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Nature Reviews. Urology May 2011Testosterone is the most abundant circulating androgen, and can be converted to dihydrotestosterone (DHT), a more potent androgen, by the 5α-reductase enzymes in target... (Review)
Review
Testosterone is the most abundant circulating androgen, and can be converted to dihydrotestosterone (DHT), a more potent androgen, by the 5α-reductase enzymes in target tissues. Current treatments for prostate cancer consist of reducing androgen levels by chemical or surgical castration or pure antiandrogen therapy that directly targets the androgen receptor (AR). Although these therapies reduce tumor burden and AR activity, the cancer inevitably recurs within 18-30 months. An approach targeting the androgen-AR axis at different levels could, therefore, improve the efficacy of prostate cancer therapy. Inhibition of 5α-reductase is one such approach; however, the two largest trials to investigate the use of the 5α-reductase inhibitors (5ARIs) finasteride and dutasteride in patients with prostate cancer have shown that, although the incidence of cancer was reduced by 5ARI treatment, those cancers that were detected were more aggressive than in patients treated with placebo. Thus, the best practice for using these drugs to prevent and treat prostate cancer remains unclear.
Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; 5-alpha Reductase Inhibitors; Animals; Dihydrotestosterone; Drug Delivery Systems; Humans; Male; Prostatic Neoplasms; Signal Transduction; Testosterone; Treatment Outcome
PubMed: 21629218
DOI: 10.1038/nrurol.2011.67 -
Prostate International Jun 2020The aim of this research is to study the influence of simultaneous taking of tadalafil and solifenacin in standard and double dosage on the lower urinary tract symptoms...
Improvement of the symptoms of lower urinary tract and sexual dysfunction with tadalafil and solifenacin after the treatment of benign prostatic hyperplasia with dutasteride.
BACKGROUND
The aim of this research is to study the influence of simultaneous taking of tadalafil and solifenacin in standard and double dosage on the lower urinary tract symptoms (LUTS) and sexual dysfunction in men with benign prostatic hyperplasia after the course of dutasteride.
MATERIALS AND METHODS
The research included 326 patients older than 50 years with benign prostatic hyperplasia coupled with LUTS and sexual dysfunction having undergone the course of treatment with dutasteride. After random division into three groups, patients from the Group A ( = 107) got tadalafil 5 mg/d as monotherapy, from the Group В ( = 107) got tadalafil 5 mg/d and solifenacin 10 mg/d, and from the Group С ( = 112) got tadalafil 5 mg/d and solifenacin 20 mg/d. The duration of treatment was 12 weeks. The rating of sexual function was made with the questionnaires International Index of Erectile Function and other.
RESULTS
The results of rating of sexual function with the questionnaires MSHQ-EjD and International Index of Erectile Function correlated among themselves. According to MSHQ-EjD, overall rating of the sexual function increased in each of the three groups (A: 67.9 (12.4)/91.5 (10.4), ≤ 0.05; B: 72.4 (14.5)/102.6 (16.9), ≤ 0.05; C: 76.6 (16.3)/109.6 (15.6), ≤ 0.05). The level of hyperactivity symptoms decreased in Groups В and С (В: urgency -2.9 (0.7)/1.1 (0.6), ≤ 0.05; nocturia 2.7 (1.0)/0.7 (0.5), ≤ 0.05; C: urgency -2.5 (0.5)/0.8 (0.6), ≤ 0.05; nocturia -2.8 (0.6)/1.0 (0.5), ≤ 0.05), and it did not change in the Group A.
CONCLUSIONS
The use of tadalafil as monotherapy significantly improves the sexual function but does not affect overactive bladder symptoms. The combination therapy of tadalafil and solifenacin leads to dramatic improvement of sexual function and reversibility of detrusor hyperactivity symptoms.
PubMed: 32647644
DOI: 10.1016/j.prnil.2019.11.005 -
Problemy Endokrinologii Sep 2022Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. There is evidence that PD has a wider prevalence among men, which... (Review)
Review
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. There is evidence that PD has a wider prevalence among men, which indicates the existing role of sex hormones in the pathogenesis of the disease. The article presents an overview of studies devoted to the study of sex differences in the incidence and symptoms of PD. Drug therapy with androgens, androgen precursors, antiandrogens and drugs that modify androgen metabolism is available for the treatment of various endocrine conditions, having translational significance for PD, but none of these drugs has yet shown sufficient effectiveness. Although PD has now been proven to be more common in men than in women, androgens do not always have any effect on the symptoms or progression of the disease. 5α-reductase inhibitors have shown neuroprotective and anti-dyskinetic activity and need further investigation. Despite the fact that the neuroprotective effect of dutasteride was observed only before damage to DA neurons, the absence of a negative effect makes it an attractive drug for use in patients with PD due to its anti-dyskinetic properties.
