Testosterone and sexual function in men Rastrelli, Giulia; Corona, Giovanni; Maggi, Mario
Maturitas,
June 2018, 2018-Jun, 2018-06-00, 20180601, Volume:
112
Journal Article
Peer reviewed
•Testosterone is deeply involved in every step of male sexual response.•Sexual dysfunctions have a multifactorial origin, including low levels of testosterone.•Testosterone treatment is able to ...improve sexual dysfunctions in men with low levels of testosterone.•It is mandatory to check serum testosterone levels in men with sexual dysfunction before testosterone therapy is prescribed.
Testosterone (T) is deeply involved in every step of the male sexual response. However, the occurrence of sexual disorders cannot be automatically related to a decline in T levels. In fact, this relationship is complicated by organic, relational and psychological factors, which can independently impair sexual function. For example, it is recognized that erectile dysfunction (ED) can result from vascular damage as well as from low levels of T. T therapy (TTh) can improve sexual function but meta-analyses show that it improves erectile function only in men with ED and overt hypogonadism. Similarly, impaired sexual desire can result from a wide range of organic, relational and psychological factors, although it is recognized as one of the most specific symptoms of hypogonadism. Accordingly, low desire is improved by TTh in men with overt hypogonadism. The association between low T levels and delayed ejaculation has not been well studied and needs further confirmation, as does the role of TTh in such cases. Meta-analyses have found that TTh can improve orgasmic function in hypogonadal men. Clinicians should bear in mind that sexual dysfunctions have multifactorial causes and hypogonadism represents only one of these. Only hypogonadal men are likely to improve their sexual symptoms when treated with TTh. The assessment of serum T levels is mandatory before patients are prescribed TTh, as are the assessment and possible treatment of other concomitant conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A database of human dermatopharmacokinetic parameters of 12 transdermal patches is established. The effect of system design, application site, and metabolism on pharmacokinetic data is discussed, and ...interindividual variability of data and its possible sources evaluated. Using multiple regression analysis, two equations based on drugs physicochemical characteristics are suggested for partial prediction of peak plasma concentration (
C
max) after patch application. Patch application presumably decreases variance as rub-off, wash and exfoliation steps are diminished.
The results showed that interindividual variation, in terms of coefficient of variation (CV) of
C
max, is inversely correlated with drugs molecular weight and lipophilicity in the range of 200
<
MW
<
400 and 1.6
<
log
K
oct
<
4.3. Multiple regression analysis of
C
max against physichochemical parameters demonstrated the prominent contribution of hydrogen bonding acceptability of the molecules on their maximal plasma concentration after patch administration.
The findings suggest that the serum concentration profile for transdermal therapeutic systems (TTS) is a net result of the system performance, drug absorption and elimination. Thus, the variability in serum concentration is a function of variability of each process involved. This should be noted in explanation of effect of molecular features of drugs on their plasma concentration profile.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To describe changes in homeostasis model assessment of insulin resistance index (HOMA-IR) following testosterone therapy in men with hypogonadism and metabolic syndrome (MetS).
A randomized, ...placebo-controlled, double-blind randomized controlled trial (RCT) comprising 184 men with MetS and hypogonadism (testosterone undecanoate TU: 113 men, placebo: 71 men) was conducted. This was followed by an open-label phase in which all men were given TU. We focused on men who were not receiving antiglycaemic agents (TU: 81 men; placebo: 54 men) as these could affect HOMA-IR. Inter-group comparison of HOMA-IR was restricted to the RCT (30 weeks), whilst intra-group comparison was carried out on men provided TU during the RCT and open-label phases (study cohort) and men given placebo during the RCT and then switched to TU during the open-label phase (confirmatory cohort). Regression analysis was performed to identify factors associated with change in HOMA-IR (∆HOMA-IR).
The median HOMA-IR was significantly reduced at almost every time point (after 18 weeks) compared to baseline in men receiving TU in both the study and confirmatory cohorts. There was a significant decrease in median values of fasting glucose (30 weeks: -2.1%; 138 weeks: -4.9%) and insulin (30 weeks: -10.5%; 138 weeks: -35.5%) after TU treatment. Placebo was not associated with significant ∆HOMA-IR. The only consistent predictor of HOMA-IR decrease following TU treatment was baseline HOMA-IR (r
≥ 0.64).
