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The Journal of Steroid Biochemistry and... Nov 201717β-Hydroxysteroid dehydrogenase 3 deficiency is a rare autosomal recessive cause of 46, XY disorders of sex development resulting from HSD17B3 gene mutations, however,... (Review)
Review
17β-Hydroxysteroid dehydrogenase 3 deficiency is a rare autosomal recessive cause of 46, XY disorders of sex development resulting from HSD17B3 gene mutations, however, no case has been reported in East Asia. The aim of this study was to report three Chinese 46, XY females with 17β-HSD3 deficiency in a single center and perform a systematic review of the literature. Clinical examination, endocrine evaluation and HSD17B3 gene sequencing were performed in the three Chinese phenotypically females (two sisters and one unrelated patient). Relevant articles were searched by using the term "HSD17B3" OR "17beta-HSD3 gene" with restrictions on language (English) and species (human) in Pubmed and Embase. All the three phenotypically female subjects showed 46, XY karyotype, inguinal masses, decreased testosterone and increased androstenedione. Two novel homozygous mutations (W284X and c.124_127delTCTT) in HSD17B3 gene were identified. A systematic review found a total of 121 pedigrees/158 patients, with 78.5% (124/158) of patients assigned as females, 15.2% (24/158) from females to males, and 5.1% (8/158) raised as males. The most common mutation was c.277+4C>T (allele frequency: 25/72) for patients from Europe, and R80Q (allele frequency: 21/54) for patients from West Asia. The testicular histology showed normal infantile testicular tissue in 100% (9/9) infantile patients, normal quantity germ cells in 44.4% (8/18) prepubertal patients and 19.0% (4/21) pubertal and adult patients. We reported the first East Asian 17β-hydroxysteroid dehydrogenase 3 deficiency cases. Additional literature reviews found founder effects among patients with different ethnic background and early orchiopexy may benefit fertility in patients assigned as males. These findings may significantly expand the clinical, ethnic and genetic spectrum of 17β-hydroxysteroid dehydrogenase 3 deficiency.
Topics: 17-Hydroxysteroid Dehydrogenases; Adolescent; Asian People; Child; Disorder of Sex Development, 46,XY; Female; Humans; Mutation
PubMed: 28847746
DOI: 10.1016/j.jsbmb.2017.08.012 -
Clinical Biochemistry Dec 2017The aim of this study was to perform a systematic review of the published literature to determine the available serum/plasma steroid reference intervals generated by... (Review)
Review
The aim of this study was to perform a systematic review of the published literature to determine the available serum/plasma steroid reference intervals generated by mass spectrometry (MS) methods across all age groups in healthy subjects and to suggest recommendations to achieve common MS based reference intervals for serum steroids. MEDLINE, EMBASE and PubMed databases were used to conduct a comprehensive search for English language, MS-based reference interval studies for serum/plasma steroids. Selection of steroids to include was based on those listed in the Royal College of Pathologists of Australasia Quality Assurance Programs, Chemical Pathology, Endocrine Program. This methodology has been registered onto the PROSPERO International prospective register of systematic reviews (ID number: CRD42015029637). After accounting for duplicates, a total of 60 manuscripts were identified through the search strategy. Following critical evaluation, a total of 16 studies were selected. Of the 16 studies, 12 reported reference intervals for testosterone, 11 for 17 hydroxy-progesterone, nine for androstenedione, six for cortisol, three for progesterone, two for dihydrotestosterone and only one for aldosterone and dehydroepiandrosterone sulphate. No studies established MS-based reference intervals for oestradiol. As far as we are aware, this report provides the first comparison of the peer reviewed literature for serum/plasma steroid reference intervals generated by MS-based methods. The reference intervals based on these published studies can be used to inform the process to develop common reference intervals, and agreed reporting units for mass spectrometry based steroid methods.
Topics: Female; Humans; Male; Mass Spectrometry; Steroids
PubMed: 28733189
DOI: 10.1016/j.clinbiochem.2017.07.002 -
Clinical Endocrinology Sep 2017A limited number of studies have evaluated the relationship between clinical and biochemical hyperandrogenism (HA). This study aimed to evaluate the association between... (Meta-Analysis)
Meta-Analysis Review
Association between biochemical hyperandrogenism parameters and Ferriman-Gallwey score in patients with polycystic ovary syndrome: A systematic review and meta-regression analysis.
BACKGROUND AND OBJECTIVE
A limited number of studies have evaluated the relationship between clinical and biochemical hyperandrogenism (HA). This study aimed to evaluate the association between biochemical hyperandrogenism parameters (BHPs) and Ferriman-Gallwey (FG) score in patients with polycystic ovary syndrome (PCOS).
