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21 décembre 2018 Non Par admin

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linkage studies identified dramatic under-diagnosis of klinefelter syndrome, an archetype of ad and its most frequent cause
only about 25% of men with this syndrome are ever diagnosed during life,14 depriving many men of effective treatment that enhances quality of life and may prevent their lifelong drift into poorer health and low socioeconomic status
these studies also imply that most men never undergo a full genital examination by a doctor during their lifetime,15 in stark contrast with women — a facet of the neglect of male reproductive health as a whole
european population-based record linkage studies of men with klinefelter syndrome also provided the first robust definition of lifetime health outcomes for androgen-deficient men
15 significantly reduced death rates from prostate cancer and ischaemic heart disease were balanced by increased deaths due to non-cardiac vascular and genitourinary disease, bone fracture and cancer, as well as excess hospitalisations
17, 18 in addition to the profound impacts of ad that do not precipitate hospitalisation or death, these findings outline numerous benefits in providing effective delivery of art in conditions characterised by lifelong ad, which impoverishes the quality of life without shortening it
pat uses androgens without a priori regard to dose or class, aiming to achieve salutary androgen effects in men with chronic disease
19 many traditional pat indications are now relegated to second-tier roles, having been overtaken by newer, more expensive drugs
as an adjunctive therapy, pat would ideally improve survival by changing the natural history of underlying fatal disease — which has not yet been proven for any disease
therefore, the objectives of pat are limited to improving quality of life, and morbidity benefits have been proven in many settings
anaemia due to marrow failure (maintaining haemoglobin, reducing transfusion requirement) or renal failure (augmenting and saving on erythropoietin);
chronic respiratory or cardiac failure (quality of life, symptoms);
steroid-dependent autoimmune disease (improving muscle and bone, symptoms);
aids wasting (muscle gain, symptoms);
preventing attacks of hereditary angioedema or urticaria; and
palliating terminal breast cancer
further controlled clinical studies are warranted to evaluate the safety, efficacy and cost-effectiveness of pat in speeding rehabilitation from severe catabolic injury (burns, critical illness or major surgery) and chronic organ failure states for which there is promising but inconclusive evidence
key considerations for clinical research in pat include distinguishing the mood-elevating properties of androgens
testosterone has modest, positive psychological effects in most treated men and was one of the first antidepressants
20 at high doses, a small minority of normal men become hypomanic
21 in the context of pat, such mood-elevating effects may non-specifically enhance quality of life without affecting the underlying disease,22- 24 rather like pharmacological glucocorticoid therapy used as a terminal palliative
this underlines the necessity for randomisation and placebo controls in future studies of adjuvant pat
nevertheless, even as new, expensive drugs overtake older indications, androgens may retain roles either for new adjuvant indications or because of their competitive cost-effectiveness
systematic over-prescribing of androgens for unproven medical indications constitutes androgen misuse
inevitably, the boundary between enthusiastic advocacy for novel but unproven use and misuse is vague, although either end of that spectrum would be readily recognisable
in the absence of any safe and effective indications, marketing by single-issue clinics and societies, sometimes with covert pharmaceutical industry support, may generate pressure for systematic over-prescribing
this may either be outside existing independent safety and efficacy guidelines or be related to “elastic guidelines”, created to cater to ill-informed consumer demand
areas of possible androgen misuse in men in australia include increasing prescriptions of testosterone for “andropause” before there is convincing safety or efficacy evidence, as well as excessive androgen prescribing for men with hiv but without aids wasting
while blood testosterone concentrations decline slowly (about 1% per year) from midlife onwards, the clinical significance of so-called andropause remains unclear and contentious
1 the risks and benefits of testosterone treatment in older men with only age-related functional decreases in blood testosterone differ markedly from those pertaining to younger men with gonadal disorders
firstly, the desired benefits are often misdirected, with older men seeking treatment prompted mostly by age-related decline in sexual (mainly erectile) function
yet, erectile dysfunction has predominantly a neurovascular rather than hormonal aetiology, with testosterone unlikely to rectify such sexual dysfunction
secondly, the background rates of cardiovascular and prostate disease are higher, so that even small increases in these adverse outcomes may negate quality-of-life benefits of androgen supplementation
ultimately, the balance of risk and benefit for testosterone treatment of older men can only be determined reliably by suitably powered, prospective placebo-controlled randomised controlled trials
a recent institute of medicine report noted that the existing efficacy evidence was so equivocal that it could not even recommend large-scale clinical trials without better short-term (about 1 year) evidence of efficacy (currently being commissioned)
26 the definitive answers are at least a decade away
in the interim, in the united states, sales of testosterone have increased 20-fold since 1990,27 whereas population-adjusted sales have remained virtually unchanged in europe, asia and australia
28 this radical dichotomy presumably reflects the effect of direct-to-public drug marketing in the us for a drug with literal sex appeal
australia was the first country to develop national prescribing guidelines specifically geared towards restraining testosterone prescribing for andropause, when the pharmaceutical benefits scheme adopted the best-practice recommendations developed by the endocrine society of australia
29 a pharmaco-epidemiological analysis of androgen prescribing patterns in australia revealed gradual increases nationally in androgen prescribing, but with specific peaks related to promotional activities by industry and, more vividly, by a single-issue andropause clinic
28 restraining inflated expectations of androgens in male ageing is a challenge for public and professional education to strengthen the focus on prudent management and to reinforce reliance on evidence-based practice
distinguishing valid but unproven indications from unjustified or unsafe prescribing is made difficult by the formidable cost of the necessary, rigorous clinical trials geared primarily towards novel chemical entities
the post-women’s health initiative era mandates that newer indications for prolonged hormonal treatment be based on adequate long-term safety, so that important but infrequent adverse effects are not overlooked
androgens are now relatively cheap, so there is little incentive for companies to undertake the costly clinical trials required for regulatory approval of new indications
as a result, many useful clinical applications of testosterone and androgens seem condemned to dwell in the limbo of off-label use, prone to misuse and possibly doing undetected harm when used with evidence-free enthusiasm
when circumstances foster off-label mass marketing, this lucrative option may circumvent the need for high quality but costly evidence — there remains a crucial role for vigilance by non-conflicted medical professionals
androgen (“anabolic

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