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European Journal of Drug Metabolism and... Jul 2021Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a...
BACKGROUND AND OBJECTIVES
Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a loss of absorptive surfaces, the absorption of orally administered drugs is also often affected. The purpose of this study was to systematically review the published literature and examine the effects of short bowel syndrome on drug pharmacokinetics and clinical outcomes.
METHODS
Studies were identified through searches of databases MEDLINE, EMBASE, Web of Science, and SCOPUS, in addition to hand searches of studies' reference lists. Two reviewers independently assessed studies for inclusion, yielding 50 studies involving 37 different drugs in patients with short bowel syndrome.
RESULTS
Evidence of decreased drug absorption was observed in 29 out of 37 drugs, 6 of which lost therapeutic effect, and 14 of which continued to demonstrate clinical benefit through drug monitoring.
CONCLUSIONS
The influence of short bowel syndrome on drug absorption appears to be drug-specific and dependent on the location and extent of resection. The presence of a colon in continuity may also influence drug bioavailability as it can contribute significantly to the absorption of drugs (e.g., metoprolol); likewise, drugs that have a wide absorption window or are known to be absorbed in the colon are least likely to be malabsorbed. Individualized dosing may be necessary to achieve therapeutic efficacy, and therapeutic drug monitoring, where available, should be considered in short bowel syndrome patients, especially for drugs with narrow therapeutic indices.
Topics: Administration, Oral; Biological Availability; Humans; Intestinal Absorption; Pharmaceutical Preparations; Pharmacokinetics; Short Bowel Syndrome
PubMed: 34196913
DOI: 10.1007/s13318-021-00696-y -
Journal of Psychiatric Practice Jul 2009Studies suggest that testosterone (TT) replacement may have an antidepressant effect in depressed patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies suggest that testosterone (TT) replacement may have an antidepressant effect in depressed patients.
OBJECTIVE
The objective of this study was to explore the effect of TT administration on depression using both a systematic review of the literature and a meta-analysis.
METHODOLOGY
A search was conducted of MEDLINE, the Clinical Trials Registry, and Cochrane Central for English-language publications concerning randomized, placebo-controlled trials involving use of TT therapy in depressed patients. We searched for additional trials in the individual reference lists of the articles identified in the search. A study was judged to be relevant for inclusion in this review and meta-analysis if it reported original data from a controlled trial comparing use of TT and placebo in patients diagnosed with a depressive disorder according to DSM criteria, and the treatment response was evaluated according to changes on the Hamilton Rating Scale for Depression (HAM-D). We extracted the following data from the identified studies: study source, total number of participants in the study and in each treatment group, participants' ages, number of participants with a diagnosis of hypogonadism or HIV/AIDS, study duration, type of intervention, and change in HAM-D scores in the groups receiving TT versus placebo. The meta-analysis evaluated the effect of TT replacement on response in depressed patients as measured by change in HAM-D scores in the available placebo-controlled, randomized clinical trails.
RESULTS
Seven studies (N=364) were identified that included a placebo-control group in a double-blind design. Eligibility criteria were clearly reported in all trials. Meta-analysis of the data from these seven studies showed a significant positive effect of TT therapy on HAM-D response in depressed patients when compared with placebo (z=4.04, P<0.0001). Subgroup analysis also showed a significant response in the subpopulations with hypogonadism (z=3.84, P=0.0001) and HIV/AIDS (z=3.33, P=0.0009) as well as in patients treated with TT gel (z=2.32, P=0.02).
CONCLUSIONS
TT may have an antidepressant effect in depressed patients, especially those with hypogonadism or HIV/AIDS and elderly subpopulations. The route by which TT is administered may play a role in treatment response.
Topics: Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Quality of Life; Registries; Sexual Behavior; Testosterone
PubMed: 19625884
DOI: 10.1097/01.pra.0000358315.88931.fc -
The Journal of Sexual Medicine Dec 2022Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual... (Review)
Review
Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning; A Systematic Literature Review.
BACKGROUND
Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual symptoms.
AIMS
To systematically review and meta-analyze the effect of systemic hormone replacement therapy (sHRT) on psychological well-being and sexual functioning in women after surgical menopause and BSO.
METHODS
Medline/Pubmed, EMBASE and PsychInfo were systematically searched until November 2021. Randomized controlled trials investigating the effect of sHRT on psychological well-being and/or sexual functioning in surgically menopausal women and women after BSO were eligible for inclusion. Two independent authors performed study selection, risk of bias assessment and data extraction. Standardized mean differences (SMDs) were calculated.
OUTCOMES
Primary outcomes for psychological well-being were defined as overall psychological well-being, depression, and anxiety. Primary outcomes for sexual functioning were defined as overall sexual functioning, sexual desire, and sexual satisfaction. All outcomes were assessed on short (≤12 weeks) or medium term (13-26 weeks).
