Hormone Agonist Research Articles

Bleeding vs Thrombosis: Treatment Strategy for Women Having Large Uterine Fibroids and DVT

Large uterine fibroids (UFs) are clonal neoplasms of the uterus that form during the mid and late-aged women. Such women generally consume oral contraceptive pills, tranexamic acid, or NSAIDS to manage heavy menstrual bleeding (HMB) and associated complications while waiting for a conclusive procedure or avoiding hysterectomy. The procoagulant effect of these medicinal agents can result in venous stasis of the lower limbs, leading to deep vein thrombosis (DVT), a challenging complication with HMB. We examine the complicated state of heavy bleeding with thrombosis and explore better management options. It has been seen that women with hypothyroidism have an increased risk of getting DVT due to an alteration in the coagulation system. These incidences are mostly associated with higher uterine weight, which is related to the extrinsic compression of the inferior vena cava. In such cases, the occurrence of postoperative thrombosis is riskier if hysterectomy/myomectomy is the only option. Utilization of appropriate anticoagulants with modification of the steroid-hormone system using hormone agonists or antagonists (e.g., levonorgestrel intrauterine system, high-dose progestin-only therapy, danazol, aromatase inhibitors, Vitamin-D supplements or selective estrogen receptor modulators) could be an effective technique, but adverse consequences of continued use should be monitored. More research is needed into the basic biology associated with the role of growth factors and genetic alterations in these malignancies. The development of new leiomyomas following conservative therapy is also a significant issue.

Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study

BackgroundDiminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin‐releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols.MethodsA total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors.ResultsThere were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted β = 0.538 (0.221–0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted β = 0.277 (0.031–0.523)] and transferable embryos [1.22 vs. 0.95, adjusted β = 0.162 (-0.005–0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR.ConclusionsDual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.

Dynamic serum testosterone concentration may predict in vitro fertilization yield during ovarian stimulation by a gonadotrophin‐releasing hormone agonist long protocol in women with normal ovarian reserve

AbstractObjectiveTo determine whether dynamic changes in serum total testosterone (TT) levels during controlled ovarian stimulation (COS) by a GnRH‐a (gonadotrophin‐releasing hormone agonist) long protocol may predict pregnancy in women with normal ovarian reserve in in vitro fertilization.MethodsThe TT measurements were added to routine hormone tests during COS. The TT dynamic changes, clinical pregnancy rate, and quality of oocytes and embryos of 109 patients were analyzed.ResultsCompared with the non‐pregnancy group, in the pregnancy group the TT level on Gn initial day (TTinitial‐d) increased sharply when the dominant follicle reached a diameter 10–12 mm [TTfΦ (10–12)‐d] and on human chorionic gonadotrophin (HCG) day (TTHCG‐d), also the ratios of TTfΦ (10–12)‐d to TTinitial‐d (1.23 ± 0.37 vs. 1.10 ± 0.58, p = 0.040) and TTHCG‐d to TTinitial‐d (2.32 ± 1.26 vs. 2.00 ± 1.43, p = 0.019) increased notably. Of the 2 TT ratios, the first tertile limit was regarded as the threshold of high TT ratios (1.00, 1.45). High tertiles had higher pregnancy rates than low tertiles (82.86% vs. 42.11%, p = 0.006; 71.43% vs. 44.83%, p = 0.040). The 2 TT ratios were positively associated with the number of metaphase II oocytes and good‐quality embryos.ConclusionOf COS in a long GnRH‐a protocol with optimized outcome, serum TT kinetics appears to be characterized by sharp rises at the early and late stages of follicle growth. The ratios of TTΦ (10–12)‐d to TTinitial‐d and TTHCG‐d to TTinitial‐d may be predictors for pregnancy and qualitative outcomes of oocytes and embryos.

Preparation and administration of androgen deprivation therapy products: Retrospective survey results

