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European Journal of Endocrinology Sep 2023Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in response to starvation and low body weight including changes in adrenocortical hormones. Our objective was to systematically review adrenocortical hormone levels in anorexia nervosa.
DESIGN/METHODS
We searched MEDLINE and EMBASE for studies that reported at least one adrenocortical hormone, including dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEA-S), progesterone, 17-hydroxyprogesterone, pregnenolone, cortisol (serum, urine, cerebrospinal fluid, and hair sample), aldosterone, androstenedione, and testosterone in patients with anorexia nervosa and normal-weight healthy controls from inception until October 2021. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). A pooled MD was then calculated by combining MDs of each study using the random-effects model.
RESULTS
We included a total of 101 studies with over 2500 females with anorexia nervosa. Mean cortisol levels were significantly higher in anorexia nervosa as compared to normal-weight controls for multiple forms of measurement, including morning cortisol, 12-hour and 24-hour pooled serum cortisol, 24-hour urine cortisol, and after an overnight dexamethasone suppression test. In contrast, mean serum total testosterone and DHEA-S levels were significantly lower among patients with anorexia nervosa.
CONCLUSIONS
Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.
Topics: Humans; Female; Anorexia Nervosa; Hydrocortisone; Aldosterone; Progesterone; Dehydroepiandrosterone Sulfate
PubMed: 37669399
DOI: 10.1093/ejendo/lvad123 -
EClinicalMedicine Sep 2023Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy...
BACKGROUND
Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS.
METHODS
We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640.
FINDINGS
From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n = 961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens + lifestyle were superior to metformin + lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]: -1.59 [-3.06, -0.12], p = 0.03; = 74%), SHBG (7.70 nmol/l [0.75, 14.66], p = 0.03; = 0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97, -0.26], p = 0.03; = 0% and -1.12 [-1.44, -0.79], p < 0.0001, = 0%, respectively), but were not superior to placebo + lifestyle for hirsutism (-0.93, [-3.37, 1.51], p = 0.45; = 76%) or SHBG (9.72 nmol/l [-0.71, 20.14], p = 0.07; = 31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58, -2.39], p < 0.0001, = 1%), and resulted in lower androstenedione levels (-0.30 ng/ml [-0.50, -0.10], p = 0.004; = 0%). Combination treatment with anti-androgens + metformin + lifestyle resulted in lower testosterone compared with metformin + lifestyle (-0.29 nmol/l [-0.52, -0.06], p = 0.01; = 61%), but there were no differences in hirsutism when anti-androgens + metformin + lifestyle were compared with either anti-androgens + lifestyle or metformin + lifestyle. In limited meta-analyses (n = 2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP ± placebo, with no differences in other outcomes.
INTERPRETATION
Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics.
FUNDING
National Health and Medical Research Council (NHMRC) of Australia Monash University.
PubMed: 37583655
DOI: 10.1016/j.eclinm.2023.102162 -
Human Reproduction Update Nov 2023Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.
OBJECTIVE AND RATIONALE
We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS.
SEARCH METHODS
Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system.
OUTCOMES
The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). Albeit myocardial infarction (OR 2.51 (1.08, 5.81)) and stroke (OR 1.75 (1.03, 2.99)) were more prevalent in women with PCOS than controls, the ORs for cardiovascular disease as a whole, coronary artery disease as a whole, breast cancer and age at menopause, were similar in patients and controls. When restricting meta-analysis to studies in which women with PCOS and controls had a similar mean BMI, the only difference that retained statistical significance was a decrease in HDL-cholesterol concentration in the former and, in the two studies in which postmenopausal women with PCOS and controls had similar BMI, patients presented with increased serum androgen concentrations, suggesting that hyperandrogenism persists after menopause, regardless of obesity.
WIDER IMPLICATIONS
Hyperandrogenism appeared to persist during the late-reproductive years and after menopause in women with PCOS. Most cardiometabolic comorbidities were driven by the frequent coexistence of weight excess and PCOS, highlighting the importance of targeting obesity in this population. However, the significant heterogeneity among included studies, and the overall low quality of the evidence gathered here, precludes reaching definite conclusions on the issue. Hence, guidelines derived from adequately powered prospective studies are definitely needed for appropriate management of these women.
Topics: Humans; Female; Middle Aged; Androgens; Polycystic Ovary Syndrome; Hyperandrogenism; Cross-Sectional Studies; Prospective Studies; Obesity; Menopause; Cholesterol
PubMed: 37353908
DOI: 10.1093/humupd/dmad015 -
Reproductive Biology and Endocrinology... Jan 2023Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.
OBJECTIVE
Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.
METHODS
The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).
RESULTS
Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).
CONCLUSION
Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.
TRIAL REGISTRATION
PROSPERO registration number: CRD42021283275.
