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Minerva Urology and Nephrology Apr 2024Patients with high-risk prostate cancer (HRPCa) are prone to have worse pathological features, resulting in early biochemical recurrence after radical prostatectomy...
INTRODUCTION
Patients with high-risk prostate cancer (HRPCa) are prone to have worse pathological features, resulting in early biochemical recurrence after radical prostatectomy (RP). There is an urgent need to develop novel treatment strategies for this group of patients to optimize their outcomes. The purpose of this study is to perform a systematic review of the role of neoadjuvant hormonal therapy (NHT) followed by RP in HRPCa patients.
EVIDENCE ACQUISITION
We performed a systematic review of the following databases, MEDLINE (PubMed), EMBASE, Cochrane Library, and clinical Trial.gov; between January 2007 and August 2023, following the PRISMA guidelines.
EVIDENCE SYNTHESIS
After screening and deduplication, we included ten studies from an initial pool of 1275. The risk of bias was low in observational studies but ranged from moderate to low in controlled trials. Five studies utilized traditional androgen deprivation treatments (ADT), revealing favorable pathological outcomes but inconsistency in evaluating oncological results. Additionally, four studies focused on RP combined with androgen receptor pathway inhibitors (ARPIs) in the NHT setting, all showing primarily positive pathological outcome, with no clear evidence of an oncological benefit. Limited long-term follow-up data and a shortage of randomized controlled trials were evident among all the studies included in this review, regardless of the type of hormonal treatment used.
CONCLUSIONS
Different hormonal treatments, including traditional ADT and ARPIs, yield positive pathology outcomes. Oncological evidence remains limited, echoing older findings predating ARPIs. Definitive conclusions require longer follow-ups and precise patient selection. Currently, insufficient evidence support ARPIs' superiority over conventional therapy before RP.
Topics: Humans; Prostatectomy; Prostatic Neoplasms; Male; Androgen Antagonists; Neoadjuvant Therapy; Risk Assessment
PubMed: 38742549
DOI: 10.23736/S2724-6051.24.05630-1 -
Endocrinology May 2024Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the...
Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.
Topics: Animals; Female; Follicle Stimulating Hormone; Mice; Ovarian Follicle; Transcriptome; Dose-Response Relationship, Drug; Oocytes; Oogenesis; Signal Transduction; Granulosa Cells; Cyclic AMP
PubMed: 38735763
DOI: 10.1210/endocr/bqae054 -
Nutrients Apr 2024Considering a lack of respective data, the primary objective of this study was to assess whether seasonal variation in vitamin D status (D-status) affects the extent of...
Considering a lack of respective data, the primary objective of this study was to assess whether seasonal variation in vitamin D status (D-status) affects the extent of improvement in physical performance (PP) in conscripts during basic military training (BMT). D-status, PP and several blood parameters were measured repeatedly in conscripts whose 10-week BMT started in July (cohort S-C; = 96) or in October (cohort A-C; = 107). D-status during BMT was higher in S-C compared to A-C (overall serum 25(OH)D 61.4 ± 16.1 and 48.5 ± 20.7 nmol/L, respectively; < 0.0001). Significant ( < 0.05) improvements in both aerobic and muscular endurance occurred in both cohorts during BMT. Pooled data of the two cohorts revealed a highly reliable ( = 0.000) but weak (R = 0.038-0.162) positive association between D-status and PP measures both at the beginning and end of BMT. However, further analysis showed that such a relationship occurred only in conscripts with insufficient or deficient D-status, but not in their vitamin D-sufficient companions. Significant ( < 0.05) increases in serum testosterone-to-cortisol ratio and decreases in ferritin levels occurred during BMT. In conclusion, a positive association exists between D-status and PP measures, but seasonal variation in D-status does not influence the extent of improvement in PP in conscripts during BMT.
Topics: Humans; Seasons; Vitamin D; Military Personnel; Male; Physical Endurance; Young Adult; Hydrocortisone; Vitamin D Deficiency; Nutritional Status; Testosterone; Adult; Cohort Studies; Adolescent
PubMed: 38732553
DOI: 10.3390/nu16091306 -
JAMA Oncology Jun 2024Metastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to... (Review)
Review
IMPORTANCE
Metastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to castration-resistant disease, the terminal phase. This review provides a summary of the most recent evidence for current and emerging management strategies, including treatment intensification with combinations of therapies. It also provides recommendations on applying the evidence in clinical practice to encourage appropriate treatment to improve survival outcomes among patients with metastatic hormone-sensitive prostate cancer.
