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Reproductive Biomedicine Online Apr 2021This systematic review aimed to assess variations in the clinical presentation and treatment outcomes of patients with polycystic ovary syndrome (PCOS) belonging to...
This systematic review aimed to assess variations in the clinical presentation and treatment outcomes of patients with polycystic ovary syndrome (PCOS) belonging to different ethnicities. A search was performed for studies comparing various clinical aspects of PCOS in two or more different ethnic groups. After screening 2264 studies, 35 articles were included in the final analysis. In comparison with White women with PCOS (wPCOS), East Asian women with PCOS (eaPCOS) were less hirsute, whereas Hispanic women with PCOS (hPCOS), South Asian women with PCOS (saPCOS) and Middle Eastern women with PCOS (mePCOS) were more hirsute. saPCOS had higher androgen and lower sex hormone-binding globulin (SHBG) concentrations, mePCOS had higher DHEAS concentrations, and hPCOS and Black women with PCOS (bPCOS) had lower SHBG and DHEAS measures than wPCOS. Menstrual disturbances were more frequent in eaPCOS. Both saPCOS and eaPCOS had lower body mass index with increased central adiposity. hPCOS and bPCOS were more obese. saPCOS, mePCOS, hPCOS and bPCOS had a higher prevalence of insulin resistance than wPCOS. bPCOS had a better lipid profile but higher blood pressure and cardiovascular risk. Indigenous Australian women with PCOS were more obese and more insulin resistant with higher androgen concentrations. The clinical phenotype of PCOS therefore shows a wide variation depending on ethnicity.
Topics: Female; Humans; Hyperandrogenism; Menstruation Disturbances; Ovary; Polycystic Ovary Syndrome
PubMed: 33487557
DOI: 10.1016/j.rbmo.2020.12.006 -
Endocrine Practice : Official Journal... Nov 2020The prevalence of adrenal tumors in congenital adrenal hyperplasia (CAH) is uncertain. Our objective was to estimate the prevalence and characteristics of adrenal tumors... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The prevalence of adrenal tumors in congenital adrenal hyperplasia (CAH) is uncertain. Our objective was to estimate the prevalence and characteristics of adrenal tumors and myelolipoma in CAH, and investigate clinical features of this population.
METHODS
We carried out systematic searches in Medline Ovid and Embase for articles published until January, 2020. Studies with confirmed CAH, biochemically and/or genetically, were included. The two authors independently extracted data from each study.
RESULTS
Six cohort studies were included in the prevalence calculation. In addition, 32 case reports on adrenal myelolipomas and CAH were included. The prevalence of adrenal tumors in CAH was 29.3%. When only studies with genetically verified cytochrome P450, Family 21, subfamily A, polypeptide 2 gene (CYP21A2) mutations were included the prevalence was 23.6%. The prevalence of myelolipoma in CAH was 7.4% (verified CYP21A2 mutations 8.6%). The proportion of myelolipoma in the adrenal tumors was 25.4% (genetically verified 36.6%). The median (range) age at tumor diagnosis was 36.0 (12 to 60) years and there were more tumors in males than in females (37.9% versus 22.1%; P<.05). In patients with myelolipomas, 93.5% had an undiagnosed or poorly managed CAH.
CONCLUSION
Patients with CAH had a high prevalence of adrenal tumors, particularly myelolipomas. Those with myelolipomas had a high frequency of late-diagnosed or poorly controlled CAH. Adrenal imaging may be considered in patients with CAH, especially if abdominal pain is present.
Topics: Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adult; Female; Humans; Male; Middle Aged; Myelolipoma; Prevalence; Steroid 21-Hydroxylase; Tomography, X-Ray Computed
PubMed: 33471666
DOI: 10.4158/EP-2020-0058 -
Archives of Gynecology and Obstetrics Mar 2021Polycystic ovarian syndrome (PCOS) is the most prevalent metabolic disorder in reproductive-age women. It is indeed a multifactorial condition evidenced by ovarian... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovarian syndrome (PCOS) is the most prevalent metabolic disorder in reproductive-age women. It is indeed a multifactorial condition evidenced by ovarian dysfunction, hyperandrogenaemia, infertility, hormonal imbalance and chronic anovulation. Experimental evidence infers that PCOS women are prone to cardiovascular problems and insulin resistance.
PURPOSE
To furnish the details about the association of inflammatory markers in PCOS.
DESIGN
An extensive literature search on PubMed, science direct and google scholar has been performed for articles about PCOS and inflammation in PCOS. A comprehensive analysis using original articles, reviews, systemic and meta-analysis was conducted for better understanding the relationship between inflammatory cytokines and PCOS.