Topics: Female; Humans; Polycystic Ovary Syndrome; Inositol; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Metformin; Testosterone; Insulins
PubMed: 36703143
DOI: 10.1186/s12958-023-01055-z -
Life (Basel, Switzerland) Jan 2023Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of the female reproductive system, including polycystic ovary syndrome (PCOS). The aim of... (Review)
Review
Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of the female reproductive system, including polycystic ovary syndrome (PCOS). The aim of this review was to summarize the knowledge about the association of EDCs (bisphenols, parabens, and triclosan) with PCOS. We conducted an electronic literature search using PubMed for studies published between January 2007 and October 2022 on EDCs related to PCOS, and evaluated the association of PCOS with bisphenols, parabens and triclosan in 15 articles. Most studies revealed significantly higher plasma, urinary or follicular fluid levels of bisphenol A (BPA) in women with PCOS, and some showed a positive correlation of BPA with insulin resistance, polycystic morphology on ultrasound, hepatic steatosis, bilirubin levels, as well as free androgen index, androstenedione and testosterone serum levels, and markers of low-grade chronic inflammation. There was a negative correlation of BPA with markers of ovarian reserve, sex hormone binding globulin and vitamin D-binding protein. Parabens and triclosan have been studied in only one study each, with no significant associations with PCOS observed. Our review revealed an association of BPA with PCOS and negative effects of BPA on human ovaries; more research is needed to assess the potential associations of parabens and triclosan with PCOS.
PubMed: 36676087
DOI: 10.3390/life13010138 -
Therapeutic Advances in Endocrinology... 2022Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing... (Review)
Review
Impact of metformin on the clinical and metabolic parameters of women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.
CONTEXT
Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition.
AIM
To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS.
DATA SOURCE
We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022.
DATA SYNTHESIS
Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
RESULTS
In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: -5.33, -0.93), body mass index (BMI) by 0.82 kg/m² (95% CI: -1.22, -0.41), fasting blood glucose [standardised mean difference (SMD): -0.23; 95% CI: -0.40, -0.06], low-density lipoprotein cholesterol (LDL-C) (SMD: -0.41; 95% CI: -0.85, 0.03), total testosterone (SMD: -0.33; 95% CI: -0.49, -0.17), androstenedione (SMD: -0.45; 95% CI: -0.70, -0.20), 17-hydroxyprogesterone (17-OHP) (SMD: -0.58; 95% CI: -1.16, 0.00) and increase the likelihood of clinical pregnancy rate [odds ratio (OR): 3.00; 95% CI: 1.95, 4.59] compared with placebo.
CONCLUSION
In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.
PubMed: 36225721
DOI: 10.1177/20420188221127142 -
Drugs Sep 2022Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women, impacting several aspects of a woman's life, including reproductive, mental,... (Meta-Analysis)
Meta-Analysis
The Effect of Oral Antidiabetic Drugs on Improving the Endocrine and Metabolic States in Women with Polycystic Ovary Syndrome: A Systematic Review and Network Meta-analysis.
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women, impacting several aspects of a woman's life, including reproductive, mental, cardiovascular, and metabolic health. Antidiabetic drugs may have beneficial effects on the endocrine and metabolic states in women with PCOS.
OBJECTIVE
This study aimed to compare the effects of oral antidiabetic drugs on reproductive hormones, metabolic and anthropometric markers, and menstrual frequency, in patients with PCOS using network meta-analysis.
METHODS
PubMed, EMBASE, and CENTRAL were searched for studies published up to May 31, 2021. Randomised clinical trials enrolling participants with PCOS were included, for which sodium-glucose cotransporter 2 (SGLT-2) inhibitors, metformin (Met), dipeptidyl peptidase 4 (DPP-4) inhibitors, alpha-glucosidase inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), and thiazolidinediones (TZDs) (alone or in combination) were compared with either each other, placebo, or no treatment. A network meta-analysis using a Bayesian approach was performed. The outcomes included changes in endocrine outcomes, metabolic results, menstrual frequency, and anthropometric findings. All research was conducted according to a protocol registered in the PROSPERO database (CRD42021248314).
RESULTS
In total, we retrieved 3383 studies, of which 47 articles enrolling 2626 participants were included for the network meta-analysis. In comparison to the control groups, Met (MD - 0.41, 95% CI - 0.73 to - 0.09) was more beneficial in reducing serum total testosterone, and GLP-1RAs+Met (MD - 5.44, 95% CI - 10.06 to - 0.89) reduced free androgen index (FAI) more effectively. Thiazolidinediones (MD 9.33, 95% CI 0.15 to 17.99) had a greater effect on sex hormone-binding globulin (SHBG) than Met. For decreasing androstenedione, Met (MD - 1.87, 95% CI - 2.73 to - 1.01), DPP-4 inhibitors (MD - 2.64, 95% CI - 4.77 to - 0.49), GLP-1RAs (MD - 3.06, 95% CI - 5.53 to - 0.62), and GLP-1RAs+Met (MD - 2.97, 95% CI - 5.85 to - 0.09) were more effective than TZDs. The confidence in evidence was often low or very low.
