Obesity is a multifactorial condition that profoundly affects female reproductive health through endocrine, metabolic, and inflammatory mechanisms that disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Women with obesity frequently develop menstrual irregularities, anovulation, amenorrhea, infertility, polycystic ovary syndrome (PCOS), impaired endometrial receptivity, and adverse pregnancy outcomes. Central obesity and insulin resistance contribute to hyperinsulinemia, reduced sex hormone-binding globulin (SHBG) levels, hyperandrogenism, altered gonadotropin secretion, and impaired folliculogenesis, while adipokines such as leptin and chronic inflammation further impair ovarian steroidogenesis and ovulatory function. Obesity-related oxidative stress and lipotoxicity also negatively affect oocyte quality, embryo development, implantation, and assisted reproductive technology outcomes, increasing the risk of gestational diabetes, preeclampsia, miscarriage, and preterm birth. This review evaluates the therapeutic potential of pharmacological weight-loss therapies in obesity-associated female reproductive dysfunction. A comprehensive literature review was conducted using various databases, focusing on anti-obesity pharmacotherapy on obesity, infertility and fertility in reproductive-aged women. Evidence suggests that several FDA-approved and off-label anti-obesity agents, including orlistat, liraglutide, semaglutide, phentermine/topiramate, bupropion/naltrexone, metformin, exenatide, and tirzepatide, may improve reproductive outcomes primarily indirectly through weight reduction and metabolic improvement. GLP-1 receptor agonists, particularly liraglutide, semaglutide, and exenatide, appear especially promising, demonstrating beneficial effects on insulin sensitivity, menstrual regularity, ovulation, androgen levels, and pregnancy rates in women with PCOS. Tirzepatide, a dual GLP-1/GIP receptor agonist, has shown potent weight-loss and metabolic effects with potential indirect fertility benefits. Metformin improves insulin sensitivity and is widely used in PCOS to regulate androgen levels and restore ovulation, although its effects on pregnancy and live birth rates remain controversial. However, evidence for several agents remains limited, and concerns persist regarding reproductive safety during pregnancy. Overall, anti-obesity pharmacotherapy may represent an important adjunctive strategy for improving reproductive and metabolic health in women with obesity, although larger randomized clinical trials are still required.

Polycystic ovarian syndrome (PCOS) is a common endocrine-metabolic condition characterized by persistent anovulation, and hormonal imbalance leading to disrupted follicular maturation, and overall ovarian dysfunction. This study aimed to investigate the regenerative effects of adipose-derived mesenchymal stem cell-derived exosomes (AD-MSCs-Exo) on ovarian restoration, and granulosa cells (GCs) functionality in a PCOS murine model. PCOS was induced via a single subcutaneous injection of estradiol valerate. Exosomes were isolated from AD-MSCs using the ExoCIB kit and characterized by DLS, TEM and flowcytometery. NMRI mice received intraperitoneal injection of AD-MSCs-Exo (25, 50, 75, and 100 µg/kg body weight) twice over a two-week period. Following treatment, the mice were anaesthesia and sacrificed by cervical dislocation. The harvested ovarian tissues were subjected to histological assessment; FSH, LH, and estradiol levels were measured from serum. Further, GCs were isolated, and identified through FSH expression. Subsequently, the levels of GCs key regulator genes including FOXO3, Map1lc3b, and SF-1 were assessed by qRT-PCR. AD-MSCs-Exosome-like nanovesicles isolated in range of 30-80 nm with bi-membrane spherical shape and 54.8% expression of CD9. The hormonal analysis revealed improved estradiol levels and a lowered LH/FSH ratio, indicating endocrine stabilization under exposure with AD-MSCs-Exo. In addition, treatment with AD-MSCs-Exo significantly improved ovarian histoarchitecture, and the optimum response was observed following exposure to 75 µg/kg of AD-MSCs-Exo. However, administration of the highest dose (100 µg/kg) was associated with inflammatory responses and partial tissue degeneration. Gene expression analysis also showed a marked up-regulation of FOXO3, along with increased Map1lc3b and SF-1 levels. Accordingly, AD-MSCs-Exosome like nanovesicles at optimum concentration exert regenerative effects on PCOS-induced ovarian dysfunction, which emphasizes the necessity for precise dose selection to achieve maximal therapeutic efficacy as a promising cell-free strategy for PCOS treatment.

