-
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 -
PloS One 2020Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrine disorders of women of reproductive age. Treatment plans for this chronic condition frequently...
BACKGROUND
Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrine disorders of women of reproductive age. Treatment plans for this chronic condition frequently include long-term use of a combination of medication and lifestyle interventions. However, treatment outcomes are dependent on adherence to treatment regimens. This study aimed to systematically review the literature for reported adherence to treatments for PCOS.
METHODS
A systematic search of Embase, Cochrane, PubMed, CINAHL, PsychINFO, SCOPUS, and International Pharmaceutical Abstracts from inception until January 2019 utilizing the terms PCOS, adherence, and patient compliance was conducted. A total of 179 possible articles were identified.
RESULTS
Fourteen articles reporting adherence data were included in the review. Self-report was the most commonly reported method of measuring adherence. Adherence to lifestyle interventions, such as prescribed diets and physical activity, was reported in ten studies and adherence to medications was reported in seven studies, with some reporting both.
CONCLUSIONS
Minimal data are available regarding factors associated with adherence in patients with PCOS. Diverse methods of adherence assessment are utilized. Future studies of PCOS treatments should effectively assess and report adherence data as it is essential to evaluating the effectiveness of PCOS treatments and is critically needed to guide clinician efforts to facilitate optimal outcomes for patients.
Topics: Body Mass Index; Female; Humans; Hyperandrogenism; Insulin Resistance; Life Style; Obesity; Patient Compliance; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Self Report; Testosterone; Treatment Outcome
PubMed: 32053629
DOI: 10.1371/journal.pone.0228586 -
BJOG : An International Journal of... Jul 2020There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility. (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility.
OBJECTIVES
To determine whether infertile women have higher levels of cardiovascular risk factors compared with fertile women.
SEARCH STRATEGY
We performed a systematic literature search using PubMed, Embase and CINAHL, Scopus and additional manual and bibliographic searches for relevant articles (end search date 6 November 2019).
SELECTION CRITERIA
We selected studies that compared cardio-metabolic risk factors in fertile and infertile women of reproductive age.
DATA COLLECTION AND ANALYSIS
At least two authors independently screened potentially eligible studies.
MAIN RESULTS
There was an increased presence of several cardio-metabolic risk factors in infertile women compared with fertile women. Infertile women had statistically significant higher body mass index (BMI), increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) compared with fertile women. Fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and mean arterial pressure were not found to be different between fertile and infertile women. A subgroup analysis revealed that TC, fasting glucose and fasting insulin were increased, and high-density lipoprotein was decreased only in women with polycystic ovarian syndrome compared with fertile women, whereas BMI, TG and LDL-C were statistically significantly increased in women with any indication of infertility compared with fertile women.
CONCLUSIONS
Infertile women have a higher level of cardio-metabolic risk factors compared with fertile women. This finding has clinical implications for infertile women in general, and those attempting to conceive through medically assisted reproduction.
TWEETABLE ABSTRACT
Infertile women appear to have a higher level of cardio-metabolic risk factors compared with fertile women.
Topics: Adult; Body Mass Index; Cardiovascular Diseases; Cholesterol, LDL; Disease Susceptibility; Female; Humans; Hyperandrogenism; Infertility, Female; Insulin Resistance; Metabolic Syndrome; Polycystic Ovary Syndrome; Risk Factors; Triglycerides
PubMed: 32048421
DOI: 10.1111/1471-0528.16171 -
The Journal of Clinical Endocrinology... Mar 2020P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with significant morbidity. However there has been limited analysis of reported PORD... (Meta-Analysis)
Meta-Analysis
CONTEXT
P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with significant morbidity. However there has been limited analysis of reported PORD cases.
OBJECTIVE
To determine, based on the cohort of reported PORD cases, genotype-phenotype relationships for skeletal malformations, maternal virilisation in pregnancy, adrenal insufficiency, and disorders of sexual development (DSD).
DATA SOURCES
PubMed and Web of Science from January 2004 to February 2018.
STUDY SELECTION
Published case reports/series of patients with PORD. Eligible patients were unique, had biallelic mutations, and their clinical features were reported.
