-
Expert Opinion on Pharmacotherapy 2023
Topics: Male; Humans; 5-alpha Reductase Inhibitors; Alopecia; Finasteride; Dutasteride
PubMed: 37942878
DOI: 10.1080/14656566.2023.2280630 -
The Journal of Urology Jan 2024Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support...
PURPOSE
Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support this idea. We tested if elevated serum testosterone or dihydrotestosterone were risk factors for lower urinary tract symptoms incidence in asymptomatic men and for lower urinary tract symptoms progression in symptomatic men.
MATERIALS AND METHODS
A post hoc analysis of REDUCE was performed in 3009 asymptomatic men and in 2145 symptomatic men. REDUCE was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated prostate-specific antigen and negative prestudy biopsy. We estimated multivariable adjusted hazard ratios and 95% confidence intervals using Cox models to test the association between quintiles of serum testosterone and dihydrotestosterone at baseline and lower urinary tract symptoms incidence and progression and tested for interaction by treatment arm (dutasteride vs placebo).
RESULTS
In asymptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms incidence ( = .9, = .4). In symptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms progression ( = .9, = .7). Results were similar in both placebo and dutasteride arms (all interaction ≥ .3).
CONCLUSIONS
In REDUCE, higher serum testosterone and higher serum dihydrotestosterone were not associated with either lower urinary tract symptoms incidence in asymptomatic men or lower urinary tract symptoms progression in symptomatic men. These data do not support the hypothesis that serum androgens in middle-aged men are associated with lower urinary tract symptoms.
Topics: Humans; Male; Middle Aged; Dihydrotestosterone; Dutasteride; Incidence; Lower Urinary Tract Symptoms; Prostatic Hyperplasia; Testosterone; Randomized Controlled Trials as Topic
PubMed: 37873943
DOI: 10.1097/JU.0000000000003738 -
Facial Plastic Surgery : FPS Apr 2024Androgenetic alopecia is a common type of hair loss, which is generally influenced by genetic factors and systemic androgens resulting in follicular miniaturization.1 It...
Androgenetic alopecia is a common type of hair loss, which is generally influenced by genetic factors and systemic androgens resulting in follicular miniaturization.1 It can cause cosmetic problems leading to psychological distress among affected men and women. Effective standard medical treatments available are topical minoxidil 2 to 5%, oral finasteride, oral dutasteride, and hair transplantation.1 However, some patients do not achieve favorable results with standard treatments. For these reasons, other novel treatments have been developed, including new medications, regenerative medicines (autologous platelet-rich plasma, adipose-derived stem cells, micrograft generation, and exosome), and low-level laser therapy.
Topics: Male; Humans; Female; Alopecia; Finasteride; Minoxidil; Low-Level Light Therapy; Platelet-Rich Plasma; Treatment Outcome
PubMed: 37871637
DOI: 10.1055/a-2196-4713 -
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 -
Prostate Cancer and Prostatic Diseases Oct 2023Modeling studies using large datasets from men with lower urinary tract symptoms/benign prostate enlargement (LUTS/BPE) can predict changes in International Prostate...
Modeling study of the effect of placebo and medical therapy on storage and voiding symptoms, nocturia, and quality of life in men with prostate enlargement at risk for progression.
BACKGROUND
Modeling studies using large datasets from men with lower urinary tract symptoms/benign prostate enlargement (LUTS/BPE) can predict changes in International Prostate Symptom Score (IPSS) and risk of acute urinary retention/surgery under different treatment regimens and according to predictors (baseline characteristics) that commonly define risk of progression. We assessed the impact of treatments on different symptom types (storage, voiding, and nocturia), quality of life (QoL; IPSS Q8), and BPH Impact Index [BII]).