RESULTS
Twelve studies were included. Estradiol had a beneficial effect on depressed mood on short term 3-6 years after surgery or 2 years (median) after surgery with high heterogeneity (SMD: -1.37, 95%CI: -2.38 to -0.37, P = .007, I 79%). Testosterone had a beneficial effect on overall sexual functioning on short to medium term 4.6 years (mean) after surgery (SMD 0.38, 95%CI 0.11-0.65, I 0%) and on sexual desire on medium term at least 3-12 months after surgery (SMD 0.38, 95%CI 0.19-0.56, I 54%). For most studies, risk of bias was uncertain.
CLINICAL IMPLICATIONS
Estradiol may beneficially affect psychological symptoms after surgical menopause or BSO and testosterone might improve sexual desire and overall sexual functioning.
STRENGTHS AND LIMITATIONS
This review only included patient-reported outcomes, thereby reflected perceived and not simply objective symptoms in surgically menopausal women and women after BSO. The small number of studies highly varied in nature and bias could not be excluded, therefore our results should be interpreted with great caution.
CONCLUSION
Independent randomized controlled clinical trials investigating the effects of estrogen-progesterone and testosterone on psychological and sexual symptoms after surgical menopause are needed.
PROSPERO REGISTRATION NUMBER
CRD42019136698. Stuursma A, Lanjouw L, Idema DL, et al. Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning: A Systematic Literature Review. J Sex Med 2022;19:1778-1789.
Topics: Humans; Female; Progesterone; Quality of Life; Hormone Replacement Therapy; Menopause; Ovariectomy; Estrogens; Testosterone; Estradiol
PubMed: 36175351
DOI: 10.1016/j.jsxm.2022.08.191 -
Frontiers in Endocrinology 2024Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT remain controversial. An updated systematic review and meta-analysis aimed to determine the effectiveness and security of TRT treating for LOH.
METHODS
Randomized controlled trials (RCTs) of TRT for LOH were searched in the databases of Pubmed, Embase, Clinicaltrials.gov and Cochrane from 1990 to 2023 and an updated meta-analysis was conducted.
RESULTS
The results of 28 RCTs involving 3461 patients were included and scrutinized in this analysis. Among these, 11 RCTs were of long-term duration (≥12 months), while 18 RCTs were short-term studies (<12 months) comparing TRT with a placebo. TRT modalities comprised injection, oral administration, and transdermal administration. International Index of Erectile Function (IIEF) (Weighted Mean difference (WMD) 3.26; 95%; 95% confidence interval (CI) 1.654.88; P<0.0001) was obviously improved in the TRT group. International Prostate Symptom Score (IPSS) (WMD 0.00; 95% CI -0.450.45; P=1.0), Prostate Volume (PV) (WMD 0.38; 95% CI -0.641.41; P=0.46), Maximum Flow Rate (Qmax) (WMD 1.86; 95% CI -0.984.69; P=0.20), Postvoid Residual Urine Volume (PVR) (WMD 3.20; 95% CI -5.8712.28; P=0.49) and Prostate-Specific Antigen (PSA) (WMD 0.08; 95% CI -0.000.17; P=0.06) were not significantly statistical between two groups.
CONCLUSION
This meta-analysis reveals that TRT could improve the IIEF score of hypogonadal men without detriment to the IPSS score, PV, Qmax, PVR and PSA regardless of the administration method or duration of treatment.The meta-analysis was registered at PROSPERO (CRD42023413434).
Topics: Humans; Male; Erectile Dysfunction; Hypogonadism; Prostate; Prostate-Specific Antigen; Testosterone; Aging
PubMed: 38344665
DOI: 10.3389/fendo.2024.1335146 -
PloS One 2017The present systematic review and meta-analysis aimed to assess the perturbations in hormonal and psychological homeostasis in response to soccer match-play. These... (Meta-Analysis)
Meta-Analysis Review
The present systematic review and meta-analysis aimed to assess the perturbations in hormonal and psychological homeostasis in response to soccer match-play. These perturbations were explored according to match outcome (i.e., win versus loss), gender, type of contest (i.e., competitive versus non-competitive fixtures) and competitive level (i.e., novice versus high-level). The review was conducted according to the Population/Intervention or Exposure/Comparison/Outcome(s) (PICO) criteria and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Match outcome, type of contest and competitive levels were moderator variables in the examined steroid hormones responses to a soccer match-play. Different testosterone responses were seen between match winners (increase) and losers (decrease) when compared to pre-game or baseline values (p <0.05), whilst no changes could be detected for cortisol relative to match outcome in female soccer players. Males (Δ% = 6.26; ES = 0.28) demonstrated a marginally lower increase in testosterone levels when compared to females (Δ% = 49.16; ES = 1.00), though not statistically significant. Females (Δ% = 162.7; ES = 0.98) did not demonstrate elevated cortisol match response compared to males (Δ% = 34.60; ES = 1.20). Male novice soccer match-play increased cortisol levels compared to high-level soccer match-play (Q = 18.08, p<0.001). Competitive soccer matches increased cortisol levels compared to non-competitive fixtures (i.e., collegiate tournament). Additionally, competitive levels moderate the relationship between a soccer match and testosterone levels (p <0.001), regardless of gender differences. From the presented systematic review and meta-analysis it appears (1) cortisol changes are associated with cognitive anxiety in starter female soccer players, while (2) testosterone changes are associated with changes in mood state in females and social connectedness in male soccer players. This apparent psycho-physiological relationship may proffer the opportunity for targeted intervention(s) by practitioners to favorably influence performance and/or recovery agendas. Further mechanistic and/or applied evidence is required in this regard in addition to further data sets from females.
