Leuprolide Acetate Depot Research Articles

7269 Interim Analysis of Gonadotropin-Releasing Hormone Agonist (GnRHa) Treatment in Children with Central Precocious Puberty: Focus on FMV Urinary LH Levels and Clinical Outcomes

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) refers to early activation of the hypothalamic–pituitary–gonadal (HPG) axis in children. There is an urgent need to understand the treatment pattern and clinical outcomes among children suffering from CPP. Studies have reported that first morning voided (FMV) urinary Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) have substantial association with CPP tested in GnRH stimulation test and can be useful in diagnosis and management of CPP in children. Gonadotropin-releasing hormone agonists (GnRHa) such as Leuprolide acetate (LA) are the recommended treatment for children suffering from CPP. The current study aimed to provide the information on level of LH and FSH in FMV urine when CPP diagnosis at baseline and the present results may also revealed trend of FMV-LH and FMV-FSH change during LA intervention in children with CPP. Here we present interim results from this study. Methods: This is an open-label, multicentre, single arm, prospective study that enrolled 31 subjects with CPP. Individuals were administered LA depot 11.25 mg, subcutaneously every 12 weeks. The study comprises a screening period; a 6-month treatment period: 24 weeks; and a post-treatment follow-up period: 12 weeks. The FMV urinary LH and FSH were diagnosed by Clopper-Pearson method with a 95% confidence interval. Results: Due to the data collection time point for the interim analysis, only 8 female subjects reached the 12-week visit time point and had a 12-week visit for FMV urinary Gn testing. Therefore, for this interim analysis, only FMV Gn decline at week 12 of the 8 subjects who had a 12-week visit will be presented. At baseline, the mean value of FMV urinary LH and FSH is 0.58 IU/L and 2.27 IU/L respectively. The FMV Gn urinary LH was demonstrated a decrease in 87.5% (95% CI: 47.35,99.68) of the children after LA intervention. Additionally, urinary FSH value of FMV urinary Gn was found to decrease in 75.00% of the children (95% CI: 34.91,96.81) compared to baseline FSH value. Conclusion: The present study reveals a decreasing trend in FMV Gn urinary LH and FSH levels in CPP children treated with LA during interim analysis. LA was shown to be safe and effective in ameliorating the level of LH and FSH in children suffering from CPP. From the study, it can be concluded that urinary LH and FSH may act as a potential biomarker for diagnosis and management of CPP. Presentation: 6/3/2024

Transient synovitis associated with leuprolide depot (Lupron).

A 6.6-year-old female presented to endocrinology with precocious puberty for evaluation and management. Workup was initiated, and a diagnosis of central precocious puberty was confirmed. A decision was made to initiate pubertal blockade using gonadotropin-releasing hormone agonist (GnRHa) therapy with depot leuprolide acetate injections every 3 months. The patient received the first depot leuprolide acetate injection in the right ventrogluteal area. Six hours following the injection, the patient was reported to be inconsolable in pain, which was localized to the right hip site of the earlier injection and associated with a refusal to ambulate. The pain and discomfort continued to progress over the next 24 h despite an alternating regimen of Tylenol and ibuprofen prompting admission to the emergency department. Vital signs demonstrated a low-grade fever and elevated C-reactive protein. An ultrasound of the right hip demonstrated fluid accumulation within the joint. Over the next week, the patient was unable to walk independently and required assistance for activities of daily living. By 2 weeks after the injection, the pain began to remit, and the patient resumed activities of daily living. Following consultation with allergy, a decision was made to continue GnRHa suppressive therapy with an alternative analog (Triptodur). The patient tolerated subsequent treatment without reaction. Although gonadotropin-releasing hormone agonists (GnRHa) have a generally good safety profile, there is a history of both local and systemic hypersensitivity reactions associated with their use. Despite the long-acting formulation of depot leuprolide acetate, the systemic reaction in this case appears to be self-limited. Discontinuation of therapy or a change to an alternative formulation of GnRHa analog should be considered based on the need for therapy versus the potential risk of rechallenge.