CONCLUSIONS
In this network meta-analysis, GLP-1 receptor agonists in combination with metformin appear to be preferable for improving hyperandrogenaemia. Metformin and TZDs offer the added benefit of improving fasting blood glucose (FBG) and low-density lipoprotein-cholesterol (LDL-C) when compared to the control groups. Metformin combined with GLP-1 receptor agonists or TZDs could be associated with a beneficial effect on menstrual recovery.
Topics: Humans; Female; Hypoglycemic Agents; Polycystic Ovary Syndrome; Glucagon-Like Peptide-1 Receptor; Network Meta-Analysis; Bayes Theorem; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Thiazolidinediones
PubMed: 36129662
DOI: 10.1007/s40265-022-01779-z -
Hormones (Athens, Greece) Dec 2022To date, no meta-analysis has been carried out to collect evidence from randomized placebo-controlled trials (RCTs) for the purpose of comprehensively summarizing the... (Meta-Analysis)
Meta-Analysis Review
The effect of androstenedione supplementation on testosterone, estradiol, body composition, and lipid profile: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
To date, no meta-analysis has been carried out to collect evidence from randomized placebo-controlled trials (RCTs) for the purpose of comprehensively summarizing the effect of androstenedione supplementation. Therefore, the aim of this research was to perform a systematic review and meta-analysis of all RCTs that explored the effect of androstenedione supplementation on individual hormonal, lipid, and anthropometric indices.
METHODS
We searched five databases (Web of Science, SCOPUS, Embase, PubMed/MEDLINE, and Google Scholar) using a combination of medical subject headings (MeSH) and non-MeSH terms. Using the random-effects model, we summarized the outcomes as weighted mean difference (WMD) with 95% confidence interval (CI).
RESULTS
Eight eligible articles were included in the meta-analysis. The pooled effect sizes suggested a significant effect of androstenedione supplementation on serum estradiol concentrations (WMD: 20.82 ng/ml, 95% CI: 7.25 to 34.38, p = 0.003), triglycerides (TG, WMD: -0.19 mg/dl, 95% CI: - 0.96, 0.57, p = 0.000), and high-density lipoprotein (HDL)-cholesterol (WMD: - 0.13 mg/dl, 95% CI: - 0.23 to - 0.03, p = 0.009); however, it had no effect on testosterone (WMD: 0.098 ng/ml, 95% CI: - 0.499 to 0.696, p = 0.748), body weight (WMD: 0.579 kg, 95% CI: - 4.02 to 5.17, p = 0.805), body mass index (BMI, WMD: - 0.73 kg/m, 95% CI: - 2.98, 1.50, p = 0.519), low-density lipoprotein (LDL)-cholesterol (WMD: - 0.074 mg/dl, 95% CI: - 0.37 to 0.22, p = 0.622), and total cholesterol (TC, WMD: - 0.15 mg/dl, 95% CI: - 0.49, 0.17, p = 0.198).
CONCLUSION
These findings indicate that androstenedione supplementation can lower TG and HDL-cholesterol and increase estradiol concentrations.
Topics: Humans; Androstenedione; Lipids; Testosterone; Estradiol; Dietary Supplements; Randomized Controlled Trials as Topic; Cholesterol, HDL; Cholesterol; Testosterone Congeners; Body Composition; Androgens
PubMed: 35841524
DOI: 10.1007/s42000-022-00385-8 -
The Journal of Obstetrics and... Jul 2022This meta-analysis was conducted to evaluate the effect of statins combined or not combined with metformin on polycystic ovary syndrome (PCOS). (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis was conducted to evaluate the effect of statins combined or not combined with metformin on polycystic ovary syndrome (PCOS).
METHODS
Databases were systematically searched from inception to February 2022. Meta-analysis was conducted by using STATA 12.0 software. In the study, standard mean difference (SMD) and 95% confidence intervals (CI) were computed as the effect size. A random effect model was used.
RESULTS
Meta-analysis showed significant decline of total testosterone, free testosterone, dehydroepiandrosterone sulphate, androstenedione, luteinizing hormone (LH), LH to follicle-stimulating hormone (FSH) ratio, and prolactin in statin group. Our study also demonstrated significant decline of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in statin group. Moreover, we found significant decline of fasting glucose, insulin sensitivity index, and high-sensitivity C-reactive protein.
CONCLUSION
The meta-analysis showed that statin therapy was good for women with PCOS, and could improve clinical signs of PCOS.
Topics: Cholesterol; Female; Follicle Stimulating Hormone; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Insulin; Luteinizing Hormone; Metformin; Polycystic Ovary Syndrome; Testosterone
PubMed: 35620917
DOI: 10.1111/jog.15301 -
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