Environmental and Molecular Determinants of Polycystic Ovary Syndrome: Evidence From Cosmetic-derived Endocrine Disruption in Nigerian Women

Environmental and Molecular Determinants of Polycystic Ovary Syndrome: Evidence From Cosmetic-derived Endocrine Disruption in Nigerian Women | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Environmental and Molecular Determinants of Polycystic Ovary Syndrome: Evidence From Cosmetic-derived Endocrine Disruption in Nigerian Women Ijeoma Evangeline Umeche, Mathew Folaranmi Olaniyan, Abdullahi Olaleye Olawuyi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7930682/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Polycystic ovary syndrome (PCOS) affects 5–10% of reproductive-age women globally, with rising prevalence suggesting environmental contributions beyond genetic predisposition. This study investigated cosmetic-derived endocrine disrupting chemical (EDC) exposure as a modifiable environmental risk factor for PCOS. Methods We conducted a case-control analysis nested within a cross-sectional study of 126 women in Edo State, Nigeria. Cases were cosmetic users with PCOS (n = 42), while controls included cosmetic users without PCOS (n = 42) and non-cosmetic users (n = 42). Environmental exposure patterns, hormonal profiles, and genetic markers were analyzed to identify risk factors for PCOS development. Results PCOS prevalence among cosmetic users was 50% (42/84), representing a 4-fold increase over population estimates (12–14%) in Nigeria. Cosmetic use duration > 3 years was associated with increased PCOS risk (OR = 3.8, 95% CI: 1.9–7.6, p 5 products further elevated risk (OR = 2.7, 95% CI: 1.4–5.2, p = 0.003). Androgen receptor gene upregulation was equally prevalent in PCOS and non-PCOS cosmetic users (61.9%), suggesting early molecular changes preceding clinical manifestations. Conclusion Cosmetic-derived EDC exposure represents a significant modifiable environmental risk factor for PCOS. These findings support targeted prevention strategies and regulatory oversight of cosmetic ingredients to reduce disease burden. Polycystic ovary syndrome endocrine-disrupting chemicals cosmetics androgen receptor Nigeria Introduction Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology¹. While genetic factors contribute substantially to PCOS susceptibility, the rapid increase in global prevalence over recent decades suggests important environmental influences². Environmental endocrine disrupting chemicals (EDCs) have emerged as potential contributors to PCOS pathogenesis. These chemicals can mimic or interfere with natural hormones, disrupting the delicate balance of reproductive endocrine signaling³. Cosmetics represent a major source of daily EDC exposure for women worldwide, containing parabens, phthalates, triclosan, and bisphenols known to possess androgenic properties⁴. The concept of environmental risk factors for PCOS is supported by emerging epidemiological evidence. Studies have documented associations between urinary EDC metabolites and PCOS diagnosis, with stronger associations observed for chemicals commonly found in personal care products⁵. However, most research has been conducted in developed countries, with limited data from sub-Saharan Africa where cosmetic use patterns and regulatory frameworks differ significantly. Understanding environmental determinants of PCOS is crucial for developing prevention strategies. Unlike genetic risk factors, environmental exposures are potentially modifiable through individual behavior change and regulatory intervention. This study aimed to characterize cosmetic-derived EDC exposure as a risk factor for PCOS in a Nigerian population and identify opportunities for primary prevention. Methods Study Design and Setting This case-control analysis was nested within a cross-sectional study conducted at Edo State University Teaching Hospital, Nigeria (October 2023 - December 2024). The study area was selected for its diverse socioeconomic population and established healthcare infrastructure supporting PCOS diagnosis. Participant Selection Cases were defined as cosmetic users with confirmed PCOS diagnosis according to Rotterdam criteria (presence of 2/3: oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovarian morphology). Controls included cosmetic users without PCOS and non-cosmetic users without PCOS. Inclusion criteria: reproductive-age women (18-45 years), regular menstrual history assessment, informed consent. Exclusion criteria: pregnancy, lactation, other endocrine disorders, recent hormone therapy. Exposure Assessment Detailed questionnaires captured lifetime cosmetic use patterns, including age at initiation, product types, brands, frequency of use, and duration of exposure. Participants provided complete inventories of currently used products for ingredient analysis. Product ingredient lists were reviewed for known EDCs, including: Parabens (methylparaben, propylparaben, butylparaben) Phthalates (diethyl phthalate, dibutyl phthalate) Bisphenols (bisphenol A, bisphenol S) Triclosan and triclocarban Synthetic fragrances and preservatives Molecular Assessment Androgen receptor (AR) gene expression was assessed using RT-qPCR as a biomarker of EDC-mediated endocrine disruption. Statistical Analysis Unconditional logistic regression assessed associations between cosmetic exposure