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Association between urinary bisphenol A levels and infertility: A logistic regression analysis
*Corresponding author: Dr. Nidhi Agastya, MBBS, Department of Medicine, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India. nidhiagastya2000@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Garg R, Agastya N, Agrawal P, Gupta P, Varshney N. Association between urinary bisphenol A levels and infertility: A logistic regression analysis. Ann Natl Acad Med Sci (India). doi: 10.25259/ANAMS_251_2025
Abstract
Objectives
To examine the association between urinary bisphenol A (BPA) levels and infertility in both females and males using case-control data from Sarojini Naidu Medical College and Hospital.
Material and Methods
Case-control studies were conducted. Fifty women with anovulatory infertility were compared to 50 fertile female controls. Fifty men with abnormal semen parameters were compared to 50 fertile male controls. Urinary BPA concentrations were measured using high-performance liquid chromatography, mass spectrometry (HPLC-MS), adjusted for creatinine, and log-transformed. Logistic regression assessed the association between BPA and infertility.
Results
In females, each log-unit increase in BPA was associated with an 8.17-fold higher odds of ovulatory infertility (95% CI: 2.29-29.15, p = 0.002). In males, the odds of infertility increased 10.49-fold per log-unit increase in BPA (95% CI: 2.66-41.36, p = 0.001). In addition, infertile men had significantly higher urinary levels of BPA, bisphenol S (BPS), and bisphenol F (BPF), alongside impaired semen parameters and hormonal imbalances compared to controls.
Conclusion
Elevated urinary BPA levels are strongly associated with increased odds of infertility in both sexes. These findings reinforce international evidence and underscore the need for BPA exposure monitoring and reproductive health policy in India.
Keywords
Anovulation
Bisphenol A
Endocrine disruptors
Male infertility
Semen quality
INTRODUCTION
Bisphenol A (BPA) is an industrial chemical used extensively in the production of polycarbonate plastics and epoxy resins. These materials are found in food and beverage containers, water bottles, baby bottles, thermal paper receipts, and dental sealants. Due to its widespread use, BPA exposure is nearly ubiquitous; studies have detected BPA in over 90% of human urine samples worldwide.1
BPA is classified as an endocrine-disrupting compound because it can bind to estrogen, androgen, and thyroid hormone receptors. This molecular mimicry can interfere with hormonal signaling pathways, particularly those critical for reproductive function. In females, BPA has been shown to affect folliculogenesis, ovulation, and hormonal feedback loops.2 In males, BPA impairs spermatogenesis, affects Leydig and Sertoli cell function, and disrupts testosterone synthesis.
Urinary BPA measurement is the most reliable and non-invasive biomarker of exposure since BPA is rapidly metabolized and excreted in urine. Because of its short biological half-life, urinary levels reflect recent exposure, making them suitable for case-control and cross-sectional epidemiological studies. Recent advances in high-performance liquid chromatography, mass spectrometry (HPLC-MS), allow precise quantification of BPA even at low environmental exposure levels.
The rationale for using BPA in infertility studies stems from growing epidemiological and toxicological evidence linking BPA to hormonal disruption and reproductive system impairments.3 As infertility rates rise globally, understanding modifiable environmental contributors like BPA is essential. This research contributes valuable data from an Indian clinical setting, an area with limited published evidence, providing insight into the potential health burden of BPA exposure and helping inform both clinicians and policymakers.
Research has indicated significant associations between BPA exposure and reproductive issues. For example, studies have shown that elevated urinary BPA levels correlate with diminished ovarian reserve, disrupted menstrual cycles, and infertility among females. BPA exposure has also been implicated in altering hormone levels, particularly estrogen and progesterone, which are essential for healthy ovarian function.4
Among males, exposure to BPA has been consistently linked to reduced sperm concentration, motility, and quality.5 Additionally, BPA has demonstrated genetic implications by affecting sperm DNA integrity, leading to fertility complications.6
This research aims to examine these associations further by evaluating data collected from SN Medical College and Hospital.
