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The subject of polycystic ovary syndrome (PCOS) has been extensively covered in the literature; however, there is a paucity of data regarding eumenorrheic women with hyperandrogenism and/or hyperandrogenemia without ultrasound evidence of PCO morphology (EuHyperA), and even less data on the comparison between PCOS and EuHyperA subjects. It has previously been shown that around half of PCOS women exhibit a hyper-response of serum 17-hydroxy-progesterone (17-OHP) to the stimulation by GnRH-agonists, also indicated as functional ovarian hyperandrogenism (FOH). Often, this stimulation test is preceded by suppression of the adrenal steroidogenesis with oral dexamethasone (Dex). FOH has been associated with an increase of the P450c17 activity in the ovaries driven by elevated insulin levels. Interestingly, treatment of women with PCOS with Dex suppression and GnRH-agonist stimulation (buserelin) highlighted the possible existence of two clusters of patients: hyper-responders (HR) and normal responders (NR). In this retrospective study, we included 15 hyper-responders (HR) EuHyperA, 34 normal responders (NR) EuHyperA, 62 HR-PCOS and 45 NR-PCOS. The demographic characteristics, glucose-metabolism indices, and the hormonal response to Dex or buserelin were analyzed, with both intra-group and inter-group comparisons performed. The rate of FOH was significantly greater in PCOS than EuHyperA women. Compared to HR-PCOS, HR-EuHyperA had [i.] significantly greater age at observation; [ii.] lower cortisol, 17-OHP, Δ4-androstenedione (Δ4-ASD), total testosterone (TT), LH, and buserelin-stimulated whole curve of dehydroepiandrosterone sulfate (DHEAS), 17-OHP, Δ4-ASD and TT. Compared to NR-PCOS, NR-EuHyperA had [i.] significantly greater FSH, and buserelin-stimulated whole curve of DHEAS; [ii.] significantly lower post-HD Dex Δ4-ASD, TT, buserelin-stimulated whole curve of 17-OHP, Δ4-ASD and TT. Compared to NR-PCOS, HR-PCOS had [i.] significantly greater body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), cortisol, DHEAS, Δ4-ASD, TT, FT, FAI, E2, and insulin AUC0-120min (area under the curve) at oral glucose tolerance test (OGTT); [ii] higher levels of post-LD and post-HD Dex 17-OHP, Δ4-ASD, TT, post-HD Dex DHEAS (with greater levels indicating weaker adrenal suppression), whole curve of DHEAS, 17-OHP, Δ4-ASD, TT and LH; [iii] significantly lower sex-hormone binding globulin (SHBG). Even if most of the parameters evaluated were statistically similar in the two sets of comparisons, interesting differences were observed. Women with PCOS exhibit higher androgen levels at baseline, after adrenal suppression and at the buserelin test, further to a higher ovarian volume. Of note, the percentage of women with HOMA-IR≥2.5 and serum insulin levels were greater in PCOS group compared to EuHyperA women. Moreover, within women with PCOS, the HR subgroup has higher insulin levels compared to the NR subgroup, when OGTT is performed. The alteration of the glucose-insulin balance and elevation of circulating androgens were more pronounced in PCOS, thus indicating that [i.] metabolic alterations might be crucial in the onset of PCOS itself and, [ii] EuHyperA might represent a milder form of PCOS.
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Androgen excess is a key feature of several clinical phenotypes of polycystic ovary syndrome (PCOS). However, the presence of FSH receptor (FSHR) and aromatase (CYP19A1) activity responses to physiological endocrine stimuli play a critical role in the pathogenesis of PCOS. Preliminary data suggest that myo-Inositol (myo-Ins) and D-Chiro-Inositol (D-Chiro-Ins) may reactivate CYP19A1 activity. We investigated the steroidogenic pathway of Theca (TCs) and Granulosa cells (GCs) in an experimental model of murine PCOS induced in CD1 mice exposed for 10 weeks to a continuous light regimen. The effect of treatment with different combinations of myo-Ins and D-Chiro-Ins on the expression of Fshr, androgenic, and estrogenic enzymes was analyzed by real-time PCR in isolated TCs and GCs and in ovaries isolated from healthy and PCOS mice. Myo-Ins and D-Chiro-Ins, at a ratio of 40:1 at pharmacological and physiological concentrations, positively modulate the steroidogenic activity of TCs and the expression of Cyp19a1 and Fshr in GCs. Moreover, in vivo, inositols (40:1 ratio) significantly increase Cyp19a1 and Fshr. These changes in gene expression are mirrored by modifications in hormone levels in the serum of treated animals. Myo-Ins and D-Chiro-Ins in the 40:1 formula efficiently rescued PCOS features by up-regulating aromatase and FSHR levels while down-regulating androgen excesses produced by TCs.
