Search Results (72)

Objective: Vitamin D has been reported to act as a tissue-protective regulator by suppressing Matrix Metalloproteinases (MMPs) and upregulating Tissue Inhibitors of Metalloproteinases (TIMPs), though changes may be body mass index (BMI)-dependent; however, the relationship between vitamin D metabolism and matrix remodeling pathways in Polyendocrine Metabolic Ovarian Syndrome (PMOS) remains poorly understood. Methods: In women with PMOS (n = 28) and controls (n = 28), 12 MMPs and 3 TIMPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D₃ (25(OH)D₃) and its metabolites (active 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) and 24,25-dihydroxyvitamin D₃ (24,25(OH)₂D₃)) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Results: Insulin resistance and systemic inflammation (normal C-reactive protein) were comparable between PMOS and control women, though PMOS had higher free androgen index and anti-Mullerian hormone levels. Vitamin D and its metabolites did not differ between groups. Only MMP16 was lower in PMOS than controls (549.6 ± 58.3 vs. 678.0 ± 304.1 Relative Fluorescent Units, p = 0.037) but did not pass the false discovery rate. In women with PMOS, 25(OH)D₃ and 24,25(OH)₂D₃ demonstrated significant inverse correlations with TIMP3 (r = −0.60, p = 0.005 and r = −0.58, p = 0.007, respectively). Multivariable regression confirmed independent inverse associations between TIMP3 and both 25(OH)D₃ (β = −51.1, p = 0.031) and 24,25(OH)₂D₃ (β = −858.7, p = 0.028) after adjustment for age, body mass index and Homeostatic Model Assessment-Insulin Resistance, and the association remained stable following bootstrap internal validation. Additional moderate associations were observed between vitamin D metabolites and membrane-type MMPs (MMP14, MMP16, MMP17). Conclusions: Exploratory analyses suggested potential inverse associations between vitamin D metabolites and TIMP3, together with weaker associations involving MMP14, MMP16 and MMP17, suggesting the novel hypothesis that vitamin D may influence extracellular matrix remodeling and ovarian stromal biology through regulation of TIMP3-dependent pathways independently of obesity and insulin resistance, rather than through MMPs directly. Full article

Background: Vitamin D has traditionally been recognized for its role in calcium homeostasis and skeletal health, but vitamin D receptor expression and vitamin D-metabolizing enzymes have also been identified in extra-skeletal tissues, including components of the male reproductive tract. Observational evidence has suggested associations between vitamin D status and androgen-related markers; however, whether vitamin D supplementation has a measurable effect on androgen bioavailability remains uncertain. Objective: This systematic review and meta-analysis evaluated the effects of vitamin D supplementation on total testosterone (TT) and androgen bioavailability markers in adult men, including sex hormone-binding globulin (SHBG), free androgen index (FAI), calculated free testosterone (calculated FT), and bioactive testosterone (BAT) where methodologically compatible. Methods: The review was registered in PROSPERO (CRD420261365005) and conducted according to PRISMA 2020 and Cochrane methodological guidance. Searches were conducted from database inception to April 2026 in PubMed, Web of Science, Scopus, ClinicalTrials.gov, and the WHO ICTRP. Embase was initially planned but was not searched because institutional access was unavailable; this amendment was made before screening, extraction, risk-of-bias assessment, and synthesis. Records were deduplicated in Zotero, screened in a structured matrix, and converted from report-level records into independent comparison-level datasets where appropriate. Meta-analyses used random-effects REML models with Hartung–Knapp adjustment. Results: The official search set comprised 2854 records, of which 703 duplicates were removed, leaving 2151 records for title and abstract screening. The full-text screening file was reconciled to 162 PRISMA-countable reports/records: 135 reports were assessed, 27 reports could not be assessed because the full text was unavailable or had not been obtained for review, and 27 reports/studies were retained for qualitative synthesis. Eighteen reports were considered candidate sources for quantitative synthesis and were operationalized into 21 comparison-level records. The primary TT model included 11 comparisons and showed no clear effect of vitamin D supplementation on final TT (MD 0.47 nmol/L, 95% CI −0.50 to 1.44; I² = 24.1%). No clear effects were observed for SHBG (MD 0.27 nmol/L, 95% CI −2.14 to 2.68), FAI (MD −0.37, 95% CI −4.28 to 3.55), calculated FT sensitivity evidence (MD −0.0096 nmol/L, 95% CI −0.0525 to 0.0332), or BAT exploratory evidence (MD −0.47 nmol/L, 95% CI −1.77 to 0.83). GRADE certainty was low for TT, SHBG, and FAI, and very low for calculated FT and BAT. Conclusions: Current randomized evidence does not demonstrate a statistically clear or reproducible effect of vitamin D supplementation on total testosterone or androgen bioavailability markers in adult men. GRADE certainty was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone. Because directly measured and calculated free testosterone are not analytically equivalent, free testosterone was not pooled as a primary outcome; method-compatible calculated FT was handled as sensitivity evidence and BAT as exploratory evidence. Full article

