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Hormone and Metabolic Research =... Jan 2019While several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and... (Meta-Analysis)
Meta-Analysis
While several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (β=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (β=-0.009; 95% CI: -0.02, -0.001), and systolic blood pressure (SBP) (β=-0.01; 95% CI: -0.03, -0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (β=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (β=-0.41; 95% CI: -0.70, -0.12). There was a positive significant association between A4 and TG (β=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (β=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (β=-0.03; 95% CI: -0.06, -0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.
Topics: Androgens; Blood Pressure; Cholesterol; Female; Humans; Hyperandrogenism; Insulin; Polycystic Ovary Syndrome; Testosterone
PubMed: 30650457
DOI: 10.1055/a-0806-8281 -
World Journal of Pediatrics : WJP Feb 2019Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells....
BACKGROUND
Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells. This equilibrium is regulated by numerous cytokines, but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis, respectively. The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1). RANKL, sclerostin and DKKs-1 are often up-regulated in bone diseases, and they are the target of new monoclonal antibodies.
DATA SOURCES
The authors performed a systematic literature search in PubMed and EMBASE to June 2018, reviewed and selected articles, based on pre-determined selection criteria.
RESULTS
We re-evaluated the role of RANKL, osteoprotegerin, sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases, such as type 1 diabetes mellitus (T1DM), alkaptonuria (AKU), hemophilia A, osteogenesis imperfecta (OI), 21-hydroxylase deficiency (21OH-D) and Prader-Willi syndrome (PWS). To do so, we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-ß-catenin signaling pathways have been investigated, and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.
CONCLUSIONS
The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases. Furthermore, for some of them, bone damage began in childhood but only manifested with age. The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children, although further studies need to be carried out.
Topics: Adrenal Hyperplasia, Congenital; Alkaptonuria; Biomarkers; Bone Remodeling; Bone Resorption; Child; Diabetes Mellitus, Type 1; Hemophilia A; Humans; Intercellular Signaling Peptides and Proteins; Osteogenesis Imperfecta; Osteoprotegerin; Prader-Willi Syndrome; RANK Ligand; Up-Regulation; Wnt Signaling Pathway
PubMed: 30343446
DOI: 10.1007/s12519-018-0198-7 -
The Journal of Clinical Endocrinology... Nov 2018Females with congenital adrenal hyperplasia (CAH) and atypical genitalia often undergo complex surgeries; however, their outcomes remain largely uncertain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Females with congenital adrenal hyperplasia (CAH) and atypical genitalia often undergo complex surgeries; however, their outcomes remain largely uncertain.
METHODS
We searched several databases through 8 March 2016 for studies evaluating genital reconstructive surgery in females with CAH. Reviewers working independently and in duplicate selected and appraised the studies.
RESULTS
We included 29 observational studies (1178 patients, mean age at surgery, 2.7 ± 4.7 years; mostly classic CAH). After an average follow-up of 10.3 years, most patients who had undergone surgery had a female gender identity (88.7%) and were heterosexual (76.2%). Females who underwent surgery reported a sexual function score of 25.13 using the Female Sexual Function Index (maximum score, 36). Many patients continued to complain of substantial impairment of sensitivity in the clitoris, vaginal penetration difficulties, and low intercourse frequency. Most patients were sexually active, although only 48% reported comfortable intercourse. Most patients (79.4%) and treating health care professionals (71.8%) were satisfied with the surgical outcomes. Vaginal stenosis was common (27%), and other surgical complications, such as fistulas, urinary incontinence, and urinary tract infections, were less common. Data on quality of life were sparse and inconclusive.
CONCLUSION
The long-term follow-up of females with CAH who had undergone urogenital reconstructive surgery shows variable sexual function. Most patients were sexually active and satisfied with the surgical outcomes; however, some patients still complained of impairment in sexual experience and satisfaction. The certainty in the available evidence is very low.
Topics: Adrenal Hyperplasia, Congenital; Female; Genitalia, Female; Gynecologic Surgical Procedures; Humans; Patient Satisfaction; Practice Guidelines as Topic; Quality of Life; Plastic Surgery Procedures; Sexual Behavior; Treatment Outcome
PubMed: 30272250
DOI: 10.1210/jc.2018-01863 -
The Journal of Clinical Endocrinology... Nov 2018Individuals with congenital adrenal hyperplasia (CAH) require glucocorticoid therapy to replace cortisol and to control androgen excess. We sought to evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Individuals with congenital adrenal hyperplasia (CAH) require glucocorticoid therapy to replace cortisol and to control androgen excess. We sought to evaluate the effects of glucocorticoid therapy on cardiovascular and metabolic outcomes in individuals with CAH.
