Typical serum testosterone responses to different hormonal agents. In practice, individual responses may vary significantly, therefore confirmation with individual measurement is important.
\r\n\tThe LED can be lingering further into three major categories are (i) Traditional inorganic LEDs, (ii) Organic LEDs (Small Molecule OLED, Polymer LED, Passive Matrix OLED Active Matrix OLED), (iii) High brightness LEDs, (iv) Deep-UV LEDs, (v) Active Matrix Organic Light-Emitting Diodes (AMOLED).
",isbn:"978-1-83968-886-7",printIsbn:"978-1-83968-885-0",pdfIsbn:"978-1-83968-887-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"97e861d1556a639f0e5cc6ee8bdb0a0f",bookSignature:"Prof. Jagannathan Thirumalai",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10559.jpg",keywords:"Aluminum Gallium Arsenide, Gallium Arsenide Phosphide, Indium Phosphide, Thin-Film-Display, Organic Rare-Earth Complexes, Colour Rendering Index, High Brightness Leds, Luminous Control, Air Purification, Skin Therapy, Organic Compounds Form the Electroluminescent Material, Specific Type of Thin-Film-Display",numberOfDownloads:4,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 21st 2020",dateEndSecondStepPublish:"October 19th 2020",dateEndThirdStepPublish:"December 18th 2020",dateEndFourthStepPublish:"March 8th 2021",dateEndFifthStepPublish:"May 7th 2021",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"As an expert in the optoelectronics and nanotechnology area, Dr.Thirumalai has been invited to examine several MSc and Ph.D. theses, invited to give a talk in various forums, and to review papers for international and national journals.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"99242",title:"Prof.",name:"Jagannathan",middleName:null,surname:"Thirumalai",slug:"jagannathan-thirumalai",fullName:"Jagannathan Thirumalai",profilePictureURL:"https://mts.intechopen.com/storage/users/99242/images/system/99242.png",biography:"Dr. J. Thirumalai received his Ph.D. from Alagappa University, Karaikudi in 2010. \n\nHe was awarded the Post-doctoral Fellowship from Pohang University of Science and Technology (POSTECH), Republic of Korea, in 2013.\nHe worked as an Assistant Professor of Physics, B.S. Abdur Rahman University, Chennai, India (2011 to 2016). \nCurrently, he is working as an Assistant Professor & Head of the Department of Physics, SASTRA Deemed to be University, Kumbakonam (T.N.), India. \n\nHis research interests focus on luminescence, self-assembled nanomaterials, thin-film optoelectronic devices & Supercapacitors. \n\nHe has published more than 60 SCOPUS/ISI indexed papers, 11 book chapters, and he edited 5 books. He is serving as a member in various national and international societies. Currently, he is acting as a principal investigator for a funded project towards the application of luminescence-based thin-film optoelectronic devices, funded by the Science and Engineering Research Board (SERB), India. \nAs an expert in optoelectronics and nanotechnology area, he has been invited to examine several MSc and Ph.D. theses, invited to give a talk in various forums and to review papers for international and national journals.",institutionString:"SASTRA University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"SASTRA University",institutionURL:null,country:{name:"India"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:[{id:"74673",title:"Economic Applications for LED Lights in Industrial Sectors",slug:"economic-applications-for-led-lights-in-industrial-sectors",totalDownloads:5,totalCrossrefCites:0,authors:[{id:"150046",title:"Prof.",name:"Muhammad M.A.S.",surname:"Mahmoud",slug:"muhammad-m.a.s.-mahmoud",fullName:"Muhammad M.A.S. Mahmoud"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"297737",firstName:"Mateo",lastName:"Pulko",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/297737/images/8492_n.png",email:"mateo.p@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"41801",title:"Testosterone Measurement and Prostate Cancer",doi:"10.5772/52525",slug:"testosterone-measurement-and-prostate-cancer",body:'\nTestosterone is important growth factor for prostate cells. If testosterone availability drops, prostate cells stop thriving. Benign prostate shrinks and the same happens with prostate cancer cells. Larger decrease in testosterone availability means larger reduction in prostate cells mass. Although only reduction in testosterone levels will not, in most occasions, permanently heal prostate cancer, it causes its regression and significantly delays further progression of prostate cancer. Therefore, reduction of body\'s testosterone level is important prostate cancer treatment modality. When surgical removal of prostate due to cancer is not an opinion (for example because of advanced age, significant comorbidity or because cancer has already spread beyond prostate) or was unsuccessful as noted by rising PSA, which indicates cancer growth, serum testosterone value becomes very important factor in treatment related decisions. If testosterone values are high, reduction of testosterone level will be helpful – it is expected prostate cells will react, shrink, PSA will fall. If testosterone values are already low, their further reduction with different agent may be possible. If testosterone values are already at the lowest reachable levels, other ways of treatment should be sought. After reduction of testosterone levels in the body (castration), prostate cancer cells with time (sometimes months, sometimes years, sometimes decades) develop alternative signaling mechanisms and ways of paracrine androgens supply. It is estimated this happens in a third of all prostate cancer patients [1].
\nAs this chapter focuses primarily on prostate cancer, some topics, like free-testosterone or salivary testosterone measurements are not included, because although they are related to testosterone measurement in general, they are, at least at present (things may change in the future), not used in day-to-day care of prostate cancer patients. All testosterone values mentioned relate to serum testosterone measurements.
\nTestosterone is principal male androgen, sex hormone and anabolic steroid. It is found not only in humans, but also in many other vertebrates. In males, testosterone is secreted by Leydig cells in testicles, in females by theca cells in ovaries. Small amount is produced also in zona reticularis of adrenal cortex in both genders and in placenta. Chemically (figure 1), it is white powder, soluble in methanol, name is17beta-Hydroxyandrost-4-en-3-on or 4-Androsten-17beta-ol-3-on, Chemical Abstracts Service number 58-22-0, ATC code G03BA03. It is a controlled substance, in US by Drug Enforcement Administration (DEA). It\'s inactive epimer – difference in configuration of OH at C17 - is called epitestosterone. Testosterone\'s biosynthesis starts from cholesterol. Metabolism: up to one tenth of testosterone is converted by 5-alpha reductase to dihydrotestosterone, less than 0.5% by aromatase to estradiol. Most of testosterone is deactivated and excreted as glucoronides.
\nTestosterone structure (Picture in public domain – Wikimedia: NEUROtiker)
Testosterone measurement in prostate cancer patients has more than 40 years history [2]. Confirmation of castrate testosterone level is necessary before identifying prostate cancer as castration resistant. Castrate states are at present defined as serum testosterone level below 20 ng/dl (=0.69 nmol/l) or below 50 ng/dl (=1.73 nmol/l) [3], but it was not always this way and different testosterone measurement methods have important implications.
\nNeed for controlling quality of chemical castration treatment of prostate cancer steams from reports of up to 15% castration failures [4,5]. This means LHRH treated patients may not reach castration levels of testosterone due to different reasons [6], not only non-compliance, application failures, but also other reasons, for example problems with depot formulation resorption due to granuloma formation on injection site [7] or may simply need more frequent dosages [8].
\nFurther reason for testosterone measurements in prostate cancer patients lies in reports of correlation between success of castration and time to PSA progression: better castration (lower testosterone value) gives longer time to progression [9,10]. Therefore hormonal treatment of prostate cancer should not be followed with PSA measurement only (as indirect indication of treatment success), but also with testosterone measurement [11].