Background/Objectives: Weight loss achieved through lifestyle interventions has been demonstrated to improve the clinical prognosis of female hyperandrogenism. However, the interplay between such interventions, androgens, and glucose–lipid metabolism remains heterogeneous. This study evaluated the effects of lifestyle-induced weight loss on glucose and lipid metabolism and androgen levels in Chinese women of reproductive age with hyperandrogenism and examined the association between the degree of weight loss and changes in androgen levels, glucose and lipid metabolism, exercise capacity, and dietary patterns. Methods: This observational study, based on real-world clinical settings, collected medical records of women of reproductive age with hyperandrogenism who underwent weight-loss interventions between July 2023 and September 2025. Correlation analysis employed Spearman’s rank correlation coefficient, whilst pre- and post-weight-loss comparisons utilised paired t-tests or Wilcoxon signed-rank tests. Results: After a follow-up of 6 to 7 months, a total of 66 participants achieved a mean weight loss of 5.67 ± 4.27 kg. Statistically significant reductions were observed in testosterone (0.40 ± 0.10 vs. 0.30 ± 0.10 ng/mL, p < 0.001), androstenedione (p < 0.001), and the free androgen index (p < 0.001). Glucose metabolism showed statistically significant improvement, with decreases in HOMA-IR (p = 0.040), fasting glucose (p = 0.001), and fasting/2 h postprandial insulin (p < 0.001). However, lipid profiles showed no statistically significant changes. Multiple linear regression revealed that change in testosterone was independently and inversely associated with change in apolipoprotein A1 (β = −0.496, p = 0.008), while change in dehydroepiandrosterone sulfate was inversely associated with change in fasting insulin (β = −0.357, p = 0.032). A non-linear, inverted U-shaped relationship was found between weight loss magnitude and change in sex hormone-binding globulin, with moderate weight loss (5–10%) yielding the greatest increase (p = 0.044). Marked weight loss (≥10%) was associated with the lowest follow-up fasting insulin levels (p = 0.039). Conclusions: Weight loss achieved through lifestyle interventions is associated with improvements in androgen levels and glucose metabolism, though its impact on lipid metabolism remains limited. The degree of improvement in insulin sensitivity correlates more strongly with the magnitude of weight reduction. Full article

