Evaluating the Role of Lipid Accumulation Product Index in Endometriosis: Findings from NHANES and Mendelian Randomization

Abstract

Purpose

Endometriosis is increasingly recognized as a condition linked to metabolic health. The lipid accumulation product (LAP) index, a simple index reflecting lipid metabolism and hormonal imbalance, is widely used in assessing metabolic disorders. This study investigates the association between LAP index and endometriosis risk.

Patients and Methods

Using data from the 1999–2006 National Health and Nutrition Examination Survey (NHANES), we examined the association between LAP index and endometriosis through multivariable logistic regression, subgroup analyses, and restricted cubic spline (RCS) models. Two-sample Mendelian randomization (MR) analysis was performed using FinnGen data to assess the potential causal effects of triglycerides (TG) and waist circumference (WC), the two key components of LAP index, on the risk of endometriosis.

Results

From the NHANES data, we included 1803 eligible participants, of whom 144 (8.0%) had endometriosis. Multivariable logistic regression models indicated that elevated LAP index levels were associated with an increased risk of endometriosis after adjusting for potential confounding variables (OR = 1.489, 95% CI: 1.074–2.065, P = 0.0218). Furthermore, restricted cubic spline analysis revealed a positive linear relationship (P = 0.0026). Two-sample Mendelian randomization analysis showed that genetic prediction supported a causal association between higher TG levels and an increased risk of endometriosis (OR= 1.14, 95% CI: 1.06–1.22, P= 0.0001, FDR = 0.00257), but the association was not observed between WC and endometriosis (OR=0.99, 95% CI: 0.83–1.20, P=0.956, FDR = 0.983).

Conclusion

LAP index is positively associated with endometriosis risk in women. MR analysis suggests a potential causal role of TG, possibly underlying this association.

Introduction

Endometriosis is a common estrogen-dependent condition defined by the presence of endometrial-like tissue outside the uterine cavity.¹ It affects approximately 6% to 10% of women of reproductive age, with chronic pelvic pain and infertility being its most prevalent clinical manifestations.^2,3 Among women presenting with pelvic pain, 50% to 80% are eventually diagnosed with endometriosis, and its prevalence among infertile women can reach up to 50%.³ These symptoms severely compromise patients’ quality of life, affecting daily functioning, sexual health, and emotional well-being.⁴ Diagnosis is typically based on imaging modalities such as transvaginal ultrasound and magnetic resonance imaging (MRI), while Laparoscopy has been conventionally considered the gold standard for diagnosing.^5,6 Therefore, early identification and effective management of endometriosis are essential to reduce disease burden.

With the global prevalence of obesity steadily increasing, there has been growing interest in the potential role of obesity and metabolic dysfunction in the pathogenesis of endometriosis.⁷ At the tissue level, endometriotic lesions have been shown to exhibit abnormal lipid accumulation, with significantly higher levels of phosphoethanolamine, sphingomyelin, diglycerides, phosphatidylcholines, and triglycerides compared to normal endometrial tissues.⁸ In parallel, a number of cross-sectional studies have identified a positive association between the triglyceride-glucose (TyG) index—a marker of insulin resistance—and the risk of endometriosis.^9,10 This relationship has been further reinforced by Mendelian randomization analyses, which support a potential causal link between metabolic dysfunction and disease development.¹¹ Moreover, other anthropometric indicators, including body mass index (BMI) and waist-to-hip ratio (WHR), have demonstrated complex associations with endometriosis risk.^12–14

The lipid accumulation product (LAP) index is a novel indicator for excess lipid accumulation, calculated based on waist circumference and fasting triglyceride levels.¹⁵ It reflects not only fat accumulation but also the metabolic statue of adipose tissue. Previous studies have demonstrated that the LAP index is closely associated with various metabolic disorders, including metabolic syndrome, type 2 diabetes, and insulin resistance.^16–18 In addition, a study demonstrated that the LAP index is a sensitive and specific marker for identify insulin resistance.¹⁹ Another study also showed that LAP index showed a better performance than BMI or WC in predicting cardiovascular risk.²⁰

However, its relationship with endometriosis remains unclear. Therefore, the present study aims to investigate the association between LAP index and endometriosis using nationally representative data from the National Health and Nutrition Examination Survey (NHANES). In addition, Mendelian randomization analysis was performed to explore the potential causal relationship.

