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Asian Journal of Andrology 2021Robust data evaluating the association of preoperative parameters of the patients with quality of life after radical prostatectomy are lacking. We investigated whether...
Robust data evaluating the association of preoperative parameters of the patients with quality of life after radical prostatectomy are lacking. We investigated whether clinical and biological preoperative characteristics of the patients were associated with impaired patient-reported quality of life (QoL) and sexual outcomes 1 year after radical prostatectomy. We evaluated patient-reported outcomes among the 1343 men participating in the AndroCan trial (NCT02235142). QoL and erectile dysfunction (ED) were assessed before and 1 year after radical prostatectomy using validated self-assessment questionnaires (Aging Male's Symptoms [AMS] and the 5-item abridged version of the International Index of Erectile Function [IIEF5]). At baseline, 1194 patients (88.9%) accepted to participate. A total of 750 (55.8%) patients answered the 1-year postoperative questionnaires. Out of them, only 378 (50.4% of responders) provided answers that could be used for calculations. One year after prostatectomy, ED had worsened by 8.0 (95% confidence interval [CI]: 7.3-8.7; P < 0.0001) out of a maximum of 20. The global AMS score has worsened by 2.8 (95% CI: 1.7-3.8; P < 0.0001). ED scores 1 year postsurgery were positively correlated with preoperative age and percentage of fat mass, and negatively correlated with total cholesterol, dehydroepiandrosterone (DHEA), and androstenediol (D5); AMS were poorly correlated with preoperative parameters. QoL and sexual symptoms significantly worsened after radical prostatectomy. Baseline bioavailable testosterone levels were significantly correlated with smaller changes on AMS somatic subscores postprostatectomy. These findings may be used to inform patients with newly diagnosed prostate cancer.
Topics: Adult; Aged; Aged, 80 and over; Androgens; Cohort Studies; Erectile Dysfunction; Humans; Male; Metabolic Syndrome; Middle Aged; Patient Satisfaction; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires
PubMed: 33565427
DOI: 10.4103/aja.aja_88_20 -
Proceedings of the National Academy of... Sep 1999Our earlier report suggested that androst-5-ene-3beta,7beta-diol (Delta(5)-androstenediol or Adiol) is a natural hormone with androgenic activity and that two potent...
Our earlier report suggested that androst-5-ene-3beta,7beta-diol (Delta(5)-androstenediol or Adiol) is a natural hormone with androgenic activity and that two potent antiandrogens, hydroxyflutamide (Eulexin) and bicalutamide (Casodex), fail to block completely the Adiol-induced androgen receptor (AR) transactivation in prostate cancer cells. Here, we report the development of a reporter assay to screen several selective steroids with anti-Adiol activity. Among 22 derivatives/metabolites of dehydroepiandrosterone, we found 4 steroids [no. 4, 1,3,5(10)-estratriene-17alpha-ethynyl-3, 17beta-diol; no. 6, 17alpha-ethynyl-androstene-diol; no. 8, 3beta, 17beta-dihydroxy-androst-5-ene-16-one; and no. 10, 3beta-methylcarbonate-androst-5-ene-7,17-dione] that have no androgenic activity and could also block the Adiol-induced AR transactivation in prostate cancer PC-3 cells. Interestingly, these compounds, in combination with hydroxyflutamide, further suppressed the Adiol-induced AR transactivation. Reporter assays further showed that these four anti-Adiol steroids have relatively lower glucocorticoid, progesterone, and estrogenic activity. Together, these data suggest some selective steroids might have anti-Adiol activity, which may have potential clinical application in the battle against the androgen-dependent prostate cancer growth.
Topics: Androstenediol; Dehydroepiandrosterone; Dihydrotestosterone; Humans; Male; Prostatic Neoplasms; Receptors, Androgen; Transcriptional Activation; Tumor Cells, Cultured
PubMed: 10500149
DOI: 10.1073/pnas.96.20.11173 -
The Journal of Urology Feb 1991To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71...