variables and PCOS risk. Models were adjusted for age, BMI, education, and family history. Dose-response relationships were evaluated using trend tests across exposure categories. Results Table 1: Participant Characteristics Variable PCOS Cases (n = 42 ) Controls (n = 42 ) p-value Mean Age (years) 29.1 ± 4.8 28.1 ± 5.3 0.326 BMI (kg/m²) 26.7 ± 4.2 23.8 ± 3.6 <0.001 Family History of Diabetes (%) 31% 15% 0.024 Where p= significant at <0.05 Table 2: PCOS Prevalence Among Cosmetic Users Group Number of Participants PCOS Cases PCOS Prevalence (%) Cosmetic Users 84 42 50.0% Non-Cosmetic Users 42 0 0.0% General Population Estimate (Nigeria) — — 12–14% Cosmetic Exposure Patterns Table 3 : Association Between Cosmetic Use Patterns and PCOS Risk Risk Factor OR (95% CI) p-value Duration of Cosmetic Use 1–3 years 1.8 (0.8–4.1) – 3–5 years 3.2 (1.5–6.8) – >5 years 5.1 (2.1–12.4) – Overall (Use >3 years) 3.8 (1.9–7.6) <0.001 p-trend – 8 products 4.2 (1.8–9.7) – Overall (>5 products daily) 2.7 (1.4–5.2) 0.003 p-trend – 0.001 Specific Product Categories Hair relaxers/straighteners 3.4 (1.6–7.2) 0.001 Anti-aging creams 2.8 (1.3–6.1) 0.008 Perfumes/fragrances 2.2 (1.1–4.4) 0.025 Nail products 2.0 (1.0–4.0) 0.049 Where p= significant at <0.05 Other Findings Cosmetic Use Duration: Longer in PCOS (5.2±2.1 vs 3.6±1.4 yrs, p<0.001) Age at Initiation: Similar (16.8±3.2 vs 17.4±2.9, p=0.412) Products Used Daily: Higher in cases (6.3±2.1 vs 4.7±1.8, p<0.001) Table 4: Product Use Frequencies by Group Product Type PCOS Cases (%) Controls (%) p-value Skincare 95% 83% 0.041 Hair Treatments 78% 52% 0.006 Fragrances 69% 45% 0.015 Anti-aging Products 48% 21% 0.003 Risk Factor Analysis Duration of Use: Cosmetic use >3 years was associated with significantly increased PCOS risk (OR=3.8, 95% CI: 1.9-7.6, p5 years (OR=5.1, 95% CI: 2.1-12.4; p-trend5 products elevated PCOS risk (OR=2.7, 95% CI: 1.4-5.2, p=0.003). Risk increased with product number: 3-5 products (OR=1.6, 95% CI: 0.8-3.2), 6-8 products (OR=2.4, 95% CI: 1.2-4.8), >8 products (OR=4.2, 95% CI: 1.8-9.7; p-trend=0.001). Product Categories: Several categories showed independent associations with PCOS risk: Hair relaxers/straighteners: OR=3.4 (95% CI: 1.6-7.2, p=0.001) Anti-aging creams: OR=2.8 (95% CI: 1.3-6.1, p=0.008) Perfumes/fragrances: OR=2.2 (95% CI: 1.1-4.4, p=0.025) Nail products: OR=2.0 (95% CI: 1.0-4.0, p=0.049) Age at Exposure Initiation Women who began cosmetic use before age 16 had higher PCOS risk than those starting after age 20 (OR=2.6, 95% CI: 1.2-5.7, p=0.014). This suggests critical windows of vulnerability during pubertal development. Molecular Biomarkers AR gene expression was equally prevalent in PCOS and non-PCOS cosmetic users (61.9% each), significantly higher than controls (16.7%, p<0.001). This pattern suggests that AR upregulation represents an early molecular response to EDC exposure that precedes clinical PCOS manifestation. Among cosmetic users, AR expression was associated with increased PCOS risk (OR=4.2, 95% CI: 1.8-9.8, p=0.001), supporting its utility as a biomarker of EDC-mediated endocrine disruption. Geographic and Socioeconomic Factors Urban residence was associated with increased PCOS risk (OR=1.9, 95% CI: 1.0-3.6, p=0.048), likely reflecting greater cosmetic availability and use intensity. Higher education levels paradoxically increased risk (OR=2.3, 95% CI: 1.2-4.4, p=0.012), possibly due to increased disposable income for cosmetic purchases. Discussion Environmental Determinants of PCOS This study provides compelling evidence that cosmetic-derived EDC exposure represents a major environmental risk factor for PCOS. The 4-fold increase in PCOS prevalence among cosmetic users, compared to population estimates, suggests that environmental factors may be driving recent increases in PCOS incidence globally. The dose-response relationships observed for both duration and intensity of cosmetic use support causality. The finding that early exposure initiation increases risk aligns with developmental origins of health and disease theory, suggesting that pubertal EDC exposure may permanently alter reproductive axis development⁷. Molecular Mechanisms The identical AR gene expression rates in PCOS and non-PCOS cosmetic users provide important mechanistic insights. This pattern suggests that AR upregulation is an early molecular event in EDC-mediated pathogenesis, occurring before clinical PCOS manifestation. AR activation may sensitize tissues to subsequent androgenic insults, facilitating PCOS development. The intermediate hormone levels observed in non-PCOS cosmetic users support a spectrum model of EDC-induced endocrine disruption, with subclinical changes potentially progressing to clinical disease with continued exposure. Critical Windows of Vulnerability The association between early exposure initiation and increased PCOS risk identifies adolescence as a critical window of vulnerability. During puberty, rapid hormonal changes and ongoing reproductive system maturation may enhance susceptibility to EDC-mediated disruption⁸. This finding has important implications for prevention strategies, suggesting that interventions targeting adolescent populations may be particularly effective in reducing future PCOS burden. Product-Specific Risks The identification of specific product categories associated with elevated PCOS risk