-
International Journal of Women's Health Aug 2013Hair loss is a commonly encountered problem in clinical practice, with men presenting with a distinctive pattern involving hairline recession and vertex balding... (Review)
Review
Hair loss is a commonly encountered problem in clinical practice, with men presenting with a distinctive pattern involving hairline recession and vertex balding (Norwood-Hamilton classification) and women exhibiting diffuse hair thinning over the crown (increased part width) and sparing of the frontal hairline (Ludwig classification). Female pattern hair loss has a strikingly overwhelming psychological effect; thus, successful treatments are necessary. Difficulty lies in successful treatment interventions, as only two medications - minoxidil and finasteride - are approved for the treatment of androgenetic alopecia, and these medications offer mediocre results, lack of a permanent cure, and potential complications. Hair transplantation is the only current successful permanent option, and it requires surgical procedures. Several other medical options, such as antiandrogens (eg, spironolactone, oral contraceptives, cyproterone, flutamide, dutasteride), prostaglandin analogs (eg, bimatoprost, latanoprost), and ketoconazole are reported to be beneficial. Laser and light therapies have also become popular despite the lack of a profound benefit. Management of expectations is crucial, and the aim of therapy, given the current therapeutic options, is to slow or stop disease progression with contentment despite patient expectations of permanent hair regrowth. This article reviews current perspectives on therapeutic options for female pattern hair loss.
PubMed: 24039457
DOI: 10.2147/IJWH.S49337 -
Journal of Translational Medicine Feb 2023The incidence of bladder cancer (BCa) is approximately four times higher in men than in women. To develop effective BCa treatments, there is an urgent need to understand...
BACKGROUND
The incidence of bladder cancer (BCa) is approximately four times higher in men than in women. To develop effective BCa treatments, there is an urgent need to understand the differences in the BCa control mechanisms based on gender. Our recent clinical study showed that androgen suppression therapy using 5α-reductase inhibitors and androgen deprivation therapy affects BCa progression, but the underlying mechanisms are still unknown.
METHODS
mRNA expression levels of the androgen receptor (AR) and SLC39A9 (membrane AR) in T24 and J82 BCa cells were evaluated by reverse transcription-PCR (RT-PCR). The effect of dutasteride, a 5α-reductase inhibitor, in BCa progression was determined in cells transfected with control and AR-overexpressing plasmids. In addition, cell viability and migration assays, RT-PCR, and western blot analysis were performed to analyze the effect of dutasteride on BCa in the presence of testosterone. Finally, steroidal 5α-reductase 1 (SRD5A1), one of the dutasteride target genes, was silenced in T24 and J82 BCa cells using control and shRNA-containing plasmids, and the oncogenic role of SRD5A1 was evaluated.
RESULTS
Dutasteride treatment led to significant inhibition of the testosterone-induced increase dependent on AR and SLC39A9 in cell viability and migration of T24 and J82 BCa cells and induced alterations in the expression level of cancer progression proteins, such as metalloproteases, p21, BCL-2, NF-KB, and WNT in AR-negative BCa. Furthermore, the bioinformatic analysis showed that mRNA expression levels of SRD5A1 were significantly higher in BCa tissues than in normal paired tissues. A positive correlation between SRD5A1 expression and poor patient survival was observed in patients with BCa. Also, Dutasteride treatment reduced cell proliferation and migration via blocking the SRD5A1 in BCa.
CONCLUSIONS
Dutasteride inhibited testosterone-induced BCa progression dependent on SLC39A9 in AR-negative BCa and repressed oncogenic signaling pathways, including those of metalloproteases, p21, BCL-2, NF-KB, and WNT. Our results also suggest that SRD5A1 plays a pro-oncogenic role in BCa. This work provides potential therapeutic targets for the treatment of BCa.
Topics: Humans; 5-alpha Reductase Inhibitors; Androgen Antagonists; Androgens; Azasteroids; Dutasteride; Hyperplasia; NF-kappa B; Oxidoreductases; Prostate; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Testosterone; Urinary Bladder Neoplasms; Cell Line, Tumor
PubMed: 36800968
DOI: 10.1186/s12967-023-03972-4 -
The Lancet Regional Health. Europe Aug 2023Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms...