Materials and Methods

Study Design Overview

This study comprises two main components. In the first phase, we conducted a comprehensive analysis of the association between the LAP index and endometriosis using data from the NHANES database, after adjusting all potential confounding factors in this study. The further subgroup analyses were conducted to evaluate the consistency of the results.

In the subsequent phase, recognizing LAP index is calculated based on triglycerides (TG) and waist circumference (WC), we extracted summary statistics for TG, WC and endometriosis from genome-wide association studies (GWAS) to conduct two-sample Mendelian randomization (MR) analyses. We further assessed the potential causal relationships between TG, WC and endometriosis at different anatomical sites through MR analysis. This study was approved by the Ethics Committee of Shanghai First Maternity and Infant Hospital (Number: 2025342).

Observational Study

NHANES Data Collection and Definitions

Data were collected from National Health and Nutrition Examination Surveys (NHANES), which is a cross-sectional survey designed about the health status of the US population. The data is available at https://wwwn.cdc.gov/nchs/nhanes/Default.aspx. In the NHANES 1999–2006 cycles, a total of 41,474 participants were included. The inclusion and exclusion criteria for participant selection are presented in Figure 1.

Figure 1.

Flowchart of participants selection from NHANES 1999–2006.

In this study, the primary outcomes was the incidence of endometriosis, which was collected by Reproductive Health Questionnaire in NHANES. The endometriosis were defined based on participants’ self-report in response to the question: “Has a doctor or other health professional ever told you that you had endometriosis?” Participants who answered “yes” were classified as having endometriosis. The potential confounding variables were identified based on a comprehensive literature review and clinical experiences of Obstetrician- gynecologist. Which included age (years), body mass index (BMI, kg/m²), waist circumference (cm), race/ethnicity (Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black, and other), age at menarche (years), number of pregnancies, number of live births, menstrual irregularities, female hormones use (yes/no), birth control pills use (yes/no), marital status, educational level (above high school, high school graduate, or below high school), family poverty-to-income ratio (PIR), alcohol consumption status (current drinker, former drinker, or never drinker), diabetes (yes/no) and hypertension (yes/no).

Specifically, age at menarche (years), number of pregnancies, number of live births, menstrual irregularities, female hormones use (yes/no) and birth control pills use (yes/no), were derived from a reproductive health questionnaire (RHQ), by answer the following items:”How old were you when you had your first menstrual period?”, “How many times have you been pregnant?”, “How many of your pregnancies resulted in a live birth?”, “Had regular periods in the past 12 months?”, “Have you ever taken birth control pills?”, and “Have you ever used female hormones?”. In addition, histories of diabetes and hypertension were obtained from self-reported information in the health survey questionnaire (BPQ, DIQ).

LAP Index Definitions

The main exposure variable was the LAP index, which was calculated using the formula: (waist circumference - 58 cm) × triglycerides (mmol/L).¹⁵

Statistical Analysis for NHANES

To account for NHANES’s complex sampling design and ensure national representativeness, all analyses incorporated the recommended sampling weights. Statistical analyses and visualizations were performed using R Studio (version 4.3.1, Build 2024.04.2). Continuous variables were expressed as mean ± SD or median (IQR), and compared using t-tests or Wilcoxon rank-sum tests, as appropriate. Categorical variables were summarized as frequencies (percentages) and compared using chi-square tests. Multivariable logistic regression models were used to assess the association between the LAP index and endometriosis. While restricted cubic spline (RCS) models were used to explore potential nonlinear relationships. Subgroup analyses were stratified by age, race, parity, menstrual irregularities, age at menarche, education level, and hypertension status. Two-sided p-values < 0.05 were considered statistically significant.