AbstractLeuprolide acetate (LA) is a gonadotropin‐releasing hormone agonist used as androgen deprivation therapy for advanced prostate cancer. LA is available in formulations intended for intramuscular (IM‐LA) or subcutaneous (SC‐LA) administration. Post‐marketing reports have noted handling errors associated with the preparation and administration of SC‐LA. This study gathered real‐world evidence on administration and management of IM‐LA and SC‐LA in large, urology‐ or oncology‐based practices. Over 200 staff were invited; 151 participated in an online survey. Main outcomes were time for each step of the ordering, inventory, mixing and administration processes. Mean values and standard errors are reported for continuous variables, and frequency and percentage are reported for categorical variables. Comparisons between groups were made with t tests and chi‐square tests as appropriate. For IM‐LA and SC‐LA, ease of ordering and time to place an order (10.8 ± 1.3 vs. 10.6 ± 1.4 min, respectively) were similar. IM‐LA was associated with a shorter time to complete preparation (2.5 ± 0.2 vs. 6.1 ± 0.6 min, P < 0.001) compared with SC‐LA. This difference of 3.6 min per preparation could result in substantial time savings annually ranging from 120 h per year to 240 h per year in clinical practices administering 2000 injections per year or 4000 injections per year, respectively. For IM‐LA vs. SC‐LA, greater ease of preparation was reported by 64% vs. 43% of respondents, respectively. Over 15% of respondents used injection sites inconsistent with prescribing information, regardless of the type of injection. This study found that it takes a significantly shorter time to prepare and administer IM‐LA than SC‐LA in large urology‐ and oncology‐based practices. The time saved could be utilized for other tasks such as seeing additional patients. Use of injection sites inconsistent with prescribing information suggests a need for more training of nursing staff in the proper administration of these drugs to ensure adequate testosterone suppression and patient safety.

Association between duration of gonadotrophin-releasing hormone agonist use and cardiovascular risks: A population-based competing-risk analysis.

Although androgen deprivation therapy has known cardiovascular risks, it is unclear if its duration is related to cardiovascular risks. This study thus aimed to investigate the associations between gonadotrophin-releasing hormone (GnRH) agonist use duration and cardiovascular risks. This retrospective cohort study included adult patients with prostate cancer receiving GnRH agonists in Hong Kong during 1999-2021. Patients who switched to GnRH antagonists, underwent bilateral orchidectomy, had <6 months of GnRH agonist, prior myocardial infarction (MI), or prior stroke was excluded. All patients were followed up until September 2021 for a composite endpoint of MI and stroke. Multivariable competing-risk regression using the Fine-Gray subdistribution model was used, with mortality from any cause as the competing event. In total, 4038 patients were analyzed (median age 74.9 years old, interquartile range (IQR) 68.7-80.8 years old). Over a median follow-up of 4.1 years (IQR 2.1-7.5 years), longer GnRH agonists use was associated with higher risk of the endpoint (sub-hazard ratio per year 1.04 [1.01-1.06], p = 0.001), with those using GnRH agonists for ≥2 years having an estimated 23% increase in the sub-hazard of the endpoint (sub-hazard ratio 1.23 [1.04-1.46], p = 0.017). Longer GnRH agonist use may be associated with greater cardiovascular risks.

The cumulative live birth rate of recombinant follicle-stimulating hormone alfa verse urinary human follicle-stimulating hormone for ovarian stimulation in assisted reproductive technology cycles

BackgroundInfertility remains a significant public health concern. An issue with controlled ovarian stimulation (COS) is the selection of an exogenous gonadotropin (Gn) regimen, which is mainly based on urinary follicle-stimulating hormone (uFSH), recombinant follicle-stimulating hormone alfa (rFSH-alfa), and human menopausal gonadotropin (HMG). In addition, most previous studies focused on the clinical pregnancy rates or live birth rates (LBR) per transfer cycle, but not on the cumulative live birth rate (CLBR) per started cycle. The CLBR, appears to be a more comprehensive and accurate universal measure of IVF treatment success. Therefore, this study aimed to compare the cumulative live birth rate (CLBR) between rFSH-alfa and uFSH regimens for ovarian stimulation.MethodsThis retrospective cohort study included patients who underwent assisted reproductive technology (ART) with gonadotropin-releasing hormone (GnRH) agonist long protocol between March 2009 and December 2018. Patients were grouped according to the Gn regimen received (rFSH-alfa or uFSH). The main outcome was CLBR, which defined as the first live birth following the use of all fresh and frozen embryos derived from a single COS cycle.ResultsA total of 1078 cycles were analyzed (314 with rFSH-alfa and 764 with uFSH). The rFSH-alfa group was characterized by a higher number of retrieved oocytes (13.3 vs. 11.0) and transferable embryos (5.0 vs. 4.0), a higher fresh embryo transfer rate (35.0% vs. 26.3%), and a higher multiple birth rate among the fresh embryo transfer cycles (8.2% vs. 2.5%) (P < 0.05). There were no differences in pregnancy rate (32.7% vs. 33.8%) and LBR (25.5% vs. 26.9%) per transfer cycle (P > 0.05). No significant difference was found in clinical outcomes among the frozen embryo transfer cycles (P > 0.05). The CLBR per started cycle in the rFSH-alfa group was higher than in the uFSH group (53.5% vs. 43.1%, P < 0.05). After adjustment, rFSH-alfa was independently associated with a higher CLBR (OR = 1.56; 95%CI = 1.18–2.05; P = 0.0018).ConclusionsrFSH-alfa and uFSH have similar pregnancy rates and LBR per transfer cycle, rFSH-alfa might achieve more transferrable blastocysts and higher CLBR per started cycle compared to uFSH.

