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BJU International Jun 2024To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the...
Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) study: ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy.
OBJECTIVE
To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti-androgen' (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration-sensitive prostate cancer (mCSPC).
PATIENTS AND METHODS
Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2->0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression-free survival (rPFS), overall survival (OS), time to castration-resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan-Meier methods were used.
RESULTS
By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide-treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14-0.54), OS (HR 0.24, 95% CI 0.13-0.43), TTCRPC (HR 0.2, 95% CI 0.11-0.38), and TTPP (HR 0.11, 95% CI 0.04-0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06-0.22; P < 0.001) in apalutamide-treated patients.
CONCLUSIONS
In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy.
PATIENT SUMMARY
Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.
PubMed: 38940282
DOI: 10.1111/bju.16449 -
Frontiers in Endocrinology 2024This study aimed to evaluate the relationship between systemic immune-inflammation index (SII) and sex hormones in children and adolescents aged 6-19 years.
OBJECTIVES
This study aimed to evaluate the relationship between systemic immune-inflammation index (SII) and sex hormones in children and adolescents aged 6-19 years.
METHODS
Data were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Inclusion criteria comprised subjects aged 6-19 years with complete data on both SII and sex hormones. We employed weighted multiple regression analysis and subgroup analytical methods to independently estimate the relationship between SII and sex hormones.
RESULTS
In this study, a total of 3767 participants were included, with an average age of 12.32 ± 3.95 years. Males constituted 50.54%, and females 49.46%. Among males, a statistically significant negative correlation emerged between SII and sex hormone-binding globulin (SHBG). Similarly, in the female population, SII exhibited a statistically significant negative correlation with total testosterone (TT), SHBG, and the Ratio of TT to estradiol, while maintaining a positive correlation with free androgen index (FAI). Subgroup analysis underscored variances in the association between sex hormones and SII within cohorts distinguished by pubertal status or different body mass index (BMI). In addition, the relationship between SII and estradiol exhibited nonlinearity. Employing a two-segment linear regression model, we identified an inverted U-shaped association between SII and estradiol, with an inflection point of 748.09 (1000cell/ml).
CONCLUSION
Our findings suggest that SII may be an independent risk factor for changes in sex hormones in both male and female children and adolescents. More prospective and experimental studies should be conducted to validate our results and elucidate the underlying molecular pathways.
Topics: Humans; Adolescent; Female; Male; Child; Gonadal Steroid Hormones; Inflammation; Young Adult; Sex Hormone-Binding Globulin; Nutrition Surveys; Cross-Sectional Studies; Body Mass Index; Testosterone; Estradiol; Immunity
PubMed: 38938517
DOI: 10.3389/fendo.2024.1355738 -
European Journal of Endocrinology Jun 2024Androgen insensitivity syndrome (AIS) manifests itself as variable symptoms of under-virilization in patients with 46, XY disorders caused by androgen receptor (AR) gene...
CONTEXT
Androgen insensitivity syndrome (AIS) manifests itself as variable symptoms of under-virilization in patients with 46, XY disorders caused by androgen receptor (AR) gene variants. This large-sample study aimed to correlate the genotypes and phenotypes to the fertility of individuals.
METHODS
This was a cohort study that analyzed genetic and clinical characteristics of patients with AIS from a single center in China.
RESULTS
The 117 patients were divided into 53 with complete AIS (CAIS) and 64 with partial AIS (PAIS). At their first visit the median age was 1.83 years (0.92-4.17) and the EMS was 3.0 (2.0-6.0). At the last follow-up, 92% (49/53) of patients with CAIS maintained their female gender, and 94% (60/64) of patients with PAIS were raised as males. No gender anxiety was observed in this study. Eighty-eight AR variants were identified, with 31 (35%) being unreported. Moreover, 24% (21/88) occurred more than once. The variants that appeared most frequently were located at amino acid 841, including p.R841H(n=5) and p.R841C(n=2). Variants p.N706S, p.R856H, and p.A871V were each observed 4 times. In terms of inheritance, 83% of patients with parental verification inherited variants from their mothers. We also observed that the variants from one case were inherited from his maternal grandfather who had hypospadias.
