Bioengineered Isoflavone–Probiotic Functional Foods for Sustainable Modulation of Metabolic and Reproductive Health in PCOS

The recent International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (PCOS) recommended healthy lifestyle interventions (dietary, exercise, behavioral modification, or combined) as the first-line therapy to mediate favorable metabolic outcomes in PCOS. However, the relationship between lifestyle modifications and reproductive health in PCOS is less clear. Specifically, a favorable dietary composition to facilitate reproductive changes in women with PCOS remains unknown. Further, the longitudinal impacts of lifestyle change programs in women with PCOS is poorly elucidated. We hypothesized that a low glycemic index pulse-based diet containing lentils, beans, split peas, and chickpeas would be more effective than the Therapeutic Lifestyle Changes (TLC) diet at improving insulin sensitivity without an energy-restricted protocol and would improve reproductive health outcomes in women with PCOS after a 16-week intervention. Our objective was to compare the effects of a nutritionally balanced pulse-based diet with the TLC diet on ultrasonographic markers of ovarian morphology, hyperandrogenism, and menstrual irregularity. Women (n=30) randomized to the pulse-based and TLC (n=31) groups completed a 16-week intervention. All women participated in aerobic exercise (minimum 5 days/week; 45 minutes/day) and received health counseling (monthly) about PCOS and the benefits of lifestyle modification. Additionally, we evaluated the effects of the intervention on the reproductive outcomes by longitudinal follow-up of all participants. Follicle numbers per ovary (FNPO, 2-9 mm), ovarian volume (OV), free androgen index (FAI), intermenstrual intervals, and insulin sensitivity (Matsuda index and homeostasis model assessment of insulin resistance [HOMA-IR] were evaluated at baseline, 16-week post-intervention, and 6- and 12-month post-intervention follow up visits. Follicle numbers per ovary (mean change ± SD, -10 ± 15), OV (-2.7 ± 4.8 mL), FAI (-3 ± 2), intermenstrual interval (-13 ± 47 days), and body mass index (BMI, -1.6 ± 4.2 kg/m2) decreased, and Matsuda index (1.1 ± 3.1) increased over time in both groups (All: P ≤ 0.01), without group-by-time interactions (All: P ≥ 0.27). Groups maintained reduced OV, FNPO, FAI, and menstrual cycles 6 months post-intervention, despite a propensity for weight regain as evidenced by increased BMI (1.0 ± 4.8 kg/m2; P < 0.01). Decreased FNPO, FAI, and HOMA-IR at 16-week tended to revert to baseline levels 12 months post-intervention in both groups (All: P ≤ 0.05). Both interventions improved ovarian dysmorphology, hyperandrogenism, and menstrual irregularity in women with PCOS. Our observations elucidate the importance of longitudinal surveillance for sustainable adherence to newly adopted healthy lifestyle behaviors and reproductive health in PCOS (ClinicalTrials.gov identifier, NCT01288638).

