ArticleBiology of sex differences2023
Sex hormones influence survival of patients with metastatic urothelial carcinoma undergoing immune checkpoint therapy.
Article in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.Biology of sex differences · 2026Review
- A Review of the Latest Evidence on Prognostic Factors in Locally Advanced and Metastatic Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors.Medicina (Kaunas, Lithuania) · 2025Review
- Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Elucidating Sex-Specific Immune Profiles in a Breast Cancer Model.International journal of molecular sciences · 2024Article
- The potential role of exercise in mitigating fertility toxicity associated with immune checkpoint inhibitors (ICIs) in cancer patients.The journal of physiological sciences : JPS · 2024Review
- Women patients with small-cell lung cancer using immunotherapy in a real-world cohort achieved long-term survival.Thoracic cancer · 2024Article
- Inhibition of inosine metabolism of the gut microbiota decreases testosterone secretion in the testis.mSystems · 2024Article
- Sexual dimorphism in bladder cancer: a review of etiology, biology, diagnosis, and outcomes.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionClinical trials investigating efficacy of immune checkpoint inhibitors (ICI) revealed sex-specific divergent outcomes in urothelial cancer (UC), suggesting that sex hormones might play an important role in gender-specific dimorphisms of response upon ICI. However, further clinical investigations are still needed to understand the influence of sex hormones in UC. The aim of this study was to get further insights on the prognostic and predictive value of sex hormone levels in patients with metastatic UC (mUC) who underwent ICI. MATERIAL AND
methodsSex hormone levels of patients with mUC including luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH ratio, prolactin, testosterone and 17β-estradiol (E2) were evaluated at baseline and during ICI at 6/8 weeks and 12/14 weeks.
resultsTwenty-eight patients (10 women, 18 men) with a median age of 70 years were included. Metastatic disease was confirmed in 21 patients (75%) after radical cystectomy while seven patients showed mUC at first diagnosis. Twelve patients (42.8%) received first line and 16 patients second line pembrolizumab. The objective response rate (ORR) was 39% (CR in 7%). The median progression-free survival (PFS) and overall survival (OS) was 5.5 and 20 months. Focusing on changes of sex hormone levels during ICI, a significant increase in FSH levels and decrease of the LH/FSH ratio was noticed in responders (p = 0.035), yet without sex-specific significance. When adjusted for sex and treatment line, a significant increase of FSH levels was confirmed in men during second line pembrolizumab. Focusing on baseline levels, LH/FSH ratio was significantly higher in female responders (p = 0.043) compared to non-responders. In women, increased LH levels and LH/FSH ratio were associated with better PFS (p = 0.014 for LH, p = 0.016 for LH/FSH ratio) and OS (p = 0.026 and p = 0.018). In male patients, increased E2 levels were linked with improved PFS (p < 0.001) and OS (p = 0.039).
conclusionIncreased LH and LH/FSH values in women as well as high E2 levels in men were significant predictors of better survival. Elevated LH/FSH ratio was predictive of better response to ICI in women. These results show first clinical evidence of the potential role of sex hormones as prognostic and predictive biomarker in mUC. Further prospective analyses are needed to corroborate our findings.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.