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Endocrine Reviews Jun 2017Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels... (Review)
Review
Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels. To assess the clinical significance of modest elevations in serum DHT and the DHT/testosterone (T) ratio observed in response to common T replacement therapy, a comprehensive review of the published literature was performed to identify relevant data. Although the primary focus of this review is about DHT in men, we also provide a brief overview of DHT in women. The available published data are limited by the lack of large, well-controlled studies of long duration that are sufficiently powered to expose subtle safety signals. Nonetheless, the preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice. Elevated DHT has not been associated with increased risk of prostate disease (e.g., cancer or benign hyperplasia) nor does it appear to have any systemic effects on cardiovascular disease safety parameters (including increased risk of polycythemia) beyond those commonly observed with available T preparations. Well-controlled, long-term studies of transdermal DHT preparations have failed to identify safety signals unique to markedly elevated circulating DHT concentrations or signals materially different from T.
Topics: 5-alpha Reductase Inhibitors; Animals; Dihydrotestosterone; Female; Humans; Male; Prostate; Prostatic Neoplasms; Sex Characteristics; Testosterone
PubMed: 28472278
DOI: 10.1210/er.2016-1067 -
Sports Medicine (Auckland, N.Z.) Jun 2022Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary...
BACKGROUND
Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary people. The potential benefits of exercise in restoring such altered hormone production and secretion compared to age-matched physically inactive individuals who are ageing remains unclear.
OBJECTIVES
The aim of this systematic review was to summarise the findings of exercise training in modulating levels of ostensibly anabolic and catabolic hormones in adults aged > 40 years.
METHODS
We searched the following electronic databases (to July 2021) without a period limit: Cochrane Library, PubMed, Science Direct, Scopus, SPORTDiscus and Web of Science. Additionally, a manual search for published studies in Google Scholar was conducted for analysis of the 'grey literature' (information produced outside of traditional commercial or academic publishing and distribution channels). The initial search used the terms 'ageing' OR 'advanced age' OR 'old people' OR 'older' OR elderly' AND 'anabolic hormones' OR 'catabolic hormones' OR 'steroid hormones' OR 'sex hormones' OR 'testosterone' OR 'cortisol' OR 'insulin' OR 'insulin-like growth factor-1' OR 'IGF-1' OR 'sex hormone-binding globulin' OR 'SHBG' OR 'growth hormone' OR 'hGH' OR 'dehydroepiandrosterone' OR 'DHEA' OR 'dehydroepiandrosterone sulfate (DHEA-S)' AND 'exercise training' OR 'endurance training' OR 'resistance training' OR ' strength training' OR 'weight-lifting' OR 'high-intensity interval training' OR 'high-intensity interval exercise' OR 'high-intensity intermittent training' OR 'high-intensity intermittent exercise' OR 'interval aerobic training' OR 'interval aerobic exercise' OR 'intermittent aerobic training' OR 'intermittent aerobic exercise' OR 'high-intensity training' OR 'high-intensity exercise' OR 'sprint interval training' OR 'sprint interval exercise' OR 'combined exercise training' OR 'anaerobic training'. Only eligible full texts in English or French were considered for analysis.
RESULTS
Our search identified 484 records, which led to 33 studies for inclusion in the analysis. Different exercise training programs were used with nine studies using endurance training programs, ten studies examining the effects of high-intensity interval training, and 14 studies investigating the effects of resistance training. Most training programs lasted ≥ 2 weeks. Studies, regardless of the design, duration or intensity of exercise training, reported increases in testosterone, sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), human growth hormone (hGH) or dehydroepiandrosterone (DHEA) (effect size: 0.19 < d < 3.37, small to very large) in both older males and females. However, there was no consensus on the effects of exercise on changes in cortisol and insulin in older adults.
CONCLUSION
In conclusion, findings from this systematic review suggest that exercise training increases basal levels of testosterone, IGF-1, SHBG, hGH and DHEA in both male and females over 40 years of age. The increases in blood levels of these hormones were independent of the mode, duration and intensity of the training programs. However, the effects of long-term exercise training on cortisol and insulin levels in elderly people are less clear.
