Testosterone Cypionate Research Articles

Anabolic steroids and their effects of on neuronal density in cortical areas and hippocampus of mice.

Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.

ANDROGEN RECEPTOR SIGNALING IN HUMAN CORPUS CAVERNOSUM IS NOT DEPENDENT UPON HALF-LIFE OF TESTOSTERONE THERAPY

Testosterone therapy can be administered either with intramuscular substitution of long-acting TRT (testosterone enanthate and testosterone cypionate) and short-acting nasal gel T (Natesto) with varying half-lives (1,2). What remains unclear is whether there are varying levels of androgen receptor signaling within the tissue with varying levels of serum testosterone. We hypothesized that men who receive testosterone therapy with eugonadal levels of serum testosterone regardless of the half-life of the testosterone preparation will have similar androgen receptor signaling within the tissue.

IMPACT OF TESTOSTERONE THERAPY ON POLYCYTHEMIA: EVALUATION OF DATA FROM TWO ONGOING OPEN-LABEL RANDOMIZED SINGLE-CENTER CLINICAL TRIALS

Testosterone (T) replacement therapy (TRT) is the mainstay treatment for male hypogonadism. The most commonly reported adverse event among men using TRT is polycythemia. What is unknown is whether the short-acting vs. long-acting testosterone preparations have different effects on hematocrit. We hypothesized that short-acting testosterone therapy will be physiologic and have lesser effect on hematocrit compared to long-acting TRT. We evaluated data from two simultaneous ongoing open-label, randomized, two-arm clinical trials to evaluate the impact of TRT on Hematocrit and compared prevalence rates of polycythemia among subcutaneous T pellets (long-acting) and Intranasal Testosterone or Intramuscular Testosterone cypionate (TC) (short-acting).

MP04-19 PROSTATIC METAPLASIA OF THE VAGINA IN TRANSGENDER MEN

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I (MP04)1 Sep 2021MP04-19 PROSTATIC METAPLASIA OF THE VAGINA IN TRANSGENDER MEN David Diamond, Richard Yu, Joseph Borer, Rena Xu, William Anderson, and Sara Vargas David DiamondDavid Diamond More articles by this author , Richard YuRichard Yu More articles by this author , Joseph BorerJoseph Borer More articles by this author , Rena XuRena Xu More articles by this author , William AndersonWilliam Anderson More articles by this author , and Sara VargasSara Vargas More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001971.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Gender-affirming surgery (GAS) of the reproductive tract in transgender males includes vaginectomy. In most centers, this is achieved by colpocleisis, with cautery ablation of the vaginal mucosa & suture ablation of the vaginal lumen. Having seen complications due to residual vaginal tissue following colpocleisis, we changed our technique to complete vaginectomy with full-thickness excision of vaginal tissue, allowing its histopathologic examination. Our institution recently reported prostatic metaplasia of vaginal epithelium in the first 6/7 patients treated in this manner. Having accrued 11 additional patients, we extend the analysis of this novel observation. METHODS: The study was IRB approved. Pathology archives were searched for vaginectomy specimens as part of GAS from 1/1/18-2/15/21. Gross features were reviewed. Hematoxylin-and-eosin-stained slides were examined in all cases. The majority were immunohistochemically stained for NKX3.1, prostate-specific antigen (PSA) and androgen receptor. 3 control cases of vaginal tissue from patients without clinical evidence of androgen supplementation were compared. RESULTS: 18 patients, ages 20-34, underwent vaginectomy or excision of vaginal remnants. Each had been assigned female gender at birth without history of endocrine or genetic abnormality. All had received long-term testosterone cypionate treatment (range, 26-60 mos). Grossly, there were no mucosal lesions identified at surgical or pathological examination. Microscopically, 17/18 cases demonstrated a patchy intraepithelial glandular proliferation along the basement membrane; the 18th had a nodular collection of prostate-type tissue within subepithelial stroma. Atrophy & transitional metaplasia of squamous epithelium was also seen. The glandular proliferation was positive for NKX3.1 (15/15; 100%), PSA (9/11; 82%), and androgen receptor (8/8; 100%). Control vaginal tissue showed no evidence of prostatic metaplasia or atrophy. CONCLUSIONS: This study further characterizes the occurrence of prostatic-type tissue in the vagina of transgender men. Prostatic tissue was present in 18/18 transgender men receiving androgen therapy and our findings are consistent with a form of androgen-associated prostatic metaplasia. This finding may have important clinical implications since some transgender men may elect to retain their vaginas, while those who do undergo GAS may have residual tissue left behind, particularly if colpocleisis is performed. Long-term follow-up of this population, with recognition of this entity, is in order. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e74-e74 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Diamond More articles by this author Richard Yu More articles by this author Joseph Borer More articles by this author Rena Xu More articles by this author William Anderson More articles by this author Sara Vargas More articles by this author Expand All Advertisement Loading ...