CONCLUSION
Most children with PAIS were raised as males. The abundance of maternally inheritable variants and the presence of case of preserved fertility indicate the fertility potential in patients with AIS. Hence, we recommend a careful evaluation of gonadectomy when fertility preservation is being considered.
PubMed: 38938059
DOI: 10.1093/ejendo/lvae082 -
Journal of Nuclear Medicine : Official... Jun 2024Homeobox 13 (HOXB13) is an oncogenic transcription factor that directly regulates expression of folate hydrolase 1, which encodes prostate-specific membrane antigen...
Homeobox 13 (HOXB13) is an oncogenic transcription factor that directly regulates expression of folate hydrolase 1, which encodes prostate-specific membrane antigen (PSMA). HOXB13 is expressed in primary and metastatic prostate cancers (PCs) and promotes androgen-independent PC growth. Since HOXB13 promotes resistance to androgen receptor (AR)-targeted therapies and regulates the expression of folate hydrolase 1, we investigated whether SUVs on PSMA PET would correlate with HOXB13 expression. We analyzed 2 independent PC patient cohorts who underwent PSMA PET/CT for initial staging or for biochemical recurrence. In the discovery cohort, we examined the relationship between HOXB13, PSMA, and AR messenger RNA (mRNA) expression in prostate biopsy specimens from 179 patients who underwent PSMA PET/CT with F-piflufolastat. In the validation cohort, we confirmed the relationship between HOXB13, PSMA, and AR by comparing protein expression in prostatectomy and lymph node (LN) sections from 19 patients enrolled in F-rhPSMA-7.3 PET clinical trials. Correlation and association analyses were also used to confirm the relationship between the markers, LN positivity, and PSMA PET SUVs. We observed a significant correlation between PSMA and HOXB13 mRNA ( < 0.01). The association between HOXB13 and F-piflufolastat SUVs was also significant (SUV, = 0.0005; SUV, = 0.0006). Likewise, the PSMA SUV was significantly associated with the expression of HOXB13 protein in the F-rhPSMA-7.3 PET cohort ( = 0.008). Treatment-naïve patients with LN metastases demonstrated elevated HOXB13 and PSMA levels in their tumors as well as higher PSMA tracer uptake and low AR expression. Our findings demonstrate that HOXB13 correlates with PSMA expression and PSMA PET SUVs at the mRNA and protein levels. Our study suggests that the PSMA PET findings may reflect oncogenic HOXB13 transcriptional activity in PC, thus potentially serving as an imaging biomarker for more aggressive disease.
PubMed: 38936974
DOI: 10.2967/jnumed.123.267301 -
In Vivo (Athens, Greece) 2024When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent...
BACKGROUND/AIM
When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent therapy. The aim of this study was to determine the factors influencing the time to recovery of testosterone levels after discontinuation of HT and the likelihood of recovery.
PATIENTS AND METHODS
The study included a total of 108 patients with prostate cancer who were treated with GnRH agonist in combination with radiotherapy and followed up for at least 12 months after discontinuation of the GnRH agonist. The presence of recovery of testosterone levels and the time to recovery were investigated. Univariate and multivariate analyses were performed on several factors contributing to testosterone recovery, including age at initiation of HT, and the duration of HT.
RESULTS
Testosterone levels recovered in 61 cases (56.5%). The median time to recovery was 14.8 months. There was a significant difference in the recovery of testosterone levels between patients aged ≥71 years and those aged <71 years at the start of HT (p=0.002), and between those who had been on HT for ≥34 months and those for <34 months (p=0.031). In both univariate and multivariate analyses, age at initiation of HT and duration of HT contributed to the recovery of testosterone levels.
CONCLUSION
The rate of recovery of testosterone levels after long-term (median 34.3 months) HT was lower in patients who were older than 71 years at the start of HT.
