Gonadotropin-releasing Hormone Agonist Therapy Research Articles

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen–thawed embryo transfer cycles

ObjectiveTo compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. Materials and methodsThis was a retrospective cohort study on patients undergoing polypectomy who underwent frozen–thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. ResultsThere were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046–2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). ConclusionGnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

Postoperative Craniopharyngioma in a 10-Year-Old Girl Presenting with Central Precocious Puberty, Central Diabetes Insipidus, and Growth Hormone Deficiency

Background: Hypopituitarism is the most common endocrinology complication of postoperative craniopharyngioma. However, we found a 10-year-old girl with a history of postoperative craniopharyngioma presenting with central precocious puberty (CPP), central diabetes insipidus (CDI), and growth hormone deficiency (GHD).
 Case presentation: A 5-year-old girl experienced breast growth followed by menstruation six months later. The patient's weight was 19 kg (weight-for-age: P25-P50), height was 109 cm (height-for-age: P10-P25), and good nutritional status (Waterlow 90%). The stage of pubertal development was M2P2. There was a history of craniopharyngioma, and it was resected at the age of 2 years. After surgery, the patient developed CDI and has received desmopressin. No new tumour growth was found from evaluation with periodic MRIs every three years. After CPP was established, with increased serum levels of LH, FSH, and estradiol, GnRH agonist therapy was given at 100 mcg/kg BW every month. During five years of follow-up, the patient experienced clinical and laboratory improvement. However, the growth is only 3-4 cm/year (<P3) with short stature (height-for-age: <P3) and overweight. Low levels of IGF1 and GH were found in the stimulation test results, so the diagnosis of GHD was confirmed. The patient will receive growth hormone therapy and is expected to reach her potential genetic height (148.5 - 165.5 cm).
 Conclusion: Even though the craniopharyngioma tumour has been resected and no recurrence has occurred, it is crucial to evaluate the hormones produced by the pituitary thoroughly.

Impact of Gonadotropin-Releasing Hormone agonist and hormone replacement therapy on pregnancy outcomes in single euploid frozen-thawed embryo transfer for patients with endometrial polyps

Objective: While consensus on the optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) is lacking, this is particularly true for patients with infertility and a history of endometrial polyps (EPs). In this study, we aimed to investigate whether a gonadotropin-releasing hormone agonist combined with hormone replacement therapy (GnRHa-HRT) could improve pregnancy outcomes in single euploid FET for patients with a history of EPs. Methods: In this retrospective cohort study, 395 women who underwent their first single euploid FET cycle were divided into groups according to endometrial preparation protocols as follows: natural cycle (NC) (n=220), hormone replacement therapy (HRT) (n=122), and GnRHa-HRT groups (n=53). Subsequently, the FET cycles in the three groups were subdivided according to maternal age. All patients underwent hysteroscopic polypectomy before FET, and their EPs were confirmed by pathology. Results: No statistically significant differences were observed in live birth rates among the three groups (58.64% vs. 58.20% vs. 56.60%, P=0.964). Furthermore, the rates of miscarriage, ectopic pregnancy, premature live birth, and pregnancy complications were comparable among the three groups (P >0.05). After adjusting for potential confounding factors, no significant differences in pregnancy outcomes were reported between the groups (adjusted odds ratios [OR] and 95% credible intervals [CI] for live birth rate, HRT vs. NC: 1.119, 0.660–1.896, P=0.677; GnRHa-HRT vs. NC: 1.165, 0.610–2.226, P=0.643). Additionally, the pregnancy outcomes of the FET cycle were not influenced by the endometrial preparation protocols in the subgroups when stratified by maternal age (P >0.05). Conclusion: GnRHa-HRT did not improve the pregnancy outcomes of the single euploid FET in patients with a history of EPs.

The effects of gonadotropin-releasing hormone agonist on final adult height among girls with early and fast puberty.

This study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty. A retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children's Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment. The treatment group was significantly older at the time of inclusion(chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht)(PAH1-Tht, -3.9 vs. -1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH-PAH1≥5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year. GnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain.

