As the most common gynecologic operation, approximately 600,000 hysterectomies are performed annually in the United States for common gynaecologic benign indications, such as uterine fibroids, abnormal uterine bleeding, endometriosis, and pelvic organ prolapse (1). Although its prevalence has declined recently, hysterectomy continues to carry significant long-term health implications (2–4). Recent studies have suggested that there were associations between hysterectomy and increased risks of cardiovascular disease (5), stroke (6), metabolic disorders (7), kidney stone disease (8), and osteoporosis (9).

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and related inflammatory joint diseases, disproportionately affects women (10). Hormonal fluctuations, genetic predisposition, obesity, and aging are established contributors. Postmenopausal women, in particular, face elevated risks due to estrogen depletion, which exacerbates joint inflammation and cartilage degradation (11). Beyond hormonal factors, environmental exposures, including heavy metals, and nutritional deficiencies have recently emerged as modifiable risk factors (12, 13). However, the interplay between gynaecological surgeries and arthritis pathogenesis remains poorly understood.

Bone health of women after hysterectomy is a brand-new study field. Its potential role in arthritis remains underexplored. Relatively, it is clear at present that hysterectomy is related to female osteoporosis. Seo and Yuk (9), Choi et al. (14), and Xu et al. (15) reported that the risk of osteoporosis was increased in women who had undergone hysterectomy regardless of bilateral oophorectomy status. The adjusted odds ratios (ORs) were 1.28 ~ 1.84. However, whether it also increases the risk of fracture was controversial (9, 15). In relation to arthritis, studies are even rarer. In J Stöve’s group, 86.2% patients after hysterectomy developed bilateral OA and 33.3% occurred generalized OA (16). Recently, a Taiwanese cohort study further identified hysterectomy as an independent risk factor for osteoarthritis, especially knee OA (adjusted OR = 1.25, 95%CI = 1.13–1.38) (17). They speculated that it might be related to estrogen deficiency. No further research has been carried out.

In recent years, the role of heavy metals in the occurrence and the development of arthritis have attracted much attention, with primary focus on arsenic, cadmium, zinc, and lead (18, 19). It is generally acknowledged that the high exposure of heavy metals may be a synergistic risk factor associated with arthritis. Interestingly, the intake of some micronutrients may reverse such damage (20, 21). However, there is still a lack of large cohort clinical studies. Meanwhile, hysterectomy may indirectly influence these metals. For instance, estrogen deficiency post-surgery could impair heavy metal detoxification pathways, increasing their long-term exposure (22, 23). In addition, heavy metals may also acts as potent xenoestrogens with the risk to human health (24). In summary, the relationship among hysterectomy, arthritis, heavy metals, and micronutrients is highly complicated.

In order to explore this scientific problem, from the National Health and Nutrition Examination Survey (NHANES) (25, 26), we investigated the relationship between hysterectomy and arthritis and explored the role of heavy metals and the protective effect of vitamins. This study offers new insights into potential health risks associated with post-hysterectomy and hope to contribute to improving public health outcomes.

The present study represents the first large-scale epidemiological investigation to systematically evaluate the relationship between hysterectomy and arthritis risk in women, with a focus on elucidating the mediating role of serum heavy metals (particularly blood lead) and the protective effects of dietary micronutrients (notably vitamin K and vitamin D). Leveraging data from the NHANES cohort (2007–2018), our findings revealed three key observations: (1) hysterectomy, especially when combined with oophorectomy, is independently associated with a 3.3 ~ 4.7-fold increased risk of arthritis in women; (2) elevated blood lead levels mediate approximately 6% of this association, exhibiting a non-linear threshold effect; and (3) higher dietary intake of vitamin K and vitamin D significantly attenuates arthritis risk in hysterectomized women, with protective thresholds identified at 16.7 mcg/day and 1.3 mcg/day, respectively. These results advance our understanding of the long-term musculoskeletal consequences of hysterectomy and highlight actionable targets for mitigating post-surgical morbidity.