The Role of Reproductive Surgeons/Surgery has Got Rekindled with Plateauing of IVF Results and Advances in Technology: A Comprehensive Narrative Review

Earlier we have reviewed the role of surgery in need for fibroids removal prior to IVF in improving success rates, management of inoperable recurrent endometrioma presenting as severe incapacitating pain following leuprolide acetate depot by aspiration, recurring again at 2 years subsequently for sclerosing therapy presented as a case report updated advances in classification along with re¬productive surgeries in mullerian anomalies. Updated management of oncofertility-does the use of vsels appear practical in the near future in human malignancies replacing cortical tissue and testicular tissue, autologous Platelet Rich Plasma (PRP) probability of it becoming a revolutionary therapy in the field of gynaecology and reproductive endocrinology and infertility, role of surgery in endometriomas and endometriosis, adenomyomas, tubal surgery. Here we have tried to outline how prior to the invention of In Vitro Fertilization (IVF), reproductive surgeries which were believed to be fertility sparing were properly acknowledged, role of reproductive surgeons became obsolete. With the plateauing of IVF result interest has got rekindled with considerable advantages of reproductive surgeries is this field. Additionally, newer instrumentation as well as along with surgical procedure has evoked and made it attractivefor reproductive surgeons for improvementof their expertise with regards to conservation of future fertility as well as train future Reproductive Endocrinology and Infertility specialist (REI) in view of solidifying this field of yielding pregnancies to maximum of infertile cases even in patients having cancer surgeries or earlier cryopreservation of oocytes in say patients with turners syndrome etc.

Puberty suppression followed by testosterone therapy does not impair reproductive potential in female mice.

More adolescents are coming out as transgender each year and are put on puberty blockers to suppress natal puberty, which is then followed by cross-hormone treatment to achieve puberty of the desired gender. Studies to examine the effects of puberty suppression and virilizing therapy on future reproductive potential among transgender males are lacking. This study used a translational murine IVF model to examine the effects of female puberty suppression with depot leuprolide acetate (LA), followed by virilizing therapy with testosterone cypionate (T), on embryologic and pregnancy outcomes. LA effectively inhibited puberty when mice were treated beginning at 3 weeks of age. LA treatment was associated with higher mouse weight but lower ovarian weight. LA-treated mice ovulated developmentally competent eggs in response to gonadotropin administration, albeit at a higher dose than controls. Ovaries from mice treated with LA and T produced oocytes that had morphologically normal meiotic spindles after in vitro maturation, and responded to gonadotropin stimulation. Eggs from mice treated with LA and T were fertilizable and produced developmentally competent embryos that led to births of fertile pups. These results suggest that fertility may not be impaired after puberty suppression and cross-hormone therapy for transgender males.

Efficacy and Safety of Leuprolide Acetate 6-Month Depot for the Treatment of Central Precocious Puberty: A Phase 3 Study.

Treatment options for central precocious puberty (CPP) are important for individualization of therapy. We evaluated the efficacy and safety of 6-month 45-mg leuprolide acetate (LA) depot with intramuscular administration. LA depot was administered at weeks 0 and 24 to treatment-naïve (n = 27) or previously treated (n = 18) children with CPP in a phase 3, multicenter, single-arm, open-label study (NCT03695237). Week 24 peak-stimulated luteinizing hormone (LH) suppression (<4 mIU/mL) was the primary outcome. Secondary/other outcomes included basal sex hormone suppression (girls, estradiol <20 pg/mL; boys, testosterone <30 ng/dL), suppression of physical signs, height velocity, bone age, patient/parent-reported outcomes, and adverse events. All patients (age, 7.8 ± 1.27 years) received both scheduled study doses. At 24 weeks, 39/45 patients (86.7%) had LH suppressed. Six were counted as unsuppressed; 2 because of missing data, 3 with LH of 4.35-5.30 mIU/mL and 1 with LH of 21.07 mIU/mL. Through 48 weeks, LH, estradiol, and testosterone suppression was achieved in ≥86.7%, ≥97.4%, and 100%, respectively (as early as week 4 for LH and estradiol and week 12 for testosterone). Physical signs were suppressed at week 48 (girls, 90.2%; boys, 75.0%). Mean height velocity ranged 5.0 to 5.3 cm/year post-baseline in previously treated patients and declined from 10.1 to 6.5 cm/year at week 20 in treatment-naïve patients. Mean bone age advanced slower than chronological age. Patient/parent-reported outcomes remained stable. No new safety signals were identified. No adverse event led to treatment discontinuation. Six-month intramuscular LA depot demonstrated 48-week efficacy with a safety profile consistent with other GnRH agonist formulations.