METHODS
We searched PubMed, Scopus, Google Scholar, ScienceDirect and Web of Sciences databases (2000-2015) to identify studies investigating clinical and biochemical parameters of HA in PCOS patients. In this meta-analysis, both fixed and random effect models were applied to estimate pooled effect size. To assess the relationships between BHPs and FG score, meta-regression analysis was used.
RESULTS
Fifty-five study groups with a total of 6593 PCOS patients were analysed. Meta-regression analysis of pooled data from all eligible studies showed significant positive relationships of FG score with androstenedione (A4) (P=.034) and dehydroepiandrosterone sulphate (DHEAS) (P=.012), whereas it showed no association with total testosterone (tT), free testosterone (fT), sex hormone bonding globulin (SHBG) and free androgen index (FAI). The results did not change after adjusting for quality assessment or method of assay. Nor did the associations between A4 and FG score remain after adjusting for age and BMI, diagnostic criteria for PCOS and study design or the association between DHEAS and FG score remain after adjusting for ethnicity.
CONCLUSION
This meta-analysis confirmed the associations of some BHPs, including A4 and DHEAS with FG score, indicating that measurement of these parameters can be useful for managing PCOS patients with hirsutism.
Topics: Androstenedione; Dehydroepiandrosterone Sulfate; Disease Management; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome
PubMed: 28575537
DOI: 10.1111/cen.13389 -
Breast Cancer Research : BCR Nov 2015Exposure to high levels of endogenous estrogens is a main risk factor for breast cancer in women, and in observational studies was found to be inversely associated with... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Exposure to high levels of endogenous estrogens is a main risk factor for breast cancer in women, and in observational studies was found to be inversely associated with physical activity. The objective of the present study is to determine the effect of physical activity interventions on sex hormone levels in healthy women.
METHODS
Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2014, and reference lists of relevant reviews and clinical trials were searched, with no language restrictions applied. Randomized controlled trials (RCTs) were included if they compared any type of exercise intervention to no intervention or other interventions, and assessed the effects on estrogens, androgens or the sex hormone binding globulin (SHBG) in cancer-free women. Following the method described in the Cochrane Handbook for Systematic Reviews of Interventions, data on populations, interventions, and outcomes were extracted, and combined using the inverse-variance method and a random-effects model. A pre-established protocol was drawn up, in which the primary outcome was the difference in circulating estradiol concentrations between the physical activity (experimental) and the control groups after intervention. Pre-specified subgroup analyses and sensitivity analysis according to the risk of bias were conducted.
RESULTS
Data suitable for quantitative synthesis were available from 18 RCTs (1994 participants) for total estradiol and from 5 RCTs (1245 participants) for free estradiol. The overall effect of physical activity was a statistically significant decrease of both total estradiol (standardized mean difference [SMD] -0.12; 95 % confidence interval [CI] -0.20 to -0.03; P = 0.01; I (2) = 0 %) and free estradiol (SMD -0.20; 95 % CI -0.31 to -0.09; P = 0.0005; I (2) = 0 %). Subgroup analyses suggest that this effect is independent of menopausal status and is more noticeable for non-obese women and for high intensity exercise. Meta-analysis for secondary outcomes found that physical activity induces a statistically significant decline of free testosterone, androstenedione, dehydroepiandrosterone-sulfate and adiposity markers, while a significant increase of SHBG was observed.
CONCLUSIONS
Although the effect is relatively modest, physical activity induces a decrease in circulating sex hormones and this effect is not entirely explained by weight loss. The findings emphasize the benefits of physical activity for women.
Topics: Androgens; Estrogens; Female; Humans; Motor Activity; Randomized Controlled Trials as Topic
PubMed: 26541144
DOI: 10.1186/s13058-015-0647-3 -
Endocrine Practice : Official Journal... Jun 2015Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and hyperlipidemia, which are predisposing factors for type 2 diabetes mellitus and CV disease. The aim of this meta-analysis is to examine the effect of insulin sensitizers on clinical and biochemical features of PCOS and risk factors for CV disease.
METHODS
A systematic literature review was conducted, and randomized controlled clinical trials were identified by a search of bibliographic databases: Medline database (from 1966 forward), EMBASE (January 1985 forward), and Cochrane Central Register of Controlled Trials. Reviews of reference lists further identified candidate trials. Data was independently abstracted in duplicate by 2 investigators using a standardized data-collection form. Articles without a comparison group and randomization allocation were excluded. Reviewers worked independently and in duplicate to determine the methodological quality of trials, then collected data on patient characteristics, interventions, and outcomes.