OBSERVATIONS
Androgen-deprivation therapy is the backbone of treatment for metastatic hormone-sensitive prostate cancer; however, it is insufficient alone to provide sustained disease control and long-term survival. Addition of an androgen receptor pathway inhibitor and/or docetaxel significantly improves survival, as demonstrated by several international phase 3 randomized clinical trials. Triplet therapy composed of androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel has been shown to improve overall survival over androgen-deprivation therapy plus docetaxel. In the ARASENS trial (darolutamide), the hazard ratios (HRs) were 0.68 (95% CI, 0.57-0.80) in the overall population; 0.71 (95% CI, 0.59-0.85) and 0.61 (95% CI, 0.35-1.05) in patients with de novo and recurrent disease, respectively; 0.69 (95% CI, 0.57-0.82) and 0.72 (95% CI, 0.41-1.13) in patients with high-volume and low-volume disease, respectively; and 0.71 (95% CI, 0.58-0.86) and 0.62 (95% CI, 0.42-0.90) in patients with high-risk and low-risk disease, respectively. In the PEACE-1 trial (abiraterone acetate + prednisone), the HRs were 0.75 (95% CI, 0.59-0.95; all de novo) in the overall population and 0.72 (95% CI, 0.55-0.95) and immature in the high-volume and low-volume subgroups, respectively. In the ENZAMET trial (enzalutamide), the HRs were 0.82 (95% CI, 0.63-1.06) in the overall population; 0.73 (95% CI, 0.55-0.99) and 1.10 (95% CI, 0.65-1.86) in the de novo and recurrent subgroups, respectively; and 0.87 (95% CI, 0.66-1.17) and 0.61 (95% CI, 0.33-1.10) in the high-volume and low-volume subgroups. Combination regimens are generally well tolerated, with adverse effects dependent on the profiles of the component drugs.
CONCLUSIONS AND RELEVANCE
The findings of this review show compelling evidence from phase 3 randomized clinical trials in favor of initiating triplet combination therapy for patients with metastatic hormone-sensitive prostate cancer for the best overall survival. Patients who are eligible for chemotherapy should be offered androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel, particularly patients with high-volume, high-risk, or de novo metastatic disease.
Topics: Humans; Male; Antineoplastic Combined Chemotherapy Protocols; Androgen Antagonists; Prostatic Neoplasms; Treatment Outcome; Neoplasm Metastasis; Androgen Receptor Antagonists; Docetaxel
PubMed: 38722620
DOI: 10.1001/jamaoncol.2024.0591 -
The Aging Male : the Official Journal... Dec 2024Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential... (Review)
Review
Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 - 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.
Topics: Humans; Male; Hypogonadism; Middle Aged; Leydig Cells; Reference Values; Proteins; Testosterone; Biomarkers; Aged; Adult; Insulins; Insulin
PubMed: 38676285
DOI: 10.1080/13685538.2024.2346322 -
Clinica Chimica Acta; International... May 2024Self-collected capillary samples are convenient for direct access testing (DAT), but exogenous testosterone use may cause falsely elevated total testosterone (TT)...
BACKGROUND
Self-collected capillary samples are convenient for direct access testing (DAT), but exogenous testosterone use may cause falsely elevated total testosterone (TT) results. We designed a quality assurance workflow to differentiate between accurate or erroneous supraphysiological TT concentrations.
METHODS
Clinical samples with TT > 1500 ng/dL were reflexed to luteinizing hormone (LH) and follicle stimulating hormone (FSH) and screened for exogenous testosterone use. Samples (n = 120) with normal TT were reflexed to LH/FSH as a control.