RESULTS
The inflammatory markers perform a substantial part in managing the functions of the ovary. Any disturbances in their levels can lead to ovarian dysfunction. Inflammatory markers are associated with PCOS pathogenesis. The interplay between inflammatory cytokines in the PCOS ovary strongly implies that inflammation is one of the most potent risk factors of PCOS.
CONCLUSION
Inflammatory markers have a significant role in regulating the ovary. This manuscript highlights the significance of metabolic and inflammatory markers with PCOS. Since PCOS is always considered as a metabolic disorder, researchers can also consider focusing on the relationship between the inflammatory markers in PCOS to establish a new treatment or management of the disease and to improve women's health.
Topics: Anovulation; Biomarkers; Cytokines; Female; Humans; Hyperandrogenism; Infertility; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Metabolic Syndrome; Polycystic Ovary Syndrome; Tumor Necrosis Factor-alpha
PubMed: 33439300
DOI: 10.1007/s00404-020-05951-2 -
The Cochrane Database of Systematic... Dec 2020The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates.
OBJECTIVES
To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020).
SELECTION CRITERIA
Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.
TYPES OF PARTICIPANTS
women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment.
PRIMARY OUTCOME MEASURES
live birth rate, incidence of ovarian hyperstimulation syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach.
MAIN RESULTS
This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision.
AUTHORS' CONCLUSIONS
This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.
Topics: Abortion, Spontaneous; Bias; Confidence Intervals; Female; Fertilization in Vitro; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Live Birth; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Placebos; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33347618
DOI: 10.1002/14651858.CD006105.pub4 -
Revista Da Associacao Medica Brasileira... Dec 2020There is no pooled information about pelvic floor parameters (muscle assessment, disorders) of women with gynecologicaL endocrinopathies (eg. polycystic ovary syndrome,...
There is no pooled information about pelvic floor parameters (muscle assessment, disorders) of women with gynecologicaL endocrinopathies (eg. polycystic ovary syndrome, congenital adrenal hyperplasia, premature ovarian insufficiency). Given that, a systematic review was performed on the Pubmed, Scopus, Google Scholar, Scielo and PEDro databases regarding the main gynecological endocrinopathies [polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPL)] since their inception to April 2020. Data quality assessment was made by the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies. A total of 4,272 results were retrieved from all databases. After excluding duplicate results and screening by title and abstract, nine studies were selected for quantitative analysis. Seven studies were performed with women with PCOS and two studies with POI. Women with PCOS presented a higher prevalence of urinary incontinence (UI) among obese women, a higher thickness of the levator ani muscle, and higher levels of muscle activity measured by surface electromyograph when compared to the control women. Regarding POI, there was no association with UI, FI, and POP. NOS found that the quality assessment for these selected studies ranged from 5 to 8. We concluded that higher pelvic muscle activity and volume were found in women with PCOS, with further studies needed to confirm this data. Literature was scant about POI, CAH, and HPL.
Topics: Cross-Sectional Studies; Female; Humans; Pelvic Floor; Polycystic Ovary Syndrome; Prevalence; Urinary Incontinence
PubMed: 33331587
DOI: 10.1590/1806-9282.66.12.1742 -
Journal of Pediatric Urology Feb 2021Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment team as some of these children develop gender identity disorder (GID) when they become adults. In this systematic review and meta-analysis we have analyzed the prevalence of GID in adolescent and adults with DSD. The secondary outcome of this review is to help physicians in appropriate sex assignment of DSD children so that development of GID in later life can be reduced.
METHODS
Pubmed/Index medicus were searched for "intersex" [All fields] OR "disorders of sexual differentiation AND "gender identity disorder OR gender dysphoria" [MeSH] for articles published between 2005 and 2020. Typical diagnoses included were congenital adrenal hyperplasia (CAH); complete androgen insensitivity syndrome (CAIS); partial androgen insensitivity syndrome (PAIS); 5 alpha reductase deficiency (5ARD); 17-hydroxysteroid dehydrogenase deficiency (17HSD); mixed gonadal dysgenesis (MGD) and complete gonadal dysgenesis (CGD). GID or gender dysphoria (a strong feeling of dissatisfaction about oneself as male or female) prevalence in DSD patients older than 12 years of age was extracted. Within each condition, GID percentage was compared between female and male rearing.