Women with polycystic ovary syndrome (PCOS) exhibit reduced skeletal muscle insulin-mediated glucose uptake. Altered muscle mass may affect insulin resistance (IR) and inflammation, thereby potentially aggravating reproductive status including ovulatory cyclicity and fertility potential. However, the relationship between PCOS and skeletal muscle mass is elusive given conflicting reports on protective or detrimental influence of PCOS endocrine derangements (hyperandrogenism, IR) on muscle. We evaluated whether muscle mass and function are affected by PCOS in response to a call to elucidate musculoskeletal alterations in the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Web of Science, and Scopus were searched (January 1990 to September 2020) to identify observational studies on 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 weighted mean differences and 95% confidence intervals. Forty-five studies (n = 3,676 [1,854, PCOS; 1,822, controls]) were eligible. Forty-one evaluated lean tissue mass and five strength. PCOS groups had increased total (0.83 [0.08, 1.58] kg; P=0.03; I2 = 72.0%) yet comparable trunk (0.84 [-0.37, 2.05] kg; P = 0.15; I2 = 73.0%) LBM/FFM. There were no associations between mean differences of groups in total testosterone (TT) or homeostatic model assessment of IR (HOMA-IR) and total/trunk LBM/FFM (All: P ≥ 0.75) by meta-regressions. However, mean differences of groups in body mass index (BMI) were associated with total (0.65 [0.23, 1.06] kg; P < 0.01; I2 = 56.9%) and trunk (0.56 [0.11, 1.01] kg; P = 0.02; I2 = 42.8%) LBM/FFM. Accordingly, PCOS sub-group with overweight/obesity (BMI ≥ 25 kg/m2) exhibited greater total LBM/FFM than controls (1.58 [0.82, 2.34] kg; P < 0.01; I2 = 64.0%) unlike a lean (BMI < 25 kg/m2) sub-group (-0.45 [-1.94, 1.05] kg; P = 0.53; I2 = 69.5%). Some study results were contradictory (i.e., increased appendicular mass or strength in PCOS group or comparable findings between groups) and study methodology varied; thus, inclusion in meta-analyses was not possible. PCOS cohorts have a tendency for increased total and trunk lean tissue mass likely attributed to obesity. However, most critically, whether PCOS influences other lean tissue areas (appendicular), morphology, and function is unclear. Our observations do not support any protective/detrimental influence of hyperandrogenism (TT) or IR (HOMA-IR) on lean mass. Heterogeneity among studies warrants research to address any contributions of lifestyle, healthcare, and biological factors to observed differences for future guideline recommendations to improve PCOS musculoskeletal and reproductive health (www.crd.york.ac.uk/PROSPERO ID, CRD42020203490).

Polycystic Ovarian Syndrome (PCOS) is a prevalent reproductive endocrinopathy which presents a significant clinical and public health problem (Morgante et al. 2015). PCOS can affect females throughout their lifespan leading to serious complications such as obesity, infertility, type two diabetes mellitus and cardiovascular disease (De Leo et al. 2016). The conventional approach to treating PCOS is guided by what symptoms affect the patient most such as infertility, hirsutism, acne and so forth. Many of the conventional treatments for PCOS such as metformin, anti-androgens and oral contraceptives can cause harmful adverse side-effects (Lamba et al 2018:65). Adverse side-effects, complications, dissatisfaction in various aspects of the patient- practitioner experience and failed therapies are among the main reasons that patients opt for Complementary and Alternative Medicine (CAM) therapy. CAM fulfils the expectations not met by conventional medicine, particularly the psychological impact of PCOS on patients, which are assessed by only a few conventional practitioners (Fauser et al. 2012). Aim of the study This study aimed to document existing therapeutic protocols in the management of PCOS from diagnosis to treatment used by practitioners within various disciplines of CAM in the context of their unique philosophical background. Furthermore, this information may be valuable in bridging any potential gap in information across the five CAM modalities investigated in this research with regards to PCOS. These modalities were: homoeopathy, Ayurveda (AV), Unani Tibb (UT), Traditional Chinese Medicine (TCM) and naturopathy. Methodology A qualitative approach was used to document the perceptions and protocols used in the diagnosis and management of PCOS by practitioners of the five selected CAM v modalities practicing within the boundaries of the eThekwini municipality. Stratified purposive sampling was implemented in order to select a sample frame of 12 participants. Data was collected by means of personalised, semi-structured interviews and the data collected was analysed using Tesch’s (Tesch 1990:329) and Creswell’s (Creswell 2014) methods. Results CAM philosophies are underpinned by the principles of innate healing, an individualised constitution and governing factors which manage homeostasis. TCM philosophy is guided by the yin and yang concept, homoeopathy by the vital force and miasms, AV by three doshas. UT by four humours and naturopathy by lifestyle factors. PCOS patients were generally classified as being sycotic and/or cancerinic (miasmatically) according to homoeopathy, having a melancholic, sanguineous temperament according to UT, presenting with excessive kapha and vata according to Ayurveda and a predominant yang deficiency with heat and moisture according to TCM. PCOS is a multi-faceted reproductive endocrinopathy which requires extensive management. The different roles of a family physician, endocrinologist, dermatologist, dietitian and gynaecologist in the diagnosis and holistic management of PCOS is performed collectively by a CAM practitioner. PCOS is considered an affliction of the woman and not merely as a disease of the ovaries and therefore much attention is drawn to the emotional drivers, particularly stress and abuse which affect these patients’ quality of life (QoL). Diagnostics reported by participants included: 1) A clinical diagnosis congruent with established diagnostic criteria such as the Rotterdam criteria which identified the pathognomonic features of PCOS and 2) A CAM-specific diagnosis which evaluated the entirety of the patient’s symptoms, emotions and characteristics in order to determine a constitutional weakness. vi This study found that management of PCOS, according to CAM participants, was aimed at correcting hormonal, ovulatory and menstrual imbalances, improving fertility, reducing obesity, managing infertility and improving the patient’s QoL. Management strategies generally comprised: 1) CAM-specific therapy which included medicines and/or procedures, 2) Adjunctive therapy which included supplements and the use of other modalities and 3) Lifestyle intervention which included dietary counselling, physical activity recommendations and emotional counselling. Conclusion In conclusion, PCOS is a multi-faceted condition which requires emotional support concomitantly with therapeutic support due to the clinical spectrum of changes that can have an impact on females’ psychological health.

