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Archives of Endocrinology and Metabolism Mar 2022The fundamental objective of military field training exercises (FTX) is to prepare military personnel for real-life operations through simulated scenarios. These... (Review)
Review
The fundamental objective of military field training exercises (FTX) is to prepare military personnel for real-life operations through simulated scenarios. These training sessions often require extreme physical efforts with prolonged, high-intensity exercises that can be combined with food restrictions and partial, or total, sleep deprivation. Such conditions can compromise an individual's physical performance and cause tissue damage, thus affecting their health. This study aimed to perform a systematic review of the literature to identify studies that measured the changes in hormone levels and biomarkers of cellular injury and oxidative stress resulting from FTX with high levels of energy expenditure combined with food and sleep restrictions. PubMed and the Scopus database were searched for articles that combined physical effort/food restriction/sleep deprivation with military training. The initial database search identified 158 articles that were reduced to 18 after confirmation. Significant reductions were reported in thyroid hormones, T3, T4, and anabolic hormones such as testosterone, insulin and androstenedione. An exception for GH was found, which increased throughout FTX. Less distinct responses to FTX were observed with cortisol, TSH and LH. The presence of biomarkers for cellular damage (myoglobin, TNF, and CRP) and increased immune response activities were also described. The scarcity of information on oxidative stress, analyses of cellular injury and biomarkers of inflammatory responses warrants the future study of these topics, which could be helpful in facilitating the safe and effective physical preparations of the members of the armed forces.
PubMed: 35289515
DOI: 10.20945/2359-3997000000443 -
Clinical Endocrinology Jul 2022To describe Asian Indian patients with 17β hydroxysteroid dehydrogenase 3 (17βHSD3) deficiency and to perform a systematic review to determine the factors influencing...
OBJECTIVES
To describe Asian Indian patients with 17β hydroxysteroid dehydrogenase 3 (17βHSD3) deficiency and to perform a systematic review to determine the factors influencing gender role in 46,XY disorder of sex development (DSD) due to 17βHSD3 deficiency.
PATIENTS AND DESIGN
We present the phenotypic and genotypic data of 10 patients (9 probands and 1 affected family member) with 17βHSD3 deficiency from our 46,XY DSD cohort (N = 150; Western India) and a systematic review of 152 probands with genetically proven, index 17βHSD3 deficiency patients from the world literature to identify the determinants of gender role.
RESULTS
17βHSD3 deficiency was the third most common (6%) cause of non-dysgenetic 46,XY DSD in our cohort. Five patients each had prepubertal (atypical genitalia) and pubertal (primary amenorrhoea) presentations. Six patients were initially reared as female of whom two (one each in prepubertal and pubertal age) changed their gender role. Ten pathogenic molecular variants (six novel) were observed. In the systematic review, initial male sex of rearing was uncommon (10.5%) and was associated with atypical genitalia, higher testosterone/androstenedione (T/A) ratio and Asian origin. Gender role change to male was seen in 10.3% of patients with initial female sex of rearing and was associated with Asian origin but unrelated to pubertal androgens or molecular variant severity. It has not been reported in patients of European origin.
CONCLUSIONS
We report the first Indian case series of 17βHSD3 deficiency, the third most common cause of 46,XY DSD, with six novel molecular variants. Distinct geographical differences in the frequency of initial male sex of rearing and gender role change to male in those initially reared as females in 17βHSD3 deficiency were noted which needs further evaluation for the underlying molecular mechanisms.
Topics: Androstenedione; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female; Gender Role; Genotype; Humans; Male
PubMed: 35170787
DOI: 10.1111/cen.14694 -
International Journal of Molecular... Nov 2021There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher... (Meta-Analysis)
Meta-Analysis
There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. An encompassing literature analysis was performed, searching for altered androgens in children with autism and using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Included were all studies published before 31 March 2021 found using the following electronic databases: PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP. Eight studies with boys and three studies with girls where steroid hormone measurements were performed from either plasma, urine, or saliva were found and analyzed. Analyses were performed for DHEA(-S/-C), androstenedione/androstenediol, and testosterone. Effect sizes were calculated for each parameter between mean concentrations for children with autism versus healthy controls. Higher levels of androgens in autism were detected, with the majority of calculated effect sizes being larger than one. We found higher levels of the main testosterone precursors DHEA, androstenedione, and androstenediol, likely causing an additionally higher level of testosterone, and an increased 17, 20-lyase activity is therefore implied. Medications already used in PCOS such as metformin might be considered to treat hyperandrogenism in autism following further research.