To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens. With age there was a significant increase in the volume of BPH. Also with age there was a significant decrease in the serum levels of free testosterone, androstenedione, dehydroepiandronsterone (DHA), dehydroepiandronsterone sulphate (DHA-S), delta 5-androstenediol, and 17-hydroxypregnenolone, and a significant increase in sex hormone-binding globulin (SHBG), LH, and FSH. When BPH volume and hormone levels were corrected for age, BPH volume correlated positively with free testosterone, estradiol, and estriol. These data indicate that with age patients with larger volumes of BPH have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of BPH with age. If so, therapeutic attempts at lowering plasma testosterone levels, reducing estrogen levels, or blocking androgenic stimulation through other mechanisms may interfere with the progression of BPH with age. Conversely, the fact that androgen production declines gradually with age may explain the observation that only 20 to 30% of men who live to age 80 require surgical treatment for urinary obstruction from BPH.
Topics: Adenocarcinoma; Adult; Aged; Aging; Androgens; Estrogens; Humans; Male; Middle Aged; Prostate; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms
PubMed: 1703242
DOI: 10.1016/s0022-5347(17)38353-2 -
Cancers Mar 2024Sex difference in the immune response may influence patients' response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine...
Sex difference in the immune response may influence patients' response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine the correlation between pretreatment sex hormone levels and response to ICIs in metastatic non-small cell lung cancer (NSCLC). Pretreatment plasma samples from 61 patients with newly diagnosed NSCLC prior to ICI therapy were collected. Six sex hormone levels [pyrazole triol, 17 β-estradiol, 5-androstenediol, 3β-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Overall survival (OS) and progression-free survival (PFS) were compared between the high- and low-level groups in the whole cohort. Among the six sex hormones measured, DHEA levels were significantly higher among patients without clinical benefits in the discovery cohort; the remaining sex hormones did not differ significantly. In the whole cohort, median PFS was 22 months for patients with low DHEA levels vs. 3.8 months for those with high DHEA [hazard ratio, 14.23 (95% CI, 4.7-43); < 0.001]. A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89-23.35); < 0.0001]. High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs.
PubMed: 38539486
DOI: 10.3390/cancers16061152 -
Frontiers in Cellular Neuroscience 2017: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this...
: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. : A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats. Each of these two rat groups was divided into two subgroups and received daily subcutaneous injections of either ADIOL (5 mg/kg) or vehicle. The brains were collected at 2, 7 and 14 days post-stereotaxic injection. Immunofluorescent staining was used to explore the impact of ADIOL on axonal integrity (neurofilament (NF)-M) and microglial activation (ionized calcium binding adapter molecule 1, Iba1). The inducible nitric oxide synthase (iNOS) and arginase-1 (arg-1), two major markers of microglial polarization towards the proinflammatory M1 and the regulatory M2 phenotypes respectively, were monitored using western blot. : ADIOL increased the density of NF fibers and decreased the extent of axonal damage in the vicinity of the demyelination lesion. ADIOL-induced decrease in axonal damage was manifested by decreased number of axonal spheroids at both 2 and 7 days post-demyelination insult. This reduced axonopathy was associated with decreased expression of iNOS and enhanced expression of arg-1 during the acute phase. : These data strongly suggest that ADIOL reduces demyelination-induced axonal damage, likely by dampening the local inflammatory response in the white matter and shifting microglial polarization towards a reparative mode.
PubMed: 28280460
DOI: 10.3389/fncel.2017.00049 -
Reproductive Biology and Endocrinology... Apr 2011The second to fourth digit ratio (2D:4D) is used as a marker of prenatal sex hormone exposure. The objective of this study was to examine whether circulating...
BACKGROUND
The second to fourth digit ratio (2D:4D) is used as a marker of prenatal sex hormone exposure. The objective of this study was to examine whether circulating concentrations of sex hormones and SHBG measured in adulthood was associated with 2D:4D.