Disorders of Sex Development.

Disorders of Sex Development.

Some groups of drugs which use is associated with development of drug-induced atrial fibrillation

Recently, more and more attention has been paid to the problem of drug‑induced (DI) atrial fibrillation (AF). It is known that the development of DI AFcan be associated with the intake of cardiovascular and anticancer drugs, drugs that affect the central nervous system or respiratory organs. However,there are other drugs that can provoke DI AF, which practitioners are less aware of. This article is a review of the current literature on DI AF associated withthe intake of other groups of drugs and individual drugs that are not included in the above groups. Analysis of the available literature has shown that theincidence of DI AF reaches 6.9% when taking zoledronic acid and 1.5% when taking alendronate, although data from different authors regarding thecausal relationship between bisphosphonate therapy and the development of AF are ambiguous. The use of high doses of glucocorticosteroids (at a dailydose of ≥ 7.5 mg in terms of prednisolone) is also associated with an increased risk of AF (OR = 6.07; 95% CI: 3.90–9.42). Treatment with non‑steroidal anti‑inflammatory drugs is also associated with a higher risk of developing DI AF compared to those who do not use it – the incidence rate is 1.17 (95% CI:1.10–1.24) for nonselective and 1.27 (95% CI: 1.20–1.34) for cyclooxygenase‑2 inhibitors. The literature contains a description of clinical cases of DI AF whiletaking immunosuppressants (azathioprine, methotrexate + etanercept, fingolimod, cyclosporine), drugs that affect the genitourinary system (vardenafil,sildenafil, yohimbine hydrochloride, hexoprenaline), local anesthetics, bupacaero testosterone, stanozolol, testosterone cypionate, nandrolone decanoateextraboline) and nicotine‑containing products (nicotine‑containing chewing gum).

Therapeutic effects of β-caryophyllene on proliferative disorders and inflammation of the gerbil prostate.

The prostate is susceptible to changes in androgen levels, which can play an important role in the development of Benign Prostatic Hyperplasia (BPH). Natural compounds have beneficial properties for organisms and can be an important therapeutic strategy in the treatment of diseases. β-Caryophyllene (BCP) is a phytocannabinoid present in several medicinal and food plants species and has shown beneficial effects in different organs. However, little is known about its effects on the prostate. The present study seeks to evaluate the effects of exposure to BCP on the morphophysiology of the ventral prostate of adult gerbils supplemented with testosterone. Animals were distributed into four groups (n = 8/group): Intact control (C); β-Caryophyllene (BCP): β-Caryophyllene (50 mg/kg/day); Testosterone (T): animals received subcutaneous injections of Testosterone Cypionate (3 mg/Kg), on alternate days, for one month and were euthanized 30 days supplementation ended; Testosterone and β-Caryophyllene (TBCP): animals were exposed to testosterone cypionate (3 mg/Kg) to induce hyperplastic alterations followed by daily BCP (50 mg/kg). Morphological, biometric, immunohistochemical, and serological analyses were performed. Proliferative disorders and inflammatory foci were present in the ventral prostate of all experimental groups. An increase in the multiplicity of benign intraepithelial neoplasm and subepithelial inflammatory foci was observed in T group. The incidence of intraluminal inflammatory foci and microinvasive carcinoma was verified only in the T group. Cellular rearrangement and tissue remodeling occurred in the prostate of groups exposed to phytocannabinoids. A reduction was observed in the frequency of PHH3 and Cox2 markers in the prostatic epithelium of TBCP in comparison with T. A decrease in F4/80 and CD163 positive macrophages were also observed in the prostatic stroma of the TBCP group in comparison with T. The results suggest that BCP had favorable effects on BPH, reducing the proliferation and frequency of some inflammatory cells. BCP impacts the tissue remodeling process in the premalignant prostate environment and that the use of this phytocannabinoid can have a promising effect in the handling of BPH.

