Search

Abstract Objective The objective of the study is to evaluate whether low nadir testosterone during treatment with triptorelin pamoate, a luteinising hormone‐releasing hormone (LHRH) agonist, is associated with improved clinical outcomes in patients with advanced prostate cancer using a retrospective analysis of clinical trial data. Patients and methods Data were pooled from three prospective, 9–12‐month Phase III studies of triptorelin monotherapy in patients with advanced prostate cancer (including NCT00751790). The serum testosterone concentration suppression targets evaluated were

Introduction: Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer. Methods: Relugolix was initiated at least 2 months prior to SBRT. Interventions to improve adherence were not utilized. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone ≤ 20 ng/dL. Early PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and ≤ 0.2 ng/mL during the first 4 months post SBRT. Results: Between July 2021 and January 2023, 52 men were treated at Georgetown with relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were African American and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were ≥ Grade Group 3. 44 patients were intermediate- and 8 were high-risk. Patients initiated relugolix at a median of 3.6 months prior to SBRT with a median duration of 6.2 total months. 92.3% of patients achieved profound castration during relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively. Discussion: Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. We observed a 96% testosterone suppresion rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients with localized prostate cancer can consistently and successfully follow an oral ADT protocol without daily reminders. Given relugolix's potential benefits over injectable GnRH receptor agonists, its usage may be preferred in specific patient populations (fear of needles, prior cardiovascular events). Future studies should focus on boundaries to adherence in specific underserved populations. [ABSTRACT FROM AUTHOR]

IntroductionInjectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer.MethodsRelugolix was initiated at least 2 months prior to SBRT. Interventions to improve adherence were not utilized. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone ≤ 20 ng/dL. Early PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and ≤ 0.2 ng/mL during the first 4 months post SBRT.ResultsBetween July 2021 and January 2023, 52 men were treated at Georgetown with relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were African American and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were ≥ Grade Group 3. 44 patients were intermediate- and 8 were high-risk. Patients initiated relugolix at a median of 3.6 months prior to SBRT with a median duration of 6.2 total months. 92.3% of patients achieved profound castration during relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively.DiscussionRelugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. We observed a 96% testosterone suppresion rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients with localized prostate cancer can consistently and successfully follow an oral ADT protocol without daily reminders. Given relugolix’s potential benefits over injectable GnRH receptor agonists, its usage may be preferred in specific patient populations (fear of needles, prior cardiovascular events). Future studies should focus on boundaries to adherence in specific underserved populations.

Abstract Background Selective androgen receptor modulators (SARMs) are becoming increasingly common amongst athletes and the general population, but their side effect profile in human subjects at recreational doses is understudied. Case presentation A 27-year-old asymptomatic male weightlifter presented for an annual physical exam and was coincidentally found to have an abnormal lipid panel, which the patient believed to be due to recreational SARMs (LGD-4033 and S-23) usage. Further work-up revealed elevated liver enzymes suggestive of hepatocellular injury and suppression of the pituitary–gonadal axis. Lipids, hepatic function, and hormones returned to baseline after cessation of SARMs. Conclusions This is the first case report on how SARMs may impact LDL, cause hepatocellular rather than cholestatic liver injury, and alter health markers despite complete lack of symptoms. It is also the first case report on the potential negative effects of the SARM S-23.

Background: Selective androgen receptor modulators (SARMs) are becoming increasingly common amongst athletes and the general population, but their side effect profile in human subjects at recreational doses is understudied. Case presentation: A 27-year-old asymptomatic male weightlifter presented for an annual physical exam and was coincidentally found to have an abnormal lipid panel, which the patient believed to be due to recreational SARMs (LGD-4033 and S-23) usage. Further work-up revealed elevated liver enzymes suggestive of hepatocellular injury and suppression of the pituitary–gonadal axis. Lipids, hepatic function, and hormones returned to baseline after cessation of SARMs. Conclusions: This is the first case report on how SARMs may impact LDL, cause hepatocellular rather than cholestatic liver injury, and alter health markers despite complete lack of symptoms. It is also the first case report on the potential negative effects of the SARM S-23. [ABSTRACT FROM AUTHOR]

