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Andrology Mar 2022Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with several side effects, including negative feedback of the hypothalamic-pituitary-gonadal axis, resulting in suppression of intratesticular testosterone production and spermatogenesis. To preserve these testicular functions while treating male hypogonadism, clomiphene citrate is used as off-label therapy. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of clomiphene citrate therapy for men with hypogonadism.
METHODS
The EMBASE, PubMed, Cochrane databases were searched in May 2021, for effectiveness studies of men with hypogonadism treated with clomiphene citrate. Both intervention and observational studies were included. The Effective Public Health Practice Project Quality Assessment Tool, a validated instrument, was used to assess methodological study quality. The primary outcome measure was the evaluation of serum hormone concentration. Secondary outcomes were symptoms of hypogonadism, metabolic and lipid profile, side effects, safety aspects.
RESULTS
We included 19 studies, comprising four randomized controlled trials and 15 observational studies, resulting in 1642 patients. Seventeen studies were included in the meta-analysis, with a total of 1279 patients. Therapy and follow-up duration varied between one and a half and 52 months. Total testosterone increased with 2.60 (95% CI 1.82-3.38) during clomiphene citrate treatment. An increase was also seen in free testosterone, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin and estradiol. Different symptom scoring methods were used in the included studies. The most frequently used instrument was the Androgen Deficiency in Aging Males questionnaire, whose improved during treatment. Reported side effects were only prevalent in less than 10% of the study populations and no serious adverse events were reported.
CONCLUSION
Clomiphene citrate is an effective therapy for improving both biochemical as well as clinical symptoms of males suffering from hypogonadism. Clomiphene citrate has few reported side effects and good safety aspects.
Topics: Clomiphene; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Testosterone
PubMed: 34933414
DOI: 10.1111/andr.13146 -
Frontiers in Pediatrics 2022Pubertal gynecomastia (PG), a benign condition with varied reported prevalence, typically appears at 13-14 years-old and is mostly idiopathic and self-limited.... (Review)
Review
BACKGROUND
Pubertal gynecomastia (PG), a benign condition with varied reported prevalence, typically appears at 13-14 years-old and is mostly idiopathic and self-limited. Psychologic impairments are common among adolescents with gynecomastia. Surgical intervention is reserved to severe cases and is offered towards the end of puberty. Pharmacological treatment is seldom given by clinicians mainly due to insufficient published data. We conducted this systematic literature review to assess the efficacy, safety, side effects, and complications of pharmacological treatments published.
METHODS
MEDLINE, Embase, and Cochrane CENTRAL were searched for the terms "gynecomastia", "pubertal", and "adolescent" in conjunction with medications from the Selective Estrogen Receptor Modulator (SERM), aromatase inhibitors (AI), and androgens groups in different combinations to optimize the search results. Exclusion criteria included: studies based on expert opinion, similar evidence-based medicine levels studies, and studies which discuss gynecomastia in adults. Selected articles were assessed by two authors. Data collected included: the level of evidence, population size, treatment regimen, follow-up, outcomes, complications, and side effects.
RESULTS
Of 1,425 published studies found and examined meticulously by the authors, only 24 publications met all the study research goals. These were divided into 16 publications of patients treated with SERM, of whom four had AI and four androgens. In general, the data regarding pharmacologic therapy for PG is partial, with insufficient evidence-based research. Tamoxifen and SERM drugs have long been used as treatments for PG. Tamoxifen was the chosen drug of treatment in most of the reviewed studies and found to be effective, safe, and with minimal side effects.
CONCLUSIONS
Pharmacological treatment as a new standard of care has an advantage in relieving behavioral and psychological distress. Although high quality publications are lacking, pharmacological intervention with tamoxifen is appropriate in select patients. Conduction large-scale high-quality studies are warranted with various drugs.
PubMed: 36389365
DOI: 10.3389/fped.2022.978311 -
Andrology Feb 2023Low testosterone levels are frequently present in men with obesity and insulin resistance. Currently available treatment options (testosterone replacement therapy or... (Review)
Review
BACKGROUND
Low testosterone levels are frequently present in men with obesity and insulin resistance. Currently available treatment options (testosterone replacement therapy or lifestyle changes) hold possible risks or are insufficient. Since low testosterone levels are closely related to obesity and type 2 diabetes, treatment modalities for these conditions could result into improvement of testosterone levels.
OBJECTIVES
To summarize the available evidence on the effects of traditional and recent treatment modalities for diabetes mellitus on testosterone levels and androgen-deficiency-related signs and symptoms.