\nBefore any treatment, at diagnosis, serum testosterone value is predictor of disease aggressiveness – lower testosterone values are related to less differentiated cancer and worse prognosis [12]. For all stated reasons, measurement of serum testosterone is important for clinicians who treat prostate cancer patients.
\nAfter long term of androgen suppression with LHRH (GnRH) analogues, sometimes testosterone levels do not recover after stopping treatment (which may be due to permanent dysfunction of Lydig cells), therefore application of LHRH drugs may be stopped in selected patients [13]. However, this should be confirmed and followed with testosterone measurement.
\nBut testosterone measurements are not important only for urologists, who, apart from main reason – decisions related to prostate cancer management, use it for example also for aging male symptomatology and evaluation of patients with erectile dysfunction. Also other medical specialties, like endocrinology, pediatrics, gynecology or oncology use testosterone measurements for their conditions, like diagnosing and monitoring hyper- or hypo- androgenic disorders in women, like polycystic ovary syndrome, alopecia, acne, hirsutism or hypoactive sexual desire disorder; androgen secreting neoplasms; congenital syndromes with ambiguous genitalia... Pediatrics and endocrinology were in the past probably most frequent users of testosterone assays, but nowadays most laboratories receive most testosterone requests from urologists.
\nProstate cancer is already most frequently diagnosed cancer among men in the developed world. As a cause of death among males, it is second in the USA and third in Europe. Large increase in prostate cancer incidence in recent years is not only due to availability of PSA (biochemical marker, which is useful for screening purposes) and due to better awareness of doctors and population at large, but in large part also due to changes in population pyramid and increased life expectancy. As breast cancer, which is most common in females over 60 years of age, also prostate cancer is cancer of older people. For example, in Slovenia (which may be in health related issues regarded somewhere in-between developed western and less advanced other parts of the world), incidence of prostate cancer increased 50% from 2000 to 2011 [14]. At the same time, population at main risk (males above age 60) increased 28%. Therefore more than half of increase of prostate cancer incidence can not be attributed to, as some people, even health care professionals, claim, “artificial” increase of incidence due to “over-screening”, but simply to the fact that population at risk has significantly increased. And among those (males between 55 and 70), screening is most appropriate because life expectancy also increases (at present, for 75 year old man in Slovenia it is on average more than 10 years) and therefore cancer control is worthwhile.
\nIn our country, recently prostate cancer incidence has been higher compared to breast cancer. Cause for this is not better prostate cancer “screening”, but simple fact of changes in population pyramid, in numbers of populations at risk: relation between males and females in most important age range for prostate and breast cancer detection has changed – number of males grows significantly faster than number of females. In year 2000, 700 more females reached age of 60 compared to males, in 2011, 500 more males reached age 60 compared to females [15]. Although among oldest old, number of females will remain higher compared to men, present big gap in number of men compared to women in age group 50-70 is getting smaller and smaller and this also contributes to further increase of significance of prostate compared to breast cancer.
\nAccording to population pyramid, further increase of burden due to prostate cancer is expected, for example in our country, until year 2050, when overall population in Slovenia will, according to present trends, decrease from current 2 to 1.9 million, but number of males, age 60 or more, will peak at 1.8 times the number in 2011. Similar trend is expected to happen in most countries in the world sooner or later and therefore prostate cancer will remain important health problem in future.
\nDespite facts about prostate cancer incidence, presented in section 4 and despite undeniable proof that population based PSA prostate cancer screening reduces mortality due to prostate cancer [16], it seems some professional bodies, like U.S. preventive services task force [17,18] recently advised against screening.
\nFurther, among young UK general practitioners, during non-formal conversation, in year 2012, one can easily hear claims like “PSA – oh I thought it is NOT for screening, it is only for follow up purposes, only for patients, who have diagnosis of prostate cancer already” (personal experience).
\nWith this recent trend by policy-makers, it seems hopes of urologists, who treat prostate cancer patients, that we will in the future find only very few patients, who will present with stage of disease, where nothing else but hormonal treatment would be possible or hormonal treatment will become necessary during the course of their disease, are dispelled. As it seems focus of attention is turned away from early detection and managing (watchful waiting, not necessary treating patients with prostate cancer), towards second and third line treatments for advanced disease, testosterone measurement in patients with prostate cancer will become even more important in the future.
\nDifferent drugs for hormonal treatment of prostate cancer have different effects on serum testosterone. Non-steroidal antiandrogens increase overall serum testosterone levels. Steroidal antiandrogen (cyproterone) reduces testosterone levels, but not to castrate values. Often old patients take two 100 mg tablets daily and testosterone values are than commonly around 7 nmol/l. With proper dosing (3 times 100 mg daily), values nearing castration levels have been reported (mean 2.5 nmol/l, [19]), on the other side, with dose 200 mg daily, relatively small decrease only to low-normal levels has been reported for healthy young to middle-aged men (mean 11.4 nmol/l [20]).
\nLHRH agonists injections are supposed to universally reduce testosterone levels to castration values, but sometimes this is not the case. LHRH antagonists are gaining popularity very slowly with similar effect on testosterone. They may reduce testosterone levels in a proportion of patients a bit further compared to LHRH agonists [21] and they do not cause microsurges of testosterone, which are often present with every re-dosing of LHRH agonists.
\nSurgical castration remains a viable opinion in many countries and for many patients. Steroids are available to further reduce serum androgen levels in castrate resistant disease states by blocking adrenal production. 5 alpha reductase inhibitors may, according to some theories, play a role in combination treatment.
\nIn the past, castrate values of testosterone were achieved with estrogens, like stilbestrol. Due to side effects (blood cloths), this is not used any more. Ketoconazole, inhibitor of steroid synthesis, is still available for fast testosterone levels reduction, but in practice is is used mainly in experimental settings after chemotherapy failure in castration resistant states [22].
\nTypical testosterone responses to some hormonal agents are summarized in Table 1.
\n\n Agent\n | \n\n Typical testosterone response\n | \n
non-steroidal antiandrogen (bicalutamide, flutamide) | \nincrease (may go above 30 nmol/l) | \n
steroidal antiandrogen (cyproterone acetate) | \n decrease, very dependent on dosage regimen, with 3x100 mg it may approach, but not reach castrate values, in a few days | \n
GnRH (LHRH) agonists (triptorelin, goserelin, leuporolide) | \n designed to decrease levels below castrate values (below 1.73 nmol/l), may take a month after first application to reach castrate level | \n
GnRH antagonists (degarelix) | \n designed to decrease levels below castrate values without surges | \n
surgical castration (bilateral orchiectomy) | \n gold standard, decrease below castration level in few hours, however, adrenal androgens remain | \n
ketoconazole | \ndecrease below castration levels if dose is high enough in 2-4 days, but sometimes variable response, corticosteroids should be supplemented simultaneously | \n
estrogens (stilbestrol – of historical interest only) | \ndecrease below castration levels after approx. 5 days, later surges may appear | \n
Typical serum testosterone responses to different hormonal agents. In practice, individual responses may vary significantly, therefore confirmation with individual measurement is important.