MATERIAL AND METHODS
Study design
A case-control study was performed. Urinary bisphenol levels of 50 females with anovulatory infertility were compared with 50 fertile women as controls. We also studied the urinary bisphenol levels of 50 men with semen abnormalities and compared them with 50 men without semen abnormalities as controls.
Setting
Patients were recruited from the outpatient clinic of Obstetrics and Gynecology at Sarojini Naidu Medical College and Hospital between January and December 2024.
Inclusion criteria
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Age 20-40 years
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Non-smokers
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No history of occupational BPA exposure
Hormonal testing in females
Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured on Day 3 of the menstrual cycle. Anovulation was confirmed using mid-luteal phase serum progesterone levels (<3 ng/mL) and ultrasound monitoring of follicular development.
Hormonal and semen analysis in males
Semen parameters were assessed per the WHO 2021 criteria. Hormonal analysis included serum testosterone, FSH, and LH levels.
BPA measurement
First-morning urine samples were analyzed using HPLC-MS (Bruker Daltonics, Bremen, Germany). Values were adjusted for creatinine and log-transformed to normalize the right-skewed distribution.
Bias and confounding
We minimized measurement bias by using blinded BPA assessments and standard protocols for hormonal and semen evaluation. However, potential confounding factors such as dietary intake, environmental co-exposures, and stress levels were not controlled and remain limitations.
Statistical analysis
Logistic regression was used to model infertility (yes/no) as a function of log-transformed BPA. Odds ratios (OR) and 95% confidence intervals (CI) were reported. Model diagnostics included the Hosmer-Lemeshow test and Nagelkerke pseudo R2.
Data collection
Urinary BPA, bisphenol S (BPS), and bisphenol F (BPF) concentrations were measured. BPA levels were log-transformed to normalize skewed data.
RESULTS
Table 1 illustrates the logistic regression results for the female study. The intercept (β₀ = -4.50) indicates the baseline log odds of infertility when BPA levels approach zero. The coefficient for log(BPA) (β₁ = 2.10) represents the change in the log odds of infertility for each unit increase in log-transformed BPA. Specifically, the odds ratio (OR = 8.17, 95% CI: 2.29-29.15) suggests that a single unit increase in log(BPA) significantly increases the odds of ovulatory infertility by ∼8 times. The wide confidence interval indicates variability likely due to the modest sample size.
| Predictor | Coefficient (β) | Standard error | Odds ratio (OR) | 95% CI for OR | p value |
|---|---|---|---|---|---|
| Intercept (β₀) | -4.50 | 1.20 | - | - | 0.001 |
| Log(BPA) (β₁) | 2.10 | 0.65 | 8.17 | 2.29-29.15 | 0.002 |
Nagelkerke R2 = 0.25 indicates moderate explanatory power. The Likelihood Ratio Test (χ2 = 18.6, p < 0.001) confirms the model’s statistical significance, while the Hosmer-Lemeshow test (p = 0.78) supports good model calibration. BPA: Bisphenol A, CI: Confidence intervals.
Table 2 provides the logistic regression results for the male study. The intercept (β₀ = -5.20) reflects baseline log odds for infertility when BPA approaches zero. The log(BPA) coefficient (β₁ = 2.35) indicates that each unit increase in log-transformed BPA increases the log odds of infertility substantially. The corresponding odds ratio (OR = 10.49, 95% CI: 2.66-41.36) strongly suggests that higher BPA exposure markedly elevates the risk of male infertility, approximately 10-fold per unit log-increase. The broad confidence interval again underscores the variability associated with a limited sample size.
| Predictor | Coefficient (β) | Standard error | Odds ratio (OR) | 95% CI for OR | p value |
|---|---|---|---|---|---|
| Intercept (β₀) | -5.20 | 1.30 | - | - | <0.001 |
| Log(BPA) (β₁) | 2.35 | 0.70 | 10.49 | 2.66-41.36 | 0.001 |
Nagelkerke R2 = 0.28 reflects adequate explanatory power. The Likelihood Ratio Test (χ2 = 20.1, p <0.001) supports strong model significance, and the Hosmer-Lemeshow test (p = 0.82) confirms good fit. BPA: Bisphenol A, CI: Confidence intervals.