DATA EXTRACTION
Patient data were manually extracted from the text of case reports/series. A malformation score, representing the severity of skeletal malformations, was calculated for each patient.
DATA SYNTHESIS
Of the 211 patients published in the literature, 90 were eligible for inclusion. More than 60 unique mutations were identified in this cohort. Four groups of mutations were identified, through regression modeling, as having significantly different skeletal malformation scores. Maternal virilization in pregnancy, reported for 21% of patients, was most common for R457H mutations. Adrenal insufficiency occurred for the majority of patients (78%) and was typically mild, with homozygous R457H mutations being the least deficient. DSD affected most patients (72%), but were less common for males (46XY) with homozygous R457H mutations.
CONCLUSIONS
PORD is a complex disorder with many possible mutations affecting a large number of enzymes. By analyzing the cohort of reported PORD cases, this study identified clear relationships between genotype and several important phenotypic features.
Topics: Adrenal Insufficiency; Antley-Bixler Syndrome Phenotype; Female; Genotype; Humans; Male; Musculoskeletal Abnormalities; Mutation; Phenotype
PubMed: 31825489
DOI: 10.1210/clinem/dgz255 -
Gynecological Endocrinology : the... Jun 2020Polycystic ovary syndrome (PCOS) is a risk factor for dysglycemia, insulin resistance, and type 2 Diabetes Mellitus (T2DM). Inefficient energy oxidation, metabolic...
Polycystic ovary syndrome (PCOS) is a risk factor for dysglycemia, insulin resistance, and type 2 Diabetes Mellitus (T2DM). Inefficient energy oxidation, metabolic inflexibility, is a marker of blunted metabolism. We conducted a systematic review on metabolic inflexibility in women with PCOS. We searched MEDLINE, EMBASE and Cochrane central (inception-October 2018) for studies evaluating metabolic inflexibility and reporting on changes in Respiratory Quotient (ΔRQ). We extracted data and assessed quality using The Newcastle-Ottawa Scale. We included five prospective cohort studies (461 women). Three compared PCOS women to unaffected subjects, one to women with obesity or T2DM, and one to adolescent girls; all had medium quality. Three studies showed higher metabolic inflexibility in women with PCOS (ΔRQ range 0.05-0.098) compared to unaffected subjects. Women with PCOS had similar metabolic inflexibility compared to those with T2DM (ΔRQ 0.05 ± 0.03 vs 0.06 ± 0.04, = .98) and obesity ( = .06). Inflexibility was higher in hyperandrogenemic women with PCOS (ΔRQ 0.091 ± 0.060 vs 0.120 ± 0.010, = .014). ΔRQ was lower in PCOS women with insulin resistance vs those with normal insulin sensitivity (0.04 ± 0.02 vs. 0.07 ± 0.04, = .007). In conclusion, women with polycystic ovary syndrome appear to have higher metabolic inflexibility associated with hyperandrogenemia and insulin resistance.
Topics: Adolescent; Adult; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Hyperandrogenism; Insulin Resistance; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Young Adult
PubMed: 31793357
DOI: 10.1080/09513590.2019.1698025 -
Clinical Endocrinology Feb 2020To assess the efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia. (Meta-Analysis)
Meta-Analysis
Efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: A systematic review and meta-analysis.
OBJECTIVE
To assess the efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia.
METHODS
MEDLINE, EMBASE, the Cochrane Library, the clinicaltrials.gov website databases were systematically searched from inception through March 2019. WMD and SMD with 95%CIs were calculated using random or fixed effects models.