The role of vitamin D in polycystic ovary syndrome

To harmonise the diagnostic processes of polycystic ovary syndrome (PCOS) and enable clinicians to provide better patient care, it is critical to understand the knowledge gaps in PCOS diagnosis. We evaluated how clinicians in endocrinology, family medicine, general practice and gynaecology diagnose PCOS. This cross-sectional survey involved 208 clinicians from specific subspecialties across various healthcare settings in Singapore. A total of 160 responses were included in the final analysis. Among all the diagnostic criteria, the Rotterdam 2003 criteria was most frequently used (66.3%). More than half of the gynaecologists reported having a standardised workplace protocol while the majority from other specialties reported otherwise. A large percentage of respondents (60.5%) were unable to identify the correct PCOS clinical features, which is concerning. Only 8.8% of respondents used clinical and biochemical hyperandrogenism, menstrual disturbances and pelvic ultrasound to diagnose PCOS without performing unnecessary and incorrect investigations. Most clinicians recognised insulin resistance/type 2 diabetes mellitus and fertility problems as complications while only a few recognised psychological complications. Many clinicians (37.3%) sought standardisation of PCOS diagnosis and management guidelines for improvement in PCOS care and 81.9% of respondents would appreciate standardised educational materials. This is the first study to the best of our knowledge that gives an insight into the diagnostic and management processes of PCOS among various healthcare institutions in Singapore. This study calls for greater harmonisation of diagnostic processes and holistic evidence-based management of patients with PCOS through standardised workplace protocols and patient education resources.

Polycystic ovarian syndrome (PCOS), a lifestyle disorder that occurs due to hyperandrogenism in women. In this, FSH (follicle stimulating hormone) levels decrease whereas testosterone levels increase at once. There are many reasons for which PCOS occurs. Etiology and pathophysiology are discussed briefly in the present article. Aloe vera (Aloe barbadensis Mill.) is a renowned medicinal herb among the whole world for its pharmacological activities like ‘anti-diabetogenic’, ‘anti-microbial’, ‘anti-inflammatory’, ‘anti-obesity’ and clinical activities including ‘PCOS management’ and ‘wound healing’, ‘skin protection’ etc. The present paper objects to summarize the impact of aloe vera in PCOS management and other PCOS-induced disorders. It inhibits the genes that induce PCOS and aloe vera also regulates the activity of insulin. Several bioactive phytochemicals, present in aloe vera like ‘barbaloin’, ‘aloe-emodin-9-anthrone’, ‘lsobarbaloin’ ,’Anthrone-C-glycosides’ and ‘chromones’, ‘phytosterols’, ‘aloin’, ‘anthrone’, ‘aloe emodin’ , ‘aloetinic acid’ , ‘choline’ and ‘choline salicylate’ etc., which are responsible for its efficacy in PCOS and PCOS-induced disorders management.