Current diagnosis and management of adenomyosis in Canada: A survey of Canadian gynaecologists

Objective: The purpose of this study was to understand how Canadian Obstetricians/Gynaecologists (OBGYNs) diagnose and manage adenomyosis. Methods: This cross-sectional study was performed via an online survey distributed to 262 OBGYNs at three Canadian universities (University of Toronto, University of Calgary, and McMaster University). Results: A total of 137 responses were obtained out of 262 OBGYNs (52.3%) with a completion rate of 98%. Adenomyosis was a diagnosis in 6%–10% of patients seen by OBGYNs. The most common clinical symptoms included heavy menstrual bleeding (HMB) (82.8%) and dysmenorrhea (91.0%). Most participants (83%) used transvaginal ultrasound (TVUS) as first-line imaging for diagnosis of adenomyosis. Many respondents (35.8%) indicated that adenomyosis was not associated with infertility or recurrent miscarriage. Treatment considerations for all patients with adenomyosis included levonorgestrel intra-uterine system (LNG-IUS) (91.8%), hysterectomy (88.8%), expectant management (85.1%), combined hormonal contraceptives (CHC) (83.6%), tranexamic acid (81.3%), gonadotropin releasing hormone (GnRH) agonists (64.2%), depo-provera (64.2%), dienogest (57.5%), and norethisterone acetate (NETA) (40.3%). Treatments for adenomyosis in patients wishing to conceive included expectant management (85.1%), tranexamic acid (79.1%), CHC (44.8%), LNG-IUS (32.8%), and GnRH agonists (35.8%). Excision of adenomyosis would only be offered by 24% of respondents. Uterine artery embolization (UAE) would not be used in the treatment of adenomyosis by 44% of respondents. Finally, 82.8% of respondents would use improvement of clinical symptoms to follow treatment success. Conclusion: Practice varies across Canada despite recent emerging evidence in the diagnosis and management of adenomyosis, highlighting the need for a clinical practice guideline on adenomyosis.

The pharmacokinetics of buserelin after intramuscular administration in pigs and cows

BackgroundBuserelin is a luteinizing hormone releasing hormone (LHRH) agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not fully understood. This study was designed to develop a sensitive method to determine the concentration of buserelin in blood plasma and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows.ResultsA sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studied in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h × ng/mL for pigs and 5.63 ± 1.86 h × ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ± 0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals.ConclusionThis study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.

For men with hormone-sensitive prostate cancer, how does degarelix compare with a gonadotropin-releasing hormone (GnRH) agonist?

For men with hormone-sensitive prostate cancer, how does degarelix compare with a gonadotropin-releasing hormone (GnRH) agonist?

A single-arm, open-label, phase 2 study evaluating pacritinib for patients with biochemical recurrence after definitive treatment for prostate cancer: Blast study.

TPS220 Background: Androgen deprivation therapy (ADT) achieved with gonadotropin releasing hormone (GnRH) agonist or antagonist is considered the standard of care for men with prostate cancer (PC) who develop biochemical recurrence (BCR) after definitive treatment. ADT is associated with significant adverse effects in this asymptomatic population, and hence there is an unmet need for alternate non-hormonal options. Androgen receptor (AR) and its variants (AR-V) are persistently expressed in the majority of the cells in recurrent PCs and drives PC growth. Jak2-Stat5 signaling has been shown to sustain PC cell viability and is critical for PC tumor growth. Stat5 activation in PC at the time of surgery predicts early PC recurrence. Our investigation of the molecular targets downstream of Jak2-Stat5 signaling have revealed the AR gene as a critical target, and the Jak2-Stat5 pathway represents a target to inhibit expression of diverse AR and AR-V species and thereby control of PC growth. Pacritinib (PAC) is a novel JAK2 inhibitor that suppresses wild-type Jak2 in cell-based assays and has demonstrated promising antitumor activity in myelofibrosis. We hypothesize that PAC inhibition of Jak2-Stat5 signaling will induce biochemical responses in men with recurrent PC by depleting AR and AR-V. Methods: BLAST (NCT04635059) is a single arm, open-label, phase 2 study of PAC (200mg BID) for patients with PC who underwent definitive treatment and developed BCR. Eligibility criteria include histologically confirmed PC, BCR with a PSA doubling time ≤ 9 months, PSA &gt; 0.5 ng/mL, and serum testosterone &gt; 150 ng/dL. 46 subjects will be enrolled with a primary objective to assess the effect of PAC on time to PSA progression. The primary endpoint is six-month PSA progression free survival per PCWG3 criteria. The null hypothesis that the median PSA-progression-free survival is six months will be tested against a one-sided alternative for the six-month PSA-progression-free survival probability exceeding 50%. Secondary endpoints include time to subsequent therapy, safety and toxicity. Exploratory endpoints include effect of PAC on geriatric domains. An interim analysis will be performed when 10 patients have been treated and followed for six months. Accrual began in July 2021. Clinical trial information: NCT04635059.