To clarify the signal transduction mechanism in the differentiation and secretion of salivary glandular cells, the present study was attempted to examine in the submandibular gland (SMG) of mice, the expression and localization of phospholipase D1 (PLD1), one of the important effector molecules working in response to the activation of intramembranous receptors by first messengers. In immunoblotting analysis, the expression of PLD1 was high at postnatal 4 weeks (P4W) and decreased at P8W, and it was at negligible levels at newborn stage (P0W) and postnatal 2 weeks (P2W). The expression of PLD1 was greater in females, and it was suppressed by administration of testosterone to female mice. In immuno‐light microscopy, immunoreactivity for PLD1 at P4W was moderate to intense, in the forms of dots and globules mainly in the apical domains of immature granular convoluted tubule (GCT)‐cells localized largely in the proximal portion of the female GCT. By P8W, it decreased in intensity and remained weak to moderate along the apical plasmalemma of cells throughout the course of the female GCT, whereas it was faint throughout the GCT of the male SMG at P4W and negligible at P8W. In immuno‐electron microscopy, immature GCT‐cells characterized by electron‐lucent granules were immunoreactive and the immunoreactive materials were deposited close to, but not within, those granules. Typical GCT cells, characterized by electron‐dense granules, were immunonegative. No significant immunoreaction for PLD1 was seen in acini of SMGs of either sex at any time point examined. It is suggested that PLD1 is involved in the signaling for secretion of immature GCT cells and influences differentiation of these cells, probably through their own secretory substances. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to evaluate whether low nadir testosterone during treatment with triptorelin pamoate, a luteinising hormone-releasing hormone (LHRH) agonist, is associated with improved clinical outcomes in patients with advanced prostate cancer using a retrospective analysis of clinical trial data., Patients and Methods: Data were pooled from three prospective, 9-12-month Phase III studies of triptorelin monotherapy in patients with advanced prostate cancer (including NCT00751790). The serum testosterone concentration suppression targets evaluated were <0.35 nmol/L (<10 ng/dl), <0.7 nmol/L (<20 ng/dl), <1.7 nmol/L (<50 ng/dl) and ≥1.7 nmol/L. Overall survival (OS) and disease-specific survival (DSS) by testosterone suppression group were assessed by Kaplan-Meier analysis, with log-rank test. The time frame for the primary analysis was Days 1-518 (median OS follow-up 254 days [range, 29-518 days]) and for the sensitivity analyses was Days 1-262. Supplementary analyses combined the ≥0.7- to <1.7-nmol/L and ≥1.7-nmol/L groups., Results: The sample size comprised 592 patients (most received triptorelin monotherapy; four reported concomitant androgen receptor-axis-targeted therapy). Nadir testosterones of <0.35, ≥0.35 to <0.7, ≥0.7 to <1.7 and ≥1.7 nmol/L were achieved by 96%, 3.2%, 0.34% and 0.17% of patients, respectively. Better OS with decreasing level of nadir testosterone was observed ( p  < 0.001) and this persisted after sensitivity/supplemental analyses (all p  < 0.001). Differences in DSS with decreasing levels of nadir testosterone were not statistically significant in the primary analysis. Sensitivity/supplemental analysis showed better DSS with decreasing level of nadir testosterone (Days 1-262, p  = 0.01; combined groups Days 1-518, p  = 0.03; combined groups Days 1-262, p  = 0.005)., Conclusion: Low nadir testosterone achieved during treatment with the LHRH agonist triptorelin was associated with improved OS and DSS in patients with advanced prostate cancer., Competing Interests: Laurence Klotz has received honoraria for academic presentations from Debiopharm and has also received research support from Debiopharm. Tri Tat is an employee of Debiopharm International, Lausanne, Switzerland., (© 2024 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Objectives: To characterize the probability of testosterone escape during a course of radiotherapy and androgen deprivation (ADT) in patients with prostate cancer, and examine predictors of testosterone escape, the prostate specific antigen (PSA) levels during testosterone escape, and the impact of testosterone escape on outcome. Patients and Methods: To participate in the database review, necessary data included: (i) type of luteinizing hormone‐releasing hormone agonist (LHRHa) administered, date of initiation, and date of cessation or duration of therapy, (ii) radiotherapy information (start date and dose) with at least 6 months of follow‐up after radiotherapy, (iii) radiotherapy to the prostate or prostate bed, and (iv) at least one serum testosterone and PSA measurement. Results: Five hundred sixty patients in the database were identified as being treated with radiotherapy and ADT. Three hundred seventy‐five patients had at least one measurement of testosterone and PSA, and the type of LHRHa used could be determined in 361 patients. Median follow‐up of patients still living was 4.7 years. The median number of testosterone measurements per patient was six. The incidence of testosterone escape per patient course of treatment was buserelin, 9.3%; goserelin, 10.5%; intramuscular leuprolide, 11.5%; leuprolide subcutaneous, 23.9%; and triptorelin, 6.7% (p = 0.02). There was no difference in either biochemical failure‐free survival or overall survival in patients stratified by testosterone escape. The modal PSA level during a testosterone escape was an undetectable PSA. Conclusions: An undetectable PSA does not rule out the presence of higher than desired levels of testosterone during ADT. In this cohort of patients, there appears to be no impact of testosterone escape on either biochemical relapse‐free survival or overall survival. [ABSTRACT FROM AUTHOR]

