely a cost benefit in receiving care through a tertiary center for patients with private insurance or Medicaid. DTCT companies can greatly expand access to transgender and gender affirming care. Disclosure No

(073) The Effects of Intranasal Testosterone (Natesto™) for Treatment of Hypogonadism on Maintenance of Spermatogenesis: Demographic Data from a Single-Institution, Prospective, Non-blinded Study

Abstract Introduction Testosterone therapy (TTh) is becoming increasingly common among men of reproductive age in the United States. An estimated 3 million men are on TTh; however, exogenous testosterone use can disrupt the hypothalamic-pituitary-gonadal axis, leading to reduced spermatogenesis and infertility. The spontaneous recovery of spermatogenesis after cessation of TTh is possible, but may take months to years and can lead the patient to experience hypogonadal symptoms. Recent preliminary results have suggested that a 4.5% intranasal testosterone gel (Natesto™) may offer the potential to offset these symptoms and re-establish eugonadal levels of circulating testosterone. It has also been shown that men on Natesto™ maintain follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels and total motile sperm count within the normal range. This prospective, non-blinded study seeks to confirm the role of Natesto™ to alleviate hypogonadal symptoms in men on gonadotropin therapy for restoration of spermatogenesis. Objective To determine if Natesto™ can alleviate hypogonadal symptoms while preserving the recovery of spermatogenesis. The primary objective of this study is to examine changes in total motile sperm count at baseline, 14 weeks, and 26 weeks. Secondary outcomes include changes in LH, FSH, testosterone, estrogen, and quality of life measurements at these time intervals. Methods IRB approval was obtained for this study. Male patients between 18 and 64 years of age with a diagnosis of testosterone-induced hypo-spermatogenesis were recruited from a tertiary referral male infertility clinic between December 2021 and June 2022. Patients ceased intramuscular testosterone therapy and initiated gonadotropin therapy with FSH 75IU and hCG 3000IU every other day as well as 4.5% testosterone gel (Natesto™) three times daily. Patients were evaluated at baseline, 14 weeks, and 26 weeks. Clinic visits consisted of a hormone profile with total testosterone, estradiol, FSH, LH, questionnaires (IIEF, SF36, and ADAM) as well as a semen analysis. Results A total of 9 patients who met inclusion criteria were identified and elected to take part in the study. Four of the patients obtained baseline intake questionnaires, bloodwork, and a semen analysis with at least 1 additional follow-up visit. Five patients are pending initial follow-up. Patient intake demographic data included a median age of 35, LH of 3.15, FSH of 3.2, testosterone 260ng/dl, IIEF 20, SF-36 energy/fatigue score of 42.5%, and ADAM of 5.5. Four patients had complete gonadotropin suppression, and 6 were azoospermic. Interval semen analyses revealed total motile sperm count increases from 17.9 to 25 million and 9.7 to 10.9 million, with 2 patients demonstrating persistent azoospermia. Mean testosterone increased by 297.5ng/dl. No patients reported adverse events. Conclusions Preliminary results are limited and suggest that men undergoing cessation of testosterone therapy for restoration of spermatogenesis have decreased sexual and overall function scores. Continuation of this study, with recruitment of a larger sample size, will provide important, novel data regarding the effect of Natesto™ therapy on the hypogonadal symptoms seen in men during TTh cessation for spermatogenesis restoration. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals

Delayed Puberty.

Testicular volume ≥4ml and appearance of breast budding are the first signs of puberty. Delayed puberty is diagnosed in the absence of thelarche by 13 y or menarche by 15 y in girls and absence of testicular enlargement by 14 y in boys. Delayed puberty can be due to hypogonadotrophic hypogonadism, hypergonadotrophic hypogonadism or eugonadotrophic eugonadism characterised by low, elevated and normal gonadotrophin levels, respectively. Constitutional Delay of Growth and Puberty (CDGP) and systemic illness should be considered before pathological causes. Assessment of sexual maturity by Tanner's staging and anthropometric assessment on growth chart is pivotal. Lack of menarche in girls with thelarche suggests structural abnormalities of reproductive tract or disorders of sexual development. Measurement of bone age helps to interpret hormone measurements and decide on timing of pubertal induction. Ultrasound assessment of abdomen gives valuable clues to pubertal onset (in girls) and possible underlying etiology. Karyotyping is mandatory in all girls with delayed puberty and short stature, and delayed menarche and boys with hypergonadotrophic hypogonadism. Gonadotrophin releasing hormone analogue stimulation test may help distinguish hypogonadotrophic hypogonadism from CDGP. Pubertal induction is done with intramuscular testosterone and oral estradiol in boys and girls, respectively. Hormone replacement is begun at low doses and slowly escalated over 2 y to mimic a physiological puberty process. Short course of testosterone for 3 to 6 mo is helpful in adolescent boys with CDGP and psychological distress. Attainment of adult sexual maturity by 18 y is mandatory to rule out disorders of hypothalamic pituitary gonadal axis.