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Despite theoretical benefits of intermittent as compared with continuous androgen-deprivation therapy in patients with metastatic prostate cancer, intermittent therapy did not result in longer survival or long-term improvement in quality of life. Prostate cancer is an androgen-dependent disease, and continuous androgen deprivation has been the standard therapy for metastatic hormone-sensitive disease. Despite a high response rate, resistance to androgen-deprivation therapy occurs in most patients, resulting in a median survival of 2.5 to 3 years. 1 , 2 There is evidence suggesting that progression to castration resistance is adaptive in part, and pathways involving the androgen receptor, as well as cell-survival pathways independent of the androgen receptor, have been implicated. 3 , 4 Data from an androgen-dependent tumor model have suggested that androgen withdrawal alters the ratio of putative stem cells in the tumor-cell population. 5 Initially, differentiated . . .

A course of androgen-deprivation therapy before and during radiotherapy prolonged 10-year survival by about 7% among men with intermediate-risk prostate cancer. The risk of erectile dysfunction from the addition of hormone therapy was also about 7% higher. In the 1980s, advances in both surgery and radiotherapy for clinically localized prostate cancer led to their acceptance as successful treatments, with considerable reductions in harmful side effects as compared with earlier treatments. 1 In the 1990s, reversible androgen suppression with the use of luteinizing hormone–releasing hormone analogues and oral antiandrogen agents was shown to induce apoptotic regression in androgen-responsive cancers, 2 potentially improving the prospects of local control and the duration of survival free of metastatic disease. Among patients with locally advanced disease, phase 3 clinical trials 3 , 4 showed that when added to radiotherapy, long-term treatment with these agents (≥2 years) . . .

Background Metastatic prostate cancer is commonly treated with androgen deprivation therapy (ADT) and chemotherapy, which often leads to treatment resistance and disease progression with limited effective interventions. Recent advances in robotic surgery and precision radiotherapy have prompted research into comprehensive treatments for low-burden metastatic prostate cancer, particularly oligometastatic prostate cancer (OMPC). Our phase I/II clinical study confirmed the safety and efficacy of neoadjuvant radiotherapy combined with endocrine therapy before radical prostatectomy, warranting further investigation. Methods This study protocol outlines a prospective, open-label, multicenter, randomized controlled trial to evaluate preoperative neoadjuvant radiohormonal therapy versus standard care in OMPC. The experimental group receives LHRHa, abiraterone, IMRT for pelvic lesions, and SBRT for extrapelvic lesions, followed by RARP and lymph node dissection. The control group receives long-term LHRHa and abiraterone. The primary endpoint is 3-year failure-free survival (FFS), and secondary endpoints include time to CRPC, 2-year FFS, OS, TRG rating, and complications. Conclusion This trial is the first to assess whether neoadjuvant radiohormonal therapy with robotic prostatectomy offers better prognostic outcomes than long-term endocrine therapy alone for OMPC. The results aim to provide high-level evidence for this approach, potentially influencing future treatment protocols. Trial registration The study has been registered on clinicaltrials.gov (NCT05707468). Registered on February 1, 2023.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

Context:The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients’ presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH.Objective:To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD.Design:Prospective, self-controlled, 3-month clinical trial.Settings:University endocrine clinic.Patients:Men with hypogonadotropic hypogonadism caused by CCPHD.Intervention:Pulsatile GnRH was administered subcutaneously for 3 months.Main outcome measures:Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis.Results:A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk.Conclusions:This study suggests that gonadotrophs in patients with CCPHD can exist and be functional—even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary–testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.This study found pulsatile gonadotropin-releasing hormone therapy restored pituitary-testis axis function in 60% of male patients with congenital combined pituitary hormone deficiency.

