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The Journal of Clinical Endocrinology... Oct 2011Low testosterone levels have been associated with outcomes that reduce survival in men. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Low testosterone levels have been associated with outcomes that reduce survival in men.
OBJECTIVE
Our objective was to perform a systematic review and meta-analysis of published studies to evaluate the association between endogenous testosterone and mortality.
DATA SOURCES
Data sources included MEDLINE (1966 to December 2010), EMBASE (1988 to December 2010), and reference lists.
STUDY SELECTION
Eligible studies were published English-language observational studies of men that reported the association between endogenous testosterone and all-cause or cardiovascular disease (CVD) mortality. A two-stage process was used for study selection. 1) Working independently and in duplicate, reviewers screened a subset (10%) of abstracts. Results indicated 96% agreement, and thereafter, abstract screening was conducted in singlicate. 2) All full-text publications were reviewed independently and in duplicate for eligibility.
DATA EXTRACTION
Reviewers working independently and in duplicate determined methodological quality of studies and extracted descriptive, quality, and outcome data.
DATA SYNTHESIS
Of 820 studies identified, 21 were included in the systematic review, and 12 were eligible for meta-analysis [n = 11 studies of all-cause mortality (16,184 subjects); n = 7 studies of CVD mortality (11,831 subjects)]. Subject mean age and testosterone level were 61 yr and 487 ng/dl, respectively, and mean follow-up time was 9.7 yr. Between-study heterogeneity was observed among studies of all-cause (P < .001) and CVD mortality (P = 0.06), limiting the ability to provide valid summary estimates. Heterogeneity in all-cause mortality (higher relative risks) was observed in studies that included older subjects (P = 0.020), reported lower testosterone levels (P = 0.018), followed subjects for a shorter time period (P = 0.010), and sampled blood throughout the day (P = 0.030).
CONCLUSION
Low endogenous testosterone levels are associated with increased risk of all-cause and CVD death in community-based studies of men, but considerable between-study heterogeneity, which was related to study and subject characteristics, suggests that effects are driven by differences between cohorts (e.g. in underlying health status).
Topics: Adult; Age Factors; Aged; Body Mass Index; Cardiovascular Diseases; Cause of Death; Humans; Male; Meta-Analysis as Topic; Middle Aged; Mortality; Risk Assessment; Smoking; Survival; Testosterone; United States
PubMed: 21816776
DOI: 10.1210/jc.2011-1137 -
Minerva Urologica E Nefrologica = the... Jun 2019Adult-onset hypogonadism is used to define androgen deficiency and its associated symptoms commonly occurring in middle-aged and elderly men, who are unable to mount an... (Review)
Review
Adult-onset hypogonadism is used to define androgen deficiency and its associated symptoms commonly occurring in middle-aged and elderly men, who are unable to mount an adequate compensatory gonadotropin response but may also have an element of testicular failure. It often occurs in relation with chronic metabolic conditions such as diabetes and the metabolic syndrome. There is a growing demand from elderly men for testosterone therapy. The physician should therefore be well-informed so as the patient can make an informed decision. Indeed, testosterone therapy in older men has been a matter of debate, especially with regard to its impact on cardiovascular events and mortality. Not all studies have reported consistent results regarding its effect on diabetes, obesity and the metabolic syndrome. In contrast, it appears to improve sexual, physical function and bone density and it does not appear to increase the risk of prostate cancer; however, it increases hematocrit and hemoglobin levels. Therefore, testosterone therapy might provide significant beneficial effects in older symptomatic hypogonadal men; treatment should be individualized, and comorbidities addressed. Further research is required into its long-term effects.
Topics: Aged; Aged, 80 and over; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Middle Aged; Testosterone
PubMed: 30700083
DOI: 10.23736/S0393-2249.19.03301-0 -
Asian Journal of Andrology 2015New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported... (Review)
Review
New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T-treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors including nearly 10% contamination of the dataset by women. The second study mistakenly used the rate of T prescriptions written by healthcare providers to men with recent myocardial infarction (MI) as a proxy for the naturally occurring rate of MI. Numerous studies suggest T is beneficial, including decreased mortality in association with TTh, reduced MI rate with TTh in men with the greatest MI risk prognosis, and reduced CV and overall mortality with higher serum levels of endogenous T. Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T-deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk.
