GnRH Agonist Research Articles

Premature ovarian insufficiency in pediatric cancer patients: a 10 year Rady Children's Hospital experience.

To highlight the occurrence of premature ovarian insufficiency in pediatric cancer patients and determine which patient characteristics or treatment modalities are associated with ovarian failure and recovery. Between August 2011-August 2021, 36 of 2,661 patients with cancer were identified to have subsequent ovarian failure. Data collected included cancer type, diagnosis age, types of chemotherapy, bone marrow transplant or radiation treatment, peak follicle-stimulating hormone (FSH), peak anti-Mullerian hormone (AMH), gonadotropin releasing hormone agonist (GnRHa) treatment, type of hormone replacement therapy, and if ovarian function recovery occurred. The most common cancer type identified was ALL. The mean age of diagnosis was 8.5±4.3 years and mean age of peak FSH value was 12.6±2.8 years. Most patients (97.2 %) were treated with alkylating agents and 72.2 % received radiation. Most patients (72.2 %) received hormone therapy, and 15.8 % of patients received GnRHa Lupron. Ten patients (27.8 %) had ovarian function recovery. Diagnosis age and treatment type were recovery predictors in multivariate regression modeling. Each year older in age was associated with a 30 % decrease in odds of recovery (OR: 0.7, CI: 0.5-0.95, p=0.035), and alkylating agent treatment without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI: 2.7-564, p=0.007). This retrospective review demonstrates that POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on potential long-term effects of cancer treatment and importance of routine surveillance. This study confirmed that recovery of ovarian function is possible, especially when diagnosed at a younger age, making continued monitoring essential.

A randomized phase II trial on the addition of dutasteride to combined androgen blockade therapy versus combined androgen blockade therapy alone in patients with advanced or metastatic salivary duct carcinoma – the DUCT study protocol

BackgroundSalivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer, frequently associated with incurable recurrences and distant metastases (R/M). Proliferation of SDC relies on androgen receptor (AR) signalling, prompting the use of combined androgen blockade (CAB, i.e., luteinizing hormone-releasing hormone agonist and/or AR antagonists) to R/M SDC patients. However, only a subset of patients benefits from such treatments. We have shown that response to CAB is associated with steroid 5α-reductase 1 (SRD5A1) mRNA expression. SRD5A1 catalyses the intracellular conversion of testosterone into the more potent AR-agonist dihydrotestosterone. This conversion can be inhibited by dutasteride, a potent SRD5A1-inhibitor, which is currently prescribed for benign prostatic hyperplasia. We hypothesize that repurposing dutasteride to target AR signalling in SDC could enhance therapeutic response and clinical outcome in SDC patients.MethodsThis prospective, open-label, randomized controlled phase II clinical trial, is designed to investigate whether dutasteride as an adjunct drug to CAB improves response rate and clinical outcome in patients with AR-positive R/M SDC. Patients are divided in two cohorts based on their prior systemic treatments. In cohort A, CAB-naïve patients (n = 74) will be randomly assigned to either a control arm (Arm 1) receiving CAB (goserelin 10.8 mg/3m and bicalutamide 50 mg/OD) or an experimental arm (Arm 2) where dutasteride (0.5 mg/OD) is added to the CAB regimen. In cohort B, patients with disease progression after adjuvant or first-line palliative CAB therapy (max. n = 24) will receive goserelin, bicalutamide, and dutasteride to assess whether the addition of dutasteride can overcome therapy resistance. The primary endpoints are the objective response rate and duration of response. Secondary endpoints are progression-free survival, overall survival, clinical benefit rate, quality of life, and safety. Translational research will be performed to explore molecular target expression differences and their correlation with clinical outcome.DiscussionThe DUCT study addresses an unmet medical need by investigating the repurposing of dutasteride to enhance treatment response and improve clinical outcome for patients with R/M SDC, especially those with limited alternative treatment options, such as HER2-negative cases. By repurposing a registered low-cost drug, this trial’s findings could be readily applied into clinical practice.Trial registrationClinicaltrials.gov Identifier: NCT05513365. Date of registration: August 24, 2022.Protocol versionCurrent protocol version 4.0, February 21, 2024.

