-
Cureus Oct 2023The foramen ovale serves as an opening between the right and left atria at the site of the fossa ovalis in the fetus during uterine life. During fetal life, it makes...
The foramen ovale serves as an opening between the right and left atria at the site of the fossa ovalis in the fetus during uterine life. During fetal life, it makes it possible for venous blood from the maternal placenta with oxygen and nutrients to bypass the immature fetal lung and get transported to the left side of the heart and onto the systemic circulation. This hole from the right to the left atrium is usually occluded at the time of birth or shortly after birth, due to increased pressures in the left-sided cardiac cavities associated with normal breathing during delivery or shortly afterwards. If the foramen ovale remains open and fails to fuse beyond the first year of life, it is known as a patent foramen ovale (PFO). PFO occurs when, during fetal life, the septum primum and secundum, which develop and overlap normally, fail to fuse at birth. This results in the persistence of communication between the right and left atria. Paradoxical embolism from the right to the left side of the heart can occur through a PFO, causing a cryptogenic stroke or embolic stroke of an undetermined source in an otherwise healthy adult. There was a debate on the long-term benefits of closure. However, data from the randomized evaluation of the recurrent stroke comparing PFO closure to established current standard of care treatment (RESPECT) trial and two randomized trials (patent foramen ovale closure or anticoagulants versus antiplatelet therapy to prevent stroke recurrence (CLOSE) and reduction by dutasteride of prostate cancer events (REDUCE)) have clarified that there is a benefit to closure. In this case report, we describe a patient who presented with cryptogenic stroke, the investigations, imaging modalities for diagnosis of PFO, and procedure for closure. We also describe long-term outcomes and management following closure.
PubMed: 37954786
DOI: 10.7759/cureus.46895 -
Reviews on Recent Clinical Trials Jun 2024Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia....
Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms.
PubMed: 38910423
DOI: 10.2174/0115748871303638240529160610 -
Research in Veterinary Science Aug 2023Inflammatory mammary cancer (IMC) is a disease that affects female dogs. It is characterized by poor treatment options and no efficient targets. However, anti-androgenic...
Inflammatory mammary cancer (IMC) is a disease that affects female dogs. It is characterized by poor treatment options and no efficient targets. However, anti-androgenic and anti-estrogenic therapies could be effective because IMC has a great endocrine influence, affecting tumor progression. IPC-366 is a triple negative IMC cell line that has been postulated as a useful model to study this disease. Therefore, the aim of this study was to inhibit steroid hormones production at different points of the steroid pathway in order to determine its effect in cell viability and migration in vitro and tumor growth in vivo. For this purpose, Dutasteride (anti-5αReductase), Anastrozole (anti-aromatase) and ASP9521 (anti-17βHSD) and their combinations have been used. Results revealed that this cell line is positive to estrogen receptor β (ERβ) and androgen receptor (AR) and endocrine therapies reduce cell viability. Our results enforced the hypothesis that estrogens promote cell viability and migration in vitro due to the function of E1SO4 as an estrogen reservoir for E2 production that promotes the IMC cells proliferation. Also, an increase in androgen secretion was associated with a reduction in cell viability. Finally, in vivo assays showed large tumor reduction. Hormone assays determined that high estrogen levels and the reduction of androgen levels promote tumor growth in Balb/SCID IMC mice. In conclusion, estrogen levels reduction may be associated with a good prognosis. Also, activation of AR by increasing androgen production could result in effective therapy for IMC because their anti-proliferative effect.
Topics: Mice; Dogs; Female; Animals; Androgens; Mice, SCID; Estrogens; Steroids; Cell Proliferation; Cell Line, Tumor
PubMed: 37290206
DOI: 10.1016/j.rvsc.2023.05.014 -
Biomolecules Feb 2024Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate...
Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure ( 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively ( 0.596). IPCa was detected in 37.6 and 62.5%, respectively ( 0.089). The tumor GG distribution based on 5-ARI exposure was similar ( 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Magnetic Resonance Imaging; 5-alpha Reductase Inhibitors; Cyanoacrylates
PubMed: 38397430
DOI: 10.3390/biom14020193 -
Cureus Dec 2023Benign prostatic hyperplasia (BPH) is a progressive disease that causes low urinary tract symptoms (LUTS). As prostatic volume grows, the prostatic urethra may become...
BACKGROUND
Benign prostatic hyperplasia (BPH) is a progressive disease that causes low urinary tract symptoms (LUTS). As prostatic volume grows, the prostatic urethra may become completely obstructed, resulting in full urine retention and acute hypogastric pain. Our research aimed to identify the optimal trial without catheter (TWOC) therapeutic approach and identify those factors that are associated with the recurrence of complete urinary retention (CUR).
METHODOLOGY
The study enrolled with complete urinary retention and BPH were included in the study, after the insertion of a Foley catheter. The patients received tamsulosin 0.4 mg/day as an alpha-blocker treatment. In our investigation, patients who encountered complete urinary retention were randomly categorized into four groups based on the duration of urinary catheterization as determined by the attending urologist.