Topics: Adult; Aged; Aging; Dehydroepiandrosterone; Exercise; Female; Hormones; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Insulins; Male; Middle Aged; Sex Hormone-Binding Globulin; Testosterone
PubMed: 34936049
DOI: 10.1007/s40279-021-01612-9 -
British Journal of Anaesthesia Jul 2015The bispectral index (BIS) monitor is a quantitative electroencephalographic (EEG) device that is widely used to assess the hypnotic component of anaesthesia, especially...
BACKGROUND
The bispectral index (BIS) monitor is a quantitative electroencephalographic (EEG) device that is widely used to assess the hypnotic component of anaesthesia, especially when neuromuscular blocking drugs are used. It has been shown that the BIS is sensitive to changes in electromyogram (EMG) activity in anaesthetized patients. A single study using an earlier version of the BIS showed that decreased EMG activity caused the BIS to decrease even in awake subjects, to levels that suggested deep sedation and anaesthesia.
METHODS
We administered suxamethonium and rocuronium to 10 volunteers who were fully awake, to determine whether the BIS decreased in response to neuromuscular block alone. An isolated forearm technique was used for communication during the experiment. Two versions of the BIS monitor were used, both of which are in current use. Sugammadex was used to antagonise the neuromuscular block attributable to rocuronium.
RESULTS
The BIS decreased after the onset of neuromuscular block in both monitors, to values as low as 44 and 47, and did not return to pre-test levels until after the return of movement. The BIS showed a two-stage decrease, with an immediate reduction to values around 80, and then several minutes later, a sharp decrease to lower values. In some subjects, there were periods where the BIS was <60 for several minutes. The response was similar for both suxamethonium and rocuronium. Neither monitor was consistently superior in reporting the true state of awareness.
CONCLUSIONS
These results suggest that the BIS monitor requires muscle activity, in addition to an awake EEG, in order to generate values indicating that the subject is awake. Consequently, BIS may be an unreliable indicator of awareness in patients who have received neuromuscular blocking drugs.
CLINICAL TRIAL REGISTRY NUMBER
ACTRN12613000587707.
Topics: Adult; Androstanols; Cognition; Electroencephalography; Electromyography; Female; Humans; Male; Middle Aged; Neuromuscular Blockade; Rocuronium; Succinylcholine; Volunteers; Wakefulness
PubMed: 26174308
DOI: 10.1093/bja/aev072 -
The Journal of Urology Feb 2020
Topics: Diet; Humans; Male; Testosterone; United States
PubMed: 31659929
DOI: 10.1097/01.JU.0000611460.62826.3d -
Frontiers in Endocrinology 2020
Topics: Hormone Replacement Therapy; Humans; Hypogonadism; Male; Testosterone
PubMed: 32695070
DOI: 10.3389/fendo.2020.00426 -
Frontiers in Endocrinology 2023
Topics: Male; Humans; Aging; Testosterone; Hypogonadism
PubMed: 37274335
DOI: 10.3389/fendo.2023.1207907 -
Andrology Nov 2020This manuscript is a review and discussion of the published results of the T Trials. (Review)
Review
BACKGROUND
This manuscript is a review and discussion of the published results of the T Trials.
OBJECTIVE
To re-examine the efficacy of testosterone replacement of hypogonadal men >65 years of age in the T Trials.
MATERIALS AND METHODS
The T Trials were a complex collection of seven double blind, placebo-controlled trials of the efficacy of testosterone as replacement therapy for older men with unequivocal hypogonadism. There were three main trials (sexual function; physical function; vitality) and four sub-trials (cognition; bone; anemia; and cardiovascular). All subjects participated in the main trials while more selective inclusion/exclusion criteria existed for the sub-trials. Subjects were excluded for perceived higher risk of prostate cancer and recent myocardial or cerebral vascular events.
RESULTS
The previously published results are reviewed here as seen in the context of this special issue on late-onset hypogonadism. In the T Trials, positive benefits were seen in the sexual function, bone, and anemia trials with small but significant benefits in the vitality trial. No benefit was seen in the cognition trial, partial benefit in physical function, and a negative benefit outcome seen in the cardiovascular trial. The later trial was underpowered and the results were described as exploratory. Adverse events were relatively uncommon in the 12-month treatment phase and additional 12-month post-treatment phase. The most frequent adverse effect ascribed to testosterone was erythrocytosis.