METHODS
Generalized least squares models were used to predict each outcome. Data from the CombAT study were used to predict outcomes for active treatments (dutasteride, tamsulosin, combination therapy). Predictors included: age; IPSS total, storage, voiding, nocturia and QoL (IPSS Q8) scores; BII; prostate volume; maximum urine flow rate (Qmax), prostate-specific antigen, postvoid residual urine (PVR); alpha-blocker usage within 12 months. Data from phase III dutasteride monotherapy studies were used to predict placebo outcomes. Results were visualized using an interactive web-based tool ( www.bphtool.com ).
RESULTS
Combination therapy provided greater predicted benefit than either monotherapy for all five outcomes for most patient profiles within the CombAT inclusion criteria. PVR and corresponding subscores were significant predictors of change in both storage and voiding subscores. Alpha-blocker use within 12 months, age (storage subscore), and Qmax (voiding subscore) were also significant predictors. PVR, age, Qmax, and nocturia score were significant predictors of change in nocturia. PVR, Qmax, previous alpha-blocker use, total IPSS, and QoL (IPSS Q8) score were significant predictors of change in QoL (IPSS Q8) score. For BII, significant predictors were PVR, age, total IPSS, and BII score. The multivariable effect of covariates and treatments is best visualized through the interactive web-based tool.
CONCLUSIONS
This predictive modeling study informs our understanding of how risk factors for disease progression interact and affect treatment impact on different symptom types and QoL scores.
PubMed: 37794168
DOI: 10.1038/s41391-023-00731-w -
Medicina (Kaunas, Lithuania) Sep 2023: Androgenetic alopecia (AGA) and alopecia areata (AA) are the most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options...
: Androgenetic alopecia (AGA) and alopecia areata (AA) are the most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options and affect patient quality of life. Pharmacogenetic tests can help predict the most appropriate treatment option by evaluating the single nucleotide polymorphisms (SNPs) corresponding to genes related to alopecia. The objective of the study was to evaluate and compare selected SNPs and genes in AA and AGA patients from Romania and Brazil. : We performed a retrospective study regarding the associations between AA and AGA and 45 tag SNPs of 15 genes in 287 Romanian and 882 Brazilian patients. The DNA samples were collected from oral mucosa using a swab. The SNPs were determined by the qPCR technique. Each genetic test displays the subject's genotype of the selected gene and the prediction of a successful treatment (e.g., genotype AA of the GR-alpha gene is related to a predisposition to normal sensibility to topical glucocorticoid, and, therefore, glucocorticoids should be effective). : The , , , and genes were statistically significantly different in Brazil compared to Romania. The activity that predicts the response to minoxidil treatment showed in our analysis that minoxidil is recommended in half of the cases of AGA and AA. Patients with AGA and a high expression of or -2 may benefit from Dutasteride or Latanoprost treatment, respectively. Most of the studied genes showed no differences between the two populations. : The DNA analysis of the patients with alopecia may contribute to a successful treatment.
PubMed: 37763773
DOI: 10.3390/medicina59091654 -
International Journal of Impotence... Sep 2023Finasteride and dutasteride, synthetic 5α-reductase inhibitors (5ARIs) are recommended in many guidelines for the treatment of benign prostatic hyperplasia/lower... (Review)
Review
Finasteride and dutasteride, synthetic 5α-reductase inhibitors (5ARIs) are recommended in many guidelines for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms and alopecia despite a variety of side effects like sexual, neurological, psychiatric, endocrinological, metabolic and ophthalmological dysfunctions and the increased incidence of high grade prostate cancer. The sexual side effects are common during the use of the drug but in a small subgroup of patients, they can persist after stopping the drug. This so-called post-finasteride syndrome has serious implications for the quality of life without a clear etiology or therapy. Three types of 5α-reductases are present in many organs in- and outside the brain where they can be blocked by the two 5ARIs. There is increasing evidence that 5ARIs not only inhibit the conversion of testosterone to 5α-dihydrotestosterone (DHT) in the prostate and the scalp but also in many other tissues. The lipophilic 5ARIs can pass the blood-brain barrier and might block many other neurosteroids in the brain with changes in the neurochemistry and impaired neurogenesis. Further research and therapeutic innovations are urgently needed that might cure or relieve these side effects. More awareness is needed for physicians to outweigh these health risks against the benefits of 5ARIs.