A Complete Guide to Understand PMS (Pre-Menstrual Syndrome) in Women’s and its Effective Ayurvedic and Allopathic Treatment

Many women around the world are suffering from common physical discomfort just before their menstrual cycle. Symptoms may vary women to women which can be mild to severe such that it could affect their regular activities. Based on the diagnostic criteria, 2.5–3% of women of reproductive age have the severe form of PMS, while 40% of these women experience the moderate type. The symptoms seen were fluid retention, pain in pelvic region, mastalgia, psychological changes, behavioural changes, gastrointestinal problems, skin related problems and nervous system affecting problem. The targeting therapies to cure PMS includes allopathic as well as ayurvedic remedies. Allopathic includes mainly targeting brain SSRIs and some pharmacotherapies including administration of NSAIDs, anxiolytic agents, gonadotropin-releasing hormone (GnRH) agonists. etc. and recent studies shows combined oral contraceptives shows good effect to cure PMS prominently. And daily physical exercise can also overcome the PMS related problems wisely.

Single-centre review of use of gonadotrophin-releasing hormone agonists - are we outliers?

Single-centre review of use of gonadotrophin-releasing hormone agonists - are we outliers?

Effect of repeated low doses of gonadotropin-releasing hormone on the secretion of luteinizing hormone and follicle-stimulating hormone, and ovarian function in dairy cows suffering from anovulation type I

The aim of the study was to evaluate the effect of repeated low doses of gonadotropin-releasing hormone (GnRH) agonist buserelin once a day for 5 days on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release, and ovarian function in dairy cows with anovulation type I. The study was conducted on 10 anovulatory Polish Holstein-Friesian cows. Cows in Group 1 (n = 5) received 4 µg of buserelin intramuscularly. once a day for 5 days. Control cows from Group 2 (n = 5) received saline. Concentrations of progesterone, FSH, and LH in the blood were analysed using radioimmunoassay (RIA). Ovarian structures were monitored weekly after the end of treatment by ultrasound for 4 weeks. Injections of buserelin increased FSH and LH concentrations. Release of FSH and LH was largely variable, but there was significant (P < 0.001) interaction between time and treatment during all treatment days. The number of follicles in the treatment group was significantly greater (P = 0.029) than in the control group on day 5, the diameter of follicles on day 12 was also larger (P < 0.01) in treated than in control cows. Ovulation occurred in 4 of the 5 treated cows, but only in 1 of the control cows in the 40 days after treatment. In conclusion, repeated low doses of GnRH analogue buserelin once a day for 5 days may increase the concentration of FSH and LH in dairy cows with anovulation type I.

Effectiveness of surgical castration by bilateral subcapsular orchiectomy as monotherapy for the treatment of advanced prostate cancer.

Prostate cancer is the most common malignancy in men and the second cause of death due to cancer [1]. Treatment of prostate cancer has been a field of many progresses, but the discovery of the role of androgen in the genesis of prostate cancer by Hugins and Hodges is really a milestone in the treatment of advanced prostate cancer [2]. In patients with advanced prostate cancer, options for androgen ablation include bilateral orchiectomy, therapy with luteinizing hormone-releasing hormone (LHRH) analogues and antagonists, and combined androgen blockade (typically a LHRH analogue plus a first-generation anti-androgen). Although orchiectomy remains the historical gold standard for androgen ablation, LHRH therapy is considered to be equivalent therapeutically. Medical castration has the advantage to induce less psychological effects comparatively to the surgery, reason why in developed countries patients are managed with medical therapy [3]. However, LHRH agonists cannot induce a complete castration levels of testosterone in some patients [4]. Instead, surgical castration can completely eliminate remaining testosterone produced by the Leydig cells in testes [5]. According to the latest recommendations of the European Association of Urology (EAU), androgen deprivation therapy (ADT) is the firstline indication in patients with advanced and metastatic PCa [6]. This first line is made of LHRH agonists, surgical castration representing the second line [7] And Several techniques of surgical castration have been described with comparable results in terms of patient survival and quality of life, but the sub-capsular technique of preserving testicular albuginea and epididymis is the most commonly used [8]. The relatively high cost of chemical castration is a constraint in the therapeutic choice in developing countries [9]. Therefore, surgical castration is an interesting alternative because of its simplicity and affordability in patients, most of whom have no health insurance. In Togo, most patients diagnosed with prostate cancer are at the metastasis stage, and surgical castration is often used as first-line treatment [10]. The aim of this study was to assess the biological and clinical effectiveness of surgical castration as the sole treatment in patients with advanced prostate cancer.