Intermittent fasting (IF) has emerged as a popular dietary intervention with potential metabolic and endocrine benefits. However, its effects on sexual function and reproductive health remain incompletely understood. This comprehensive review synthesizes current evidence from human clinical trials and animal studies examining the impact of various IF protocols—including time-restricted eating (TRE), alternate-day fasting (ADF), and Ramadan fasting—on male and female sexual function, reproductive hormones, and fertility outcomes. In males, limited human data suggest preserved erectile function but reduced sexual desire during Ramadan fasting, with neutral effects on testosterone in obese adults undergoing TRE. Animal studies demonstrate context-dependent effects, with IF protecting against high-fat diet-induced reproductive dysfunction while potentially impairing spermatogenesis under prolonged energy restriction. In females, IF shows promise for improving hyperandrogenism and menstrual regularity in polycystic ovary syndrome (PCOS), mediated by enhanced insulin sensitivity and reduced free androgen index. However, direct measurements of female sexual function domains (libido, arousal, lubrication, orgasm) are largely absent from the literature. Mechanistic pathways involve modulation of the hypothalamic–pituitary–gonadal (HPG) axis, insulin–adipokine signaling, sex hormone-binding globulin (SHBG), and oxidative stress pathways. Evidence quality is limited by small sample sizes, heterogeneous protocols, short follow-up periods, and predominance of animal data. While IF may offer reproductive benefits in metabolically compromised populations, particularly women with PCOS, caution is warranted in young, lean, or energy-deficient individuals. Future research should employ standardized IF protocols, validated sexual function instruments, and long-term fertility endpoints to establish evidence-based clinical recommendations. Full article

Triple-negative breast cancer (TNBC), particularly the androgen receptor-low (AR-low) subtype, is one of the most aggressive and hard-to-treat forms of BC, characterized by a high index of proliferation, chromosomal instability (CIN), and high prevalence of TP53 mutations. These features fuel therapy resistance, metastases, and poor clinical outcomes. An integrated framework describing the dysregulated molecular networks that support the pathobiology of AR-low TNBC is lacking. Multiple published studies in breast cancer have previously proposed mechanistic links between TP53 loss, AR-low states, and heightened FOXM1-driven G2/M transcriptional programs, potentially via deregulation of E2F activity, chromatin-associated co-regulators (e.g., ATAD2), and disruption of repressive networks involving p53–p21–DREAM and SPDEF. Additional reports suggest that FOXM1-associated circuitry may be reinforced by chromatin regulators such as WDR5 and by mitotic/spindle factors such as ASPM, including through feedback interactions and condensate-associated transcriptional organization. We previously showed that FOXM1, a master regulator transcription factor, is upregulated and is a biomarker of poor prognosis in AR-low TNBC. In this study, we filtered a set of “TNBC core genes” known to promote transcriptional chaos downstream of FoxM1. We identified a set of 15 cell cycle regulators—including mitotic kinesin motors (KIF14, KIF11, KIF4A, KIF2C, and KIF20A), centromeric proteins (CENPA, CENPO, CENPL, CENPF, and OIP5), and regulators of proteolysis (UBE2C, UBE2S, UBE2T, PSMD14, and TUBA1B). These 15 genes, which were ranked highly among genes overexpressed in TNBC featured prominently in gene signatures of chromosomal instability and were also overexpressed among AR-low TNBCs and TP53-mutant breast tumors. We show that expression of each of these 15 genes correlates positively with proliferation markers (Ki67, PCNA, and MCM2) in TNBC, and that the overexpression of this gene set is associated with shorter relapse-free survival and distinct immune/stromal infiltration patterns. In light of prior work, our findings point to a FOXM1-associated 15-gene signature enriched in AR-low TNBC and associated with the high-proliferation and high-CIN phenotypes of this clinically challenging tumor type. This 15-gene set represents an actionable vulnerability with therapeutic potential for AR-low TNBC and provides a framework for rethinking how to manage highly proliferative, genomically unstable BCs. Full article