Impact of Testosterone Therapy on Hematocrit and Polycythemia: Evaluation of Data From Two Ongoing Open-Label Randomized Single-Center Clinical Trials

Introduction & Objective: Testosterone (T) replacement therapy (TRT) is the mainstay treatment for male hypogonadism. The most commonly reported adverse event among men using TRT is polycythemia. What is unknown is whether the short-acting vs. long-acting testosterone preparations have different effects on hematocrit. We hypothesized that short-acting testosterone therapy will be physiologic and have lesser effect on hematocrit compared to long-acting TRT. We evaluated data from two simultaneous ongoing open-label, randomized, two-arm clinical trials to evaluate the impact of TRT on Hematocrit and compared prevalence rates of polycythemia among subcutaneous T pellets (long-acting) and Intranasal Testosterone (Natesto) or Intramuscular Testosterone cypionate (TC) (short-acting). Subject and Methods: Hypogonadal men (2 AM serum T < 300 ng/dL assayed by LC-MS/MS) aged 18-65 years were randomized into open-label randomized clinical trials. Eligible subjects received: Trial 1: 800mg subcutaneous Testopel T pellets; Trial 2: 11mg TID Intranasal testosterone (Natesto) or 200mg x 2 weeks TC for 2 months. Serum T, Hematocrit (HCT), and prevalence of polycythemia (as defined as HCT >50%) were collected at baseline and after 2 months of therapy. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as median and interquartile range [25th-75th], paired sample analysis (baseline versus follow-up) was performed with the Wilcoxon rank test to determine change during time within the different TRT modalities, with p<0.05 considered significant. Results: Median change for serum T between baseline and 2mo follow-up to subcutaneous T pellets was 542 [454-757] ng/dL, Intranasal Testosterone 706 [517-1010] ng/dL, and TC 525 [280-712]ng/dL. T pellets showed a statistically significant increase in HCT from 44.6 [42.0-46.6] to 46.7 [42.6-48.9] (p<0.001), with a prevalence of 7/47 (14%) men developing polycythemia. A safety trigger for HCT greater than 54% occurred in 2/47 (4%). The treatment effect was independent of baseline serum testosterone. TRT with Natesto decreased HCT, from 43.4 [41.6-46.1] to 43.4 [40.6-46.5], however not statistically significant (p=0.262). TC statistically increased HCT from 41.6 [40.3-43.1] to 43.8 [43.5-47.4] (p=0.018), with 0% of men developing polycythemia in both groups. Conclusions: Long acting TRT appears to increase hematocrit compared to short-acting testosterone therapies. Treatment of hypogonadal men with Intranasal T Natesto and testosterone cypionate successfully achieved target serum T level and maintained HCT levels. Longer-term durability and safety effects of the intervention remain to be further investigated.

Impact of Short-Acting vs Long-Acting Testosterone Therapy on Intratesticular Testosterone Using Data From Two Open-Label Randomized Clinical Trials of Testosterone Pellets, Injections, and Intranasal Gel in Hypogonadal Men