Topics: Humans; Testosterone; Male; Aged; Prostatic Neoplasms; Middle Aged; Aged, 80 and over; Gonadotropin-Releasing Hormone; Combined Modality Therapy; Treatment Outcome; Antineoplastic Agents, Hormonal
PubMed: 38936898
DOI: 10.21873/invivo.13666 -
The Journal of Nutrition Jun 2024Infertility impacts 16% of North American couples, with male factor infertility contributing to ∼30% of cases. Reproductive hormones, especially testosterone, are...
BACKGROUND
Infertility impacts 16% of North American couples, with male factor infertility contributing to ∼30% of cases. Reproductive hormones, especially testosterone, are essential for spermatogenesis. Age-independent population-level decline in testosterone concentrations over the past few decades has been proposed to be a result of diet and lifestyle changes. Vitamin B is present in the testes and has been suggested as an adjuvant nutritional therapy for male infertility due to its potential to improve sperm parameters. However, evidence examining the relationship between vitamin B and reproductive hormones is limited.
OBJECTIVE
The objective was to cross-sectionally examine the relationship between serum vitamin B and male reproductive hormones (luteinizing hormone, follicular stimulating hormone, total testosterone, estradiol and prolactin).
METHODS
Men with infertility (n = 303) were recruited from Mount Sinai Hospital in Toronto, Canada. Serum was analyzed for vitamin B and reproductive hormones. Statistical analyses included non-parametric Spearman's rank correlation coefficient, linear regression, logistic regression and effect modification by age and BMI linear regressions.
RESULTS
An independent monotonic relationship between serum vitamin B and total testosterone (rho = 0.19, P = 0.001) was observed. Serum vitamin B was linearly associated with total testosterone (unadjusted ß = 0.0007, P = 0.008 and adjusted ß = 0.0005, P = 0.03). Compared to individuals in the lowest tertile of serum vitamin B, those in the middle tertile (adjusted OR = 0.48, 95% CI [0.25, 0.93], P = 0.03) and the highest tertile (unadjusted OR = 0.41, 95% CI [0.22, 0.77], P = 0.005 and adjusted OR = 0.44, 95% CI [0.22, 0.87], P = 0.02) had reduced odds of testosterone deficiency.
CONCLUSIONS
These findings suggest that among men with infertility, low serum vitamin B is associated with higher risk of testosterone deficiency and impaired androgenic hormonal profiles that impact spermatogenesis and consequently, fertility.
PubMed: 38936552
DOI: 10.1016/j.tjnut.2024.06.013 -
The Lancet. Oncology Jul 2024
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Antineoplastic Combined Chemotherapy Protocols; Androgen Antagonists; Neoplasm Metastasis; Treatment Outcome; Androgen Receptor Antagonists
PubMed: 38936382
DOI: 10.1016/S1470-2045(24)00335-8 -
American Society of Clinical Oncology... Jun 2024The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen... (Review)
Review
The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen deprivation therapy to an era of advanced imaging, precision diagnostics, genomics, and targeted treatment options. Concurrently, the emergence of large language models (LLMs) has dramatically transformed the paradigm for artificial intelligence (AI). This convergence of advancements in prostate cancer management and AI provides a compelling rationale to comprehensively review the current state of AI applications in prostate cancer care. Here, we review the advancements in AI-driven applications across the continuum of the journey of a patient with prostate cancer from early interception to survivorship care. We subsequently discuss the role of AI in prostate cancer drug discovery, clinical trials, and clinical practice guidelines. In the localized disease setting, deep learning models demonstrated impressive performance in detecting and grading prostate cancer using imaging and pathology data. For biochemically recurrent diseases, machine learning approaches are being tested for improved risk stratification and treatment decisions. In advanced prostate cancer, deep learning can potentially improve prognostication and assist in clinical decision making. Furthermore, LLMs are poised to revolutionize information summarization and extraction, clinical trial design and operations, drug development, evidence synthesis, and clinical practice guidelines. Synergistic integration of multimodal data integration and human-AI integration are emerging as a key strategy to unlock the full potential of AI in prostate cancer care.
