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European Journal of Clinical... Apr 2023To summarize the effects of metformin treatment on markers of hyperandrogenism in patients diagnosed with polycystic ovary syndrome (PCOS). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To summarize the effects of metformin treatment on markers of hyperandrogenism in patients diagnosed with polycystic ovary syndrome (PCOS).
METHODS
A systematic review, with meta-analysis, of randomized placebo-controlled clinical trials that evaluated the effects of metformin treatment in adult patients with PCOS on the levels of hyperandrogenism markers was conducted. The literature search, data extraction, risk of bias, and the assessment of certainty of evidence were performed independently by two reviewers using a structured form. The results were combined by applying the random effect, and the effect measure presented as a standardized mean difference (SMD). Significant values were considered as p < 0.05 with 95% CI. Furthermore, sensitivity analyses were performed in order to explore possible heterogeneity between studies.
RESULTS
Were included 18 studies in the quantitative evaluation and 17 studies (23 reports) in the quantitative evaluation. A significant reduction in total testosterone levels was seen in the metformin-treated group when compared to the control group after combining the results by the sensitivity analysis [SMD: - 0.46 (95% CI: - 0.89 to - 0.02)]. Therefore, FAI values were also regulated by metformin treatment.
CONCLUSION
We showed that metformin proved to be effective in reducing total testosterone levels, and the same was observed for free androgen index (FAI) values-a measure influenced by testosterone levels. The protocol of this study was registered at Prospero (CRD42021235761).
Topics: Humans; Female; Polycystic Ovary Syndrome; Metformin; Hyperandrogenism; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Testosterone
PubMed: 36763111
DOI: 10.1007/s00228-023-03461-z -
Frontiers in Endocrinology 2022Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to genitalia abnormalities, anovulation, unreceptive endometrium and metabolic disturbances. Despite those challenges, many live births have been reported. In this systematic review, we focused on the key to successful assisted reproduction strategies and the potential pregnancy complications. We did a systematic literature search of Pubmed, Medline and Scopus for articles reporting successful pregnancies in CAH other than 21-hydroxylase deficiency, and found 25 studies reporting 39 pregnancies covering deficiency in steroidogenic acute regulatory protein, 17α-hydroxylase/17,20-lyase, 11β-hydroxylase, P450 oxidoreductase, cytochrome b5 and 3β-hydroxysteroid dehydrogenase. We summarized various clinical manifestations and tailored reproduction strategy for each subtype. Furthermore, a meta-analysis was performed to evaluate the pregnancy complications of CAH patients. A total of 19 cross-sectional or cohort studies involving 1311 pregnancies of classic and non-classic CAH patients were included. Surprisingly, as high as 5.5% (95% CI 2.3%-9.7%) of pregnancies were electively aborted, and the risk was significantly higher in those studies with a larger proportion of classic CAH than those with only non-classical patients (8.43% (4.1%-13.81%) VS 3.75%(1.2%-7.49%)), which called for better family planning. Pooled incidence of miscarriage was 18.2% (13.4%-23.4%) with a relative risk (RR) of 1.86 (1.27-2.72) compared to control. Glucocorticoid treatment in non-classical CAH patients significantly lowered the miscarriage rate when compared to the untreated group (RR 0.25 (0.13-0.47)). CAH patients were also more susceptible to gestational diabetes mellitus, with a prevalence of 7.3% (2.4%-14.1%) and a RR 2.57 (1.29-5.12). However, risks of preeclampsia, preterm birth and small for gestational age were not significantly different. 67.8% (50.8%-86.9%) CAH patients underwent Cesarean delivery, 3.86 (1.66-8.97) times the risk of the control group. These results showed that fertility is possible for CAH patients but special care was necessary when planning, seeking and during pregnancy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=342642, CRD42022342642.
Topics: Abortion, Spontaneous; Adrenal Hyperplasia, Congenital; Cross-Sectional Studies; Cytochromes b5; Female; Glucocorticoids; Humans; Hydroxysteroid Dehydrogenases; Infant, Newborn; Pregnancy; Pregnancy Complications; Premature Birth; Reproduction; Steroid 17-alpha-Hydroxylase
PubMed: 36120452
DOI: 10.3389/fendo.2022.982953 -
Hormone Research in Paediatrics 2023Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of cortisol, aldosterone, or both. The most common type is the 21-hydroxylase enzyme deficiency in approximately 95% of cases resulting from CYP21A2 gene mutations or deletions.