Objectives: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with diverse pathogenetic mechanisms and clinical manifestations. Phenotype D PCOS is characterized by oligomenorrhoea and polycystic ovaries without hyperandrogenism. Altered adipokine profiles may contribute to reproductive and metabolic disturbances. Chemerin is an adipokine involved in inflammatory and metabolic processes. It remains unclear whether altered chemerin levels in PCOS reflect metabolic dysfunction alone or are directly associated with hyperandrogenism. The aim of this study was to compare serum chemerin levels in women with normoandrogenic PCOS and a control group. Methods: This cross-sectional preliminary study included 49 women with phenotype D PCOS and 40 healthy, age- and body mass index (BMI)-matched controls. Anthropometric, biochemical, hormonal parameters, and serum chemerin concentrations were assessed. Results: Serum chemerin concentrations did not differ significantly between the groups. In the PCOS group, the 95% confidence interval ranged from 198.61 to 234.37, while in the controls, it ranged from 187.13 to 216.21. In women with PCOS, chemerin showed significant positive correlations with weight, BMI, waist and hip circumference, total adipose tissue, and both gynoid and android fat content. Positive correlations were also observed with highly sensitive C-reactive protein (hs-CRP), insulin, glucose, triglycerides, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and a negative correlation was found with high-density lipoprotein (HDL) cholesterol. Chemerin was weakly negatively correlated with sex hormone binding globulin (SHBG) and positively correlated with the free androgen index (FAI). In the control group, chemerin correlated positively with CRP, insulin, triglycerides, total and gynoid adipose tissue, and negatively correlated with HDL cholesterol and SHBG. Conclusions Although chemerin levels did not differ from controls, chemerin was associated with metabolic and inflammatory markers in both groups. These findings should be considered preliminary due to the limited sample size. Chemerin may reflect metabolic and inflammatory status rather than hyperandrogenism in normoandrogenic PCOS. Full article

Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and insulin resistance (IR) mediate this association. Methods: This retrospective study included 577 women diagnosed with PCOS at a tertiary academic center from 2010 to 2018. Clinical data included age at diagnosis, BMI, and diagnoses of hypertension, non-alcoholic fatty liver disease, and metabolic syndrome. Laboratory measures included total testosterone, sex hormone-binding globulin, anti-Müllerian hormone, luteinizing hormone, fasting glucose, insulin, and triglycerides (TG). Derived indices included a free androgen index (FAI), homeostasis model assessment of insulin resistance (HOMA-IR), and fasting glucose-to-insulin ratio. PTCs were identified through imaging or surgical findings. Structural equation modeling (SEM) assessed direct and indirect relationships between FAI, BMI, HOMA-IR, and PTCs, while adjusting for diagnostic age. Results: PTCs were identified in 2.77% of participants. BMI, FAI, TG, and IR indices were significantly higher for women with PTCs than those without PTCs. SEM revealed significant indirect effects of FAI on PTCs via BMI and HOMA-IR. The direct effect was negative, resulting in a non-significant total effect. A sensitivity model using HOMA-IR as the predictor showed a significant direct effect on PTCs without mediation via FAI. Conclusions: Biochemical HA may influence PTC development in PCOS through metabolic pathways, establishing the need to consider metabolic context when evaluating adnexal cysts in hyperandrogenic women. Full article

Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent evidence indicates that intermittent fasting (IF) could effectively enhance health outcomes and regulate circadian rhythm; however, its impact on PCOS remain unclear. Objective: Therefore, this systematic review and meta-analysis aims to examine the effect of IF on women diagnosed with PCOS. Methods: Comprehensive research was conducted across three major databases including PubMed, Scopus, and Web of Science without date restrictions. Meta-analysis was performed using Cochrane Review Manager Version 5.4 software. Results: Five studies fulfilled the inclusion criteria. IF significantly reduced body weight (MD = −4.25 kg, 95% CI: −7.71, −0.79; p = 0.02), BMI (MD = −2.05 kg/m², 95% CI: −3.26, −0.85; p = 0.0008), fasting blood glucose (FBG; MD = −2.86 mg/dL, 95% CI: −4.83, −0.89; p = 0.004), fasting blood insulin (FBI; MD = −3.17 μU/mL, 95% CI: −5.18, −1.16; p = 0.002), insulin resistance (HOMA-IR; MD = −0.94, 95% CI: −1.39, −0.50; p < 0.0001), triglycerides (TG; MD = −40.71 mg/dL, 95% CI: −61.53, −19.90; p = 0.0001), dehydroepiandrosterone sulfate (DHEA-S; MD = −33.21 μg/dL, 95% CI: −57.29, −9.13; p = 0.007), free androgen index (FAI; MD = −1.61%, 95% CI: −2.76, −0.45; p = 0.006), and C-reactive protein (CRP; MD = −2.00 mg/L, 95% CI: −3.15, −0.85; p = 0.006), while increasing sex hormone-binding globulin (SHBG; SMD = 0.50, 95% CI: 0.22, 0.77; p = 0.004). No significant changes were observed in waist-to-hip ratio (WHR), total cholesterol (TC), LDL, HDL, total testosterone (TT), or anti-Mullerian hormone (AMH). Conclusions: IF represents a promising strategy for improving weight and metabolic, hormonal, and inflammatory profiles in women with PCOS. However, the existing evidence remains preliminary, necessitating further robust studies to substantiate these findings. Full article

