GnRHa Treatment Research Articles

8265 Premature Ovarian Insufficiency in Pediatric Cancer Patients: a 10-Year Rady Children's Hospital Experience

Abstract Disclosure: M. Robinson: None. L. Meller: None. M.E. Patterson: None. Objective: To highlight the occurrence of premature ovarian insufficiency in cancer patients treated at a children’s hospital and to determine which patient characteristics or treatment modalities are associated with ovarian failure and subsequent recovery of ovarian function. Study design: A retrospective chart review. Setting: Rady Children’s Hospital San Diego. Subjects and Methods: Between August 2011 and August 2021, the cases of 36 patients with cancer and ovarian failure were reviewed. Data collected included type of cancer, age at diagnosis, types of chemotherapy used in treatment, whether a bone marrow transplant or radiation was part of the treatment plan, peak FSH value and age when this occurred, peak AMH value, whether GnRHa treatment was used, type of hormone replacement therapy used, and whether there was recovery of ovarian function. Results: The most common type of cancer identified in this group of patients was acute lymphoblastic leukemia (ALL) (13, 36.1%). The mean age of diagnosis was 8.5 ± 4.3 years and the mean age of peak FSH value was 12.6 ± 2.8 years. Nearly all patients (97.2%) were treated with alkylating agents as part of their chemotherapy regimen and 72.2% received some form of radiation. Most patients (26, 72.2%) also received some form of hormone therapy, most commonly transdermal hormone therapy (13, 36.1%) or oral contraceptive pill (10, 27.8%), and 15.8% of patients were treated with the GnRHa Lupron. Fertility planning was offered or discussed in 36.1% of patients. Ten patients (27.8%) were noted to have some degree of recovery in their ovarian function. Age at diagnosis and type of cancer treatment were significant predictors of recovery in multivariate regression modeling. Specifically, 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 treatment with an alkylating agent without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI:2.7-564, P = 0.007). Conclusion: This retrospective review demonstrates that, while uncommon, POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on the potential long-term effects of cancer treatment and routine surveillance for these complications. This study also confirmed that recovery of ovarian function is possible in these patients, especially when diagnosed at a younger age, so continued monitoring is essential. Presentation: 6/3/2024

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 FSH, peak AMH, 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.

Growth pattern, growth deceleration, and relevant predictors in girls treated with GnRHa: a retrospective longitudinal study.

This study aimed to analyze the height growth pattern and the incidence of significant growth deceleration in girls with CPP and EFP on GnRHa treatment, and thereby identify relevant predictors of growth deceleration. The data of 99 girls diagnosed with CPP and 47 girls with EFP were included in this retrospective analysis. The incidence of growth deceleration was calculated in both the first and second years. Multivariate logistic regression analysis was used to identify predictors indicative of growth deceleration. Growth velocity (GV) trajectories showed gradual decreases to the nadir at 18months of treatment, and then they recovered till the 24th month of treatment, especially in girls with CPP. Nevertheless, the recovery was significantly greater in the CPP group than EFP. In the first year, no significant difference in the incidence of growth deceleration was found between the CPP group and the EFP group [17.35 vs. 25.53 %, p=0.249]; in the second year, the CPP group had alower incidence than the EFP group [42.86 vs. 76.92 %, p=0.027]. The multivariate logistic regression analysis suggested that bone age (BA) was an independent predictor of growth deceleration (OR=2.264, 95 % CI: 1.268-4.042, p=0.006). The result of ROC curves showed the cut-off value of BA was 11.05 years. GV varies at different periods during GnRHa treatment. GnRHa should be used with more caution for EFPtreatment than for CPP. BA can be used to predict the occurrence of growth deceleration during GnRHa treatment.

Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a+LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a+LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision+LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision+LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5years are needed. Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.

Electrocardiographic Findings in Children Treated with Leuprolide Acetate for Precocious Puberty: Does it Cause Prolonged QT?