The novel oral gonadotropin-releasing hormone receptor antagonist relugolix is a new option for controlled ovarian stimulation cycles.

PurposeRelugolix is an oral gonadotropin‐releasing hormone antagonist (GnRHant), which was first introduced in 2019. This study investigated the effects of the conventional injectable GnRHant formulation and this new oral GnRHant formulation on controlled ovarian stimulation (COS) cycles.MethodsRelugolix was administered in 126 cycles and conventional GnRHant injection was administered in 658 cycles (controls). The follicle stimulation was performed by an antagonist method, and for final oocyte maturation, recombinant human chorionic gonadotropin (rHCG), or gonadotropin‐releasing hormone agonist (GnRHa), or both (dual trigger) were selected. The number of retrieved oocytes was counted and then they were evaluated for subsequent development up to cleavage stage.ResultsThe number of retrieved oocytes which was the primary outcome of this research was affected by the combination of GnRHant type and the final oocyte maturation agent. The combination of relugolix and a GnRHa trigger showed a significantly lower number of retrieved oocytes (p < 0.001) than the other combinations.ConclusionsRelugolix is a new option for COS cycles, but should be carefully combined with the final maturation agent.Clinical trial approvalThis study was conducted after approval by the Medical Corporation Sankeikai Institutional Ethics Committee (approval number: 2019‐34).

Medical Arrangement Strategies for Infertility Female Patients during COVID-19 Mini-Outbreak.

Over the past two years, COVID-19 pandemic is an unprecedented health emergency. All countries have taken their own measures to mitigate the spread of the virus in the first and subsequent mini-outbreaks of infection. In view of the current situation of small outbreaks of COVID-19, guidelines on epidemic prevention should be developed specifically for reproductive medical centers. It is necessary to establish a dynamic patient assessment and management system to identify patients who need priority fertility treatment during epidemic control. Female Patients were assigned as grade A and required hospitalization in the inpatient ward after egg retrieval. Patients who underwent controlled ovarian stimulation were classified as grade B, and they can choose to be hospitalizedat home according to their own convenience. Patients undergoing frozen embryo transfer (FET) cycle or planned downregulation with gonadotropinreleasing hormone agonists were defined as grade C, who could continue the assisted reproductive technology (ART) treatment cycle with negative COVID-19 nucleic acid test and there was no fever or respiratory symptoms. This brief comment summarizes the working procedure of the reproductive medical center in the first hospital of Lanzhou University in China to minimize the probability of hospital infection and ensure the safe conduct of assisted reproductive technology therapy.

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol

Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis.

Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients' prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients.

Long‐term reproductive evaluation of a bitch neonatally treated with a gonadotropin‐releasing hormone agonist

AbstractIn mammals, high concentrations of gonadotropins are necessary early in life to reach a full‐sized pool of ovarian follicles at the age of puberty. This case report describes the reproductive status of a 28‐month‐old, 9.1 kg, crossbred bitch (Bitch 1) which had been treated neonatally with 18.8 deslorelin acetate subcutaneously for contraceptive purposes. The female had just passed pubertal oestrus when hormones were measured and then spayed. The ovaries were histologically assessed. Two crossbred bitches were used for comparisons. Bitch 1's anti‐Müllerian hormone (AMH) and progesterone serum concentrations were 0.35 and 16.7 ng/ml, respectively. The total number of ovarian follicles and proportions were normal and the number of primary and antral follicles was increased. These findings might suggest an enhanced recruitment of the follicle pool to the growing population which could be related to the relatively low AMH concentrations.

