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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 -
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 -
Phlebology Oct 2014The etiology of primary chronic venous insufficiency is poorly understood. This systematic review aimed to summarize published evidence assessing the association of... (Review)
Review
OBJECTIVES
The etiology of primary chronic venous insufficiency is poorly understood. This systematic review aimed to summarize published evidence assessing the association of circulating markers with primary chronic venous insufficiency.
METHODS
A search was undertaken through the PubMed database using the terms "venous insufficiency" and "biological marker" or "plasma" or "serum". Search limits included English language, human subjects and studies with publication dates from 1994. Studies which classified patients using the Clinical-Etiology-Anatomy-Pathophysiology system of venous disease were analyzed.
RESULTS
Seventeen studies were included, which have examined > 60 different biomarkers. A total of 13 markers were assessed in >1 study with the number of primary chronic venous insufficiency cases ranging from 41 to 244 and the number of controls ranging from 30 to 144 in these studies. Circulating estradiol, homocysteine and vascular endothelial growth factor were the most consistently associated with primary chronic venous insufficiency.
CONCLUSIONS
Whilst a number of studies have examined biomarkers associated with primary chronic venous insufficiency, further studies are required using improved and standardized approaches on larger populations. Biomarker research may increase pathogenic knowledge and result in opportunities to decrease chronic venous insufficiency burden.
Topics: Adult; Aged; Biomarkers; Chronic Disease; Estradiol; Female; Homocysteine; Humans; Male; Middle Aged; Testosterone; Vascular Endothelial Growth Factor A; Venous Insufficiency
PubMed: 23928282
DOI: 10.1177/0268355513494375 -
Human Reproduction Update Jul 2012Increasing age and post-menopausal status are associated with decreasing androgen concentrations in females. Women with premature loss of ovarian function, such as... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Increasing age and post-menopausal status are associated with decreasing androgen concentrations in females. Women with premature loss of ovarian function, such as primary ovarian insufficiency (POI) or iatrogenic menopause may be at increased risk for diminished testosterone levels at a relatively young age. Differentiation between a hypoandrogenic or normoandrogenic state in women with premature loss of ovarian function is problematic due to trueness and precision problems using various testosterone assays. The current meta-analysis was conducted to evaluate current literature reporting serum total testosterone concentrations under these conditions, including stratification for various testosterone assays.
METHODS
A systematic review and meta-analysis of controlled observational studies were performed. The electronic databases of Pubmed, Embase and the Cochrane Library were systematically searched until October 2011 for comparative studies on total testosterone concentrations in women with spontaneous POI or iatrogenic menopause compared with controls. The literature search, data extraction and critical appraisal, using the Newcastle-Ottawa Scale, were performed by two independent investigators. The effect measure was the weighted mean difference (WMD) with 95% confidence interval (95% CI) in a random effects model.
RESULTS
A total of 206 articles for spontaneous POI and 1358 for iatrogenic menopause were reviewed, of which 9 and 17 papers, respectively, were selected for final analysis. Both groups demonstrated significantly lower total testosterone concentrations compared with controls [WMD (95% CI) -0.38 (-0.55 to -0.22) nmol/l, and -0.29 (-0.39 to -0.18) nmol/l, respectively], but with substantial between-study heterogeneity. Subgroup analysis for assay type was statistically significant for spontaneous POI only. Sensitivity analyses of high-quality studies did not change the results, and resulted in a substantial decrease in heterogeneity in spontaneous POI studies.
CONCLUSIONS
The current meta-analysis demonstrates that total testosterone concentrations are decreased in women with spontaneous POI or iatrogenic menopause. The potential implications of hypoandrogenism in these women remain to be elucidated.
Topics: Female; Humans; Iatrogenic Disease; Immunoassay; Menopause; Postmenopause; Primary Ovarian Insufficiency; Testosterone
PubMed: 22525963
DOI: 10.1093/humupd/dms013 -
Obstetrics and Gynecology Sep 2023To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of...
OBJECTIVE
To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM).
DATA SOURCES
MEDLINE, EMBASE, ClinicalTrials.gov , and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators.
METHODS OF STUDY SELECTION
We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group.
TABULATION, INTEGRATION, AND RESULTS
Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO 2 ) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO 2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function.
CONCLUSION
Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.
Topics: Female; Humans; Hyaluronic Acid; Menopause; Vagina; Estrogens; Testosterone; Dehydroepiandrosterone
PubMed: 37543737
DOI: 10.1097/AOG.0000000000005288 -
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 -
European Journal of Endocrinology May 2012Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in... (Review)
Review
BACKGROUND
Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men.
AIM
The aim of this review was to assess the studies that evaluated the relationship between vitamin D and fertility in women and men as well as in animals.
METHODS
We performed a systematic literature search in Pubmed for relevant English language publications published until October 2011.
RESULTS AND DISCUSSION
The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. Vdr knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Moreover, we present evidence that vitamin D is involved in female reproduction including IVF outcome (clinical pregnancy rates) and polycystic ovary syndrome (PCOS). In PCOS women, low 25-hydroxyvitamin D (25(OH)D) levels are associated with obesity, metabolic, and endocrine disturbances and vitamin D supplementation might improve menstrual frequency and metabolic disturbances in those women. Moreover, vitamin D might influence steroidogenesis of sex hormones (estradiol and progesterone) in healthy women and high 25(OH)D levels might be associated with endometriosis. In men, vitamin D is positively associated with semen quality and androgen status. Moreover, vitamin D treatment might increase testosterone levels. Testiculopathic men show low CYP21R expression, low 25(OH)D levels, and osteoporosis despite normal testosterone levels.