METHODS
We searched bibliographical databases through January 2016 for studies evaluating cardiovascular risk factors in individuals with CAH treated with glucocorticoids compared with controls without CAH. We used a random-effects model to synthesize quantitative data.
RESULTS
We included 20 observational studies (14 longitudinal, six cross-sectional) with a moderate to high risk of bias. The average dose of glucocorticoids (in hydrocortisone equivalents) was 9 to 26.5 mg/m2/d. In the meta-analysis (416 patients), compared with controls without CAH, individuals with CAH had increased systolic blood pressure [weighted mean difference (WMD), 4.44 mm Hg; 95% CI, 3.26 to 5.63 mm Hg], diastolic blood pressure (WMD, 2.35 mm Hg; 95% CI, 0.49 to 4.20 mm Hg), homeostatic model assessment of insulin resistance (WMD, 0.49; 95% CI, 0.02 to 0.96), and carotid intima thickness (WMD, 0.08 mm; 95% CI, 0.01 to 0.15 mm). No statistically significant differences were noted in fasting blood glucose, insulin level, glucose, or insulin level after 2-hour glucose load or serum lipids. Data on cardiac events were sparse, and most of the literature focused on surrogate outcomes.
CONCLUSION
Individuals with CAH demonstrate a high prevalence of cardiovascular and metabolic risk factors. The current evidence relies on surrogate outcomes. Long-term prospective studies are warranted to assess strategies for reducing cardiovascular risk in individuals with CAH.
Topics: Adrenal Hyperplasia, Congenital; Blood Pressure; Cardiovascular Diseases; Cardiovascular System; Carotid Intima-Media Thickness; Endocrinology; Glucocorticoids; Humans; Metabolic Syndrome; Practice Guidelines as Topic; Prevalence; Risk Factors
PubMed: 30272185
DOI: 10.1210/jc.2018-01862 -
Endocrine Oct 2018Congenital adrenal hyperplasia (CAH) has been shown to potentially affect psychological adjustment. However, most research has focused on females, and knowledge about...
PURPOSE
Congenital adrenal hyperplasia (CAH) has been shown to potentially affect psychological adjustment. However, most research has focused on females, and knowledge about psychological challenges in males remains sparse. The aim of this systematic review was therefore to assess these in males with CAH.
METHODS
We systematically searched the OVID Medline, PsycINFO, CINAHL, and Web of Science databases, for articles published up to April 20, 2018, investigating psychological adjustment in males with CAH.
RESULTS
Eleven studies were included in the review. Three main health domains were identified: psychological and psychiatric health, quality of life (QoL), and self-perceptions of reproductive health. Some studies covered more than one health domain. Seven studies explored psychological adjustment and/or the presence of psychiatric symptoms or disorders. Results indicated that males with CAH had more problems related to internalizing behaviors (negative behaviors directed toward the self) and more negative emotionality compared to reference groups. Six studies examined QoL, five of them reporting reduced QoL compared to reference groups. Three studies explored the impact of fertility and sexual health issues on psychological health with varying results from impaired to normal sexual well-being.
CONCLUSIONS
CAH seems to have an impact on males' psychological health. However, the number of identified studies was limited, included few participants, and revealed divergent findings, demonstrating the need for larger studies and highlighting a number of methodological challenges that should be addressed by future research.
Topics: Adrenal Hyperplasia, Congenital; Emotional Adjustment; Humans; Male; Mental Health; Quality of Life; Self Concept
PubMed: 30128958
DOI: 10.1007/s12020-018-1723-0 -
The Journal of Clinical Endocrinology... May 2018Management of congenital adrenal hyperplasia (CAH) involves suppression of the hypothalamic-pituitary-adrenal axis using supraphysiological doses of exogenous... (Meta-Analysis)
Meta-Analysis
CONTEXT
Management of congenital adrenal hyperplasia (CAH) involves suppression of the hypothalamic-pituitary-adrenal axis using supraphysiological doses of exogenous glucocorticoids. This can pose a challenge, with Cushing syndrome a frequent complication of adequate suppression. Bilateral adrenalectomy, with subsequent replacement of glucocorticoids and mineralocorticoids at physiological doses, has been proposed as an alternative therapeutic strategy.