Clinical development of the GnRH agonist leuprolide acetate depot

Leuprolide acetate is the first GnRH agonist that entered clinical development after the discovery of the native GnRH. Several long-acting depot formulations of leuprolide acetate (ranging from 1-month to 6-month intramuscular injections) have been successively developed for various suppressive treatments in men, women, and children, which are available in the United States and globally. This mini review aims to summarize the key clinical studies that led to regulatory approval of leuprolide acetate depot suspension for injection.

Abstract 54: Clinical and biochemical outcomes of gonadotropin -Releasing hormone analogue therapy in a cohort of children with central precocious puberty from Kerala

Background: Large scale studies of outcomes of Gonadotropin-releasing hormone analogue (GnRHa) therapy for Central Precocious puberty (CPP) are not available from our part of the country.Aim: To evaluate the efficacy of GnRHa with clinical and biochemical parameters in a cohort of children with CPP.Methodology: Retrospective analysis of case records of 33children (30 females and 3 males) diagnosed with CPP on GnRHa (Leuprolide acetate depot) was done.Results: CPP was idiopathic in 20 and organic in 13 children. Median age at onset of puberty was 6.75years (range 0.75 – 8.9 years) and at start of treatment was 7years. The Median duration of therapy was 2.75years (range= 5months-9years). 52% attained LH Suppression in one year and 81% in two years. 92% patients had regression in tanner's stage by a median of 11months. BA was advanced by a median of 4.45 SD which reduced to 2.8SD at the end of therapy. Duration of therapy had significant effect in halting BA progression (p=0.004). The median height centile of 86.25 at presentation normalised in 89% at treatment completion.Conclusion: GnRHa therapy in our cohort of CPP children was effective in reversing puberty and slowing bone age advancement despite a late age of onset of treatment.

Treatment with gonadotropin-releasing hormone analogs (GnRHa) in childhood and adolescence

For several decades, gonadotropin releasing hormone analogs (GnRHa) are the medical treatment selected for central precocious puberty (CPP) in girls and boys. They generate an inhibition of the hypothalamus-pituitary-gonadal axis decreasing LH, FSH, estradiol and testosterone secretion and, in this way, they produce a regression of secondary sexual characters under treatment. In the last years, these analogs are also used in trans adolescents, in adolescents and young adults with oncological diseases, in some very particular situations in children with short stature and in patients with neurodevelopmental disorders. In Argentina the most commonly used formulations are triptorelin and leuprolide acetate depot forms. These analogs have proven both their efficacy and their safety. The aim of this paper is to review and update about the use of GnRHa in children and adolescents.

Transgender Youth Referred to Clinics for Gender-Affirming Medical Care in Canada.

Referrals of transgender and gender-diverse (trans) youth to medical clinics for gender-affirming care have increased. We described characteristics of trans youth in Canada at first referral visit. Baseline clinical and survey data (2017-2019) were collected for Trans Youth CAN!, a 10-clinic prospective cohort of n = 174 pubertal and postpubertal youth <16 years with gender dysphoria, referred for hormonal suppression or hormone therapy, and 160 linked parent-participants. Measures assessed health, demographics, and visit outcome. Of youth, 137 were transmasculine (assigned female) and 37 transfeminine (assigned male); 69.0% were aged 14 to 15, 18.8% Indigenous, 6.6% visible minorities, 25.7% from immigrant families, and 27.1% low income. Most (66.0%) were gender-aware before age 12. Only 58.1% of transfeminine youth lived in their gender full-time versus 90.1% of transmasculine (P < .001). Although transmasculine youth were more likely than transfeminine youth to report depressive symptoms (21.2% vs 10.8%; P = .03) and anxiety (66.1% vs 33.3%; P < .001), suicidality was similarly high overall (past-year ideation: 34.5%, attempts: 16.8%). All were in school; 62.0% reported strong parental gender support, with parents the most common support persons (91.9%). Two-thirds of families reported external gender-related stressors. Youth had met with a range of providers (68.5% with a family physician). At clinic visit, 62.4% were prescribed hormonal suppression or hormone therapy, most commonly depot leuprolide acetate. Trans youth in Canada attending clinics for hormonal suppression or gender-affirming hormones were generally healthy but with depression, anxiety, and support needs.

Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate Depot Formulation With Tamoxifen for Postoperative Premenopausal Estrogen Suppression in Hormone Receptor-Positive Breast Cancer.

