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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 -
Human Reproduction Open 2024Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)?
STUDY QUESTION
Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation.
WHAT IS KNOWN ALREADY
Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear.
STUDY DESIGN SIZE DURATION
Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group).
PARTICIPANTS/MATERIALS SETTING METHODS
Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed.
MAIN RESULTS AND THE ROLE OF CHANCE
Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe (<0.05) and MDA (<0.05), and upregulated nuclear receptor coactivator 4 protein levels, and downregulated ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) proteins were observed in the hGCs in patients with PCOS and ovaries of PCOS rats (<0.05 versus control). DHT was shown to induce ferroptosis via activation of NOCA4-dependent ferritinophagy. The inhibition of ferroptosis with Fer-1 in rats ameliorated a cluster of PCOS traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality (<0.05). Treating rats with RSL3 resulted in polycystic ovaries and hyperandrogenism (<0.05).
LARGE-SCALE DATA
N/A.
LIMITATIONS REASONS FOR CAUTION
Although ovarian-targeted ferroptosis inhibition may be a more targeted treatment for PCOS, the underlying mechanisms in the cycle between ferroptosis and hyperandrogenism require further exploration. Additionally, since PCOS shows high heterogeneity, it is important to investigate whether ferroptosis increases are present in all patients with PCOS.
WIDER IMPLICATIONS OF THE FINDINGS
Androgen-induced ovarian ferroptosis appears to play a role in the pathogenesis of PCOS, which potentially makes it a promising treatment target in PCOS.
STUDY FUNDING/COMPETING INTERESTS
This study was supported by the National Key R&D Program of China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), National Natural Science Foundation of China (No. 82130046, 82320108009, 82101708, 82101747, and 82001517), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (No. SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003) and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No. 20161413), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors report no competing interests.
PubMed: 38550897
DOI: 10.1093/hropen/hoae013 -
Frontiers in Endocrinology 2024Triple A syndrome, caused by autosomal recessively inherited mutations in the gene is characterized by alacrima, achalasia, adrenal insufficiency, and neurological...
OBJECTIVE
Triple A syndrome, caused by autosomal recessively inherited mutations in the gene is characterized by alacrima, achalasia, adrenal insufficiency, and neurological impairment. To the best of our knowledge, no patients of both sexes have been reported to have offspring. Our aim was to assess the causes of infertility in male patients with this multisystemic syndrome, and to present a female patient that spontaneously conceived a child.
DESIGN
Cross-sectional study.
METHODS
Six males aged 19-48 years were included. Gonadotropins, testosterone, DHEAS, androstenedione, inhibin B, anti-Mullerian hormone measurements and testicular ultrasound were performed.
RESULTS
All six male patients had impaired general health and neurological symptoms including erectile and ejaculatory dysfunction. None of them had an offspring. The only demonstrated cause of infertility in our male patients was erectile and ejaculatory dysfunction which precludes sexual intercourse. Our patients had normal libido but were sexually abstinent. Except for low adrenal androgen levels, the concentrations of all measured hormones as well as testicular ultrasound were normal which may indicate the possibility of spermatogenesis in male patients with triple A syndrome. Little is known about fertility in female patients, but based on our observations spontaneous pregnancies seem to be possible.
CONCLUSION
Our results contribute to still scarce knowledge on fertility in patients with Triple A syndrome and as well represents a foundation for further research on causes of infertility and possible treatment options.
Topics: Child; Humans; Male; Female; Esophageal Achalasia; Cross-Sectional Studies; Adrenal Insufficiency; Infertility; Sexual Behavior; Fertility
PubMed: 38544685
DOI: 10.3389/fendo.2024.1357084 -
Cell Communication and Signaling : CCS Mar 2024Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a...
PURPOSE
Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target.
METHODS
Sleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated.
RESULTS
SD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-β. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse.
CONCLUSIONS
The cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.
Topics: Humans; Male; Animals; Mice; Sleep Deprivation; Dihydrotestosterone; Melatonin; Prostatitis; Proteomics; Sleep; DNA, Mitochondrial; Nucleotidyltransferases
PubMed: 38491517
DOI: 10.1186/s12964-024-01554-5 -
Annals of Pediatric Endocrinology &... Feb 2024Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was...
PURPOSE
Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was performed to investigate the clinical utility of prenatal diagnosis of 21-OHD using molecular genetic testing in families at risk.
METHODS
This study included 27 pregnant women who had previously borne a child with 21-OHD. Fetal tissues were obtained using chorionic villus sampling (CVS) or amniocentesis. After the genomic DNA was isolated, Sanger sequencing of CYP21A2 and multiplex ligation-dependent probe amplification were performed. The clinical and endocrinological findings were reviewed retrospectively.