Use of a Vaginally Administered Gel Containing the GnRH Agonist Triptorelin and a Single, Fixed-Time Artificial Insemination in Pigs under Commercial Conditions: Productive and Economic Impacts.

Fixed-time artificial insemination is an important technique in swine production that can improve reproductive efficiency and meat production quality through making better use of the genetic potential of breeding males and reducing the costs associated with double or multiple inseminations. Our goal was to evaluate the vaginal application of the GnRH agonist triptorelin acetate to synchronize ovulation in post-weaning sows and facilitate the implementation of a single, fixed-time insemination. In the first experiment, the efficacy of treatment with triptorelin in animals with or without signs of estrus was analyzed using a single insemination at a fixed time, compared to a control group following the standard insemination strategy. The farrowing rate was comparable between the triptorelin and control groups (100 vs. 87.50%), but triptorelin treatment without estrus had a lower rate (50%). Litter size did not differ between the groups. Estradiol and progesterone levels at 96 and 120 h post-weaning were similar in the control and triptorelin groups (p > 0.05). These results suggest that triptorelin has the potential to synchronize ovulation in pigs without affecting post-weaning hormonal profiles. In a second experiment, the objective was to evaluate the productive and economic impact of implementing a treatment with triptorelin acetate 96 h after weaning, compared to the standard insemination protocol. Sows were grouped according to treatment (control vs. triptorelin) and estrus onset (≤5 days and >5 days after weaning, which was considered late estrus). The farrowing rate was lower in the late-estrus control group than in the control and triptorelin groups, and similar to that in the late-estrus triptorelin group. No differences were found in litter size and live or dead piglets born (p > 0.05). We developed an estimation model to assess the cost/benefit of intravaginal triptorelin administration at 96 h post-weaning. The overall result was that the use of triptorelin increased the financial benefit per inseminated sow by EUR 15-20. This improvement was mainly related to an increase in the reproductive performance of the treated sows compared to the control sows and the reduction in the number of inseminations per sow. These results highlight the potential of triptorelin to optimize reproductive management in pigs, improving efficiency and economic viability.

Effects of management of heavy menstrual bleeding of patients undergoing haploidentical hematopoietic stem cell transplantation.

To investigate the benefits of menstrual management in women undergoing hematopoietic stem cell transplantation (HSCT), in whom heavy menstrual bleeding (HMB) can be an underestimated bleeding complication. This was a retrospective cohort study. Patients who had undergone HSCT in the Gynecological Endocrinology Clinic of Peking University People's Hospital were included over 10 years. The data of hematology and menstruation for all participants were collected. The management methods of the intervention group include gonadotropin-releasing hormone agonists (GnRHa), combined oral contraceptives (COC), or low-dose mifepristone. Patients who did not receive management were included in the control group. There were 112 patients included in the intervention group and 218 patients included in the control group. In all, 90.0%(297/330) of patients presented with HMB before HSCT. In the control group, 83.5%(182/218)of patients experienced menstruation in the laminar air-flow room (LAFR), whereas only 22.3%(25/112) did in the intervention group. After leaving the LAFR, the incidence of recurrent uterine bleeding was significantly reduced in the intervention group (17.9%(20/112/)versus 50.9%(111/218), p < 0.001). Patients who did not undergo menstrual management had a higher risk of bleeding than those who did (odds ratio 18.12, p < 0.001). Menstrual management significantly reduces the incidence of HMB in HSCT patients and acts as a protective factor to prevent menstrual bleeding in the LAFR.

Comparison of ultra-long gonadotropin releasing hormone agonist versus standard downregulation in women with adenomyosis undergoing frozen-thawed embryo transfer: a randomized clinical trial