MR Analysis

Two-Sample MR Analysis

Mendelian randomization (MR) analysis was based on three core assumptions to infer a causal relationship between the exposure and the outcome: (i) a strong and independent association with the exposure of interest, (ii) no association with confounding factors influencing the outcome, and (iii) an effect on the outcome mediated solely through the exposure, not through alternative pathways.^21,22

The data in our study were obtained from the Finnish cohort (finngen_R12_N14_ENDOMETRIOSIS, https://www.finngen.fi/en) within the FinnGen study, a large-scale public-private partnership combining genome information with digital health care data from Finnish health registries.²³ FinnGen aims to analyze genetic variation in relation to disease susceptibility in the Finnish population. In this study, we utilized a summary-level genome-wide association study (GWAS) dataset for endometriosis, based on the FinnGen R12 release, which includes data from approximately 377,277 individuals of Finnish ancestry, comprising 8288 endometriosis cases and 369,248 controls.

SNPs associated with TG and WC were obtained from GWAS summary statistics (p<5×10-8) based on the UK Biobank cohort, a large prospective cohort of approximately 500,000 individuals of predominantly European ancestry. SNPs were excluded based on linkage disequilibrium ((r² < 0.001, kb=10 Mb), particularly those associated with BMI, Smoking to address potential horizontal pleiotropy (P<5 × 10–8). Ultimately, 264 SNPs were selected as instrumental variables for the TG (Table S2).

Univariate Two-Sample MR Analysis

To evaluate the causal relationship between TG, WC and endometriosis, we utilized GWAS data. The primary MR analysis employed the inverse variance-weighting (IVW) method to estimate the outcome. Additional analyses were conducted using the weighted median, MR-Egger, Simple mode, and weighted mode approaches to complement the primary findings.

Sensitivity Analysis

The sensitivity analyses encompassed a heterogeneity test and a horizontal multiplicity test to assess potential biases influencing the results. Heterogeneity was evaluated using Cochran’s Q-test and MR-PRESSO. The presence of horizontal pleiotropy was assessed through MR-Egger regression. Furthermore, a “leave-one-out” sensitivity analysis was conducted, whereby each single nucleotide polymorphisms (SNPs) was sequentially excluded to compute the meta-effects of the remaining SNPs, thereby determining whether the results remained consistent following each exclusion. The analysis was deemed robust if the results were stable and consistent with the overall Mendelian randomization estimate.

Results

Baseline Characteristics

For NHANES data, the baseline characteristics of participants with and without endometriosis are presented in Table 1. Among the 1803 eligible participants, 144 (8.0%) were diagnosed with endometriosis. The mean age of the study population was 40.0 years. Participants with endometriosis were older, had larger waist circumferences, higher BMI, and a higher prevalence of smoking and hypertension compared to those without endometriosis. Significant differences were also observed in race/ethnicity, female hormones use and menstrual irregularities between the two groups. The mean LAP index in the overall population was 0.40, with a significantly higher mean LAP index in participants with endometriosis compared to those without (0.49 vs 0.39, P = 0.024).

Table 1.