Central precocious puberty is treated with long-acting GnRH analogues. Some adult patients undergoing GnRHa treatment experienced prolonged QT syndrome, which is associated with an increased risk of serious cardiac events such as myocardial infarction, stroke, arrhythmias, and sudden cardiac death. Seventy-four patients, aged between 5 and 11 years and diagnosed with central precocious puberty but with no other concomitant disease or medication use, underwent electrocardiogram assessment. They had been receiving 3.75 mg leuprolide acetate (Lucrin® Depot) injections every 28 days for at least three months. The electrocardiograms of all patients showed a QTc interval within normal limits, consistent with the data of healthy Turkish children of the same age and gender. No other pathological physical examination or ECG findings were observed. Furthermore, there was no significant difference in QTc interval in relation to age, anthropometric data, or the duration or cumulative dose of the treatment. The study found no correlation between QTc interval values and age, treatment duration, total cumulative dose, and anthropometric data. The findings suggest that cardiovascular adverse events associated with GnRHa may be related to age and other underlying physiopathological conditions rather than the drug.

Zhibai dihuang pill (ZBDH) exhibits therapeutic effects on idiopathic central sexual precocity in rats by modulating the gut microflora

To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.

The effect of GnRH analog treatment on BMI in children treated for precocious puberty: a systematic review and meta-analysis.

The purpose of the present meta-analysis was to systematically evaluate the effect of GnRHa treatment on the BMI of children with precocious puberty after GnRHa treatment as compared to before, and to analyze the effect of GnRHa treatment on the body composition of children with precocious puberty at different BMIs by classifying into normal body mass, overweight, and obese groups according to BMI at the time of initial diagnosis. A meta-analysis was performed using Stata 12.0 software by searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), and Wan fang database for relevant literature on standard deviation score of body mass index (BMI-SDS) after GnRHa treatment as compared to before in children with precocious puberty. A total of eight studies were included with a total sample size of 715 cases, and the results of meta-analysis showed that BMI-SDS increased in children with precocious puberty after GnRHa treatment as compared to before starting [(weighted mean difference (WMD)=0.23, 95 % CI: 0.14-0.33, p=0.000)] and also increased in children with normal body mass [(WMD=0.37, 95 % CI: 0.28-0.46, p=0.000)], and there was no significant change in BMI-SDS in children in the overweight or obese group [(WMD=0.01, 95 % CI:-0.08-0.10, p=0.775)]. Overall, there was an observed increase in BMI-SDS at the conclusion of GnRHa treatment in children with precocious puberty. Additionally, it was found that the effect of GnRHa treatment on body composition varied among children with different BMI status. Clinicians should emphasize the promotion of a healthy lifestyle and personalized dietary managementfor children.

Oncologic and reproductive outcomes after fertility-sparing surgery for bilateral borderline ovarian tumors: A retrospective study

ObjectivesTo investigate the oncological safety and fertility outcomes of different fertility-sparing surgery procedures for bilateral borderline ovarian tumors (BOTs) and to identify the safest and most effective approach to help patients conceive with minimal risk. Study DesignA retrospective study of 144 patients (≤40 years) with pathologically confirmed bilateral BOTs were included in the study.The effects of surgery type on fertility outcome and recurrence were compared. Cox regression analysis was employed to determine potential prognostic factors. Survival analysis utilized the Kaplan–Meier method. ResultsThree therapeutic modalities were applied in our study, including bilateral ovarian cystectomy (BOC; n = 29), unilateral adnexectomy + contralateral cystectomy (UAC; n = 4) and radical surgery (n = 61). Totally 33 cases (22.9 %) relapsed during the follow-up period. In 37 % of cases administered conservative surgery, relapses were diagnosed in the first 2 years. Only conservative surgery and adjuvant chemotherapy were risk factors for recurrence. Meanwhile, a pregnancy rate of 55.4 % was obtained in patients with bilateral BOTs. The pregnancy rate was slightly higher but no significant (P = 0.539) difference in patients treated with BOC (n = 17, 63 %) compared with UAC (n = 29, 55.8 %) group. GnRHa treatment significantly improved the clinical pregnancy rate in this study(P = 0.029). ConclusionsSatisfactory pregnancy rate can be achieved after conservative surgery in patients with bilateral BOTs. BOC is worth recommending for bilateral borderline ovarian tumors and a critical factor in fertility is the preservation of maximum healthy ovarian tissue. Patients should make a pregnancy plan in 2 years after the first surgery. GnRHa increase the rate of successful clinical pregnancies.