BackgroundAdenomyosis can lead to infertility and failure of in vitro fertilization. Limited evidence suggests that the use of long-term treatment with gonadotropin-releasing hormone (GnRH) agonists followed by frozen-thawed embryo transfer (FET) may be the preferred approach for women with adenomyosis.ObjectiveThe aim of this randomized controlled trial is to compare the efficacy of an ultra-long GnRH agonist with standard downregulation in women with adenomyosis undergoing FET.Materials and methodsThis randomized controlled trial enrolled 72 women with adenomyosis diagnosed by sonographic criteria who underwent FET cycles at the Avicenna Infertility Center. These women were randomly assigned to two equal groups: one received GnRH agonist treatment for three months before the FET cycle and the other served as the standard downregulation group. Results were reported as chemical and clinical pregnancy rates.ResultsThe two groups were similar in age, body mass index, anti-Müllerian hormone levels, number of previous pregnancies and miscarriages, presence of uterine myomas, and endometriosis. However, the total dose of estradiol used until embryo transfer was significantly higher in the ultra-long GnRH agonist group than in the standard group (96.14 mg vs. 80.52 mg, p-value = 0.004). Nevertheless, chemical and clinical pregnancy rates did not differ significantly between the two groups.ConclusionsUltra-long GnRH agonist downregulation did not improve the chemical and clinical pregnancy rate in the FET cycle in women with adenomyosis compared with standard GnRH agonist downregulation in the other words, ultra-long GnRH agonist downregulation is not superior to standard protocol. In women with adenomyosis (without history of endometriosis), downregulation of standard GnRH agonists prior to frozen-thawed embryo transfer may be the preferred embryo transfer protocol to gain higher clinical/chemical pregnancy rate.Trial registrationClinical trial registry: IRCT20160717028967N9, available at: https://irct.behdasht.gov.ir/trial/36103.

The Protective Effect of GnRH Agonist Triptorelin on the Histomorphometric Parameters of the Utero-ovarian Tissue in the Doxorubicin- and Cyclophosphamide-treated Mice.

One of the common side effects of chemotherapy drugs is ovarian failure and uterine dysfunction, which can occur after the administration of doxorubicin and/or cyclophosphamide. In clinics, gonadotropin-releasing hormone agonists (GnRHa) are used to modulate the toxic effect of chemotherapy and intercept infertility with some controversy and limited histological knowledge. This study aimed to evaluate the serological and histological features of protective effects of triptorelin, (GnRHa), on utero-ovarian tissue in the mice treated with cyclophosphamide and/or doxorubicin. Forty-eight female BALB/c mice were randomly divided into 8 groups as follows: Group I: normal saline; Group II: triptorelin; Group III: cyclophosphamide; Group IV: doxorubicin; Group V: cyclophosphamide + doxorubicin; and Groups VI, VII, and VIII: after injection of cyclophosphamide, doxorubicin, or cyclophosphamide + doxorubicin, administration of triptorelin (1 mg/kg; intraperitoneally) for 15 consecutive days, respectively. On the 21st day, the ovaries and uterine horns were dissected and weighed. Then, tissue processing and staining were performed for further histological and stereological studies. Triptorelin treatment in the damaged groups significantly increased the number of primordial and pre-antral follicles and granulosa cells. It decreased the number of atretic follicles compared to cyclophosphamide and/or doxorubicin-treated groups (P < 0.05). Triptorelin also significantly improved the volume of the ovary, cortex, medulla, oocytes in the primordial and antral follicles, uterus, endometrium, myometrium, uterine glands, and endometrial blood vessels in the damaged groups (P < 0.05). Triptorelin treatment prevents the destructive effects of cyclophosphamide and/or doxorubicin on utero-ovarian tissue.

Effects of pretreatment with long-acting gonadotropin-releasing hormone agonists on pregnancy outcomes in patients with minimal and mild peritoneal endometriosis: A retrospective study of 274 frozen-thawed embryo transfer cycles.

To investigate the effects of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) before frozen-thawed embryo transfer (FET) on pregnancy outcomes in patients after minimal-mild (stages I-II) peritoneal endometriosis surgery. A retrospective cohort study was performed from March 2018 to May 2019. Overall, 274 patients met inclusion criteria of undergoing FET after minimal/mild peritoneal endometriosis surgery. For the FET protocol, patients were divided into 2 groups: GnRH-a plus hormone replacement therapy (HRT) (group A, n = 154) and HRT-only (group B, n = 120), with the former divided into 2 subgroups receiving 1 (group A1, n = 80) or 2 doses (group A2, n = 74) of GnRH-a. Basic characteristics and pregnancy outcomes of groups A and B and groups A1 and A2 were compared. Clinical pregnancy rate (CPR) and live birth rate (LBR) were the primary outcomes and logistic regression was used to analyze independent correlation factors. The CPR and LBR in group A were 58.4% and 50.0%, respectively, and were not significantly higher than in group B (49.2% and 40.0%; respectively, χ2 = 2.339, P = .126 and χ2 = 2.719, P = .099, respectively). CPR and LBR in group A1 were not significantly lower than those in group A2 (52.5% and 45.0% vs 64.9% and 55.4%, respectively; χ2 = 2.420, P = .120 and χ2 = 1.665, P = .197, respectively). However, group A2's CPR and LBR were significantly higher than group B's (64.9% and 55.4% vs 49.2% and 40.0%, respectively; χ2 = 4.560, P = .023 and χ2 = 4.375, P = .026, respectively). Logistic regression analysis showed that GnRH-a pretreatment (1 or 2 doses) had no significant effect on CPR and LBR compared with the HRT-only group. Patients with minimal-mild (stages I-II) peritoneal endometriosis surgery may not require GnRH-a pretreatment before FET.