Baseline Characteristics of NHANES Participants 1999–2006 with or without Endometriosis

Characteristic	Overall (n= 1803)	No Endometriosis (n= 1659, 88.88%)	Endometriosis (n= 144, 11.12%)	P-value
Age, years	40.00 (32.00–46.00)	39.00 (31.00–47.00)	41.00 (35.00–46.00)	<0.001
BMI, kg/m2	26.82 (23.14–32.11)	26.23 (22.70–31.33)	27.35 (23.09–32.16)	0.985
Waist circumference (WC)	90.60 (80.90–102.90)	90.50 (80.50–102.20)	93.30 (82.00–105.20)	0.762
Race, n (%)				<0.001
Mexican American	431 (7.89)	422 (8.67)	9 (1.66)
Other Hispanic	79 (5.26)	75 (5.67)	4 (1.96)
Non-Hispanic White	826 (68.31)	724 (66.25)	102 (84.86)
Non-Hispanic Black	387 (12.98)	363 (13.72)	24 (7.11)
Other race	80 (5.55)	75 (5.69)	5 (4.40)
Age at menarche, years	13.00 (12.00–14.00)	13.00 (12.00–14.00)	12.00 (12.00–13.00)	0.315
Gravidity	3.00 (2.00–4.00)	3.00 (2.00–4.00)	3.00 (2.00–4.00)	0.669
Parity	2.00 (1.00–3.00)	2.00 (1.00–3.00)	2.00 (1.00–3.00)	0.031
Menstrual disorder, n (%)	711 (38.31)	626 (35.82)	85 (58.24)	<0.001
Marital status, n (%)	1122 (65.94)	1028 (65.23)	94 (71.66)	0.486
Education, n (%)				0.001
Under high school	468 (17.41)	449 (18.13)	19 (11.63)
High school or equivalent	417 (25.81)	374 (24.64)	43 (35.20)
Above high school	918 (56.78)	836 (57.23)	82 (53.17)
Family PIR	2.99 (1.44–4.79)	2.94 (1.42–4.79)	3.39 (1.52–4.96)	0.003
Smoking status, n (%)				0.002
Current smoker	401 (26.13)	355 (24.79)	46 (36.84)
Former smoker	322 (19.26)	291 (18.67)	31 (24.02)
Never smoker	1080 (54.61)	1013 (56.54)	67 (39.14)
Female hormones use	246 (17.56)	192 (15.83)	54 (21.06)	<0.001
Birth control pills use	1449 (83.68)	1322 (83.09)	127 (88.33)	0.1681
Diabetes mellitus, n (%)	87 (4.20)	81 (4.31)	6 (3.29)	0.856
Hypertension, n (%)	359 (20.34)	317 (20.06)	42 (22.59)	0.005
Lipid accumulation product (LAP) index	0.40 (0.24–0.67)	0.39 (0.24–0.66)	0.49 (0.30–0.85)	0.024

Abbreviations: NHANES, National Health and Nutrition Examination Survey; BMI, body mass index; Family PIR, Family poverty income ratio.

Association of the LAP Index with Endometriosis: Result Form NHANES

The LAP index was evaluated as a continuous and categorical variable to assess its association with the risk of endometriosis in the NHANES 1999–2006. After comprehensive adjustment for potential confounders, a linear association was observed between the LAP index and endometriosis (P for nonlinearity =0.1354) (Figure 2). Notably, there was a 47.9% increase in the risk of endometriosis for each unit increase in LAP index level as a continuous variable. A 147.7% increase in risk was observed for each unit increase in LAP index level in the Q4 group. Trend analysis indicated a statistically significant association between increasing LAP levels and increased the risk of endometriosis (P= 0.0314) (Table 2). In addition, sensitivity analyses evaluating the robustness of the association between the LAP index and endometriosis after excluding participants with hypertension and/or diabetes are presented in Table S1.

Figure 2.

Restricted cubic spline for linear association of LAP index with endometriosis. The gray shaded area is the 95% confidence interval, and the black dashed line represents an OR of 1. The model adjusted for Age, BMI, Race, Age at menarche, Gravidity, parity, Menstrual disorder, Marital status, Education, Family PIR, Smoking status, Diabetes mellitus, Hypertension, female hormones use and birth control pills use.

Table 2.