Study question What gut microbiota and metabolic alterations are associated with Polycystic ovary syndrome (PCOS) and linked to adverse pregnancy outcomes (APOs)? Summary answer In PCOS, P. merdae decreases, BCAAs increase, raising the risk of APOs. Meanwhile, endometrial senescence and decidualization impairment are found, worsening with higher Ile concentration. What is known already PCOS, a prevalent and complex endocrine disorder, stands as the primary cause of anovulatory infertility. The rising prevalence of PCOS in China over the past decade has led to a substantial increase in disease burden. Our previous ten-year retrospective analysis revealed that PCOS patients undergoing their first fresh embryo transfer faced a heightened risk of APOs, such as miscarriage. However, the factors influencing disease progression and future obstetric outcomes in PCOS remain elusive. Study design, size, duration This prospective cohort study encompassed a diverse cohort of 220 women (110 with PCOS and 110 controls) from 44 cities across China, with a median follow-up duration of 16.6 months. Participants/materials, setting, methods Women aged &amp;lt; 35 years with PCOS (Rotterdam criteria) and age-/BMI-matched controls were recruited. Fecal microbiomes were analyzed using 16S rRNA sequencing and metagenomics, while serum metabolites were assessed through both untargeted and targeted metabolomics. Endometrial stromal cell senescence was evaluated based on a constellation of markers, including cell proliferation, senescence-associated secretory phenotype factors, cell cycle, ROS levels, and SA-β-Gal activity. Endometrial decidualization was gauged by measuring prolactin and IGFBP-1 levels using ELISA. Main results and the role of chance Our study revealed significant gut microbiota alterations, including reduced α-diversity and a notable decline in Parabacteroides merdae (P. merdae), a key species differentiating PCOS from controls. Serum metabolomics identified 45 differential metabolites, with branched-chain amino acids (BCAAs), especially isoleucine (Ile), exhibiting strong diagnostic potential. Targeted metabolomics further validated BCAAs’ (Valine, Leucine, and Ile) upregulation and short-chain fatty acids’ downregulation in PCOS. During follow - up, PCOS patients had a higher cumulative incidence of APOs despite similar pregnancy rates. And the adjustment for potential confounders did not substantially change the estimates. Intriguingly, individuals who experienced APOs showed a reduction in gut P. merdae levels and an elevation in serum BCAAs, suggesting their potential association with APOs occurrence. Further analysis revealed increased Ile levels in the endometrial tissue of PCOS (P &amp;lt; 0.05) and higher proportions of cells positive for senescence markers (P21, P16, IL6, and IL1β), indicating aggravated cellular senescence, particularly in endometrial stromal cells (ESCs). ESCs from PCOS patients displayed classical senescence features, including proliferation loss, increased SA-β-Gal activity, cell cycle arrest, and elevated ROS levels. The accumulation of senescent ESCs in PCOS endometrium ultimately resulted in a disrupted decidualization process, which was exacerbated by increasing concentrations of Ile supplementation. Limitations, reasons for caution However, we must acknowledge certain limitations of this study. While our study makes a significant contribution to existing scientific knowledge, it is crucial to validate these findings in diverse populations. In addition, clinical translatability of biomarkers needs further exploration. Wider implications of the findings This study highlights gut microbiota-metabolite crosstalk as a novel axis influencing reproductive health in PCOS. Moreover, the identification of P. merdae and BCAAs as potential biomarkers for PCOS patients and the associated APOs risk opens up new avenues for risk stratification and personalized interventions. Trial registration number No

36. Primary Care Provider Behaviors, Attitudes and Beliefs In the Diagnosis and Management of Polycystic Ovary Syndrome in Adolescents