The effect of gonadotropin-releasing hormone analog treatment on the endocrine system incentral precocious puberty patients: a meta-analysis.

Gonadotropin-releasing hormone (GnRHa) is the first choice for the treatment of patients with central precocious puberty (CPP). However, the effects of GnRHa on the endocrine system of CPP patients, including insulin sensitivity, lipid level, thyroid function, bone mineral density (BMD), and testosterone (T)level, are currently contradictory. Therefore, the long-term safety of GnRHa therapy remains controversial. A systematic literature search was performed using PubMed, Embase, Cochrane Library, and CNKI databases. The changes in HOMA-IR, TG, LDL-C, HDL-C, TSH, FT3, FT4, T, and BMD in CPP patients before and after GnRHa treatment were compared by meta-analysis. As the heterogeneity between studies, we estimated standard deviation mean differences (SMDs) and 95 % confidence intervals (CIs) using a random-effects model. Egger's test was used to assess publication bias. A total of 22 studies were included in our meta-analysis. Compared with before GnRHa treatment, there were no statistically significant differences in endocrine indicators including HOMA-IR, TG, LDL-C, HDL-C, TSH, FT4, FT3, T, and BMD of CPP patients treated with GnRHa. Treatment with GnRHa for central precocious puberty will not increase the adverse effect on the endocrine system.

Implication of biosignatures in the progression of endometriosis

Endometriosis is an estrogen-dependent chronic inflammatory disorder involving the placement and growth of endometrial tissue outside the uterine cavity. It is the most common multifactorial disease that affects the life quality of women in reproductive age. Due to its multicomponent nature, early diagnosis of the disease is challenging. Since many genetic, epigenetic alterations and non-genetic factors contribute to the pathology of endometriosis, devising a drug therapy that directly acts on the ectopic tissue is extremely difficult. Endometriosis is a hormone-driven disease with estrogen considered as a primary driver for the development of endometriotic lesions. This study aims to identify biosignatures involved in endometriosis with and without gonadotropin releasing hormone agonists (GnRHa). GnRHa is a short peptide analog of GnRH that causes inhibition of estrogen and androgen synthesis. Microarray based-gene expression profiling was performed on total RNA extracted from endometriotic tissue samples with and without GnRHa-treated patients already published in our previous paper. The untreated group were considered as the control. Genes were then selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR analysis confirmed significant downregulation in(p < 0.05) expression of DARC (p = 0.0042), CDH1 (p = 0.0027), CDH5 (p = 0.0283), ATP2A3 (p < 0.001), RGS5 (p = 0.0032), and CD36 (p = 0.0162) in endometriosis patients treated with GnRHa analogs. Although, CTNNAL1 (p = 0.0136) also showed significant results but there was upregulation in their expression levels after GnRHa treatment. Thus, an altered expression of these genes makes them a possible candidate determinant of endometriosis treated with GnRHa.

Timing of puberty in F1-generation hatchery-produced greater amberjack (Seriola dumerili)

We evaluated the onset of puberty of first-generation (F1) hatchery-produced greater amberjack (Seriola dumerili) reared in sea cages for 5 years. Fish were sampled every year in June, at the expected peak of the spawning period in the Mediterranean Sea. No sexual dimorphism in body weight was observed in the study. The ovaries of 1 and 2-year-old (yo) females consisted of primary oocytes only, while at the age of 3-yo early vitellogenic (Vg) oocytes were also identified, but with extensive follicular atresia. At the age of 4-yo, late Vg oocytes were observed, but again extensive follicular atresia characterized the ovaries of 50 % of females. At the age of 5-yo, follicular atresia of Vg oocytes was very limited. In males, gametogenesis was evident already in 1- and 2-yo fish, and 100 % of sampled 3-yo males produced collectable viable sperm. Plasma testosterone (T), 17β-estradiol (E2), and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) remained similar in 3 – 5-yo females, with T and E2 levels being highest in females in advanced vitellogenesis or with significant follicular atresia, compared to immature females. In males, plasma T declined over the years, while 11-ketotestosterone (11-KT) and 17,20β-P were highest in 4 and 5-yo males, with spermatozoa motility characteristics being improved from the 4th year onwards. The administration of GnRHa implants to 5-yo fish induced only two spawns, albeit no fertilized eggs were obtained. The results indicate that hatchery-produced greater amberjack males mature well and within the same age observed in the wild, however with smaller gonad size. On the contrary, females mature later than in the wild, also with a smaller gonad size. Spawning in response to GnRHa treatment was not effective, suggesting that Mediterranean hatchery-produced broodstocks may be dysfunctional, and further research is needed to document any improvement as the fish get older, or to determine if the results may be related to the specific stock of fish.