Association Between LAP Index and Endometriosis From NHANES 1999–2006

Characteristic	Model 1a			Model 2b			Model 3c
	ORs	95% CI	P-value	ORs	95% CI	P-value	ORs	95% CI	P-value
Continuous values	1.616	1.222–2.137	0.001	1.618	1.203–2.177	0.002	1.479	1.046–2.090	0.0327
Quartile Categories
Q1	-	-		-	-		-	-
Q2	1.335	0.701–2.542	0.382	1.467	0.759–2.837	0.260	1.487	0.742–2.983	0.271
Q3	1.096	0.701–2.542	0.798	1.351	0.644–2.833	0.429	1.117	0.519–2.401	0.779
Q4	2.445	1.344–4.447	0.005	3.123	1.486–6.562	0.004	2.477	1.148–5.342	0.0266
P for trend			0.004			0.003			0.0314

Notes: ^aModel 1: adjusted for none. ^bModel 2: adjusted for Age, BMI and Race. ^cModel 3: adjusted for Age, BMI, Race, Age at menarche, Gravidity, parity, Menstrual disorder, Marital status, Education, Family PIR, Smoking status, Diabetes mellitus, Hypertension, female hormones use and birth control pills use.

Abbreviations: ORs, Odd rations; 95% CI, 95% Confidence Interval; LAP, index Lipid accumulation product index.

Furthermore, the results of the subgroup analysis examining the relationship between LAP index and endometriosis, stratified by Age, BMI, Race, Parity, Menstrual disorder, Age at menarche, Education, Hypertension and Diabetes mellitus are presented in Table 3. The association remained consistent across various subgroups, and no significant interactions were observed among the variables (all P for interaction > 0.05).

Table 3.

Subgroup Analysis of LAP and Endometriosis from NHANES 1999–2006

Subgroup	ORs	95% CI	P-value	P for interaction
All subjects	1.489	1.074–2.065	0.022
Age (year)				0.734
≥40	1.606	1.084–2.380	0.023
<40	1.462	0.718–2.978	0.301
BMI (kg/m2)				0.309
<25	1.604	0.950–2.709	0.086
≥25	1.152	0.647–2.051	0.634
Race				0.229
Non-Hispanic White	1.565	1.068–2.293	0.028
Others	0.806	0.216–3.002	0.750
Parity				0.665
≥2	1.596	1.145–2.198	0.008
<2	1.208	0.592–2.465	0.606
Menstrual disorder				0.060
Yes	0.751	0.464–1.216	0.253
No	2.463	1.524–3.979	0.001
Age at menarche				0.732
≥13	1.607	1.534–2.239	0.008
<13	1.362	0.738–2.514	0.329
Education				0.637
Above high school	1.597	0.783–3.379	0.246
Others	1.628	1.067–2.484	0.029
Hypertension				0.314
Yes	4.313	1.130–16.456	0.041
No	1.291	0.877–1.900	0.203
Diabetes mellitus				0.124
Yes	NA	NA	NA
No	1.457	1.031–2.061	0.039

Abbreviations: ORs, Odd rations; 95% CI, 95% Confidence Interval; LAP index, Lipid accumulation product index.

Two-Sample Mendelian Analysis of TG, WC and Endometriosis

To further validate our observational findings across the NHANES data, we conducted a one-way two-sample MR to assess the causal relationship. Considering the LAP index was calculated by TG and WC, we analysis the causal relationship between TG, WC and endometriosis to indirectly explain the causal relationship between LAP and endometriosis (Table 4). The results revealed a significant association, indicating that an elevated TG was associated with an increased risk of endometriosis (OR 1.14, 95% CI: 1.06–1.22, P= 0.0001, FDR=0.00257). But the the associated was not observed in WC (OR 0.99, 95% CI: 0.83–1.20, P= 0.956, FDR=0.983).The scatter plot also showing the causality of TG, WC on endometriosis (Figure 3).

Table 4.