Topics: Cardiovascular Diseases; Drug Prescriptions; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Male; Risk Factors; Survival Rate; Testosterone
PubMed: 25432501
DOI: 10.4103/1008-682X.143248 -
Biomolecules Mar 2021Testosterone's role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization... (Meta-Analysis)
Meta-Analysis
Testosterone's role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.
Topics: Adult; Aged; Biological Availability; Case-Control Studies; Depression; Female; Humans; Mendelian Randomization Analysis; Menopause; Middle Aged; Sex Hormone-Binding Globulin; Testosterone; Young Adult
PubMed: 33802106
DOI: 10.3390/biom11030409 -
European Urology May 2016The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has... (Review)
Review
CONTEXT
The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer.
OBJECTIVE
To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer.
EVIDENCE ACQUISITION
We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer.
EVIDENCE SYNTHESIS
The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events.
CONCLUSIONS
An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life-and the ability of testosterone therapy to mitigate these effects-has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency.
PATIENT SUMMARY
In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard.
Topics: Androgens; Contraindications, Drug; Hormone Replacement Therapy; Humans; Male; Prostatic Neoplasms; Testosterone
PubMed: 26719015
DOI: 10.1016/j.eururo.2015.12.005 -
Asian Journal of Andrology 2014The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of... (Review)
Review
The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of the first scientific encounters in reproductive biology. Over centuries, castration has been performed as punishment and to produce obedient slaves, but also to preserve the soprano voices of prepubertal boys. The Chinese imperial (and other oriental) courts employed castrates as overseers in harems who often obtained high-ranking political positions. The era of testis transplantation and organotherapy was initiated by John Hunter in London who transplanted testes into capons in 1786. The intention of his experiments was to prove the 'vital principle' as the basis for modern transplantation medicine, but Hunter did not consider endocrine aspects. Arnold Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849 in Göttingen and is thus considered the father of endocrinology. Following his observations, testicular preparations were used for therapy, popularized by self-experiments by Charles-Edouard Brown-Séquard in Paris (1889), which can at best have placebo effects. In the 1920s Sergio Voronoff transplanted testes from animals to men, but their effectiveness was disproved. Today testicular transplantation is being refined by stem cell research and germ cell transplantation. Modern androgen therapy started in 1935 when Enrest Lacquer isolated testosterone from bull testes in Amsterdam. In the same year testosterone was chemically synthesized independently by Adolf Butenandt in Göttingen and Leopold Ruzicka in Basel. Since testosterone was ineffective orally it was either compressed into subcutaneous pellets or was used orally as 17α-methyl testosterone, now obsolete because of liver toxicity. The early phases of testosterone treatment coincide with the first description of the most prominent syndromes of hypogonadism by Klinefelter, by Kallmann, DelCastillo and Pasqualini. In the 1950s longer-acting injectable testosterone enanthate became the preferred therapeutic modality. In the 1950s and 1960s, research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. Although anabolic steroids have largely disappeared from clinical medicine, they continue to live an illegal life for doping in athletics. In the 1970s the orally effective testosterone undecanoate was added to the spectrum of preparations. Recent transdermal gels and long-acting injectable preparations provide options for physiological testosterone substitution therapy.
Topics: History, 19th Century; History, 20th Century; Humans; Male; Puberty; Testis; Testosterone
PubMed: 24435052
DOI: 10.4103/1008-682X.122358 -
Clinical Interventions in Aging 2009Transdermal testosterone gels were first introduced in the US in 2000. Since then, they have emerged as a favorable mode of testosterone substitution. Serum testosterone... (Review)
Review
Transdermal testosterone gels were first introduced in the US in 2000. Since then, they have emerged as a favorable mode of testosterone substitution. Serum testosterone levels reach a steady-state in the first 24 hours of application and remain in the normal range for the duration of the application. This pharmacokinetic profile is comparable to that of testosterone patch but superior to injectable testosterone esters that are associated with peaks and troughs with each dose. Testosterone gels are as efficacious as patches and injectable forms in their effects on sexual function and mood. Anticipated increases in prostate-specific antigen with testosterone therapy are not significantly different with testosterone gels, and the risk of polycythemia is lower than injectable modalities. Application site reactions, a major drawback of testosterone patches, occur less frequently with testosterone gels. However, inter-personal transfer is a concern if appropriate precautions are not taken. Superior tolerability and dose flexibility make testosterone gel highly desirable over other modalities of testosterone replacement. Androgel and Testim, the two currently available testosterone gel products in the US, have certain brand-specific properties that clinicians may consider prior to prescribing.