Predictive value of a basal LH instead of an LHRH test in assessing pubertal suppression in children on GnRH agonist therapy

Predictive value of a basal LH instead of an LHRH test in assessing pubertal suppression in children on GnRH agonist therapy

SAT403 Long-term Metabolic Effects Of Gonadotropin Releasing Hormone Agonist (GnRH) Therapy In Transgender Women Veterans

Abstract Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. L. Gondin Hernandez: None. M. Mok: None. A. endoza: None. D. Tripathy: None. There is controversy regarding the effects of long-term GnRH agonist therapy on cardiovascular risk factors in older men with prostate cancer. GnRH agonists are used for gender affirming hormone therapy in adolescents and in adults who fail to suppress testosterone adequately. We examined the cardiometabolic effects of long-term GnRH agonist therapy in transwomen veterans. A retrospective chart review was performed on 74 transwomen veterans who were followed at the ALM VA Endocrinology clinic for at least 12 months and had detailed clinical, hormonal and biochemical profile (testosterone, estradiol, HbA1c, lipid profile) measured. Thirtytwo transwomen on GnRH agonist therapy (age 48 ± 2 yrs, BMI 28 ± 1 kg.m2) followed for 45 ± 5 months were compared with 22 transwomen (age 44 ± 3 yrs, BMI 28 ± 2 kg.m2) followed for 41 ± 7 months not on GnRH therapy. In the GnRH group, 14 were on oral E2, 12 on E2 patch and 6 were on E2 Injection. Similarly, in the non-GnRH group, the number of subjects on oral E2, E2 patch or E2 Injection were 17, 1, and 4 respectively. The average oral estrogen dose in both groups was 4 ± 0.4 mg. In the GnRH group, serum testosterone declined from 420 ± 36 ng/dl to 40 ± 5 ng/dL and serum estradiol before and after therapy was 39 ± 9 vs 89 ± 12 pg/mL. GnRH therapy led to increase in BMI (28 ± 1 vs 31 ± 2 kg.m2, p=0.006), though no difference was observed in SBP (126 ± 2 vs 120 ± 2 mmHg, p=ns), total Cholesterol (170 ± 7 vs 171 ± 8 mg/dL), HDL Cholesterol (45 ± 2 vs. 46 ± 2 mg/dL), LDL Cholesterol (98 ± 7 vs 99 ± 5 mg/dL) before and after treatment. There was no change in BMI (28 ± 2 vs 29 ± 1 kg.m2), SBP (121 ± 3 vs 125 ± 3, p=ns), total cholesterol (173 ± 5 vs. 170 ± 9 mg/dL), HDL chol (46 ± 2 vs. 49 ± 2 mg/dL), or LDL chol (97 ± 6 vs. 95 ± 7 mg/dL) in the control group. Plasma triglycerides increased in both the GnRH (134 ± 10 vs 168 ± 16 mg/dL, p&amp;lt;0.05) as well as in the control group (154 ± 30 vs 167 ± 20 mg/dL, p&amp;lt;0.05) after treatment. In conclusion, long-term estrogen therapy in transwomen increased plasma triglyceride. Concomitant GnRH agonist therapy was associated with greater weight gain, but did not affect other cardiovascular risk factors. Presentation: Saturday, June 17, 2023

SAT398 Pubertal Status And Trends In Gender Affirming Treatment Of Transgender And Gender Diverse Youth

Abstract Disclosure: C. Lin: None. M. Oransky: None. R. Fader: None. N.R. Malhotra: None. E.M. Baldiserroto: None. C.J. Romero: None. J.D. Safer: None. M. Yau: None. Background: Transgender and gender diverse (TGD) youth seek care to affirm their gender identities and improve quality of life and mental health. Gender affirming care of youth includes pubertal assessment, pubertal suppression with gonadotropin-releasing hormone agonist (GnRHa) and gender-affirming hormone therapy (GAHT). Management choices are made collaboratively among the patient, the patient’s family, and the multidisciplinary treatment team. Objective: We sought to characterize the pubertal status of the TGD youth to consider medical intervention. Method: The medical records of 58 TGD youth referred to pediatric endocrinology from 2020-2022 were retrospectively analyzed. Pubertal assessments were made by visualization of pubic hair and breast development according to the Tanner scale and determination of testicular volume with an orchidometer. We labeled Tanner stage 1 as prepuberty; stages 2-3 as early puberty; and stages 4-5 as late puberty. Results: The median age was 15 years (range 8-18 years). 46.6% were trans girls (n=27), 44.8% were trans boys (n=26), and 8.6% were non-binary (n=1 natal male and n=4 natal female). Of the trans girls, 7.4% were prepubertal (n=2), 51.9% were in early puberty (n =14), and 40.7% were in late puberty (n=11). Of the trans boys, none were prepubertal, 3.6% were in early puberty (n=1), and 96.4% were in late puberty (n=25). Of the non-binary youth, 20% were in early puberty (n=1) and 80% were in late puberty (n=4).For the prepubertal patients, monitoring for onset of puberty without treatment was recommended. Of the 15 patients in early puberty, 73.3% started GnRHa (10 trans girls, 1 trans boy) and 26.7% started GAHT (4 trans girls). Of the 36 patients in late puberty, 2.8% received no treatment (1 trans boy), 25.0% started GnRHa (7 trans girls, 2 trans boys) and 72.2% started GAHT (4 trans girl, 22 trans boy). Of the 5 non-binary patients, 1 patient in early puberty (1 natal female) was treated with GnRHa, and 4 were in late puberty and initiated on GAHT (1 natal male, 3 natal female). Conclusion: In our multidisciplinary practice, trans feminine patients are evenly divided between those who present in early and late puberty. This presents possible implications for fertility preservation strategies. Trans masculine patients overwhelmingly present in late puberty, perhaps owing in part to earlier timing for typical “female” puberty. This means that even prompt initiation of GnRHa therapy cannot entirely prevent the potential future need for chest masculinization surgery. Presentation: Saturday, June 17, 2023