RESULTS
Maintaining the urethrovesical catheter for three to seven days was related to the highest success of spontaneous urination, which was statistically significant compared to other study groups. (p=0.0007). Age over 70 years, no alpha-blocker before the urinary retention episode, and prostatic volume exceeding 50 ml were all associated with decreased TWOC efficacy. We found the highest rates of spontaneous urination were after three to seven days of urinary catheterization.
CONCLUSION
BPH and complete urine retention can be managed by TWOC in many cases. Several factors affect the test's efficacy. Prolonged urinary catheter maintenance over seven days, prostatic volume over 50 ml, and age over 70 years are poor prognostic indicators.
PubMed: 38259407
DOI: 10.7759/cureus.50980 -
International Journal of Molecular... Jan 2024The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no...
The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no overexpression of HER-2. However, TNBC can express the androgen receptor (AR) or estrogen receptor β (ERβ). Also, TNBC secretes steroid hormones and is influenced by hormonal fluctuations, so the steroid inhibition could exert a beneficial effect in TNBC treatment. The aim of this study was to evaluate the effect of dutasteride, anastrozole and ASP9521 in in vitro processes using human TNBC cell lines. For this, immunofluorescence, sensitivity, proliferation and wound healing assays were performed, and hormone concentrations were studied. Results revealed that all TNBC cell lines expressed AR and ERβ; the ones that expressed them most intensely were more sensitive to antihormonal treatments. All treatments reduced cell viability, highlighting MDA-MB-453 and SUM-159. Indeed, a decrease in androgen levels was observed in these cell lines, which could relate to a reduction in cell viability. In addition, MCF-7 and SUM-159 increased cell migration under treatments, increasing estrogen levels, which could favor cell migration. Thus, antihormonal treatments could be beneficial for TNBC therapies. This study clarifies the importance of steroid hormones in AR and ERβ-positive cell lines of TNBC.
Topics: Humans; Androgens; Receptors, Estrogen; Triple Negative Breast Neoplasms; Estrogen Receptor beta; Cell Line, Tumor; Estrogens; Receptors, Androgen; Steroids; Estrogen Receptor alpha; Cell Proliferation
PubMed: 38338747
DOI: 10.3390/ijms25031471 -
Urology Annals 2024Dutasteride is used in the treatment of benign prostate enlargement with reported many side effects.
CONTEXT
Dutasteride is used in the treatment of benign prostate enlargement with reported many side effects.
AIMS
The purpose of this study is to examine how different doses of dutasteride (0.5 mg) in combination with tamsulosin affect the outcome of treatment of benign prostatic enlargement (BPE).
SETTINGS AND DESIGN
Prospective study (phase III trial).
SUBJECTS AND METHODS
Between April 2017 and March 2020, this randomized study was conducted on 300 patients with moderate-to-severe lower urinary tract symptoms attributable to BPE and a prostate volume of more than 40 cc. The patients were divided into three therapy groups at random (one-to-one randomization), each with 100 patients: (Group I) daily tamsulosin 0.4 mg plus dutasteride (0.5 mg). (Group II) every other day tamsulosin 0.4 mg plus dutasteride 0.5 mg. (Group III) once a week tamsulosin 0.4 mg plus dutasteride 0.5 mg.
STATISTICAL ANALYSIS
Statistical analysis was carried out with the help of the SPSS program 22. (IBM, Armonk, NY, USA). The mean and standard deviation (SD) are used to express quantitative data (SD). When comparing two means, an independent-samples -test of significance was used. To compare more than two means, a one-way analysis of variance was utilized. For multiple comparisons between distinct variables, a test was performed.
RESULTS
Patients were followed up every 3 months, with a 1-year follow-up to examine the medications' efficacy, prostate size reduction, and erectile function. After 1 year of treatment, all groups showed significant improvement in their symptom scores. However, Groups I and II experienced a considerable reduction in prostate size after therapy, but Group III experienced no meaningful reduction. In terms of sexual dysfunction, there was a considerable shift in Group I after 12 months.
CONCLUSIONS
Dutasteride treatment on the other day schedule has the same efficacy as the daily dose on prostate size at the same time; the other day scheduled dose has better preservation of sexual function.
PubMed: 38818435
DOI: 10.4103/ua.ua_15_22 -
Spectrochimica Acta. Part A, Molecular... Apr 2024Here, we present the new application of solid-state Vibrational Circular Dichroism (VCD) spectroscopy to differentiate several dutasteride (DS) solvatomorphs - the model...
Here, we present the new application of solid-state Vibrational Circular Dichroism (VCD) spectroscopy to differentiate several dutasteride (DS) solvatomorphs - the model active pharmaceutical ingredient (API). Several crystalline DS hydrochloride hydrates solvated with methanol, ethanol, acetonitrile, acetone, and acetic acid were prepared. In contrast to almost identical IR spectra, the VCD ones were very sensitive to changes in the sample composition. We marked significant differences in the shape of VCD spectra of studied DS solvatomorphs, DS hydrates, and DS polymorphic forms. Our findings, supported by DFT calculations, show that VCD spectroscopy has the pronounced ability to distinguish their crystal arrangements. We believe that this contribution will extend the use of VCD in the pharmaceutical industry for developing and designing new chiral drug products for the identification, description, and in-depth probing of several pharmaceutical solvatomorphs in the future.