Prostatic artery embolisation versus medical treatment in patients with benign prostatic hyperplasia (PARTEM): a randomised, multicentre, open-label, phase 3, superiority trial.
BACKGROUND
Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms improvement after PAE and medical treatment.
METHODS
A randomised, open-label, superiority trial was set in 10 French hospitals. Patients with bothersome lower urinary tract symptoms (LUTS) defined by International Prostatic Symptom Score (IPSS) > 11 and quality of life (QoL) > 3, and BPH ≥50 ml resistant to alpha-blocker monotherapy were randomly assigned (1:1) to PAE or Combined Therapy ([CT], oral dutasteride 0.5 mg/tamsulosin hydrochloride 0.4 mg per day). Randomisation was stratified by centre, IPSS and prostate volume with a minimisation procedure. The primary outcome was the 9-month IPSS change. Primary and safety analysis were done according to the intention-to-treat (ITT) principle among patients with an evaluable primary outcome. ClinicalTrials.gov Identifier: NCT02869971.
FINDINGS
Ninety patients were randomised from September 2016 to February 2020, and 44 and 43 patients assessed for primary endpoint in PAE and CT groups, respectively. The 9-month change of IPSS was -10.0 (95% confidence interval [CI]: -11.8 to -8.3) and -5.7 (95% CI: -7.5 to -3.8) in the PAE and CT groups, respectively. This reduction was significantly greater in the PAE group than in the CT group (-4.4 [95% CI: -6.9 to -1.9], p = 0.0008). The IIEF-15 score change was 8.2 (95% CI: 2.9-13.5) and -2.8 (95% CI: -8.4 to 2.8) in the PAE and CT groups, respectively. No treatment-related AE or hospitalisation was noticed. After 9 months, 5 and 18 patients had invasive prostate re-treatment in the PAE and CT group, respectively.
INTERPRETATION
In patients with BPH ≥50 ml and bothersome LUTS resistant to alpha-blocker monotherapy, PAE provides more urinary and sexual symptoms benefit than CT up to 24 months.
FUNDING
French Ministry of Health and a complementary grant from Merit Medical.
PubMed: 37415648
DOI: 10.1016/j.lanepe.2023.100672 -
Medicine Nov 2022We performed a retrospective study to clarify the characteristics of prostate biopsies in patients treated with dutasteride, a benign prostate hyperplasia treatment drug...
We performed a retrospective study to clarify the characteristics of prostate biopsies in patients treated with dutasteride, a benign prostate hyperplasia treatment drug that inhibits 5α-reductase. We studied the digital clinical data of 677 patients, including 96 cases treated with dutasteride, with suspected localized prostate cancer. All patients underwent transrectal ultrasonography-guided prostate biopsy between 2014 and 2017 in our department. A propensity score matching analysis was performed based on prostate-specific antigen (PSA) (calculated as double the PSA value for the dutasteride group) and age. Ninety-six patients in each of the dutasteride and control groups were assessed and their characteristics were compared. The characteristics of the patients in the dutasteride and control groups were well balanced by matching. There were fewer prostate cancer-positive patients in the dutasteride group. When comparing only the prostate cancer-positive patients in each group, there were significantly more cases of high-grade cancers and abnormal magnetic resonance imaging (MRI) findings in the dutasteride group. In the dutasteride group, abnormal MRI findings and advanced age were significant predictors of high grade cancer. This study shows the characteristics of prostate biopsies in patients treated with dutasteride and indicates that patients on dutasteride with advanced age and abnormal MRI findings should undergo prostate biopsy.
Topics: Male; Humans; Dutasteride; Prostate; Prostate-Specific Antigen; Azasteroids; 5-alpha Reductase Inhibitors; Retrospective Studies; Biopsy; Prostatic Neoplasms
PubMed: 36343082
DOI: 10.1097/MD.0000000000031658 -
Asian Journal of Urology Jan 2018Benign prostatic hyperplasia (BPH) is characterized by an enlarged prostate, lower urinary tract symptoms (LUTS), and a decreased urinary flow rate. Common in older men,... (Review)
Review
Benign prostatic hyperplasia (BPH) is characterized by an enlarged prostate, lower urinary tract symptoms (LUTS), and a decreased urinary flow rate. Common in older men, BPH is a progressive disease that can eventually lead to complications including acute urinary retention (AUR) and the need for BPH-related surgery. Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone (DHT), which is formed from testosterone under the influence of 5-alpha reductase. Thus, 5-alpha reductase inhibitors (5-ARIs) effectively reduce the serum and intraprostatic concentration of DHT, causing an involution of prostate tissue. Two 5-ARIs are currently available for the treatment of BPH-finasteride and dutasteride. Both have been demonstrated to decrease prostate volume, improve LUTS and urinary flow rates, which ultimately reduces the risk of AUR and BPH-related surgery. Therefore, either alone or in combination with other BPH medications, 5-ARIs are a mainstay of BPH management.