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Aromatase , Modelos Animais de Doenças , Inositol , Ovário , Síndrome do Ovário Policístico , Receptores do FSH , Feminino , Animais , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/tratamento farmacológico , Inositol/farmacologia , Camundongos , Aromatase/metabolismo , Aromatase/genética , Receptores do FSH/metabolismo , Receptores do FSH/genética , Ovário/metabolismo , Ovário/efeitos dos fármacos , Ovário/patologia , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Células Tecais/metabolismo , Células Tecais/efeitos dos fármacos , Esteroides/biossínteseRESUMO
Background: Human papilloma virus (HPV) infection and the management of its persistence is still a great medical challenge. Recently, scientific evidence has supported the potential therapeutic effects of four combined natural molecules-epigallocatechin gallate (EGCG), folic acid, vitamin B12 and hyaluronic acid (HA)-in counteracting HPV DNA positivity and related cytological lesions. Methods: Each patient of these five clinical cases had persistent HPV positivity in the anogenital site and assumed a dietary supplement based on a combination of 200 mg of EGCG, 50 mg of HA, 1 mg of vitamin B12 and 400 mcg of folic acid (Pervistop®, Farmares s.r.l., Rome, Italy) at a dosage of 1 or 2 caps/day for 6 or 3 months, respectively, depending on clinical history. Results: After treatment, all the patients reported a negative HPV DNA test and improved cytological lesions, thus demonstrating the ability of these combined molecules to counteract both anal and cervical HPV infection and related manifestations. Conclusions: Overall, these data corroborate previous evidence about the effectiveness of such natural molecules in the management of HPV infection and its persistence. Naturally, further studies with a larger population and long-term follow-up will contribute to reinforce the positive effects of this dietary supplement in counteracting HPV infection.
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Polycystic ovary syndrome (PCOS) is defined as the combination of polycystic morphology, hyperandrogenism, and ovulatory disruption; this heterogeneity presents a conundrum for the medical community. The Rotterdam criteria have governed the diagnosis of PCOS, separating the patient cohort into four distinct phenotypes. It has been suggested that the lone normoandrogenic phenotype, so-called phenotype D, should not be classified as a PCOS subtype, with phenotypes A, B, and C displaying a hyperandrogenic biochemical and clinical profile thought to be characteristic of PCOS. To understand how to treat phenotype D patients, this review shines a spotlight on the phenotype, gathering various reports of how phenotype D is differentiated from the other PCOS phenotypes.
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Hiperandrogenismo , Fenótipo , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/diagnóstico , Feminino , Hiperandrogenismo/diagnósticoRESUMO
BACKGROUND:
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Inositol , Resistência à Insulina , Obesidade , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Humanos , Inositol/uso terapêutico , Resistência à Insulina/fisiologia , Androgênios/deficiência , Aromatase , Estrogênios/deficiênciaRESUMO
SETTING: Insulin resistance (IR) and compensatory hyperinsulinemia are considered contributing factors toward polycystic ovary syndrome (PCOS). OBJECTIVES: This study evaluates the frequency of metabolic abnormalities in PCOS patients and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio on hormonal and metabolic parameters. PARTICIPANTS: Thirty-four women with PCOS phenotype A (endocrine-metabolic syndrome [EMS-type 1]) between the ages of 20-40. DESIGN: Open prospective study with phenotype A (EMS-type I, n = 34) supplemented with 2,255 mg/day of inositol (MI and DCI in a 40:1 ratio) for 3 months. METHODS: The following were measured before and after treatment: serum levels of follicular stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), anti-Müllerian hormone, glucose, insulin, HOMA-IR, and body mass index (BMI). RESULTS: 55.9% of the enrolled patients were overweight or obese, 50% affected by IR, 17.6% with a history of gestational diabetes mellitus, and 61.8% had familial diabetes mellitus. At the conclusion of the study, BMI (p = 0.0029), HOMA-IR (p < 0.001) significantly decreased, along with decreased numbers of patients with elevated insulin levels. The supplementation resulted in decreased total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001); increased SHBG (p < 0.001) and estradiol (p < 0.001). LIMITATIONS: The present analysis was limited to a 12-week follow-up, which precluded a long-term evaluation of the effects of MI and DCI combination. Also, this period was insufficient to achieve and analyze clinical changes such as restoration of the menstrual cycle, restoration of reproductive function, and clinical manifestations of hyperandrogenism. CONCLUSIONS: Supplementation improved metabolic and hormonal profile in PCOS phenotype A (EMS-type I) patients. This builds upon previous work that demonstrated that combined inositol treatment may be effective in PCOS. The study presented herein, used a reduced concentration than in prior literature; however, a significant change in hormonal and metabolic parameters was still observed.
