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BMJ Clinical Evidence Jan 2009Polycystic ovary syndrome (PCOS) is diagnosed in up to 10% of women attending gynaecology clinics, but the prevalence in the population as a whole is unclear. PCOS has... (Review)
Review
INTRODUCTION
Polycystic ovary syndrome (PCOS) is diagnosed in up to 10% of women attending gynaecology clinics, but the prevalence in the population as a whole is unclear. PCOS has been associated with hirsutism, infertility, acne, weight gain, type 2 diabetes, cardiovascular disease (CVD), and endometrial hyperplasia.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: finasteride, flutamide, metformin, spironolactone, cyproterone acetate-ethinylestradiol (co-cyprindiol), interventions to achieve weight loss, ketoconazole, and mechanical hair removal.
Topics: Diabetes Mellitus, Type 2; Flutamide; Hair Removal; Hirsutism; Humans; Metformin; Polycystic Ovary Syndrome; Weight Loss
PubMed: 19445767
DOI: No ID Found -
BMC Molecular and Cell Biology Nov 2022To establish castration-resistant prostate cancer (CRPC) - Lncap androgen-independent (AI) cell line from Lncap androgen-dependent (AD) cell line, and explore the...
BACKGROUND
To establish castration-resistant prostate cancer (CRPC) - Lncap androgen-independent (AI) cell line from Lncap androgen-dependent (AD) cell line, and explore the different molecular biological between these two cell lines.
METHODS
The Lncap-AD cell line was cultured and passaged 60 times over 16 months. The morphology of the Lncap-AI cell line was observed. AR levels identification were detected in qRT-PCR and Western Blot assay. CCK-8, EdU assay, wound healing assay and cell adhesion assays were used to observe the ability of proliferation, migration, and adhesion. SEM and TEM were used to observe microculture structure. At last, the PSA secrete ability was evaluated by Elisa assay.
RESULTS
The Lncap-AD cell line was cultured and passaged 60 times over 16 months. The Lncap-AI cell line showed a morphologic change at the end stage of culture, the cells turned slender and cell space turned separated compared to the Lncap-AD cell line. The relative levels of AR-related genes in the Lncap-AI cell line were up-regulation compared to the Lncap-AD cell line both in mRNA and protein levels. The expression of AR and HK2 proteins were influenced and down-regulation by Enzalutamide in the Lncap-AD cell line, but no obvious difference in Lncap-AI cell lines. Lncap-AI cell line showed strong viability of proliferation, migration, and adhesion by CCK-8, EdU assay, wound healing assay, and adhesion assay. The microstructure of Scanning Electron Microscopy (SEM) showed many synapses in the Lncap-AI cell line and PC3 cell line, but not in the Lncap-AD cell line. At last, the PSA secrete ability was evaluated by Elisa assay, and PCa cell lines showed no significant difference.
CONCLUSION
Simulation of CRPC progression, Lncap-AD cell line turned to Lncap-AI cell line with androgen deprivation therapy.
Topics: Male; Humans; Flutamide; Androgens; Androgen Antagonists; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Sincalide; Cell Line
PubMed: 36443669
DOI: 10.1186/s12860-022-00453-2 -
European Review For Medical and... Mar 2017Flutamide (FLU) is a non-steroidal antiandrogen drug approved for the treatment of advanced prostate cancer. While this indication limits the use to male patients, FLU... (Review)
Review
OBJECTIVE
Flutamide (FLU) is a non-steroidal antiandrogen drug approved for the treatment of advanced prostate cancer. While this indication limits the use to male patients, FLU is widely prescribed to women, off-label, for the treatment of polycystic ovary syndrome (POCS) related hirsutism and acne. According to the literature, its assumption is associated with a higher incidence of adverse events in women than in male patients.
MATERIALS AND METHODS
A literature search was conducted in main databases targeting unwilling FLU effects in hepatic and reproductive function. References in the selected paper were also considered as an additional source of data. Human- and animal-based studies were separately considered.
RESULTS
Twenty-three human-based studies were evaluated: ten were case reports, six were retrospective studies, four were prospective, two were surveillance studies, while the last was an observational study. Nine animal-based studies were also evaluated.