Might retrigger with human chorionic gonadotropin be a solution for empty follicle syndrome after gonadotropin releasing hormone agonist trigger?

This study aimed to determine whether the use of human chorionic gonadotropin (hCG) as a trigger could offer a potential solution for addressing empty follicle syndrome following the administration of a trigger for gonadotropin-releasing hormone agonist. A retrospective cohort analysis was conducted using data extracted from the hospital database pertaining to 415 patients who underwent in vitro fertilization (IVF) with an antagonist protocol triggered by a gonadotropin-releasing hormone (GnRH) agonist between December 2019 and January 2023 at the Acıbadem Maslak Hospital Assisted Reproductive Technologies Unit. All cases that failed to obtain oocytes and required rescue were analyzed. This study analyzed 415 women who underwent IVF using GnRH agonist-triggered antagonist protocols. Among them, 6 (1.4%) had empty folicle syndrome (EFS). Patients with EFS had lower luteinizing hormone levels and fewer oocytes, embryos, and blastocysts, resulting in lower oocyte utilization rate. However, pregnancy rates were similar, with no biochemical or ectopic pregnancies observed in the EFS group. Use of an hCG retrigger in hyperresponders with no oocytes after GnRHa trigger may prevent cycle cancelation. Although the rates of egg utilization may decrease, oocyte maturity remains comparable. Frozen embryo transfer following hCG retrigger administration yields similar positive pregnancy test results and live birth rates.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol

BackgroundAround 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes.MethodsThis study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence.Ethics and disseminationThe protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association’s Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal.ConclusionsProspective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH.Trial registration numberChinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

LBA69 Prostate cancer efficacy results from a randomised phase III evaluation of transdermal oestradiol (tE2) versus luteinising hormone releasing hormone agonists (LHRHa) for androgen suppression in non-metastatic (M0) prostate cancer

LBA69 Prostate cancer efficacy results from a randomised phase III evaluation of transdermal oestradiol (tE2) versus luteinising hormone releasing hormone agonists (LHRHa) for androgen suppression in non-metastatic (M0) prostate cancer

P194 VERY LOW-DOSE CYPROTERONE ACETATE (12.5 MG/DAY) IS EFFECTIVE AS ANDROGEN BLOCKER; WELL TOLERATED AND NOT ASSOCIATED WITH HYPERTENSION DEVELOPMENT IN YOUNG FEMALE TRANSGENDER PEOPLE

Background and Objective: Cyproterone acetate (CPA) has serious adverse effects (hyperprolactinemia, obesity, depression, thrombogenesis, liver toxicity, meningioma…) but the optimal dose has not been established. CPA is associated with a high risk of hypertension development, even with doses as low as 25 mg/day. We sought to establish if a very low CPA dose (12.5 mg/day) is effective as antiandrogen, its side effect profile, and if it is associated with hypertension development. Methods: Consecutive non-orchidectomized transgender women &lt;30 years were offered CPA 12.5 mg/day instead of the regular 50-100 mg/day dose, along with estradiol (individually titrated); CPA dose was increased to 25 (eventually 50) mg/day if plasma testosterone was &gt;2 nmol/L or there was clinical hyperandrogenism. Body weight, blood pressure, AST, ALT, GGT, prolactin, FSH, LH, estradiol and testosterone were monitored. A matched group of patients with LHRH agonist as antiandrogen plus estradiol served as control. Hypertension was diagnosed according to the current ESH guidelines. All patients gave informed consent. Results: 39 patients were recruited, median follow-up was 2.3 years. 32 were maintained on CPA 12.5 mg/day, two increased to 25 mg/day, one to 50 mg/day, two withdrew due to gender-affirming surgery; one was lost to follow-up. There were no serious side effects or related withdrawals. The control group included 35 patients without significant differences at baseline. Suppression of testosterone, LH and FSH were effective and comparable with the control group but a moderate increase in prolactin was observed (26±12 to 38±22 ng/mL, p=0.034). Neither group had changes in liver enzymes. Blood pressure and body weight did not increase significantly in either group; the incidence of hypertension was low in both groups (1 patient each). Conclusions: Very low-dose CPA was effective and well tolerated as antiandrogen in a large majority of our patients. While CPA is reportedly associated with a striking dose-dependent increase in the incidence of hypertension in the 25-100 mg/day dose-range, the 12.5 mg/day dose appears to be safer.