Introduction: Androgen deprivation therapy (ADT) is a mainstay of treatment against advanced prostate cancer (PC). As a treatment goal, suppression of plasma testosterone levels to <50 ng/dl has been established over decades. Evidence is growing though that suppression to even lower levels may add further clinical benefit. Therefore, we undertook a pooled retrospective analysis on the efficacy of 1-, 3-, and 6-month sustained-release (SR) formulations of the gonadotropin-releasing hormone (GnRH) agonist triptorelin to suppress serum testosterone concentrations beyond current standards.Methods: Data of 920 male patients with PC enrolled in 9 prospective studies using testosterone serum concentrations as primary endpoint were pooled. Patients aged 42-96 years had to be eligible for ADT and to be either naïve to hormonal treatment or have undergone appropriate washout prior to enrolment. Patients were treated with triptorelin SR formulations for 2-12 months. Primary endpoints of this analysis were serum testosterone concentrations under treatment and success rates overall and per formulation, based on a testosterone target threshold of 20 ng/dl.Results: After 1, 3, 6, 9, and 12 months of treatment, 79%, 92%, 93%, 90%, and 91% of patients reached testosterone levels <20 ng/dl, respectively. For the 1-, 3-, and 6-month formulations success rates ranged from 80-92%, from 83-93%, and from 65-97% with median (interquartile range) serum testosterone values of 2.9 (2.9-6.5), 5.0 (2.9-8.7), and 8.7 (5.8-14.1) ng/dl at study end, respectively.Conclusion: In the large majority of patients, triptorelin SR formulations suppressed serum testosterone concentrations to even <20 ng/dl. Testosterone should be routinely monitored in PC patients on ADT although further studies on the clinical benefit of very low testosterone levels and the target concentrations are still warranted. [ABSTRACT FROM AUTHOR]

The GnRH antagonist, acyline, has not yet been investigated in the stallion. Our study aimed to: (1) evaluate the downregulation of the stallion hypothalamic-pituitary-gonadal axis by acyline through assessment of seminal parameters, testicular volume, and sexual behavior; (2) assess hormonal response of acyline-treated stallions to GnRH stimulation; and (3) verify reversibility after treatment. Stallions were assessed pretreatment and subsequently treated (every five days) for 50 days: acyline (n = 4; 330 μg/kg acyline) or control (n = 4, vehicle). The stallions were then monitored for 62 days after the last day of treatment. Treatment-induced declines (P < 0.05) in FSH, LH, testosterone, and estrone sulfate. Gonadotropins and testosterone returned to control values within 9 days, and estrone sulfate by 14 days, after discontinuation of treatment. Acyline-treated stallions failed to respond with a rise in FSH, LH, and testosterone after exogenous GnRH stimulation (gonadorelin) at Day 46 of treatment compared to pretreatment stimulation and control stallions. Decreases (P < 0.05) were observed in total sperm numbers and motility (week 2) in acyline-treated stallions, as well as total seminal plasma protein (week 2) and testicular volume (week 5). Over the course of the study, the time to erection, time to ejaculation, and number of mounts increased (P < 0.0001) across both groups of stallions; however, there was no effect of treatment or treatment by time interactions on these parameters. Testicular volume, and most seminal parameters regained normal levels within 62 days after treatment ended; on follow-up, sperm output of acyline-treated stallions was regained within 7 months after the end of experiment. In conclusion, acyline reversibly suppresses the stallion hypothalamic-pituitary-gonadal axis. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Previous reports, with small numbers of patients, have described the problem of incomplete testosterone suppression (>1.1 or 1.7 nmol/L) with LHRH agonists. Various predisposing factors have been suggested: different drug agents and patient factors such as age, pretreatment testosterone levels and weight. Such incomplete testosterone suppression has been shown in one small report to be associated with increased PSA failure rates and in another report in those with metastases, with worse survival. This study used testosterone assays that are more accurate at low levels than those used in most previous reports in a large dataset of 2196 men, and confirmed incomplete testosterone suppression (breakthrough) rates >1.7 nmol/L of 3.4% and >1.1 nmol/L of 6.6%. We showed that younger age was strongly associated with the risk of breakthrough, with a minor effect of increasing body mass index. Repeated breakthroughs were more common (16%) in those who had already had one breakthrough. Interim measures of cancer control (PSA kinetics during LHRH therapy) were inferior in those with a breakthrough, and those with breakthroughs between 1.1 and 1.7 nmol/L had worse long-term biochemical control rates. OBJECTIVES To describe breakthrough rates above castrate levels of testosterone, in a population-based series of men undergoing adjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy with curative radiation therapy., To explore the predisposing factors for such breakthroughs and their impact on subsequent outcomes., PATIENTS AND METHODS All men treated for prostate cancer between 1998 and 2007 with curative radiation in the province of British Columbia, Canada were potentially eligible ( n= 11 752). Of these, 2196 fulfilled the eligibility criteria., Serial testosterone measurements were obtained during continuous LHRH therapy., Breakthrough rates >1.1 nmol/L and >1.7 nmol/L were calculated for each LHRH injection and for each patient course., Predisposing factors were identified, and early surrogates of oncological outcome (neoadjuvant nadir and post-treatment nadir) were determined., RESULTS The risk of a breakthrough >1.1 nmol/L was 6.6%, and >1.7 nmol/L was 3.4% per patient course and 5.4% and 2.2% per LHRH injection (inclusive ranges)., Repeated breakthroughs occurred in 16% of patients., Younger men were more liable to breakthroughs ( P < 0.001)., Early PSA kinetic surrogates of cancer control were inferior in those with breakthroughs., Neither overall biochemical non-evidence of disease (bNED) nor survival were compromised, although subgroup analysis showed inferior 5-year bNED in those with breakthroughs of 1.1-1.7 nmol/L vs those without (58% vs 73%, respectively; P= 0.048)., CONCLUSIONS Breakthroughs with LHRH agonists occur occasionally per injection, but occur commonly per patient course of treatment, and adversely affect early surrogate measures of outcome., The monitoring of testosterone levels during therapy is therefore advised. [ABSTRACT FROM AUTHOR]