Topics: Circular Dichroism; Bulk Drugs; Spectrophotometry, Infrared; Methanol; Stereoisomerism
PubMed: 38295593
DOI: 10.1016/j.saa.2024.123851 -
Journal of the American Pharmacists... 2024Transgender and gender-diverse (TGD) people have a high prevalence of psychotropic medication use, yet knowledge about the patient-level psychotropic medication burden...
BACKGROUND
Transgender and gender-diverse (TGD) people have a high prevalence of psychotropic medication use, yet knowledge about the patient-level psychotropic medication burden is limited. TGD patients may take hormone therapy to meet their gender expression goals. Potential drug-hormone interactions exist between psychotropic medications and hormone therapy, requiring increased knowledge about psychotropic medication use for TGD adults undergoing hormone therapy.
OBJECTIVES
The objective of this study was to examine the extent of psychotropic medication polypharmacy in a cohort of TGD adults within 2 years of starting hormone therapy. We also characterized potential drug-hormone interactions and the association with psychotropic polypharmacy.
METHODS
Retrospective cross-sectional analysis of patients with ≥1 transgender health-related visit (2007-2017) in the University of Washington Medical System (Seattle, WA). Eligible patients had ≥1 psychotropic medication including antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics ordered within 2 years of starting hormone therapy (testosterone or estradiol with or without spironolactone, progesterone, finasteride, or dutasteride). We defined psychotropic polypharmacy as ≥2 psychotropic medication orders with overlapping treatment durations for at least 90 days and characterized potential drug-hormone interactions (Lexicomp, Hudson, OH). We descriptively summarized patients with and without polypharmacy (frequencies and percentages) and compared drug-hormone interactions using chi-square or Fishers exact tests (P < 0.05 considered significant).
RESULTS
A total of 184 patients had ≥1 psychotropic medication order within 2 years of hormone therapy; 68 patients (37.0%) had psychotropic polypharmacy. The most frequent type of psychotropic polypharmacy was antidepressant+sedative-hypnotic (18 of 68, 26.5%). More patients had a potential drug-hormone interaction among those with psychotropic polypharmacy (23 of 68, 33.8%) versus those without (8 of 116, 6.9%, P < 0.001).
CONCLUSION
Among TGD patients on psychotropic medications within 2 years of hormone therapy, one-third had psychotropic polypharmacy. Most polypharmacy types appeared to align with mental health treatment guidelines. The number of patients with a potential drug-hormone interaction was significantly higher among those with polypharmacy. Prospective studies are needed to characterize drug-hormone interactions.
Topics: Adult; Humans; Retrospective Studies; Transgender Persons; Cross-Sectional Studies; Psychotropic Drugs; Antidepressive Agents; Polypharmacy; Hypnotics and Sedatives; Hormones
PubMed: 37839699
DOI: 10.1016/j.japh.2023.10.005 -
Andrology Jun 2024Real-world big data studies on drug-reduced male semen quality are few and far between, with most studies based on animal trials, small scale retrospective studies, or a...
BACKGROUND
Real-world big data studies on drug-reduced male semen quality are few and far between, with most studies based on animal trials, small scale retrospective studies, or a limited number of pre-market clinical trials.
METHODS
This study aimed to identify culprit drugs that reduced male semen quality based on the United States Food and Drug Administration adverse event reporting system. The Medical Dictionary for Regulatory Activities preferred terms and standardized Medical Dictionary for Regulatory Activities queries were used to define reduced male semen quality. Adverse events related to drug-reduced male semen quality were then analyzed by disproportionality analysis using the United States Food and Drug Administration adverse event reporting system data between 2004 and 2023.
RESULTS
At the preferred term level, 59 drugs with risk signals were detected to be associated with drug-reduced male semen quality, with the three most frequently reported second-level Anatomical Therapeutic Chemical groups being antineoplastic agents (n = 16, 27.12%), psychoanaleptics (n = 9, 15.25%), and psycholeptics (n = 6, 10.17%). At the standardized Medical Dictionary for Regulatory Activities queries level, the five drugs with the greatest number of cases were finasteride (845 cases, IC = 7.72), dutasteride (163 cases, IC = 7.22), tamsulosin (148 cases, IC= 5.99), testosterone (101 cases, IC= 4.08), and valproic acid (54 cases, IC= 2.44). Additionally, clinical information about drug-reduced male semen quality is absent from the Summary of Product Characteristics of 41 drugs in our study.
CONCLUSIONS
Using the United States Food and Drug Administration adverse event reporting system database, we offer a list of drugs with risk signals for reducing male semen quality. In the future, there is still a need for more studies on drugs whose effects on male semen quality are not fully understood.
PubMed: 38831673
DOI: 10.1111/andr.13668