CONCLUSIONS
Scientific contributions highlight that FLU is responsible for specific hepatotoxic profiles in the female gender. From the ethical point of view, off-label prescribing of FLU in women is not only substantially unlawful, but also, without major safeguards being granted, a potential source of liability for prescribers.
Topics: Androgen Antagonists; Chemical and Drug Induced Liver Injury; Female; Flutamide; Humans; Male; Prospective Studies; Retrospective Studies
PubMed: 28379593
DOI: No ID Found -
Journal of Cachexia, Sarcopenia and... Aug 2023Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb...
BACKGROUND
Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb muscles impairs sarcomere myofibrillar organization and decreases muscle strength in male mice. However, despite numerous studies performed in men and rodents, the signalling pathways controlled by androgens via their receptor in skeletal muscles remain poorly understood.
METHODS
Male AR (n = 7-12) and female AR mice (n = 9), in which AR is selectively ablated in myofibres of musculoskeletal tissue, and male AR , in which AR is selectively ablated in post-mitotic skeletal muscle myofibres (n = 6), were generated. Longitudinal monitoring of body weight, blood glucose, insulin, lipids and lipoproteins was performed, alongside metabolomic analyses. Glucose metabolism was evaluated in C2C12 cells treated with 5α-dihydrotestosterone (DHT) and the anti-androgen flutamide (n = 6). Histological analyses on macroscopic and ultrastructural levels of longitudinal and transversal muscle sections were conducted. The transcriptome of gastrocnemius muscles from control and AR mice was analysed at the age of 9 weeks (P < 0.05, 2138 differentially expressed genes) and validated by RT-qPCR analysis. The AR (4691 peaks with false discovery rate [FDR] < 0.1) and H3K4me2 (47 225 peaks with FDR < 0.05) cistromes in limb muscles were determined in 11-week-old wild-type mice.
RESULTS
We show that disrupting the androgen/AR axis impairs in vivo glycolytic activity and fastens the development of type 2 diabetes in male, but not in female mice. In agreement, treatment with DHT increases glycolysis in C2C12 myotubes by 30%, whereas flutamide has an opposite effect. Fatty acids are less efficiently metabolized in skeletal muscles of AR mice and accumulate in cytoplasm, despite increased transcript levels of genes encoding key enzymes of beta-oxidation and mitochondrial content. Impaired glucose and fatty acid metabolism in AR-deficient muscle fibres is associated with 30% increased lysine and branched-chain amino acid catabolism, decreased polyamine biosynthesis and disrupted glutamate transamination. This metabolic switch generates ammonia (2-fold increase) and oxidative stress (30% increased H O levels), which impacts mitochondrial functions and causes necrosis in <1% fibres. We unravel that AR directly activates the transcription of genes involved in glycolysis, oxidative metabolism and muscle contraction.
CONCLUSIONS
Our study provides important insights into diseases caused by impaired AR function in musculoskeletal system and delivers a deeper understanding of skeletal muscle pathophysiological dynamics that is instrumental to develop effective treatment for muscle disorders.
Topics: Animals; Female; Male; Mice; Androgens; Diabetes Mellitus, Type 2; Dihydrotestosterone; Flutamide; Muscle Contraction; Muscle, Skeletal; Receptors, Androgen
PubMed: 37208984
DOI: 10.1002/jcsm.13251 -
The Oncologist Jul 2023Before 2018, there was no standard of care for non-metastatic (M0) castration resistant prostate cancer nmCRPC. Androgen receptor antagonists (ARAs) were commonly used... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Before 2018, there was no standard of care for non-metastatic (M0) castration resistant prostate cancer nmCRPC. Androgen receptor antagonists (ARAs) were commonly used sequentially nmCRPC.
METHODS
This was a multicenter, randomized clinical trial comparing the ARA flutamide+/-PROSTVAC, a pox viral vaccine targeting PSA that includes T-cell co-stimulatory molecules. Eligible men had negative CT and Tc99 bone scans, and rising PSA on ADT. Previous treatment with ARA was a stratification factor. Patients were also evaluated for antigen-specific immune responses using intracellular cytokine staining.