FRI312 Diplopia And Headache After Treatment With GnRH Agonist

Abstract Disclosure: A.A. Zakkar: None. M. Al Mushref: None. M. Fadanelli: None. Case Report: The Patient is a 46-year-old male with past medical history of hypertension and prostate cancer, currently undergoing treatment with leuprolide acetate injections, who presented to the emergency department with a complaint of worsening headache. He received his second injection 3 days prior to admission and within hours he developed a headache in the frontal area that was continuous and worsening over time, increasing with positional changes of his head. One day after the treatment he developed persistent double vision. The patient reported that he has had worsening vision over the last year and was to see an ophthalmologist but was diagnosed with prostate cancer at the same time so he became more focused on the oncologic care. He also reported poor balance, excessive thirst and increased urination of large volumes of urine every hour with nocturia several times. On exam the vital signs were normal, he was A&amp;Ox4 and in no distress. He had left abducens and oculomotor nerve palsy but an otherwise benign exam. MRI of the brain revealed a sellar mass measuring 2.2 x 1.7 x 2.3 cm consistent with pituitary macroadenoma extending into the suprasellar cistern, compressing the pituitary stalk and the optic chiasm. Patient was evaluated by ophthalmology who noted +2 optic nerve edema of the left eye. Laboratory evaluation revealed low ACTH of 6 pg/mL at 5:30AM along with corresponding cortisol level of only 1.6 mcg/dL. FSH was low and LH undetectable as expected with GnRH agonist therapy. Growth hormone level, IGF-1, l and prolactin levels were all normal. The TSH was 0.50 microunits/mL with a freeT4 of 1.0. Urinalysis revealed dilute urine with specific gravity &amp;lt;1.006. Serum sodium on admission was 137 mmol/L and after overnight fasting was 140 mmol/L. The patient was started on desmopressin 0.1 mg po at bedtime and on intravenous dexamethasone 4 mg q6hrs. He was evaluated by neurosurgery and ENT who recommended trans-sphenoidal resection of the mass. Pathology report of the specimen was consistent with a pituitary adenoma with infarction without hemorrhage. The patient reported an improvement in his left eye vision and lateral rectus palsy. He was transitioned to oral hydrocortisone 20 mg daily and 10 mg every afternoon prior to discharge. On follow up with endocrinology several months later he was found to have persistent adrenal insufficiency and developed central hypothyroidism that required treatment. Conclusion: Patients with an undiagnosed pituitary adenoma are at risk of tumor expansion and mass effect as well as pituitary apoplexy during treatment with GnRH agonists. In our case clinical presentation was consistent with pituitary apoplexy without evidence of pituitary hemorrhage soon after GnRH agonist. A full ophthalmologic exam may be an appropriate screening prior to initiation of such therapy. Presentation: Friday, June 16, 2023

Cancer Therapy-Related Cardiac Dysfunction in Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