PubMed: 29379733
DOI: 10.1016/j.ajur.2017.11.005 -
F1000Research 2021Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including... (Review)
Review
Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including targeting the regulation of 5-alpha-Reductase (5αR) enzyme activity, aimed to limit the progression of CaP by inhibiting the conversion of potent androgen dihydrotestosterone from testosterone that is thought to play a role in pathogenesis of CaP, by using the 5-alpha-Reductase inhibitors (5αRis) such as finasteride and dutasteride. However, 5αRis are reported to exhibit numerous adverse side effects, for instance erectile dysfunction, ejaculatory dysfunction and loss of libido. This has led to a surge of interest on plant-derived alternatives that might offer favourable side effects and less toxic profiles. Phytochemicals from plants are shown to exhibit numerous medicinal properties in various studies targeting many major illnesses including CaP. Therefore, in this review, we aim to discuss the use of phytochemicals namely phytosterols, polyphenols and fatty acids, found in various plants with proven anti-CaP properties, as an alternative herbal CaP medicines as well as to outline their inhibitory activities on 5αRs isozymes based on their structural similarities with current 5αRis as part of CaP treatment approaches.
Topics: Cholestenone 5 alpha-Reductase; Humans; Male; Oxidoreductases; Phytochemicals; Prospective Studies; Prostatic Neoplasms
PubMed: 34316358
DOI: 10.12688/f1000research.51066.3 -
Experimental Neurology May 2023Growing preclinical and clinical evidence highlights neurosteroid pathway imbalances in Parkinson's Disease (PD) and L-DOPA-induced dyskinesias (LIDs). We recently...
Growing preclinical and clinical evidence highlights neurosteroid pathway imbalances in Parkinson's Disease (PD) and L-DOPA-induced dyskinesias (LIDs). We recently reported that 5α-reductase (5AR) inhibitors dampen dyskinesias in parkinsonian rats; however, unraveling which specific neurosteroid mediates this effect is critical to optimize a targeted therapy. Among the 5AR-related neurosteroids, striatal pregnenolone has been shown to be increased in response to 5AR blockade and decreased after 6-OHDA lesions in the rat PD model. Moreover, this neurosteroid rescued psychotic-like phenotypes by exerting marked antidopaminergic activity. In light of this evidence, we investigated whether pregnenolone might dampen the appearance of LIDs in parkinsonian drug-naïve rats. We tested 3 escalating doses of pregnenolone (6, 18, 36 mg/kg) in 6-OHDA-lesioned male rats and compared the behavioral, neurochemical, and molecular outcomes with those induced by the 5AR inhibitor dutasteride, as positive control. The results showed that pregnenolone dose-dependently countered LIDs without affecting L-DOPA-induced motor improvements. Post-mortem analyses revealed that pregnenolone significantly prevented the increase of validated striatal markers of dyskinesias, such as phospho-Thr-34 DARPP-32 and phospho-ERK, as well as D-D receptor co-immunoprecipitation in a fashion similar to dutasteride. Moreover, the antidyskinetic effect of pregnenolone was paralleled by reduced striatal levels of BDNF, a well-established factor associated with the development of LIDs. In support of a direct pregnenolone effect, LC/MS-MS analyses revealed that striatal pregnenolone levels strikingly increased after the exogenous administration, with no significant alterations in downstream metabolites. All these data suggest pregnenolone as a key player in the antidyskinetic properties of 5AR inhibitors and highlight this neurosteroid as an interesting novel tool to target LIDs in PD.