Topics: Androgens; Androstenediol; Androstenedione; Autistic Disorder; Child; Child, Preschool; Dehydroepiandrosterone; Female; Humans; Hyperandrogenism; Lyases; Male; Saliva; Testosterone
PubMed: 34830216
DOI: 10.3390/ijms222212324 -
Surgery For Obesity and Related... Sep 2021Most studies have shown beneficial effect of bariatric surgery (BS) on serum levels of sex hormones. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most studies have shown beneficial effect of bariatric surgery (BS) on serum levels of sex hormones.
OBJECTIVE
A systematic review and meta-analysis was conducted to examine the magnitude of possible changes in levels of sex hormones following BS.
SETTINGS
Electronic databases were searched, including PubMed, Scopus, Web of Science, and Embase, for relevant studies.
METHODS
The heterogeneity of the studies was examined by χ tests and the degree of heterogeneity was estimated using I statistic.
RESULTS
The results of pooled analyses revealed that BS caused a significant increase in luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) levels and conversely, decreased dehydroepiandrosterone (DHEA) and estradiol (E2) levels in males. For females, BS significantly increased LH, FSH, and SHBG levels and conversely, decreased androstenedione (AE), E2 and TT levels. Additionally, the level of progesterone (P), prolactin (PRL), free testosterone (FT) and dehydroepiandrosterone sulfate (DHEA-S) showed no significant changes in patients who had undergone BS.
CONCLUSION
BS changed most sex hormones levels including LH, FSH, TT, SHBG, AE, DHEA, and E2. It seems that BS is able to exert substantial impacts on sex hormones levels and as well as sexual function, however, larger, and more precise trials are required to specifically focus on these claims.
Topics: Bariatric Surgery; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Luteinizing Hormone; Male; Sex Hormone-Binding Globulin
PubMed: 34187743
DOI: 10.1016/j.soard.2021.05.003 -
The Cochrane Database of Systematic... Jan 2021Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial.
OBJECTIVES
Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work.
SELECTION CRITERIA
RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 μmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels.
AUTHORS' CONCLUSIONS
We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.
Topics: Aged; Androgens; Androstenedione; Atorvastatin; Bias; Dehydroepiandrosterone Sulfate; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Placebos; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Sex Factors; Sex Hormone-Binding Globulin; Testosterone
PubMed: 33482034
DOI: 10.1002/14651858.CD013211.pub2 -
International Journal of Endocrinology 2020Metformin is an important component of PCOS treatment. At present, the effect of metformin in overweight women with PCOS has not been evaluated. Therefore, we conducted... (Review)
Review
OBJECTIVE
Metformin is an important component of PCOS treatment. At present, the effect of metformin in overweight women with PCOS has not been evaluated. Therefore, we conducted a systematic review to assess the effects of metformin in overweight women with PCOS and to analyze the effects of metformin in overweight women with PCOS.
METHODS
We searched the PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang databases for studies published before March 2020. Randomized controlled trials were identified to study the effects of metformin in overweight women with PCOS. Data from studies including body mass index (BMI), waist circumference (WC), follicle-stimulating hormone (FSH), homeostasis model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglycerides (TG), fasting blood glucose (FBG), fasting insulin, testosterone, and androstenedione were pooled. Qualified trials were selected, and methodological quality was strictly assessed. Two reviewers chose the studies independently of each other.
RESULTS
Twelve trials were included. The intervention group and the control group had significant differences in the changes in body mass index (BMI) (WMD = -1.25, 95% CI (-1.60, -0.91), < 0.00001) and waist circumference (WC) (WMD = -1.41, 95% CI (-2.46, -0.37), =0.008) after metformin. The comprehensive results show that, in all studies, overweight women with polycystic ovary syndrome treated with metformin had significantly improved endocrine and metabolic indicators, including testosterone, follicle-stimulating hormone, luteinizing hormone, and low-density lipoprotein cholesterol. However, metformin did not regulate the secretion indexes of fasting insulin, homeostasis model assessment of insulin resistance, sex hormone-binding globulin, high-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting blood glucose, and androstenedione.
CONCLUSIONS
Compared with control interventions, metformin appears to be an effective intervention for overweight women with PCOS.
PubMed: 33014044
DOI: 10.1155/2020/5150684 -
Journal of Obstetrics and Gynaecology :... Jul 2021The aim of this systematic review is to assess the effect of Berberine (BBR) on women's health to provide greater insights about its effect on women with polycystic...