MATERIALS AND METHODS
PubMed was searched from the year 2000 till present using MESH terms: "hypogonadism," "testosterone," "testosterone deficiency," "functional hypogonadism," and the different classes of medications. Studies with observational and experimental designs on humans that evaluated the effect of antidiabetic medications on gonadotropins and testosterone were eligible for inclusion.
RESULTS
Current available data show no or only limited improvement on testosterone levels with the classic antidiabetic drugs. Studies with GLP1-receptor analogues show beneficial effects on both body weight and testosterone levels in men with low testosterone levels and obesity with or without type 2 diabetes. However, data are limited to small and heterogeneous study groups and only few studies report data about impact on androgen-deficiency-related signs and symptoms.
DISCUSSION AND CONCLUSION
With the recent advances in the knowledge of the pathophysiological pathways in obesity, there is an enormous progress in the development of medications for obesity and type 2 diabetes. Newer incretin-based agents have a great potential for the treatment of functional hypogonadism due to obesity since they show promising weight reducing results. However, before the use of GLP1-receptor analogues can be suggested to treat functional hypogonadism, further studies are needed.
Topics: Humans; Male; Androgens; Diabetes Mellitus, Type 2; Eunuchism; Hypoglycemic Agents; Hypogonadism; Obesity; Testosterone
PubMed: 36251281
DOI: 10.1111/andr.13318 -
Endocrine Connections Mar 2018Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders. (Review)
Review
BACKGROUND
Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders.
AIM
The aim of this review was to provide an overview on the effects of vitamin D on polycystic ovary syndrome (PCOS) in women and androgen metabolism in men.
METHODS
We performed a systematic literature search in PubMed for relevant English language publications published from January 2012 until September 2017.
RESULTS AND DISCUSSION
The vitamin D receptor and vitamin D-metabolizing enzymes are found in reproductive tissues of women and men. In women, vitamin D status has been associated with several features of PCOS. In detail, cross-sectional data suggest a regulatory role of vitamin D in PCOS-related aspects such as ovulatory dysfunction, insulin resistance as well as hyperandrogenism. Moreover, results from randomized controlled trials (RCTs) suggest that vitamin D supplementation may be beneficial for metabolic, endocrine and fertility aspects in PCOS. In men, vitamin D status has been associated with androgen levels and hypogonadism. Further, there is some evidence for a favorable effect of vitamin D supplementation on testosterone concentrations, although others failed to show a significant effect on testosterone levels.
CONCLUSION
In summary, vitamin D deficiency is associated with adverse fertility outcomes including PCOS and hypogonadism, but the evidence is insufficient to establish causality. High-quality RCTs are needed to further evaluate the effects of vitamin D supplementation in PCOS women as well as on androgen levels in men.
PubMed: 29449314
DOI: 10.1530/EC-18-0009 -
Physiological Reports Nov 2022Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and... (Meta-Analysis)
Meta-Analysis
Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and mortality. This review aimed to systematically evaluate current findings on the association of sex hormone levels with the risk of CVD events and mortality (CVD and all-cause) in the CKD population. Articles were systematically searched in CINAHL, Cochrane, and PubMed. A total of 1739 articles were independently screened by two reviewers and 17 prospective cohort studies were included. The clinical conditions of the patients were those with non-dialysis CKD [mean/median estimated glomerular filtration rate (eGFR) between 15-51 ml/min/1.73 m ] and those on chronic dialysis (mean/median vintage between 6-125 months). The sample size ranged from 111 to 2419 and the mean/median age of subjects ranged from 52 to 72 years. The sex hormones studied were testosterone, estradiol, prolactin, dehydroepiandrosterone sulfate, and relaxin. A random-effects model was used to generate a pooled hazard ratio (HR) to evaluate the association of total testosterone levels with the risk of CVD and all-cause mortality. Most studies examined total testosterone levels (11 out of 17 studies) and studied only male patients (12 out of 17 studies). A lower total testosterone level was associated with a higher risk of CVD mortality [HR 4.37 (95% CI 1.40-13.65)] and all-cause mortality [1.96 (1.35-2.83)] in males with CKD. To conclude, there is a strong need for additional studies examining the association of sex hormones with cardiovascular and mortality risk in female patients with CKD.