RESULTS
Thirty-three patients randomized to flutamide and 31 to flutamide+vaccine. The median age was 71.8 and 69.8 years, respectively. The median time to treatment failure after a median potential follow-up of 46.7 months was, 4.5 months (range 2-70) for flutamide alone vs. 6.9 months (2.5-40; P = .38) with flutamide+vaccine. Seven patients in each arm had a >50% PSA response. Antigen-specific responses were similar in both arms (58% of patients in flutamide alone and 56% in flutamide+vaccine). The treatments were well tolerated. The most common side effect > grade 2 was injection site reaction seen in 29/31 vaccine patients which were self-limiting.
CONCLUSION
The combination of flutamide+PROSTVAC did not improve outcomes in men with nmCRPC compared with flutamide alone. (ClinicalTrials.gov Identifier: NCT00450463).
Topics: Male; Humans; Flutamide; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms; Androgen Antagonists; Castration
PubMed: 37134294
DOI: 10.1093/oncolo/oyad058 -
Drug Metabolism and Disposition: the... Apr 2016The nonsteroidal androgen-receptor antagonist flutamide is associated with hepatic injury. Oxidative stress and reactive metabolite formation are considered contributing...
The nonsteroidal androgen-receptor antagonist flutamide is associated with hepatic injury. Oxidative stress and reactive metabolite formation are considered contributing factors to liver toxicity. Here we have used flutamide as a model drug to study the generation of reactive drug metabolites that undergo redox cycling to induce oxidative stress (OS) in vitro and in vivo. Lipid peroxidation (LPO) markers, as well as genes regulated by the redox-sensitive Nrf2 pathway, have been identified as surrogates for the characterization of OS. These markers and metabolism biomarkers for drug bioactivation have been investigated to characterize drug-induced hepatic damage. Rat hepatocytes and in vivo studies showed that several LPO markers, namely the isoprostanes 15R-PD2, dihydro keto PE2, and iPF(2α)-VI, as well as hydroxynonenal mercapturic acid metabolites, had increased significantly by 24 hours after flutamide treatment from 4.9 to 15.3-fold in hepatocytes and from 2.6 to 31.0-fold in rat plasma. Induction of mRNA expression levels for Nrf2-regulated genes was evident as well, with heme oxygenase 1, glutathione-S-transferase π1 and NAD(P)H dehydrogenase showing a 3.6-, 4.1-, and 1.9-fold increase in hepatocytes and 5.6-, 7.5-, and 94.1-fold in rat liver. All effects were observed at drug concentrations that did not show overt liver toxicity. Addition of an in situ hydrogen peroxide-generating system to in vitro experiments demonstrated the formation of a reactive di-imine intermediate as the responsible metabolic pathway for the generation of OS. The dataset suggests that hepatic oxidative stress conditions can be mediated via metabolic activation and can be monitored with suitable biomarkers preceding the terminal damage.
Topics: Androgen Antagonists; Animals; Biomarkers; Cells, Cultured; Flutamide; Hepatocytes; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Inbred F344; Rats, Wistar
PubMed: 26817949
DOI: 10.1124/dmd.115.066522 -
PloS One 2019Patients with polycystic ovary syndrome (PCOS), characterized by anovulation, hyperandrogenemia and polycystic ovaries, are still vulnerable to undergo recurrent...
BACKGROUND/AIM
Patients with polycystic ovary syndrome (PCOS), characterized by anovulation, hyperandrogenemia and polycystic ovaries, are still vulnerable to undergo recurrent pregnancy loss and premature labor even though the ovulatory process is pharmacologically recovered. However, its potential mechanism remains unknown. Thus, our aim was to investigate the effect and mechanism of hyperandrogenemia and flutamide (a non-steroidal anti-androgen) on the embryo implantation and pregnancy during mid-pregnancy.
METHODS
We used a mouse model in which PCOS-like hyperandrogenemia was induced by subcutaneous injection of testosterone propionate. In this model, we observed the effect of hyperandrogenemia and flutamide on the decidualization, angiogenesis and uNK cells by methods of immunohistochemistry, quantitative PCR, western blotting and Dolichos biflorus agglutinin (DBA) lectin staining.