RESULTS
Of 455 studies, 44 trials were eligible. A random effects model was used. Significant unadjusted results favoring treatment with insulin sensitizers were obtained for body mass index (BMI) (effect size [ES] of 0.58), waist to hip ratio (WHR) (ES of 0.02), low-density-lipoprotein cholesterol (LDL-C) (ES of 0.11), fasting insulin (ES of 2.82), fasting glucose (ES of 0.10), free testosterone (ES of 1.88), and androstenedione level (ES of 0.76).
CONCLUSION
Treatment with insulin sensitizers in women with PCOS results in improvement in CV factors such as BMI, WHR, LDL-C, fasting insulin, glucose, free testosterone, and androstenedione.
Topics: Cardiovascular Diseases; Female; Humans; Insulin Resistance; Polycystic Ovary Syndrome; Risk Factors
PubMed: 25716630
DOI: 10.4158/EP14396.RA -
Age (Dordrecht, Netherlands) Feb 2015The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a... (Meta-Analysis)
Meta-Analysis Review
The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a meta-analysis of randomized controlled studies. We systematically searched PubMed database until 4th October 2013. We included randomized placebo-controlled trials (RCT) that studied testosterone replacement therapy in men over 60 years of age, with total testosterone levels ≤550 ng/dl, observing gains in weight, lean mass tissue and fat mass as outcome. We excluded duplicated studies, studies which mixed men and women, and studies using weak androgens such as dehydroepiandrosterone or androstenedione. The initial search yielded 2681 articles, of which 26 were selected for full text analysis. In the end, 11 studies were included. However, 3 studies were not included in the meta-analysis. Meta-analysis showed that mean weight increased (lean mass), ranging from 1.65 (95 % CI, 1.61-1.69) to 6.20 (95 % CI, 5.22-7.18) kg, although it was heterogeneous (I (2) = 98 %). Effect estimate was 3.59 [2.38-4.81]. Androgen therapy decreased fat mass; effect estimate was -1.78 [-2.57, -0.99] that analysis had also a high level of heterogeneity (I (2) = 81 %). The results suggest that testosterone replacement therapy is able to increase muscle mass in elderly men and that is affected by the time that the treatment is carried out and the method of administration of the drug.
Topics: Aged; Aged, 80 and over; Androgens; Body Mass Index; Body Weight; Hormone Replacement Therapy; Humans; Male; Middle Aged; Testosterone
PubMed: 25637335
DOI: 10.1007/s11357-014-9742-0 -
Steroids Jul 2015A systematic review of the literature on sex steroid measurement in breast tissue identified only 19 articles meeting the following criteria: menopausal status given;... (Meta-Analysis)
Meta-Analysis Review
A systematic review of the literature on sex steroid measurement in breast tissue identified only 19 articles meeting the following criteria: menopausal status given; steroids measured in tissue homogenates by conventional RIA with a purification step or by mass spectrometry; and values reported per g tissue or per g protein. Twelve articles were analyzed in detail for: ratios of sex steroid hormone levels in cancerous or benign tissues to blood levels, stratified by menopausal status; ratios between the different hormone levels within tissues or within blood; and difference in these ratios between tissue and blood compartments. Estrogen and androgen concentrations varied greatly in benign and cancerous tissues and in blood between individuals. Postmenopausal, but not premenopausal, estradiol concentrations were significantly higher in cancerous compared to benign breast tissue. The estradiol/estrone ratio was lowest in premenopausal benign tissue, and substantially higher in premenopausal cancerous tissue and postmenopausal benign and cancerous tissues. Estradiol and estrone levels were considerably higher in tissue than in plasma in both premenopausal and postmenopausal women. Androgen levels were generally higher in the benign than the cancerous tissue, and tissue androgen levels were higher than in plasma, suggesting in situ aromatization of androgens to estrogens in breast cancer tissue. Limited available data on levels of hydroxylated estrogens in breast tissue compared to corresponding levels in plasma or urine were reviewed, but due to the paucity of studies no conclusions can presently be drawn regarding the relationship of the 2-hydroxyestrone:16α-hydroxyestrone ratio to breast cancer risk and genotoxic effects of 4-hydroxylated estrogens. Finally, data on hormone levels in breast adipose tissue were analyzed; high levels of androstenedione and testosterone and significant estrone and estradiol levels in breast adipocytes from postmenopausal breast cancer patients are consistent with an obesity-inflammation-aromatase axis occurring locally in breast tissue. The controversies regarding the source of intratumoral estrogens in the breast are summarized.
Topics: Adipose Tissue; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Estrogens; Female; Gonadal Steroid Hormones; Humans; Mammary Glands, Human; Premenopause; Reference Values; Steroids
PubMed: 25554581
DOI: 10.1016/j.steroids.2014.12.011 -
Endocrine Connections 2014Polycystic ovarian syndrome (PCOS) affects 18-22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of...