Topics: Humans; Male; Female; Middle Aged; Aged; Cardiovascular Diseases; Prospective Studies; Risk Factors; Renal Insufficiency, Chronic; Gonadal Steroid Hormones; Testosterone
PubMed: 36394074
DOI: 10.14814/phy2.15490 -
Testosterone Supplementation and Cognitive Functioning in Men-A Systematic Review and Meta-Analysis.Journal of the Endocrine Society Aug 2019Testosterone supplementation (TS) is assumed important for cognitive functioning in men, but conflicting results have prevented firm conclusions. The current study...
Testosterone supplementation (TS) is assumed important for cognitive functioning in men, but conflicting results have prevented firm conclusions. The current study systematically reviewed available randomized controlled trials (RCTs) on effects of TS on cognitive functioning in men, subjected the findings to meta-analysis, and explored between-study differences as possible moderators of the effects. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, two authors independently searched for eligible records in the electronic databases of PubMed, PsycINFO, Web of Science, the Cochrane Library, Cumulative Index of Nursing and Allied Health, and Embase and determined eligibility using the following (population, intervention, comparison, outcome) criteria: population, male adults (>18 years); intervention, TS; comparison, placebo; and outcome, results of standardized neuropsychological tests. Following duplicate removal, 3873 records were screened with 92 remaining for full-text screening. Twenty-one papers reporting results of 23 independent RCTs were included, of which none treated samples of clinically hypogonadal men. The small improvement found in overall cognitive functioning (Hedges = 0.09; CI 95%: -0.02 to 0.19) failed to reach statistical significance ( = 0.108) and approached zero when adjusting for possible publication bias ( = 0.04). The effects for the 11 individual cognitive domains did not reach statistical significance (: -0.04 to 0.19, : 0.061 to 0.989). Small statistically significant ( < 0.05) effects were found for five study subsets but failed to meet the fail-safe criterion. The available evidence indicates that effects of TS on cognitive functioning in men with testosterone levels within normal ranges are less robust and of insufficient magnitude to be of clinical relevance. The effects in clinically hypogonadal men remain to be investigated.
PubMed: 31384712
DOI: 10.1210/js.2019-00119 -
The Cochrane Database of Systematic... Oct 2014Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial.
OBJECTIVES
The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD.
SEARCH METHODS
We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014.
SELECTION CRITERIA
All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).
MAIN RESULTS
We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently.
AUTHORS' CONCLUSIONS
We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.
Topics: Adult; Androgens; Anemia; Cholesterol; Erythropoietin; Hematocrit; Humans; Nandrolone; Nandrolone Decanoate; Oxymetholone; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Triglycerides
PubMed: 25300168
DOI: 10.1002/14651858.CD006881.pub2 -
Menopause (New York, N.Y.) Jan 2019This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women with premature ovarian failure and to establish if there is evidence of diminished androgen levels in these women.
METHODS
Various Internet sources of PubMed, Cochrane library, and Medline were searched systematically until February, 2018. Out of a pool of 2,461 studies, after applying the inclusion/exclusion criterion, 14, 8, 10, and 9 studies were chosen for testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin, respectively, for this meta-analysis. The effect measure was the standardized mean difference with 95% confidence interval (95% CI) in a random-effects model.
RESULTS
The testosterone concentrations in premature ovarian insufficiency were compared with fertile controls: stamdard mean difference (IV, random, 95% CI) -0.73 [-0.99, -0.46], P value < 0.05. The dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency compared to fertile controls: standard mean difference (IV, random, 95% CI) -0.65 [-0.92, -0.37], P value < 0.05. Androstenedione in premature ovarian insufficiency were compared with fertile controls: standard mean difference (IV, random, 95% CI) -1.09 [-1.71, -0.48], P value < 0.05. Sex hormone-binding globulin levels did not show statistical significance. The dehydroepiandrosterone sulfate levels were reduced in premature ovarian insufficiency cases, but still showed a higher level than in postmenopausal women.
CONCLUSIONS
Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone, dehydroepiandrosterone sulfate, and androstenedione. Dehydroepiandrosterone sulfate levels were more reduced in postmenopausal controls when compared with premature ovarian insufficiency cases.
Topics: Adult; Androgens; Androstenedione; Dehydroepiandrosterone Sulfate; Female; Fertility; Humans; Menopause, Premature; Middle Aged; Postmenopause; Primary Ovarian Insufficiency; Sex Hormone-Binding Globulin; Testosterone; Women's Health; Young Adult
PubMed: 29994966
DOI: 10.1097/GME.0000000000001161 -
Human Reproduction Update Jul 2018Testicular sperm extraction (TESE) is a surgical procedure to retrieve spermatozoa from the testes of men with azoospermia to help them achieve biological parenthood.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Testicular sperm extraction (TESE) is a surgical procedure to retrieve spermatozoa from the testes of men with azoospermia to help them achieve biological parenthood. Although effective, the surgical procedure is not without complications and haematoma, devascularization, inflammation and a decrease in testosterone levels have been described as such. The prevalence and duration of hypogonadism and associated symptoms after TESE have not been studied systematically.