Background The risk of cardiac dysfunction for patients with prostate cancer undergoing androgen deprivation therapy (ADT) in the real-world setting remains unclear. Methods and Results A total of 1120 patients with prostate cancer and a baseline echocardiography scan were identified from Chang Gung Research Database between January 1, 2001 and December 31, 2019. Patients were treated with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, or bilateral orchiectomy. Changes in left ventricular ejection fraction (LVEF) were further assessed in 421 patients using repeated measurements of LVEF before and during ADT treatment. The incidence of cancer therapy-related cardiac dysfunction (CT-RCD) was evaluated and defined as a ≥10% absolute decline in LVEF from baseline to a value of <53%. Among 421 patients undergoing ADT, LVEF declined from 66.3±11.3% to 62.5±13.6% (95% CI of mean difference: -5.0% to -2.7%) after a mean follow-up period of 1.6±0.8 years. CT-RCD occurred in 58 patients (13.7%) with a nadir LVEF of 40.3±9.1% after ADT. Lower baseline LVEF was significantly associated with CT-RCD (odds ratio, 1.07 [95% CI, 1.04-1.10]). The area under the curve of baseline LVEF for discriminating CT-RCD was 75.6%, with the corresponding optimal cutoff value of 64.5% (sensitivity, 79.3%; specificity, 67.2%). Conclusions ADT with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, and bilateral orchiectomy were associated with an increased risk of CT-RCD in patients with prostate cancer. In addition, lower baseline LVEF was a significant predictor of CT-RCD in patients with prostate cancer undergoing treatment with ADT.

Rare presentation of pituitary stalk lipoma as central precocious puberty in a girl

Central precocious puberty (CPP) in girls is most commonly idiopathic. Here, we present a case of a 5-year 3-month-old child who presented with CPP with a stalk lipoma on magnetic resonance imaging. On examination, the sexual maturity rating was A1P1B (Rt B1, Lt B2), respectively. The hormonal evaluation revealed pubertal gonadotropin and E2 levels, respectively, with pubertal ultrasound (USG) parameters. She was started on gonadotropin-releasing hormone agonist therapy and is on regular follow-up. This case highlights stalk lipoma as a cause of CPP.

Fertility and Obstetric Outcomes of Assisted Reproductive Technology (ART) in Women With Adenomyosis Following Gonadotropin-Releasing Hormone Agonist Therapy: A Single-Center Experience.

Adenomyosis is an ambiguous disorder causing a wide variety of implications from dysmenorrhea, heavy menstrual bleeding, and infertility to pregnancy complications. Adenomyosis is associated with altered endocrine and inflammatory milieu, resulting in impaired implantation and reduced fertility potential. It is also associated with increased incidence of obstetric complications such as miscarriage, antepartum hemorrhage, placental mal-position, hypertensive disorders, small for gestational age-intrauterine growth restriction (SGA-IUGR), cesarean section, preterm labor, preterm premature rupture of membranes (PPROM), and neonatal intensive care unit (NICU) admissions. The aim of our study was to investigate the fertility and obstetric outcomes in women with adenomyosis treated with GnRH agonists compared to controls with normal uteri undergoing in-vitro fertilization (IVF) at our center, thereby establishing the role of gonadotropin-releasing hormone (GnRH) agonists in managing sub-fertile women with adenomyosis. We carried out a retrospective cohort study at our hospital to analyze the effects of adenomyosis on IVF and pregnancy outcomes. This study (n=83) involves women with adenomyosis between the ages of 21 and 37 years who were followed up at our center between 2013 and 2022. The controls (n=83) were selected from women who underwent IVF-intracytoplasmic sperm injection (IVF-ICSI) for tubal or mild male factor infertility with normal appearing uterus within the same time frame. Women with adenomyosis were given GnRH agonist as long/ultralong agonist protocol before controlled ovarian stimulation or as down-regulated frozen embryo transfer (FET). The length of suppression was between one and six months based on the size of the uterus and response to treatment. Fertility and obstetric outcomes were analyzed. The implantation rates were found to be equivocal: 54.2% and 53% in the adenomyosis and control groups, respectively (p=0.208). The cumulative live birth rate was 50.6% and 48.2% in the study and control groups,respectively (p=0.341). The biochemical pregnancy rate and the first- and second-trimester miscarriage rates were not significantly different between the group with adenomyosis and the group with normal uterus. The incidence of preterm deliveries and antepartum hemorrhage was found to be significantly increased in the study group. Medical management in women with adenomyosis optimizes the live birth rates giving results at par with the control population.

Which method is more effective in predicting adult height in pubertal girls treated with gonadotropin-releasing hormone agonist?