Mendelian Randomization to Determine the Causal Association Between TG and Endometriosis

Characteristic	Method	SNPs	β	SE	ORs 95% CI	P	FDR
TG	MR Egger	264	0.132	0.051	1.14 (1.03–1.26)	0.010	–
	Weighted median	264	0.078	0.048	1.08 (0.98–1.19)	0.104	–
	Inverse variance weighted (multiplicative random effects)	264	0.130	0.035	1.14 (1.06–1.22)	0.0001	0.00257
	Weighted mode	264	0.127	0.043	1.14 (1.04–1.23)	0.003	–
	Simple mode	264	0.148	0.106	1.16 (0.94–1.43)	0.164	–
WC	MR Egger	130	−0.428	0.262	0.65 (0.39–1.09)	0.105	–
	Weighted median	130	−0.185	0.131	0.83 (0.64–1.07)	0.158	–
	Inverse variance weighted (multiplicative random effects)	130	−0.005	0.0939	0.99 (0.83–1.20)	0.956	0.983
	Weighted mode	130	−0.266	0.178	0.77 (0.54–1.09)	0.139	–
	Simple mode	130	−0.144	0.3478	0.87 (0.44–1.71)	0.679	–

Abbreviations: TG, triglyceride; WC, Waist circumferences; ORs, Odd rations; 95% CI, 95% Confidence Interval; SNPs, single nucleotide polymorphisms.

Figure 3.

Scatter plot showing the causality of TG (A), WC (B) on endometriosis identified by IVW, MR egger, weighted median and weighted mode.

The MR-Egger intercept test revealed no evidence of directional pleiotropy for TG (intercept = –0.0001, P = 0.943), suggesting that the instrumental variables were not biased by horizontal pleiotropy (Table S3). And “Leave-one-out” method also showed similar results (Figure S1). Cochran’s Q test indicated significant heterogeneity (Q = 23.15, P = 0.034), suggesting potential differences in effects among the instrumental variables (Table S3). However, we conducted the MR-PRESSO analysis to demonstrated the robustness of the causal estimates, namely, after correcting for outlier variants, the association remained significant and even became stronger (Raw: beta= 0.1124, P = 0.0029; Outlier-corrected: beta = 0.1296, P = 0.0002), reinforcing the reliability of our findings (Table S4).

Discussion

In this study, we conducted a cross-sectional analysis using data from NHANES from 1999 to 2006 to explore the relationship between endometriosis and the LAP index. Our findings suggest that a higher LAP index is associated with an increased risk of endometriosis among US adults. Additionally, the two-sample Mendelian randomization analysis provided further evidence for a potential causal role of TG levels in this association, with a genetic prediction showing that higher TG levels are associated with an increased risk of endometriosis. Given its simplicity and clinical accessibility, the LAP index may serve as a potential metabolic marker for identifying women at elevated risk.

The etiology of endometriosis is multifactorial, with body weight and metabolic status emerging as significant contributors.²⁴ First, epidemiological studies have demonstrated that women with obesity or overweight exhibit an increased risk of developing endometriosis,²⁵ likely mediated by imbalances in adipokines (such as leptin and adiponectin) and pro-inflammatory cytokines secreted by adipose tissue.^26,27 Furthermore, Excessive visceral fat accumulation may also perturb estrogen metabolism and disrupt local immune microenvironments, thereby facilitating the growth and invasion of ectopic endometrial tissues.²⁸ Second, metabolic abnormalities, including insulin resistance and dyslipidemia, are commonly observed in patients with endometriosis, suggesting a pivotal role of metabolic dysregulation in disease pathogenesis.^24,26,29,30

The lipid accumulation product index(LAP), a robust indicator of visceral fat accumulation and metabolic risk, has been extensively investigated in the context of various metabolic disorders.³¹ Accumulating evidence has established significant associations between LAP and conditions such as metabolic syndrome, type 2 diabetes, cardiovascular diseases, and non-alcoholic fatty liver disease,^32–34 which are frequently characterized by insulin resistance, chronic low-grade inflammation, and dyslipidemia, and are also may implicated in the pathogenesis of endometriosis.³⁰

