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Human Reproduction Update Jul 2024The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of exercise, diet and/or pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity: a systematic review and network meta-analysis.
BACKGROUND
The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback between excess adiposity and the hypothalamic-pituitary-ovarian axis. Consequently, finding the most appropriate strategies to lose weight and improve ovulation in women with overweight or obesity is a clinically relevant matter that needs to be investigated. A comprehensive comparison of the independent and combined efficacy of lifestyle and/or pharmacological interventions on BMI, ovulation, and hormonal profile in women with overweight or obesity at risk of anovulatory infertility would facilitate improving fertility strategies in this population.
OBJECTIVE AND RATIONALE
This study aimed to evaluate the comparative efficacy of exercise, diet, and pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity.
SEARCH METHODS
A systematic review was performed by searching PubMed, Scopus, Web of Science, PsycINFO, and Cochrane Library up to 14 December 2023, for randomized controlled trials assessing the effects of exercise, diet and/or pharmacological interventions (i.e. weight-lowering drugs or ovulation inducers) on BMI, ovulation, and/or hormonal profile in reproductive-aged women with overweight or obesity. We performed frequentist random-effect network meta-analyses and rated the certainty of the evidence. The primary outcomes were BMI and ovulation rate, and the secondary outcomes were serum reproductive hormone levels (gonadotrophins, androgens, or oestrogens). We performed sensitivity analyses, including the studies that only involved women with PCOS.
OUTCOMES
Among 1190 records screened, 148 full texts were assessed for eligibility resulting in 95 trials (9910 women), of which 53% presented a high or unclear risk of bias. The network meta-analyses revealed that, compared to control: diet combined with weight-lowering drugs (mean difference (MD) -2.61 kg/m2; 95% CI -3.04 to -2.19; τ2 = 0.22) and adding exercise (MD -2.35 kg/m2; 95% CI -2.81 to -1.89; τ2 = 0.22) led to the greatest decrease in BMI; exercise combined with diet and ovulation inducers (risk ratio (RR) 7.15; 95% CI 1.94-26.40; τ2 = 0.07) and exercise combined with diet and weight-lowering drugs (RR 4.80; 95% CI 1.67-13.84; τ2 = 0.07) produced the highest increase in ovulation rate; and exercise combined with diet and weight-lowering drugs was the most effective strategy in reducing testosterone levels (standardized mean difference (SMD) -2.91; 95% CI -4.07 to -1.74; τ2 = 2.25), the third most effective strategy in increasing sex hormone-binding globulin levels (SMD 2.37; 95% CI 0.99-3.76; τ2 = 2.48), and it was coupled with being ranked first in terms of free androgen index reduction (SMD -1.59; 95% CI -3.18 to 0.01; τ2 = 1.91). The surface under the cumulative ranking curve scores suggested that: diet combined with weight-lowering drugs is the strategy most likely (94%) to produce the highest BMI reduction; and exercise combined with diet and ovulation inducers is the strategy most likely (89%) to produce the highest ovulation rate improvement. The sensitivity analyses, which exclusively included studies involving women diagnosed with PCOS, were consistent with the results presented above.
WIDER IMPLICATIONS
Overall, the findings of this network meta-analysis indicate that the combination of exercise, diet, and pharmacological interventions is effective for weight loss, improving ovulation, and normalizing the androgen levels of women with overweight or obesity. Although higher quality studies are needed, these results support that the optimal treatment strategy for women with overweight or obesity wishing to conceive must consider exercise, diet, and pharmacological interventions during the shared decision-making process.