Monozygotic twins with short stature due to temple syndrome and GH plus GnRHa treatment in one twin

Monozygotic twins with short stature due to temple syndrome and GH plus GnRHa treatment in one twin

Add-Back and Combined Regulation in GnRH-a Treatment of Endometriosis

Add-Back and Combined Regulation in GnRH-a Treatment of Endometriosis

Using change in predicted adult height during GnRH agonist treatment for individualized treatment decisions in girls with central precocious puberty.

It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care. Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3years preceding the first observed BA of≥12years. Relationships were characterized using plot inspection andlinear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models. BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of≥33/≥55months). These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH.

Efficacy and safety of medical treatment in the clinical management of adolescents with gender dysphoria (gd): a prospective follow-up study

<h3>Objectives</h3> The present study assessed the efficacy of Gonadotropin-Releasing Hormone agonists (GnRHas) treament and Gender Affirming Hormonal Treatment (GAHT) in terms of psychological functioning and physical changes in a sample of adolescents with GD assessed at the Florence Gender Incongruence Unit. <h3>Methods</h3> Thirty adolescents -17 assigned Female at birth (AFAB) and 13 assigned male at birth (AMAB)- were evaluated at first referral (T0), shortly before the start of GnRHa (Triptorelin; T1) and after an average follow-up of 7 ±3.18 months (T2). Moreover, a subgroup of seventeen adolescents (11 AFAB and 6 AMAB) was evaluated after six months (T3) of GAHT. At each time point physical and biochemical examinations were performed, and general phsychopatology, depressive symptoms and suicidal risk were measured through validated questionnaires (Youth Self Report (YSR), Beck Depression Inventory (BDI); Multi-Attitude Suicide Tendency Scale (MAST)). <h3>Results</h3> Average age of adolescents at T1 was 14.4± [if gte msEquation 12]><m:oMath><i style='mso-bidi-font-style:normal'><span lang=EN-GB style='font-size:12.0pt; line-height:107%;font-family:"Cambria Math",serif;mso-fareast-font-family: Calibri;mso-fareast-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-GB;mso-fareast-language: EN-US;mso-bidi-language:AR-SA'><m:r>±</m:r></span></i></m:oMath><![endif][if gte vml 1]><v:shapetype id="_x0000_t75" coordsize="21600,21600" o:spt="75" o:preferrelative="t" path="m@4@5l@4@11@9@11@9@5xe" filled="f" stroked="f"> <v:stroke joinstyle="miter"/> <v:formulas> <v:f eqn="if lineDrawn pixelLineWidth 0"/> <v:f eqn="sum @0 1 0"/> <v:f eqn="sum 0 0 @1"/> <v:f eqn="prod @2 1 2"/> <v:f eqn="prod @3 21600 pixelWidth"/> <v:f eqn="prod @3 21600 pixelHeight"/> <v:f eqn="sum @0 0 1"/> <v:f eqn="prod @6 1 2"/> <v:f eqn="prod @7 21600 pixelWidth"/> <v:f eqn="sum @8 21600 0"/> <v:f eqn="prod @7 21600 pixelHeight"/> <v:f eqn="sum @10 21600 0"/> </v:formulas> <v:path o:extrusionok="f" gradientshapeok="t" o:connecttype="rect"/> <o:lock v:ext="edit" aspectratio="t"/></v:shapetype><v:shape id="_x0000_i1025" type="#_x0000_t75" style='width:9pt; height:15pt'> <v:imagedata src="file:///C:/Users/User/AppData/Local/Temp/msohtmlclip1/01/clip_image001.png" o:title="" chromakey="white"/></v:shape><![endif]2.06 years old. A significant reduction in gonadotropins levels and Tanner stage were observed at T2 vs. T1 in both genders (all p<0.05). Body mass index (BMI) and mean arterial blood pressure (BP) showed no significant increase in adolescents treated with GnRHas. After six months of GAHT BMI significantly increased in transboys (p<0.05), but no impact on mean arterial BP was observed in both genders. Psychological support alone resulted in no changes in psychological functioning, whereas a significant increase in attraction to life (MAST scale) and a significant decrease in general phsychopatology (YRS internalizing subscale) was observed with GnRHa treatment together with psychological support (p<0.05). Depressive symptoms progressively decreased at T2 and at T3 (p<0.05). <h3>Conclusions</h3> These preliminary data show that GnRHa therapy is effective in suppressing pubertal changes with no impact on mean arterial BP and BMI in trans adolescents; GAHT had no impact on mean BP. Also, puberty suppression together with psychological support showed efficacy in improving psychological functioning. <h3>Conflicts of Interest</h3> The Authors have no conflict of interest