Topics: Competitive Behavior; Female; Humans; Hydrocortisone; Male; Sex Characteristics; Soccer; Testosterone
PubMed: 29023546
DOI: 10.1371/journal.pone.0186100 -
Cancer Epidemiology, Biomarkers &... Jul 2023Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent.
METHODS
We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models.
RESULTS
Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and three case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06-1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48-2.96), particularly in men (OR = 2.63; 95% CI, 1.65-4.18), Asian populations (OR = 3.27; 95% CI, 1.57-6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80-0.98 and OR = 0.88; 95% CI, 0.80-0.97, respectively) but not in women.
CONCLUSIONS
Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer.
IMPACT
Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.
Topics: Male; Humans; Female; Prospective Studies; Risk Factors; Gonadal Steroid Hormones; Testosterone; Gastrointestinal Neoplasms; Liver Neoplasms; Colorectal Neoplasms; Sex Hormone-Binding Globulin; Estradiol
PubMed: 37104672
DOI: 10.1158/1055-9965.EPI-23-0039 -
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 -
Clinical Breast Cancer Dec 2023Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing... (Meta-Analysis)
Meta-Analysis Review
Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67 pg/mL (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < .001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but 1 study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.
Topics: Female; Humans; Breast Neoplasms; Cancer Survivors; Neoplasm Recurrence, Local; Vaginal Diseases; Vagina; Estradiol; Survivors; Testosterone; Estrogens; Atrophy; Estriol
PubMed: 37806915
DOI: 10.1016/j.clbc.2023.08.003 -
Frontiers in Neuroendocrinology Oct 2023Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females,... (Review)
Review
Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.
Topics: Female; Humans; Male; Dopamine; Epigenesis, Genetic; Gonadal Steroid Hormones; Meta-Analysis as Topic; Progesterone; Sex Characteristics; Substance-Related Disorders; Systematic Reviews as Topic; Testosterone
PubMed: 37543184
DOI: 10.1016/j.yfrne.2023.101085 -
Preventive Medicine Apr 2016Recently Health Canada and the Food and Drug Administration warned about the cardiovascular risk of testosterone, making environmental drivers of testosterone potential... (Meta-Analysis)
Meta-Analysis Review
Recently Health Canada and the Food and Drug Administration warned about the cardiovascular risk of testosterone, making environmental drivers of testosterone potential prevention targets. Cotinine, a tobacco metabolite, inhibits testosterone breakdown. We assessed the association of smoking with testosterone in a systematic review and meta-analysis, searching PubMed and Web of Science through March 2015 using ("testosterone" or "androgen" or "sex hormone") and ("smoking" or "cigarette"). Two reviewers independently searched, selected, assessed quality and abstracted with differences resolved by consensus or reference to a third reviewer. The initial search yielded 2881 studies; 28 met the selection criteria. In 22 studies of 13,317 men, mean age 18-61years, smokers had higher mean testosterone than non-smokers (1.53nmol/L, 95% confidence interval (CI) 1.11 to 1.96) using a random effects model with inverse variance weighting. In 6 studies of 6089 women, mean age 28-62years, smoking was not clearly associated with testosterone (0.11nmol/L, 95% CI -0.08 to 0.30). Fixed effects models provided similar results, but suggested a positive association in women. Whether products which raise cotinine, such as e-cigarettes or nicotine replacement, also raise testosterone, should be investigated, to inform any regulatory action for e-cigarettes, which emit nicotine into the surrounding air, with relevance for both active and passive smokers.
Topics: Adolescent; Adult; Cotinine; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Smoking; Testosterone; Young Adult
PubMed: 26763163
DOI: 10.1016/j.ypmed.2015.12.021