RESULTS
There was a significant reduction in virilization in the DEX-treated group (WMD: -2.39, 95%CI: -3.31,-1.47). No significant differences were found in newborn physical outcomes for birth weight (WMD: 0.09, 95%CI: -0.09, 0.27) and birth length (WMD = 0.27, 95%CI: -0.68, 1.21). Concerning cognitive functions, no significant differences in the domains of psychometric intelligence (SMD: 0.05, 95%CI: -0.74, 0.83), verbal memory (SMD: -0.17, 95%CI: -0.58, 0.23), visual memory (SMD: 0.10, 95%CI: -0.14, 0.34), learning (SMD: -0.02, 95%CI: -0.27, 0.22) and verbal processing (SMD: -0.38, 95%CI: -0.93, 0.17). Regarding behavioural problems, no significant differences in the domains of internalizing problems (SMD: 0.16, 95%CI: -0.49, 0.81), externalizing problems (SMD: 0.07, 95%CI: -0.30, 0.43) and total problems (SMD: 0.14, 95%CI: -0.23, 0.51). With respect to temperament, no significant differences in the domains of emotionality (SMD: 0.13, 95%CI: -0.79, 1.05), activity (SMD: 0.04, 95%CI: -0.32, 0.39), shyness (SMD: 0.25, 95%CI: -0.70, 1.20) and sociability (SMD: -0.23, 95%CI: -0.90, 0.44).
CONCLUSIONS
Prenatal DEX treatment reduced virilization with no significant differences in newborn physical outcomes, cognitive functions, behavioural problems and temperament. The results need to be interpreted cautiously due to the existence of limitations.
Topics: Adrenal Hyperplasia, Congenital; Adult; Cognition; Dexamethasone; Female; Genetic Predisposition to Disease; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Memory; Pregnancy; Prenatal Exposure Delayed Effects; Problem Behavior; Risk Factors; Treatment Outcome; Virilism
PubMed: 31715010
DOI: 10.1111/cen.14126 -
Frontiers in Endocrinology 2019Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000...
Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000 individuals and the frequency varies according to ethnicity. On the other hand, polycystic ovary syndrome has a familial basis and it is inherited under a complex hereditary trait. This syndrome affects 6 to 10% of women in reproductive age and it is the most common endocrine disorder in young women. Our aim was to investigate, through a systematic review, the distinct characteristics and common findings of these syndromes. The search period covered January 1970 to November 2018, using the scientific databases PubMed. Inclusion criteria were adult women patients with PCOS or NC-CAH. Search terms were "polycystic ovary syndrome," "PCOS," "non-classical adrenal hyperplasia," "NC-CAH," "21-hydroxylase deficiency." From an initial 16,255 titles, the evaluations led to the final inclusion of 97 papers. The clinical features of NC-CAH are hirsutism and ovulatory and menstrual dysfunction therefore; differentiation between these two syndromes is difficult based on clinical grounds only. Additionally, NC-CAH and PCOS are both associated with obesity, insulin resistance, and dyslipidaemia. Reproductive abnormalities are also common between these hyperandrogenemic disorders since in patients with NC-CAH polycystic ovarian morphology and subfertility are present as they are in women with PCOS. The diagnosis of PCOS, is confirmed once other disorders that mimic PCOS have been excluded e.g., conditions that are related to oligoovulation or anovulation and/or hyperandrogenism, such as hyperprolactinaemia, thyroid disorders, non-classic congenital adrenal hyperplasia, and androgen-producing neoplasms. The screening tool to distinguish non-classic adrenal hyperplasia from PCOS is the measurement of 17-hydroxyprogesterone levels. The basal levels of 17-hydroxyprogesterone may overlap, but ACTH stimulation testing can distinguish the two entities. In this review these two common endocrine disorders are discussed in an effort to unveil their commonalities and to illuminate their shadowed distinctive characteristics.
PubMed: 31275245
DOI: 10.3389/fendo.2019.00388 -
Journal of the Endocrine Society Jun 2019Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that...
Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that children with CAH be treated with hydrocortisone, but the appropriate glucocorticoid regimen in adults is uncertain. In order to review the outcomes of different glucocorticoid regimens in the management of CAH, a systematic search of PubMed/MEDLINE and Web of Science was conducted, including reports published up to 25 February 2019. Studies that compared at least two types of glucocorticoid preparation were included. The following information was extracted from each study: first author, year of publication, number and characteristics of patients and control subjects, types and doses of glucocorticoid regimen used, study design and outcomes [ biochemical tests, weight, height, body mass index (BMI), bone mineral density (BMD)]. A total of 23 studies were included in the qualitative synthesis, with 19 included in the quantitative synthesis. Dexamethasone was associated with the greatest degree of adrenal suppression; there was no significant difference in 17-hydroxyprogesterone (17OHP) and androstenedione levels between patients treated with hydrocortisone or prednisolone. Patients treated with dexamethasone had the lowest BMD and the highest BMI. Although dexamethasone therapy is associated with significantly lower 17OHP and androstenedione levels, it is also associated with more adverse effects. There do not appear to be significant differences between hydrocortisone and prednisolone therapy, and the choice of agent should be based on individual patient factors.