RESULTS
The I2statistics for prevalence of GID in DSD showed high heterogeneity with I2 of 93% (95% C.I 90-95%) among the 20 articles included. The overall prevalence of GID among those with DSD was 15% (95% C.I 13-17%). CAH reared females had 4% GID while CAH reared males had significantly higher GID at 15% (p = 0.0056). All CAIS patients were raised as females and the prevalence of GID was 1.7%. GID prevalence was 12% in PAIS raised as females while 25% in those raised as males with no significant difference (p = 0.134). GID was significantly high in 5ARD (53%) and 17HSD (53%) reared as females with half of them virilizing at puberty forcing a gender change. Among sex chromosome DSD 22% of those reared as females had GID while none in those raised as male with no significant difference.
CONCLUSIONS
GID is low in women with CAH, CAIS and CGD favoring female sex of rearing in these conditions. GID is high in women with 5ARD/17HSD favoring male sex of rearing in these conditions. GID is variable in PAIS or MGD and no recommendations on sex of rearing could be made in these conditions. Each DSD patient is unique and they warrant multi-disciplinary care and long term psycho sexual support.
Topics: Adolescent; Adult; Child; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female; Gender Dysphoria; Gender Identity; Humans; Male; Sexual Development; Steroid Metabolism, Inborn Errors
PubMed: 33246831
DOI: 10.1016/j.jpurol.2020.11.017 -
Hormones and Behavior Nov 2020The ratio of length between the second and fourth fingers (2D:4D) is commonly used as an indicator of prenatal sex hormone exposure. Several approaches have been used to... (Meta-Analysis)
Meta-Analysis
The ratio of length between the second and fourth fingers (2D:4D) is commonly used as an indicator of prenatal sex hormone exposure. Several approaches have been used to try to validate the measure, including examining 2D:4D in people with congenital adrenal hyperplasia (CAH), a suite of conditions characterised by elevated adrenal androgen production secondary to defective steroidogenesis. We present a systematic review and meta-analysis that examines the relationship between these two variables. Twelve articles relating to nine CAH cohorts were identified, and 2D:4D comparisons have been made between cases and controls in eight of these cohorts. Altogether, at least one 2D:4D variable has been compared between n = 251 females with CAH and n = 358 unaffected females, and between n = 108 males with CAH and n = 204 unaffected males. A previous meta-analysis (Hönekopp and Watson, 2010) reported lower right hand (R2D:4D) and left hand (L2D:4D) digit ratios in patients with CAH relative to sex-matched controls. Our meta-analysis showed the same pattern, with medium effect sizes for R2D:4D and small effect sizes for L2D:4D. Differences of small magnitude were also observed for M2D:4D, and no significant effects were observed for D. Notably, the only effects that remained statistically significant when stratified by sex were R2D:4D in males and L2D:4D in females, and the average effect size had reduced by 46.70% since the meta-analysis of Hönekopp and Watson (2010). We also found that individual comparisons in this literature were considerably underpowered, and that patterns of sexual dimorphism in 2D:4D were similar in CAH samples as in typically developing populations. Findings are discussed in relation to the prenatal androgen hypothesis as well as alternative explanations.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adult; Androgens; Body Weights and Measures; Case-Control Studies; Child; Child, Preschool; Female; Fingers; Gonadal Steroid Hormones; Humans; Male; Pregnancy; Prenatal Exposure Delayed Effects; Sex Characteristics; Young Adult
PubMed: 32998030
DOI: 10.1016/j.yhbeh.2020.104867 -
Frontiers in Endocrinology 2020Decreased bone mineral density (BMD) is a concern in patients with congenital adrenal hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date... (Meta-Analysis)
Meta-Analysis
Decreased bone mineral density (BMD) is a concern in patients with congenital adrenal hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date have yielded conflicting results. We wanted to systematically evaluate the available evidence regarding BMD in adult patients with CAH. We searched Medline, Embase and Cochrane Central Register of Controlled Trials to identify eligible studies. Studies comparing BMD in CAH patients with age- and sex-matched controls were included. Age <16 years and absence of controls were exclusion criteria. Two authors independently reviewed abstracts, read full-text articles, extracted data, assessed risk of bias using Newcastle-Ottawa scale, and determined level of evidence using Grading of Recommendations Assessment, Development, and Evaluation methodology. Nine case-control studies with a total sample of 598 (cases = 254, controls = 344) met eligibility criteria. Median age was 31 years (IQR 23.9-37) and 65.7% were female. Total body BMD (Mean Difference [MD]-0.06; 95%CI -0.07, -0.04), lumbar spine BMD (MD -0.05; 95%CI -0.07, -0.03) and femoral neck BMD (MD -0.07; 95%CI -0.10, -0.05) was lower in cases compared to controls. Lumbar spine -scores (MD -0.86; 95%CI -1.16, -0.56) and -scores (MD -0.66; 95%CI -0.99, -0.32) and femoral neck -scores (MD -0.75 95%CI -0.95, -0.56) and -scores (MD -0.27 95%CI -0.58, 0.04) were lower in cases. BMD in adult patients with CAH was lower compared to controls. Although insufficient data precludes a dose-response relationship between glucocorticoid dose and BMD, it would be prudent to avoid overtreatment with glucocorticoids.
