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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 Pediatric Urology Dec 2016Disorders of sex development (DSD) are a heterogeneous group of complex conditions that can affect chromosomal, gonadal, and/or phenotypical sex. In addition to impacts... (Review)
Review
INTRODUCTION
Disorders of sex development (DSD) are a heterogeneous group of complex conditions that can affect chromosomal, gonadal, and/or phenotypical sex. In addition to impacts on internal and external genitalia,these conditions can affect fertility potentialto various degrees. In this review we discuss fertility issues including gonadalpreservation and reproductive outcomes based on specific DSD conditions.
METHODS AND MATERIALS
A systematic literature review was performed on Embase, PubMed, and Google Scholar for disordersof sex development and infertility. Original research articles and relevant reviews were examinedand a synopsis of these data was generated for a comprehensive review of fertility potential in disorders of sex development.
RESULTS
While patients with some DSDs may have functioning gonads with viable germ cells but an inability to achieve natural fertility secondary to incongruent internal or external genitalia, other patients may have phenotypically normal genitalia but infertility due to abnormal gonad development. Fertility rates in females with congenital adrenal hyperplasia (CAH) depend on phenotype and are inversely proportionalto the severity of the disease. Men with classic CAH have reduced fertility and due to the presence of testicular adrenal rest tumors and to suppression of the hypothalamic-pituitary-gonadal axis by high systemic levels of androgens. Infertility is seen in complete androgen insensitivity and subfertility is common in partial cases. Fertility is rare in pure or mixed gonadal dysgenesis, ovotesticular disorder, Klinefelter syndrome, and XX males.
CONCLUSION
Fertility potential appears to be the highest in patientswith XX or XY CAH, especially non-classic forms. Advancements in assisted reproduction techniques has in rare cases produced offspring in some diagnoses thought to be universally infertile. Discussion of fertility issues with the patient and family is essential to the optimal treatment of each patient and an important part of the multi-disciplinary approach to evaluating and counseling these families.
Topics: Disorders of Sex Development; Female; Humans; Infertility; Male
PubMed: 27856173
DOI: 10.1016/j.jpurol.2016.09.015 -
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 -
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 -
BMC Public Health May 2023Polycystic ovary syndrome (PCOS) is among the predominant endocrine disorders of reproductive-aged women. The prevalence of PCOS has been estimated at approximately...
BACKGROUND
Polycystic ovary syndrome (PCOS) is among the predominant endocrine disorders of reproductive-aged women. The prevalence of PCOS has been estimated at approximately 6-26%, affecting 105 million people worldwide. This systematic review aimed to synthesize the evidence on the effects of physical activity on reproductive health functions among PCOS women.
METHODS
The systematic review includes randomization-controlled trials (RCTs) on physical exercise and reproductive functions among women with PCOS. Studies in the English language published between January 2010 and December 2022 were identified via PubMed. A combination of medical subject headings in terms of physical activity, exercise, menstrual cycle, hyperandrogenism, reproductive hormone, hirsutism, and PCOS was used.
RESULTS
Overall, seven RCTs were included in this systematic review. The studies investigated interventions of physical activity of any intensity and volume and measured reproductive functions and hormonal and menstrual improvement. The inclusion of physical activity alone or in combination with other therapeutic interventions improved reproductive outcomes.
CONCLUSION
The reproductive functions of women with PCOS can be improved with physical activity. Furthermore, physical activity can also reduce infertility, as well as social and psychological stress among women.
PROSPERO SYSTEMATIC REVIEW REGISTRATION
CRD42020213732.
Topics: Female; Humans; Adult; Polycystic Ovary Syndrome; Reproductive Health; Hyperandrogenism; Exercise; Menstrual Cycle
PubMed: 37173672
DOI: 10.1186/s12889-023-15730-8 -
Gynecologic and Obstetric Investigation 2024Polycystic ovary syndrome (PCOS) is a common hormonal disorder among young women, correlated with hyperandrogenism. Among the symptoms of PCOS, vocal alterations are... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Polycystic ovary syndrome (PCOS) is a common hormonal disorder among young women, correlated with hyperandrogenism. Among the symptoms of PCOS, vocal alterations are quite unknown. Dysphonia may be related to hyperandrogenism, and there is no consensus about its prevalence and the severity of vocal disorders, which can cause noticeable discomfort.