With introduction of indirect RIA techniques (double isotope derivative dilution technique) to measure serum testosterone in 1970ties and later automated chemiluminescent assays, serum testosterone values became widely available to practicing urologists.
\nManufacturers mainly use similar principles of assays. As an example of principle, Abbott\'s chemiluminescent assay is described [23]. It is “delayed one step”, competitive heterogeneous assay. First, testosterone in serum sample is displaced from sex binding globulin (SHBG) with low-pH buffer. Sample is mixed with microparticles, coated with mouse monoclonal anti-testosterone antibody. After incubation, addition of labeled testosterone (in this case, conjugated with alkaline phosphatase), follows. Labeled testosterone binds to unoccupied sites on microparticles, coated with the antibodies against testosterone. More testosterone in the sample – less sites are free for labeled testosterone to bind. After another incubation, reaction mixture is transferred to cells, where microparticles fix and bind. Wash step follows – it removes unbound conjugate (labeled testosterone and other substances which may interfere with next step). Then, labeled antigen is visualized and measured. Signal is inversely proportional to amount of testosterone in the sample – as according to principle of competitive assay – stronger signal indicates more added, with marker conjugated testosterone present, therefore less “original” testosterone in the sample. In Abbott\'s example, 4-methylumbelliferyl phosphate is added and alkaline phosphatase, conjugated to added testosterone, hydrolyzes phosphate from 4-methylumbelliferryl phosphate to 4-methylumbelliferone, which fluorescence is measured [23].
\nIn direct RIA methods, principle is the same, only marking of competing antigen is performed with radioactive substance instead of alkaline phosphatase or other enzymatic, fluorescence-based technique. Large variability was observed for direct RIA methods [24]. In indirect RIA methods, quantification follows organic solvent extraction and purification steps with monitoring of procedural losses. Although correlations between indirect RIA and mass spectrometry methods are good (above 0.9), absolute concentrations were reported to be significantly higher, probably (as in direct assays), due to cross-reaction of immunoreactive material [25].
\nIndirect assays (extraction and chromatography followed by RIA) are not available any more in our practice. Main method for serum testosterone determination in most present day clinical laboratories around the world (perhaps it is different in parts of US) is still direct automated chemiluminescent assay [26]. This assay mixes antibodies directly with serum and skips extraction step. This holds true for all direct assays, not only chemiluminescent but also radio-immuno (RIA) based.
\nMass spectrometry (MS) of steroid compounds, which includes testosterone, has a long history of research and development [27]. It is coupled to liquid chromatography (LC, a separation technique in which the mobile phase is liquid) or gas chromatography (GC, a separation technique where the mobile phase is gas). After first separation and before ionization, in the past, derivatization (conversion of chemical compound into derivative) was often used to improve, for example, ionization efficiency and other characteristics of analyte[28]. With development of more sensitive techniques, today derivatization seem not included any more in a typical setting for testosterone determination with HPLC-tandem mass spectrometry. Sample must be ionized before ions are separated according to mass and charge in the spectrometer. Among methods of ionization are for example atmospheric pressure photoionization (suggested to be most optimal for testosterone analysis) or (less optimal for testosterone) electrospray ionization. Tandem mass spectrometry (MS/MS) means that spectrometry is performed in an arrangement in which ions are subjected to two or more sequential stages of analysis (which may be separated spatially or temporally).
\nHigh throughput LC/MS/MS has become gold standard for measurement of testosterone and other well defined steroid substances in biological fluids. GC/MS can also be used to quantify testosterone, but represents today mainly a “discovery tool” which provides “integrated picture of individual\'s metabolome” [29].
\nSome characteristics of testosterone assays are summarized in Table 2.
\n\n Type\n | \n\n Characteristics\n | \n
chemiluminescet | \nuses antibodies, direct, most laboratory platforms (Abbott, Siemens, Roche) have their own antibodies, which all cross react to some extent to other substances and give consistent, but different results, typically higher than reference methods in/near castrate range | \n
RIA – radio -immuo assay | \nuses antibodies, rarely in use those days, typically good results if indirect – radio- immuno - detection after chromatography step, for direct RIA\'s, same as for chemiluminescence – problems with antibody selectivity | \n
LC-MS/MS: liquid chromatography – tandem mass spectrometry | \nuses molecular mass based identification, indirect, uses different liquid chromatography methods to extract testosterone from sample (for example “high turbulent flow”) and tandem mass spectrometry to confirm and quantify sample, gold standard | \n
GC-MS: gas chromatography – mass spectrometry | \nuses molecular mass based identification, indirect, research mainly, useful for profiling different steroids in the sample, reference method, issues with “in-house” development, sample preparation, most labor and resource intensive | \n
Most prevalent types of testosterone assays.
Guidelines [3] state testosterone values in ng/dl only and some countries still use old values (for example US, Germany, Belgium), but in many countries laboratory results only in SI units - International System of Units - (nmol/l) - are available (for example Slovenia). Some articles, to further confusion, use other combinations, like ng/ml or mg/dl. To allow easier reference to practicing physicians, in Table 3, some typical serum testosterone values are presented in different units.
\nConversion factors: as molecular formula of testosterone is C19H28O2, molecular mass of testosterone is 288.42 g/mol. Therefore, if value in ng/dl is available, multiply it with 0.0347 nmol/l / ng/dl to get value in nmol/l. If value in nmol/l is available and one needs ng/dl, value in nmol/l should be multiplied by 28.8 ng/dl / nmol/l to get ng/dl. 1 ng/ml (or microg/l) = 100 ng/dl.
\n\n Clinical meaning\n | \n\n value\n | \n
normal morning value for males, above | \n12 nmol/l (= 346 ng/dl = 3.46 ng/ml) | \n
advised supplementation for healthy males, regardless of symptoms, below | \n8 nmol/l (= 231 ng/dl = 2.31 ng/ml) | \n
“old” castration value | \n1.73 nmol/l (= 50 ng/dl = 0.5 ng/ml) | \n
median value for premenopausal females | \n1.39 nmol/l (= 40 ng/dl = 0.4 ng/ml) | \n
“Morote\'s” value | \n1.11 nmol/l (= 32 ng/dl = 0.32 ng/ml) | \n
“new” castration value | \n0.69 nmol/l (= 20 ng/dl = 0.2 ng/ml) | \n
Typical serum testosterone values in different units. “Morote\'s” value represents level of serum testosterone, determined with direct chemiluminescent immuno assay in prostate cancer patients on hormonal treatment, above which shorter time to progression was observed compared to patients with testosterone values below this level [9]. For curiosity, median value for premenopausal females can also be used as guideline for supplementation in hypoactive sexual desire disorder [30].
Circadian and “ultradian” mean testosterone level fluctuations peak is around 8 AM and through level around 8 PM. Over this, there is a 90 min oscillation in testosterone values as reflection of pulsatile secretory pattern.
\nSleeping increases testosterone values [31]. Some even claim sleep, not circadian rhythm to be more important for regulation of testosterone [31]. Pattern of physical activity (physical work or training in the morning versus evening) does not influence testosterone concentrations or testosterone diurnal pattern [32]. Food (mixed meal) decreases testosterone value, if blood is taken 1-2 hours after, by 30% in comparison to overnight fast [33]. Better sleep increases testosterone value [34]. Anxiety may increase testosterone levels, it was even suggested, patient\'s samples on the day of admission to hospital should not be used because anxiety may be associated with increased testosterone level [35]. On LHRH agonists, diurnal pattern is expected to be abolished [36]. Age reduces circadian fluctuations [37].
