leuprolide (Lutrate)

Efficacy and safety of goserelin vs. leuprolide in premenopausal breast cancer patients receiving adjuvant endocrine therapy: A retrospective cohort study.

Xu Jiahao J, Tai Yicheng Y, Fang Qi Q, Xue Hui H et al.

Goserelin and leuprolide are gonadotropin-releasing hormone (GnRH) agonists used for ovarian function suppression in premenopausal breast cancer patients. Whether their different molecular structures lead to clinically meaningful differences in efficacy and safety remains unclear. To compare the efficacy and safety of goserelin versus leuprolide as adjuvant endocrine therapy (combined with tamoxifen) in premenopausal women with hormone receptor-positive breast cancer after curative surgery. This retrospective cohort study initially recruited 215 young cancer patients receiving adjuvant chemotherapy with tamoxifen combined with a gonadotropin-releasing hormone agonist. After applying inclusion and exclusion criteria, 187 patients were included and divided into two groups according to the gonadotropin-releasing hormone agonist they actually received: leuprolide (n=90) or goserelin (n=97). The primary efficacy outcome was the proportion of patients achieving substantial estrogen reduction (estradiol ≤30 pg/mL or falling into the pre-specified laboratory range) after 6 months. Secondary outcomes included liver function parameters and thyroid function parameters. Exploratory outcomes included changes from baseline to six months in testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels, as well as descriptive assessment of the tumor marker carcinoembryonic antigen (CEA). Between-group differences were expressed as risk differences (RDs) with 95% confidence intervals (CIs). Baseline demographic and cancer-related characteristics were balanced between the two groups. After six months of adjuvant therapy, the two groups showed similar primary efficacy: the proportion of patients with substantial estrogen reduction was 88.89% in the leuprolide group and 92.78% in the goserelin group (RD = -3.89%, 95% CI: -12.18% to 4.40%; p = 0.354). Regarding safety, the leuprolide group had a significantly higher rate of liver function abnormalities (30.00% vs. 13.40%; RD = 16.60%, 95% CI: 4.96% to 28.24%; p = 0.012), driven mainly by a lower rate of normal aspartate aminotransferase (AST) levels (85.56% vs. 96.91%; RD = -11.35%, 95% CI: -19.39% to -3.31%; p < 0.05). In contrast, the leuprolide group had a higher rate of normal thyroid function (88.89% vs. 76.29%; RD = 12.60%, 95% CI: 1.94% to 23.26%; p = 0.018), mainly due to a higher normal thyroid-stimulating hormone rate (93.33% vs. 83.51%; RD = 9.82%, 95% CI: 0.82% to 18.82%; p < 0.05). Carcinoembryonic antigen normalization rates were also comparable (93.33% vs. 92.78%; RD = 0.55%, 95% CI: -6.74% to 7.84%; p = 0.549). Leuprolide and goserelin demonstrate similar efficacy when used as adjuvant therapy in combination with tamoxifen for young women with breast cancer. However, leuprolide may pose a potential risk of hepatic impairment, whereas goserelin appears to be associated with a higher incidence of thyroid injury. These findings provide a theoretical basis for personalized clinical management in this patient population.

Divergent Effects of GnRH Agonist and GnRH Antagonist Treatment on Platelet Activity and Transcriptome.

Beitzen-Heineke Antonia A, Siskin Matthew M, Muller Matthew M, Bhatt Anshini A et al.

Prostate cancer is associated with increased cardiovascular risk. Among androgen deprivation therapy (ADT) modalities, the gonadotropin-releasing hormone (GnRH) antagonist relugolix appears to confer a lower risk for cardiovascular events than the GnRH agonist leuprolide. The aim of this prospective study was to investigate the impact of relugolix and leuprolide on platelet phenotype. Patients with prostate cancer initiating first-line ADT were prospectively enrolled. Blood samples were collected at baseline and 8 ± 4 weeks after treatment initiation. Platelet activation was assessed using flow cytometry (P-selectin, PAC-1, CD40, CD40L, and monocyte-platelet aggregates). Platelet RNA sequencing was performed to characterize treatment-associated transcriptomic changes. Compared with healthy control subjects, patients (n = 69) exhibited elevated P-selectin expression and enrichment of thromboinflammatory pathways. During leuprolide treatment (n = 40), PAC-1 expression increased compared with baseline in response to epinephrine, thrombin, adenosine diphosphate (ADP) and arachidonic acid (AA), while P-selectin increased in response to epinephrine and was higher with ADP and AA, though not statistically different. In contrast, during relugolix treatment (n = 29), AA-induced P-selectin expression and CD40 decreased. Platelet RNA sequencing in relugolix-treated patients demonstrated down-regulation of pathways associated with platelet activation and aggregation. Finally, leuprolide-treated patients on aspirin (n = 6) did not exhibit increased AA-induced platelet activation and in vitro P2Y12 inhibition of patient-derived platelets attenuated activation induced by epinephrine, ADP, and AA. Prostate cancer is associated with heightened platelet activation and thromboinflammatory signaling. Treatment with leuprolide, but not relugolix, was associated with further augmented platelet activity. These findings support further studies to clarify links with platelet-mediated cardiovascular risk and the potential role of platelet-targeted strategies.

Statin Use Attenuates Leuprolide-Associated Coronary Atherosclerosis Progression: A Secondary Analysis of the REVELUTION Trial.

Yadalam Adithya K AK, Liu Chang C, van Assen Marly M, Sebastian Nikhil T NT et al.

Revisiting the Association of Central Precocious Puberty with Neurovisceral Diseases owing to a Girl with Niemann-Pick Disease Type C.

Arslan Gülten Zümrüt Z, Karacabey Burçin Nazlı BN, Aydın Behram Bilge B, Onay Hüseyin H et al.

Niemann-Pick type C disease (NP-C) is a rare neurovisceral disorder caused by mutations in the NPC1 or NPC2 genes. Clinical symptoms of NP-C can appear at any age. Here we report a case of a girl diagnosed with NP-C who subsequently developed central precocious puberty (CPP). To our knowledge, this association has not been described in the literature till now. An 8 year old girl was referred to the pediatric metabolism outpatient clinic due to poor school performance, behavioral changes and periventricular white matter signal changes observed on cranial magnetic resonance imaging (MRI). The physical examination revealed vertical supranuclear gaze palsy (VSGP) and splenomegaly. The patient was diagnosed NP-C through genetic analysis and was started miglustat treatment. The patient was also referred to the pediatric endocrinology outpatient clinic due to breast development (Tanner stage 3) and pubic hair (Tanner stage 3). Laboratory work up revealed normal basal serum LH (0. 2 U/L) and the LHRH test showed a LH value of 8.48 U/L and a peak LH/ FSH ratio of 2. 8 (>0.66). Pelvic ultrasonography revealed an uterine length of 45 mm and mean ovarian volume of 5. 5 mL, Leuprolide acetate was started and at the first year of follow-up the patient's height velocity was 0.4 SDS and Tanner's pubertal staging was 3. This case report highlights a potential association of NP-C with CPP and confirms the need for careful assessment of pubertal development in patients with white matter disease.