We present a case report of a patient with prostate cancer who failed to demonstrate consistent testosterone suppression to castration levels and incomplete suppression of serum prostate-specific antigen, although treated with gonadotropin releasing hormone agonists for 48 months. Serum dehydroepiandrosterone, dehydroepiandrosterone sulphate, as well as the androgen metabolite, androsterone glucuronide, were elevated compared to the other patients. The present data suggest that those prostate cancer patients who have even marginally elevated adrenal androgens may especially benefit from combined androgen blockade.Prostate Cancer and Prostatic Diseases (2009) 12, 100–103; doi:10.1038/pcan.2008.15; published online 24 June 2008 [ABSTRACT FROM AUTHOR]

Gonadotrophin-releasing hormone (GnRH) agonists are currently the mainstay in the management of advanced prostate cancer. Used either as monotherapy or combined with antiandrogens, GnRH agonists suppress serum testosterone levels and thus slow the growth of the tumour cells that depend on testosterone for growth. GnRH agonists have largely replaced orchidectomy in the management of advanced prostate cancer, because patients are reluctant to undergo surgical castration. However, can we do better in androgen-deprivation therapy? There is some evidence to suggest that GnRH agonists do not achieve the level of testosterone suppression attained with orchidectomy, or as rapidly, factors which could be expected to affect overall survival. Together, these observations highlight the need to develop newer agents that can achieve rapid, profound and sustained testosterone suppression, equivalent to that with orchidectomy. Preliminary data for the GnRH blocker, degarelix, suggest that this new agent might overcome the shortcomings associated with GnRH agonists. Further clinical data are therefore awaited with much interest. [ABSTRACT FROM AUTHOR]