METHODS
This analysis was based on a random sample from the Melbourne Collaborative Cohort Study. The sample consisted of of 1036 men and 620 post-menopausal women aged between 39 and 70 at the time of blood draw. Concentrations of circulating sex hormones were measured from plasma collected at baseline (1990-1994), while digit length was measured from hand photocopies taken during a recent follow-up (2003-2009). The outcome measures were circulating concentrations of testosterone, oestradiol, dehydroepiandrosterone sulphate, androstenedione, Sex Hormone Binding Globulin, androstenediol glucoronide for men only and oestrone sulphate for women only. Free testosterone and oestradiol were estimated using standard formulae derived empirically. Predicted geometric mean hormone concentrations (for tertiles of 2D:4D) and conditional correlation coefficients (for continuous 2D:4D) were obtained using mixed effects linear regression models.
RESULTS
No strong associations were observed between 2D:4D measures and circulating concentrations of hormones for men or women. For males, right 2D:4D was weakly inversely associated with circulating testosterone (predicted geometric mean testosterone was 15.9 and 15.0 nmol/L for the lowest and highest tertiles of male right 2D:4D respectively (P-trend = 0.04). There was a similar weak association between male right 2D:4D and the ratio of testosterone to oestradiol. These associations were not evident in analyses of continuous 2D:4D.
CONCLUSIONS
There were no strong associations between any adult circulating concentration of sex hormone or SHGB and 2D:4D. These results contribute to the growing body of evidence indicating that 2D:4D is unrelated to adult sex hormone concentrations.
Topics: Adult; Age Factors; Aged; Body Weights and Measures; Cohort Studies; Estradiol; Female; Fingers; Gonadal Steroid Hormones; Humans; Male; Middle Aged; Osmolar Concentration; Sex Characteristics; Testosterone
PubMed: 21521531
DOI: 10.1186/1477-7827-9-57 -
Scientific Reports May 2016Animal studies suggest that estrogen receptor β (ERβ)-agonists, but not ERα-agonists, are antidepressants. Several endogenous ligands for ERβ have been proposed,... (Comparative Study)
Comparative Study
Animal studies suggest that estrogen receptor β (ERβ)-agonists, but not ERα-agonists, are antidepressants. Several endogenous ligands for ERβ have been proposed, including 5α-androstane-3β, 17β-diol (3βAdiol), Androstenediol (Δ5-diol), and 7α-hydroxydehydroepiandrosterone (7α-OH-DHEA). The aim of this study was to determine the serum and salivary levels of natural ERβ ligands in men and women with and without past depressive episodes in the elderly population. DHEA (a precursor of 3βAdiol, Δ5-diol, and 7α-OH-DHEA), 17β-estradiol (E2), and cortisol (F) were also measured. Samples were collected from 51 subjects and liquid chromatography tandem mass spectrometry was used for measurement. Comparisons were made between groups based on sex and depression history. E2, 3βAdiol, and Δ5-diol levels were significantly lower in women than in men regardless of depression history. There were no significant differences between men and women in DHEA or 7α-OH-DHEA levels. DHEA was significantly lower in women with depression than in women without depression. Reduced DHEA levels may be related to depression vulnerability in women. Further studies are needed to determine the mechanism underlying sex differences in the prevalence of depression and increased risk of depression during menopause. Not only E2 but also two other estrogenic steroids (3βAdiol and Δ5-diol) should be involved in these studies.
Topics: Aged; Chromatography, Liquid; Dehydroepiandrosterone; Depression; Estradiol; Estrogen Receptor beta; Female; Humans; Hydrocortisone; Ligands; Male; Middle Aged; Sex Characteristics; Tandem Mass Spectrometry
PubMed: 27165125
DOI: 10.1038/srep25878 -
International Journal of Molecular... Oct 2022Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more...
Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3β, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 μM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.
Topics: Androstenes; Animals; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Immunoglobulin G; Lung Neoplasms; Mice; Models, Theoretical; Vascular Endothelial Growth Factor A
PubMed: 36233245
DOI: 10.3390/ijms231911944 -
BMC Cancer Aug 2011To evaluate the metabolic changes in urinary steroids in pre- and post-menopausal women and men with papillary thyroid carcinoma (PTC).
BACKGROUND
To evaluate the metabolic changes in urinary steroids in pre- and post-menopausal women and men with papillary thyroid carcinoma (PTC).
