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Human Reproduction Update Sep 2019Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of fractures, bone mineral density (BMD) or bone markers led to uncertainty whether PCOS might improve or deteriorate bone health.
OBJECTIVE AND RATIONALE
This study aimed to investigate the impact of PCOS on bone markers, BMD and fracture risk.
SEARCH METHODS
A systematic review and a meta-analysis were carried out. PubMed, EMBASE and Cochrane databases were searched for eligible studies from 1st of January of 1990 to 9th of October of 2018. Eligible studies enrolled women older than 18 years with PCOS, which should be diagnosed according to the Rotterdam Consensus, the Androgen Excess Society, the National Institutes of Health Consensus or the International Classification of Diseases. The studies were grouped according to patient mean BMI: <27 kg/m2 or ≥27 kg/m2. The results were polled as mean difference (MD), standardized MD (SMD) and hazard ratio (HR).
OUTCOMES
Overall, 921 studies were retrieved, and 31 duplicated studies were removed. After screening the titles and abstracts, 80 studies were eligible for full text reading. Of those, 23 studies remained for qualitative synthesis. With the exception of one study, all studies were considered high quality based on the Newcastle-Ottawa scale (NOS; score ≥6). Meta-analysis was performed in 21 studies, with a total of 31 383 women with PCOS and 102 797 controls. Women with PCOS with BMI <27 kg/m2 had lower BMD of the total femur (MD, -0.04; 95% CI, -0.07 to 0.00; I2 = 31%; P = 0.22) and spine (MD, -0.07; 95% CI, -0.13 to -0.01; I2 = 70%; P < 0.01) when compared with the control group, whereas for women with BMI ≥27 kg/m2 no difference was observed (femur: MD, 0.02; 95% CI, -0.02 to 0.05; I2 = 20%, P = 0.29; spine: MD, 0.02; 95% CI, -0.06 to 0.05; I2 = 0%; P = 0.84). Osteocalcin was remarkably reduced in women with PCOS with BMI <27 kg/m2 (SMD, -2.68; 95% CI, -4.70 to -0.67; I2 = 98%; P < 0.01), but in women with BMI ≥27 kg/m2, there were no differences between PCOS and controls. Few studies (n = 3) addressed the incidence of bone fractures in women with PCOS. The HR for total bone fractures did not identify differences between women with PCOS and controls.
WIDER IMPLICATIONS
On the basis of the available evidence, it is possible to assume that PCOS in women with BMI <27 kg/m2 is associated with reduced BMD in the spine and femur, and decreased bone formation, as manifested by lower levels of circulating osteocalcin. These findings suggest that bone parameters in PCOS may be linked, to some extent, to adiposity. These studies included premenopausal women, who have already achieved peak bone mass. Hence, further prospective studies are necessary to clarify the existence of increased risk of fractures in women with PCOS.
Topics: Bone Density; Female; Femur; Fractures, Bone; Humans; Incidence; Obesity; Osteocalcin; Osteogenesis; Osteoporosis; Polycystic Ovary Syndrome; Prospective Studies; Spine
PubMed: 31374576
DOI: 10.1093/humupd/dmz020 -
The Cochrane Database of Systematic... Mar 2019Polycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions.
OBJECTIVES
To assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD).
MAIN RESULTS
We included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m) (-0.34 kg/m, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I = 0%, low-quality evidence).
AUTHORS' CONCLUSIONS
Lifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.
Topics: Abdominal Fat; Exercise; Female; Humans; Insulin Resistance; Life Style; Obesity; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Virilism; Waist Circumference; Weight Loss
PubMed: 30921477
DOI: 10.1002/14651858.CD007506.pub4 -
The Journal of Clinical Endocrinology... Jul 2019To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss (FPHL), a common form of hair loss in women that is characterized by the reduction of hair density in the central area of the scalp, whereas the frontal hairline is generally well conserved.
PARTICIPANTS
An expert task force appointed by the Androgen Excess and PCOS Society, which included specialists from dermatology, endocrinology, and reproductive endocrinology.
DESIGN
Levels of evidence were assessed and graded from A to D. Peer-reviewed studies evaluating FPHL published through December 2017 were reviewed. Criteria for inclusion/exclusion of the published papers were agreed on by at least two reviewers in each area and arbitrated by a third when necessary.