RESULTS
A total of 8572 TT samples were evaluated, of which 533 (6.2 %) had TT > 1500 ng/dL and were reflexed. Of these, 441 (82.7 %) had significantly decreased LH/FSH (<0.85/<0.7mIU/mL, respectively), 72 (13.5 %) had normal or borderline normal LH/FSH, and 20 (3.8 %) had insufficient plasma volume. In patients with TT > 1500 ng/dL, injectable exogenous testosterone use was most commonly accompanied by significantly decreased LH/FSH, while topical testosterone use was most commonly accompanied by detectable LH/FSH. Control samples were almost all (99.2 %) within or above the LH/FSH reference intervals. Unique patients ordered 351 TT tests where at least one TT result was > 1500 ng/dL. Based on TT and LH/FSH results, we hypothesized that patients were intermittently or consistently overusing exogenous testosterone, resolved elevated TT with recollection, or repeatedly contaminated their sample.
CONCLUSION
Self-collected capillary specimens are acceptable for TT testing. A quality assurance reflex to LH/FSH can determine the validity of supraphysiological TT results in a consumer initiated/DAT population.
Topics: Humans; Testosterone; Male; Luteinizing Hormone; Follicle Stimulating Hormone; Adult; Middle Aged; Capillaries; Female; Blood Specimen Collection
PubMed: 38631605
DOI: 10.1016/j.cca.2024.119676 -
Diagnostics (Basel, Switzerland) Mar 2024Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women, and its diagnosis rests on three principal features: ovulatory/menstrual dysfunction, clinical...
Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women, and its diagnosis rests on three principal features: ovulatory/menstrual dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology (PCOM). Currently, data on age- and ethnicity-dependent features of PCOM remain insufficient. We aimed to estimate ethnicity- and age-dependent differences in ovarian volume (OV) and follicle number per ovary (FNPO) in a healthy, medically unbiased population of Caucasian and Asian premenopausal women, who participated in the cross-sectional Eastern Siberia PCOS epidemiology and phenotype (ESPEP) study (ClinicalTrials.gov ID: NCT05194384) in 2016-2019. The study population consisted of 408 non-hirsute, normo-androgenic, eumenorrheic premenopausal women aged 18-44 years. All participants underwent a uniform evaluation including a review of their medical history and a physical examination, blood sampling, and pelvic ultrasonography. The statistical analysis included non-parametric tests and the estimation of the upper normal limits (UNLs) by 98th percentiles for OV and FNPO. In the total study population, the upper OV percentiles did not differ by ethnicity or age group. By contrast, the UNL of FNPO was higher in Caucasian women than in Asian women, and women aged <35 years demonstrated a higher UNL of FNPO compared to older women. In summary, these data suggest that the estimation of FNPO, but not OV, should take into account the ethnicity and age of the individual in estimating the presence of PCOM.
PubMed: 38611586
DOI: 10.3390/diagnostics14070673 -
Arquivos Brasileiros de Cardiologia 2024Testosterone deficiency (TD) is a prevalent condition in our midst and still very neglected. Arterial hypertension (AH) is one of the possible associated factors.
BACKGROUND
Testosterone deficiency (TD) is a prevalent condition in our midst and still very neglected. Arterial hypertension (AH) is one of the possible associated factors.
OBJECTIVES
To determine the prevalence of TD in a hypertensive male population and the factors associated with its occurrence, such as age, time since hypertension diagnosis, number of antihypertensive classes, body mass index (BMI), diabetes, dyslipidemia, chronic kidney disease (CKD), positive symptoms of TD (positive ADAM questionnaire) and use of spironolactone.
METHODS
Cross-sectional study with administration of the ADAM questionnaire, assessment of biochemical, clinical, and anthropometric data. Patients were stratified into DT and normal testosterone groups. Categorical variables were compared using the chi-squared test and continuous variables using the Mann-Witney test; variables with significance (p<0,05) were analyzed by multivariable linear regression.
RESULTS
The prevalence of TD was 26.36%. There was an association between TD and body mass index (BMI) (p=0.0007) but there was no association with age (p=0.0520), time of hypertension diagnosis (p=0.1418), number of classes of antihypertensive drugs (p=0.732), diabetes (p=0.1112); dyslipidemia (p=0.3888); CKD (p=0.3321); use of spironolactone (p=0.3546) or positive ADAM questionnaire (p=0.2483).
CONCLUSIONS
TD was highly prevalent and positively associated with BMI. Total testosterone (TT) declined by 8.44ng/dL with a one unit increase in BMI and dropped by 3.79ng/dL with a one-year increase in age.