Introduction & Objective: Exogenous testosterone (T) replacement therapy (TRT) is typically long-acting and can potentially cause infertility in a majority of men due to suppression of HPG axis. Intratesticular testosterone is vital for spermatogenesis and can be reliably evaluated with serum 17-hydroxyprogesterone (17-OHP). Based on this observation, we hypothesized that we used serum 17-OHP as a serum biomarker for evaluating intratesticular T in men receiving TRT. We hypothesized that long-acting TRT will have a significant impact on suppressing HPG axis as compared to short-acting preparations. We evaluated data from two simultaneous open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous T pellets and (Trial II) Intranasal Testosterone (Natesto) or Intramuscular Testosterone cypionate (TC).Subject & Methods: Hypogonadal men (2 AM serum T < 300 ng/dL assayed by LC-MS/MS) aged 18-65 years were randomized into open-label randomized clinical trials. Eligible subjects received: 800mg subcutaneous Testopel T pellets (n=47); or 11mg TID Intranasal testosterone (Natesto) (n=10) or 200mg x 2 weeks TC (n=10) for 2 months. Serum T and 17-OHP were collected at baseline and after 2 months of therapy. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as the median and interquartile range [25th-75th], paired sample analysis (baseline versus follow-up) was performed with the Wilcoxon test to determine change during time within the different TRT modalities, with p<0.05 considered significant. Results: Median change for serum T between baseline and 2mo follow-up to subcutaneous T pellets was 542 [454-757] ng/dL, Intranasal Testosterone 706 [517-1010] ng/dL, and TC 525 [280-712]ng/dL.; 96% of subjects in each trial achieved mean T concentrations in the eugonadal range. We demonstrated that serum T levels were within normal range among men receiving the various therapies. As expected, we found a statistically significant decrease amongst the different T preparations in serum 17-OHP. Longer acting T preparations such as T pellets and TC demonstrated the greatest decrease in 17-OHP, from 41 [20.3-65.6] to 14 [10.3-20.8] ng/dL and 80 [48-121] ng/dL to 20 [17-36] ng/dL (p<0.001), respectively. Shorter acting T preparations such as Natesto demonstrated a statistically significant decrease in 17-OHP, from 52.5 [26-67] ng/dL to 26.5 [18-39.8]ng/dL (p=0.007), but to a lesser extent as compared to the longer-acting preparations.Conclusions: Natesto, and other short acting forms of TRT may help hyogonadal men maintain Intratesticular T that is critical for maintaining spermatogenesis. The differential effects of TRT on intratesticular T based on their half-lives is novel and should be considered during the decision making for hypogondal men who wish to preserve fertility and / or testis size.

Pesticide Dichlorvos Promotes Morphological Alternations in the Rat Prostate

The complex process of carcinogenesis can be modulated by the action of environmental endocrine disruptors, such as the organophosphate pesticide Dichlorvos (DDVP), capable of interfering in homeostasis of different organs and leading to the development of neoplastic lesions. Considering that prostate cancer is the second most common neoplasm in men, worldwide, it is emphasized the importance of studying morphological alterations using animal models. In rodents, tumor initiation can be induced by the carcinogen N-methyl-N-nitrosourea (MNU) and tumor promotion can be stimulated by the administration of testosterone, combinated or not with the use of pesticides. The present study aimed to evaluate the influence of DDVP on the development of morphological alterations in the ventral prostate of rats, after chemical induction by MNU. Thereunto, 32 Fischer 344 rats, aged 90 days, were randomly separated into four experimental groups: Control, DDVP, MNU, MNU+DDVP. For chemical induction, the MNU and MNU+DDVP groups were inoculated with MNU (15 mg/kg), followed by daily subcutaneous injections of testosterone cypionate (2.5 mg/kg), for 20 days. Animals of the DDVP and MNU+DDVP groups, from 120 to 240 days old, received the basal diet supplemented with 10 mg/kg of DDVP. Subsequent to the experimental period, the prostatic ventral lobe of each animal was collected and subjected to morphometric-stereological and histopathological analysis, for the classification of the lesions found. The incidence of alterations in epithelium and stroma of all experimental groups was evaluated, such as epithelial hyperplasia (increased cell population with stratification, without atypia) (Figure A and B); atrophy (retraction of the epithelium with reduction of the secretory cytoplasm) (Figure C and D); periacinary inflammatory foci (presence of inflammatory cell infiltrate) (Figure E and F); cell atypia with presence of cytoplasmic inclusions (Figure G and H) and metaplasia with stromal hyperplasia (change in the pattern of the original epithelium without proliferative change, with an increase in the adjacent stroma) (Figure I to L). The results showed a significant increase of epithelial hyperplasia areas in MNU and MNU+DDVP groups, with 100% of the animals showing this lesion (Table 1), which demonstrates a relation between chemical induction and the proliferative process. The morphometric-stereological analysis confirmed this finding, revealing a relatively greater volume of the epithelial compartment in MNU+DDVP, compared to the Control group (Table 2). Thus, it can be concluded that DDVP, even in low concentration, associated with chemical induction by MNU, was able to disturb the morphology of the ventral prostate, promoting proliferative epithelial lesions, strongly associated with the process of carcinogenesis.