BackgroundIn patients with hormone receptor-positive (HR+)/premenopausal breast cancer, luteinizing hormone-releasing hormone analogs (LHRHas) are used as standard endocrine treatment. Based on previous clinical studies, 1-month formulations are recommended in most breast cancer treatment guidelines, but long-acting formulations facilitate reductions in side effects and patient discomfort caused by frequent administration. However, few efficacy studies have been conducted on 6-month formulations. Therefore, this study aimed to evaluate the efficacy of 6-month formulations of LHRHas.MethodsThis retrospective study was conducted from January 2018 to December 2019 and involved premenopausal patients with HR+ breast cancer administered 6-month LHRHas as adjuvant treatment after surgery, and those previously administered chemotherapy or other LHRHa types were excluded. Patients’ estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured before surgery, and their E2 levels were also measured at 3, 6, 12, 18, and 24 months at periodic postsurgical examinations.ResultsA total of 228 patients were included, and the median patient age was 44 (range, 25–54) years. The mean serum E2 and FSH levels before surgery were 69.7 (range, 4–683) pg/mL and 7.3 (range, 0.4–88.9) mIU/mL, respectively, whereas the mean serum E2 level monitored at intervals during the 6-month LHRHa administration was 5.5 (range, 4.0–52) pg/mL. No women menstruated during the follow-up period after the LHRHas administration, and the E2 levels were less than 30 pg/mL in all patients except one.ConclusionsThe 6-month LHRHa formulation adequately suppressed ovarian function in premenopausal patients with HR+ breast cancer. This indicates that long-acting LHRHas can be effectively used for patient convenience and that there is high compliance with long-term use.

24. Peri-urethral cyst mistaken for imperforate hymen in a patient with distal vaginal agenesis

<h3>Background</h3> Imperforate hymen is the most common obstructive genital tract anomaly and typically presents in adolescence with primary amenorrhea, worsening pelvic pain, and a bulging hymenal membrane at the introitus. When the hymen is normally visualized, other obstructive anomalies should be considered, as establishing the correct diagnosis prior to making management decisions is paramount. We present a case of a peri-urethral cyst misdiagnosed as an imperforate hymen in a patient with vaginal agenesis, highlighting strategies for accurate diagnosis and options for management. <h3>Case</h3> An 11 year old premenarchal female presented to the Emergency Department (ED) with several months of worsening intermittent lower abdominal pain. In the ED, she had transabdominal pelvic imaging showing a large hematometrocolpos and per the provider an imperforate hymen external genital exam. After achieving adequate pain control, she was discharged to follow up with Pediatric and Adolescent Gynecology. At her follow up visit, examination findings were notable for an annular hymen with membranous tissue blocking the vagina immediately behind the hymen. On rectal exam, the hematocolpos was palpated approximately 4 cm from the introitus. The patient was started on menstrual suppression with depot leuprolide and norethindrone acetate. Follow up magnetic resonance imaging (MRI) confirmed a cyst near the introitus and distal vaginal agenesis. When the genitalia were re-examined under anesthesia, adequate labial traction revealed a peri-urethral cyst. Due to ongoing pain, interventional radiology placed a transuterine drain under ultrasound guidance. Tissue plasminogen activator (TPA) was used through the drain to thin the obstructed blood and facilitate drainage. Approximately 500 ml of blood was drained from uterus and vagina before the drain was removed. The patient remains asymptomatic and will continue menstrual suppression until she reaches an age when she can participate in post-operative care. <h3>Comments</h3> In this case, the diagnosis of distal vaginal agenesis was obscured by the presence of a peri-urethral cyst. The case illustrates the importance of thorough examination including rectal exam and pelvic MRI when the diagnosis is unclear. Vaginal dilation or use of a vaginal stent is usually required after definitive surgical management of distal vaginal agenesis and therefore it is important to consider age and maturity before any surgical decisions are made. Accurate diagnosis is of utmost importance and management efforts aimed at delaying definitive surgical management should be considered.

Myopic Progression in Girls with Gonadotrophin-Releasing Hormone Agonist Treatment for Central Precocious Puberty.