Topics: Animals; Female; Fertility; Humans; Male; Pregnancy; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency
PubMed: 22275473
DOI: 10.1530/EJE-11-0984 -
European Urology Oncology Sep 2019Advanced prostate cancer (PCa) is treated with androgen deprivation therapy (ADT) which results in loss of bone mineral density (BMD) and osteoporosis. (Meta-Analysis)
Meta-Analysis
CONTEXT
Advanced prostate cancer (PCa) is treated with androgen deprivation therapy (ADT) which results in loss of bone mineral density (BMD) and osteoporosis.
OBJECTIVE
To perform a systematic review and meta-analysis of evidence to determine the most effective methods of preventing BMD loss in patients with PCa treated with ADT.
EVIDENCE ACQUISITION
A systematic search of the Medline, Embase, and EBM Reviews databases was conducted on July 20, 2016 to identify studies on men who received an intervention to prevent osteoporosis after diagnosis of PCa and treatment with ADT. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed and the studies found were critically appraised.
EVIDENCE SYNTHESIS
Twenty-five studies were included in the review and 13 had quantitative data sufficient for meta-analysis of BMD loss. Bisphosphonates led to a significant improvement in areas assessed: the mean difference was 7.09% (95% confidence interval [CI] 5.05-9.13%; p<0.00001) for lumbar BMD, 4.63% (95% CI 0.87-8.4; p=0.02) for femoral neck BMD, and 3.16% (95% CI 0.09-6.23%; p=0.04) for total hip BMD. Selective estrogen receptor modulators (SERMs) were less effective, exercise studies had inconsistent effects, and denosumab could not be quantitatively analyzed.
CONCLUSIONS
Bisphosphonates and denosumab are effective treatments in preventing BMD loss in men with PCa taking ADT. SERMs are a less effective alternative. Exercise programs are insufficient in isolation but have a role as an adjunct for holistic care.
PATIENT SUMMARY
In this review we determined the best option for preventing osteoporosis in men with prostate cancer being treated with androgen deprivation therapy. We found that bisphosphonates, denosumab, and selective estrogen receptor modulators (SERMs) were effective, but exercise was not useful in isolation. We conclude that bisphosphonates, denosumab, or SERMs should be used and exercise encouraged.
Topics: Androgen Antagonists; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Exercise Therapy; Feasibility Studies; Femur Neck; Holistic Health; Humans; Lumbar Vertebrae; Male; Osteoporosis; Prostatic Neoplasms; Selective Estrogen Receptor Modulators
PubMed: 31411986
DOI: 10.1016/j.euo.2018.11.001 -
Clinical Endocrinology Mar 2023P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction...
OBJECTIVE
P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction between classic and nonclassic steroidogenic acute regulatory protein deficiency has been described, whereas in SCCD is unclear. The data on gonadal function and its correlation with SCCD genotype has not been studied. We describe our experience and perform a systematic review of genetically proven SCCD patients to determine the distinct phenotypic and genotypic characteristics of 46,XY SCCD patients with typical male external genitalia (SCCD-TMG) and atypical (SCCD-AG) external genitalia.
DESIGN, PATIENTS AND MEASUREMENTS
Retrospective review of three genetically proven SCCD patients from our centre and per-patient data analysis from a systematic review of 52 probands was performed. SCCD-TMG (n = 19) was defined as external genitalia of Sinnecker score 1 with 46,XY karyotype; the rest (Sinnecker 2-5) were classified as SCCD-AG (n = 15).
RESULTS
We report two new Indian cases of SCCD with three novel likely pathogenic variants and pubertal follow-up of a previously reported patient. In systematic review, age at diagnosis of PAI and elevated renin were not different between 46,XY SCCD-TMG (n = 19) and SCCD-AG (n = 15), whereas spontaneous puberty (9/9 vs. 0/3, p = .0045), normal prepubertal (5/5 vs. 6/6, p = .002), pubertal gonadotropins (2/9 vs. 0/3, p = 1) and normal pubertal testosterone (9/11 vs. 0/3, p = .027) were more common in SCCD-TMG. Testicular adrenal rest tumours were exclusive to SCCD-TMG (n = 4). SCCD-TMG was associated with four particular genotypes [monoallelic p.Glu314Lys with another deleterious variant on the second allele (p.Glu314Lys/X-CHS: X-compound heterozygous state), biallelic p.Arg451Trp, p.Phe215Ser/p.Arg232Ter and monoallelic p.Val79Ile]. 46,XX SCCD patients with p.Glu314Lys/X-CHS also had normal gonadotropins with spontaneous puberty.
CONCLUSION
SCCD-TMG is associated with four specific genotypes and distinct gonadal characteristics from SCCD-AG with overlapping features of PAI.
Topics: Humans; Male; Testosterone; Puberty; Testicular Neoplasms; Mutation
PubMed: 36357326
DOI: 10.1111/cen.14848