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Resistência à Insulina , Síndrome do Ovário Policístico , Feminino , Humanos , Adulto Jovem , Adulto , Inositol/uso terapêutico , Inositol/farmacologia , Estudos Prospectivos , Hormônio Luteinizante , Insulina , Estradiol , Testosterona , Fenótipo , MetabolomaRESUMO
INTRODUCTION: This Expert Opinion covers recent updates in the use of Inositol in polycystic ovary syndrome (PCOS) and type II diabetes and gives support to researchers and clinicians. AREAS COVERED: This article discusses the role of Myo-Inositol (MI) and D-Chiro-Inositol (DCI) in physiological function, the use of MI in PCOS, the risks of using DCI in reproductive conditions, the 40:1 combination of MI/DCI in PCOS. Furthermore, we discuss the issues of insulin resistance and how α-lactalbumin may increase the intestinal bioavailability of MI. The paper then transitions to talk about the use of inositols in diabetes, including type II diabetes, Gestational Diabetes Mellitus (GDM), and double diabetes. Literature searches were performed with the use of PubMed, Google Scholar, and Web of Science between July and October 2023. EXPERT OPINION: Inositol therapy has grown in the clinical field of PCOS, with it demonstrating an efficacy like that of metformin. The use of α-lactalbumin has further supported the use of MI, as issues with intestinal bioavailability have been largely overcome. In contrast, the effect of inositol treatment on the different PCOS phenotypes remains an outstanding question. The use of inositols in type II diabetes requires further study despite promising analogous data from GDM.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Resistência à Insulina , Síndrome do Ovário Policístico , Gravidez , Feminino , Humanos , Inositol/farmacologia , Inositol/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Lactalbumina/uso terapêuticoRESUMO
Inositols are insulin-sensitizing compounds of promising efficacy in the management of polycystic ovary syndrome (PCOS). On the one hand, myo-inositol (myo-ins) plays a regulatory role in male and female reproductive function, influencing the development of oocytes, spermatozoa, and embryos. On the other hand, high concentrations of D-chiro-inositol (D-chiro-ins) in the ovary may adversely affect oocyte quality. This review analyses the available literature, which encourages the clinical use of myo-ins in assisted reproductive technologies (ARTs) due to its beneficial effects on female and male reproduction.
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Inositol , Síndrome do Ovário Policístico , Masculino , Feminino , Humanos , Inositol/uso terapêutico , Técnicas de Reprodução Assistida , Síndrome do Ovário Policístico/tratamento farmacológico , Oócitos , InsulinaRESUMO
OBJECTIVES: Luteinizing hormone (LH) plays a key role in normal follicular development and oocyte maturation in controlled ovarian stimulation. LH stimulates the proliferation and differentiation of theca cells for the secretion of androgens, synergistically increasing estrogen production. This study aimed to investigate the effects of low LH concentrations on oocyte retrieval, fertilization, and embryo development in patients undergoing in vitro fertilization/intracytoplasmic sperm injection. DESIGN: We prospectively (ClinicalTrials ID: NCT05755529) analyzed patients undergoing in vitro fertilization/intracytoplasmic sperm injection, subdividing them into three groups according to their age. Serum LH levels were evaluated on day 3, during stimulation (day 10) and before ovulation induction (day 12). PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty-three consecutive women were scheduled for IVF and received ovarian stimulation with follitropin alfa (Gonal F, Merck Serono, Germany) and ganirelix (Fyremaldel, Sun Pharma, Italy). Statistical analysis was performed with InStat 3.10, GraphPad software, San Diego, CA, USA. Normal distribution was tested by the Shapiro-Wilk test. Continuous variables were expressed as the mean and standard deviation. Categorical variables are expressed as frequencies and percentages. RESULTS: Our data analysis suggests that serum LH levels progressively decrease during controlled ovarian stimulation, and this effect is more evident in the early phase of this procedure. From this perspective, circulating LH levels may significantly decrease during the late follicular phase due to the negative feedback of ovarian hormones from multiple follicular developments or after the suppressive effects of gonadotropin-releasing hormone antagonists. LIMITATIONS: Although our study confirms that exogenous LH can be considered a strategy in women with reduced LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome, the generalizability of the results is limited by the low number of participants enrolled. CONCLUSIONS: Exogenous LH may be considered a strategy in women with a decrease in LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome.
