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The Cochrane Database of Systematic... 2000Dysfunctional uterine bleeding (DUB) is "excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognizable pelvic or... (Review)
Review
BACKGROUND
Dysfunctional uterine bleeding (DUB) is "excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognizable pelvic or systemic disease". Anovulation may be inferred from a number of observations but in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those at the extremes of reproductive life and in women known to have the polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is usually poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB, but the regime, dose and type of progestogen used varies widely with little consensus about the optimum treatment approach.
OBJECTIVES
To determine the effectiveness and acceptability of progestogens alone, and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation.
SEARCH STRATEGY
The search strategy of the Menstrual Disorders Group was used to identify all randomised trials of progestogens alone or in combination with oestrogens in the management of irregular menstrual bleeding associated with anovulation. In addition a search of the Cochrane Controlled Trials Register was undertaken.
SELECTION CRITERIA
All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation.
DATA COLLECTION AND ANALYSIS
Study quality assessment and data extraction were carried out independently by two reviewers. Both reviewers were experts in the content matter.
MAIN RESULTS
No randomised trials were identified which compared progestogens with oestrogens and progestogens in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in subjects with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in subjects with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia. No studies were found which compared progestogens with oestrogens and progestogens in combination or with placebo in the management of irregular bleeding associated with anovulation.
REVIEWER'S CONCLUSIONS
There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.
Topics: Adult; Anovulation; Drug Therapy, Combination; Estrogens; Female; Humans; Menorrhagia; Progestins
PubMed: 10796833
DOI: 10.1002/14651858.CD001895 -
Reproductive Biology and Endocrinology... Feb 2017Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 9-18% of women in reproductive age that causes hyperandrogenism and infertility due to... (Review)
Review
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 9-18% of women in reproductive age that causes hyperandrogenism and infertility due to dysfunctional follicular maturation and anovulation. The etiology of PCOS is still poorly known, and information from experimental animal models may help improve current understanding of the mechanisms of PCOS initiation and development. Therefore, we conducted a systematic review of currently available methods for simulation of PCOS in experimental models, focusing on two main endocrine traits: ovarian morphology changes and circulating levels of sex hormones and gonadotropins.We searched the MEDLINE database for articles in English or Spanish published until October 2016. Of 933 studies identified, 39 were included in the systematic review. One study compared interventions with androgens versus estrogens, 18 used androgen-induced stimulation, 9 used estrogens or drugs with estrogen action, including endocrine disruptors, to induce PCOS-like models, and 12 used miscellaneous interventions. Broad differences were found among the studies concerning hormonal interventions, animal species, and developmental stage at the time of the experiments, and most models resulted in ovarian morphology changes, mainly increases in the number of cystic and antral follicles and decreases in the corpus luteum. Hyperandrogenism was produced by using androgens and other drugs as the stimulatory agent. However, studies using drugs with estrogenic effect did not observe changes in circulating androgens.In conclusion, medium- or long-term testosterone administration in the pre- and postnatal periods performed best for induction of a PCOS-like phenotype, in rhesus macaque and rat models respectively. In rats, postnatal exposure to androgens results in reprogramming of the hypothalamic-pituitary-ovarian-axis. Thus, comparisons between different intervention models may be useful to define the timing of reproductive PCOS phenotypes in experimental animal models.
Topics: Animals; Disease Models, Animal; Female; Gonadal Steroid Hormones; Gonadotropins; Humans; Hyperandrogenism; MEDLINE; Ovary; Polycystic Ovary Syndrome
PubMed: 28183310
DOI: 10.1186/s12958-017-0231-z -
Journal of Medicine and Life 2015To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the... (Review)
Review
RATIONALE
To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman's life.
OBJECTIVE
To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood.
METHODS AND RESULTS
A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease.
DISCUSSION
The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis.
ABBREVIATIONS
PCOS = Polycystic Ovary Syndrome.
Topics: Adolescent; Diagnosis, Differential; Diagnostic Imaging; Female; Humans; Polycystic Ovary Syndrome; Puberty; Risk Factors
PubMed: 26351529
DOI: No ID Found -
Reproductive Sciences (Thousand Oaks,... Jan 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that is frequently linked to anovulation in women who are experiencing infertility.... (Review)
Review
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that is frequently linked to anovulation in women who are experiencing infertility. Intestinal flora, also known as the "second genome" of the host, is closely associated with chronic metabolic diseases. Recently, there has been increasing attention on the connection between PCOS and the gut microbiome, and experiments have been conducted. However, the results were unsatisfactory and inconsistent. This review aims to provide a comprehensive overview of the literature investigating the associations between the gut microbiome and PCOS in adults. The goal is to identify whether there are changes in the composition of the gut microbiome in individuals with PCOS. This is the first systematic review to focus on functional alterations in the gut microbiome, which could provide insights into potential mechanisms of microbial involvement in the development of PCOS. We found that there was no significant change in gut microbiome biodiversity in PCOS. Meta-analyses of three studies revealed a significantly higher abundance of Proteobacteria (1.12, 95% CI, 0.21, 2.02, I = 0%) in adults with PCOS. At the genus level, Bacteroides, Enterococcus, and Escherichia-Shigella were found to be enriched in patients with PCOS. Species such as Ruminococcus gnavus group, Parabacteroides distasonis, and Bacteroides fragilis showed an increase in PCOS. Metabolic pathways associated with glucose, lipid metabolism, bile acid metabolism, and protein absorption were found to be enriched in individuals with PCOS. The gut microbiome in PCOS is not characterized by lower diversity, but the composition is altered at the phylum, family, genus, or species level. Consequently, the metabolic pathway differs according to the phenotype of PCOS.