Relugolix: A new kid on the block among gonadotrophin-releasing hormone antagonists

ABSTRACT Androgen-deprivation therapy (ADT) is the cornerstone of metastatic prostate cancer treatment. ADT can be achieved through surgical castration, or it may be induced either by gonadotrophin-releasing hormone (GnRH) agonists or GnRH antagonists. GnRH antagonists provide a more rapid castration alongside with a safer profile regarding adverse events. Degarelix is the sole GnRH antagonist used in clinical practice. Injection site reactions are the commonest adverse events related to the use of degarelix. Relugolix, a novel molecule, represents the first orally administered United States Food and Drug Administration approved GnRH antagonist, with clinical efficacy equal to that of the established ADT regimens. The main advantages of relugolix are the avoidance of the injection site reactions of GnRH antagonists such as degarelix alongside its patient-friendly oral administration. The aim of the present review article is to present novel data regarding the role of relugolix as ADT for the treatment of prostate cancer. Abbreviations: ADT: androgen-deprivation therapy; FDA: United States Food and Drug Administration

Treatment patterns in women seeking care for endometriosis at an endometriosis center

Objective: To determine the clinical characteristics and prior medical and surgical treatments in women undergoing surgical excision of endometriosis for pelvic pain at a single institution. Methods: In this retrospective cohort study we identified 140 women with pathology-proven endometriosis who completed a preoperative standardized pain form and underwent surgery at an endometriosis center. Women were stratified into three groups for analysis: no prior surgery, 1 prior surgery, and 2+ prior surgeries. Results: The most common treatments used prior to seeking care were hormonal contraceptives (51.6%) and surgery (46.1%). More than half of women were diagnosed with pelvic floor dysfunction at time of presentation or prior to consultation. There was a significant relationship between an increasing number of surgeries (none vs 1 vs 2+) and gonadotropin-releasing hormone (GnRH) agonist use (19.0% vs 27.5% vs 56.0%, p = 0.003). Though not significant, a trend was noted between increasing surgeries and opioid use (20.6% vs 30.0% vs 40.0%, p = 0.17). There was a statistically significant relationship between multiple surgeries and illicit drug use ( p &lt; 0.001). Conclusion: Patients with pelvic pain and endometriosis who have undergone multiple surgeries are more likely to have used GnRH agonists and report illicit drug use prior to presenting to specialized care.

P–644 Effect of a reduced dose of long-acting gonadotropin releasing hormone (GnRH) agonist versus short-acting GnRH agonist on pregnancy outcome in patients undergoing ICSI/ET cycles

Abstract Study question Are pregnancy outcome different between reduced dose of long-acting GnRH agonist and short-acting GnRH agonist in patients undergoing ICSI/ET cycles? Summary answer Clinical outcomes were not significantly different between the two group. What is known already There is no consensus on which of two GnRH agonist protocol is the most effective form and it has been challenging which one improves the clinical pregnancy rate. Study design, size, duration This is randomized clinical trial that 394 patients, who were candidates for ICSI/ET, were included in this study between April 2019 and January 2020. Participants/materials, setting, methods Patients were randomly divided into two groups using blocks of 8; hereby every 8 subjects were randomized, four were allocated to the long-acting GnRH agonist, and four were allocated to the short-acting GnRH agonist randomly. Main results and the role of chance No significant difference was noted between the two groups in progesterone and estradiol levels at hCG administration day. Despite no significant difference between the two groups in ART outcomes, interestingly rate of ovarian hyperstimulation syndrome (OHSS) occurrence was significantly higher in the short-acting group (P = 0.005). Limitations, reasons for caution We couldn’t evaluate the long-term consequence of pregnancy including live birth rate and effect of GnRH analogue on fetus. Wider implications of the findings: A lower rate of OHSS occurrence in the long-acting group, and similar ART outcomes in both groups. Trial registration number IRCT20190609043845N1

Does Transdermal Estrogen Therapy for Prostate Cancer Decrease Cardiovascular Toxicities

Luteinizing hormone–releasing hormone (LHRH) agonists are the most widely used agents to achieve medical castration. The original nonsurgical option

Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer.

BackgroundMedical castration, gonadotropin‐releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration.Methods and ResultsThis study included 149 patients who underwent medical castration using gonadotropin‐releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied. The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [P<0.001]; QTc, 416±27 to 439±31 ms [P<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy. In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients.ConclusionsMedical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.