Topics: Female; Humans; Male; 5-alpha Reductase Inhibitors; Androgens; Dutasteride; Neurodegenerative Diseases; Parkinson Disease
PubMed: 36689720
DOI: 10.14341/probl13148 -
JAMA Dermatology Jan 2021There is ongoing controversy about the adverse events of finasteride, a drug used in the management of alopecia and benign prostatic hyperplasia (BPH). In 2012, reports...
IMPORTANCE
There is ongoing controversy about the adverse events of finasteride, a drug used in the management of alopecia and benign prostatic hyperplasia (BPH). In 2012, reports started emerging on men who had used finasteride and either attempted or completed suicide.
OBJECTIVE
To investigate the association of suicidality (ideation, attempt, and completed suicide) and psychological adverse events (depression and anxiety) with finasteride use.
DESIGN, SETTING, AND PARTICIPANTS
This pharmacovigilance case-noncase study used disproportionality analysis (case-noncase design) to detect signals of adverse reaction of interest reported with finasteride in VigiBase, the World Health Organization's global database of individual case safety reports. To explore the strength of association, the reporting odds ratio (ROR), a surrogate measure of association used in disproportionality analysis, was used. Extensive sensitivity analyses included stratifying by indication (BPH and alopecia) and age (≤45 and >45 years); comparing finasteride signals with those of drugs with different mechanisms but used for similar indications (minoxidil for alopecia and tamsulosin hydrochloride for BPH); comparing finasteride with a drug with a similar mechanism of action and adverse event profile (dutasteride); and comparing reports of suicidality before and after 2012. Data were obtained in June 2019 and analyzed from January 25 to February 28, 2020.
EXPOSURES
Reported finasteride use.
MAIN OUTCOMES AND MEASURES
Suicidality and psychological adverse events.
RESULTS
VigiBase contained 356 reports of suicidality and 2926 reports of psychological adverse events (total of 3282 adverse events of interest) in finasteride users (3206 male [98.9%]; 615 of 868 [70.9%] with data available aged 18-44 years). A significant disproportionality signal for suicidality (ROR, 1.63; 95% CI, 1.47-1.81) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) in finasteride was identified. In sensitivity analyses, younger patients (ROR, 3.47; 95% CI, 2.90-4.15) and those with alopecia (ROR, 2.06; 95% CI, 1.81-2.34) had significant disproportionality signals for increased suicidality; such signals were not detected in older patients with BPH. Sensitivity analyses also showed that the reports of these adverse events significantly increased after 2012 (ROR, 2.13; 95% CI, 1.91-2.39).
CONCLUSIONS AND RELEVANCE
In this pharmacovigilance case-noncase study, significant RORs of suicidality and psychological adverse events were associated with finasteride use in patients younger than 45 years who used finasteride for alopecia. The sensitivity analyses suggest that these disproportional signals of adverse events may be due to stimulated reporting and/or younger patients being more vulnerable to finasteride's adverse effects.
Topics: 5-alpha Reductase Inhibitors; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Alopecia; Anxiety; Case-Control Studies; Depression; Female; Finasteride; Humans; Male; Pharmacovigilance; Prostatic Hyperplasia; Sex Factors; Suicide; Young Adult
PubMed: 33175100
DOI: 10.1001/jamadermatol.2020.3385 -
Prostate International Dec 2022Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health...
OBJECTIVES
Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health concern in the aging population. The purpose of this study is to identify modifiable factors, which would prevent or delay BPH development.
METHODS
The association between BPH marker drugs and climate-, socioeconomic-, health condition-, and lifestyle habits-related variables was investigated by analyzing nationwide datasets which were collected in 2018, aggregated by prefecture (administrative unit), and published by Japanese ministries. Uroselective α receptor blockers and dutasteride were used as marker drugs referring to BPH prevalence. Correlation analysis, multiple linear regression analysis, and binomial logistic regression analysis were conducted with 47 Japanese prefectures as the unit.