OBJECTIVES
This study aimed to systematically review the national differences in CAH incidence and analyze the pooled results to determine disparities and whether ethnicity can predispose people to develop CAH.
METHODS
PubMed, Scopus, and LILACS were used to achieve results until June 22, 2018. Study eligibility criteria included availability of full-text; English, Spanish, or Portuguese languages; incidence or number of new cases; and number of live births or sample population. Only the classic CAH type (salt-wasting and simple-virilizing) was considered, and no distinction was made between the enzyme deficiency types.
RESULTS
This study summarizes the findings of 58 studies and 31 countries (from 1969 to 2017), in which the overall CAH incidence was 1:9,498 (95% confidence interval: 1:9,089, 1:9,945). Countries from the Eastern Mediterranean and Southeast Asia revealed the highest CAH incidence. The lowest incidence was reported in countries of the Western Pacific of Asia. No remarkable difference was observed in the Hispanics/Latino and White groups. However, they manifested a higher incidence of CAH than people identified as Black or of African descent. Published studies on CAH incidence in the sub-Saharan African region and parts of Europe were insufficient.
CONCLUSIONS
This study highlights the at-risk population for CAH and regions that need monitoring for CAH. The highest CAH incidence could be attributed to higher consanguinity, less genetic diversity, or other genetic causes since CAH is an inherited genetic disorder. Cultural practices in some places regarding consanguineous unions or geographic isolation may directly affect the incidence. Newborn screening for CAH may be unavailable in many developing countries, thereby affecting the actual CAH incidence. Therefore, healthcare workers should be trained to recognize CAH at an early stage to reduce its complications and mortality.
Topics: Infant, Newborn; Humans; Adrenal Hyperplasia, Congenital; Neonatal Screening; Adrenal Cortex; Mutation; Steroid 21-Hydroxylase
PubMed: 35973409
DOI: 10.1159/000526401 -
Journal of Endocrinological... Jan 2023P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also... (Review)
Review
BACKGROUND
P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown.
AIM
To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature.
METHODS
The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated.
RESULTS
Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants.
CONCLUSION
This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.
Topics: Humans; Pregnancy; Male; Female; Adrenal Hyperplasia, Congenital; Infertility, Male; Mutation; Phenotype; Heterozygote
PubMed: 35842891
DOI: 10.1007/s40618-022-01849-9 -
Journal of Child Neurology Aug 2022Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that affects the adrenal glands and is the most common cause of primary adrenal insufficiency in...
BACKGROUND
Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that affects the adrenal glands and is the most common cause of primary adrenal insufficiency in children. In the past few decades, magnetic resonance imaging (MRI) has been implemented to investigate how the brain may be affected by CAH. A systematic review was conducted to evaluate and synthesize the reported evidence of brain findings related to CAH using structural, functional, and diffusion-weighted MRI.
METHODS
We searched bibliographical databases through July 2021 for brain MRI studies in individuals with CAH.
RESULTS
Twenty-eight studies were identified, including 13 case reports or series, 10 studies that recruited and studied CAH patients vs unaffected controls, and 5 studies without a matched control group. Eleven studies used structural MRI to identify structural abnormalities or quantify brain volumes, whereas 3 studies implemented functional MRI to investigate brain activity, and 3 reported diffusion MRI findings to assess white matter microstructure. Some commonly reported findings across studies included cortical atrophy and differences in gray matter volumes, as well as white matter hyperintensities, altered white matter microstructure, and distinct patterns of emotion and reward-related brain activity.
CONCLUSIONS
These findings suggest differences in brain structure and function in patients with CAH. Limitations of these studies highlight the need for CAH neuroimaging studies to incorporate larger sample sizes and follow best study design and MRI analytic practices, as well as clarify potential neurologic effects seen across the lifespan and in relation to clinical and behavioral CAH phenotypes.