The aim of the present study was to determine the efficiency of three different predictive models [Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner-Whitehouse 2 (TW2)] by comparing their predictions with near-adult height data of girls receiving gonadotropin-releasing hormone agonist (GnRHa) therapy. Clinical findings were retrospectively analyzed. Bone ages obtained before treatment were evaluated from left hand and wrist radiographs by three researchers. Predicted adult height (PAH) was calculated using the BP, RWT, and TW2 methods for each patient at the beginning of therapy. The median age at diagnosis of the 48 patients included in the study was 8.8 (8.9-9.3) years. There was no significant difference between the mean bone ages evaluated separately with the Greulich-Pyle atlas and the TW3-RUS method (p=0.34). Among the PAH methods, only PAH measured by the BP method was very close to and no different from near adult height (NAH) [159.8±6.3 vs. 158.8±9.3 cm. p=0.3; (-0.5±1.1) vs. (-0.7±1.6) standard deviation score, p=0.1]. Accordingly, the BP method was found to be the most accurate prediction tool in girls with puberty treated with GnRHa. The BP method is more effective at predicting adult height than the RWT and TW2 methods in female patients who will receive GnRHa treatment.

Leuprolide and triptorelin treatment in children with idiopathic central precocious puberty: an efficacy/tolerability comparison study.

Central precocious puberty (CPP) results from premature activation of hypothalamic-pituitary-gonadal axis, with the consequent increase of gonadotropin-releasing hormone (GnRH); GnRH agonists (GnRHa) represent the gold-standard therapy in children with CPP although their use might be responsible for pituitary GnRH receptors down-regulation, that in turn suppresses luteinizing hormone (LH) and follicle stimulating hormone (FSH) and blocks of gonadal sex hormones release. The most prescribed GnRHa in the clinical practice are leuprolide and triptorelin, whose use is generally safe and well tolerated; however, mild menopausal-like side effects could appear. The aim of the present study was to investigate and compare the efficacy and tolerability profile of leuprolide and triptorelin in CPP patients. 110 girls affected by CPP were enrolled in this retrospective study, carried out from 2018 to 2020. The enrolled patients received leuprolide (n = 48) or triptorelin (n = 62). Efficacy was investigated by the means of clinical parameters and radiological changes and side effects were also recorded to evaluate the possible relationship between the two GnRHa treatments and side effects appearance. At baseline triptorelin patients had significantly higher LH and LH peak levels than leuprolide patients, whereas no significant difference in other patient characteristics was observed between the two groups. The leuprolide treatment lasted 971 days [790-1,171 days] while the duration of triptorelin administration was 792 days [760-1,003 days] (p < 0.001). Overall 46 (41.8%) of the studied patients reported mild menopausal-like symptoms: among these 27 were treated with triptorelin and 19 with leuprolide (p = 0.558). Patients treated with triptorelin, or leuprolide showed headache (27.4% vs. 16.7%), mood swings (12.9% vs. 16.7%), increased appetite (12.9% vs. 18.8%) and nausea (1.6% vs. 10.4%) respectively. Moreover, the onset of side effects appearance related to GnRHa therapy significantly reduces with the increase of the initial bone age (p = 0.038). Leuprolide and triptorelin treatment appear to be effective and safe without significant difference between the two drugs in term of efficacy and tolerability, making both good options for treating CPP.

Treatment of Adolescent Endometriosis Before, During, and After Use of Gonadotropin-Releasing Hormone Agonists: A Retrospective Cohort Study

To explore the use duration of a gonadotropin-releasing hormone agonists (GnRHa) plus add-back in adolescents with laparoscopically confirmed endometriosis and the treatment course before and after GnRHa therapy. Retrospective cohort study. We identified 51 subjects with laparoscopically confirmed endometriosis who had participated in a randomized trial of a GnRHa plus add-back as adolescents between 2008 and 2012. Electronic medical records were reviewed to obtain demographic data, clinical characteristics, and treatment outcomes after trial completion. The study was deemed IRB exempt. The average age of participants during trial enrollment was 17.9±1.7 years. Thirty-three participants had stage I endometriosis (65%). The most common treatments trialed before GnRHa therapy were combined oral contraceptives (n=47, 92%) and progestin-only pills (n=23, 45%). The average duration of GnRHa use during the trial was 9.5±3.5 months; 34 subjects (67%) completed the 1-year trial. After trial completion, 23 subjects (45%) continued to use a GnRHa with add-back therapy. The mean duration of additional GnRHa use was 31.7±28.6 months, and the longest identified duration was an additional 96 months. Twenty-four subjects switched to other hormonal treatments after trial participation, most commonly oral progestins (n=15) or combined oral contraceptives (n=6). Thirteen participants (25%) returned to a therapy that had been trialed before GnRHa use. Almost half the participants in this cohort continued to use a GnRHa with add-back for treatment of endometriosis beyond the 12-month recommended duration. Treatment varied widely after discontinuation of GnRHa, with many participants returning to previously trialed medical therapies.