United Kingdom data collection of semen quality in transgender adolescent females seeking fertility preservation

ObjectiveIncreasing numbers of adolescents with gender dysphoria start gonadotropin-releasing hormone agonists to halt puberty, minimising psychological distress. The uncertainty of long-term effects of this medication, and the subsequent likelihood of accessing gender affirming hormone treatment, highlights the importance of fertility preservation prior to starting hormone treatment. We investigated the take up, hormonal profile and sperm quality in adolescents undergoing fertility preservation via cryopreservation by masturbation or surgical sperm retrieval, prior to starting hormonal therapy. DesignData was prospectively maintained from a tertiary UK-based hospital. 122 people under 19 years, mean age 15.2 +/- 1.7 years, referred by gender clinics and GPs, were included in this cohort study. SubjectsParticipants were counselled for fertility preservation, and serum testosterone, follicle stimulating hormone, and luteinizing hormone levels were recorded prior to providing semen samples. InterventionMasturbation semen samples were classified as normal (>15mil/ml), oligozoospermia (1mil-15mil/ml), cryptozoospermia (<1mil/ml) or azoospermia. If the sample was insufficient or the person was unwilling to masturbate, surgical sperm retrieval was offered in a stepwise manner using electroejaculation, TESE +/- mTESE. Main Outcome measurementsQuality of semen produced by participants, via masturbation or surgical sperm retrieval, was analysed to determine if it was good enough to cryopreserve for future fertility use. Results23/122 (19%) participants declined sample storage.In the masturbation group (average age 16.3), 78 people produced 106 samples. 86/106 were stored - 43.7% were normospermic, 35.9% oligozoospermic, 8.7% cryptozoospermic, 11.7% azoospermic. Overall, semen parameters varied but were generally abnormal, illustrated by only 43.7% of the masturbation samples produced being normospermic.For surgical sperm retrieval subjects (average age 15.2), electroejaculation was successful in 4/21 people, while the rest proceeded with TESE/mTESE. Encouragingly, 16/21 subjects had an average of 5 vials stored, and all participants had a testosterone level >8nmol/l. Semen parameters in this sub-cohort were poor but possibly adequate for intracytoplasmic sperm injection. ConclusionsIn this large database of transgender girls referred for fertility preservation in the UK, fertility preservation is possible, even with those unwilling to masturbate. Long-term data is required to check the health of these gametes, observing live birth rates using these preserved gametes.

Comparing Ribociclib versus Palbociclib as a Second Line Treatment in Combination with Fulvestrant in Metastatic Breast Cancer: A Randomized Clinical Trial.

Assessment of CBR, PFS, QOL and toxicity profile of palbociclib and ribociclib. This is an interventional concurrent randomised phase III open label clinical trial. It took place at the Oncology Centre Mansoura University, Egypt from July 2022 till December 2023. Patients with pathologically proved ER+ HER2- metastatic breast cancer who either progressed on adjuvant hormonal or progressed on 1st line hormonal for metastatic disease. Patients in arm A received palbociclib 125 mg/day orally for 3 weeks and 1 week rest, plus fulvestrant. Patients in Arm B received ribociclib at a dose of 600 mg, administered orally once daily for 3 weeks and 1 week rest, plus fulvestrant. Pre- and peri-menopausal women received the LHRH agonist goserelin. Patients who lost their endorsement and were considered to be lost to follow up. Quality of life was analysed using the (EORTC) quality-of-life questionnaire (QLQ)-C30 V3.0. Patients were asked to complete the questionnaires at screening; at the 2nd and 6th month. Toxicity was assessed and graded using (CTCAE) v5.0. Patients were evaluated clinically for response and toxicity monthly and radiologically by CT and tumor markers/ 3 months. Treatment continued until objective Progressive Disease (PD), symptomatic deterioration, unacceptable toxicity or death. Both arms had similar baseline characteristics. There was no statistically significant difference regarding the CBR (58.6% for both arms at 6 months and 13.8% in the palbociclib VS 17.2% in the ribociclib arm at 12 months). The median PFS to the whole population was 13 months. COX multivariate analysis revealed that postmenopausal had 2.85 more likely to survive than premenopausal patients. Patients with ECOG performance status 2 and 3 are 0.13 and 0.39 less likely to survive compared to patients with PS 1. Dose reduction increased the likelihood of survival 3.36 compared with no dose reduction. The median PFS was 13.67 months in the palbociclib arm and 12.69 months in the ribociclib arm with no statistically significant difference. During follow up, there was statistically significant improvement in insomnia in both arms and constipation in the palbociclib arm alone. Comparing the two arms, no statistically significant deterioration in the QOL domains except in fatigue and financial difficulties, with more deterioration in the palbociclib arm. Regarding common toxicities there was no statistically significant difference between the 2 arms. Both Ribociclib and palbociclib have similar CBR, PFS and toxicity profile.