The aim of this systematic review is to assess the effect of Berberine (BBR) on women's health to provide greater insights about its effect on women with polycystic syndrome for both patients and health care providers. Electronic databases such as PubMed, Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from the base to July 1th, 2019 to identify clinical trials and randomised controlled trials that had explored the effect of BBR on the polycystic syndrome. With regard to the weight and composition body, BBR did not have any significant effect on reducing body weight and conflicting findings had been reported about waist circumference (WC) and body mass index (BMI). However, BBR led to a significant decrease in waist to hip ratio (WHR), profile hormonal insulin resistance (IR), and insulin resistance (HOMA-IR). Further, androstenedione dropped significantly following treatment with BBB. However, BBB did not have a significant effect on follicle stimulating hormone (FSH) and luteinizing hormone (LH).
Topics: Adult; Androstenedione; Berberine; Body Mass Index; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Treatment Outcome; Waist Circumference; Waist-Hip Ratio
PubMed: 32811221
DOI: 10.1080/01443615.2020.1787964 -
Reproductive Biology and Endocrinology... Aug 2020Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. It is reported that intrauterine exposure to hyperandrogenism... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. It is reported that intrauterine exposure to hyperandrogenism may induce the development of PCOS and associated complications in later life. To analyze the intrauterine androgen levels in infants born to PCOS mothers, we evaluated the androgen levels in fetal cord blood through a meta-analysis of observational studies.
MATERIAL AND METHODS
The following online databases were systematically searched: PubMed, EMBASE, Cochrane library databases and Web of Science up to December 2019. Human studies compared cord blood androgen levels, including testosterone (T) and androstenedione (ADION), in fetal cord blood of mothers with and without PCOS. Statistical analysis was performed in Review Manager, Version 5.3, with the inverse variance method based on a random-effects model.
RESULTS
A total of 7 articles were scrutinized and a total of 570 samples including 268 female and 222 male infants were qualified for review. In the mass spectrograph (MS) subgroup, PCOS mothers showed no signs of increased T concentration in umbilical cord blood at birth (4 studies; hazard ratio [HR] = - 0.05; 95% confidence interval [CI] = [- 0.33,0.24]; I = 7%; P = 0.75; fixed-effects model). ADION level tends to be lower in daughters' cord blood of PCOS mothers (3 studies; HR = -0.59; 95%CI = [- 1.00, - 0.19]; I = 0%; P = 0.004; fixed-effects model).
CONCLUSIONS
Fetal cord blood T level is not related to PCOS, while ADION levels tend to be lower in the cord blood of daughters born to mothers with PCOS.
Topics: Adult; Androgens; Child; Child of Impaired Parents; Female; Fetal Blood; Humans; Infant, Newborn; Observational Studies as Topic; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 32782029
DOI: 10.1186/s12958-020-00634-8 -
Archives of Sexual Behavior Oct 2020Lesbian and bisexual women may have different levels of sex hormones compared to heterosexual women. We systematically reviewed comparative studies measuring any sex... (Meta-Analysis)
Meta-Analysis
Lesbian and bisexual women may have different levels of sex hormones compared to heterosexual women. We systematically reviewed comparative studies measuring any sex hormones. A protocol was prospectively registered (PROSPERO-CRD42017072436) and searches conducted in six databases. Any relevant empirical studies published within the last 50 years reporting any circulating sex hormones in sexual minority women compared to heterosexual women were included, with no language or setting restrictions. Inclusions, data extraction, and quality assessment were conducted in duplicate. Random-effects meta-analyses of hormone levels, using standardized-mean-differences (SMD) were conducted where five or more studies reported results. From 1236 citations, 24 full papers were examined and 14 studies of mixed designs included, 12 in women without known ovarian problems. Hormones were measured in plasma (n = 9), saliva (n = 4), and urine (n = 2) and included androstenedione, luteinizing hormone, estradiol, pregnanediol, progesterone, testosterone, and several other hormones. Most studies were small, biased, and had considerable heterogeneity. Few found statistically significant differences between groups. All-sample meta-analysis showed increased testosterone in sexual minority women compared to heterosexual women (n = 9; SMD = 0.90; 95% Confidence interval (CI) 0.22, 1.57, I = 84%). This was the only difference found. We conclude that the small amount of heterogeneous research, from 50 years to date, suggests little discernable difference in sex hormone levels between lesbian, bisexual, and heterosexual women excepting possibly higher testosterone. A large-scale primary study would be required before placing any certainty in the findings or their implications.
Topics: Bisexuality; Female; Gonadal Steroid Hormones; Heterosexuality; Humans; Prospective Studies; Sexual and Gender Minorities
PubMed: 32405900
DOI: 10.1007/s10508-020-01717-8 -
The Cochrane Database of Systematic... Mar 2020Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency in children. In over 90% of cases, 21-hydroxylase enzyme deficiency is found which is caused by mutations in the 21-hydroxylase gene. Managing individuals with CAH due to 21-hydroxylase deficiency involves replacing glucocorticoids with oral glucocorticoids (including prednisolone and hydrocortisone), suppressing adrenocorticotrophic hormones and replacing mineralocorticoids to prevent salt wasting. During childhood, the main aims of treatment are to prevent adrenal crises and to achieve normal stature, optimal adult height and to undergo normal puberty. In adults, treatment aims to prevent adrenal crises, ensure normal fertility and to avoid the long-term consequences of glucocorticoid use. Current glucocorticoid treatment regimens can not optimally replicate the normal physiological cortisol level and over-treatment or under-treatment is often reported.