Polycystic ovarian syndrome (PCOS) affects 18-22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966-April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39 IU/l (95% CI 0.09 to 0.70, P=0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37 nmol/l (95% CI 1.27 to 3.47, P<0.0001), total testosterone levels, MD -0.13 nmol/l (95% CI -0.22 to -0.03, P=0.008), androstenedione levels, MD -0.09 ng/dl (95% CI -0.15 to -0.03, P=0.005), free androgen index (FAI) levels, MD -1.64 (95% CI -2.94 to -0.35, P=0.01) and Ferriman-Gallwey (FG) score, MD -1.01 (95% CI -1.54 to -0.48, P=0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42 IU/l (95% CI 0.11 to 0.73, P=0.009), SHBG levels, MD 3.42 nmol/l (95% CI 0.11 to 6.73, P=0.04), total testosterone levels, MD -0.16 nmol/l (95% CI -0.29 to -0.04, P=0.01), androstenedione levels, MD -0.09 ng/dl (95% CI -0.16 to -0.03, P=0.004) and FG score, MD -1.13 (95% CI -1.88 to -0.38, P=0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS.
PubMed: 24488490
DOI: 10.1530/EC-14-0010 -
[CYP17A1 inhibitors in prostate cancer: mechanisms of action independent of the androgenic pathway].Progres En Urologie : Journal de... Oct 2013The objective of this article is to review the mechanisms of action of abiraterone acetate, independently of the androgenic pathway. (Review)
Review
INTRODUCTION
The objective of this article is to review the mechanisms of action of abiraterone acetate, independently of the androgenic pathway.
MATERIAL AND METHOD
A systematic review of the literature was carried out on Medline and Embase databases.
RESULTS
Inhibition of CYP17A1 with abiraterone acetate induces changes in steroid metabolism, whose main component is the reduction of DHEA and androstenedione synthesis. This results in inhibition of androgen pathway in prostatic cancerous epithelial cell. Regardless of androgen activation pathway, abiraterone acetate could also act via an alternative mechanism of action not fully elucidated. Stromal cells, like tumor cells, could undergo the effects of CYP17A1 inhibition, resulting in blocking the production of secondary mediators that contribute to tumor progression. Similarly, it has been suggested that abiraterone acetate efficacy may be related to its ability to alter intratumoral concentrations of estrogen and progesterone.
CONCLUSION
The validation of these mechanisms could contribute to improved therapeutic strategies based on the use of abiraterone acetate alone or in combination.
Topics: Abiraterone Acetate; Adjuvants, Immunologic; Androgens; Androstadienes; Androstenedione; Antineoplastic Agents; Dehydroepiandrosterone; Disease Progression; Humans; Male; Prostatic Neoplasms; Steroid 17-alpha-Hydroxylase; Treatment Outcome
PubMed: 24314739
DOI: 10.1016/S1166-7087(13)70041-1 -
Reproductive Biomedicine Online Jul 2013Although much research focuses on hormones during gestation, little is known about the actual hormone concentrations within the fetal surroundings. The aim of this study... (Review)
Review
Although much research focuses on hormones during gestation, little is known about the actual hormone concentrations within the fetal surroundings. The aim of this study was to combine all available oestrogen, androgen, sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), inhibin, gonadotrophin and dehydroepiandrosterone sulphate (DHEAS) concentrations during gestation and post partum into graphical representations reporting weighted mean hormone values. A systematic search was performed in Pubmed and Embase from inception to March 2012. Studies were evaluated by two reviewers; manuscripts were included if the actual hormone concentrations were reported together with the gestational age at time of sampling. A total of 97 articles were found eligible for this review. Maternal serum oestrogens, inhibin A, SHBG, androstenedione and testosterone rise during gestation, which is followed by a rapid decline in the post-partum period. For AMH and DHEAS, an inverse relationship is found, while gonadotrophin concentrations are negligible during gestation. For girls cord blood oestriol and post-partum FSH concentrations are higher, while for boys cord blood FSH and neonatal testosterone, inhibin B, LH and AMH concentrations are higher. In conclusion, longitudinally measured endocrine data during gestation and in the peri- and post-natal period are lacking, especially for twin pregnancies.
Topics: Amniotic Fluid; Androgens; Estrogens; Female; Fetal Blood; Fetus; Gestational Age; Hormones; Humans; Infant; Infant, Newborn; Inhibins; Male; Pregnancy; Pregnancy, Twin
PubMed: 23669015
DOI: 10.1016/j.rbmo.2013.03.009