In cattle, low progesterone (P4) concentrations have been linked to anovulation. To study the local effects of P4 on granulosa cells, in the present study we aimed: (a) to characterise the expression of receptors (progesterone receptor (PR), oestrogen receptors α and β (ERα and β), FSH receptor (FSHR) and LH receptor (LHR)), as well as the co-expression of PR and signal transducer and activator of transcription 5 (STAT5) and a cytochrome P450 aromatase A1 (CYP19A1), in a bovine granulosa cell line (BGC-1) sensitive to P4 stimuli; and (b) to evaluate the effects of P4 on cell viability, apoptosis and reactive oxygen species (ROS) production in BGC-1 cells after 12, 24 and 48 h of stimulation. BGC-1 cells expressed CYP19A1, as well as ERα and β, PR, FSHR and LHR. The mean fluorescence intensity of STAT5 and PR and the percentage of simple and double-positive cells (STAT5/PR) were lower in control cells than in P4-stimulated cells after 12, 24, and 48 h of stimulation. Regarding the effects of P4 on cell viability, after 12, 24, and 48 h of stimulation, the percentage of living cells was high and the number of apoptotic and necrotic cells was low. Finally, BGC-1 cells responded to P4 stimulation by stimulating ROS production, without inducing damage. These results support the potential use of P4-stimulated BCG-1 cells to study the mechanisms underlying follicular persistence in cows.

Women of reproductive age who suffer from polycystic ovarian syndrome (PCOS), a common and complex endocrine-metabolic illness, are characterized by hyperandrogenism, anovulation, insulin resistance, and persistent inflammation. Its multifaceted etiology includes psychological, environmental, genetic, and epigenetic variables. The potential of nutrigenomics in individualized treatment techniques is highlighted by new research that implicates gene-diet interactions in modifying PCOS susceptibility, phenotypic expression, and therapeutic results. Numerous gene polymorphisms, including those involving the fat mass and obesity-associated gene, methylenetetrahydrofolate reductase, and transcription factor 7-like 2, have been linked to insulin signaling, metabolic disorders, obesity risk, and hormonal imbalances in PCOS. At the same time, dietary bioactives such as flavonoids, omega-3 fatty acids, and folate have demonstrated anti-inflammatory, insulin-sensitizing, and epigenetic-modulating properties, suggesting that they may be utilized to target gene-nutrient interactions and mitigate illness. In order to maximize individualized nutritional therapy for PCOS, this review seeks to investigate integrative nutrigenomics approaches that incorporate dietary interventions with genetic profiling. The review offers a thorough synthesis of recent research by investigating the molecular mechanisms by which gene variations interact with functional nutrition. It determines possible nutraceutical targets for customized treatment. Additionally, the translational significance of these integrative methods is examined in enhancing precision nutrition in PCOS therapy, lowering metabolic risks, and improving clinical outcomes. However, this review underlines the need for an interdisciplinary approach that combines genetics, nutritional science, and clinical practice to promote evidence-based, patient-centric medications for PCOS.