OBJECTIVES
To compare and determine the efficacy and safety of different glucocorticoid replacement regimens in the treatment of CAH due to 21-hydroxylase deficiency in children and adults.
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews, and trial registries (ClinicalTrials.gov and WHO ICTRP). Date of last search of trials register: 24 June 2019.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing different glucocorticoid replacement regimens for treating CAH due to 21-hydroxylase deficiency in children and adults.
DATA COLLECTION AND ANALYSIS
The authors independently extracted and analysed the data from different interventions. They undertook the comparisons separately and used GRADE to assess the quality of the evidence.
MAIN RESULTS
Searches identified 1729 records with 43 records subject to further examination. After screening, we included five RCTs (six references) with a total of 101 participants and identified a further six ongoing RCTs. The number of participants in each trial varied from six to 44, with participants' ages ranging from 3.6 months to 21 years. Four trials were of cross-over design and one was of parallel design. Duration of treatment ranged from two weeks to six months per treatment arm with an overall follow-up between six and 12 months for all trials. Overall, we judged the quality of the trials to be at moderate to high risk of bias; with lack of methodological detail leading to unclear or high risk of bias judgements across many of the domains. All trials employed an oral glucocorticoid replacement therapy, but with different daily schedules and dose levels. Three trials compared different dose schedules of hydrocortisone (HC), one three-arm trial compared HC to prednisolone (PD) and dexamethasone (DXA) and one trial compared HC with fludrocortisone to PD with fludrocortisone. Due to the heterogeneity of the trials and the limited amount of evidence, we were unable to perform any meta-analyses. No trials reported on quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility or final adult height. Five trials (101 participants) reported androgen normalisation but using different measurements (very low-quality evidence for all measurements). Five trials reported 17 hydroxyprogesterone (17 OHP) levels, four trials reported androstenedione, three trials reported testosterone and one trial reported dehydroepiandrosterone sulphate (DHEAS). After four weeks, results from one trial (15 participants) showed a high morning dose of HC or a high evening dose made little or no difference in 17 OHP, testosterone, androstenedione and DHEAS. One trial (27 participants) found that HC and DXA treatment suppressed 17 OHP and androstenedione more than PD treatment after six weeks and a further trial (eight participants) reported no difference in 17 OHP between the five different dosing schedules of HC at between four and six weeks. One trial (44 participants) comparing HC and PD found no differences in the values of 17 OHP, androstenedione and testosterone at one year. One trial (26 participants) of HC versus HC plus fludrocortisone found that at six months 17 OHP and androstenedione levels were more suppressed on HC alone, but there were no differences noted in testosterone levels. While no trials reported on absolute final adult height, we reported some surrogate markers. Three trials reported on growth and bone maturation and two trials reported on height velocity. One trial found height velocity was reduced at six months in 26 participants given once daily HC 25 mg/m²/day compared to once daily HC 15 mg/m²/day (both groups also received fludrocortisone 0.1 mg/day), but as the quality of the evidence was very low we are unsure whether the variation in HC dose caused the difference. There were no differences noted in growth hormone or IGF1 levels. The results from another trial (44 participants) indicate no difference in growth velocity between HC and PD at one year (very low-quality evidence), but this trial did report that once daily PD treatment may lead to better control of bone maturation compared to HC in prepubertal children and that the absolute change in bone age/chronological age ratio was higher in the HC group compared to the PD group.
AUTHORS' CONCLUSIONS
There are currently limited trials comparing the efficacy and safety of different glucocorticoid replacement regimens for treating 21-hydroxylase deficiency CAH in children and adults and we were unable to draw any firm conclusions based on the evidence that was presented in the included trials. No trials included long-term outcomes such as quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility and final adult height. There were no trials examining a modified-release formulation of HC or use of 24-hour circadian continuous subcutaneous infusion of hydrocortisone. As a consequence, uncertainty remains about the most effective form of glucocorticoid replacement therapy in CAH for children and adults. Future trials should include both children and adults with CAH. A longer duration of follow-up is required to monitor biochemical and clinical outcomes.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Dexamethasone; Glucocorticoids; Humans; Infant; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32190901
DOI: 10.1002/14651858.CD012517.pub2