METHODS
Quantitative steroid profiling combined with gas chromatography-mass spectrometry was used to measure the urinary concentrations of 84 steroids in both pre- (n = 21, age: 36.95 ± 7.19 yr) and post-menopausal female (n = 19, age: 52.79 ± 7.66 yr), and male (n = 16, age: 41.88 ± 8.48 yr) patients with PTC. After comparing the quantitative data of the patients with their corresponding controls (pre-menopause women: n = 24, age: 33.21 ± 10.48 yr, post-menopause women: n = 16, age: 49.67 ± 8.94 yr, male: n = 20, age: 42.75 ± 4.22 yr), the levels of steroids in the patients were normalized to the mean concentration of the controls to exclude gender and menopausal variations.
RESULTS
Many urinary steroids were up-regulated in all PTC patients compared to the controls. Among them, the levels of three active androgens, androstenedione, androstenediol and 16α-hydroxy DHEA, were significantly higher in the pre-menopausal women and men with PTC. The corticoid levels were increased slightly in the PTC men, while progestins were not altered in the post-menopausal PTC women. Estrogens were up-regulated in all PTC patients but 2-hydroxyestrone and 2-hydroxy-17β-estradiol were remarkably changed in both pre-menopausal women and men with PTC. For both menopausal and gender differences, the 2-hydroxylation, 4-hydroxylation, 2-methoxylation, and 4-methoxylation of estrogens and 16α-hydroxylation of DHEA were differentiated between pre- and post-menopausal PTC women (P < 0.001). In particular, the metabolic ratio of 2-hydroxyestrone to 2-hydroxy-17β-estradiol, which could reveal the enzyme activity of 17β-hydroxysteroid dehydrogenase, showed gender differences in PTC patients (P < 1 × 10-7).
CONCLUSIONS
These results are expected be helpful for better understanding the pathogenic differences in PTC according to gender and menopausal conditions.
Topics: Adult; Androstenediol; Androstenedione; Carcinoma, Papillary; Dehydroepiandrosterone; Estradiol; Estrogens; Female; Gas Chromatography-Mass Spectrometry; Humans; Hydroxyestrones; Male; Middle Aged; Multivariate Analysis; Postmenopause; Premenopause; Sex Factors; Steroids; Thyroid Neoplasms
PubMed: 21824401
DOI: 10.1186/1471-2407-11-342 -
International Journal of Molecular... Dec 2023The hydroxylation of steroids in the C7β position is one of the rare reactions that allow the production of value-added precursors in the synthesis of ursodeoxycholic...
The hydroxylation of steroids in the C7β position is one of the rare reactions that allow the production of value-added precursors in the synthesis of ursodeoxycholic acid and other pharmaceuticals. Recently, we discovered this activity in the ascomycete sp. VKM F-3040. In this study, the novel gene of 7-hydroxylase (P450) was identified as being heterologously expressed and functionally characterized in . Transcriptome data mining and differential expression analysis revealed that 12 putative genes in sp. mycelia significantly increased their expression in response to dehydroepiandrosterone (DHEA). The transcriptional level of the most up-regulated cytochrome P450 gene was increased more than 300-fold. A two-gene construct with a candidate P450 gene and the gene of its natural redox partner, NADPH-cytochrome P450 reductase (CPR), which is interconnected by a T2A element, was created. Using this construct, recombinant strains co-expressing fungal P450 and CPR genes were obtained. The functional activity of the recombinant P450 was studied in vivo during the bioconversion of androstane steroids. The fungal 7-monooxygenase predominantly catalyzed the 7β-hydroxylation of androstadienedione (ADD), DHEA, and androstenediol, whereas 1-dehydrotestosterone was hydroxylated by P450 mainly at the C7-Hα position. To our knowledge, this is the first report of a recombinant yeast capable of catalyzing the 7α/β-hydroxylation of ADD and DHEA.
Topics: Saccharomyces cerevisiae; Cytochrome P-450 Enzyme System; Hydroxylation; Steroids; Dehydroepiandrosterone; Pichia
PubMed: 38139084
DOI: 10.3390/ijms242417256