Renal Alterations Induced by Chronic Testosterone Therapy in Adult Female Rats

Testosterone esters are used in clinical conditions such as male hypogonadism. Additionally, it has been used to improve sports performance, increasing muscle mass in both genders, and to affirm gender identity by transgender men. However, few experimental studies have been carried out to evaluate the repercussion of testosterone on female rodents on renal function and blood pressure. Thus, the present study aims to evaluate the blood pressure and renal function in female rats subjected chronically to testosterone therapy. Adult female Wistar rats weighing 200 ± 20 g were randomly assigned to receive testosterone (T) or vehicle (control group - C). Group T received testosterone cypionate (3.0 mg/kg, i.m.) and C received vehicle oil every 10 days for 4 months. Renal function and blood pressure were evaluated at 6 months of age. Urine was collected in metabolic cages for 24 h. Plasma and urine concentrations of urea, creatinine, sodium, potassium, osmolality, and glomerular filtration rate (GFR) were measured. The kidneys were weighed, paraffin-embedded, and histological sections were prepared to evaluate the glomerular area. When compared to C, the group T had higher values of BP [C: 119±1.0; T: 131±1.4; mmHg], lower GFR [C: 0.78±0.02; T: 0.67±0.03; ml/min/g kidney weight], increased proteinuria [C: 2.9±0.2; T: 6.2±0.9 mg/24 h], increased kidney weight [C: 1.8±0.04; T: 2.2±0.06; g] and glomerular hypertrophy [C: 7884±112.8; T: 8917±152.4; µm2]. Urinary osmolality and sodium and potassium excretion were similar in both groups. Testosterone therapy in female rats increased blood pressure and induced renal changes that may be related to adaptations caused by the hormonal treatment that carried female rats close to male physiological conditions.

Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of females.

Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (D0). Fasting blood was collected on D0, D3, D5, D11, and D13, and females were euthanized on D13. On D13, TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations (D13) were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated AR and ESR1 in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT.NEW & NOTEWORTHY Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.

Cross-sex testosterone therapy modifies the renal morphology and function in female rats and might underlie increased systolic pressure.

Testosterone esters are hormones commonly used for affirming gender identity in transmen. The present study evaluates the effect of testosterone on renal morphology and function in an animal model submitted to cross-sex hormone therapy used for transmen. Two-month-old Wistar rats were divided into three groups: male control (MC), female control (FC), and female on testosterone therapy (FTT). The FTT group received testosterone cypionate (3.0mg/kg, i.m.), and the MC and MF groups received vehicle oil every 10days for 4months. Renal function and indirect systolic blood pressure (SBP) measurements were evaluated at 6months of age. Plasma and urine concentrations of urea, creatinine, sodium, potassium, osmolality, and glomerular filtration rate (GFR) were measured. The kidneys were weighed, paraffin-embedded, and histological sections were prepared to evaluate the glomerular area. We verified that the FTT group, in comparison to FC, had increased kidney weight [MC,3.2±0.05; FC,1.8±0.04; FTT,2.2±0.06; g], decreased urine osmolarity [MC,486.9±18.3; FC,1012.0±5.4; FTT,768.2±40.3mOsm/L/g kw], reduced GFR [MC,0.77±0.04; FC,0.78±0.02; FTT,0.67±0.03; mL/min/gkw], larger glomerular area [MC,9334±120.8; FC,7884±112.8; FTT,9078±133.4µm2 ], and higher SBP [MC,126±3.4; FC,119±1.0; FTT,131±1.4; mmHg]. Sodium excretion was higher in FC and FTT in comparison to MC [MC,0.34±0.05; FC,0.56±0.06; FTT,0.54±0.04; mEq/24h/g kw]. Cross-sex hormone therapy with testosterone in female rats induces renal morphofunctional changes and may underlie increased systolic pressure, suggesting an adaptation similar to what is observed in transmen on long-term testosterone therapy.