Background Diphereline is a Gonadotropin-Releasing Hormone agonist commonly used in patients with breast cancer. This study aimed to compare the efficacy and safety of one-month and three-month Microrelin injections produced by Homa Pharmed Company with three-month Diphereline injections manufactured by IPSEN, France. Methods The study was a non-inferiority randomized clinical trial conducted between 2019 and 2023 on premenopausal women candidates for endocrine therapy. The participants were randomly assigned in blocks of six to one of three groups named A (Diphereline 11.25 mg), B (Microrelin 11.25 mg), and C (Microrelin 3.75 mg). The participants’ menopausal symptoms, estradiol, and FSH serum levels were recorded in three-month intervals for one year. The efficacy of each medication and its side effects were compared among the three groups by statistical analysis during the one-year follow-up. Results The study included 133 patients with breast cancer. A decreasing trend in the serum levels of FSH and estradiol and an increasing trend of menopausal symptoms were recorded during the study. No specific side effects leading to drug disruption, hospitalization, or exclusion from the study were observed. Adjusting the effect of study group and time showed no significant changes in estradiol levels between groups B (p = 0.506) and C (p = 0.607) and group A. Also, serum FSH changes between groups B (p = 0.132) and C (p = 0.104) compared to group A were not significant. Moreover, the menopausal symptoms during the one-year follow-up did not significantly increase in group B (p = 0.108) and C (p = 0.113) compared to group A. Conclusions It can be concluded that injections of both Microrelin 11.25 mg and 3.75 mg, produced by Homa Pharmed, Iran, are non-inferior in terms of effectiveness and incidence of menopausal symptoms compared to Diphereline, manufactured by IPSEN, France. Trial registration IRCT.ir, IRCT20201227049847N1; Registered on 09/01/2021.

Background The selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation. Methods A total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed. Results Out of a total of 681 oocytes, 189 (27.8 %) were morphologically normal, 220 (32.3 %) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist-treated groups ( P  ≫ 0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups ( P  ≫ 0.05). Conclusions Our randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.

PurposeTo compare the effects of preoperative dienogest (DNG) and gonadotropin-releasing hormone (GnRH) agonist administration on the improvement of preoperative symptoms and surgical outcomes in patients who underwent laparoscopic cystectomy for ovarian endometriomas.MethodsSeventy patients who were scheduled for laparoscopic surgery were enrolled in the study. They were divided into two groups: 35 patients who received DNG for 4 months preoperatively (group D) and 35 patients who received low-dose sustained-release goserelin acetate for 4 months preoperatively (group G). Preoperative outcomes, including pain score associated with endometriosis, using the numerical rating scale (NRS), adverse events of hormonal therapy and Kupperman index (KI) before and after treatment, surgical outcomes including total surgical duration and blood loss, and postoperative recurrence of endometrioma were compared between the two groups.ResultsRegarding preoperative symptoms, NRS and KI at 4 months after preoperative hormonal therapy were significantly lower in group D than in group G (NRS, 5.3 ± 5.5 vs. 2.7 ± 3.9; P = 0.01; KI, 16.0 ± 11.0 vs. 9.2 ± 7.6; P = 0.006). Regarding adverse events, the incidence of hot flashes was significantly lower in group D than in group G (P < 0.001). Meanwhile, the incidence of breast pain and metrorrhagia was significantly higher in group D than in group G (P = 0.04 and P < 0.001, respectively). The total surgical duration and blood loss were not significantly different between the groups. At 12 months after surgery, ovarian endometrioma did not recur in either group.ConclusionPreoperative administration of DNG is more valuable for patients with endometriosis and scheduled for laparoscopic surgery to improve symptoms with good efficacy and tolerability than the administration of GnRH agonist.

Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (follicle-stimulating hormone (FSH) level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12–45 years were evaluated (7 in the intervention group and 10 in the observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at a median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure.

Objective To compare the efficacy of dienogest and GnRH-a after endometriosis surgery. Methods Patients with endometriosis who were admitted to our hospital from December 2020 to March 2022 were randomly collected. A total of 81 patients were collected and divided into 40 cases in the control group and 41 cases in the observation group. Among them, the control group was treated with GnRH-a drug, and the observation group was treated with dienogest (DNG). Results The study found that the therapeutic effects of the two drugs were basically the same in patients with endometriosis. The VAS and Kupperman scores of the control group were 0.78 ± 0.8, 3.9 ± 1.84, P  < 0.05, respectively; the VAS and Kupperman scores of the observation group were 0.73 ± 0.78, 1.55, respectively ± 1.24, P  < 0.05, the difference was statistically significant.In the case of postoperative recurrence, the observation group was better than the control group, with 8 cases of recurrence in the control group and 2 cases of recurrence in the observation group,  P  < 0.05. Conclusion In the comparison of postoperative efficacy of the two drugs on patients with endometriosis, dienogest is better than GnRH-a adjuvant drug in postoperative recurrence, and has a good improvement and application, which is worthy of further promotion in clinical practice.