Table 3 suggests that infertile men experience significantly higher exposure to environmental bisphenols, BPA, BPS, and BPF, compared to fertile controls, with all differences reaching strong statistical significance (p <0.001). This elevated exposure coincides with marked impairments in semen quality, including reduced sperm count, motility, and morphology. Hormonal analysis reveals a pattern of hypogonadism, with lower testosterone and compensatory increases in FSH and LH, indicating underlying testicular dysfunction. Importantly, demographic factors like age and BMI, as well as urinary creatinine levels, did not differ significantly between groups, reinforcing the validity of these associations. Together, these findings implicate bisphenol exposure as a potential contributor to male infertility, possibly mediated by endocrine disruption and oxidative stress mechanisms.
| Category | Parameter | Infertile group (Mean ± SD) | Control group (Mean ± SD) | p value | Test used |
|---|---|---|---|---|---|
| Demographics | Age (years) | 32.4 ± 4.5 | 31.9 ± 3.8 | 0.543 | Independent t-test |
| BMI (kg/m2) | 26.1 ± 3.2 | 25.7 ± 2.9 | 0.481 | Independent t-test | |
| Urinary bisphenols (ng/mL) | BPA (ng/mL) | 3.8 ± 1.2 | 1.5 ± 0.6 | <0.001 | Mann-Whitney U test |
| BPS (ng/mL) | 2.1 ± 0.9 | 0.8 ± 0.3 | <0.001 | Mann-Whitney U test | |
| BPF (ng/mL) | 1.6 ± 0.7 | 0.5 ± 0.2 | <0.001 | Mann-Whitney U test | |
| Urinary creatinine | Urinary creatinine (mg/dL) | 1.3 ± 0.4 | 1.2 ± 0.3 | 0.192 | Independent t-test |
| Semen parameters | Sperm count (million/mL) | 18.3 ± 7.5 | 65.4 ± 11.2 | <0.001 | Independent t-test |
| Motility (%) | 29.6 ± 9.8 | 70.1 ± 8.4 | <0.001 | Mann-Whitney U test | |
| Morphology (% normal) | 4.2 ± 1.5 | 12.7 ± 2.1 | <0.001 | Mann-Whitney U test | |
| Hormonal profile | Testosterone (ng/dL) | 305 ± 78 | 465 ± 85 | <0.001 | Independent t-test |
| FSH (mIU/mL) | 9.8 ± 2.7 | 4.9 ± 1.6 | <0.001 | Independent t-test | |
| LH (mIU/mL) | 6.5 ± 1.9 | 4.1 ± 1.2 | <0.001 | Mann-Whitney U test |
p<0.001 is statistically significant, BPA: Bisphenol A, BPS: Bisphenol S, BPF: Bisphenol F, BMI: Body mass index, FSH: Follicle stimulating hormone, LH: Luteinizing hormone, SD: Standard deviation.
DISCUSSION
Our findings strongly support previous research indicating significant associations between urinary BPA levels and infertility. In females, increased BPA exposure correlates with anovulatory infertility and disrupted ovarian function. The odds ratio of 8.17 closely aligns with recent studies reporting similar associations.
For males, our findings demonstrate a strong association between BPA and poor semen parameters, consistent with earlier studies that found a significant reduction in sperm quality and motility with elevated BPA exposure. The calculated odds ratio of 10.49 corroborates earlier research findings that report notable declines in sperm parameters linked to BPA exposure.
Numerous studies have investigated BPA’s effects on reproductive health:
Yuan et al.7 (2025) reported a 21% decrease in clinical pregnancy rates and a 19% lower live birth rate in women with the highest urinary BPA quartile undergoing IVF. Mok-Lin et al.8 (2010) found that a 1 ng/mL increase in urinary BPA was associated with a 12% decline in the number of oocytes retrieved during IVF. Li et al.5 (2021) reported a pooled mean difference of -15.8 million/mL in sperm count and -7.3% in motility in high BPA exposure groups. Wang et al.6 (2022) found that men in the highest BPA tertile had 1.8 times the odds of sperm DNA fragmentation index (DFI) >30% compared to those in the lowest tertile. Tavares et al.9 (2023) observed a 35% decrease in mitochondrial membrane potential and widespread seminiferous tubule degeneration following high-dose BPA exposure in a murine model. Duan et al.4 (2023) showed a 48% increase in testicular malondialdehyde (MDA) levels and a 30% reduction in sperm production in BPA-exposed rats.