RESULTS
The variables which showed || > 0.5 by correlation analysis were exercise habits ( = -0.5696), smoking habits ( = 0.6116), and daily drinking ( = 0.6001) for uroselective α receptor blockers, and antihypertensive medication ( = 0.5971), smoking habits ( = 0.6598), a small amount of drinking ( = -0.5292), and serum alanine aminotransferase ( = 0.6814) for dutasteride. Multiple linear regression equations were constructed by including these variables ( = 0.5453 for uroselective α receptor blockers and = 0.5673 for dutasteride). Binomial logistic regression analysis found a significant association between climate in the resident area and BPH development.
CONCLUSION
This ecological study, analyzing Japanese nationwide datasets, demonstrates that healthy lifestyle habits, especially avoidance of smoking, implementation of exercise in daily life, and a small amount of alcohol consumption, are important to prevent or delay BPH development. High blood pressure and high serum alanine aminotransferase are suggested as risk factors of BPH development.
PubMed: 36570647
DOI: 10.1016/j.prnil.2022.06.004 -
Dermatology Online Journal Apr 2013Hidradenitis suppurativa (HS), a pathological follicular disease, impacts patients' lives profoundly. HS most commonly involves cutaneous intertriginous areas, such as... (Review)
Review
Hidradenitis suppurativa (HS), a pathological follicular disease, impacts patients' lives profoundly. HS most commonly involves cutaneous intertriginous areas, such as the axilla, inner thighs, groin and buttocks, and pendulous breasts, but can appear on any follicular skin. Protean, HS manifests with variations of abscesses, folliculitis, pyogenic granulomas, scars (oval honeycombed), comedones, tracts, fistulas, and keloids. The pathophysiology might involve both defects of the innate follicular immunity and overreaction to coagulase negative Staphylococcus. Treatment depends on the morphology, extent, severity, and duration. Topical clindamycin and dapsone are often adequate for treating mild HS. For Stage 1 and 2 HS, first line treatment combines rifampin with either oral clindamycin or minocycline. Other HS treatments include: fluoroquinolones with metronidazole and rifampin, oral dapsone, zinc, acitretin, hormone blockers (oral contraceptive pills, spironolactone, finasteride, and dutasteride), and oral prednisone. For severe HS, cyclosporine, adalimumab, or infliximab (used at double psoriatic doses) and intravenous carbapenems or cephalosporins are often required. Isotretinoin, etanercept, isoniazid, lymecycline, sulfasalazine, methotrexate, metformin, colchicine, clarithromycin, IVIG, and thalidomide are less favored treatments. The role of botulinum toxin is uncertain. The most important life style modification is weight loss. De-roofing fluctuant nodules and injection of intralesional corticosteroids ameliorates the disease and perhaps, if done at regular intervals, improves HS more permanently. Surgical excision and CO2 laser ablation are more definitive treatments. The 1064 nm laser for hair removal aids in the treatment of HS. This article centers on medical therapies and will only passingly mention surgical and laser treatments. This article summarizes my treatment experience with over 350 HS patients.
Topics: Abscess; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bandages; Biofilms; Combined Modality Therapy; Drainage; Gonadal Steroid Hormones; Hair Follicle; Hair Removal; Hidradenitis Suppurativa; Hormone Antagonists; Hormones; Humans; Hyperbaric Oxygenation; Immunosuppressive Agents; Metformin; Obesity; Pain Management; Retinoids; Staphylococcal Skin Infections; Tumor Necrosis Factor-alpha; Weight Loss
PubMed: 24021361
DOI: No ID Found -
International Journal of Molecular... Aug 2016Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and... (Review)
Review
Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.