RESULTS
Testosterone and flutamide treatment did not significantly influence the numbers of implanted embryo compared with the control group. However, different doses of testosterone significantly increased the ratio of resorbed /implanted embryo, decreased the level of prl8a2 mRNA and cyclin D3 protein, inhibited the uterine angiogenesis and reduced the numbers of uNK cells, but combined treatment with flutamide markedly decreased the resorbed embryos, increased expressions of prl8a2 mRNA and cyclin D3 protein and angiogenesis and numbers of uNK cells.
CONCLUSION
Flutamide treatment can efficiently ameliorate the hyperandrogenemia-induced the disorders in aspects of decidualization, angiogenesis and uNK cells, which further improve the poor endometrial receptivity in PCOS patients.
Topics: Androgen Antagonists; Animals; Decidua; Disease Models, Animal; Embryo Implantation; Female; Flutamide; Hyperandrogenism; Male; Mice; Neovascularization, Pathologic; Polycystic Ovary Syndrome; Pregnancy; Testosterone; Uterus
PubMed: 31150416
DOI: 10.1371/journal.pone.0217095 -
Fertility and Sterility Jan 2023
Topics: Female; Humans; Flutamide; Polycystic Ovary Syndrome; Androgen Antagonists; Hirsutism
PubMed: 36372099
DOI: 10.1016/j.fertnstert.2022.11.009 -
Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature.Annals of Hepatology 2011Flutamide is a non-steroidal anti-androgenic drug, commonly used in the treatment of advanced prostate cancer, acne and hirsutism. This drug may induce various degrees... (Review)
Review
Flutamide is a non-steroidal anti-androgenic drug, commonly used in the treatment of advanced prostate cancer, acne and hirsutism. This drug may induce various degrees of liver injury, including acute liver failure (ALF), with further need for liver transplantation. Here, we present a report of 10 consecutive patients seen in a period of 14 years, with acute liver toxicity induced by flutamide (in most cases severe hepatotoxicity): 3 men and 7 women, with a mean age of 75 and 29 years old, respectively. All men received flutamide as treatment of advanced prostate carcinoma and they developed hepatotoxicity without ALF, and three months after withdrawal of the drug, they recovered completely. In contrast, in 7 young female with liver toxicity caused by flutamide as treatment of various hyperandrogenic conditions (acne and hirsutism), ALF was observed in 5 patients, all of them requiring urgent liver transplantation, with excellent outcome and survival in 4 of them. Based on the above, we believe that flutamide treatment should be preferentially avoided in young female patients with benign pathologies, or if it is used, patients should be warned of its potential severe complications. Also, serial liver tests should be closely monitored and, in case of elevations, the drug should be immediately withdrawn.
Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Female; Flutamide; Humans; Liver; Liver Transplantation; Male; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Treatment Outcome; Young Adult
PubMed: 21301018
DOI: No ID Found -
Scientific Reports Jul 2017The effects of testosterone and flutamide on reproduction in Brachionus calyciflorus were studied. Asexual reproduction in B. calyciflorus was not affected by...
The effects of testosterone and flutamide on reproduction in Brachionus calyciflorus were studied. Asexual reproduction in B. calyciflorus was not affected by testosterone at different concentrations of flutamide. Flutamide in combination with 0, 25, 50, or 75 µg L testosterone had a significant effect on mixis rate. The combination of 5 µg L flutamide with 25 µg L or 50 µg L testosterone resulted in a mixis rate that was 2.2× lower than that with flutamide alone. Fertilization rate was significantly decreased by 7.5 µg L flutamide in combination with 25, 50, or 75 µg L testosterone. The number of resting eggs produced per mictic female was significantly lower at all concentrations of testosterone. A low concentration of flutamide in combination with testosterone resulted in antagonism, increasing the number of resting eggs produced. However, when testosterone was combined with a higher concentration of flutamide, resting egg production declined. Therefore, long-term exposure to either testosterone, flutamide, or a combination of these two compounds may significantly reduce resting egg production in rotifers. This implies that resting egg production is affected differently by hormone pathways.
Topics: Androgen Antagonists; Androgens; Animals; Female; Fertilization; Flutamide; Rotifera; Sexual Behavior; Testosterone
PubMed: 28747724
DOI: 10.1038/s41598-017-05517-4