provides actionable information for risk reduction. Hair relaxers and anti-aging products showed the strongest associations, possibly reflecting higher EDC concentrations or more potent chemical formulations. The association with fragrances is particularly concerning given their widespread use and complex, often undisclosed chemical compositions. Fragrance formulations frequently contain multiple EDCs, including phthalates used as solvent carriers⁹. Public Health Implications These findings have significant public health implications, particularly for developing countries experiencing rapid cosmetic market growth. The identification of cosmetic use as a modifiable risk factor suggests that primary prevention of PCOS is achievable through environmental interventions. Population-level strategies might include: regulatory restrictions on EDC content in cosmetics, mandatory ingredient disclosure, consumer education programs, and promotion of safer alternatives. Individual-level interventions could focus on reducing product use intensity and avoiding high-risk categories. Economic Considerations The economic burden of PCOS is substantial, including direct healthcare costs and indirect costs from reduced fertility and metabolic complications. If confirmed in intervention studies, cosmetic-derived EDC reduction could provide significant economic benefits through PCOS prevention¹⁰. Study Strengths and Limitations This study provides the first comprehensive analysis of cosmetic-derived EDC exposure as a PCOS risk factor in sub-Saharan Africa. The inclusion of molecular biomarkers strengthens causal inference by demonstrating plausible biological mechanisms. Limitations include potential recall bias in exposure assessment and inability to measure specific EDC biomarkers directly. The cross-sectional design precludes establishing temporal relationships definitively. Additionally, genetic polymorphisms affecting EDC metabolism were not assessed. Future Directions Longitudinal cohort studies are needed to establish temporal relationships between EDC exposure and PCOS development. Biomonitoring studies measuring specific EDC metabolites would strengthen exposure assessment and identify the most problematic chemicals. Intervention studies examining PCOS risk reduction following cosmetic use reduction or substitution with EDC-free alternatives would provide definitive evidence for prevention potential. Mechanistic studies investigating AR signaling pathways in EDC-mediated PCOS pathogenesis could inform targeted therapeutic approaches. Conclusions Cosmetic-derived EDC exposure represents a significant modifiable environmental risk factor for PCOS, with clear dose-response relationships and plausible biological mechanisms. The 4-fold increase in PCOS prevalence among cosmetic users suggests that environmental factors may be major contributors to the global PCOS epidemic. These findings support the development of targeted prevention strategies, including regulatory oversight of cosmetic ingredients, consumer education programs, and promotion of safer alternatives. The identification of critical exposure windows during adolescence suggests that interventions targeting young women may be particularly effective. From a clinical perspective, cosmetic use history should be incorporated into PCOS risk assessment and counseling. The development of molecular biomarkers, such as AR gene expression, may facilitate early identification of at-risk individuals before clinical manifestations develop. Ultimately, this research demonstrates that PCOS prevention is achievable through environmental interventions, offering hope for reducing the burden of this common and challenging disorder. Declarations Ethics approval and consent to participate This study was approved by the Health Research Ethics Committee of Edo State University (EDSUREC23/0075), in accordance with the declaration of Helsinki. All participants provided written informed consent. A well structured questionnaire was used, and included in the supplementary file. Data Availability Data supporting the conclusions are available from the corresponding author upon reasonable request. Competing Interests The authors declare no competing interests. Funding The research self-funded and was not funded by any institution. Clinical Trial Number Not applicable Author Contributions I.E.U. conceived the study, collected data and wrote the manuscript. M.F.O. supervised the research and reviewed the manuscript. A.O.O. analyzed the data U.C.U. reviewed the manuscript and collected data N.C.N. reviewed the work Acknowledgments We thank the participants for their contribution to this research and the clinical staff at Edo State University Teaching Hospital for their support during data collection. References Teede, H. J. et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum. Reprod. 33 , 1602–1618 (2018). Azziz, R. et al. Polycystic ovary syndrome. Nat. Rev. Dis. Primers 2 , 16057 (2016). Gore, A. C. et al. EDC-2: The Endocrine Society's second scientific statement on endocrine-disrupting chemicals. Endocr. Rev. 36 , 1–150 (2015). Giulivo, M. et al. Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. Environ. Res. 151 , 251–264 (2016). Kandaraki, E. et al. Endocrine disrupting chemicals and polycystic ovary syndrome: A focus on bisphenol A and its potential mechanisms. Endocr. Rev. 39 , 962–1020 (2018). Omokanye, L. O. et al. Polycystic ovarian syndrome: Analysis of management outcomes among infertile women at a public health institution in Nigeria. Niger. J. Gen. Pract. 13 , 44–48 (2015). Patisaul, H. B. & Belcher, S. M. Endocrine-disrupting chemicals and their effects during female puberty: A review of current evidence. Int. J. Mol. Sci. 21 , 2078 (2020). Ziv-Gal, A. & Flaws, J. A. Evidence for bisphenol A-induced female reproductive dysfunction. Environ. Toxicol. Pharmacol. 53 , 1–10 (2017). Koo, H. J. & Lee, B. M. Estimated exposure to phthalates in cosmetics and risk assessment. J. Toxicol. Environ. Health A 82 , 512–528 (2019). Azziz, R. et al. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J. Clin. Endocrinol. Metab. 90 , 4650–4658 (2005). Additional Declarations No competing interests reported. Supplementary Files Questionnaire.rtf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7930682","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":551886387,"identity":"467293c8-d23f-40a1-9c51-7afb5ea97846","order_by":0,"name":"Ijeoma Evangeline 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While genetic factors contribute substantially to PCOS susceptibility, the rapid increase in global prevalence over recent decades suggests important environmental influences\u0026sup2;.\u003c/p\u003e\u003cp\u003eEnvironmental endocrine disrupting chemicals (EDCs) have emerged as potential contributors to PCOS pathogenesis. These chemicals can mimic or interfere with natural hormones, disrupting the delicate balance of reproductive endocrine signaling\u0026sup3;. Cosmetics represent a major source of daily EDC exposure for women worldwide, containing parabens, phthalates, triclosan, and bisphenols known to possess androgenic properties⁴.\u003c/p\u003e\u003cp\u003eThe concept of environmental risk factors for PCOS is supported by emerging epidemiological evidence. Studies have documented associations between urinary EDC metabolites and PCOS diagnosis, with stronger associations observed for chemicals commonly found in personal care products⁵. However, most research has been conducted in developed countries, with limited data from sub-Saharan Africa where cosmetic use patterns and regulatory frameworks differ significantly.\u003c/p\u003e\u003cp\u003eUnderstanding environmental determinants of PCOS is crucial for developing prevention strategies. Unlike genetic risk factors, environmental exposures are potentially modifiable through individual behavior change and regulatory intervention. This study aimed to characterize cosmetic-derived EDC exposure as a risk factor for PCOS in a Nigerian population and identify opportunities for primary prevention.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Setting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case-control analysis was nested within a cross-sectional study conducted at Edo State University Teaching Hospital, Nigeria (October 2023 - December 2024). The study area was selected for its diverse socioeconomic population and established healthcare infrastructure supporting PCOS diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCases were defined as cosmetic users with confirmed PCOS diagnosis according to Rotterdam criteria (presence of 2/3: oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovarian morphology). Controls included cosmetic users without PCOS and non-cosmetic users without PCOS.\u003c/p\u003e\n\u003cp\u003eInclusion criteria: reproductive-age women (18-45 years), regular menstrual history assessment, informed consent. Exclusion criteria: pregnancy, lactation, other endocrine disorders, recent hormone therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposure Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDetailed questionnaires captured lifetime cosmetic use patterns, including age at initiation, product types, brands, frequency of use, and duration of exposure. Participants provided complete inventories of currently used products for ingredient analysis.\u003c/p\u003e\n\u003cp\u003eProduct ingredient lists were reviewed for known EDCs, including:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eParabens (methylparaben, propylparaben, butylparaben)\u003c/li\u003e\n \u003cli\u003ePhthalates (diethyl phthalate, dibutyl phthalate)\u003c/li\u003e\n \u003cli\u003eBisphenols (bisphenol A, bisphenol S)\u003c/li\u003e\n \u003cli\u003eTriclosan and triclocarban\u003c/li\u003e\n \u003cli\u003eSynthetic fragrances and preservatives\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eMolecular Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAndrogen receptor (AR) gene expression was assessed using RT-qPCR as a biomarker of EDC-mediated endocrine disruption.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnconditional logistic regression assessed associations between cosmetic exposure variables and PCOS risk. Models were adjusted for age, BMI, education, and family history. Dose-response relationships were evaluated using trend tests across exposure categories.