Topics: Male; Rats; Animals; Levodopa; Parkinson Disease; Dutasteride; Oxidopamine; Neurosteroids; Rats, Sprague-Dawley; Dyskinesia, Drug-Induced; Corpus Striatum; Antiparkinson Agents; Disease Models, Animal
PubMed: 36878398
DOI: 10.1016/j.expneurol.2023.114370 -
Skin Therapy Letter Jun 2012Androgenetic alopecia (AGA) may affect up to 70% of men and 40% of women at some point in their lifetime. While men typically present with a distinctive alopecia pattern... (Review)
Review
Androgenetic alopecia (AGA) may affect up to 70% of men and 40% of women at some point in their lifetime. While men typically present with a distinctive alopecia pattern involving hairline recession and vertex balding, women normally exhibit a diffuse hair thinning over the top of their scalps. The treatment standard in dermatology clinics continues to be minoxidil and finasteride with hair transplantation as a surgical option. Here we briefly review current therapeutic options and treatments under active investigation. Dutasteride and ketoconazole are also employed for AGA, while prostaglandin analogues latanoprost and bimatoprost are being investigated for their hair growth promoting potential. Laser treatment products available for home use and from cosmetic clinics are becoming popular. In the future, new cell mediated treatment approaches may be available for AGA. While there are a number of potential treatment options, good clinical trial data proving hair growth efficacy is limited.
Topics: Alopecia; Female; Finasteride; Hair; Humans; Laser Therapy; Male; Minoxidil; Sex Factors
PubMed: 22735503
DOI: No ID Found -
Iranian Journal of Allergy, Asthma, and... Oct 2022Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation...
Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β), and nitric oxide (NO) in the Lipopolysaccharides (LPS)-stimulated U-87 MG cell line. Human astrocytoma U-87 MG cell line was cultured and incubated with 10 μg/mL of LPS for 24 hours to create a neuro-inflammation model, using two different treatment approaches. The first approach included LPS treatment for 24 hours, followed by dutasteride (20 μg/mL) incubation for the next 72 hours. In the second treatment approach, the cells were co-incubated with LPS and dutasteride for 72 hours. Expression of TLR4, MyD88, NF-κBp65, and secretory IL-1 was evaluated by Western blotting while expression of NO was assessed by NO assay. TLR4, MyD88, NF-κBp65, and secretory IL-1β levels increased in LPS-treated cells after 24 hours. Dutasteride significantly decreased the secretion of NO and also, the levels of TLR4, MyD88, and NF-κBp65 in both treatment approaches. No difference in IL-1β level was seen with the second treatment approach. Dutasteride has anti-inflammatory properties and probably analgesic effects, by mechanisms different from conventional analgesics.
Topics: Humans; Toll-Like Receptor 4; Lipopolysaccharides; Myeloid Differentiation Factor 88; Dutasteride; Signal Transduction; NF-kappa B; Pain
PubMed: 36341565
DOI: 10.18502/ijaai.v21i5.11044 -
Neurobiology of Stress May 2020The presence of side effects during pharmacological treatment is unfortunately a quite common problem. In this review, we focused our attention on adverse events related...
The presence of side effects during pharmacological treatment is unfortunately a quite common problem. In this review, we focused our attention on adverse events related to 5 alpha-reductase (5α-R) inhibitors (i.e., finasteride and dutasteride), approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia (AGA). Although these drugs are generally well tolerated, many reports described adverse effects in men during treatment, such as sexual dysfunction and mood alteration. In addition, it has been also reported that persistent side effects may occur in some AGA patients. This condition, termed post-finasteride syndrome (PFS) is characterized by sexual side effects (i.e., low libido, erectile dysfunction, decreased arousal and difficulty in achieving orgasm), depression, anxiety and cognitive complaints that are still present despite drug withdrawal. Indeed, some national agencies (e.g., Swedish Medical Products Agency, the Medicines and Healthcare Products Regulatory Agency of UK and the U.S. Food and Drug Administration) required to include multiple persistent side effects within the finasteride labels. As here reported, these observations are mainly based on self-reporting of the symptomatology by the patients and few clinical studies have been performed so far. In addition, molecular mechanisms and/or genetic determinants behind such adverse effects have been poorly explored both in patients and animal models. Therefore, results here discussed indicate that PFS is an emerging clinical problem that needs to be further elucidated.
PubMed: 32435662
DOI: 10.1016/j.ynstr.2019.100209