OR05-5 Body Mass Index (BMI) as a Predictor of Bone Mineral Density (BMD) in Gender Diverse Youth

Abstract Objective GnRH agonists (GnRHa), used to prevent development of undesired secondary sex characteristics for gender diverse youth (GDY), may impede pubertal bone mineral accrual increasing the risk for osteopenia/osteoporosis during adulthood. Based on findings of low bone mineral density (BMD) scores (relative to natal sex) prior to GnRHa [1], we hypothesized BMD might be associated with body mass index (BMI) in GDY.Method: To test our hypothesis, we reviewed medical records for 27 GDY; 16 were designated female at birth (DFAB) and 11 were designated male at birth (DMAB). Age at presentation, gender identity, ages at initiation of GnRHa and gender affirming hormone treatment (GAHT), duration of GnRHa treatment prior to GAHT initiation, auxologic parameters including BMI, and lumbar spine BMD obtained from GE lunar IDXa dual-energy X-ray absorptiometry (DEXA) were extracted. Lumbar spine BMD was used for statistical analysis. Statistical analysis was performed with Microsoft Excel Analysis ToolPak. A linear regression model was used to determine significance of BMI and GnRHa as predictors of BMD Z-score using a significance level of 0.05. Legal gender marker was used to determine BMD Z-scores. Results BMI ranged from 16.93 kg/m2 to 35.79 kg/m2 (5th to the 99th percentile). DEXA scan results were available for 27 GDY with age range 10-25 years; mean age (±SD) was 17±3 years. BMD of the lumbar spine was obtained from 0-61 months (mean 30 ± 21 months) following initiation of GnRHa. Length of GnRHa treatment prior to GAHT initiation ranged from 0-53 months (mean 14 ± 12 months).Individuals were at different stages of the gender affirmation process including 1) No medical treatments, 2) GnRH agonist only, 3) GAHT only, and 4) combined GnRH agonist and GAHT. Using a linear regression model, length of GnRHa therapy and length of GnRHa without GAHT were not significantly associated with lumbar spine BMD in our sample (p = 0.44 and 0.29, respectively). Using a linear regression model, BMI was a significant positive predictor of higher lumbar bone mineral density (p = 0.03). Conclusion Sex hormone exposure during adolescence and young adulthood is essential for bone health. While GnRH agonists lower endogenous sex hormone exposure, in our sample, lower BMD was not associated with total duration of GnRHa therapy or duration of GnRHa treatment prior to GAHT. Rather BMD was positively associated with BMI regardless of gender affirming medical therapies. Limitations include small sample size, retrospective design, and the use of legal gender marker for normative values. The next step will be larger, prospective studies to identify predictors of low BMD in GD youth. This information will guide future management regarding BMD monitoring.