Evaluation of different treatment modalities for diffuse uterine leiomyomatosis: A case series report and review of the literature.

To provide perspectives on preoperative diagnosis and conservative treatment for diffuse uterine leiomyomatosis (DUL). The clinical characteristics, management, and outcome of the five cases diagnosed with DUL receiving surgical treatment at Peking Union Medical College Hospital between January 2010 and December 2021 were retrospectively analyzed. DUL is a diagnosis based on histopathology. It is a subtype of uterine leiomyoma, characterized by innumerable, poorly circumscribed hypercellular nodules of bland smooth muscle cells with no cytologic atypia diffusely involving the myometrium. Clinical manifestations, including menorrhagia, anemia, and infertility, are similar to those of typical uterine leiomyomas, making a definitive preoperative diagnosis difficult. Magnetic resonance imaging plays an important role in the pre-treatment mapping. Conservative surgery can reduce the uterine volume and improve the contour of the uterine cavity, thereby relieving symptoms of menorrhagia and improving the chance of conception. Gonadotropin-releasing hormone (GnRH) agonist therapy is of great significance for controlling vaginal bleeding, reducing uterine volume, and delaying postoperative recurrence, and can be used alone or as postoperative adjuvant therapy for conservative surgery. The treatment goal for DUL patients with fertility-sparing request should not aim at complete fibroid removal. A successful pregnancy can be achieved following conservative surgery and/or GnRH agonist therapy.

Effect of gonadotropin-releasing hormone agonist treatment in Vietnamese children with central precocious puberty

Gonadotropin-releasing hormone agonists (GnRHa) are generally indicated in central precocious puberty (CPP) patients. We aimed to analyze the auxological outcomes of GnRHa treatment on CPP children. A cross-sectional study with observational data were collected from 143 CPP patients who finished GnRHa therapy in Children Hospital 2, Vietnam. Anthropometry and sexual maturity rating were assessed after 6 months and each year of the therapy. The Bayley-Pinneau method was used to estimate the predicted adult height (PAH). The mean calendar age and bone age at the start of the treatment were 8.0 ± 0.7 years and 10.5 ± 0.1 years, respectively. The mean treatment period was 2.4 ± 0.6 years. GnRHa led to the regression of pubertal symptoms after treatment. The pre-treatment PAH was 157.8 ± 0.6 cm (girls) and 172.3 ± 2.4 cm (boys). The PAH at treatment discontinuation (162.0 ± 0.5 cm in girls and 176.7 ± 2.3 cm in boys) was higher than the initial PAH (p&lt;0.05). For girls with treatment before 6 years old, GnRHa results in a predicted average gain in adult height of 10.2 ± 3.2 cm, whereas the predicted height advancement in the 6-8 age group was 5.3 ± 0.7 cm. The predicted average height gain of girls aged over 8 years was 3.2 ± 0.6 cm. GnRHa therapy was effective for CPP treatment with the improvement of predicted final height. Predicted height advancement was still documented in females who started the treatment after 8 years old.

Uterocutaneous fistula managed medically: A case report.

Background: The uterocutaneous fistula is an abnormal connection or passageway between the uterus and the skin. The most common causes include infections, trauma, or surgery, a severe medical condition requiring prompt medical attention and treatment.&#x0D; Case Presentation: Here, we describe the case of a 36-year-old female who developed a uterocutaneous fistula after cesarean delivery. Her post-cesarean recovery was complicated by wound infection, and after healing the wound, she presented with cyclical bloody discharge from a pinpoint opening in the healed wound scar.&#x0D; Management: On ultrasound and MRI, she was diagnosed as having a uterocutaneous fistula. She opted for non-surgical management and underwent successful medical management with GnRH agonists. She remained symptom-free after the resumption of her menstrual cycle.&#x0D; Conclusion: In younger populations hoping to avoid surgery, pharmacological care with GnRH agonist therapy can be a reasonable alternative to surgical resection of the fistulous tract. Healthcare professionals should have a high index of suspicion to diagnose this condition.&#x0D;

Ongoing increasing trends in central precocious puberty incidence among Korean boys and girls from 2008 to 2020.