PubMed: 37697052
DOI: 10.1038/s41443-023-00759-5 -
Cureus Jul 2023Androgenic alopecia (AGA), commonly known as male pattern baldness (MPB), is a hereditary condition characterized by hair follicles that are sensitive to androgens. This... (Review)
Review
Androgenic alopecia (AGA), commonly known as male pattern baldness (MPB), is a hereditary condition characterized by hair follicles that are sensitive to androgens. This article focuses on examining the recent advancements in the comprehension and management of AGA. The genetic factors and pathophysiology of AGA, including the role of dihydrotestosterone (DHT) and the androgen receptor gene, are discussed. The consequences of hair loss on self-esteem and identity, as well as on mental health, are examined. Diagnostic methods, such as the hair-pull test and trichoscopy, are discussed. The article also presents the Hamilton-Norwood classification, which is the most commonly employed system for classifying MPB. The article then delves into the various treatment options available, including topical minoxidil, oral finasteride, platelet-rich plasma therapy, low-level light therapy, hair transplant, and other alternative treatments. The efficacy and combination therapies for these treatments are examined. Additionally, emerging treatments such as caffeine-based solutions and prostaglandin inhibitors are discussed. By examining the recent advancements in AGA treatment, this article provides a comprehensive overview for healthcare professionals to make informed decisions when selecting the best treatment options for their patients.
PubMed: 37663989
DOI: 10.7759/cureus.42768 -
Biochemical Pharmacology Oct 2023Trypanosoma cruzi is the causative agent of Chagas' disease, an endemic and neglected disease. The treatment is limited to only two drugs, benznidazole (BZL) and...
Trypanosoma cruzi is the causative agent of Chagas' disease, an endemic and neglected disease. The treatment is limited to only two drugs, benznidazole (BZL) and nifurtimox (NFX), introduced more than fifty years ago and no new advances have been made since then. Nucleoside diphosphate kinases (NDPK) are key metabolic enzymes which have gained interest as drug targets of pathogen organisms. Taking advantage of the computer-assisted drug repurposing approaches, in the present work we initiate a search of potential T. cruzi nucleoside diphosphate kinase 1 (TcNDPK1) inhibitors over an ∼ 12,000 compound structures database to find drugs targeted to this enzyme with trypanocidal activity. Four medicines were selected and evaluated in vitro, ketorolac (KET, an anti-inflamatory), dutasteride (DUT, used to treat benign prostatic hyperplasia), nebivolol and telmisartan (NEB and TEL, used to treat high blood pressure). The four compounds were weak inhibitors and presented different trypanocidal effect on epimastigotes, trypomastigotes and intracellular stages. NEB and TEL were the most active drugs with increased effect on intracellular stages, (IC = 2.25 µM and 13.21 µM respectively), and selectivity indexes of 13.01 and 8.59 respectively, showing comparable effect to BZL, the first line drug for Chagas' disease treatment. In addition, both presented positive interactions when combined with BZL. Finally, transgenic epimastigotes with increased expression of TcNDPK1 were more resistant to TEL and NEB, suggesting that TcNDPK1 is at least one of the molecular targets. In view of the results, NEB and TEL could be repurposed medicines for Chagas' disease therapy.
PubMed: 37634596
DOI: 10.1016/j.bcp.2023.115766 -
International Journal of Molecular... Aug 2023Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low...
Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)-generally used for treatment of benign prostatic enlargement-and lovastatin (Lova)-a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 μM Duta and ≥1 μM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 μM Duta + 0.5 μM Lova or 0.5 μM Duta + 1 μM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).
Topics: Male; Humans; Dutasteride; Prostate; Lovastatin; Glutamate Carboxypeptidase II; Antigens, Surface; Prostatic Neoplasms; Prostate-Specific Antigen; Cell Line, Tumor
PubMed: 37569712
DOI: 10.3390/ijms241512338