Postmenopausal vaginal bleeding is reported by 90% of patients with a diagnosis of endometrial cancer. Risk factors for endometrial cancer include obesity, increasing age, type 2 diabetes, use of unopposed estrogen, polycystic ovary syndrome, chronic anovulation, and family history of gynecologic cancers. Evaluation includes a detailed history and physical examination, focusing on bleeding characteristics, pain, and vaginal discharge. First-line diagnostic tests include transvaginal ultrasonography to measure endometrial thickness and endometrial biopsy. If thickening or irregularities are observed on ultrasonography, further workup is indicated. In postmenopausal patients, an endometrial thickness of 4 mm or less has a negative predictive value greater than 99% for endometrial cancer. The risks and benefits of deferring endometrial biopsy should be discussed with the patient because some type 2 endometrial cancers can develop from atrophic endometrium and may progress more aggressively. Persistent uterine bleeding or a change in menstrual bleeding warrants inclusion of biopsy in the workup. Endometrial intraepithelial neoplasia, previously atypical endometrial hyperplasia, is clinically significant on pathology reports because it is considered a precursor for endometrioid adenocarcinoma, requiring urgent referral to gynecologic oncology. Family physicians play a critical role in early identification of endometrial cancer, clearing patients for surgery, and long-term surveillance.

Ovulatory failure in dairy cows can stem from various causes, including the formation of follicular cysts, which disrupt the estrous cycles and extend reproductive intervals, ultimately hindering herd management and reproductive performance. Reproductive dysfunctions are frequently associated with metabolic disorders, commonly observed in these animals. Therefore, this study aimed to evaluate key components of lipid metabolism, primarily related to β-oxidation, including AdipoR1, AdipoR2, AMPK, PPARγ, ObR, ACC1, CPT1, and ACOX1 in ovary, as well as adiponectin, leptin, triglyceride (TG) and non-esterified fatty acid (NEFA) concentrations in plasma and follicular fluid of dairy cows with induced persistent follicles, spontaneous follicular cysts and dominant control follicles. Ovary protein immunoexpression was assessed in situ by immunohistochemistry, plasma and follicular fluid adiponectin and leptin concentrations were quantified by ELISA, and TG and NEFA concentrations were determined by colorimetric methods. The results indicated increased protein expression of adiponectin receptors in follicles of 15 days of persistence, along with an upregulation of CPT1 expression. ACC1 expression was lower in both follicles of 15 days of persistence and in spontaneous cysts than in preovulatory follicles. Furthermore, PPARγ expression was decreased in follicles of 15 days of persistence compared to dominant control follicles. These findings indicate changes in key molecules involved in ovarian lipid metabolism, with a pronounced shift towards β-oxidation pathways and decreased lipid synthesis and lipid storage. Such metabolic disruptions may contribute to impaired ovarian function, potentially leading to ovulatory failure of the preovulatory follicle.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. The condition can have an enduring negative effect on women's reproductive health from menarche to menopause, although its impact can vary significantly. PCOS is associated with premature pubarche and a wider age range of menarche. Diagnosis of PCOS in adolescents remains challenging. Oligo/anovulation is the most common feature of PCOS, and leads to subfertility. This may require induction of ovulation with medical therapies, such as oestrogen receptor antagonists, aromatase inhibitors or by giving exogenous follicle-stimulating hormone, which are effective for most women with PCOS. Pregnancy in women with PCOS is associated with a higher risk of complications including gestational diabetes, particularly in those with obesity. Optimisation of pre-conception health, including weight management, is recommended in order to maximise fertility potential and improve pregnancy outcomes. The other key feature of PCOS is hyperandrogenism, which may contribute to ovulatory dysfunction and results in hirsutism and persistent acne, and also negatively impacts mental health, quality of life and psychosexual function. Women with PCOS may also have a later age of menopause, although longitudinal studies are lacking. This narrative review explores the impact of PCOS on women's reproductive health throughout their reproductive lifespan.