\nDue to stated variations in testosterone levels during the day, morning fasting blood samples are standard.
\nWide availability of automated testosterone assays should make easy for clinicians to follow prostate cancer patients testosterone levels, as at present almost every clinical laboratory offers testosterone measurement with one of direct chemiluminescent assays methods.
\nAim was to evaluate use of such a testosterone measurement tool in every-day clinical practice and consequences that might follow. Claims from some pharmaceutical company representatives on their LHRH agonist formulations to be better than others were also addressed.
\nIn a cross-sectional audit study, serum testosterone level was determined in all patients on 3-month LHRH formulations, treated in out-patient clinic in two months period. Blood samples were taken immediately before the next injection. Only patients, who previously received more than one injection and with previous injection exactly 3 months or less before examination were eligible.
\nThree preparations were found to be used: Diphereline (triptorelin 11.25 mg), Eligard (modern leuprolide formulation, 22.5 mg) and Zoladex (goserelin 10.8 mg).
\nFurther 10 samples were taken from patients with surgical castration performed more than 6 months ago, who appeared on regular follow up out-patient visit during the study period.
\nTestosterone measurement was performed with direct chemiluminescent microparticle immunoassay Architect from Abbott Laboratories. According to procedural leaflet, functional sensitivity of this assay was 0.49 nmol/l (95% confidence interval 0.38 – 0.59) and analytical sensitivity 0.28 nmol/l.
\nAs SI units (nmol/L) are obligatory in our country, all testosterone measurements were originally reported in SI units and conversion to US units (ng/dl) was performed for the purpose of this report using conversion factor of 0.0347.
\nFor statistical evaluation of differences between groups of patients on different LHRH agonist formulations, analysis of variance between groups was calculated using open source statistical software R [38].
\n125 patients aged 50 to 92 (median 74 years, lower quartile 70, upper quartile 78 years) were included.
\nFor the whole group, serum testosterone values ranged from 14 ng/dl (0.5 nmol/l, lowest reportable result) to 107 ng/dl (3.7 nmol/l), median 37 ng/dl (1.3 nmol/l), lower quartile 32 ng/dl (1.1 nmol/l), upper quartile 58 ng/dl (2.0 nmol/l).
\nAccording to those results, considering castrate level of 20 ng/dl (=0.694 nmol/l), only 7% of patients on LHRH treatment and 2/10 patients after surgical castration could be classified to castrate state of disease. Considering castrate level of 50 ng/dl (1.735 nmol/l), 66% of patients on chemical castration and 8/10 patients after surgical castration would comply.
\nTestosterone measurement results, according to LHRH agonist, are presented in Table 4. According to analysis of variance, differences between groups of patients, treated with different LHRH agonists, were not significantly different (F=0.69, p=0.5).
\n\n LHRH formulation \n | \n\n N\n | \n\n TST:min-max\n | \n\n TST-median\n | \n\n TST-75%\n | \n\n TST-90%\n | \n
triptorelin 11.25 mg | \n53 | \n20-98 | \n37 | \n58 | \n72 | \n
goserelin 10.8 mg | \n41 | \n14-107 | \n37 | \n52 | \n69 | \n
leuprolide 22.5 mg | \n21 | \n14-84 | \n49 | \n63 | \n72 | \n
Testosterone measurement results with Abbot Architect assay in patients on different 3-month LHRH agonists. Samples were taken immediately before next injection. TST – testosterone. Units: ng/dl (1,73nmol/L=50 ng/dl). Differences between different LHRH formulations were not statistically significant.
Large differences were reported from measurements of the same serum sample with chemiluminescent assays from different manufacturers [39,40]. Direct RIA techniques were not better [41]. In the low range (values of interest for castration control in patients with prostate cancer), which was close to range of female testosterone levels, direct assays gave results more than 20% different from the gold standard [41]. Abbot Architect assay was also reported to give consistently up to 20% higher results compared to standard in this range of values [39].
\nOne of the reasons for variability is in the fact that antibodies are different among manufacturers, with different cross-reactivity profiles. All present direct chemiluminescent assays are matrix dependent, which was extensively studied by the British group [42]. It was confirmed there was significant cross-reactivity for example with dehydroepiandrosteronesulphate (DHEA-S) [43]. The described issue is not only in urology regarding testosterone – also other areas of endocrinology where steroid hormones measurements are important, have reported and discussed similar issues [44,45]. College of American Pathologists proficiency testing revealed in 2008, highest mean compared to lowest mean for testosterone, to differ by factor 2.8 [46]. Differences for mass spectrometry assays were much lower, by factor 1.4.
\nMass spectrometry (MS) assays are not commercially available in classical sense, but are to much larger extent dependent on each laboratory’s own development. As mass spectrometry technology is capable of very high sensitivity and specificity, those assay are accepted as gold standard. But, they are more than direct commercial assays dependent on proper calibration and sample preparation[47]. Research has shown biases as high as 25.3% for testosterone values near castrate ranges [47]. Others reported up to 26% of results outside total error limit of 14% due to improper calibration and between-run calibration [48]. Although MS techniques are becoming standard assays for steroid hormones, this presents several challenges, for example affordability for smaller laboratories, high operating costs of equipment, need for standardization of MS assays and in many occasions, actually setting new reference ranges [49] and relating them to physiological and pathological conditions, as happens with testosterone, where castrate values have been moved from 50 ng/dl to 20 ng/dl.
\nSerum testosterone value around 1.735 nmol/l or 50 ng/dl as castrate level for the purpose of hormonal treatment of prostate cancer was used already in 1970’ties [2]. Later, some LHRH formulations were designed to achieve serum testosterone below this value in 95% of treated patients. It was accepted as standard value in guidelines [50]. Guidelines have at present gone even a step further and stated testosterone levels above 50 ng/dl to be in-sufficient and additional hormonal manipulation to be warranted in such patients [3]. It is further generally accepted patients with surgical castration to have lower levels of testosterone – around 15 ng/dl and certainly below 30 ng/dl [51]. As surgical castration provides lower testosterone levels, there were always claims one should aim as low as possible with testosterone levels and should try to reach below 20 ng/dl – for example in a small study of 38 patients, treated with LHRH agonists, Oefelein found 5% did not reach values below 50 ng/dl and 13% did not reach values below 20 ng/dl [52]. This movement, which aims to decrease castrate testosterone level, was further supported by publication which claims patients with castrate testosterone levels below 32 ng/dl (1.1 nmol/l) – Morote\'s value - to have longer time to biochemical progression [9]. In their study, which also used chemiluminescent antibody testosterone assay, in 25% of patients testosterone levels above 50 ng/dl were identified. Further, with serial measurements, 55% of patients on chemical castration had testosterone values found above 20 ng/dl [8]. Studies which use HPLC/MS/MS for determination of testosterone levels do see lower values [53].
\nSome studies seem to oversee guidelines and post their own castrate testosterone levels, which are significantly higher and set to a value which offers approximately 95% successful castration. In their article on testosterone escape, group from Norway claims their castration level is 2.8 nmol/l which equals 81 ng/dl [6]. This value was selected as their laboratory’s upper normal limit for women. And with this value, they identified 10% of patients who failed to reach this castration level. The present study was similar to this in testing patient’s serum for testosterone at the end of 3 month dosing interval, which may also influence results.