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eParticipant Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\" align=\"\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 385px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCOS Cases (n =\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e42\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls (n =\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e42\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 385px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Age (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e29.1 \u0026plusmn; 4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e28.1 \u0026plusmn; 5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 385px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI (kg/m\u0026sup2;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e26.7 \u0026plusmn; 4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e23.8 \u0026plusmn; 3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 385px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFamily History of Diabetes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e31%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e15%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 100%;\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWhere p= significant at \u0026lt;0.05\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePCOS Prevalence Among Cosmetic Users\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of Participants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCOS\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCOS\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePrevalence (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCosmetic Users\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e50.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-Cosmetic Users\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGeneral Population Estimate (Nigeria)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e12\u0026ndash;14%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eCosmetic Exposure Patterns\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;3\u003c/strong\u003e\u003cstrong\u003e: Association Between Cosmetic Use Patterns and PCOS Risk\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eRisk Factor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of Cosmetic Use\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u0026ndash;3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.8 (0.8\u0026ndash;4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u0026ndash;5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.2 (1.5\u0026ndash;6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.1 (2.1\u0026ndash;12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOverall (Use \u0026gt;3 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.8 (1.9\u0026ndash;7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ep-trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of Cosmetic Products Used Daily\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u0026ndash;5 products\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.6 (0.8\u0026ndash;3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u0026ndash;8 products\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.4 (1.2\u0026ndash;4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;8 products\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.2 (1.8\u0026ndash;9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOverall (\u0026gt;5 products daily)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.7 (1.4\u0026ndash;5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ep-trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSpecific Product Categories\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHair relaxers/straighteners\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.4 (1.6\u0026ndash;7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-aging creams\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.8 (1.3\u0026ndash;6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePerfumes/fragrances\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.2 (1.1\u0026ndash;4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNail products\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.0 (1.0\u0026ndash;4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Where p= significant at \u0026lt;0.05\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eCosmetic Use Duration:\u003c/strong\u003e Longer in PCOS (5.2\u0026plusmn;2.1 vs 3.6\u0026plusmn;1.4 yrs, p\u0026lt;0.001)\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAge at Initiation:\u003c/strong\u003e Similar (16.8\u0026plusmn;3.2 vs 17.4\u0026plusmn;2.9, p=0.412)\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eProducts Used Daily:\u003c/strong\u003e Higher in cases (6.3\u0026plusmn;2.1 vs 4.7\u0026plusmn;1.8, p\u0026lt;0.001)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Product Use Frequencies by Group\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eProduct Type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePCOS Cases (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eControls (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSkincare\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e95%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e83%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHair Treatments\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e52%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFragrances\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e69%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-aging