PubMed: 31187081
DOI: 10.1210/js.2019-00136 -
Journal of Pediatric Endocrinology &... Jun 2019Study objective Polycystic ovary syndrome (PCOS) in adolescence, a disorder of exclusion, has proved to be a timeless diagnostic challenge for the clinician. Since 1990,...
Study objective Polycystic ovary syndrome (PCOS) in adolescence, a disorder of exclusion, has proved to be a timeless diagnostic challenge for the clinician. Since 1990, several attempts to provide clear diagnostic criteria have been published, most of the time leading to inconsistencies. We attempted to elucidate the controversies and convergences of this subject by conducting a systematic review of the literature concerning official guidelines or proposed criteria for the diagnosis of PCOS in adolescent girls. Design Based on a term search sequence via electronic databases such as Pubmed, Cochrane, Embase, Scopus and a hands-on review of references and learned societies, all available data were classified and analyzed. Single case reports, original studies with adult population or articles with incomplete diagnostic guidelines were excluded. Results Twelve reports dated from 2006 to 2018 fulfilled the inclusion criteria. Seven of them were endorsed or published by learned societies. All suggested a stricter diagnosis than in adulthood. Polycystic ovarian morphology was used as a necessary criterion only in three guidelines, and there was a tendency for a more objective diagnosis of hyperandrogenism, defined either by clinical features or by biochemical hyperandrogenemia, although in one case both were required. Conclusion Irregular menstrual cycles, allowing for an interval of at least 2 years postmenarche, and hyperandrogenism, usually reinforced by biochemical confirmation, are the main accepted features for PCOS diagnosis in adolescence. Discrepancies among endocrine and reproductive medicine societies still remain, although recent intensified attempts at reaching a consensus should allow for more universally accepted diagnostic criteria.
Topics: Adolescent; Adolescent Health; Female; Humans; Hyperandrogenism; Menstruation Disturbances; Polycystic Ovary Syndrome
PubMed: 31141485
DOI: 10.1515/jpem-2019-0024 -
The Journal of Clinical Endocrinology... Jul 2019To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss (FPHL), a common form of hair loss in women that is characterized by the reduction of hair density in the central area of the scalp, whereas the frontal hairline is generally well conserved.
PARTICIPANTS
An expert task force appointed by the Androgen Excess and PCOS Society, which included specialists from dermatology, endocrinology, and reproductive endocrinology.
DESIGN
Levels of evidence were assessed and graded from A to D. Peer-reviewed studies evaluating FPHL published through December 2017 were reviewed. Criteria for inclusion/exclusion of the published papers were agreed on by at least two reviewers in each area and arbitrated by a third when necessary.
CONCLUSIONS
(i) The term "female pattern hair loss" should be used, avoiding the previous terms of alopecia or androgenetic alopecia. (ii) The two typical patterns of hair loss in FPHL are centrifugal expansion in the mid scalp, and a frontal accentuation or Christmas tree pattern. (iii) Isolated FPHL should not be considered a sign of hyperandrogenism when androgen levels are normal. (iv) The assessment of patients with FPHL is primarily clinical. (v) In all patients with FPHL, assessment of a possible androgen excess is mandatory. Measurement of vitamin D, iron, zinc, thyroid hormones, and prolactin are optional but recommended. (vi) Treatment of FPHL should start with minoxidil (5%), adding 5α-reductase inhibitors or antiandrogens when there is severe hair loss or hyperandrogenism.
Topics: 5-alpha Reductase Inhibitors; Alopecia; Androgen Antagonists; Female; Humans; Hyperandrogenism; Low-Level Light Therapy; Mineralocorticoid Receptor Antagonists; Minoxidil; Platelet-Rich Plasma; Polycystic Ovary Syndrome; Scalp; Spironolactone; Vasodilator Agents
PubMed: 30785992
DOI: 10.1210/jc.2018-02548