\nAnother group from Turkey, which evaluated influence of androgen deprivation therapy on hand function in 2008 article used radioimmunoassay for testosterone measurement and in a castrate group mean value of testosterone was 52 ng/dl +- 35 ng/dl [54]. One can assume for approximately half of their patients testosterone levels were not in castrate area according to guidelines. Surgical castration study, using chemiluminescent assay, found values up to or above 50 ng/dl for surgically castrated patients [55]. Further surgical castration study found patients on LHRH treatment before surgical castration to have values above 50 ng/dl in 28% of patients and after surgical castration in up to 8% [56]. Unfortunately method of testosterone measurement is not stated in this article, but it correlates perfectly with data presented here, where chemiluminescent method was used. Further, recent LHRH agonists report from Canada, which also used “competitive immunoassay using direct chemiluminescent technology” [57], found median testosterone values for different LHRH agonists to be (in nmol/l) 1.2, 1.3, 1.1 and 1.3 and in two of five formulations, upper quartal value was 1.8, indicating 25% of patients on particular formulation to be even above “old” castration value of 1.72 nmol/l (50 ng/dl). Another study from Canada, also using chemiluminescent immunoassays, although claiming they were “newer technology”, indicates risk for breakthrough levels of serum testosterone (value measured higher than castrate value) in patients on LHRH agonist injections to be 5.4% and 2.2% (for castration values 1.1 nmol/l and 1.7 nmol/l, respectively) per each LHRH injection [58]! Cancer control was claimed to be inferior in patients with breakthroughs of serum testosterone measured [58].
\nProbably one of most important reasons for observed discrepancies in testosterone measurements lies in “matrix” issue, in cross-reactivity. Immunolite assay and Abbot Architect both cross-react with DHEA and give consistently higher values for serum testosterone in range of castration male values [39,42]. Therefore results of studies, which use direct chemiluminescent testosterone assays in clinical setting cannot be compared to studies, which use chromatography followed by mass spectrometry techniques, because they do not measure the same things.
\nInaccuracy of present day direct testosterone assays is already recognized in the field of female and male testosterone replacement, in pediatrics [59] and should be recognized also in the field of prostate cancer. Until indirect testosterone assays applying mass spectroscopy become widely available, publications should set realistic values of castrate levels and precisely state measurement methods used. They may be universally available in the USA, but in Europe, even western university hospitals are not quick in replacing direct immuno-assays with gas chromatography methods – for example in Ghent they changed only recently, also for reasons like “one can not publish any more anything about testosterone without this method”. And even mass spectrometry methods show significant errors and inconsistencies.
\nOn the downside, it becomes clear using direct present day techniques to control castration methods (either chemical or surgical) is not appropriate and invariably leads to disputable results. Above findings also in part explain long term debate about subcapsular or classical simple orchiectomy and part of an occasional finding of non-castrate testosterone level after orchiectomy [56]. Also our own impulse for studying the field come from initial observations that patients after surgical castration have higher testosterone values compared to guideline\'s requests.
\nOn the upside, direct chemiluminescent assays do measure something. They can unmask occasional testosterone outlier (skipped dose of drug, granuloma formation or an individual in need for more frequent dose of a drug – reduced dose interval, as explained for example in dr. Garnick\'s editorial comment [8]). They can identify hypogonadal men with prostate cancer before starting androgen deprivation therapy, who have very bad prognosis or may in the future benefit from modified treatments, like incorporating early use of new antiandrogens (for example MDV3100 [60]). They are necessary if one embarks on “on demand” re-dosing of LHRH agonists [61].
\nIt is obvious chemiluminescent direct testosterone measurements do not show only testosterone values and as such can not serve as a tool to decide which LHRH agonist reduces testosterone more compared to other drugs. But results of such assays, as for example Abbot Architect testosterone assay, are consistent [39] and according to published and our results, there are great differences in measured levels of androgens in patients on LHRH agonist therapy (740%, from 0.5 to 3.7 nmol/L, 14 – 107 ng/dL). Perhaps, at present a pure speculation, chemiluminescent assays, which give consistent results, only with some cross-reactivity and therefore systematic overestimation of testosterone values in the low range, like Architect and Immunolite, can give estimation of overall serum androgen levels. Importance of extratesticular androgens is becoming more and more evident [62,63]. This may explain findings from Morote et al, who used same technically problematic direct chemiluminiscent assay and found correlation between assay results and time to biochemical progression [9] or from Perachino et al, who found even correlation between assay results and survival [10]. Also Hashimoto et al [64], although failing to provide details about their testosterone assay and reporting questionably low testosterone values, report usefulness of testosterone measurement for prediction of antiandrogen treatment results – when testosterone levels were low, no additional clinical benefit of antiandrogen treatment was observed, when testosterone was higher, antiandrogens were useful. If future can confirm those propositions, direct testosterone tests, despite their imprecision for their original purpose, may well serve us in selecting patients for antiandrogen addition to castration or for secondary hormonal treatment, especially in perspective of new androgen manipulating drugs, like abiraterone acetate (Zytiga) and MDV3100 [60].
\nSerum testosterone levels provide objectivity for proper prostate cancer disease states characterization. Testosterone level before treatment may add to prognosis. More importantly, testosterone levels during treatment become main issue in individual\'s prostate cancer treatment decisions, as soon as increasing PSA levels indicate failure of primary local treatment.
\nApparent difference between guidelines (which ask for 20ng/dl) and practice in serum testosterone values of hormonally treated prostate cancer patients was investigated and could be explained in methodologies of testosterone determination. Most present day available testosterone assays in hospitals are direct assays, which overestimate testosterone values in the castrate range. Antibodies cross-react with other androgens in serum (which prevail in low testosterone range) and result is overall androgen estimation, not pure testosterone value. Studies should recognize this and find use for this “overall androgen” value, which is, contrary to indirect mass spectroscopy assays, universally available and was found to be related to disease progression and treatment results. Further, it is useful for identification of high risk patients with low testosterone values at diagnosis and identification of patients with poor response to LHRH agonists. Testosteron results are necessary for prolongation of interval between injections, which may be possible in approximately half of patients on LHRH agonists treatment where values are well below castration levels and at the same time, some patients may need injections of LHRH agonists in shorter intervals. In the future, tests which estimate not only pure testosterone, but overall androgen level, may become clinically relevant with awareness of prostate cancer cell\'s ability to use different androgen molecules and as a consequence patient tailored use of new androgen manipulating drugs.
\nStudy was strongly supported by Prim. KarelKisner, Former Head of Department of Urology in UKC Maribor, Slovenia and Mag. MaksimiljanGorenjak, Head of Department of Laboratory Medicine at the same institution.
\nToday, information has become the main component of what we produce, do, buy, and consume. Having an economic value in almost all products and services that meet the needs of today’s societies, it has been now obligatory for individuals and organizations to obtain information technologies and to actively use them in both work and social life domains. Hence, in the current information age, where information is seen as power, this situation has made it imperative for organizations to become increasingly information-based and to benefit from information technologies in many processes and activities.