OBJECTIVE
To review the outcomes after bilateral adrenalectomy for CAH.
DATA SOURCES
A systematic search of PubMed/MEDLINE and Web of Science, identifying relevant reports published up to 10 January 2018.
STUDY SELECTION
Case reports or case series were included if they reported individual patient data from patients with CAH who had undergone bilateral adrenalectomy.
DATA EXTRACTION
Information regarding the following was extracted: first author, country, sex, age at adrenalectomy, year of adrenalectomy, diagnosis, molecular abnormality, pre- and postoperative biochemistry, pre- and postoperative medications, pre- and postoperative body mass index, indication for adrenalectomy, surgical technique, gross and microscopic adrenal characteristics, follow-up duration, and short- and long-term postoperative outcomes.
DATA SYNTHESIS
We identified 48 cases of bilateral adrenalectomy for CAH, with patients aged from 4 months to 56 years at surgery. The most common indication for surgery was the inability to control hyperandrogenism/virilization and/or Cushing syndrome (n = 30; 62%). Most patients (n = 34; 71%) reported symptomatic improvement postoperatively, with some cases of short-term (n = 5; 10%) and long-term (n = 13; 27%) adverse outcomes.
CONCLUSIONS
Bilateral adrenalectomy for CAH appears to be a reasonable therapeutic option for carefully selected patients who have had unsatisfactory outcomes with conventional medical management.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adrenalectomy; Adult; Child; Child, Preschool; Cushing Syndrome; Female; Fertility; Glucocorticoids; Hormone Replacement Therapy; Humans; Hyperandrogenism; Infant; MEDLINE; Male; Middle Aged; Mineralocorticoids; Postoperative Complications; Pregnancy; Treatment Outcome; Virilism
PubMed: 29554355
DOI: 10.1210/jc.2018-00217 -
The European Journal of Contraception &... Feb 2018Nowadays, selection of COCs with maximum antiandrogenic effects is one the main issues in treatment of women with polycystic ovary syndrome (PCOS). (Meta-Analysis)
Meta-Analysis Review
Effects of combined oral contraceptives on the clinical and biochemical parameters of hyperandrogenism in patients with polycystic ovary syndrome: a systematic review and meta-analysis.
INTRODUCTION
Nowadays, selection of COCs with maximum antiandrogenic effects is one the main issues in treatment of women with polycystic ovary syndrome (PCOS).
OBJECTIVE
This systematic review and meta-analysis aimed to compare the effects of COCs on the clinical and biochemical parameters of hyperandrogenism (HA) in patients with PCOS.
METHODS
Electronic databases (PubMed, Scopus, ScienceDirect and web of science) were searched from 1987 to November 2015 to identify clinical trials investigating effect of the various COCs on the clinical and biochemical parameters of HA in patients. In this meta-analysis, both fixed and random effect models were used. Potential sources of heterogeneity were explored by meta-regression and subgroup analyses.
RESULTS
Findings showed that COC use for 3-12 months was significantly associated with an increase in sex hormone-binding globulin (SHBG) levels and a decrease in Ferriman-Gallwey (FG) score, total testosterone (TT), free testosterone (FT), androstenedione (A4) and dehydroepiandrosterone sulphate (DHEAS) levels. Type of progestin or duration of treatment had no important effects on declining androgen levels. Long-term use of COCs (6-12 months) was more effective in improving hirsutism, compared to short term. COCs containing cyproterone acetate (CPA) for 12 months had the strongest effect in improving hirsutism.
CONCLUSIONS
This study shows that, in patients with PCOS, COCs can effectively improve biochemical and clinical parameters of HA. All COCs studies have similar effects on the hormonal profiles of these patients, and products containing CPA may be an effective treatment in hirsute patients with PCOS.
Topics: Contraceptives, Oral, Combined; Ethinyl Estradiol; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Progestins; Regression Analysis; Sex Hormone-Binding Globulin; Treatment Outcome
PubMed: 29457756
DOI: 10.1080/13625187.2018.1435779 -
Human Reproduction Update Sep 2017Non-classic congenital hyperplasia (NCAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by androgen excess. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-classic congenital hyperplasia (NCAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by androgen excess.