Topics: Adrenal Hyperplasia, Congenital; Brain; Diffusion Magnetic Resonance Imaging; Emotions; Humans; Magnetic Resonance Imaging
PubMed: 35746874
DOI: 10.1177/08830738221100886 -
Gynecological Endocrinology : the... Aug 2022This study proposes a review of nutraceuticals used in the treatment of typical symptoms of Polycystic Ovary Syndrome (PCOS).The aim is to provide a classification of...
This study proposes a review of nutraceuticals used in the treatment of typical symptoms of Polycystic Ovary Syndrome (PCOS).The aim is to provide a classification of the most widely used nutraceutical supplements identifying the most effective nutraceuticals on glucose and insulin metabolism, the androgenic hormone profile, fertility, ovulatory capacity, inflammation, and oxidative stress.We included randomized controlled trials on PCOS patients undergoing administration of nutraceuticals, in particular vitamin D, vitamin E, probiotics, and inositols. These administrations are variable in terms of dosage, single supplementation, or combined with other compounds, dosage, and duration of the intervention.The supplementation of inositols, at the physiologic ratio of 40: 1 of myo- and D-chiro-inositols, resulted to be the most effective in improving the glucose homeostasis and fertility, with a restoration of ovulatory capacity and menstrual regularity. Other nutraceuticals are particularly effective in reducing hyperandrogenism, with promising results demonstrated by the combinations of vitamin D and probiotics, vitamin E and coenzyme Q10, and the enrichment of inositol therapy with group B vitamins. An improvement in the inflammatory status and antioxidant capacity is obtained with the co-supplementation of probiotics and selenium or with vitamin E combined with omega 3.Inositol supplementation is effective in the treatment of insulin resistance and fertility. Probiotics reduced hyperandrogenism, inflammatory and oxidative conditions, and resulted more effective when combined with selenium. Although these results proved to be satisfactory, further studies are needed with larger samples and a more homogeneous analysis of the outcomes.
Topics: Dietary Supplements; Female; Glucose; Humans; Hyperandrogenism; Inositol; Polycystic Ovary Syndrome; Selenium; Vitamin D; Vitamin E; Vitamins
PubMed: 35713558
DOI: 10.1080/09513590.2022.2089106 -
Endocrine Journal Aug 2022Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes menstrual cycle irregularities and infertility. PCOS is diagnosed based on hyperandrogenism,... (Meta-Analysis)
Meta-Analysis
Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes menstrual cycle irregularities and infertility. PCOS is diagnosed based on hyperandrogenism, polycystic ovarian morphology (PCOM), and an-/oligo-ovulation. Upregulation of anti-Müllerian hormone (AMH) in the serum of women with PCOS may be another suitable alternative diagnostic criterion for PCOM. However, previous meta-analyses have reported conflicting results due to the age-dependent decline in serum AMH levels. Therefore, we performed a meta-analysis to evaluate the threshold of AMH for the diagnosis of PCOS in adolescents and women in their early twenties. Fifteen trials were included in this meta-analysis. PCOS is diagnosed with either Rotterdam criteria, NIH, or AE-PCOS. AMH levels were significantly higher in adolescents with PCOS (weighted mean difference, 3.05; 95% confidence interval: 2.09-4.01) than in the control group. The cutoff values of AMH for the diagnosis of adolescent PCOS were 6.1, 6.26, 7.03, 7.11, 7.2, and 7.25 ng/mL in the studies that reported the usefulness of AMH levels. The summary receiver operating characteristic analysis of the diagnostic accuracy demonstrated that the specificity and sensitivity were 81% and 66.3%, respectively. Our meta-analysis demonstrates that AMH may be a useful diagnostic test for adolescent PCOS and, based on the previous studies included in the meta-analysis, its cutoff value was estimated to be 6-7 ng/mL.
Topics: Adolescent; Anti-Mullerian Hormone; Female; Humans; Hyperandrogenism; Infertility; Peptide Hormones; Polycystic Ovary Syndrome; ROC Curve
PubMed: 35675999
DOI: 10.1507/endocrj.EJ22-0081 -
Archives of Gynecology and Obstetrics May 2023Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. (Meta-Analysis)
Meta-Analysis Review
Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.
CONTEXT
Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess.
AIM
To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS.
DATA SOURCE
We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021.