The aim of this study was to investigate whether women with polycystic ovary syndrome (PCOS) had a unique metabolomic profile that was different from controls and to assess the feasibility of a definitive study. Twelve women with PCOS and 10 healthy women as controls had measurements of demographic and anthropometric data, venepunctures and assays on plasma samples for metabolomic profiles using hydrogen-1, nuclear magnetic resonance ((1)H NMR) spectroscopy. There did not appear to be any clear differences between the metabolomic profiles of women with PCOS compared with controls when the NMR spectra were visually inspected and initial principal component analysis showed only a subtle differentiation between the two groups which was spread over three principal components. However, 'supervised' data analysis in the form of partial least-squares discriminant analysis (PLS-DA) and non-parametric univariate analysis allowed a stable PLS-DA model to be built, which appeared to differentiate between the two groups in a robust manner. Peak assignments for those spectral regions which appeared to differentiate between control and PCOS were consistent with amino acids (arginine, lysine, proline, glutamate and histidine), organic acids (citrate) and potentially lipids (CH(2)-CH(2)-C=C) with significant decreases noted in the levels of citrulline, lipid (CH(2)-CH(2)-C=C), arginine, lysine, ornithine, proline, glutamate, acetone, citrate and histidine in PCOS compared with controls. Women with PCOS may have a unique metabolomic finger print and a definitive study is feasible. These findings may enable sample size calculations for confirmatory studies and stimulate further research using metabolomics to improve the understanding and management of PCOS.

Do contraception use, pregnancy outcome and number of children differ in women with and without polycystic ovary syndrome (PCOS)? Women with PCOS were less likely to report use of contraception and more likely to report a miscarriage, whilst number of children was similar between groups. The oral contraceptive pill is used in the management of PCOS, but the patterns of contraception use in women with PCOS is not known. In women with PCOS who undergo assisted reproduction, the risk of pregnancy loss appears higher, yet pregnancy loss and family size among community-based women with PCOS is not known. This is a cross-sectional analysis of a longitudinal cohort study. Mailed survey data were collected at five time points (years 1996, 2000, 2003, 2006 and 2009). Data from respondents to Survey 4 (2006), aged 28-33 (n = 9145, 62% of the original cohort aged 18-23 years) were analysed. This study was conducted in a general community setting. Data from participants who responded to the questions on PCOS, contraception and pregnancy outcome were analysed. The main outcome measures were self-reported PCOS, body mass index (BMI), contraception use, pregnancy loss and number of children. In women aged 28-33 years, women with PCOS were less likely to be using contraception (61 versus 79%, P < 0.001) and more likely to be trying to conceive (56 versus 45%, P < 0.001), compared with women not reporting PCOS. A greater proportion of women with PCOS reported pregnancy loss (20 versus 15%, P = 0.003). PCOS was not independently associated with pregnancy loss; however, BMI was independently associated with pregnancy loss in the overweight and obese groups (OR 1.2, 95% CI 1.04-1.4, P = 0.02 and OR 1.4, 95% CI 1.1-1.6, P = 0.001, respectively). Fertility treatment use was also independently associated with pregnancy loss (adjusted OR 3.2, 95% CI 2.4-4.2, P < 0.001). There was no significant difference in number of children between women with and without PCOS. PCOS, contraception use and pregnancy outcome data were self-reported. Attrition occurred, but is reasonable compared with similar longitudinal cohort studies. This community-based cohort aged 28-33 years provides insights into the contraceptive use, pregnancy loss and family size of a large cohort of unselected women. Women reporting PCOS had lower rates of contraception use and were more likely to be currently trying to conceive, suggesting that they may be aware of potential fertility challenges, yet in those not planning to conceive, contraceptive use was low and further education may be required. Despite prior reports of higher rates of pregnancy loss in PCOS, usually from infertility services, in this community-based population, PCOS was not independently associated with pregnancy loss, yet independent risk factors for pregnancy loss included higher BMI, were higher in PCOS. The number of children per woman was similar in the both groups, albeit with more infertility treatment in PCOS. This may reassure women with PCOS that with access to fertility treatment, family sizes appear similar to women not reporting PCOS.