Association of Gonadotropin-Releasing Hormone Analogue Use With Subsequent Use of Gender-Affirming Hormones Among Transgender Adolescents

Gonadotropin-releasing hormone analogue (GnRHa) use during puberty improves mental health among transgender and gender-diverse (TGD) adolescents. In previous studies, most (96.5%-98.1%) TGD adolescents who started GnRHa subsequently started gender-affirming hormones (GAH), raising concerns that GnRHa use promotes later use of GAH. To determine whether GnRHa use among TGD adolescents is associated with increased subsequent GAH use. This is a retrospective cohort study of administrative records collected between 2009 and 2018. The current analysis was completed in August 2022. Participants were enrolled in the US Military Healthcare System (MHS) with an initial TGD-related encounter occurring between ages 10 and 17 years. GnRHa use. Initiation of GAH. The 434 patients were a mean (SD) of 15.4 (1.6) years old at the time of their first TGD-related encounter; 312 (71.9%) were assigned female at birth, and 300 (69.1%) had an enlisted insurance sponsor. GnRHa use was more common among patients who were assigned male at birth (28 patients [23.0%]) than those assigned female (42 patients [13.5%]), but GAH use was not. Socioeconomic status was not associated with GnRHa or GAH use. Compared with older patients (aged 14-17 years), those who were younger (aged 10-13 years) at the time of the initial TGD-related encounter had a higher rate of GnRHa use (32 patients [57.1%] vs 38 patients [10.1%]) and a longer median time to starting GAH. The median interval from the date of the initial encounter to starting GAH decreased over time, from 2.3 years (95% CI, 1.7-2.8 years) between October 2009 and December 2014 to 0.6 years (95% CI, 0.5-0.6 years) between September 2016 and April 2018. Patients who were prescribed GnRHa had a longer median time to starting GAH (1.8 years; 95% CI, 1.1-2.4 years) than patients who were not (1.0 years; 95% CI, 0.8-1.2 years) and were less likely to start GAH during the 6 years after their first TGD-related encounter (hazard ratio, 0.52; 95% CI, 0.37-0.71). Among 54 younger (aged 10-13 years) patients who were not eligible to start GAH at their first encounter, GnRHa use was associated with a longer median time to starting GAH, but age at the first TGD-related visit was not. In this cohort study of TGD adolescents, GnRHa use was not associated with increased subsequent GAH use. These findings suggest that clinicians can offer the benefits of GnRHa treatment without concern for increasing rates of future GAH use.

A model for pregnancy rates after IVF-ET in patients with infertility and endometriosis.

The objective of the present study was to examine the clinical factors influencing the pregnancy rate of infertile patients with endometriosis and establish a predictive model. This study included 158 patients (158 cycles) with infertility and endometriosis who underwent laparoscopic surgery, and in vitro fertilization and embryo transfer (IVF-ET) were evaluated retrospectively between January 2019 and December 2020. The clinical factors in the pregnant and non-pregnant group were analyzed by univariate analysis. Statistically significant variables were subsequently used for multivariate logistic regression to establish the prediction model. Multivariate logistic regression analyses showed that GnRH-a treatment after operation (OR, 6.562; 95% CI: 2.782-15.477; p<0.01), ASRM stage (OR, 0.218; 95% CI: 0.093-0.509; p<0.05), the number of high-quality transferred embryos (OR, 3.155; 95% CI: 1.647-6.047; p<0.05) were independently associated with successful pregnancy. The area under the curve (AUC) of the prediction model was 0.774 (95% CI: 0.700-0.847). According to Hosmer-Lemeshow, the model was well fitted (p>0.05). We applied the bootstrapping method to internal validation, and the result showed that the pregnancy rate predicted by the model and the real data were consistent. The models for predicting pregnancy rates after IVF-ET in infertility and endometriosis patients showed high accuracy. The effective methods to increase the number of high-quality embryos need further study.