PubMed: 38212581
DOI: 10.1007/s43032-023-01440-4 -
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 -
Reproductive Sciences (Thousand Oaks,... Jun 2024Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to anovulation. This research aims to evaluate the diagnostic potential of oxidative stress biomarkers, including advanced oxidation protein products (AOPP), malondialdehyde (MDA), uric acid (UA), and nitric oxide (NO), in identifying PCOS.
METHODS
A literature search was conducted in the EMBASE, PubMed, Cochrane Library, and Scopus databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were employed to assess the correlation between free radical product and PCOS. Moreover, the presence of heterogeneity among the studies was assessed utilizing the I statistic and Cochran Q test. The methodological rigor of the incorporated studies was assessed through the application of the Newcastle-Ottawa Scale. Furthermore, the presence of publication bias was determined via Begg and Egger tests.
RESULTS
This meta-analysis reviewed 38 observational studies, including 17,845 women. The results revealed a significant association between PCOS in women and alterations in free radical levels. The study revealed that the PCOS group had significantly higher levels of AOPP (SMD = 3.193; 95% CI, 2.86 to 3.25), UA (SMD = 0.68; 95% CI, 0.24 to 1.13), and MDA (SMD = 1.16; 95% CI, 0.77 to 1.56) compared to the healthy control group. Furthermore, the analysis found a significantly lower level of NO (SMD = (- 0.59); 95% CI, - 1.15 to - 0.03) in the PCOS patient.
CONCLUSION
Screening of specific biomarkers associated with free radical products could provide valuable benefits in the prognosis and diagnosis of PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Biomarkers; Oxidative Stress; Free Radicals; Uric Acid; Nitric Oxide; Advanced Oxidation Protein Products; Malondialdehyde
PubMed: 38212583
DOI: 10.1007/s43032-023-01447-x -
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 -
Frontiers in Pharmacology 2022Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or...
Metformin With or Without Clomiphene Citrate Versus Laparoscopic Ovarian Drilling With or Without Clomiphene Citrate to Treat Patients With Clomiphene Citrate-Resistant Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.
Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or even contradictory views. The present meta-analysis aimed to evaluate the effectiveness and safety of Metformin with or without CC and to compare them with LOD with or without CC (Met/Met-CC vs. LOD/LOD-CC) in women with CCR-PCOS who also have anovulation. The PubMed, Cochrane, and Embase databases were searched to identify relevant studies reported between 1 Jan 1966 and 31 Aug 2019; the search was updated on 17 May 2022. We included randomized controlled trials (RCTs) of CCR-PCOS that had considered Met/Met-CC and LOD/LOD-CC as the exposure variables and fertility as the main outcome variable. We assessed study quality using the Cochrane risk-of-bias tool. The primary effectiveness outcome was live birth/ongoing pregnancy rate and the primary safety outcome was miscarriage rate. A fixed-effect meta-analysis was performed. The robustness of the results was assessed using sensitivity analyses. Meta-regression and subgroup analysis were performed to examine the reasons for heterogeneity. Publication bias was examined using the funnel plot, Egger linear regression, and Begg rank correlation tests. The quality of this meta-analysis was estimated according to the GRADE approach. This meta-analysis has been registered in PROSPERO (CRD42021240156). Among 71 potentially relevant studies, we included five RCTs in our meta-analysis. We found no difference in effectiveness between Met-CC and LOD in terms of live birth/ongoing pregnancy (RR = 1.02, 95% CI: 0.87-1.21, z = 0.28; = 0.780), and miscarriage rates (RR = 0.79, 95% CI: 0.46-1.36, z = 0.86; = 0.390). I2 tests results revealed moderate or no heterogeneity (I2 = 51.4%, = 0.083; I2= 0.0%; = 0.952). Sensitivity analysis confirmed the robustness of the results. Funnel plot, Egger linear regression, and Begg rank correlation tests implied no publication bias ( > 0.05). LOD was more expensive than Met (€1050 vs. €50.16). The evidence quality was moderate. There is no evidence on the difference in the outcomes between the two interventions regarding ovulation, pregnancy, and live birth. As LOD is an invasive procedure and carries inherent risks, the use of Met/Met-CC should be the second-line treatment for women with CCR-PCOS. identifier CRD42021240156.