Testosterone Therapy Effects on Bone Mass and Turnover in Hypogonadal Men with Type 2 Diabetes.

Male hypogonadism is associated with low bone mineral density (BMD) and increased fragility fracture risk. Patients with type 2 diabetes (T2D) have relatively higher BMD, but greater fracture risk. Evaluate the skeletal response to testosterone therapy in hypogonadal men with T2D compared with hypogonadal men without T2D. Single arm, open-label clinical trial (NCT01378299) involving 105 men (40-74 years old), with average morning testosterone <300 ng/dL. Subjects were injected intramuscularly with testosterone cypionate (200 mg) every 2 weeks for 18 months. Testosterone and estradiol were assessed by liquid chromatography/mass spectrometry; serum C-terminal telopeptide of type I collagen (CTX), osteocalcin and sclerostin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD (aBMD) and body composition by dual-energy x-ray absorptiometry; tibial volumetric BMD (vBMD) and bone geometry by peripheral quantitative computed tomography. Among our population of hypogonadal men, 49 had T2D and 56 were non-T2D. After 18 months of testosterone therapy, there were no differences in circulating testosterone and estradiol between the groups. Hypogonadal men with T2D had increased osteocalcin, reflecting increased osteoblast activity, compared with non-T2D men (P < .01). T2D men increased lumbar spine aBMD (P < .05), total area at 38% tibia (P < .01) and periosteal and endosteal circumferences at the same site (P < .01 for both). T2D men had reduced tibial vBMD (P < .01), but preserved bone mineral content (P = .01). Changes in HbA1c or body composition were similar between the 2 groups. Testosterone therapy results in greater improvements in the skeletal health of hypogonadal men with T2D than their nondiabetic counterparts.

029 Improved Maintenance on Index Therapy and Decreased Risk of Hypertension Among Men Treated with Injections of Long-Acting Testosterone Undecanoate Compared with Short-Acting Testosterone Cypionate

Hypogonadism affects 4-5 million males in the United States (US), and is associated with a number of important health problems, including obesity, metabolic syndrome, type 2 diabetes mellitus, and increased cardiovascular risk. Patients are typically treated using testosterone therapy (TTh), including long-acting testosterone undecanoate (TU) and short-acting injectables like testosterone cypionate (TC). Although the efficacy and safety of testosterone injections have been widely studied, the comparative advantages of long-acting TU, such as patient compliance and the subsequent potential health benefits, have not been examined in detail.

027 Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate Versus Subcutaneous Testosterone Enanthate

027 Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate Versus Subcutaneous Testosterone Enanthate

Baseline pathogenic mutations in non-AR/non-TP53 genes and prediction of response to high-dose testosterone.

146 Background: The fact that high dose of testosterone (HDT) elicits positive responses in a subset of prostate cancer patients (pts) is surprising and puzzling. Genomics data differentiating responders (Rs) from non-responders (NRs) is sparse. Pts with mutations in DNA repair pathway genes may be particularly sensitive to HDT (see BA Teply et al. Eur Urol 71:499, 2017). Herein we perform exploratory analyses to better understand the role of pathogenic mutations (muts) in ctDNA as a predictive biomarker for patients treated with HDT. Methods: ctDNA essays were performed with the Guardant360 methodology pre-HDT. Point mutations were classified by cancervar (http://cancervar.wglab.org). Truncating mutations (frameshift and nonsense) were manually curated to assess for pathogenicity. All patients had CRPC and were pre-treated with abiraterone and/or enzalutamide. HDT was typically administered as 400 mg testosterone cypionate q 3-4 weeks. Rs were compared to NRs. All Rs had &gt;3 more cycles of HDT and a &gt;50% PSA decline (N = 17). Non-responders had &lt;3 cycles and no PSA decline (N = 23). Only muts with an allelic fraction of &gt;0.5% were analyzed given dubious importance of mutations with lower allelic fractions. Results: AR muts (4/17 vs 6/23 in Rs and NRs) and TP53 muts (10/17 vs 11/23 in Rs and NRs) were similar ( P= 0.85 and 0.49, respectively) but the number of pts with non-AR/non-TP53 muts was distinct (3/17 for Rs, and 12/23 for NRs; P= 0.026). The average number of non-AR/non-TP53 muts (Rs = 0.23 and NRs = 0.83) was higher in the NRs (P = 0.046). When analyzing DNA repair alterations, no differences were noted in those with BRCA1/BRCA2/ATM mutations in the Rs and NRs (1/17 vs 6/23 respectively; P= 0.09). Conclusions: AR and TP53 pathogenic mutations are common in both Rs and NRs but other pathogenic mutations are more common in non-responders. We hypothesize that genetic pathways outside of the AR/TP53 axis drive resistance to HDT. Additional studies are warranted to assess whether or not these pathways drive resistance to HDT. Limitations are acknowledged with regard to the Guardant assay gene selection for CRPC pts.