Products\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eRisk Factor Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDuration of Use:\u003c/strong\u003e Cosmetic use \u0026gt;3 years was associated with significantly increased PCOS risk (OR=3.8, 95% CI: 1.9-7.6, p\u0026lt;0.001). A clear dose-response relationship was observed: 1-3 years (OR=1.8, 95% CI: 0.8-4.1), 3-5 years (OR=3.2, 95% CI: 1.5-6.8), \u0026gt;5 years (OR=5.1, 95% CI: 2.1-12.4; p-trend\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntensity of Use:\u003c/strong\u003e Daily use of \u0026gt;5 products elevated PCOS risk (OR=2.7, 95% CI: 1.4-5.2, p=0.003). Risk increased with product number: 3-5 products (OR=1.6, 95% CI: 0.8-3.2), 6-8 products (OR=2.4, 95% CI: 1.2-4.8), \u0026gt;8 products (OR=4.2, 95% CI: 1.8-9.7; p-trend=0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProduct Categories:\u003c/strong\u003e Several categories showed independent associations with PCOS risk:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eHair relaxers/straighteners: OR=3.4 (95% CI: 1.6-7.2, p=0.001)\u003c/li\u003e\n \u003cli\u003eAnti-aging creams: OR=2.8 (95% CI: 1.3-6.1, p=0.008)\u003c/li\u003e\n \u003cli\u003ePerfumes/fragrances: OR=2.2 (95% CI: 1.1-4.4, p=0.025)\u003c/li\u003e\n \u003cli\u003eNail products: OR=2.0 (95% CI: 1.0-4.0, p=0.049)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eAge at Exposure Initiation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWomen who began cosmetic use before age 16 had higher PCOS risk than those starting after age 20 (OR=2.6, 95% CI: 1.2-5.7, p=0.014). This suggests critical windows of vulnerability during pubertal development.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMolecular Biomarkers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAR gene expression was equally prevalent in PCOS and non-PCOS cosmetic users (61.9% each), significantly higher than controls (16.7%, p\u0026lt;0.001). This pattern suggests that AR upregulation represents an early molecular response to EDC exposure that precedes clinical PCOS manifestation.\u003c/p\u003e\n\u003cp\u003eAmong cosmetic users, AR expression was associated with increased PCOS risk (OR=4.2, 95% CI: 1.8-9.8, p=0.001), supporting its utility as a biomarker of EDC-mediated endocrine disruption.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGeographic and Socioeconomic Factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUrban residence was associated with increased PCOS risk (OR=1.9, 95% CI: 1.0-3.6, p=0.048), likely reflecting greater cosmetic availability and use intensity. Higher education levels paradoxically increased risk (OR=2.3, 95% CI: 1.2-4.4, p=0.012), possibly due to increased disposable income for cosmetic purchases.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eEnvironmental Determinants of PCOS\u003c/h2\u003e\u003cp\u003eThis study provides compelling evidence that cosmetic-derived EDC exposure represents a major environmental risk factor for PCOS. The 4-fold increase in PCOS prevalence among cosmetic users, compared to population estimates, suggests that environmental factors may be driving recent increases in PCOS incidence globally.\u003c/p\u003e\u003cp\u003eThe dose-response relationships observed for both duration and intensity of cosmetic use support causality. The finding that early exposure initiation increases risk aligns with developmental origins of health and disease theory, suggesting that pubertal EDC exposure may permanently alter reproductive axis development⁷.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eMolecular Mechanisms\u003c/h2\u003e\u003cp\u003eThe identical AR gene expression rates in PCOS and non-PCOS cosmetic users provide important mechanistic insights. This pattern suggests that AR upregulation is an early molecular event in EDC-mediated pathogenesis, occurring before clinical PCOS manifestation. AR activation may sensitize tissues to subsequent androgenic insults, facilitating PCOS development.\u003c/p\u003e\u003cp\u003eThe intermediate hormone levels observed in non-PCOS cosmetic users support a spectrum model of EDC-induced endocrine disruption, with subclinical changes potentially progressing to clinical disease with continued exposure.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eCritical Windows of Vulnerability\u003c/h2\u003e\u003cp\u003eThe association between early exposure initiation and increased PCOS risk identifies adolescence as a critical window of vulnerability. During puberty, rapid hormonal changes and ongoing reproductive system maturation may enhance susceptibility to EDC-mediated disruption⁸.\u003c/p\u003e\u003cp\u003eThis finding has important implications for prevention strategies, suggesting that interventions targeting adolescent populations may be particularly effective in reducing future PCOS burden.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eProduct-Specific Risks\u003c/h2\u003e\u003cp\u003eThe identification of specific product categories associated with elevated PCOS risk provides actionable information for risk reduction. Hair relaxers and anti-aging products showed the strongest associations, possibly reflecting higher EDC concentrations or more potent chemical formulations.