PubMed: 35814214
DOI: 10.3389/fphar.2022.576458 -
Sports Medicine (Auckland, N.Z.) Aug 2017Infertility has been described as a devastating life crisis for couples, and has a particularly severe effect on women, in terms of anxiety and depression. Anovulation... (Review)
Review
BACKGROUND
Infertility has been described as a devastating life crisis for couples, and has a particularly severe effect on women, in terms of anxiety and depression. Anovulation accounts for around 30% of female infertility, and while lifestyle factors such as physical activity are known to be important, the relationship between exercise and ovulation is multi-factorial and complex, and to date there are no clear recommendations concerning exercise regimes.
OBJECTIVES
The objective of this review was to systematically assess the effect of physical activity on ovulation and to discuss the possible mechanisms by which exercise acts to modulate ovulation in reproductive-age women. This was done with a view to improve existing guidelines for women wishing to conceive, as well as women suffering from anovulatory infertility.
SEARCH METHODS
The published literature was searched up to April 2016 using the search terms ovulation, anovulatory, fertility, sport, physical activity and exercise. Both observational and interventional studies were considered, as well as studies that combined exercise with diet. Case studies and articles that did not report anovulation/ovulation or ovarian morphology as outcomes were excluded. Studies involving administered drugs in addition to exercise were excluded.
RESULTS
In total, ten interventions and four observational cohort studies were deemed relevant. Cohort studies showed that there is an increased risk of anovulation in extremely heavy exercisers (>60 min/day), but vigorous exercise of 30-60 min/day was associated with reduced risk of anovulatory infertility. Ten interventions were identified, and of these three have studied the effect of vigorous exercise on ovulation in healthy, ovulating women, but only one showed a significant disruption of ovulation as a result. Seven studies have investigated the effect of exercise on overweight/obese women suffering from polycystic ovary syndrome (PCOS) or anovulatory infertility, showing that exercise, with or without diet, can lead to resumption of ovulation. The mechanism by which exercise affects ovulation is most probably via modulation of the hypothalamic-pituitary-gonadal (HPG) axis due to increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. In heavy exercisers and/or underweight women, an energy drain, low leptin and fluctuating opioids caused by excess exercise have been implicated in HPA dysfunction. In overweight and obese women (with or without PCOS), exercise contributed to lower insulin and free androgen levels, leading to the restoration of HPA regulation of ovulation.
CONCLUSIONS
Several clear gaps have been identified in the existing literature. Short-term studies of over-training have not always produced the disturbance to ovulation identified in the observational studies, bringing up the question of the roles of longer term training and chronic energy deficit. We believe this merits further investigation in specific cohorts, such as professional athletes. Another gap is the complete absence of exercise-based interventions in anovulatory women with a normal body mass index (BMI). The possibly unjustified focus on weight loss rather than the exercise programme means there is also a lack of studies comparing types of physical activity, intensity and settings. We believe that these gaps are delaying an efficient and effective use of exercise as a therapeutic modality to treat anovulatory infertility.
Topics: Anovulation; Exercise; Female; Humans; Infertility, Female; Ovulation; Polycystic Ovary Syndrome
PubMed: 28035585
DOI: 10.1007/s40279-016-0669-8 -
Clinical Endocrinology Feb 2009To date, no systematic review or meta-analysis has been published of direct head-to-head studies comparing clomiphene citrate (CC) vs. metformin, or the combination of... (Meta-Analysis)
Meta-Analysis Review
Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and meta-analysis.
BACKGROUND
To date, no systematic review or meta-analysis has been published of direct head-to-head studies comparing clomiphene citrate (CC) vs. metformin, or the combination of both drugs as first-line therapy in anovulatory polycystic ovary syndrome (PCOS) patients seeking pregnancy. The aim of the current paper was to define, if possible, the best evidence-based recommendations regarding the use of CC and/or metformin as the initial treatment of PCOS women with anovulatory infertility.
DESIGN
Systematic review and meta-analysis of the head-to-head randomized controlled trials (RCTs) available in the literature.
METHODS
A bibliographic search was performed using the following bibliographic databases: Medline, EMBASE, Biological Abstracts, Cochrane Controlled Trials Register and Cochrane Database of Systematic Reviews. Reference lists of included studies, other relevant review articles and textbooks were checked for additional citations of interest.
RESULTS
Four head-to-head RCTs were identified and qualified for inclusion in the analysis. No difference in fertility improvement was observed comparing CC with metformin (OR = 1.22, 95% CI 0.23-6.55, P = 0.815), whereas a significant (P < 0.0001) heterogeneity was observed. Homogeneous data showed no difference in fertility improvement between the combination treatment and CC monotherapy (OR = 0.99, 95% CI 0.70-1.40, P = 0.982), but a significant difference in comparison with metformin monotherapy (OR = 0.23, 95% CI 0.14-0.37, P < 0.0001).
CONCLUSIONS
In PCOS patients with anovulatory infertility and not previously treated, the administration of metformin plus CC is not better than monotherapy (metformin alone or CC alone), whereas to date no specific recommendation can be given regarding the use of CC or metformin as first-step drug.
Topics: Anovulation; Clomiphene; Drug Therapy, Combination; Female; Humans; Infertility, Female; Metformin; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 18691273
DOI: 10.1111/j.1365-2265.2008.03369.x