Background/Objectives: Acne vulgaris is a chronic skin infection characterized by high sebum secretion, keratosis around hair follicles, inflammation, and imbalance in androgen levels. Acne vulgaris causes permanent scars or skin pigmentation in cases of improper treatment. Oral or topical isotretinoin, contraceptives, and antibiotics are used to treat acne. Minocycline is one of the widely used tetracyclines for this purpose; it inhibits the synthesis of proteins in bacterial ribosomes. Commonly, minocycline is prescribed daily for several months for acne vulgaris. Systemic minocycline is highly distributed into body fluids, and it is associated with several side effects and antibiotic resistance. Additionally, minocycline is highly metabolized in the liver, leading to reduced bioavailability upon systemic delivery. This study aims to develop and characterize minocycline nanocrystals for targeted skin delivery and evaluate their antimicrobial efficacy in treating acne vulgaris. Methods: Minocycline nanocrystals were synthesized using milling or solvent evaporation techniques. Nanocrystals were characterized in terms of particle size, particle distribution index (PDI), zeta potential, and morphology. The antibacterial efficacy against Propionibacterium acne, Staphylococcus aureus, and Staphylococcus epidermidis was evaluated using a minimum inhibitory concentration assay (MIC) and agar well diffusion test in comparison to coarse minocycline. Results: Minocycline nanocrystals had a particle size of 147.4 ± 7.8 nm and 0.27 ± 0.017 of PDI. The nanocrystals exhibited a loading efficiency of 86.19 ± 16.7%. Antimicrobial testing showed no significant difference in activity between minocycline and its nanoparticle formulation. In terms of skin deposition, the nanocrystals were able to deliver minocycline topically to rat skin significantly more than free minocycline. The nanocrystal solution deposited 554.56 ± 24.13 μg of minocycline into rat skin, whereas free minocycline solution deposited 373.99 ± 23.32 μg. Conclusions: Minocycline nanocrystals represent a promising strategy for targeted skin delivery in the treatment of acne vulgaris, potentially reducing systemic side effects and antibiotic resistance and improving patient outcomes. Full article

Background/Objectives: This study aims to assess ovarian stromal vascularity using microvascular imaging in reproductive-aged women with polycystic ovarian morphology (PCOM) and to explore its associations with endocrine parameters and polycystic ovary syndrome (PCOS) phenotypes. Methods: We conducted a retrospective, single-center study between January 2021 and November 2023. Women aged 18–49 who met the PCOM criteria (≥20 follicles measuring 2–9 mm or an ovarian volume >10 cm³ in at least one ovary) were included. Pelvic ultrasound with MV-Flow Doppler imaging was used to quantify the stromal vascularity index (VI). On the same day, serum levels of FSH, LH, total and free testosterone, DHEAS, and estradiol were measured. PCOS phenotypes (A, C, D, and non-PCOS) were classified according to the Rotterdam criteria. Statistical analysis involved interobserver agreement using intraclass correlation coefficients (ICCs), correlation analysis for hormonal associations, and group comparisons using ANOVA. Results: A total of 111 women (mean age: 27.4 ± 6.1 years) were evaluated. The mean VI was 43.88 ± 19.84, with good interobserver agreement (ICC = 0.79; 95% CI: 0.65–0.88). VI was highest in Phenotype A (61.36 ± 10.11), followed by Phenotype C (42.57 ± 3.59), Phenotype D (26.47 ± 4.24), and Non-PCOS individuals (9.95 ± 5.44; p < 0.001). VI showed strong positive correlations with total testosterone (r = 0.797) and free testosterone (r = 0.778), and a moderate negative correlation with DHEAS (r = −0.483; p < 0.001). Conclusions: Microvascular imaging is a promising tool for quantifying ovarian stromal vascularity in PCOM. Its strong correlation with androgen levels, especially in hyperandrogenic phenotypes, highlights its potential role in enhancing diagnostic precision and deepening our understanding of PCOS pathophysiology. Full article