CONCLUSIONS
(i) The term "female pattern hair loss" should be used, avoiding the previous terms of alopecia or androgenetic alopecia. (ii) The two typical patterns of hair loss in FPHL are centrifugal expansion in the mid scalp, and a frontal accentuation or Christmas tree pattern. (iii) Isolated FPHL should not be considered a sign of hyperandrogenism when androgen levels are normal. (iv) The assessment of patients with FPHL is primarily clinical. (v) In all patients with FPHL, assessment of a possible androgen excess is mandatory. Measurement of vitamin D, iron, zinc, thyroid hormones, and prolactin are optional but recommended. (vi) Treatment of FPHL should start with minoxidil (5%), adding 5α-reductase inhibitors or antiandrogens when there is severe hair loss or hyperandrogenism.
Topics: 5-alpha Reductase Inhibitors; Alopecia; Androgen Antagonists; Female; Humans; Hyperandrogenism; Low-Level Light Therapy; Mineralocorticoid Receptor Antagonists; Minoxidil; Platelet-Rich Plasma; Polycystic Ovary Syndrome; Scalp; Spironolactone; Vasodilator Agents
PubMed: 30785992
DOI: 10.1210/jc.2018-02548 -
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 -
Human Reproduction Update Nov 2018Polycystic ovary syndrome (PCOS) prevalence estimates vary when different diagnostic criteria are applied. Lack of standardization of individual elements within these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) prevalence estimates vary when different diagnostic criteria are applied. Lack of standardization of individual elements within these criteria may contribute to prevalence differences.
OBJECTIVE AND RATIONALE
A systematic review of studies reporting prevalence of PCOS, using at least one of the National Institutes of Health (NIH), Rotterdam or Androgen Excess Society (AE-PCOS) criteria, was conducted. The aim was to investigate the impact on prevalence reporting of different definitions of the clinical elements for PCOS diagnosis.
SEARCH METHODS
A systematic search of Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Emcare and BIOSIS was conducted. The search was limited to English language and studies published between January 1990 and January 2018. Included articles needed to define PCOS by at least one of the NIH, Rotterdam or AE-PCOS criteria, be of an unselected population and be published as a full text article. Risk-of-bias was assessed.
OUTCOMES
A total of 21 studies met the inclusion criteria. The random-effects pooled prevalence of PCOS in studies that used the NIH criteria (7% [95% CI: 6-7%]), was significantly different from that identified in studies that used the Rotterdam criteria (12% [95% CI: 10-15%], P < 0.0001) but not studies that used the AE-PCOS criteria (10% [95% CI: 6-13%], P = 0.075). The pooled estimates for Rotterdam and AE-PCOS were not significantly different from each other (P = 0.201). Pooled prevalence estimates were compared between studies separated on the basis of: oligo-amenorrhoea vs oligo-amenorrhoea plus short cycles, clinical androgen excess requiring hirsutism vs any clinical androgen excess, use of different versions and cut-offs for the Ferriman-Gallwey (F-G) score, and inclusion vs non-inclusion of oral contraceptive users. There were no statistically significant differences for any of these comparisons. There was insufficient information to allow subgroup analyses of definitions of polycystic ovaries.
WIDER IMPLICATIONS
Inclusion of ovarian morphology results in statistically significantly higher pooled prevalence estimates for PCOS. Heterogeneity in prevalence estimates for PCOS reflect the broad clinical spectrum of the condition, lack of standardization of the elements within each set of diagnostic criteria and the use of a range of diagnostic cut-offs, as well as potential differences between study populations. The use of different definitions for anovulation and clinical androgen excess did not appear to contribute to differences in the estimated prevalence of PCOS in this study. However, as the number of studies in most of the comparison groups was small, real differences may have been missed. Uncertainty surrounding the diagnosis of PCOS urgently needs to be addressed in order to provide clinicians and their patients with greater diagnostic certainty, and hence reduce inappropriate labelling and the potential psychological harm that may accompany misdiagnosis.
Topics: Amenorrhea; Anovulation; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Prevalence
PubMed: 30059968
DOI: 10.1093/humupd/dmy022 -
Prostate Cancer and Prostatic Diseases Nov 2018Whether androgen deprivation therapy (ADT) causes excess thromboembolic events (TEs) in men with prostate cancer (PCa) remains controversial and is the subject of the US... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whether androgen deprivation therapy (ADT) causes excess thromboembolic events (TEs) in men with prostate cancer (PCa) remains controversial and is the subject of the US Food and Drug Administration safety warning. This study aims to perform a systematic review and meta-analysis on previous studies to determine whether ADT is associated with TEs in men with PCa.