CONCLUSIONS
The T Trials studied the efficacy of testosterone replacement therapy on 788 men with low testosterone and symptoms of hypogonadism. The studies demonstrated benefits in four trials (sexual function, vitality, bone, and anemia); partial benefit in the physical function trial; no effect in the cognition trial; and a negative effect in the exploratory cardiovascular trial. The T Trials were not designed to assess long-term risks of testosterone in men.
Topics: Age of Onset; Biomarkers; Controlled Clinical Trials as Topic; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Testosterone; Time Factors; Treatment Outcome
PubMed: 32902162
DOI: 10.1111/andr.12901 -
The Canadian Journal of Urology Aug 2020Over the past decade, there have been concerns with safety of testosterone therapy (TTh) in hypogonadal men. Several concerns have centered on the use of TTh and its... (Review)
Review
INTRODUCTION
Over the past decade, there have been concerns with safety of testosterone therapy (TTh) in hypogonadal men. Several concerns have centered on the use of TTh and its potential link to cardiovascular (CV) events, prostate cancer, and benign prostatic hyperplasia (BPH). There has also been controversy in determining which patients are appropriate candidates for TTh and if lifestyle modification has any role in improving serum testosterone values in hypogonadal men.
MATERIALS AND METHODS
A literature review of all articles assessing testosterone and the use of TTh and the association with CV events, prostate cancer, BPH and lifestyle modification was conducted.
RESULTS
Majority of patients treated with TTh today are treated off-label. Low serum testosterone levels have been associated with increased CV events. Currently, there is inconclusive evidence to support that TTh increases the risk of CV events. There is an absence of evidence linking TTh to the development of prostate cancer or worsening of BPH symptoms. Finally, lifestyle modification, such as decreasing weight and improving sleep, can improve serum testosterone levels in hypogonadal men.
CONCLUSIONS
Clinicians prescribing testosterone should be aware of the current controversies associated with TTh. The current literature does not suggest that there is a significant risk with TTh and prostate cancer, worsening of BPH symptoms or CV events. However, more studies, including randomized placebo-controlled trials, are needed. Finally, patients should be counseled appropriately regarding the indications for TTh and the benefits of lifestyle modification prior to initiating TTh.
Topics: Humans; Hypogonadism; Male; Testosterone
PubMed: 32875998
DOI: No ID Found -
Cleveland Clinic Journal of Medicine Feb 2024
Topics: Humans; Testosterone
PubMed: 38307603
DOI: 10.3949/ccjm.91b.02024 -
Anesthesiology Jul 2023The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less... (Clinical Trial)
Clinical Trial
BACKGROUND
The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less than 2 but there is a posttetanic count of at least 1. The purpose of this dose-finding study was to titrate sugammadex to produce a train-of-four ratio 0.9 or greater at the conclusion of cardiac surgery, and to continue monitoring neuromuscular blockade in the intensive care unit to identify recurrent paralysis. The hypothesis was that many patients would require less than the recommended dose of sugammadex, but that some would require more, and that recurrent paralysis would not occur.
METHODS
Neuromuscular blockade was monitored using electromyography during cardiac surgery. Administration of rocuronium was at the discretion of the anesthesia care team. During sternal closure, sugammadex was titrated in 50-mg increments every 5 min until a train-of-four ratio 0.9 or greater was obtained. Neuromuscular blockade was monitored with electromyography in the intensive care unit until sedation was discontinued before extubation or for a maximum of 7 h.
RESULTS
Ninety-seven patients were evaluated. The dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.43 to 5.6 mg/kg. There was a statistically significant relationship between the depth of neuromuscular blockade and the sugammadex dose required for reversal, but there was a large variation in dose required at any depth of neuromuscular blockade. Eighty-four of 97 patients (87%) required less than the recommended dose, and 13 (13%) required more. Two patients required additional sugammadex administration for recurrent paralysis.
CONCLUSIONS
When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Recurrent paralysis was observed in two patients.
Topics: Humans; Androstanols; Cardiac Surgical Procedures; gamma-Cyclodextrins; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Paralysis; Rocuronium; Sugammadex
PubMed: 37027807
DOI: 10.1097/ALN.0000000000004578