Topics: Humans; Male; Prevalence; Spironolactone; Cross-Sectional Studies; Testosterone; Hypertension; Diabetes Mellitus; Dyslipidemias; Renal Insufficiency, Chronic
PubMed: 38597552
DOI: 10.36660/abc.20230138 -
Sexual Medicine Apr 2024Less is known about the sexual life and information seeking of Chinese patients with prostate cancer (PCa) after androgen deprivation therapy (ADT) treatment.
BACKGROUND
Less is known about the sexual life and information seeking of Chinese patients with prostate cancer (PCa) after androgen deprivation therapy (ADT) treatment.
AIM
To identify the experiences of sex and information needs among Chinese patients with PCa after ADT treatment.
METHODS
This qualitative study included 15 Chinese patients with PCa in urology inpatient wards, selected via a purposive sampling method. Semistructured interviews were conducted face-to-face or by telephone regarding sexual experiences and information needs after ADT treatment.
OUTCOMES
Themes and subthemes were assessed among patients with PCa.
RESULTS
Two themes and 5 subthemes emerged from the interview data. The first theme was "altered sexual life and attitude" with 3 subthemes: (1) undesirable sexual function and altered sexuality, (2) sexual attitudes and sociocultural cognition, and (3) behavior adjustment and intimacy. The second theme was "scarce information sources" with 2 subthemes: (1) uncertainty and lack of information support and (2) barriers to access sexual information.
CLINICAL IMPLICATIONS
The present findings suggest that the following may help patients with PCa manage treatment and develop appropriate sexual attitudes: a tailored sexual health education program, well-equipped consultations rooms, and information delivery innovations.
STRENGTHS AND LIMITATIONS
Strengths of this study included adding unique evidence among patients with PCa within an Asian context to reveal the understudied topic of sexual health and information needs after ADT treatment. This study was limited in being representative of all Chinese patients with PCa, with different marital statuses, treatment therapies, sexual orientations, and barriers of information seeking.
CONCLUSION
Sexual life and attitude among patients with PCa were affected by their sociocultural cognition and ADT treatment, and most patients received insufficient information and sexual health education from health care providers.
PubMed: 38596664
DOI: 10.1093/sexmed/qfae019 -
Giant Bilateral Adrenal Myelolipomas in a Non-Compliant Patient with Congenital Adrenal Hyperplasia.The American Journal of Case Reports Apr 2024BACKGROUND 21-hydroxylase deficiency, an essential enzyme for glucocorticoid and mineralocorticoid synthesis, is the cause of congenital adrenal hyperplasia (CAH) in...
BACKGROUND 21-hydroxylase deficiency, an essential enzyme for glucocorticoid and mineralocorticoid synthesis, is the cause of congenital adrenal hyperplasia (CAH) in more than 95% of cases. It is an autosomal recessive disorder encoded by the CYP21A2 gene, categorized into classical forms, which encompass the salt-wasting (SW) and simple virilizing (SV) forms, as well as the nonclassical form (NC). The aim of medical treatment is to replace missing glucocorticoids and, if necessary, mineralocorticoids, while also reducing elevated adrenal androgens. CASE REPORT We present the case of a 42-year-old woman with CAH who discontinued therapy during adolescence and was admitted to hospital with fatigue, nausea, and severe abdominal pain. A CT scan showed an extreme enlargement of the adrenal glands. Laboratory tests revealed elevated levels of 17-hydroxyprogesterone and other adrenal androgens, along with normal plasma metanephrine levels. Decreased morning cortisol levels suggested partial adrenal insufficiency requiring glucocorticoid replacement therapy. Due to the development of several serious complications and clinical deterioration, the multidisciplinary team recommended bilateral removal of masses measuring 300×250×200 mm on the right side and 250×200×200 mm on the left side. Histological and immunochemical examination confirmed the presence of giant myelolipomas with adrenal cortex hyperplasia. CONCLUSIONS Adrenal tumors, particularly myelolipomas, have a higher prevalence in patients with CAH. Our case report provides further evidence of the suspected link between non-compliant CAH therapy and the development of myelolipomas, along with promotion of their pronounced growth.
Topics: Adult; Female; Humans; Adrenal Gland Neoplasms; Adrenal Glands; Adrenal Hyperplasia, Congenital; Glucocorticoids; Lipoma; Myelolipoma; Steroid 21-Hydroxylase
PubMed: 38582958
DOI: 10.12659/AJCR.943005