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Recuperação de Oócitos , Sêmen , Humanos , Feminino , Masculino , Gravidez , Estudos Prospectivos , Hormônio Luteinizante , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina , Indução da Ovulação/métodos , Estudos de Coortes , Fertilização , Taxa de GravidezRESUMO
Accumulating evidence suggests that oral supplementation with myo-Inositol (myo-Ins) is able to reduce the amount of gonadotropins and days of controlled ovarian hyperstimulation (COS) necessary to achieve adequate oocyte maturation in assisted reproduction technology (ART) protocols, particularly in women affected by polycystic ovary syndrome (PCOS). We used computational calculations based on simulation modellings. We simulated in vitro fertilization (IVF) procedures-with or without intracytoplasmic sperm injection (ICSI)-with 100,000 virtual patients, accounting for all the stages of the entire IVF procedure. A Monte Carlo technique was used to account for data uncertainty and to generate the outcome distribution at each stage. We considered virtual patients with PCOS undergoing IVF cycles to achieve pregnancy. Computational data were retrieved from clinical experience and published data. We investigated three parameters related to ART protocols: cost of single procedure; efficacy to achieve ongoing pregnancy at 12 gestational weeks; overall cost per single pregnancy. The administration of oral myo-Ins during COH protocols, compared to the standard COH with recombinant Follicle Stimulating Hormone (rFSH) only, may be considered a potential strategy to reduce costs of ART for the Italian Health System.
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Síndrome do Ovário Policístico , Masculino , Gravidez , Humanos , Feminino , Análise Custo-Benefício , Sêmen , Hormônio Foliculoestimulante , Fertilização in vitro/métodos , Inositol/uso terapêutico , Taxa de GravidezRESUMO
Precise diagnoses are essential for defining appropriate treatments. This is particularly true for polycystic ovary syndrome (PCOS), whose phenotypical manifestations have recently suggested a possible diversity of etiological factors. PCOS is defined on the basis of gynecological and endocrinological alterations, but the patients often display considerable metabolic impairments, such as insulin resistance, that may worsen typical symptoms. The Rotterdam criteria fail to address this aspect, and the medical community has recently started to consider them as misleading diagnostic tools, casting doubts on whether the term PCOS is suited to describe all the clinical manifestations observed. This Opinion collects and critically discusses the scientific reports that question the definition of PCOS, calling for a revision of the current diagnostic criteria.
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Background-Pregnancy represents a nutritional challenge, since macro- and micronutrients intake can affect mother' health and influence negative outcomes. The aim of this retrospective pilot study is to evidence whether the oral supplementation with high molecular weight hyaluronic acid (HMWHA), in association with alpha lipoic acid (ALA), magnesium, vitamin B6 and vitamin D, in pregnant women, could reduce adverse effects, such as PTB, pelvic pain, contraction and hospitalization. Methods-Data were collected from n = 200 women treated daily with oral supplements of 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6 and 50 mcg vitamin D (treatment group) and from n = 50 women taking with oral supplements of 400 mg magnesium (control group). In both groups, supplementation started from the 7th gestational week until delivery. Results-Oral treatment with HMWHA, in association with ALA, magnesium, vitamin B6 and vitamin D in pregnant women, significantly reduced adverse events, such as PTB (p < 0.01), pelvic pain and contractions (p < 0.0001), miscarriages (p < 0.05) and admission to ER/hospitalization (p < 0.0001) compared with the control group. Conclusions-Despite HMWHA having been poorly used as a food supplement in pregnant women, our results open a reassuring scenario regarding its oral administration during pregnancy.
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The primary control of dysmetabolic patients is extremely challenging worldwide, with inadequate dietary habits and sporadic physical activity among the key risk factors for metabolic syndrome onset. Nowadays, there is no exclusive treatment for this condition, and considering that preventive measures usually fail, new therapeutic approaches need to be proposed and investigated. This present pilot study compared the effects of diet alone and in association with a combination of myo-inositol and d-chiro-inositol in their 40:1 ratio, α-lactalbumin, and Gymnema sylvestre on different metabolic parameters in obese dysmetabolic patients. To this purpose, 37 patients with BMI between 30 and 40 and fasting blood glucose between 100 and 125 mg/dL were divided into two groups: (i) the control group followed a hypocaloric Mediterranean diet, (ii) while the study group was also supplemented with a daily dosage of two sachets, each one containing 1950 mg myo-inositol, 50 mg d-chiro-inositol, 50 mg α-lactalbumin, and 250 mg Gymnema Sylvestre. After a 6-month treatment, all parameters improved in both groups. Nevertheless, the treated group experienced a greater improvement, especially concerning the variation from the baseline of HOMA index, triglycerides, BMI, body weight, and waist circumference. These findings support the supplementation with myo-inositol and d-chiro-inositol in the 40:1 ratio, α-lactalbumin, and Gymnema sylvestre as a therapeutical strategy to potentiate the beneficial effects induced via dietary programs in dysmetabolic patients.