The intensive use of information technologies in many functions and processes has also required some changes in organizations [1]. This is due to the fact that information technologies, unlike traditional technologies, do not only change the technical fields but also affect the communication channels, decision-making functions and mechanisms, control, etc. [2]. Consequently, one of the most striking developments is on organizational structures that are becoming increasingly flattened and horizontal. Relatedly, information technologies have begun to take over the role of middle management, which supports decision-making processes of senior management and has reduced the importance of this level [3, 4, 5]. Similarly, while information technologies enable managers to obtain faster, more accurate, and more information [6, 7, 8], it also provides lower-level managers with more information about the general situation of the organization, the nature of current problems, and important organizational matters [9, 10, 11, 12].
Moreover, information technologies also have an important potential in determining whether organizations have a mechanical or an organic structure [13]. Within the mechanical organizational structures, people do not have much autonomy, and behaviors expected from employees are being careful and obedience to upper authority and respect for traditions. In such organizations, predictability, consistency, and stability are desirable phenomena. In contrast, people in organic structures have more freedom in shaping and controlling their activities, and being enthusiastic, creative, and taking risks have important places among the desired behaviors [14].
Accordingly, information technologies begin to influence the cultural values of the organization over time, through these transformations they create on organizational structures, processes, and operations. In other words, the fact that organizational structures are mechanical or organic causes the formation of diverse cultural values in organizations [15]. Therefore, the desired cultural values in mechanical organizations are quite different from those in organic structures [1, 16, 17]. In this context, this chapter deals with the influences of information technologies on cultural characteristics of organizations along with the reflections of the use of these technologies on organizational structures and their functioning.
When we look at studies on the relations between organizational culture and information technologies, we generally see the studies on the effects of culture on technology adaptation or use [18, 19, 20, 21], as well as on the effects of certain specific information technologies and applications (e.g., e-mail use, group support practices, etc.) on some aspects of any organizational culture [22, 23, 24, 25, 26, 27, 28, 29, 30, 31]. However, the number of studies that consider the use of information technologies as a “whole” and that address “why” and “how” its effects on organizational culture occurred is still limited. And so, this chapter aims to examine and discuss the overall effects of the usage and intensity of information technologies established in organizations on the cultural life within.
In this context, the chapter plan is as follows: Firstly, the basic concepts related to information and information technologies are included. Emphasis is placed on the meaning differences between knowledge and information, and their connections to information technologies are tried to be explained briefly. Secondly, the effects of information technologies on organizational structure are given particular attention. The reason for this is that as a system of values, beliefs, assumptions, and practices [32], organizational culture encompasses many features closely related to structures of organizations. Thirdly, possible links between organizational structure and organizational culture are included. Fourthly, important theoretical approaches and studies on the relationships between information technologies and organizational culture are provided. Finally, by deepening a bit more and by emphasizing key points, some important arguments are discussed.
In the literature, the concepts of information and knowledge are sometimes expressed by a single term, “information.” However, although the concepts of knowledge and information are intertwined, they are two different concepts that have different meanings and describe different phenomena. The reason for this is that knowledge is also included in the concept of information as it is transformed into a commodity when it begins to be processed, stored, and shared by information technologies.
Becoming the basic elements of today’s economic, social, and cultural systems, information is obtained in a certain hierarchy. The images are at the beginning of the process, and the process is completed with a hierarchical staging in the form of data, information, and knowledge, respectively [33]. Image is located in the first step of the process. Humans copy the picture of any object and event they previously perceived by sensory organs. When faced with a similar phenomenon in the later stages of life, these pictures in the mind are redesigned. We call these pictures of realities occurring in the human mind as images [33]. The next stage, the data, contains symbols that represent events and their properties. For this reason, data are expressed as figures and/or facts without content and interpretation [34]. Information that constitutes the next stage of the process and is mixed with knowledge and used interchangeably is expressed as a reporting of one system’s own status to another system [33]. In information, associated data are combined for a specific purpose. Therefore, we can explain information as meaningful data [35]. Knowledge, on the other hand, is defined as personalized information that allows people to fully and accurately grasp what is happening around them and manifests itself in the form of thoughts, insights, intuition, ideas, lessons learned, practices, and experiences [36]. According to Kautz and Thaysen [37] who stated that knowledge is found only in the people’s minds, knowledge is, therefore, a subjective formation. In other words, knowledge is the form of information enriched with interpretation, analysis, and context [38]. However, here, it should be emphasized again by highlighting a very important issue that knowledge is also accepted as information when this knowledge begins to be processed, stored, shared, and used over information technologies. Therefore, after this, when talking about information, one should consider not only the information created by the data brought together in a meaningful way but also the knowledge shared and used over information technologies.
On the other hand, information technologies, used as the most important tool of generating value today, are defined as the technologies that enable processes such as recording and storing data, producing information through certain operational processes, and accessing, storing, and transmitting this produced information effectively and efficiently [39, 40, 41, 42, 43, 44, 45, 46]. The term information technologies is used to cover computer and electronic communication technologies, as they are now inseparably intertwined in literature and everyday use and are generally used in this way [47]. In this context, data processing systems, management information systems (MIS), office automation systems, executive support systems, expert systems, intranet and extranet, electronic mail (e-mail), group applications (groupware), database management systems, decision support systems, artificial intelligence, and telecommunication systems can be given as examples of information technologies [33, 48, 49].
Towards the end of the twentieth century, the rapid changes with the impact of developments in information technologies led to the emergence of customer satisfaction-based, learning, knowledge-based, and constantly changing organizations [50]. The fact that organizations have become considerably information-based and benefit from information technologies intensively in their activities and processes has made also the changes in their organizational structures mandatory [1]. Accordingly, the effects of information technologies on organizational structure will be summarized under the subtitles of differentiation, centralization, and standardization/formalization, which are the three main components of organizational structure [15].
Differentiation within an organization occurs in three ways: Specialization/division of labor, horizontal and vertical differentiation, and hierarchy and size [15]. Specialization refers to the amount of different expertise or types of work [51, 52]. Specialization generally increases the number of subunits and makes it harder to understand the larger structure that people contribute to with their skills and expertise [53]. Information technologies have the potential to reduce this tendency by providing more access to information and experts at this point. In this way, access to information resources provides synergy [54].
Vertical and horizontal differentiation refers to the amount of hierarchical levels in an organization [55]. Information technologies, with the support of problem solving and decision-making, lead to the emergence of more flattened organizational structures as they require fewer levels within the hierarchy [56]. Since information technologies give employees in lower positions more autonomy to harmonize their activities, this can allow them to find and try better methods while performing their work. In this context, we can increasingly see that organizational structures have become horizontal and strengthened and that virtual organizations have begun to emerge as the most cost-effective structure [17].
In terms of hierarchy and size, Heinze and Stuart [4] argue that the mid-level management staff is unnecessary, increases bureaucracy, reduces efficiency, and has no function in organizations any more. Since most of the tasks performed by mid-level executives can be fulfilled by computers, both less costly and faster, information technology has begun to take over the role of mid-level management, which supports the decision-making process of senior management [5]. Sharing the same opinion, Fulk and DeSanctis [57] also stated that the largely witnessed situation in modern organizational designs is the reduction of intermediate-level managers and administrative support.