Topics: Humans; Female; Body Mass Index; Ovulation; Obesity; Overweight; Exercise; Network Meta-Analysis; Adult; Diet
PubMed: 38627233
DOI: 10.1093/humupd/dmae008 -
Women's Health (London, England) 2024Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including... (Review)
Review
Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including hyperandrogenism, chronic anovulation, and polycystic ovaries. In addition, half of women with polycystic ovary syndrome have insulin resistance, and obesity or overweight, type 2 diabetes, hypertension, and hyperlipidemia are the most common metabolic abnormalities affecting (30%) women with polycystic ovary syndrome. Weight loss is regarded as the first-line treatment as it can potentially improve polycystic ovary syndrome parameters (androgen levels, menstrual cyclicity, lipid and glucose metabolism). However, achieving and maintaining weight loss can be challenging, and pharmacological agents could be essential to achieve optimal glycemic control and improve the endocrine disturbance associated with polycystic ovary syndrome. Glucagon-like peptide-1 receptor agonist has been demonstrated as monotherapy or in combination with metformin for managing obesity and insulin resistance associated with polycystic ovary syndrome. Yet, its effect on endocrine and metabolic parameters remains elusive, and further research is needed to close the gap. The aim is to evaluate the efficacy of glucagon-like peptide-1 receptor agonist monotherapy and/or a combined treatment between glucagon-like peptide-1 receptor agonist and metformin for improving anthropometric measurements, endocrine and metabolic parameters in lean and obese women with polycystic ovary syndrome. A systematic review of longitudinal cohort studies was conducted across databases including Ovid Medline, PubMed Central, and Cochrane Library between 2015 and 2022. Eligible studies included participants with polycystic ovary syndrome diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health criteria. A total of eight studies including 486 patients with polycystic ovary syndrome were analyzed. The mean age was between 18 and 45 years with mean follow-up period between 12 and 32 weeks. In all these studies, results were comparable for the reduction in body mass index, waist circumference, fat mass, and visceral fat mass; however, it was more in combination therapy versus comparator. In conclusion, glucagon-like peptide-1 receptor agonists effectively reduce body weight and improve some of the endocrine and metabolic parameters of polycystic ovary syndrome. A combined treatment with glucagon-like peptide-1 receptor agonist and metformin had significant effects on weight loss and favorable results on endocrine and metabolic parameters, yet further research is needed to discover the long-term safety of combined therapy in women diagnosed with polycystic ovary syndrome and obesity or overweight.
Topics: Female; Humans; Infant; Male; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor Agonists; Insulin Resistance; Longitudinal Studies; Metformin; Obesity; Overweight; Polycystic Ovary Syndrome; United States; Weight Loss
PubMed: 38444070
DOI: 10.1177/17455057241234530 -
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 -
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 -
International Journal of Gynaecology... Jul 2024Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved.
OBJECTIVE
To investigate the association between exposure to BPA and PCOS.
SEARCH STRATEGY
Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases.
SELECTION CRITERIA
Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS.
DATA COLLECTION AND ANALYSIS
Following PRISMA guidelines, study characteristics and relevant data were extracted.
MAIN RESULTS
Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present.
CONCLUSIONS
Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.
Topics: Humans; Polycystic Ovary Syndrome; Female; Phenols; Benzhydryl Compounds; Endocrine Disruptors; Environmental Exposure
PubMed: 38197560
DOI: 10.1002/ijgo.15349 -
Reproductive Sciences (Thousand Oaks,... Apr 2024Clomiphene citrate (CC) and letrozole are the predominant medical interventions for the management of infertility in patients with polycystic ovary syndrome (PCOS). To... (Meta-Analysis)
Meta-Analysis Review
Clomiphene citrate (CC) and letrozole are the predominant medical interventions for the management of infertility in patients with polycystic ovary syndrome (PCOS). To comprehensively summarize the evidence, a systematic review and meta-analysis of randomized clinical trials (RCTs) was carried out to assess the effect of letrozole and CC on pregnancy outcomes in PCOS patients. We searched PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2023. We included RCTs conducted on PCOS women comparing letrozole to CC and assessing endometrial thickness, the number and size of follicles, and ovulation and pregnancy rates. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) using the random-effects model. Heterogeneity was examined using the I statistic. Fifty trials met our inclusion criteria. The mean endometrial thickness was significantly higher in the letrozole group compared to CC group (SMD: 0.89; 95% CI: 0.49, 1.28; I=97.72%); however, the number of follicles was higher in the CC group (SMD: -0.56; 95% CI: -0.96, -0.17; I=96.34%). Furthermore, letrozole intake induced higher ovulation rate (RR: 1.20; 95% CI: 1.13, 1.26; I=54.49%) and pregnancy rate (RR: 1.44; 95% CI: 1.28, 1.62; I=65.58%) compared to CC. Compared to CC, letrozole has a positive effect on endometrial thickness, monofollicular development, and ovulation and pregnancy rates suggesting that letrozole may be a strong alternative to CC as a first-line medical intervention for chronic anovulation in PCOS women. Larger studies are warranted to further clarify these findings.