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Gymnema sylvestre , Síndrome do Ovário Policístico , Humanos , Feminino , Lactalbumina/metabolismo , Inositol/uso terapêutico , Projetos Piloto , Dieta , Obesidade/complicações , Obesidade/tratamento farmacológico , Peso Corporal , MetabolomaRESUMO
Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS.
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BACKGROUND: The aim of the present study is to investigate the effects produced by a treatment with myo-Inositol (myo-Ins) in women presenting polycystic ovary syndrome (PCOS) of different phenotypes. METHODS: We performed a retrospective study to evaluate whether patients presenting different PCOS phenotypes, treated for 6 months with myo-Ins, might exhibit a differential response to the treatment. On this premise, we clustered women with PCOS phenotypes A, B, and C in the first study group (hyperandrogenic PCOS or H-PCOS), and women presenting PCOS phenotype D in a separate study group (non-hyperandrogenic PCOS or NH-PCOS) to evaluate if the presence of hyperandrogenism, shared by H-PCOS, might imply a metabolic/endocrine condition rather than a gynecological issue. RESULTS: The administration of myo-Ins induced a significant improvement in metabolic and endocrine parameters in H-PCOS, while the effects on NH-PCOS were negligible. Additionally, myo-Ins treatment improved the endometrial thickness of H-PCOS. CONCLUSIONS: Subjects selected for the study exhibited a differential response to myo-Ins therapy according to their PCOS phenotypes. The data suggest that the same treatment might not equally improve the parameters of the PCOS condition in each sub-group of patients. It is crucial to distinguish the various phenotypes to properly select the therapeutical approach.
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Epithelial-Mesenchymal Transition (EMT), triggered by external and internal cues in several physiological and pathological conditions, elicits the transformation of epithelial cells into a mesenchymal-like phenotype. During EMT, epithelial cells lose cell-to-cell contact and acquire unusual motility/invasive capabilities. The associated architectural and functional changes destabilize the epithelial layer consistency, allowing cells to migrate and invade the surrounding tissues. EMT is a critical step in the progression of inflammation and cancer, often sustained by a main driving factor as the transforming growth factor-ß1 (TGF-ß1). Antagonizing EMT has recently gained momentum as an attractive issue in cancer treatment and metastasis prevention. Herein, we demonstrate the capability of myo-inositol (myo-Ins) to revert the EMT process induced by TGF-ß1 on MCF-10A breast cells. Upon TGF-ß1 addition, cells underwent a dramatic phenotypic transformation, as witnessed by structural (disappearance of the E-cadherin-ß-catenin complexes and the emergence of a mesenchymal shape) and molecular modifications (increase in N-cadherin, Snai1, and vimentin), including the release of increased collagen and fibronectin. However, following myo-Ins, those changes were almost completely reverted. Inositol promotes the reconstitution of E-cadherin-ß-catenin complexes, decreasing the expression of genes involved in EMT, while promoting the re-expression of epithelial genes (keratin-18 and E-cadherin). Noticeably, myo-Ins efficiently inhibits the invasiveness and migrating capability of TGF-ß1 treated cells, also reducing the release of metalloproteinase (MMP-9) altogether with collagen synthesis, allowing for the re-establishment of appropriate cell-to-cell junctions, ultimately leading the cell layer back towards a more compact state. Inositol effects were nullified by previous treatment with an siRNA construct to inhibit CDH1 transcripts and, hence, E-cadherin synthesis. This finding suggests that the reconstitution of E-cadherin complexes is an irreplaceable step in the inositol-induced reversion of EMT. Overall, such a result advocates for the useful role of myo-Ins in cancer treatment.
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Asthma is a heterogeneous inflammatory disease characterized by abnormalities in immune response. Due to the inherent complexity of the disease and the presence of comorbidities, asthma control is often difficult to obtain. In asthmatic patients, an increased prevalence of irregular menstrual cycles, infertility, obesity, and insulin resistance has been reported. Given that these conditions are also common in patients with polycystic ovary syndrome (PCOS), we propose the definition of "asthma-PCOS overlap syndrome" to indicate a medical condition which shares characteristics of both diseases. The aim of this review is to analyze the links between asthma and PCOS and evaluate the therapeutic role of myo-inositol, a natural compound currently utilized in patients with PCOS, in the management of asthma patients.