Long-term treatment of dienogest with symptomatic adenomyosis: retrospective analysis of efficacy and safety in clinical practice

ABSTRACT Objective: To evaluate the efficacy and safety of dienogest (DNG) in women with symptomatic adenomyosis.Methods: Women with symptomatic adenomyosis were included in this retrospective observation study. Group 1 (maximum uterine dimension ≥ 100.0 mm) began DNG after 4 months of GnRH-a administration, Group 2 (maximum uterine dimension < 100.0 mm) received DNG with no prior GnRH-a treatment. All women were assessed for their pain symptoms, uterine size, adverse effects and laboratory hematology at baseline and every 6 months during the treatment.Results: 123 women were enrolled in this study, in Group 1 (71 women) with severe uterine enlargement, the median VAS score was 80 mm prior to GnRH-a administration and 10, 10, 10, 20, and 20 mm, respectively, after 0, 6,12,18, and 24 months of DNG treatment. The mean uterine volume decreased from 262.9 ml to 104.7 ml after GnRH-a therapy, and slowly increased from 104.7 ml to 139.5 ml after 24 month-treatment of DNG. Another 52 women with mild uterine enlargement received DNG without prior GnRH-a administration, median VAS score was 70 mm at baseline and decreased to 20, 20, 10, and 10 mm at 6,12,18, and 24 months. The mean uterine volume slightly decreased from 157.9 ml to 153.3 ml after 24 months of DNG treatment (p > 0.05). All laboratory parameters were in the normal range.Conclusions: DNG is effective and well tolerated as a long-term treatment for symptomatic adenomyosis, and it can be used as maintenance therapy after discontinuation of GnRH-a administration.

P-312 Effect on pregnancy outcomes of depot GnRH agonist pre-treatment before frozen-thawed embryo transfer cycles in patients with adenomyosis

Abstract Study question Is there any difference between using or not using depot GnRH agonist pre-treatment on pregnancy outcomes in patients with adenomyosis before frozen-thawed embryo transfer cycles? Summary answer GnRH agonist pre-treatment before frozen-thawed embryo transfer has no effect on pregnancy outcomes in adenomyosis patients. What is known already Uterine adenomyosis negatively affects implantation and clinical pregnancy rates and also increases the risk of early pregnancy loss. Increased inflammatory markers and increased myometrial peristalsis are thought to decrease the rate of implantation. Depot GnRH agonist pre-treatment is thought to increase implantation rate by both decreasing myometrial contractility and reducing inflammatory marker production. Study design, size, duration This retrospective cohort study was conducted at ART and Reproductive Genetics Centre, Memorial Sisli Hospital, Istanbul, Turkey. Patients with adenomyosis undergoing a FET cycle between 2011 and 2021 were evaluated. Patients between 25-45 years old with good and top-quality blastocysts were included and preimplantation genetic diagnosis (PGD) was applied to patients who were &amp;gt;37 years old. A total of 144 frozen embryo transfer cycles were examined. Participants/materials, setting, methods Diagnosis of adenomyosis was made using transvaginal ultrasound and/or pelvic magnetic resonance imaging which revealed an asymmetrically thickening between the anterior and posterior uterine walls, focal adenomyosis, myometrial cysts and irregular/interrupted junctional zone of the endometrium. 65 patients in the study group (Group I) who received depot GnRH agonist pre-treatment for minimum 2 and maximum 6 months and 79 patients without GnRH agonist pre-treatment (Group 2) were evaluated. Main results and the role of chance There was no significant difference in patient characteristics such as age, endometrial thickness on embryo transfer day, BMI, infertility duration, and anti mullerian hormone levels between groups 1 and 2. Endometrial preparation was done using artificial cycle in the depot agonist group, whereas both artificial and modified natural cycle were used in patients without depot GnRH agonist pre-treatment.The pregnancy rate was 53.8%(n = 35) in group 1 and 54.4%(n = 43) in group 2. The clinical pregnancy loss rate was 20% (n = 9) in group 1 and 15.7% (n = 6)in group 2. The live birth rate was 40% (n = 26) in group I and 39.2. (n = 31) in group II. There were no statistically significant differences in pregnancy rates, clinical pregnancy losses, and live birth rates between the groups. Limitations, reasons for caution The limitation of the study is its retrospective nature. Wider implications of the findings The lack of any statistically significant differences in pregnancy outcomes in this study suggests the need for further evaluation of the value/effectiveness of GnRHa treatment in adenomyosis patients before embryo transfer cycles. Trial registration number not applicable