METHODS
Medline, Embase, and Cochrane Library databases were searched for relevant studies. These studies comprised those that compared ADT versus control to treat PCa, reported TEs as outcome, and were published before January 2018. Multivariate adjusted hazard ratios (HRs) and associated 95% confidence intervals (CIs) were calculated using random- or fixed-effects models.
RESULTS
Five retrospective population-based cohort studies involving 170,851 ADT users and 256,704 non-ADT users were identified. Deep venous thrombosis (DVT) was found significantly associated with gonadotropin-releasing hormone (GnRH) agonists alone (HR = 1.47, 95% CI: 1.07-2.03; P = 0.017; I = 96.3%), GnRH agonists plus oral antiandrogen (AA) (HR = 2.55, 95% CI: 2.21-2.94; P < 0.001; I = 0.0%), and AA alone (HR = 1.49, 95% CI: 1.13-1.96; P = 0.004; I = 0.0%), but not with orchiectomy (HR = 1.80, 95% CI: 0.93-3.47; P = 0.079; I = 94.8%). In addition, pulmonary embolism (PE) was significantly associated with GnRH agonists alone (HR = 2.26, 95% CI: 1.78-2.86; P < 0.001; I was unavailable) and orchiectomy (HR = 2.12, 95% CI: 1.44-3.11; P < 0.001; I = 57.2%). This relationship was also supported with subgroup analyses based on different continents and races.
CONCLUSIONS
GnRH agonists alone, GnRH plus AA, and AA alone cause excess DVT in men with PCa after controlling the demographic and disease characteristics and other confounding factors, although statistically significant difference was not observed in orchiectomy group. Additionally, GnRH agonists alone and orchiectomy can increase the incidence of PE.
Topics: Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Humans; Incidence; Male; Orchiectomy; Patient Outcome Assessment; Population Surveillance; Prostatic Neoplasms; Retrospective Studies; Thromboembolism; Venous Thromboembolism
PubMed: 29988099
DOI: 10.1038/s41391-018-0059-4 -
Fertility and Sterility May 2018To formulate clinical consensus recommendations for screening depression, anxiety, health-related quality of life (HRQoL), and disordered eating symptoms in women with...
OBJECTIVE
To formulate clinical consensus recommendations for screening depression, anxiety, health-related quality of life (HRQoL), and disordered eating symptoms in women with polycystic ovary syndrome (PCOS) and review prevalence based on phenotypes and ethnicity, changes over time, etiology, and impact of treatment.
DESIGN
Systematic reviews and preparation of position statement.
SETTING
Not applicable.
PATIENT(S)
Women with PCOS and controls screened using validated tools.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Depressive symptoms, anxiety symptoms, disordered eating, and HRQoL scores.
RESULT(S)
Several studies demonstrate that women with PCOS have an increased prevalence of higher depression and anxiety scores and higher odds of moderate and severe depressive and anxiety symptoms compared with controls. Obesity, hyperandrogenism, and fertility have a weak association with these symptoms. HRQoL scores are consistently reduced in PCOS, with infertility and weight concerns having the most significant impact. Some studies suggest an increased prevalence of disordered eating in women with PCOS compared with controls. The few studies that have evaluated the impact of PCOS-related treatments (lifestyle interventions and pharmacotherapy) show no detrimental effect or some improvement in depressive and anxiety symptoms and HRQoL scores.
CONCLUSION(S)
In women with PCOS, screening for depressive and anxiety symptoms should be offered at the time of diagnosis and screening for disordered eating should be considered. Further research is required across PCOS phenotypes, in longitudinal cohorts and on impact of therapy on depressive and anxiety syptoms, HRQOL, and disordered eating.
Topics: Androgens; Anxiety; Depression; Feeding and Eating Disorders; Female; Humans; Polycystic Ovary Syndrome; Quality of Life; Societies, Medical
PubMed: 29778388
DOI: 10.1016/j.fertnstert.2018.01.038 -
Obesity Reviews : An Official Journal... Apr 2018Metabolic syndrome (MetS) is highly correlated with cardiovascular diseases. Although an excess of body fat is a determinant factor for MetS development, a reduced level...
Metabolic syndrome (MetS) is highly correlated with cardiovascular diseases. Although an excess of body fat is a determinant factor for MetS development, a reduced level of testosterone plays a fundamental role in its regulation. Low testosterone level is highly related to insulin resistance, visceral obesity and MetS. We have searched in Pubmed clinical trial with the password: testosterone and insulin resistance, and testosterone and MetS. We found 19 studies on the correlation between testosterone level with insulin resistance and 18 on the effect of testosterone therapy on MetS. A high correlation between low testosterone and insulin resistance has been found in men, but not in women. Testosterone administration in hypogonadal men improved MetS and reduced the mortality risk. Androgen and oestrogen receptors are expressed in adipocytes, muscle and liver tissue, and their activation is necessary to improve metabolic control. Normalization of testosterone level should be the primary treatment in men, along with caloric restriction and physical exercise. These findings come mainly from correlative data, and there remains a need for randomized trials to strengthen this evidence. This review will consider the effects of testosterone on the regulation and development of MetS in men and women.