We sought to determine whether the myopic progression of patients with central precocious puberty (CPP) who were undergoing treatment differed from that of their healthy peers with normal pubertal onset and progression. Eighteen girls with CPP and 14 age-matched controls who underwent regular ophthalmic examinations for at least 1 year were included. All the CPP patients received a 3.75 mg leuprolide acetate depot subcutaneously every 28 days. The spherical equivalent (SE) and axial length (AL) for myopia progression and the pubertal parameters (height, body weight, body mass index, Tanner stage, and bone age) were compared between the two groups. Of 32 subjects with a mean age of 8.6 ± 0.7 years, the SEs and ALs did not differ at baseline between the two groups, which had similar weight and similar body mass index. After 1 year, both the CPP patients and controls showed myopic progression, with an average myopic shift of −0.73 ± 0.48 diopters (D) and AL elongation with a mean change of 0.44 ± 0.61 mm. The SE and AL changes over 1 year were greater in the controls than those in the CPP patients, which was not statistically significant (–0.85 ± 0.55 D vs. –0.64 ± 0.41 D and 0.55 ± 0.89 mm vs. 0.35 ± 0.22 mm, respectively). The change in AL correlated significantly with the change in the height (β = 0.691, p = 0.039). In this 1-year study, the CPP patients with treatments trended to show less myopic progression than the controls.

SAT-074 A Rare Endocrine Cause of Pseudotumor Cerebri

Introduction: Idiopathic intracranial hypertension, also known as pseudotumor cerebri, can be associated with various medications, obesity, systemic conditions, and inherited disorders. To the best of our knowledge, this is the second pediatric case of a GnRH agonist reported to cause pseudotumor cerebri.Case presentation: Our patient, a 12 5/12-year-old transgender male (birth-assigned female), started depot leuprolide acetate to suppress puberty at 11 10/12 years of age (early Tanner 2 breast development). He received Lupron Depot® 7.5 mg intramuscularly for 4 doses, then 22.5 mg intramuscular every 13 weeks thereafter. Five months after his first injection, a routine eye examination revealed bilateral papilledema and enlarged blind spots, which was confirmed by a Pediatric Ophthalmologist. He was asymptomatic. There was no marked weight gain in the previous year with a BMI of 24.5 kg/m2 (+1.85 SD). His blood pressure was 110–123 mmHg systolic and 71–85 mmHg diastolic. Neurological examination was normal. CT head was normal. Cranial MRI showed slight flattening of the optic nerve heads, mild engorgement of optic nerve sheath fluid, and no space-occupying mass. Sedated lumbar puncture revealed elevated opening pressure of 31 cm H2O. CSF analysis, including pathology, was benign. He was managed with acetazolamide. Based on these findings, he was diagnosed with pseudotumor cerebri secondary to the GnRH agonist. Follow-up by the Ophthalmologist one month after starting acetazolamide showed significant improvement of the papilledema.Conclusion: This case highlights that patients on GnRH agonist therapy are at risk for pseudotumor cerebri, and we recommend periodic ophthalmologic surveillance.

Treatment with Depot Leuprolide Acetate in Girls with Idiopathic Precocious Puberty: What Parameter should be Used in Deciding on the Initial Dose?

Objective:Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose.Methods:Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate.Results:Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001).Conclusion:Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis.

Management of Inoperable Recurrent Endometrioma Presenting as Severe Incapacitating Pain Following Leuprolide Acetate Depot by Aspiration, Recurring Again a 2 Yrs Subsequently for Sclerosing Therapy at Present: A Case Report

Management of Inoperable Recurrent Endometrioma Presenting as Severe Incapacitating Pain Following Leuprolide Acetate Depot by Aspiration, Recurring Again a 2 Yrs Subsequently for Sclerosing Therapy at Present: A Case Report

Ovarian protection with gonadotropin-releasing hormone agonists during cyclophosphamide therapy in systemic lupus erythematosus.

Administration of cyclophosphamide (CYC), an alkylating agent used to treat malignancies and severe rheumatic diseases, creates a risk of ovarian insufficiency that is related to the intensity and duration of therapy and the age of the patient. To preserve reproductive capacity in the appropriate clinical setting, oocyte, embryo, and/or ovarian tissue cryopreservation are recommended. Medical protection with depot gonadotropin-releasing hormone agonists (GNRHa) has emerged as a potential means to preserve both fertility and ovarian function through the suppression of ovarian activity during treatment with alkylators. We review the trials of GNRHa for ovarian protection in both cancer and rheumatic disease patients. Trials in cancer patients receiving CYC alone, or in combination with other gonadotoxic agents that have employed several different GNRHa have yielded mixed results. Trials in lupus patients receiving lower doses of CYC alone utilizing depot leuprolide acetate have tended to show favorable results.