Over the last few decades, there has been growing evidence of earlier onset and progression of puberty worldwide. This population-based longitudinal cohort study aimed to analyze the change in the annual incidence rate of central precocious puberty (CPP) among Korean children over the most recent decade, using the national registry data. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and insurance claims for gonadotropin-releasing hormone agonist (GnRHa) treatment were used to identify CPP patients who were using the Korean Health Insurance Review & Assessment Service (HIRA) database between 2008 and 2020. Patients who began GnRHa therapy before the age of 9 and 10 for girls and boys, respectively, were included in the study. A total of 6,906 boys and 126,377 girls were diagnosed with CPP between 2008 and 2020. The annual incidence of CPP increased by 83.3 times in boys (from 1.2 to 100 per 100,000 persons) and by 15.9 times in girls (from 88.9 to 1414.7 per 100,000 persons). The age-specific annual incidence of CPP increased remarkably more in older children than in younger ones; the 2020 CPP incidence among 9-year-old boys and 8-year-old girls reached 705.2 and 7,967.3 per 100,000 persons, respectively. The annual prevalence of CPP in boys and girls increased from 2.7 to 206.5 (76.5 times) and from 141.8 to 3439.9 (24.3 times) per 100,000 persons, respectively. Based on GnRHa treatment insurance claims, our study suggests that the annual incidence of CPP has substantially increased in Korea during the past 13 years. These findings highlight the importance of meticulous judgment by doctors in determining GnRHa treatment.

Mitigating the economic burden of GnRH agonist therapy for progestogen-resistant endometriosis: why not?

Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens? An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief. Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted. A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected. Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded. Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or 'draw-back' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%). The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed. Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access. This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. N/A.

Fertility preservation in transfeminine adolescents using TESE at the time of Histrelin Acetate subcutaneous implant placement: A Case Series

Fertility preservation (FP) is an important aspect of the care of transgender patients in whom Gender Affirming Medical Treatment (GAT) may begin before puberty is completed. While there are overall few studies that can be used to guide conversations about long-term effects of GAT, there are concerns that GAT could negatively impact fertility. Prior studies have shown low utilization of FP in this population, with avoidance of delay in starting GAT cited as one of the most common reasons for foregoing FP. It is possible that strategies to mitigate delay in commencement of GAT can facilitate higher FP utilization, maintaining options for future family building. To describe our institution's experience with Testicular Sperm Extraction (TESE) for FP and Histrelin Acetate (Supprelin) Subcutaneous Implantation for GAT commencement. A retrospective review of transfeminine adolescents at our institution from 2010 to 2022 who underwent TESE for FP at the time of Supprelin placement for GAT (FP/SP). Outcomes of interest included successful sperm retrieval, age at first visit to our institution's Transgender Multispecialty Service Health clinic (GeMS), age at time of FP/SP, testicular volume, and Tanner stage at time of FP/SP, and age when GnRH agonist (GnRHa) therapy was prescribed. Testosterone, LH, FSH, and Inhibin B values prior to combination FP/SP were also obtained. Ten patients from 2017 to 2022 underwent FP/SP after prescription of GnRHa based on Endocrine Society Guidelines. Successful sperm retrieval and storage was achieved in all patients. Median age at FP/SP was fourteen years 5.5 months (range 12y5m-16y8m). Median time from GnRHa prescription to FP/SP was two months (range 2-5m). Mean testicular volume at time of FP/SP was 13.2cc (SD 3.38cc, range 8-17cc), and median Tanner Stage was IV (range III-V). Average testosterone level was 301.60 (SD 173.04), LH 3.00 (SD 1.25), FSH 3.33 (SD 1.71), Inhibin B 208.50 (SD 87.44). Performing TESE for FP is feasible for transgender youth undergoing Histrelin implant placement, leading to short delays in starting GAT. Testicular volume and endocrine markers can provide preoperative insight into likelihood of successful sperm retrieval during TESE, are needed to identify which patients will have successful sperm retrieval to ensure optimal counseling and informed decision making for providers, patients and families.