These findings align with our observed trends and reinforce BPA’s detrimental effect on human reproductive health through oxidative stress and hormonal disruption mechanisms.
Despite growing evidence globally, Indian data remains sparse. This study investigates urinary BPA and infertility associations among Indian patients.
Our data from SN Medical College and Hospital highlight the urgency for comprehensive public health strategies and policy measures aimed at reducing BPA exposure, particularly among populations at risk for infertility.
This study reinforces the hypothesis that BPA is a significant risk factor for infertility. The observed 8-fold increase in ovulatory infertility risk per log-unit BPA is consistent with international reports. For example, Li et al.5 (2021) observed a 4.2-fold increase in women at the highest BPA exposure. The dose-response pattern seen in our study parallels that in Minguez-Alarcon et al.10 (2018), where fecundability was reduced by 23% per unit increase in BPA.
Male findings show an even stronger association, with over a 10-fold increased risk, in line with reports of deteriorating semen quality in BPA-exposed populations. Zatecka et al.11 (2024) reported a 16% drop in semen parameters, while Meeker et al. (2018)12 linked BPA to increased sperm disomy.
Mechanistically, BPA mimics estrogen and antagonizes androgen pathways, inducing oxidative stress, mitochondrial dysfunction, and Sertoli cell damage, all central to gonadal function. Duan et al.4 (2023) detail how BPA impairs spermatogenesis and testicular histology in animal models.
On comparing our study with a study conducted in Danish men, strikingly similar trends were observed.13 Infertile participants in both populations had significantly higher urinary levels of BPA, BPS, and BPF, 3.8, 2.1, and 1.6 ng/mL, respectively, in our study vs. 3.1, 1.8, and 1.4 ng/mL in the Danish cohort, compared to their respective control groups. These elevated bisphenol levels were consistently associated with impaired semen parameters. Sperm count in our study was 18.3 million/mL in infertile men vs. 65.4 million/mL in controls, closely matching the Danish data (20.0 vs. 60.0 million/mL). Similarly, sperm motility (29.6% vs. 70.1%) and morphology (4.2% vs. 12.7%) in our study mirrored the Danish findings (35.0% vs. 68.0%, and 5.0% vs. 11.0%, respectively).
Limitations
The observed broad confidence intervals in our results likely reflect limitations due to small sample sizes and natural variability in BPA concentrations and fertility outcomes. Larger, longitudinal studies that account for potential confounding factors such as lifestyle, dietary habits, occupational exposure, genetic factors, and other environmental contaminants would enhance the precision of these associations.
Limitations of our study include sample size and lack of longitudinal data. Confounders such as diet, BMI, and co-exposures were not controlled. However, our study adds to the limited Indian evidence base and underscores BPA’s reproductive toxicity.
CONCLUSION
The study confirms a significant association between BPA exposure and infertility in both genders, echoing findings from existing literature. While it provides critical insights, addressing methodological limitations through larger, controlled studies is vital for confirming these associations and informing health policy.
This research provides robust evidence of BPA’s deleterious impact on human fertility in an Indian population. BPA levels were significantly higher in infertile individuals of both sexes, with strong associations confirmed through regression modelling. These results echo findings from six international studies and call for urgent public health actions to monitor and regulate BPA exposure.
Future work should focus on larger, prospective cohorts with biomarker-adjusted exposure estimates and fertility endpoints.
Authors’ contributions
RG, NA: Concepts, design, definition of intellectual content, literature search, clinical studies, experimental studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing and review; PA: Concepts, design; PG: Clinical studies, literature search, NV: Definition of intellectual content, manuscript preparation.
Ethical approval
The research/study approved by the Institutional Ethics Committee of Sarojini Naidu Medical College and Hospital, 216/25, dated 07th August 2025.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
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