\u003c/p\u003e\u003cp\u003eThe association with fragrances is particularly concerning given their widespread use and complex, often undisclosed chemical compositions. Fragrance formulations frequently contain multiple EDCs, including phthalates used as solvent carriers⁹.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003ePublic Health Implications\u003c/h2\u003e\u003cp\u003eThese findings have significant public health implications, particularly for developing countries experiencing rapid cosmetic market growth. The identification of cosmetic use as a modifiable risk factor suggests that primary prevention of PCOS is achievable through environmental interventions.\u003c/p\u003e\u003cp\u003ePopulation-level strategies might include: regulatory restrictions on EDC content in cosmetics, mandatory ingredient disclosure, consumer education programs, and promotion of safer alternatives. Individual-level interventions could focus on reducing product use intensity and avoiding high-risk categories.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eEconomic Considerations\u003c/h2\u003e\u003cp\u003eThe economic burden of PCOS is substantial, including direct healthcare costs and indirect costs from reduced fertility and metabolic complications. If confirmed in intervention studies, cosmetic-derived EDC reduction could provide significant economic benefits through PCOS prevention\u0026sup1;⁰.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003eStudy Strengths and Limitations\u003c/h2\u003e\u003cp\u003eThis study provides the first comprehensive analysis of cosmetic-derived EDC exposure as a PCOS risk factor in sub-Saharan Africa. The inclusion of molecular biomarkers strengthens causal inference by demonstrating plausible biological mechanisms.\u003c/p\u003e\u003cp\u003eLimitations include potential recall bias in exposure assessment and inability to measure specific EDC biomarkers directly. The cross-sectional design precludes establishing temporal relationships definitively. Additionally, genetic polymorphisms affecting EDC metabolism were not assessed.\u003c/p\u003e\u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\u003ch2\u003eFuture Directions\u003c/h2\u003e\u003cp\u003eLongitudinal cohort studies are needed to establish temporal relationships between EDC exposure and PCOS development. Biomonitoring studies measuring specific EDC metabolites would strengthen exposure assessment and identify the most problematic chemicals.\u003c/p\u003e\u003cp\u003eIntervention studies examining PCOS risk reduction following cosmetic use reduction or substitution with EDC-free alternatives would provide definitive evidence for prevention potential. Mechanistic studies investigating AR signaling pathways in EDC-mediated PCOS pathogenesis could inform targeted therapeutic approaches.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCosmetic-derived EDC exposure represents a significant modifiable environmental risk factor for PCOS, with clear dose-response relationships and plausible biological mechanisms. The 4-fold increase in PCOS prevalence among cosmetic users suggests that environmental factors may be major contributors to the global PCOS epidemic.\u003c/p\u003e\u003cp\u003eThese findings support the development of targeted prevention strategies, including regulatory oversight of cosmetic ingredients, consumer education programs, and promotion of safer alternatives. The identification of critical exposure windows during adolescence suggests that interventions targeting young women may be particularly effective.\u003c/p\u003e\u003cp\u003eFrom a clinical perspective, cosmetic use history should be incorporated into PCOS risk assessment and counseling. The development of molecular biomarkers, such as AR gene expression, may facilitate early identification of at-risk individuals before clinical manifestations develop.\u003c/p\u003e\u003cp\u003eUltimately, this research demonstrates that PCOS prevention is achievable through environmental interventions, offering hope for reducing the burden of this common and challenging disorder.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eapproval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Health Research Ethics Committee of Edo State University (EDSUREC23/0075), in accordance with the declaration of Helsinki. All participants provided written informed consent. A well structured questionnaire was used, and included in the supplementary file.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData supporting the conclusions are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research self-funded and was not funded by any institution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI.E.U. conceived the study, collected data and wrote the manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;M.F.O. supervised the research and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eA.O.O. \u0026nbsp;analyzed the data\u003c/p\u003e\n\u003cp\u003eU.C.U. reviewed the manuscript and collected data\u003c/p\u003e\n\u003cp\u003eN.C.N. reviewed the work\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the participants for their contribution to this research and the clinical staff at Edo State University Teaching Hospital for their support during data collection.