Topics: Pregnancy; Female; Humans; Letrozole; Pregnancy Outcome; Polycystic Ovary Syndrome; Fertility Agents, Female; Infertility, Female; Birth Rate; Ovulation Induction; Clomiphene; Pregnancy Rate
PubMed: 38030814
DOI: 10.1007/s43032-023-01404-8 -
Sports Medicine (Auckland, N.Z.) Oct 2023Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in...
BACKGROUND
Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in sports continues to increase, understanding the prevalence of a range of MC disorders and MC-related symptoms may guide preventive strategies to protect the health and optimise the performance of female athletes.
OBJECTIVE
To examine the prevalence of MC disorders and MC-related symptoms among female athletes who are not using hormonal contraceptives and evaluate the assessment methods used to identify MC disorders and MC-related symptoms.
METHODS
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Six databases were searched until September 2022 for all original research that reported the prevalence of MC disorders and/or MC-related symptoms in athletes not using hormonal contraceptives, which included the definitions of the MC disorders examined, and the assessment methods used. MC disorders included amenorrhoea, anovulation, dysmenorrhoea, heavy menstrual bleeding (HMB), luteal phase deficiency (LPD), oligomenorrhoea, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). MC-related symptoms included any affective and physical symptoms related to the MC that do not cause significant personal, interpersonal or functional impairment. The prevalence data across eligible studies were combined, and all studies were qualitatively synthesised to evaluate the assessment methods and tools used to identify MC disorders and MC-related symptoms. The methodological quality of studies was assessed using a modified Downs and Black checklist.
RESULTS
Sixty studies involving 6380 athletes were included. A wide range of prevalence was observed for all types of MC disorders, with a dearth of data on anovulation and LPD. Based on pooled data, dysmenorrhoea (32.3%; range 7.8-85.6%) was the most prevalent MC disorder. Studies reporting MC-related symptoms mostly examined the premenstrual and menstruation phases, where affective symptoms appeared more prevalent than physical symptoms. A larger proportion of athletes reported symptoms during the initial days of menstruation compared with the premenstrual phase. MC disorders and MC-related symptoms were retrospectively assessed using self-report methods in 90.0% of studies. Most studies (76.7%) in this review were graded as moderate quality.
DISCUSSION
MC disorders and MC-related symptoms are commonplace among female athletes, warranting further research examining their impact on performance and preventive/management strategies to optimise athlete health. To increase the quality of future studies, researchers should adopt standardised definitions of MC disorders and assessment methods such as a combination of calendar counting, urinary ovulation tests and a mid-luteal phase serum progesterone measurement when assessing menstrual function. Similarly, standardised diagnostic criteria should be used when examining MC disorders such as HMB, PMS and PMDD. Practically, implementing prospective cycle monitoring that includes ovulation testing, mid-luteal blood sampling (where feasible) and symptom logging throughout the MC could support athletes and practitioners to promptly identify and manage MC disorders and/or MC-related symptoms.
TRIAL REGISTRATION
This review has been registered in the PROSPERO database (CRD42021268757).
Topics: Female; Humans; Dysmenorrhea; Prevalence; Prospective Studies; Anovulation; Retrospective Studies; Menstrual Cycle; Premenstrual Syndrome; Menstruation Disturbances; Premenstrual Dysphoric Disorder; Athletes; Contraceptive Agents
PubMed: 37389782
DOI: 10.1007/s40279-023-01871-8