Molecular and clinical characterization of metastatic castration-resistant prostate cancer (mCRPC) patients achieving deep PSA responses to bipolar androgen therapy (BAT).

127 Background: BAT is an emerging treatment strategy for men with mCRPC, whereby testosterone concentrations are cycled from supraphysiologic to castrate levels each month. BAT has been shown to be safe, and induces clinical responses in a proportion of patients, some of which are extreme. We explored the clinical and molecular characteristics of mCRPC pts that achieved deep PSA responses on BAT. Methods: We identified N= 22/114 (19%) mCRPC pts who achieved &gt;70% PSA reductions on treatment with BAT. All pts were treated on-protocol at Johns Hopkins using 400mg testosterone cypionate intramuscularly every 28 days, together with continuous LHRH agonist therapy. Pts remained on study until clinical or radiographic progression, as per protocol. Clinical-grade molecular sequencing was obtained using commercially available assays. Results: Next-generation somatic DNA sequencing was obtained on 15/22 (68%) pts. Of these 15 pts with sequencing data who achieved a &gt;70% PSA response on BAT, 14/15 (93%) harbored a pathogenic mutation in TP53 and/or a homologous recombination DNA repair (HRD) gene. Among patients with measureable disease (N=15), 10 pts (67%) achieved an objective response including one pt with a complete response. The median radiographic progression-free survival (rPFS) of these deep PSA responders on BAT was 11.3 (95% CI, 7.9-25) months. Conclusions: We observed an enrichment of TP53 and/or HRD mutations in mCRPC pts with extreme PSA responses to BAT, with durability lasting about a year These data support the hypothesis that BAT may work best in DNA repair-deficient mCRPC pts. Further study of BAT in biomarker selected mCRPC populations (i.e. TP53/HRD mutated) is warranted. [Table: see text]

The Prevalence and Management of Secondary Erythrocytosis in Transgender Individuals Undergoing Masculinizing Therapy