Baseline HOMA-IR predicted ΔHOMA-IR, with a greater percentage change in insulin than in fasting glucose. In men with MetS/type 2 diabetes (T2DM) not on antiglycaemic therapy, improvements in HOMA-IR may be greater than suggested by change in fasting glucose. Our results suggest that hypogonadism screening be included in the management of men with MetS/T2DM.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Diagnosing testosterone deficiency requires accurate and precise measurement of total testosterone levels by an accurate method, such as liquid chromatography-tandem mass spectrometry in a laboratory ...certified by an accuracy-based program (eg, Centers for Disease Control and Prevention's Hormone Standardization (HoST) Program), and, if needed, free testosterone level. Free testosterone level should ideally be measured by equilibrium dialysis method. Testosterone levels should be measured in 2 or more fasting samples obtained in the morning. Harmonized reference ranges for total testosterone can be applied to laboratories that certified by the HoST Program.
IMPORTANCE: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. OBJECTIVE: To test the hypothesis that testosterone treatment of older ...men with low testosterone slows progression of noncalcified coronary artery plaque volume. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. INTERVENTION: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). RESULTS: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, −27 Agatston units; 95% CI, −80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. CONCLUSIONS AND RELEVANCE: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
This study, designed to determine the relative degree of testosterone deficiency, estradiol deficiency, or both at which undesirable bodily changes occur, showed that some features of male ...hypogonadism are due to both androgen deficiency and estrogen deficiency.
Testosterone therapy is prescribed for millions of men each year, and the number is increasing rapidly. Prescription sales of testosterone increased by 500% in the United States between 1993 and 2000.
1
Most testosterone prescriptions are written to treat nonspecific symptoms, such as fatigue or sexual dysfunction, when accompanied by testosterone levels below the laboratory reference range. Currently, testosterone levels that are at least 2 SD below the mean value for healthy young adults are classified as low.
1
,
2
Although convenient, this classification fails to consider the physiological consequences of specific testosterone levels.
More than 80% of circulating estradiol in men . . .
Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may ...have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system.
This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users.
An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation.
Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n = 17; five studies, n = 27, respectively). During AAS intake, significant reductions in luteinizing hormone weighted mean difference (WMD) -3.37 IU/L, 95% confidence interval (CI) -5.05 to -1.70, p < 0.001, follicle-stimulating hormone (WMD -1.73 IU/L, 95% CI -2.67 to -0.79, p < 0.001), and endogenous testosterone levels (WMD -10.75 nmol/L, 95% CI -15.01 to -6.49, p < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13-24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD -9.40 nmol/L, 95% CI -14.38 to -4.42, p < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility.
The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Testosterone and other anabolic–androgenic steroids enhance athletic performance in men and women. As a result, exogenous androgen is banned from most competitive sports. However, due to variability ...in endogenous secretion, and similarities with exogenous testosterone, it has been challenging to establish allowable limits for testosterone in competition. Endogenous androgen production is dynamically regulated by both exercise and winning in competition. Furthermore, testosterone may promote athletic performance, not only through its long-term anabolic actions, but also through rapid effects on behavior. In women, excess production of endogenous testosterone due to inborn disorders of sexual development (DSD) may convey a competitive advantage. For many years, female competitors have been subject to tests of sexual genotype and phenotype known as gender verification. Although gender verification has not identified any normal man competing as a woman, this process has identified women athletes with DSD. As understanding of DSD has expanded in recent years, women with DSD are increasingly able to continue athletic competition.
► Endogenous and exogenous androgens convey a competitive advantage in sports. ► Androgens can have rapid effects in brain to enhance competition. ► Winning a competition stimulates endogenous androgen secretion. ► Disorders of sexual differentiation may increase androgens among female athletes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of ...testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety. OBJECTIVES To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease. DESIGN, SETTING, AND PATIENTS A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke. RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%) at 3 years after coronary angiography. In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41). CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this ...study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke.
We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46, risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3.
In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.
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