Topics: Apoptosis; Dutasteride; Endocrine System; Finasteride; Humans; Male; Prostatic Hyperplasia; Quinazolines; Sulfonamides; Tamsulosin; Urological Agents
PubMed: 27529214
DOI: 10.3390/ijms17081311 -
Pharmaceutics Nov 2017Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into... (Review)
Review
Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into self-emulsifying drug delivery systems (SEDDS). Several such pharmaceutical products have appeared in the market for medium dose (Neoral for Cyclsoprin A, Kaletra for Lopinavir and Ritonavir), or low dose medications (Rocaltrol for Calcitriol and Avodart for Dutasteride). However, these are in the form of viscous liquids or semisolid presentations, characterized by the disadvantages of high production cost, stability problems and the requirement of large quantities of surfactants. Solid SEDDS (S-SEDDS), as coarse powders, granules or pellets, besides solubility improvement, can be filled easily into capsules or processed into tablets providing a handy dosage form with instant release, which can be further developed into controlled release by mixing with suitable polymers or coating with polymeric films. In this review, the materials used for the preparation of S-SEDDS, their properties and role in the formulations are detailed. Factors affecting the physical characteristics, mechanical properties of S-SEDDS as well as their in vitro release and in vivo absorption are discussed. The mechanisms involved in the formation of instant and sustained release self-emulsifying granules or pellets are elucidated. Relationships are demonstrated between the characteristics of S-SEDDS units (size, shape, mechanical properties, re-emulsification ability, drug migration and drug release) and the properties of the submicron emulsions used as massing liquids, with the aim to further elucidate the formation mechanisms. The influence of the composition of the powdered ingredients forming the granule or pellet on the properties of S-SEDDS is also examined. Examples of formulations of S-SEDDS that have been reported in the literature in the last thirteen years (2004-2017) are presented.
PubMed: 29099779
DOI: 10.3390/pharmaceutics9040050 -
Frontiers in Oncology 2014The first advance in the history of studies on prostate cancer (PCa) and androgens was the development of treatment with castration and administration of estrogen by... (Review)
Review
The first advance in the history of studies on prostate cancer (PCa) and androgens was the development of treatment with castration and administration of estrogen by Charles B. Huggins, who won the Nobel Prize in Physiology and Medicine. Since then, and for 70 years, androgen deprivation therapy has been the standard therapy for advanced PCa and the center of studies on PCa. However, recent advances have shed light on the relationship between androgens and the development or the progression of PCa. The use of 5AR inhibitors to prevent progression of PCa continues to be widely discussed. Discussion has been fueled by the findings of two large randomized, placebo-controlled trials: the Prostate Cancer Prevention Trial with finasteride and the Reduction by Dutasteride of Prostate Cancer Events trial. Does the development of PCa or progression to castration-resistant PCa depend on dihydrotestosterone (DHT)? Here, we summarize and discuss recent topics of local androgen production of DHT in PCa.
PubMed: 25279351
DOI: 10.3389/fonc.2014.00247 -
Translational Andrology and Urology Feb 2020The objective of this study is to review our 12-year experience with the 5-α reductase inhibitor dutasteride as a potential long-term treatment option for stuttering...
BACKGROUND
The objective of this study is to review our 12-year experience with the 5-α reductase inhibitor dutasteride as a potential long-term treatment option for stuttering priapism. Dutasteride has a uniquely long half-life of 35 days which offers a theoretical advantage as a chronic therapy for management of stuttering priapism.
METHODS
We retrospectively reviewed patients with stuttering priapism in our database from 2006-2018 treated with dutasteride. Men with concurrent use of medications other than dutasteride to treat stuttering priapism were excluded. Patients were started on a dose of 0.5 mg daily and tapered to a more infrequent dosing schedule, ranging from 0.5 mg every other day to once weekly. The frequency of priapism episodes before and after initiation of dutasteride therapy was analyzed.
RESULTS
Among 21 cases, 13 patients met our inclusion criteria (mean age 43 years). Median follow-up on daily dutasteride was 79 days, and median follow-up on tapered dutasteride was 607 days. A total of 11/13 (85%) men treated with dutasteride had some degree of improvement-5/13 (38%) had complete resolution of their symptoms and 6/13 (46%) had reduced frequency and/or severity of their episodes. Among 5/13 (38%) men who had >2 emergency room (ER) visits for ischemic priapism prior to therapy, most (3/5, 60%) did not require any ER visits while on dutasteride therapy. Among the five men who received chronic, tapered-dose therapy, all reported continued suppression of priapistic episodes. Among 4 patients with sickle cell disease (SCD), 3/4 (75%) ultimately chose more invasive therapy including androgen deprivation therapy (ADT) and penile prosthesis. Side effects were minimal and included gynecomastia (8%), decreased libido (8%), and fatigue (8%).
CONCLUSIONS
In patients with stuttering priapism, daily dutasteride therapy is a promising treatment option to reduce the frequency and severity of priapistic episodes without significant side effects. Therapy can effectively be tapered to once weekly dosing without a reduction in efficacy.
PubMed: 32055472
DOI: 10.21037/tau.2019.07.15