Abstract: Following the discovery that prostate tumour growth is androgen-dependent, androgen suppression as achieved with orchiectomy (standard of castration) has been shown to delay tumour progression, improve symptoms and disease specific survival. Since the seventies hormone therapy with luteinising hormone releasing hormone (LHRH) agonists has constituted the main approach for suppressing testosterone in the treatment of advanced and metastatic prostate cancer. The availability of sustained-release formulations of LHRH agonists has greatly increased the patients’ treatment compliance and contributed to the current widespread use of these agents. So far, it was assumed that LHRH agonists are equivalent to surgical castration in terms of achieving similar low levels of testosterone and maintaining these low levels over time. With the advent of new generation testosterone assays, several authors have reported that a considerable proportion of the patients receiving conventional LHRH agonists do not reach the testosterone levels as achieved with surgical castration (bilateral orchiectomy). In addition, testosterone rises, manifesting as breakthrough or acute-on-chronic testosterone responses, are relatively common. Hence, in order to optimise the proportion of patients achieving testosterone levels similar to surgical castration, and to reduce the occurrence of breakthrough and acute-on-chronic responses, a new sustained-release formulation of leuprolide, Eligard®, has been developed. Eligard® has been shown to suppress testosterone to a level similar to orchiectomy in almost all patients, with a very low prevalence of breakthrough and acute-on-chronic responses. This is achieved through providing a higher dose of leuprolide compared to other formulations and by delivering an improved sustained release over the delivery period. Side effects seen with Eligard® are similar to those seen with the older LHRH agonist formulations. It this sense Eligard® provides an optimised control of testosterone levels without increasing the side effects typically associated with LHRH agonist therapy. [Copyright &y& Elsevier]

The primary objective of this study was to evaluate the effect of drug loading on the release of leuprolide acetate from an injectable polymeric implant, formed in situ, and efficacy of the released drug in suppressing serum testosterone levels in dogs for at least 90 days. An additional objective was to compare the optimum implant formulation with commercial microsphere product. Evaluated implant formulations contained 45% w/w 75/25 poly (DL-lactide-coglycolide) polymer having an intrinsic viscosity of 0.20 dL/g, dissolved in N-methyl-2-pyrrolidone. Irradiated polymer solution was mixed with leuprolide at different drug loads (3%, 4.5% and 6% w/w) prior to subcutaneous administration to dogs. Dog serum was analyzed for testosterone (RIA) and leuprolide (LC/MS/MS) levels and comparisons within the three implant formulation groups were made. Varying the drug load did not significantly affect the release of leuprolide or efficacy of the implant formulation. Thus, the 6% w/w formulation with the smaller injection volume was selected for comparison with the commercial LUPRON® Depot product, which was administered intramuscularly at a similar dosage. These comparisons of serum testosterone and leuprolide levels showed no significant difference in the pharmacologic efficacy even though drug levels were different at a number of points. This was mainly due to associated high standard deviations. Based on these studies, the 6% w/w leuprolide implant formulation was considered to be a suitable candidate for further development. Additional benefits of this system include its simple manufacturing and lower costs. [ABSTRACT FROM AUTHOR]

Background: 11β-methyl-19-nortestosterone (11β-MNT) is a modified testosterone (T) with androgenic and progestational activity. A single oral dose of the prodrug, 11β-MNT dodecylcarbonate (11β-MNTDC), was well tolerated in healthy men., Methods: We conducted a randomized, double-blind study at 2 academic medical centers. 42 healthy men (18-50 years) were randomized to receive oral placebo or 11β-MNTDC, 200 or 400 mg daily, for 28 consecutive days. Primary outcome (safety and tolerability) measures were assessed twice per week. Subjects underwent serial blood sampling over 24 hours on days 1 and 28 to assess secondary outcomes: pharmacokinetics (serum drug concentrations); pharmacodynamics of 11β-MNTDC (serum sex steroids and gonadotropins); and mood and sexual function (via validated questionnaires)., Results: There were no serious adverse events. No participants discontinued because of an adverse event or laboratory test abnormality. 11β-MNTDC resulted in a dose-related increase in serum 11β-MNTDC and 11β-MNT concentrations sustained over 24 hours. Administration of 11β-MNTDC resulted in a marked suppression of serum gonadotropins, T, calculated free T, estradiol, and SHBG over the treatment period (P < 0.01). Adverse effects that may be related to 11β-MNTDC included weight gain, acne, headaches, fatigue, and mild mood changes, with 5 men reporting decreased libido and 3 decreased erectile/ejaculatory function. Serum low-density lipoprotein cholesterol, weight (~2 kg), hematocrit, and hemoglobin increased and serum high-density lipoprotein cholesterol decreased in both 11β-MNTDC groups., Conclusion: Daily oral 11β-MNTDC for 28 days in healthy men markedly suppressed serum gonadotropin and T concentrations without serious adverse effects. These results warrant further evaluation of 11β-MNTDC as a potential male oral contraceptive., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve this. We investigated the effectiveness of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since 2008 treated with oral estradiol. We looked at the success of achieving serum levels of testosterone and 17-β estradiol in the normal range on various doses of estradiol (with and without antiandrogens spironolactone and finasteride). Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized., Competing Interests: No competing financial interests exist.