RESULTS
A total of 39 prenatal genetic tests was performed on 27 pregnant women and their fetal tissues. The mean gestational age at the time of testing was 11.7 weeks for CVS and 17.5 weeks for amniocentesis. Eleven fetuses (28.2%) were diagnosed with 21-OHD. Among them, 10 fetuses (90.9%) harbored the same mutation as siblings who were previously diagnosed with 21-OHD. Among these, 4 fetuses (3 males and 1 female) identified as affected were born alive. All 4 patients have been treated with hydrocortisone, 9α-fludrocortisone, and sodium chloride since a mean of 3.7 days of life. The male patients did not show hyponatremia and dehydration, although they harbored pathogenic variants associated with the salt-wasting type of 21-OHD.
CONCLUSION
This study demonstrated the diagnostic efficacy and clinical consequences of diagnosis by prenatal genetic testing in families at risk for 21-OHD. All patients identified as affected were treated with hydrocortisone and 9α-fludrocortisone early after birth, which can prevent a life-threatening adrenal crisis.
PubMed: 38461806
DOI: 10.6065/apem.2346014.007 -
Frontiers in Endocrinology 2024Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic...
INTRODUCTION
Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic patients, the underlying mechanisms remain elusive.
METHODS AND RESULTS
Herein, we generated a rat SCI model, which recapitulated complications in human males, including low testosterone levels and spermatogenic disorders. Proteomics analyses showed that the differentially expressed proteins were mostly enriched in lipid metabolism and steroid metabolism and biosynthesis. In SCI rats, we observed that testicular nitric oxide (NO) levels were elevated and lipid droplet-autophagosome co-localization in testicular interstitial cells was decreased. We hypothesized that NO impaired lipophagy in Leydig cells (LCs) to disrupt testosterone biosynthesis and spermatogenesis. As postulated, exogenous NO donor (S-nitroso-N-acetylpenicillamine (SNAP)) treatment markedly raised NO levels and disturbed lipophagy via the AMPK/mTOR/ULK1 pathway, and ultimately impaired testosterone production in mouse LCs. However, such alterations were not fully observed when cells were treated with an endogenous NO donor (L-arginine), suggesting that mouse LCs were devoid of an endogenous NO-production system. Alternatively, activated (M1) macrophages were predominant NO sources, as inducible NO synthase inhibition attenuated lipophagic defects and testosterone insufficiency in LCs in a macrophage-LC co-culture system. In scavenging NO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO)) we effectively restored lipophagy and testosterone levels both and , and importantly, spermatogenesis . Autophagy activation by LYN-1604 also promoted lipid degradation and testosterone synthesis.
DISCUSSION
In summary, we showed that NO-disrupted-lipophagy caused testosterone deficiency following SCI, and NO clearance or autophagy activation could be effective in preventing reproductive dysfunction in males with SCI.
Topics: Mice; Male; Rats; Humans; Animals; Nitric Oxide; Rats, Sprague-Dawley; Testosterone; Macrophages; Spinal Cord Injuries
PubMed: 38455652
DOI: 10.3389/fendo.2024.1360499 -
Maturitas Jun 2024Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or... (Review)
Review
The effect of dietary interventions or patterns on the cardiometabolic health of individuals treated with androgen deprivation therapy for prostate cancer: A systematic review.
Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or management of cardiovascular disease for these individuals are lacking. This review synthesizes the evidence on the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk in prostate cancer survivors receiving androgen deprivation therapy. A systematic review was conducted across PubMed, CINAHL, Embase, and Cochrane CENTRAL. Intervention or observational cohort studies evaluating diets, nutrients, or nutraceuticals with or without concurrent exercise interventions on cardiovascular disease, cardiovascular events, or cardiovascular disease biomarkers in those treated with androgen deprivation therapy were included. Confidence in the body of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. Twelve studies reported across fifteen papers were included. Interventions were heterogenous, with most studies including an exercise co-intervention (n = 8). Few significant findings for the effects of diet on cardiometabolic markers were likely due to weak methodology and sample sizes. Strongest evidence was for the effect of a healthy Western dietary pattern with exercise on improved blood pressure (Confidence: moderate). The healthy Western dietary pattern with exercise may improve high-density lipoprotein cholesterol (Confidence: Low) and flow-mediated dilation. Soy may improve total cholesterol (Confidence: Very low). A low-carbohydrate diet with physical activity may improve high-density lipoprotein cholesterol, incidence of metabolic syndrome, and Framingham cardiovascular disease risk score. Evidence of the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk of prostate cancer survivors receiving androgen deprivation therapy is insufficient to inform practice. Well-designed dietary interventions aimed at improving cardiometabolic outcomes of this population are warranted to inform future dietary recommendations.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Cardiovascular Diseases; Exercise; Diet; Dietary Supplements
PubMed: 38430616
DOI: 10.1016/j.maturitas.2024.107940 -
European Urology Open Science Feb 2024There is insufficient evidence on the oncologic risks of testosterone therapy for men with prostate cancer managed with active surveillance. We carried out a...