OBJECTIVE AND RATIONALE
We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of NCAH. A meta-analysis of epidemiological data was also performed.
SEARCH METHODS
Peer-reviewed studies evaluating NCAH published up to October 2016 were reviewed. Multiple databases were searched including MEDLINE, EMBASE, Cochrane, ERIC, EBSCO, dissertation abstracts, and current contents.
OUTCOMES
The worldwide prevalence of NCAH amongst women presenting with signs and symptoms of androgen excess is 4.2% (95% confidence interval: 3.2-5.4%). The clinical consequences of NCAH expand from infancy, i.e. accelerated growth, to adolescence and adulthood, i.e. premature pubarche, cutaneous symptoms and oligo-ovulation in a polycystic ovary syndrome (PCOS)-like clinical picture. The diagnosis of NCAH relies on serum 17-hydroxyprogesterone (17-OHP) concentrations. A basal 17-OHP concentration ≥2 ng/ml (6 nmol/l) should be used for screening if more appropriate in-house cut-off values are not available. Definitive diagnosis requires a 17-OHP concentration ≥10 ng/ml (30 nmol/l), either basally or after cosyntropin-stimulation. Molecular genetic analysis of the CYP21A2 gene, which is responsible for 21-hydroxylase activity, may be used for confirmation purposes and should be offered to all patients with NCAH along with genetic counseling because these patients frequently carry alleles that may result in classic CAH, the more severe form of the disease, in their progeny. Treatment must be individualized. Glucocorticoid replacement therapy may benefit pediatric patients with accelerated growth or advanced bone age or adult women seeking fertility, whereas adequate control of menstrual irregularity, hirsutism and other cutaneous symptoms is best served by the use of oral contraceptive pills and/or anti-androgens. Some women may need ovulation induction or assisted reproductive technology to achieve pregnancy. Patients with NCAH have a higher risk of miscarriage and may benefit from glucocorticoid treatment during pregnancy.
WIDER IMPLICATIONS
Evidence-based diagnostic and treatment strategies are essential for the proper management of women with NCAH, especially considering that these patients may need different therapeutic strategies at different stages during their follow-up and that appropriate genetic counseling may prevent the occurrence of CAH in their children.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Androgen Antagonists; Female; Hirsutism; Humans; Infertility, Female; Menstruation Disturbances
PubMed: 28582566
DOI: 10.1093/humupd/dmx014 -
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 -
The European Journal of Contraception &... Jun 2017Hyperandrogenism affects approximately 10-20% of women of reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne, seborrhea and alopecia are associated... (Review)
Review
INTRODUCTION
Hyperandrogenism affects approximately 10-20% of women of reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne, seborrhea and alopecia are associated with significant quality of life and psychological impairment. Women with abnormalities in androgen metabolism may have accompanying anovulation and/or polycystic ovary syndrome (PCOS), both of which have reproductive and metabolic implications if left untreated. Cyproterone acetate (CPA), combined with ethinylestradiol (EE), is indicated for the treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhea) and/or hirsutism, in women of reproductive age.
OBJECTIVE
To review the data on the efficacy and safety of CPA 2 mg/EE 35 μg for the treatment of hyperandrogenic skin symptoms in women.
METHODS
A non-systematic narrative review based on a literature search of the PubMed database.
RESULTS
Seventy-eight studies were identified. The majority of sufficiently powered studies show a high efficacy of CPA 2 mg/EE 35 μg in the treatment of severe acne and hirsutism. Studies show that therapeutic response in women with hirsutism requires a long-term approach and that hyperandrogenic skin symptoms in patients with PCOS are efficiently treated. Additional benefits include cycle control and, in some women, improvement in mood and perception of body image. Safety and tolerability data are summarized by the pharmacovigilance risk assessment committee (PRAC) of the European Medicine's Agency's (EMA).
CONCLUSIONS
This review provides a comprehensive overview about the efficacy of CPA 2 mg/EE 35 μg in the treatment of hyperandrogenic skin symptoms, thus allowing both health care professionals and women to balance the risks and benefits of treatment based on evidence.
Topics: Acne Vulgaris; Adult; Androgen Antagonists; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Hirsutism; Humans; Hyperandrogenism; Skin Diseases; Treatment Outcome
PubMed: 28447864
DOI: 10.1080/13625187.2017.1317339