Centralization points to the extent to which decision-making power within an organization is scattered or centered [58]. Due to increasing local and global competition, many companies have started to leave their strategic decision-making task further down the organization to benefit from the expert people with more precise and timely local knowledge [10]. Information technologies affect these efforts directly in two ways. Firstly, information technologies increase local knowledge by contributing to obtaining closer information about market trends, opportunities, and customers. Secondly, information technologies can create synergies for organizations because, thanks to information technologies, communication and coordination between distributed decision makers, central planners, and senior managers can be realized more effectively and efficiently [59].
However, whether information technologies will lead to centralization or decentralization is a very controversial question. Regarding centralization, it enables managers to acquire faster, more accurate, and more information, reduces uncertainty, and allows them to make decisions that they cannot make before [6, 7, 8]. Conversely, by the use of other forms of information technologies (e.g., electronic bulletin boards), decentralization provides more information to lower- and mid-level managers about the general situation of the organization and the nature of current matters and problems [9, 10, 11, 12]. Raymond et al. [60] argued that because information technologies facilitate the use and transmission of information by all levels and units in the organization, it enables top management, which is the decision authority, to be disabled in certain areas and the decentralization of control. Thach and Woodman [61] maintained that this is due to the fact that as a result of sharing information at lower levels with the help of information technologies, this power of senior management has decreased to a certain extent, and the knowledge and participation of the staff in organizational matters have increased.
The literature shows that information technologies allow both centralization and decentralization. Researchers are in the agreement that information technologies make it possible for organizational managers to leave their decision-making power to a large part of the hierarchical levels without compromising the quality and timeliness of the decision [62, 63]. Keen [64] combined the concepts of centralization and decentralization and used the term “federated organization” in which organizations do not have to choose either because information technologies simultaneously allow centralization-decentralization [64, 65].
Formalization is the process of detailing how activities are coordinated for organizational purposes in order for employees and organizational units to respond routinely to recurring situations [51, 66]. Formalization involves rules, instructions, shared values, and norms [67]. In fact, formalization is based on the objective of more efficiency and less uncertainty [13].
Information technologies provide the ability to reduce the negative effects of formalization by facilitating the documenting and retrieving of information on organizational occurrences and endeavors that make behaviors and processes more consistent through formalization [63]. The more information technologies assist in reducing search times and preventing downtime, the more the administrative cost of formalization decreases and the productivity increases, which ultimately benefits the path to innovation [68].
Different organizational structures lead to the development of different cultural values [15]. The fact that the structure which an organization has established to control its activities and is defined as a formal system consisting of duties and authority relations is mechanical or organic causes the emergence of completely different cultural values, rules, and norms [69]. While mechanical structures are vertical, highly centralized, and almost everything in them are standardized, organic structures are horizontal, decentralized, and based on mutual adaptation [14]. People feel relatively less autonomous in vertical and centralized organizations, and being careful, obeying the upper authority, and respecting traditions are among the desired behaviors. Therefore, in a mechanical organizational structure, there are cultural values where predictability and stability are important [69]. In contrast, in horizontal and decentralized organizations, people can freely choose their own activities and control them. Creativity, courage, and risk-taking are given importance as desired behaviors. Therefore, organic structures contribute to the formation of cultures that value innovation and flexibility [15].
Organizational structure is also important for the development of cultural values that support integration and coordination. In a structure with stable task and role relations, sharing of rules and norms is more since there will be no communication problems and the information flow will be fast [70]. In organizations where the sharing of cultural values, norms, and rules is at a high level, the level of performance also increases [15]. Particularly in team or matrix structures where face-to-face communication is intense, the sharing of these cultural values and common reactions to the problems develop more rapidly [9].
Whether an organization is centralized or not causes different cultural values to emerge. In decentralized structures, authority is divided into subordinate levels, and an environment is created for the formation of cultural values in which creativity and innovation are rewarded [13]. Employees are allowed to use the organization’s resources and work in projects that they want, by spending some of their time in these projects, thus contributing to the production of innovative and creative products and services [15]. The structures of such organizations constitute the cultural values that give their employees the message “as long as it is in the interest of the organization, it is okay to do things in an innovative and the way you want.”
Conversely, in some organizations, it may be more important for employees not to decide on their own and all activities to be followed and controlled by their superiors. In such cases, a centralized structure is preferred to create cultural values that will ensure accountability and obedience [71]. Through norms and rules, all employees are expected to behave honestly and consistently and inform their superiors about wrongs or mistakes, because this is the only acceptable form of behavior within these structures [72].
Since working on the factors that determine the consequences of the adoption and use of information technologies, researchers have focused on people’s beliefs, values, assumptions, and codes of conduct. As a result, they have given names to this research field such as “socio-technical systems,” “social system,” “social structure,” and most recently “culture” [73]. For example, Markus and Robey [23] using “social elements” and Barley [26] using “social system” or “social structure” tried to explain this phenomenon. When examined more closely, it is seen that the details that these authors emphasize while depicting the case are the assumptions, beliefs, and values that exist in common among the group members, and this corresponds to the definition of organizational culture.
Research examining the relationships between information technologies and values, beliefs, and norms belonging to a particular group has gone through certain stages and used rich and complex research models to explain the relationships in each of these stages [74]. In the first studies on information technology applications, it has been suggested that information technologies cause changes in various organizational phenomena including structural features and thus have certain effects on organizations [74]. For instance, in some studies on adoption of groupware software, several researchers have used this deterministic approach to describe how groupware use affects communication and collaboration among employees and their productivity [27, 28]. These studies assume that certain results will certainly emerge after the adoption of information technologies, without considering the motives or activities that shape the use of information technologies by managers and employees. Like much more deterministic studies, these authors often assumed that information technologies would have predetermined influences on the adoption of information technologies, regardless of the environment in which information technologies were applied, how they were applied, and the users’ specific behaviors and particular purposes.
The second group of views concerning the relationships between organizational culture and information technologies includes the fact that information technologies are seen as a tool that can be used for any change that managers desire to make in organizational practices [22]. In studies in this approach, researchers believe that there is a wide range of possibilities to identify changes in organizational culture, structure, processes, and performance [22, 75]. Researchers from this tradition presume that with the right choice of information technologies and appropriate system design, managers can achieve whatever goals they desire.
These works were mostly adopted in the 1980s and reflect a perspective that managers think can manipulate organizational culture in the way they want. Often called “management and control,” “a functional or instrumental approach” to organizational culture, this methodology has caused serious debate in the literature [76]. This approach attributes great powers to the management level in this regard, which conflicts with anthropologists’ views that culture cannot be consciously controlled and goes much deeper to understand it [76]. Robey and Azevido [77] also do not accept the rational thought on the assumption that culture can be manipulated directly in this way.
Studies with this rational perspective in the information technology literature assume that managers can use information technologies as a leverage to make changes in the norms of behavior, strategy, structure, and performance among members within the organization. For example, in studies on group support systems (GSS), we find managers’ beliefs that they can use collaborative technologies to create a more cooperative organizational culture. This perspective was not accepted by Karsten [78] and some experimental research on GSS [30, 79]. Organizational necessity is no longer accepted, as it is viewed by information technology researchers as an overly simple approach [23, 80].