Topics: Humans; Male; Prostatic Neoplasms; Artificial Intelligence
PubMed: 38935882
DOI: 10.1200/EDBK_438516 -
Indian Journal of Public Health Oct 2023Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrinological disorders affecting 6%-8% of women in reproductive years. An early liberal...
BACKGROUND
Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrinological disorders affecting 6%-8% of women in reproductive years. An early liberal PCOS screening appears to be a cost-effective strategy, benefiting earlier diagnosis and intervention.
OBJECTIVES
The objectives are to measure the prevalence of PCOS and factors associated with PCOS among young girl students of a University in Central Gujarat.
MATERIALS AND METHODS
All consenting girl medical students enrolled in MBBS curriculum during 2013-2017 were given a self-administered questionnaire (for signs and symptoms of PCOS), taking due prior permissions; during January 2018-June 2019. Using Rotterdam (2006) criteria, those who were screened for PCOS were subjected to abdominal ultrasonography (USG) and if required, laboratory investigations (random blood sugar, thyroid-stimulating hormone, and free testosterone). The proportion of young women having PCOS as per the Rotterdam and European Society for Human Reproduction and Embryology (EHSRE) Criteria are reported.
RESULTS
The study enrolled 308 girl medical students. More than one-tenth of the study participants (11.7%, 36/308) had confirmed PCOS (Rotterdam Criteria). As per the EHSRE criteria, 24/36 had classic PCOS, 11/36 had ovulatory phenotype, and 01/36 had the non-hyperandrogenic phenotype PCOS. USG was required in 123/308 (39%); of which 91 consented and 16/91 (18%) had conclusive PCOS. Twenty-three girls required laboratory investigations, of which two had abnormal values suggestive of PCOS. Irregular menses and hirsutism were significantly associated with the PCOS (P < 0.05).
CONCLUSION
The proportion of young medical students with PCOS was 12%. Irregular menses and hirsutism were significantly associated with PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Cross-Sectional Studies; India; Adolescent; Prevalence; Universities; Young Adult; Students, Medical; Hirsutism
PubMed: 38934823
DOI: 10.4103/ijph.ijph_1508_22 -
Medicine and Science in Sports and... Jun 2024Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations...
PURPOSE
Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations between acute and chronic changes in skeletal muscle total AR, cytoplasmic AR (cAR), nuclear AR (nAR) and AR DNA-binding (AR-DNA) induced by resistance training (RT) and hypertrophy outcomes in women and men. This study aimed to investigate the acute and chronic effects of RT on skeletal muscle total AR, cAR, nAR contents and AR-DNA in women and men. Additionally, we investigated whether these acute and chronic changes in these markers were associated with muscle hypertrophy in both sexes.
METHODS
Nineteen women and 19 men underwent 10 weeks of RT. Muscle biopsies were performed at baseline, 24 h after the first RT session and 96-120 h after the last session. AR, cAR and nAR were analyzed using Western blotting, and AR-DNA using an ELISA-oligonucleotide assay. Fiber cross-sectional area (fCSA) was analyzed through immunohistochemistry and muscle cross-sectional area (mCSA) by ultrasound.
RESULTS
At baseline, men demonstrated greater nAR than women. Baseline cAR was significantly associated with type II fCSA hypertrophy in men. Acutely, both sexes decreased AR and cAR, whereas men demonstrated greater decreases in nAR. After 10 weeks of RT, AR and nAR remained unchanged, men demonstrated greater cAR compared to women, and both sexes decreased AR-DNA activity. Acute and chronic changes in AR markers did not correlate with muscle hypertrophy (type I/II fCSA and mCSA) in women or men.
CONCLUSIONS
Baseline cAR content may influence hypertrophy in men, while neither RT-induced acute nor chronic changes in AR, cAR, nAR, and AR-DNA are associated with muscle hypertrophy in women or men.
PubMed: 38934511
DOI: 10.1249/MSS.0000000000003509