Background/Objectives: Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting up to 15% of reproductive-age women, characterized by hyperandrogenism, chronic oligo-ovulation, and metabolic dysfunction. This study aims to evaluate serum sortilin levels in women with PCOS for the first time and investigate their potential associations with metabolic and hormonal alterations. Material and Methods: Eighty PCOS patients and 80 healthy controls were included; serum sortilin levels were measured using ELISA kits, with documented intra-assay and inter-assay variations below 6% and 8%, respectively, ensuring high specificity and sensitivity. Results: Serum sortilin levels were significantly elevated in PCOS patients (69.51 ± 27.75 pg/mL) versus controls (48.60 ± 21.20 pg/mL) (p < 0.001). PCOS patients exhibited higher mean HOMA-IR, free androgen index values, serum glucose, insulin, triglycerides, high-sensitivity C-reactive protein, luteinizing hormone, total testosterone, and DHEA-S levels, alongside reduced high-density lipoprotein cholesterol and sex hormone-binding globulin levels (all, p < 0.05). Notably, inverse correlations were observed between sortilin and low-density lipoprotein cholesterol levels in both groups (p = 0.028 and 0.033). Conclusions: This pioneering study indicates that serum sortilin may be implicated in PCOS pathogenesis and serves as a potential biomarker for metabolic dysfunction in PCOS. Larger, diverse studies with longitudinal designs are needed for further validation. Full article

Background: Acne is a pathology of the pilosebaceous unit. It is characterized by a highly complex etiopathology which includes inflammation, hyperkeratinization, increased sebum production, colonization of Cutibacterium acne, hyperandrogenemia, and hyperinsulinemia. This condition, together with hirsutism, androgenic alopecia, and acanthosis nigricans, are highly prevalent cutaneous manifestations of the polycystic ovary syndrome (PCOS). While conventional therapies represent effective treatment options, they are not free from side effects which may reduce compliance. In this context, considerable attention has been directed toward nutraceutical supplements, which include different molecules with great potential to reduce inflammation, hyperkeratinization, hyperseborrhea, and hyperinsulinemia. Myo-inositol has been shown to be effective in improving some of the signs and symptoms of patients with microcystic ovaries: reducing body mass index (BMI), testosterone free levels, dehydroepiandrosterone sulfate (DHEAS) levels, and improving ovarian function and insulin sensitivity. Methods: The authors conducted a retrospective study that included 200 patients suffering from PCOS. Over 6 months, they analyzed the effects of the supplementation of LEVIGON™ (Sanitpharma; Milan, Italy)—a specific nutraceutical formulation containing myo-inositol, microlipodispersed magnesium, and folic acid—on the clinical picture of acne and hirsutism. Results: The supplementation of LEVIGON™ showed a significant reduction of BMI, testosterone, testosterone free, and DHEAS levels, thus improving the clinical picture of acne and hirsutism. Moreover, the impact of acne on the quality of life, assessed using the Cardiff Acne Disability Index (CADI) and Dermatology Life Quality Index (DLQI) scale, improved significantly after 3 and 6 months. Women with hirsutism benefited also from a significant improvement of the Ferriman-Gallwey score after both 3 and 6 months (p < 0.0001; p < 0.0001 respectively compared to the baseline). Conclusions: Myo-inositol supplementation, associated with microlipodispersed magnesium in a bioaccessible form, proved to be extremely useful in reducing acne and hirsutism in patients suffering from microcystic ovaries. In addition, there were no side effects, thus confirming excellent compliance. Further long-term randomized clinical trials are needed to confirm this preliminary evidence. Full article