Topics: Androgens; Blood Glucose; Humans; Male; Men's Health; Metabolic Syndrome; Obesity; Testosterone
PubMed: 29356299
DOI: 10.1111/obr.12633 -
Human Reproduction Update Mar 2018Androgen excess is a key pathogenetic mechanism in polycystic ovary syndrome (PCOS), although hyperinsulinism also contributes to androgen secretion. Therapeutic...
BACKGROUND
Androgen excess is a key pathogenetic mechanism in polycystic ovary syndrome (PCOS), although hyperinsulinism also contributes to androgen secretion. Therapeutic approaches for adult patients not seeking fertility include combined oral contraceptives (COC), antiandrogens (AA) and/or insulin sensitizers, although these practices are supported by limited high-quality evidence.
OBJECTIVE AND RATIONALE
We aimed to assess the efficacy and safety of these common treatments for PCOS by conducting a meta-analysis of RCTs with the following review questions: Which is the more appropriate therapeutic approach for hyperandrogenic symptoms, hyperandrogenemia, and ovulatory dysfunction in adult women with PCOS not seeking fertility; What is the impact on classic cardiometabolic risk factors of the more common treatments used in those women; Does the combination of the antiandrogenic therapy plus metformin have any impact on efficacy or cardiometabolic profile?
SEARCH METHODS
We searched PubMed and EMBASE for articles published up to 16 September 2017. After deleting duplicates, the abstracts of 1522 articles were analysed. We subsequently excluded 1446 articles leaving 76 studies for full-text assessment of eligibility. Of them, 43 articles were excluded. Hence, 33 studies and 1521 women were included in the quantitative synthesis and in the meta-analyses. Meta-analyses calculated mean differences (MD), standardized mean differences (SMD), odds ratio (OR) and 95% CIs. Heterogeneity and inconsistency across studies was assessed by χ2 test and Higgins's I2 statistics. Quality and risk of bias of individual studies were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. We then used the approach recommended by the Grading of Recommendations, Assessments, Development, and Evaluation (GRADE) group to indicate the global quality of evidence for a selection of primary outcomes.
OUTCOMES
Regarding efficacy, the MD in hirsutism score between COC and/or AA and metformin were not significant. The exclusion of one single study including most women with severe hirsutism yielded a significant effect in favour of COC and/or AA. When only those studies including an AA were compared with metformin, there were significant differences favouring antiandrogenic therapy. The combination of COC and/or AA with metformin was similar to COC and/or AA therapy alone in the whole group of patients. Post-intervention OR for the presence of regular menses favoured COC therapy. In terms of cardiometabolic impact, the MD in BMI were in favour of metformin. The negative effect of COC therapy on BMI was blunted by its combination with metformin. The MD in homoeostasis model assessment of insulin resistance (HOMA-IR) were also in favour of metformin therapy compared to COC and/or AA. The combination of COC and/or AA and metformin decreased MD in HOMA with respect to antiandrogenic therapy alone. There were no significant post-intervention SMD in circulating glucose levels between COC and/or AA and metformin. However, adding metformin to COC and/or AA yielded a beneficial effect on fasting glucose levels. Post-intervention OR for abnormal glucose tolerance showed no significant differences between COC and/or AA and metformin, although after excluding studies including an AA as a comparator (without COC) a significant effect in favour of metformin therapy was observed. There were no significant differences among therapies in lipid profile, blood pressure or prevalence of hypertension. The global quality of evidence was very low when addressing the impact of the treatments explored on prevalence of hypertension and lipid profiles, low in the case of hirsutism, BMI and blood pressure values, and high for endometrial protection and glucose tolerance.
WIDER IMPLICATIONS
These data provide further scientific evidence for the choice of treatment of women with PCOS. COC and AA are more effective than metformin for hyperandrogenic symptoms and endometrial protection. Their combination with metformin adds a positive effect on BMI and glucose tolerance.
PROSPERO CRD REGISTRATION NUMBER
CRD42016053457.
PubMed: 29293982
DOI: 10.1093/humupd/dmx039