BACKGROUND AND OBJECTIVE
There is insufficient evidence on the oncologic risks of testosterone therapy for men with prostate cancer managed with active surveillance. We carried out a retrospective study to assess the effect of testosterone therapy on oncologic outcomes for men on active surveillance for prostate cancer.
METHODS
Surveillance, Epidemiology and End Results (SEER)-Medicare linked data were used to identify men diagnosed with prostate cancer from 2008 to 2017 who were managed with active surveillance and received testosterone ( = 167) or no testosterone ( = 6658) therapy. Outcomes included conversion from active surveillance to active treatment (radical prostatectomy, cryotherapy, radiation, or androgen deprivation therapy), prostate cancer-specific mortality, and overall mortality. Statistically significant factors on univariable analysis were included in a Cox proportional-hazards regression model for multivariable analysis.
KEY FINDINGS AND LIMITATIONS
The median age was 71 yr (interquartile range [IQR] 68-74) in the testosterone group and 72 yr (IQR 69-75) in the no-testosterone group, with corresponding median follow-up after prostate cancer diagnosis of 5.2 yr (IQR 3.4-7.8) and 4.7 yr (IQR 3.2-6.9). There were no prostate cancer-specific deaths in the testosterone group and 39 (0.6%) in the no-testosterone group. Testosterone therapy was not associated with conversion to active treatment (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46-0.97; = 0.033) or overall mortality (HR 1.02, 95% CI 0.68-1.53; > 0.9).
CONCLUSIONS AND CLINICAL IMPLICATIONS
In the first population-based, nationally representative study of testosterone therapy for men on active surveillance for prostate cancer, testosterone therapy did not increase the risk of conversion to active therapy or worsen mortality. Prospective studies are needed to confirm these findings.
PATIENT SUMMARY
For men on active surveillance for prostate cancer, we assessed the effect of testosterone therapy. We found that testosterone therapy did not increase the risk of proceeding to active therapy or of death from prostate cancer.
PubMed: 38375342
DOI: 10.1016/j.euros.2024.01.005 -
NEJM Evidence Jan 2024BACKGROUND: Prostate cancer is regulated by steroid hormones, even in castration-resistant disease. ODM-208, a novel inhibitor of cytochrome P450 11A1 (which catalyzes...
BACKGROUND: Prostate cancer is regulated by steroid hormones, even in castration-resistant disease. ODM-208, a novel inhibitor of cytochrome P450 11A1 (which catalyzes the first step of steroid-hormone biosynthesis), was investigated in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). METHODS: CYPIDES is a first-in-human phase 1 (3 + 3 design) and phase 2 study. We administered ODM-208 twice daily with glucocorticoid/mineralocorticoid replacement and ongoing androgen deprivation therapy to adults with previously treated mCRPC, regardless of androgen receptor gene (AR) ligand-binding domain mutations (phase 1) and with activating AR ligand-binding domain mutations (ARmut; phase 2). Safety, pharmacokinetics, steroid-hormone pharmacodynamics, and preliminary efficacy were the key outcomes. RESULTS: Ninety-two patients received one or more doses of ODM-208: 47 in phase 1 (20 [42.6%] with ARmut) and 45 in phase 2 (all ARmut). A dose of ODM-208 of 5 mg twice a day with dexamethasone 1 mg/fludrocortisone 0.1 mg provided a balance between decreased steroidogenesis and toxicity. Treatment-related adrenal insufficiency was the most common toxicity in phase 1 (n=17, 36.2%; necessitating ODM-208 discontinuation in one patient); this toxicity occurred in six patients (13.3%) at 5 mg twice a day in phase 2. Median circulating testosterone levels declined from 3.0 ng/dl (interquartile range, 1.3 to 6.2 ng/dl) at baseline to undetectable levels within the first week of ODM-208 5 mg twice a day treatment in 46 of 53 (87%) patients. A decrease in prostate-specific antigen levels of 50% or more occurred in 14 of 19 (73.7%) patients with ARmut and 2 of 23 (8.7%) patients with AR wild type in phase 1 and in 24 of 45 (53.3%) patients with ARmut in phase 2. CONCLUSIONS: ODM-208 potently inhibited steroid-hormone biosynthesis with the expected toxicity of adrenal insufficiency. Evidence of antitumor activity was observed in this heavily pretreated mCRPC population, especially in those with ARmut. (Funded by Orion Pharma; ClinicalTrials.gov number, NCT03436485.)
Topics: Male; Humans; Receptors, Androgen; Prostatic Neoplasms, Castration-Resistant; Cholesterol Side-Chain Cleavage Enzyme; Prostate-Specific Antigen; Treatment Outcome; Androgen Receptor Antagonists
PubMed: 38320513
DOI: 10.1056/EVIDoa2300171