Researchers who take another approach suggest that information technologies and organizational culture can interact with each other to produce various results [22, 23]. These results can be in the form of adoption and effective use of information technologies (if there is a harmony between organizational culture and information technologies) or user reluctance, refusal, or sabotage (if no fit). Researchers who have been working on information systems since the 1980s have focused on understanding information technology features and functionality that cause effective or problematic information technology applications and the interaction between users’ values, assumptions, and other elements of organizational culture. In this regard, Romm et al. [81] argued that many forms of information technologies comprise cultural assumptions embedded within themselves and these assumptions may conflict with existing values of a particular organization. The authors argued that these embedded assumptions present information technologies as a “cultural boundary” and that a cultural analysis should be made to predict compliance or incompatibility. The authors in this approach warn managers to think of organizational culture as a binding limitation in information technology applications. In a warning by Pliskin et al. [76], managers are advised not to try to change the culture of the organization. Regarding this issue, Orlikowski [30] cites Lotus Notes (a group software) application at Alpha Corporation, a consultancy company. In this example, this system, which was established by the CEO of the company only with the benefits to be obtained, did not create the expected effects, became unsuccessful, and disappointed due to reasons such as no cultural analysis and inadequate training. Employees responded to the use of Notes with resistance and refrained from using it. The reason for this was that the employees in this organization, which had a competitive culture where information was seen as a power, avoided sharing information with others. As a result, this incompatibility between the collaborative culture that Notes had in itself and the competitive culture of the organization in question had failed this application of information technologies.
In a different approach, it is stated that information technologies and culture are not fixed and they are more flexible in terms of change [23, 75]. Managers in this approach may set specific goals for the use of information technologies, but actual results of the use of information technologies are not deterministic, and results cannot be predicted or controlled even under the best conditions [23]. The effects of information technologies are not deterministic because technology has interpretable flexibility considering that it can have different meanings for different employees. Similar technology can be interpreted in a different way by distinct people, based on certain assumptions, beliefs, and values. Robey and coauthors [24, 25], for instance, showed that it would be an empty attempt for organizational managers to try to intentionally manipulate the effects of these technologies, since there are many ways that diverse employees can configure a particular technology in different social environments.
Gopal and Prasad [31] also achieved similar results in their work on group support system (GSS), claiming that for researchers seeking fixed laws or regulations on how information technologies affect user behaviors, this would be an impossible goal to pursue. Conversely, the results of using information technologies depend on the symbolic meanings that information technologies have for a particular user. This work of Gopal and Prasad [31] expresses similar results with the work of Barley [26] and Robey and Sahay [25]. The authors stated that the symbolic meanings of certain technologies for users affect their perceptions of information technologies and their specific behaviors.
In the light of the above-mentioned approaches, arguments, and important studies in the literature, it will be useful to discuss some important points by deepening a little more and by emphasizing the key features related to the concepts of information, information technologies, and organizational culture.
First, organizational culture is a complex phenomenon that develops and changes in a historical process [32, 82, 83]. Thus, although it might seem like a plain and simple concept, organizational culture includes many subdimensions and processes. When considered as a complex pattern of these interactions of many factors with each other, it is also a difficult process to identify the direct and indirect effects of information technologies on organizational culture within this cluster of relationships and interactions. Moreover, culture is not a phenomenon that changes and develops in a short time and is therefore open to manipulations of managers. On the contrary, from this point of view, it is not possible to easily achieve control over cultural changes, and it is necessary to go much deeper [76]. So, it is not rational to expect that the rapid developments and changes in information technologies will cause changes in cultural characteristics at the same speed. In this sense, it could be inaccurate to seek direct relationships between two phenomena in question, whose rates of change are quite different.
Second, for cultural changes, there must also be changes in the basic assumptions, beliefs, and values on which the culture is built [84]. It would be misleading to expect little or intensive use of information technologies to cause changes in these rooted assumptions. For the desired changes in these basic assumptions, beliefs, and values, it is necessary to design the structure accordingly, to recruit employees who are qualified for the targeted culture, and to set ethical values and property rights to employees in accordance with this culture [15]. In this sense, information technologies may only catalyze the contribution of organizational structure to organizational culture.
Third, there are many and different types of hardware and software that fall under the scope of information technologies. It is not logical to accept all of them as homogeneous technologies in all aspects (with the same functions and features, similar usage areas, standard conditions they are applied, similar intentions, and behaviors of all users), and it can be, therefore, misleading to carry out research under a single “IT” concept from this perspective. The reason for this is that, as stated in the sections above, cultural features of each information technology application or product embedded in it might be different. The interactions between the cultural characteristics of the environment in which information technologies are applied and the unique cultural contents of information technologies may cause different results on the culture of the organization.
Fourth, contrary to what is believed, some of cultural features that we anticipate to support information technology applications and products may be interpreted otherwise by diverse people contingent on different assumptions, beliefs, and values. In fact, Robey et al. [24, 25] showed that managers cannot control the effects of these technologies, since different users can configure a particular technology in numerous ways in different social environments. Also, Gopal and Prasad [31] argued that this would be an impossible achievement for researchers looking for fixed laws or regulations on how information technologies affect user behaviors.
Fifth, information technologies were defined above as technologies that enable processing, storage, and sharing of information. The key concept in this definition is “knowledge-based” information and not the technology itself. Therefore, what makes information technologies essential and important is the information itself. According to the definition of knowledge, the most significant characteristic that differentiates it from information is its being a product of the human mind [37]. Because knowledge is the interpretation of information and expresses the value produced from it, qualifying information technologies as good-bad, useful-useless, and necessary-unnecessary can be a meaningless evaluation. So, the basic thing that creates value-added for organizations is not the technology used but the information itself, which is processed, stored, and shared on this technology. In this context, even if it is the latest, most advanced, and most expensive technology in the world, if the organization does not have a qualified human resource capable of producing knowledge that will create value-added, an appropriate organizational structure and culture that will activate this creative potential, and a management approach, all investments in these technologies will also be wasted.
This chapter has aimed to examine the impacts of information technologies on organizations’ cultures, and for this purpose, a special emphasis is given to the concept of “organizational structure” within the theoretical framework presented above. The most important reason for this is that relevant literature shows that organizational culture and organizational structure are in a very close relationship. Indeed, when the question items in the Denison organizational culture scale [85], which is the most frequently used in the literature, are examined, it is possible to see that most of these items point to many features of organizational structure concerning centralization, formalization, and differentiation dimensions. Therefore, it is a very rational approach to expect that information technologies can have direct and indirect effects on organizational cultures based on the influences of information technologies on structures of organizations. However, it should be underlined that different and controversial approaches and findings in the literature mentioned above on the relations between information technologies and organizational culture generate question marks in the minds as well.
In this regard, it is already quite difficult to draw a clear picture of the impacts of information technologies on cultural characteristics of organizations. The number of studies on the subject in the literature is still very limited. Accordingly, it is necessary to underline the great need for interdisciplinary studies in this field. But still, this study argues that the main factor that determines the actual impact and value of information technologies, which have become an integral part of human life in today’s world, is the information itself rather than technology, and it should be kept in mind that information technologies can only function as a means or tool in this knowledge-based social, economic, and cultural life. In other words, the determinant of the benefits, meaning, and importance of information technologies might be the conditions created by organizational factors such as cultural environment and organizational structure where knowledge is created, developed, and used and human resources have become the most important capital element and source of wealth.
The author declares no conflict of interest.
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