Topics: Adult; Aged; Aged, 80 and over; Androgens; Dosage Forms; Gels; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Middle Aged; Testosterone; Treatment Outcome; Young Adult
PubMed: 19966909
DOI: 10.2147/cia.s4466 -
Asian Journal of Andrology 2014With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are... (Review)
Review
With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.
Topics: Evidence-Based Medicine; Hormone Replacement Therapy; Humans; Male; Obesity; Testosterone
PubMed: 24407187
DOI: 10.4103/1008-682X.122365 -
Investigative and Clinical Urology Nov 2016Although testosterone therapy in men with testosterone deficiency was introduced in the early 1940s, utilization of this effective treatment approach in hypogonadal men... (Review)
Review
Although testosterone therapy in men with testosterone deficiency was introduced in the early 1940s, utilization of this effective treatment approach in hypogonadal men is met with considerable skepticism and resistance. Indeed, for decades, the fear that testosterone may cause prostate cancer has hampered clinical progress in this field. Nevertheless, even after considerable knowledge was acquired that this fear is unsubstantiated, many in the medical community remain hesitant to utilize this therapeutic approach to treat men with hypogonadism. As the fears concerning prostate cancer have subsided, a new controversy regarding use of testosterone therapy and increase in cardiovascular disease was introduced. Although the new controversy was based on one ill-fated clinical trial, one meta-analysis with studies that utilized unapproved formulation in men with liver cirrhosis, and two retrospective studies with suspect or nonvalidated statistical methodologies and database contaminations, the flames of such controversy were fanned by the lay press and academics alike. In this review we discuss the adverse effect of testosterone deficiency and highlight the numerous proven benefits of testosterone therapy on men's health and debunk the myth that testosterone therapy increases cardiovascular risk. Ultimately, we believe that there is considerable scientific and clinical evidence to suggest that testosterone therapy is safe and effective with restoration of physiological levels in men with testosterone deficiency, irrespective of its etiology.
Topics: Cardiovascular Diseases; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Prostatic Neoplasms; Testosterone
PubMed: 27847912
DOI: 10.4111/icu.2016.57.6.384 -
Behavioural Brain Research Aug 2022Anabolic androgenic steroids (AAS) are frequently used to improve physical appearance and strength. AAS are known to affect muscle growth, but many AAS-users also...
Anabolic androgenic steroids (AAS) are frequently used to improve physical appearance and strength. AAS are known to affect muscle growth, but many AAS-users also experience psychiatric and behavioral changes after long-term use. The AAS-induced effects on the brain seem to depend on the type of steroid used, but the rationale behind the observed effect is still not clear. The present study investigated and compared the impact of nandrolone decanoate and testosterone undecanoate on body weight gain, levels of stress hormones, brain gene expression, and behavioral profiles in the male rat. The behavioral profile was determined using the multivariate concentric squared field test (MCSF-test). Blood plasma and brains were collected for further analysis using ELISA and qPCR. Nandrolone decanoate caused a reduction in body weight gain in comparison with both testosterone undecanoate and control. Rats receiving nandrolone decanoate also demonstrated decreased general activity in the MCSF. In addition, nandrolone decanoate reduced the plasma levels of ACTH in comparison with the control and increased the levels of corticosterone in comparison with testosterone undecanoate. The qPCR analysis revealed brain region-dependent changes in mRNA expression, where the hypothalamus was identified as the region most affected by the AAS. Alterations in neurotransmitter systems and stress hormones may contribute to the changes in behavior detected in the MCSF. In conclusion, both AAS affect the male rat, although, nandrolone decanoate has more pronounced impact on the physiological and the behavioral parameters measured.
Topics: Anabolic Agents; Animals; Body Weight; Male; Nandrolone; Nandrolone Decanoate; Neurotransmitter Agents; Rats; Testosterone
PubMed: 35738337
DOI: 10.1016/j.bbr.2022.113971