Topics: Adrenal Hyperplasia, Congenital; Bone Density; Bone and Bones; Case-Control Studies; Humans
PubMed: 32903805
DOI: 10.3389/fendo.2020.00493 -
Molecular Metabolism May 2020Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism,...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in the etiology of this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods is proposed as a major driver of the metabolic and reproductive perturbations associated with PCOS. However, the current understanding of the pathophysiology of PCOS-associated metabolic disease is incomplete, and therapeutic strategies used to manage this syndrome's metabolic complications remain limited.
SCOPE OF REVIEW
This study is a systematic review of the potential etiopathogenic mechanisms of metabolic dysfunction frequently associated with PCOS, with special emphasis on the metabolic impact of androgen excess on different metabolic tissues and the brain. We also briefly summarize the therapeutic approaches currently available to manage metabolic perturbations linked to PCOS, highlighting current weaknesses and future directions.
MAJOR CONCLUSIONS
Androgen excess plays a prominent role in the development of metabolic disturbances associated with PCOS, with a discernible impact on key peripheral metabolic tissues, including the adipose, liver, pancreas, and muscle, and very prominently the brain, contributing to the constellation of metabolic complications of PCOS, from obesity to insulin resistance. However, the current understanding of the pathogenic roles of hyperandrogenism in metabolic dysfunction of PCOS and the underlying mechanisms remain largely incomplete. In addition, the development of more efficient, even personalized therapeutic strategies for the metabolic management of PCOS patients persists as an unmet need that will certainly benefit from a better comprehension of the molecular basis of this heterogeneous syndrome.
Topics: Adipose Tissue; Androgens; Animals; Bariatric Surgery; Female; Humans; Hyperandrogenism; Insulin Resistance; Metabolic Syndrome; Mice; Obesity; Polycystic Ovary Syndrome
PubMed: 32244180
DOI: 10.1016/j.molmet.2020.01.001 -
Frontiers in Behavioral Neuroscience 2020Congenital adrenal hyperplasia (CAH) is a genetic condition of the steroidogenic enzymes in the adrenal cortex normally leading to variable degrees of cortisol and...
Congenital adrenal hyperplasia (CAH) is a genetic condition of the steroidogenic enzymes in the adrenal cortex normally leading to variable degrees of cortisol and aldosterone deficiency as well as androgen excess. Exposure to androgens prenatally might lead to ambiguous genitalia. The fetal brain develops in traditional male direction through a direct action of androgens on the developing nerve cells, or in the traditional female direction in the absence of androgens. This may indicate that sexual development, including sexual orientation, are programmed into our brain structures prenatally. The objective of this study was to perform a systematic review of the literature, investigating sexual orientation in individuals with CAH. The study also aimed at identifying which measures are used to define sexual orientation across studies. The review is based on articles identified through a comprehensive search of the OVIDMedline, PsycINFO, CINAHL, and Web of Science databases published up to May 2019. All peer-reviewed articles investigating sexual orientation in people with CAH were included. Quantitative, qualitative, and mixed methods were considered, as well as self-, parent-, and third-party reports, and no age or language restrictions were enforced on publications. The present review included 30 studies investigating sexual orientation in patients with CAH assigned female at birth (46, XX) ( = 927) or assigned male at birth (46, XY and 46, XX) ( = 274). Results indicate that assigned females at birth (46, XX) with CAH had a greater likelihood to not have an exclusively heterosexual orientation than females from the general population, whereas no assigned males at birth (46, XY or 46, XX) with CAH identified themselves as non-heterosexual. There was a wide diversity in measures used and a preference for unvalidated and self-constructed interviews. Hence, the results need to be interpreted with caution. Methodological weaknesses might have led to non-heterosexual orientation being overestimated or underestimated. The methodological challenges identified by this review should be further investigated in future studies.
PubMed: 32231525
DOI: 10.3389/fnbeh.2020.00038