Background:Gender-affirming hormone therapy is integral to the care of transgender individuals, but the hematologic complications of this therapy are not entirely understood. While secondary erythrocytosis is a widely recognized complication of testosterone administration, the exact prevalence of erythrocytosis in patients receiving exogenous testosterone for gender transition and the optimal management of this condition remain unclear. We performed a retrospective analysis of transgender individuals undergoing masculinizing therapy with testosterone at our institution to assess the prevalence of secondary erythrocytosis and review the management techniques utilized. Methods:We performed a retrospective observational study of transgender individuals over the age of 18 years undergoing masculinizing therapy with exogenous testosterone between June 30, 2019 and June 30, 2020 at Oregon Health &amp; Science University Hospital in Portland, Oregon. We collected data on average pre-testosterone hemoglobin and hematocrit values, formulation of testosterone and route of administration, peak hemoglobin and hematocrit values after the initiation of endocrine therapy, management of secondary erythrocytosis, and thrombotic events in those with secondary erythrocytosis. Descriptive statistics were employed to determine the prevalence of erythrocytosis using the reference ranges for cisgender males and to quantify average increase in hemoglobin and hematocrit levels from pre-therapy levels. Seaborn and Matplotlib libraries in Python were used for data visualization and pandas library in Python was used for statistical analysis. Results:A total of 234 individuals were included in this study with a mean age of 29 years. Testosterone cypionate was the most commonly administered formulation at 77.8% of cases, followed by transdermal testosterone formulations 14.5%, testosterone enanthate 4.2%, and combination transdermal testosterone plus cypionate 2.1%. Intramuscular injection was the most common route of administration at 65.4% followed by subcutaneous injection 15.8% and transdermal gel 12% and patch 2.1%. The mean pre-testosterone hemoglobin was 13.5 g/dL and hematocrit was 40.3%. After initiation of hormone therapy, the mean hemoglobin peak was 15.7 g/dL and hematocrit peak was 47.2% (Figures 1 and 2). It took an average of 21 months after initiation of therapy to reach peak hemoglobin and hematocrit levels. 23.5% of patients met the definition of erythrocytosis using our institutional cisgender male reference range for hematocrit above 50%, and 8.5% exceeded a hemoglobin threshold of 17.5 g/dL. Only one thrombotic event, a superficial venous thrombosis, occurred in those with secondary erythrocytosis. Dose reduction of testosterone was performed for 14.5% of patients who developed erythrocytosis, and no other management strategies, including therapeutic phlebotomy, were documented. 88.9% of patients with erythrocytosis had received testosterone cypionate, with other formulations infrequently associated with polycythemia-range hematocrit levels. Discussion:Our analysis of transgender individuals undergoing masculinizing therapy with testosterone revealed an average increase in hemoglobin of 2.2 g/dL and in hematocrit of 6.9% after the onset of endocrine therapy. In total, 23.5% of patients met the threshold for secondary erythrocytosis using the hematocrit reference range for cisgender men after initiation of testosterone while only 8.5% met the hemoglobin threshold of 17.5 g/dL. The clinical consequences of this hematologic shift are unclear, with only one patient documented as developing a superficial venous thrombosis, and no occurrences of deep venous thrombosis, pulmonary embolism, or other thrombotic events. It also remains uncertain if utilizing the reference range for cisgender men is an appropriate method of predicting thrombotic risk in this population. The sole management strategy recorded was testosterone dose reduction as no patients had documentation of any therapeutic phlebotomy to lower their hematocrit levels. Of note, some providers recommended that their patients with erythrocytosis donate blood, which was not able to be documented in the medical record. Further studies are required to better define the clinical sequelae of erythrocytosis in this patient population and to determine optimal management of this condition. Figure Disclosures Shatzel: Aronora, Inc.:Consultancy.

A cross-sectional comparison of secondary polycythemia in testosterone-deficient men treated with nasal testosterone gel vs. intramuscular testosterone cypionate.

Secondary polycythemia is a known adverse effect of testosterone replacement therapy (TRT). Different testosterone formulations are available, with significantly different half-lives, which have varying influences on the development of secondary polycythemia. Herein, we compared the prevalence of secondary polycythemia in testosterone-deficient men treated with intranasal testosterone gel (Natesto®) vs. intramuscular testosterone cypionate (TC) therapy. We performed a cross-sectional analysis of secondary polycythemia (hematocrit [Hct] ≥54%) in men who received TRT. We included a total of 60 men: 30 men who received Natesto (4.5% testosterone gel [tid, 5.5 mg/nostril, 11 mg/dose, 33 mg/day]), and 30 who received TC (between 0.5 and 1.0 mL or 100-200 mg intramuscularly weekly). A univariable and multiple regression analysis was performed considering last Hct measurement as the main outcome. The analyzed variables included were age, body mass index (BMI), smoking history, treatment group, and testosterone levels on followup. We identified polycythemia (Hct ≥54%) in 10% (3/30) of men who received TC. Additionally, in men treated with TC, 33.3% (10/30) had a Hct ≥50% during therapy. None of the men who received Natesto had a Hct ≥50% during therapy. On multivariable linear regression analysis, we demonstrated that the use of TC increased Hct by 3.24% (95% confidence interval [CI] 0.74-5.73%, p=0.012) compared to Natesto. The prevalence of polycythemia in men treated with Natesto was markedly lower compared to the men who received TC therapy.