Osteocalcin: A potential marker to identify and monitor girls with rapidly progressive central precocious puberty.

To evaluate the suitability of serum osteocalcin (OC) as a marker to distinguish between rapidly and non-rapidly progressive central precocious puberty (RP-CPP and NRP-CPP), as well as its potential to assess growth rates following treatment with gonadotropin-releasing hormone agonist (GnRHa). Serum levels of OC were measured using enzyme-linked immunosorbent assays in girls diagnosed with either RP-CPP or NRP-CPP as well as in normal control subjects. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for OC. Multivariate linear regression analysis was used to analyse the main influencing factors associated with OC. Serum OC levels were higher in the CPP girls when compared to normal controls (110.76 ± 43.69 vs 55.97 ± 20.96 ng/mL, P < 0.001). The level in the RP-CPP group was higher than the NRP-CPP group (153.28 ± 33.89 vs 88.33 ± 29.26 ng/mL, P < 0.001). The cut-off value of OC levels for distinguishing between RP-CPP and NRP-CPP was 107.05 ng/mL, the sensitivity was 94.7% and the specificity was 77.8%, which was superior to using the basal luteinising hormone (B-LH) levels, and the area under ROC curve (AUC) were 0.933 versus 0.695, respectively. Following 1-2 years of treatment with GnRHa for girls with CPP, both OC levels and the growth rates decreased to pre-pubertal values. B-LH levels, bone age and body weight were also significant factors, which affected OC levels. Serum OC levels may be a useful marker for distinguishing RP-CPP from NRP-CPP. In addition, it was also found to be a useful predictor for growth rate during GnRHa treatment.

738: High-dose bicalutamide is equivalent to LHRH agonist in combination with EBRT of prostate cancer

738: High-dose bicalutamide is equivalent to LHRH agonist in combination with EBRT of prostate cancer

Androgen deprivation as initial and backbone therapy for prostate carcinoma cancer : Aretrospective data analysis from urological practices in Germany

The aim of this study was to determine the proportion of patients with prostate cancer (PCa) who remained on primary androgen deprivation therapy (ADT) after starting treatment for castration-resistant prostate cancer (CRPC) and to describe their treatment patterns. The study comprises aretrospective analysis of 609,308patients in urological practices in Germany from 2011 to 2020 based on anonymized secondary data from the UROscience webserver. PCa patients were eligible for inclusion if they received ADT after a6-month prescription-free pre-index period. Atotal of 3,112patients (mean age 75.5 [±8.0]years) were included. Most patients received gonadotropin-releasing hormone (GnRH) agonists (72.3%), followed by antiandrogens (24.9%). The median duration of ADT treatment was 25.9months. The estimated probabilities of continuing ADT 3, 6, and 8years after starting treatment were 40.7%, 20.1%, and 12.7%, respectively. Interruption across all ADTs occurred in 42.7% of patients, switching of primary ADT in 52.2% and discontinuation in 82.2% of patients. After starting ADT, 14.6% of patients received treatment for CRPC, of whom 76.4% continued primary ADT. The median duration of CRPC treatment was 11.0months. The estimated probabilities of developing CRPC 3, 6, and 8years after starting ADT were 11.1%, 20.1%, and 25.9%, respectively. This study has shown that arelevant proportion of patients discontinued primary ADT after starting treatment for CRPC, although guidelines recommend continuing ADT if the disease progresses.