DATA SYNTHESIS
Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
RESULTS
Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI - 0.49 to - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI - 1.34 to - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD: - 0.47; 95% CI - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD: - 0.37 µg/dL; 95% CI - 0.05 to - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD: - 1.67; 95% CI - 2.27 to - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed.
CONCLUSION
Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects.
PROSPERO REGISTRATION NO
CRD42020178783.
Topics: Female; Humans; Polycystic Ovary Syndrome; Flutamide; Androgens; Rosiglitazone; Hyperandrogenism; Metformin; Testosterone; Dexamethasone; Randomized Controlled Trials as Topic
PubMed: 35434762
DOI: 10.1007/s00404-022-06549-6 -
Frontiers in Endocrinology 202211-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide...
BACKGROUND AND OBJECTIVES
11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of.
DESIGN AND METHODS
We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021.
RESULTS
We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions.
CONCLUSIONS
11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable.
SYSTEMATIC REVIEW REGISTRATION
Open Science Framework, 10.17605/OSF.IO/NR7UV.
Topics: Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adult; Aldosterone; Carcinoma; Desoxycorticosterone; Female; Humans; Hyperplasia; Hypertension; Male; Middle Aged
PubMed: 35432204
DOI: 10.3389/fendo.2022.846865 -
Human Reproduction Update Jun 2022An increased prevalence of functional hyperandrogenism-including polycystic ovary syndrome (PCOS)-has been described in women with type 1 diabetes (T1D). However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An increased prevalence of functional hyperandrogenism-including polycystic ovary syndrome (PCOS)-has been described in women with type 1 diabetes (T1D). However, heterogeneity between studies is frequent, and prevalence rates vary according to different criteria used for the diagnosis of PCOS and the population studied.
OBJECTIVE AND RATIONALE
We aimed to perform a systematic review and meta-analysis of the prevalence of PCOS and related hyperandrogenic traits in premenopausal women with T1D. This way, we intend to increase the precision of the estimates of prevalence of PCOS and related traits in women with T1D, and to explore sources of heterogeneity while providing prevalence estimates for clinically relevant subgroups such as the different phenotypes.
SEARCH METHODS
We conducted a systematic review of the literature using Medline-OVID and Embase databases (Open Science Framework registry for systematic review protocols, https://osf.io/6cv9p/). Studies published up to 29 March 2021 were considered. We selected cross-sectional or prospective studies that reported, in patients with T1D, prevalence data on PCOS according to current definitions and different phenotypes, and/or prevalence rates of other related traits (hirsutism, hyperandrogenaemia, oligo-amenorrhoea and/or polycystic ovarian morphology: PCOM). Exclusion criteria for the review were studies addressing types of diabetes other than T1D; and studies using diagnostic definitions of PCOS different than those mentioned above. Two independent researchers performed data extraction. To assess the risk of bias, we used a tool developed specifically to appraise population-based prevalence studies.
OUTCOMES
We selected 19 studies (1042 women) reporting the prevalence of PCOS and/or other hyperandrogenic traits. Regarding bias, 12 studies were considered of low-risk, and the remaining seven studies were considered intermediate risk. The pooled prevalence of PCOS when considering all possible phenotypes (ESHRE- American Society for Reproductive Medicine criteria) in T1D was 26% (95% CI: 19-34%; 13 studies, 684 women). Pooled prevalence of classic PCOS (US National Institutes of Health criteria) was 16% (95% CI: 10-22%; 9 studies, 614 women). Pooled prevalence of hyperandrogenic PCOS (Androgen Excess and PCOS Society criteria) was 26% (95% CI: 16-41%; 5 studies, 329 women). Hirsutism (24%), hyperandrogenaemia (29%), oligomenorrhoea (24%) and PCOM (34%) were also prevalent. Heterogeneity was high in almost all these meta-analyses.
WIDER IMPLICATIONS
This systematic review and meta-analysis showed that PCOS and related hyperandrogenic traits are present in approximately one in every four women with T1D. Larger studies are needed to confirm this association, to address the effect of different variables on the occurrence of PCOS.
Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Hirsutism; Humans; Hyperandrogenism; Phenotype; Polycystic Ovary Syndrome; Prevalence; Prospective Studies
PubMed: 35237802
DOI: 10.1093/humupd/dmac011