The impact of high-intensity interval training on insulin resistance, oxidative stress, and muscle function in a PCOS rat model.

BackgroundAcne vulgaris is one of the most common dermatological conditions worldwide, particularly affecting women of reproductive age. It is often linked to underlying hormonal imbalances, including those seen in polycystic ovary syndrome (PCOS). PCOS is a prevalent endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which contribute to acne vulgaris development. This systematic review and meta-analysis aimed to estimate the global prevalence of acne vulgaris among women with PCOS and identify contributing factors, thereby highlighting the burden of this skin condition in the context of a common endocrine disorder. Methods In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, a systematic review of cross-sectional studies was conducted to assess the prevalence of acne vulgaris among women with PCOS. The literature search included studies published up to January 2025 and was performed in 5 major databases: PubMed, EMBASE, Scopus, Web of Science, and Google Scholar. Study selection was guided by the POLIS framework, focusing on women diagnosed with PCOS based on established criteria (Rotterdam, National Institute of Health [NIH], or Androgen Excess Society [AES]). Only cross-sectional studies reporting the prevalence of acne vulgaris in this population were included. A random-effects (REM) meta-analysis was performed using data from 95 eligible studies. Subgroup analyses were conducted based on geographical region, age, body mass index (BMI), PCOS diagnostic criteria, and acne vulgaris severity to explore sources of heterogeneity.Results As per the findings, acne vulgaris, the pooled prevalence of which was 49% (95% CI: 47%-52%), determined 95 studies, with high heterogeneity (I² = 98.86%, P = 0.04) and evidence of publication bias (P < 0.001), remained the most frequent comorbidity in women with PCOS. However, after trim and fill adjustment, the prevalence fell to 37% (95% CI: 35%-39%). The subgroup analyses also revealed the prevalence of the highest in Oceania (76%, 95% CI: 69%-83%), whereas the prevalence of adolescents <18 years was 66%, 95% CI: 49%-81%, and less in Europe (32%, 95% CI: 28%-36%) and women >30 years (42%, 95% CI: 38%-46%), respectively. The rate was somewhat higher among women with a BMI ≤25 kg/m2 (53%) in comparison with those with a BMI of >25 kg/m2 (48%). Mild acne vulgaris scored the most (40%, 95% CI: 27%-53%) among the research participants.ConclusionThe prevalence of acne vulgaris among women with PCOS varies widely across studies, with subgroup analyses revealing a range influenced by factors such as region, age group, and diagnostic criteria. These findings highlight the need for standardized diagnostic tools for PCOS and comprehensive management approaches that address hormonal, metabolic, and psychological aspects to improve outcomes for affected women.

Management of Polycystic Ovarian Syndrome: A Qualitative Inquiry among Complementary and Alternative Medicine Practitioners in South Africa.

Polycystic Ovarian Syndrome (PCOS) is one of the most common hormonal issues which affects most of the women among reproductive years which can lead to infertility, miscarriages, irregular menstrual cycles, and excessive facial hairs. Infertility, obesity, lipid metabolism problems, and insulin resistance all are the major causes of PCOS. Its diagnosis is done with the help of ultrasound and blood hormonal tests. Asia, Europe, and the Mediterranean region are home to fenugreek. Fenugreek may regulate estrogen and testosterone levels, which is effective against PCOS. In women with polycystic ovary syndrome, fenugreek improved body weight, number of ovarian cysts, ovary size, irregular hair growth, and monthly regularity. This evaluates the impact of fenugreek on insulin resistance in PCOS- affected women. Sonographic results and menstrual cycle are improved in PCOS women receiving adjuvant therapy to the fenugreek seed extract. The effectiveness of a patented, standardized Trigonella foenum- graecum extract (Furocyst®) as a phytotherapeutic for the efficient management of PCOS is reported. Thus, fenugreek seeds act as functional foods that can give various health related benefits beyond basic nutrition. The aim of this study is to highlight the therapeutic effects of fenugreek seeds in the management of PCOS.

Lower serum apelin levels in women with polycystic ovary syndrome