Tamsulosin

A full blood count was measured on an XE-5000 automated flow cytometer (Sysmex UK); hemoglobin A1c by reverse-phase HPLC (HA8160 analyzer; Menarini); glucose, C-peptide, renal, liver, and thyroid function tests, and lipids by autoanalyzer (Architect c16000 analyzer; Abbott Diagnostics Ltd); serum SHBG by automated chemiluminescent assay (Immulite 2000 system; Siemens); plasma insulin by ultrasensitive ELISA (DRG); salivary cortisol by high-sensitivity ELISA (Salimetrics); plasma cortisol by ¹²⁵I RIA (MP Biomedicals); plasma CBG by (¹²⁵I RIA; DIAsource ImmunoAssays SA); plasma nonesterified fatty acids (NEFAs) by a coupled enzyme reaction assay (Zen-Bio, Inc); plasma leptin, monocyte chemoattractant protein 1, IL-8, adiponectin, and resistin by Milliplex immunoassay (Merck Millipore); and plasma estradiol by chemiluminescent microparticle immunoassay (Abbott Diagnostics) using an Architect c16000 analyzer. Tamsulosin was quantified from serum by liquid chromatography tandem mass spectrometry (LC-MS/MS) (15 ). Urinary steroids were extracted (16 (link)) and analyzed (17 (link)) as described previously, with the inclusion of the following transitions (collision energy) for androgens (androsterone, etiocholanolone m/z 360→270, 5α-androstane-3α,17α-diol (internal standard) m/z 331→241 [15 V]). mRNA abundance in sc adipose tissue was determined by real-time quantitative PCR (18 (link)), as detailed in Supplemental Table 1, and presented as abundance of gene of interest normalized to the mean of a panel of reference genes (PPIA, TBP, and GAPDH), the abundance of which did not differ between groups.

This study was conducted using retrospective clinical data from VGHTC database, and was approved by institutional review board with No. CE21221A. The study endpoints included the usage of adrenergic alpha-blockers and antispasmodics after surgery for at least three months. Most patients returned back to the outpatient clinic one week after discharge and were followed up every three months afterward. The cut-off of minimum three months was identical to previous study, and was determined based on the fact that some patients may require short-term medications for LUTS [6 (link)]. The adrenergic alpha-blockers and antispasmodics prescribed within a month postoperatively were neglected since these medicines prescribed then may be for operation-related symptom relief. Data collected were classified into preoperative data and perioperative data. Preoperative data included age, body mass index (BMI), prostate specific antigen (PSA), comorbidities (hypertension, ICD9 401–405, ICD10 I10-I16; diabetes mellitus [DM], ICD9 250, ICD 10 E08-E13; ischemic heart disease, ICD9 410–414, ICD10 I20-I25; cerebrovascular disease, ICD9 430–438, ICD I60-I69; hyperlipidemia, ICD9 272, ICD10 E78; chronic obstructive pulmonary disease [COPD], ICD9 490–496, ICD10 J40-J47; peripheral vascular disease, ICD9 440–449, ICD10 I70-I79; chronic kidney disease [CKD], ICD9 585, ICD10 N18; sleep disorder, ICD9 327, ICD10 G47; gout ICD9 274, ICD10, M10), history of prostate surgery, urodynamic testing results, and the usage of adrenergic alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and antispasmodics before surgery. The age and BMI data was collected at time of operation. PSA level was collected within a year before surgery. Urodynamic testing included maximum flow rate, average flow rate, voided volume and post-void residual volume, and was performed within a year preoperatively. The adrenergic alpha-blockers, 5-ARIs and antispasmodics were coded using anatomical therapeutic chemical classification. The adrenergic alpha-blockers and 5-ARIs included Doxazosin 2mg and 4mg (C02CA04), Alfuzosin 10mg (G04CA01), Tamsulosin 0.2mg and 0.4mg (G04CA02), Terazosin 1mg and 2mg (G04CA03), Silodosin 4mg (G04CA04), Tamsulosin plus Dutasteride 0.4mg/0.5mg (G04CA52), Dutasteride 0.5mg (G04CB02), Finasteride 5mg (G04CB01). The antispasmodics included Oxybutynin 5mg (G04BD04), Tolterodine 2mg and 4mg (G04BD07), Solifenacin 5mg (G04BD08), Trospium 10mg (G04BD09), and Mirabegron 25mg and 50mg (G04BD12). Usage of adrenergic alpha-blockers, 5-ARIs and antispasmodics preoperatively were only adopted if the usage duration last at least three months.
On the contrary, perioperative data included surgical methods and resected prostate volume to preoperative prostate volume ratios. Surgical methods contained TURP, which included monopolar TURP and bipolar TURP, and laser procedure, which included laser enucleation of prostate and photoselective vaporization. Resected prostate weight to preoperative prostate volume ratios were calculated using resected prostate weight, which was based on final histopathology weight, and preoperative prostate volume, which was measured by trans-abdominal ultrasound performed within a year before surgery.

Men taking TZ/DZ/AZ were matched to men taking tamsulosin in a two-stage process. We used the “gold standard” design in pharmacoepidemiology studies known as the active comparator, new user design^{30 (link)} and extreme restriction to limit the cohort to the same condition^{31 (link)}. First, we estimated a propensity score model incorporating the following criteria: age; health care utilization during the lookback period (rate of hospitalization, rate of outpatient encounters); baseline health status (mean number of diagnoses per outpatient encounter, rate of unique outpatient diagnoses, the 29 Elixhauser comorbidities); factors for prescribing decision (diagnosis of benign prostatic hyperplasia, diagnosis of slow urinary stream, diagnosis of abnormal prostate-specific antigen (PSA), diagnosis of orthostatic hypotension, diagnosis of other hypotension, procedural claim for testing PSA, procedural claim for a uroflow study, procedural claim for a cystometrogram); and medication start date. The propensity score model was estimated using a boosted tree with the depth and number of rounds selected by testing performance on a 25% held-out validation set. Once the depth and number of rounds were selected, we used the entire data set to generate and estimate the propensity score model. Second, we required the time between the diagnosis of PD and the medication start date to be +/−180 days between possible matches. This was done to ensure a similar duration of disease and to potentially reduce unobserved heterogeneity due to differing PD severity. Within the set of possible matches based on the time between PD diagnosis and the medication start date, we selected the nearest possible match based on the log odds estimated by our propensity score model. We imposed a 20% pooled standard deviation caliper to exclude poor matches. After matching, we followed the medical records of men for 8 years to track the rates of developing dementia. We compared the hazard of developing dementia with Kaplan-Meier survival curves and Cox proportional hazards regression. Standard errors were clustered to account for the propensity score matching.

In a separate group of mice (n = 8) trained in the interval timing switch task, we investigated the acute effects of terazosin and tamsulosin. Tamsulosin is an α₁-adrenergic antagonist used for similar clinical interventions as terazosin but does not enhance glycolysis^{4 (link)}. Mice were injected (IP) once per day with either saline, terazosin (0.01 mg/kg or 0.4 mg/kg), or tamsulosin (0.01 mg/kg or 0.4 mg/kg) in a pseudorandomized, counterbalanced design. Injections were administered approximately 20 min prior to starting the interval timing switch task.