Our analysis corroborates emerging evidence linking hysterectomy to arthritis morbidity. The adjusted odds ratio (OR = 3.33, 95%CI: 2.49–5.04) for arthritis in hysterectomized women aligns with prior reports, such as the Taiwanese cohort study identifying a 25% increased risk of knee osteoarthritis (OA) post-hysterectomy (adjusted OR = 1.25). Notably, the risk escalated further in women who underwent concurrent oophorectomy (OR = 4.67), underscoring the compounded effects of estrogen depletion. Mechanistically, the uterus is not merely a reproductive organ but an endocrine-active tissue contributing to extra-ovarian estrogen synthesis and immunomodulation. Its removal disrupts systemic estrogen signalling, which regulates cartilage homeostasis, synovial inflammation, and osteoclast activity (31). Estrogen deficiency post-hysterectomy may accelerate joint degeneration via upregulation of matrix metalloproteinases (MMPs) (32) and interleukin-1β (IL-1β) (33), pathways implicated in both OA and rheumatoid arthritis (RA) pathogenesis. Furthermore, surgical trauma and postoperative inflammation could induce epigenetic modifications in joint tissues, priming them for accelerated aging.

A groundbreaking finding of this study is the identification of blood lead as a partial mediator (6.02%, p < 0.001) of the hysterectomy-arthritis relationship. Women with hysterectomy exhibited significantly higher levels of blood lead. Blood lead exposure amplified arthritis risk disproportionately, suggesting that even subclinical elevations may synergize with post-surgical metabolic shifts to harm joint health. Lead’s role in arthritis pathogenesis is well documented. Our mediation analysis suggested that hysterectomy exacerbated lead retention and further led to the occurrence and development of arthritis. However, the exact reason is still unclear. Studies have found that the expression of metallothionein I (MT-I) shows estrogen-dependent characteristics (34), while metallothionein has a broad potential for application in alleviating environmental heavy metal pollution (35). This might be one reason for the storage of blood lead due to estrogen deficiency after a hysterectomy. Interestingly, for blood lead, the inflection point at 0.10 μmol/L represents a toxicity threshold: below this level, each unit increase in lead amplified arthritis risk greatly. The threshold effect (0.10 μmol/L) corresponds to blood lead levels observed in populations with environmental or occupational exposure, highlighting the need for stricter monitoring in hysterectomized women. Public health interventions targeting lead reduction could mitigate arthritis risks in this vulnerable group, such as minimizing exposure to contaminated water, cosmetics, or ceramics.

Our study pioneers the exploration of dietary micronutrients as modifiers of hysterectomy-associated arthritis. Hysterectomy induces a dual deficiency state: estrogen loss impairs vitamin D activation, while an altered gut microbiota reduces vitamin bioavailability. Hysterectomized women may face additional barriers to adequate intake, such as post-surgical dietary restrictions or gut dysbiosis. The uterus and ovaries interact with the gut microbiota through estrogen-mediated modulation of intestinal permeability. Hysterectomy disrupts this axis, potentially impairing fat-soluble vitamin absorption (e.g., vitamins K and D). Dietary interventions emphasizing leafy greens (rich in vitamin K) and fortified dairy products (vitamin D sources) could counteract these deficits. Vitamin K emerged as a potent protective factor, with intake above 212.0 mcg/day reducing arthritis odds by 20% (p < 0.001). Vitamin D exhibited similar benefits with the optimal inflection points 212.0 mcg/day The protective threshold of vitamin K, particularly through matrix Gla-protein (MGP), is essential for bone health and may help prevent joint calcification and inflammation (36, 37). Additionally, hysterectomy may induce vitamin D deficiency through estrogen, thus indicating that even moderate intake confers benefits. The non-linear dose–response relationships suggest that optimal—rather than maximal—intake confers protection.

However, there are some limitations to the present study. The study’s cross-sectional design limits the ability to establish causality. We did not further classify arthritis, such as osteoarthritis and rheumatoid arthritis. There was the potential for selection bias due to exclusion of participants with missing data (>50% of the initial sample). We could not clarify the arthritis that occurred after uterine surgery due to a large number of missing data. We could only analyze the average ages of the two events that occurred, which were 40.85 (age when had hysterectomy) and 57.87 (age when told you had arthritis), respectively. The sample size of G2 (only having undergone ovaries removal) was too small, which might affect the analysis results of the subsequent group. However, in the results section, we focused on women who underwent hysterectomy (G1 and G3). The measurement of main variables (such as hysterectomy, arthritis, and dietary vitamin intake) relies on self-reported data, which is susceptible to recall bias. Additionally, despite adjusting for several potential confounders, the absence of important covariates (such as menopausal status, hormone replacement therapy, and time since surgery) could influence the results.

In conclusion, hysterectomy is associated with an increased risk of arthritis, with focus on blood lead as a mediating factor and vitamin intake as a potential protective factor. It will contribute to long-term health management after hysterectomy.