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology (PCOM). Despite the widespread use of the Rotterdam criteria, challenges in diagnostic accuracy persist. Anti-Müllerian hormone (AMH), a glycoprotein secreted by ovarian follicles, has emerged as a promising biomarker for refining diagnosis due to its strong correlation with follicular count and elevated levels in women with PCOS. This review critically evaluates the advantages and limitations of incorporating AMH into PCOS diagnostic criteria. Elevated AMH levels are indicative of PCOM and anovulation, offering a non-invasive diagnostic tool that minimizes interobserver variability in ultrasound-based assessments. Additionally, AMH remains stable throughout the menstrual cycle and aligns with phenotypic diversity in PCOS, potentially supporting individualized management strategies. However, significant challenges remain. Variability in AMH assay methods, the absence of comparable cut-off values, and influences of age, ethnicity, and obesity on AMH levels limit its universal applicability. Additionally, AMH cut-offs for PCOS diagnosis, ranging from 3.5 to 5 ng/mL, raises questions about its clinical relevance, as there is not clear evidence of its biological significance. The review also highlights AMH's clinical utility in reproductive medicine, particularly in predicting ovarian response to stimulation, tailoring gonadotropin dosages, and optimizing assisted reproductive technology outcomes. While AMH holds promise as a complementary diagnostic criterion for PCOS, its fully integration into clinical practice requires further validation through standardized assays, population-specific cut-offs, and robust studies to address existing limitations. In conclusion, AMH harbours the potential to enhance the specificity and sensitivity of PCOS diagnosis, particularly in dubious cases. However, the inclusion of AMH in the current criteria for diagnosing PCOS still requires addressing methodological challenges and balancing its benefits against inherent limitations.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women at various stages of life, presenting a wide range of symptoms and health implications. The term "Polycystic Ovary Syndrome" can be misleading, prompting many within the medical community and advocacy groups to advocate for a name change. Critics argue that this terminology can complicate understanding and awareness of the disease among patients. The primary concern is that PCOS emphasizes the ovarian aspect, fostering the misconception that PCOS is merely a gynecological disorder. In reality, PCOS impacts multiple organ systems, particularly metabolic health. Patients frequently experience insulin resistance, weight gain, irregular menstrual cycles, and hirsutism-symptoms that extend beyond ovarian dysfunction. In light of these issues, there is increasing support for renaming PCOS to better reflect its systemic implications and minimize confusion. The current name may hinder understanding and potentially lead to inadequate disease management. Alternative names have been proposed, including "Ovarian Dysmetabolic Syndrome," which our team supports, as well as "Metabolic Reproductive Syndrome" and "Hyperandrogenic Persistent Ovulatory Dysfunction Syndrome." These alternatives aim to highlight the hormonal imbalances and metabolic disturbances associated with the condition, fostering inclusivity and reducing stigma for all affected individuals. This narrative review provides a historical overview of PCOS, tracing its recognition from early descriptions to contemporary guidelines. We discuss the evolving understanding of its pathophysiology and the rationale behind the proposed name change. By adopting a new nomenclature, we can enhance understanding among healthcare professionals, increase inclusivity for affected women, reduce the stigma and anxiety linked to the diagnosis, and offer a more accurate representation of the condition's complex pathophysiology.

One of the initial causes of cystic ovarian disease (COD) is a failure in the normal ovulation mechanism. This study aimed to characterize the populations of immune cells (T-lymphocytes, B-lymphocytes, monocytes-macrophages and granulocytes) present in the ovary of cows with COD and induced follicular persistence, and evaluate their relation with follicular persistence and cyst formation. The follicular persistence model was developed using a progesterone (P4) slow-release intravaginal device, to obtain subluteal concentrations of P4. Results evidenced that T-lymphocytes, B-lymphocytes and monocytes-macrophages in the cortex, medulla, and theca externa and interna of dominant follicles were higher in the control group than in the COD and all persistence groups. Granulocytes in the medulla and theca externa of dominant follicles were lower in the control group than in the COD group, and those in the cortex and medulla were lower in the control group than in the persistence groups. The presence of T-lymphocytes, B-lymphocytes and granulocytes in the follicular fluid was abundant, especially that of granulocytes, without differences between control and COD cows. These results suggest that the immune system potentially plays a role in the local mechanisms of COD pathogenesis in dairy cows. In spontaneous COD and in our follicular persistence model, the distribution of the cells studied was different from that in the control group. However, to our knowledge, this is the first report describing the presence of immune cells in bovine follicular fluid samples and the expression of steroid hormone receptors in infiltrating immune cells in the bovine ovary.