Effect of single-dose depot leuprolide acetate on embryonal implantation: an experimental rat model

The objective of this article is to investigate the effect of single-dose depot leuprolide acetate in rat embryonal implantation and its association with glycodelin A, mucin-1 and leukemia inhibitory factor expression. Thirty-two pregnant Wistar Albino rats were divided into four equal groups: untreated control rats in group I (n = 8) and untreated pregnant rats in group II (n = 8) were injected intraperitoneally with single dose of normal saline, treated rats in group III (n = 8) and treated pregnant rats in group IV (n = 8) were given single 1 mg/kg subcutaneous injection of leuprolide acetate at day 8 of pregnancy. The dams were sacrificed on the 15th day of gestation, uterine horn samples were removed. Immunohistochemical examination of the tissue samples prepared from the control and experimental groups, a statistically significant difference was observed between the groups in the luminal-glandular-decidualized epithelium of the uterus with glycodelin A, mucin-1 and leukemia inhibitory factor. A statistically significant difference was observed between the groups for the concentration of glycodelin A but no statistically significant difference was found for the other two molecules. In light of our findings, leuprolide acetate adversely affected expression and concentration of all three molecules in embryonal implantation model.

Efficacy of Mifepristone versus GNRH Analogue in the Treatment of Uterine Leiomyoma- A Comparative Study

Background: Uterine fibroids also called as uterine leiomyoma is the most common benign tumor of the uterus. Most women develop one or more uterine leiomyoma during their reproductive years. Hence; we assessed the efficacy of Mifepristone 25mg versus Inj.Leuprolide acetate 3.75mg in reducing size of uterine myoma. Subjects and Methods: The study was planned for detecting difference of 15 percent in the outcome variables between the two groups and Standard deviation of 156.00, with 90% statistical power and 5% level of significance, the sample size was calculated to be 70 for the study. The study subjects were randomly assigned into 2 groups of 35 patients each. Group 1: Patients treated with Tablet Mifepristone 25mg once daily for 3 months; Group 2: Patients treated with Inj. Leuprolide acetate depot preparation 3.75mg IM once a month for 3 months. Demographic data, history, clinical examination, details of drug prescription, laboratory investigations and imaging reports were recorded in the study proforma. Various clinical assessment parameters were assessed. Results: After three months of treatment, there was a marked relief with significant decrease in visual analog scale score in both the groups (p <0.001). 21 patients (60%) in group 1 and 25 patients (71%) in group 2 presented with mild anemia at the beginning of the study. After three months of treatment, there was a significant (p <0.001) rise in the hemoglobin and hematocrit values in both the groups. There was an increase in mean hemoglobin level by 2.9gm/dl in mifepristone group and 3gm/dl in leuprolide group. Conclusion: Treatment with either mifepristone or leuprolide acetate in uterine leiomyoma is safe and causes significant but temporary reductions in uterine size and myoma related symptoms.

Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression.

To evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic. All subjects had at least 1year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group. Women in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group. Women with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pre-treated with medical and surgical management.

Increased final adult height by gonadotropin-releasing hormone agonist in girls with idiopathic central precocious puberty.

ObjectiveGonadotropin-releasing hormone agonists (GnRHa) are the treatment of choice for central precocious puberty (CPP) and have been widely used for several decades. We determined the effect of GnRHa treatment on the auxological outcomes of girls with idiopathic CPP.MethodsThis study included 84 girls treated monthly with depot leuprolide acetate who had reached adult height. We compared their final adult height (FAH) with their initial predicted adult height (PAH). We performed a multivariate analysis of the factors associated with FAH on all girls diagnosed with CPP.ResultsWe performed the final evaluations at a mean age of 14.1 ± 0.8 years after a mean treatment duration of 2.98 ± 0.73 years (ranging from 1.5–4.8 years). Menarche had occurred at 12.6 ± 0.6 years of age, which was 16.5 ± 6.1 months after discontinuation of GnRHa therapy. Mean FAH was 160.1 ± 5.0 cm, which was significantly higher than the initial PAH (156.1 ± 5.7 cm; P < 0.001). To investigate whether growth outcomes were influenced by the age at initial treatment, we divided all patients into two groups, those treated between 6 and 8 years (n = 23) and those treated after 8 years (n = 61); no significant differences were observed in FAH between the two groups. FAH was significantly and positively correlated with the height standard deviation score (SDS) at the end of treatment and with the target height, whereas the difference between bone age and chronological age at the start and end of treatment was negatively correlated with FAH.ConclusionFAH was significantly higher than the initial PAH in girls with CPP who were treated with GnRHa. Also, GnRHa treatment was still effective even after 8 years of age in girls with CPP.