METHODS
A systematic review of the literature was conducted. Four studies on PCOS that evaluated the phonatory system were included for a total of 174 patients (96 PCOS, 78 controls), and a meta-analysis on comparable data was performed.
RESULTS
Four studies evaluated parameters related to vocal symptomatology, altered audiometric examination, and findings at the laryngoscopy in patients affected by PCOS versus controls. Although the individual studies showed increased incidence of alterations and a tendency to develop speech fatigue in women with PCOS, when the results of studies were pulled in meta-analysis, the overall difference was not statistically significant. The studies themselves were very different from each other; therefore, it is hard to draw any firm conclusions.
DISCUSSION
The aim of this study was to assess the prevalence of vocal alterations, the correlation with hyperandrogenism, the quality of life, and the voice changes after starting a therapy for PCOS. The present meta-analysis failed to find any difference in terms of PCOS and control cohort. However, the lack of high-quality studies makes it difficult to draw firm conclusions. New and larger studies or big population program data are therefore warranted.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Quality of Life
PubMed: 38194939
DOI: 10.1159/000535819 -
Obesity Reviews : An Official Journal... Aug 2021Women with polycystic ovary syndrome (PCOS) exhibit reduced muscle insulin-mediated glucose uptake, potentially attributed to altered muscle mass; however, this is... (Meta-Analysis)
Meta-Analysis Review
Obesity, but not hyperandrogenism or insulin resistance, predicts skeletal muscle mass in reproductive-aged women with polycystic ovary syndrome: A systematic review and meta-analysis of 45 observational studies.
Women with polycystic ovary syndrome (PCOS) exhibit reduced muscle insulin-mediated glucose uptake, potentially attributed to altered muscle mass; however, this is inconclusive. Altered muscle mass may aggravate PCOS complications. Our systematic review and meta-analysis evaluated whether PCOS alters muscle mass and function. Databases (MEDLINE, Web of Science, Scopus) were searched through September 2, 2020, for studies documenting skeletal muscle mass (lean tissue mass) and function (strength) in PCOS and control groups. The primary outcome was total lean body mass (LBM) or fat-free mass (FFM). Data were pooled by random-effects models and expressed as mean differences and 95% confidence intervals. Forty-five studies (n = 3676 participants) were eligible. Women with PCOS had increased total (0.83 [0.08,1.58] kg; p = 0.03; I = 72.0%) yet comparable trunk (0.84 [-0.37,2.05] kg; p = 0.15; I = 73.0%) LBM or FFM versus controls. Results of meta-regression analyses showed no associations between mean differences between groups in total testosterone or homeostatic model assessment of insulin resistance and total or trunk LBM or FFM (All: p ≥ 0.75). Mean differences in body mass index (BMI) were associated with total (0.65 [0.23,1.06] kg; p < 0.01; I = 56.9%) and trunk (0.56 [0.11,1.01] kg; p = 0.02; I = 42.8%) LBM or FFM. The PCOS subgroup with BMI ≥ 25 kg/m had greater total LBM or FFM versus controls (1.58 [0.82,2.34] kg; p < 0.01; I = 64.0%) unlike the PCOS subgroup with BMI < 25 kg/m (-0.45 [-1.94,1.05] kg; p = 0.53; I = 69.5%). Appendicular lean mass and muscle strength data were contradictory and described narratively, as meta-analyses were impossible. Women with PCOS have higher total and trunk lean tissue mass attributed to overweight/obesity, unlike hyperandrogenism or insulin resistance.
Topics: Adult; Body Mass Index; Female; Humans; Hyperandrogenism; Insulin Resistance; Muscle, Skeletal; Obesity; Polycystic Ovary Syndrome
PubMed: 33855800
DOI: 10.1111/obr.13255 -
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 -
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 -
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