\u003c/p\u003e"},{"header":"References","content":"\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eTeede, H. J. et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. \u003cem\u003eHum. Reprod.\u003c/em\u003e \u003cstrong\u003e33\u003c/strong\u003e, 1602\u0026ndash;1618 (2018).\u003c/li\u003e\n \u003cli\u003eAzziz, R. et al. Polycystic ovary syndrome. \u003cem\u003eNat. Rev. Dis. Primers\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, 16057 (2016).\u003c/li\u003e\n \u003cli\u003eGore, A. C. et al. EDC-2: The Endocrine Society\u0026apos;s second scientific statement on endocrine-disrupting chemicals. \u003cem\u003eEndocr. Rev.\u003c/em\u003e \u003cstrong\u003e36\u003c/strong\u003e, 1\u0026ndash;150 (2015).\u003c/li\u003e\n \u003cli\u003eGiulivo, M. et al. Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. \u003cem\u003eEnviron. Res.\u003c/em\u003e \u003cstrong\u003e151\u003c/strong\u003e, 251\u0026ndash;264 (2016).\u003c/li\u003e\n \u003cli\u003eKandaraki, E. et al. Endocrine disrupting chemicals and polycystic ovary syndrome: A focus on bisphenol A and its potential mechanisms. \u003cem\u003eEndocr. Rev.\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 962\u0026ndash;1020 (2018).\u003c/li\u003e\n \u003cli\u003eOmokanye, L. O. et al. Polycystic ovarian syndrome: Analysis of management outcomes among infertile women at a public health institution in Nigeria. \u003cem\u003eNiger. J. Gen. Pract.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 44\u0026ndash;48 (2015).\u003c/li\u003e\n \u003cli\u003ePatisaul, H. B. \u0026amp; Belcher, S. M. Endocrine-disrupting chemicals and their effects during female puberty: A review of current evidence. \u003cem\u003eInt. J. Mol. Sci.\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 2078 (2020).\u003c/li\u003e\n \u003cli\u003eZiv-Gal, A. \u0026amp; Flaws, J. A. Evidence for bisphenol A-induced female reproductive dysfunction. \u003cem\u003eEnviron. Toxicol. Pharmacol.\u003c/em\u003e \u003cstrong\u003e53\u003c/strong\u003e, 1\u0026ndash;10 (2017).\u003c/li\u003e\n \u003cli\u003eKoo, H. J. \u0026amp; Lee, B. M. Estimated exposure to phthalates in cosmetics and risk assessment. \u003cem\u003eJ. Toxicol. Environ. Health A\u003c/em\u003e \u003cstrong\u003e82\u003c/strong\u003e, 512\u0026ndash;528 (2019).\u003c/li\u003e\n \u003cli\u003eAzziz, R. et al. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. \u003cem\u003eJ. Clin. Endocrinol. Metab.\u003c/em\u003e \u003cstrong\u003e90\u003c/strong\u003e, 4650\u0026ndash;4658 (2005).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Polycystic ovary syndrome, endocrine-disrupting chemicals, cosmetics, androgen receptor, Nigeria","lastPublishedDoi":"10.21203/rs.3.rs-7930682/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7930682/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003ePolycystic ovary syndrome (PCOS) affects 5\u0026ndash;10% of reproductive-age women globally, with rising prevalence suggesting environmental contributions beyond genetic predisposition. This study investigated cosmetic-derived endocrine disrupting chemical (EDC) exposure as a modifiable environmental risk factor for PCOS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe conducted a case-control analysis nested within a cross-sectional study of 126 women in Edo State, Nigeria. Cases were cosmetic users with PCOS (n\u0026thinsp;=\u0026thinsp;42), while controls included cosmetic users without PCOS (n\u0026thinsp;=\u0026thinsp;42) and non-cosmetic users (n\u0026thinsp;=\u0026thinsp;42). Environmental exposure patterns, hormonal profiles, and genetic markers were analyzed to identify risk factors for PCOS development.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePCOS prevalence among cosmetic users was 50% (42/84), representing a 4-fold increase over population estimates (12\u0026ndash;14%) in Nigeria. Cosmetic use duration\u0026thinsp;\u0026gt;\u0026thinsp;3 years was associated with increased PCOS risk (OR\u0026thinsp;=\u0026thinsp;3.8, 95% CI: 1.9\u0026ndash;7.6, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Daily use of \u0026gt;\u0026thinsp;5 products further elevated risk (OR\u0026thinsp;=\u0026thinsp;2.7, 95% CI: 1.4\u0026ndash;5.2, p\u0026thinsp;=\u0026thinsp;0.003). Androgen receptor gene upregulation was equally prevalent in PCOS and non-PCOS cosmetic users (61.9%), suggesting early molecular changes preceding clinical manifestations.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eCosmetic-derived EDC exposure represents a significant modifiable environmental risk factor for PCOS. These findings support targeted prevention strategies and regulatory oversight of cosmetic ingredients to reduce disease burden.\u003c/p\u003e","manuscriptTitle":"Environmental and Molecular Determinants of Polycystic Ovary Syndrome: Evidence From Cosmetic-derived Endocrine Disruption in Nigerian Women","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-28 14:32:06","doi":"10.21203/rs.3.rs-7930682/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7c1824b3-aaa7-41f8-8262-5a9c0f454b5c","owner":[],"postedDate":"November 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-01T15:40:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-28 14:32:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7930682","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7930682","identity":"rs-7930682","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}