OBJECTIVE AND RATIONALE
In this systematic review we addressed the following research questions: Are serum testosterone levels decreased after TESE and, if so, do these levels recover over time? What is the prevalence of symptoms and signs related to hypogonadism after TESE and are they related to testosterone levels?
SEARCH METHODS
We searched the databases Pubmed and Embase from 1 January 1993 to 26 June 2017. We combined subject headings with terms in title and/or abstract for participants, intervention and outcomes. We included all studies that reported on TESE, regardless of the specific technique used, that measured testosterone and/or LH, and/or had information on signs or symptoms related to hypogonadism as defined by hypogonadism guidelines. An additional inclusion criterion was that studies described these measurements both before and after TESE. The quality of the included studies was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool.
OUTCOMES
We identified 15 studies reporting on total testosterone levels of which five studies also reported on testicular volume and one study on erectile dysfunction. Men with Klinefelter syndrome and men with non-obstructive azoospermia had the strongest decrease in total testosterone levels 6 months after TESE, with a mean decrease of 4.1 and 2.7 nmol/l, respectively, which recovered again to baseline levels 26 and 18 months after TESE, respectively. At 6 months after TESE, some studies reported serum total testosterone concentrations below a cut-off value of 12 nmol/l, where symptoms and signs related to hypogonadism may appear. Furthermore, an increased prevalence of erectile dysfunction related to decreased total testosterone levels 6 months after TESE was reported. Also, in some men a decrease in testicular volume was reported. However, it is not clear if this is related to low testosterone levels.
WIDER IMPLICATIONS
The transient, but statistically significant, decrease in total testosterone levels indicates that men are at risk of developing a temporary hypogonadism after TESE, but there is insufficient evidence for whether patients actually experience clinical symptoms in case of decreased serum testosterone levels. To be able to properly counsel TESE patients, more large-scale monitoring on signs and symptoms of hypogonadism, in combination with testosterone measurements, needs to be performed in men undergoing TESE.
Topics: Adult; Azoospermia; Humans; Hypogonadism; Klinefelter Syndrome; Male; Risk Factors; Sperm Retrieval; Spermatozoa; Testosterone
PubMed: 29726895
DOI: 10.1093/humupd/dmy015 -
Journal of Cancer Research and... Mar 2019To estimate association between androgen receptor (AR) gene polymorphisms and testicular germ cell tumor (TGCT) susceptibility. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate association between androgen receptor (AR) gene polymorphisms and testicular germ cell tumor (TGCT) susceptibility.
MATERIALS AND METHODS
Systematic search of studies on the association between AR gene polymorphisms and TGCT susceptibility was conducted. Odds ratios and 95% confidence intervals were used to pool effect size.
RESULTS
For CAG repeat, no evidence was found for association between (>25 vs. ≤25), (>25 vs. 21-25), (<21 vs. 21-25), (others vs. 21-25), (>23 vs. ≤23), (<21 vs. ≥21), (<21 vs. ≥21)'s some subgroups and TGCT susceptibility, which showed stability. In (>24 vs. ≤24), (>24 vs. 21-24), (<21 vs. 21-24), and (others vs. 21-24) and almost all of their subgroups, increased TGCT risk was found without sensitivity analysis. For GGN, no statistical change of TGCT risk was found in (<23 vs. ≥23), (<23 vs. 23), which showed stability. For single nucleotide polymorphism (SNP) rs6152 G > A, rs1204038 G > A and rs2361634 A > G, no statistical change was found without sensitivity analysis.
CONCLUSIONS
GGN repeat number <23 may not be associated with TGCTs susceptibility. However, there was insufficient data to fully confirm association in GGN repeat number >23, CAG repeat number, SNP rs6152, rs1204038, and rs2361634.
Topics: Genetic Predisposition to Disease; Humans; Male; Neoplasms, Germ Cell and Embryonal; Polymorphism, Single Nucleotide; Receptors, Androgen; Testicular Neoplasms; Trinucleotide Repeats
PubMed: 30900623
DOI: 10.4103/0973-1482.181175