The association between LAP and endometriosis likely involves several interrelated biological pathways. First, high LAP is frequently associated with insulin resistance, increased triglyceride and reduced adiponectin levels, particularly in individuals with endometriosis. These metabolic disturbances may impair the regulation of estrogen metabolism and immune function, further promoting disease onset and progression.^35–38 Second, chronic low-grade inflammation may play an important role in the development of endometriosis, which is defined as a long-lasting, low-intensity inflammatory state that arises when a harmful stimulus persists or the inflammatory resolution process is deficient, leading to sustained activation of inflammatory pathways.³⁹ In this study, excessive visceral fat accumulation, reflected by an elevated LAP index, may induce systemic low-grade inflammation via the release of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α).^34,38 In addition, visceral fat accumulation can promote oxidative stress, which subsequently triggers cellular senescence. Senescent cells secrete a range of senescence-associated secretory phenotype (SASP) factors, including IL-1β, IL-6, IL-8, and matrix metalloproteinases (MMPs), thereby establishing and maintaining a chronic low-grade inflammatory state, which further facilitates the migration and invasion of ectopic endometrial cells.^40–42 Moreover, increased LAP levels may upregulate the expression of estrogen-synthesizing enzymes, such as aromatase (CYP19A1), while simultaneously reducing estrogen clearance. This hormonal imbalance can lead to elevated circulating estrogen levels, thereby increasing the risk of endometriosis.^43–45

Limitations and Strengths

The strengths of our study are as follows. First, the data was based on nationally representative data from NHANES to investigate the association between the LAP index and endometriosis. Given its simplicity and clinical accessibility, the LAP index may serve as a potential metabolic marker for identifying women at elevated risk. And the application of weighted regression analysis ensures broad generalizability to the US population. Second, we performed comprehensive adjustments for potential confounding factors and conducted subgroup analyses to enhance the robustness of our findings. Third, we conducted Mendelian randomization analysis to further explore the relationship between the LAP index and endometriosis. The results indicated that triglycerides, rather than waist circumference, were the primary driving factor associated with endometriosis risk.

However, there were also several limitations in present study. First, in the cross-sectional part of our study, the outcome was based on self-reported diagnoses, which may be subject to recall bias. Second, as the MR analysis was limited to individuals of European ancestry, the generalizability of the findings to other populations requires further validation. Third, other potential risk factors for endometriosis, such as hormone levels, menstrual characteristics, use of alternative contraceptive methods, and polycystic ovary syndrome (PCOS) status, were not included in our analysis, which may still be residual confounding variables which would affect our results. Despite these limitations, our findings underscore the potential associated between the LAP index and endometriosis, which highlight the importance of further research into the metabolic and lifestyle factors influencing endometriosis risk.

Conclusion

Our findings indicate that a higher lipid accumulation product index is associated with an increased risk of endometriosis among women in the US. Complementary evidence from two-sample Mendelian randomization suggests that elevated triglyceride levels may contribute to this observed association. Given its simplicity and clinical accessibility, the LAP index may serve as a potential metabolic marker for identifying women at elevated risk. However, further prospective and mechanistic studies are warranted to confirm these findings and clarify underlying causal pathways.

Funding Statement

The study were supported by Tongji University “Medicine + X” cross-disciplinary research project (No.20250049) and Popular science project of Shanghai Jing‘an District (No. KP2025088).

Data Sharing Statement

All National Health and Nutrition Examination Survey data were accessed from https://wwwn.cdc.gov/nchs/nhanes/Default.aspx. And in the present MR analysis, the data utilized were derived from the Finnish cohort (finngen_R12_N14_ENDOMETRIOSIS, https://www.finngen.fi/en) within the FinnGen study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no competing interests in this work.