Background/Objectives: Hirsutism is excessive male-patterned hair in postpubertal women with multifactorial etiology and is an indicator of hyperandrogenism associated with polycystic ovary syndrome (PCOS). Indeed, it can be caused by the enhanced peripheral conversion of androgen precursors to testosterone, as in idiopathic hirsutism (IH). Moreover, hirsutism can be caused by hirsutism-related hyperandrogenic syndromes like non-classic congenital adrenal hyperplasia (NCAH) and idiopathic hyperandrogenism (IHA). Methods: In this study, we characterized a large cohort of Portuguese women referred for hirsutism and estimated the prevalence of PCOS, NCAH, IHA, and IH. The levels of androgens and gonadotropins and body mass index (BMI) were measured and compared with controls. The correlation between each variable was calculated. Results: In the cohort, we found a prevalence of PCOS of 56.2%, IH of 20.2%, IHA of 17.3%, and NCAH of 6.2%. Subjects with PCOS were the only ones showing a significant difference in BMI compared to the controls and had the lowest levels of sex hormone-binding globulin (SHBG). Those with NCAH were younger and more hirsute with higher levels of testosterone, among other androgens. Those with IH had lower luteinizing hormone (LH) and LH/follicle-stimulating hormone (FSH) ratios than those with PCOS. Those with IH had lower SHBG levels compared to the controls and a higher free androgen index (FAI). Those with IHA had higher androgens compared to those with IH, in particular, adrenal-derived androgens. Conclusions: The pathogenesis of hirsutism is complex, and the contributions of the pituitary gland, ovaries, adrenals, adipose tissue, and liver have to be ascertained to understand the clinical manifestations and delineate appropriate treatments. This study sheds new light on the fine hormonal regulation of these diseases. Full article

Background/Objectives: This systematic review and meta-analysis aimed to investigate the effect of prebiotics, alone or as part of synbiotics, on cardiometabolic parameters in polycystic ovary syndrome (PCOS) women. Methods: Databases, including PubMed, Scopus, ISI Web of Science, Embase, and the Cochrane Central Register of Controlled Trials, were searched for relevant randomized-controlled trials (RCTs) until 12 December 2024. Changes in mean ± standard deviations were extracted and combined using a random-effects model. Bias was assessed using Cochrane risk of bias and evidence quality with GRADE. Results: Twenty RCTs with 1271 participants were included. Results showed high-quality evidence supporting prebiotics’ effects, alone or as part of synbiotics, in reducing body-mass index [n = 853; weighted-mean difference (WMD): −0.510, 95%CI: −0.669, −0.351 kg/m²] and diastolic blood pressure (WMD: −2.218, 95%CI: −4.425, −0.010 mmHg), moderate-quality evidence for weight, waist-to-hip ratio, and triglycerides improvements, and low or very-low-quality evidence for waist circumference (WC), fat mass, fasting plasma glucose, fasting insulin, low-density lipoprotein (LDL), total cholesterol (TC), high sensitive-C reactive protein, total testosterone, follicle-stimulating hormone and free androgen index improvements. Subgroup analyses revealed possible reduction in LDL with prebiotics, as well as possible decreases in WC, TC, and total testosterone with synbiotics. Dietary approaches to stop hypertension diet improved insulin sensitivity. Conclusions: This study suggests that prebiotics may beneficially affect several cardiometabolic parameters in PCOS women. Approximately one-third of the results were based on moderate-to-high-quality evidence. This study highlights the need for future well-designed, larger RCTs with longer treatment duration to strengthen the evidence base and guide clinical decision-making. Full article