Elevated levels of nitrous dioxide are associated with lower AMH levels: a real-world analysis

Abstract

STUDY QUESTION Are there any associations between environmental pollutants and ovarian reserve, expressed by anti-Mullerian hormone (AMH) serum levels? SUMMARY ANSWER In this first real-world approach to demonstrate the relationship between air pollutants and serum AMH levels, adverse associations were observed for nitrogen dioxide (NO2) but not with particulate matter. WHAT IS KNOWN ALREADY In recent years, air pollution has emerged as a potential disrupter to the homeostasis of physiological hormones, possibly affecting human reproduction. Although the influence of age and smoking on AMH levels is largely accepted, the relationship between AMH and the environment has not currently been established. STUDY DESIGN, SIZE, DURATION A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed in a single laboratory from January 2007 to October 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Serum AMH data were connected to patients’ age and residential address, to include air pollution data after geo-localisation. The air pollution considered daily particulate matter (PM) and NO2 values. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1463 AMH measurements were collected (mean 1.94 ng/ml, median 0.90 ng/ml). AMH was inversely related to patients’ age in women older than 25 years (adjusted R-squared 0.120, P < 0.001), but not in those younger than 25 years (adjusted R-squared 0.068, P = 0.055). AMH levels were inversely related to environmental pollutants, such as PM10 (Rho = −0.088, P = 0.001), PM2.5 (Rho = −0.062, P = 0.021) and NO2 (Rho = −0.111, P < 0.001). After subdividing the dataset into quartiles for PM10 and PM2.5, the influence of age on AMH serum levels was found to be a stronger influence than that exerted by PM (P = 0.833 and P = 0.370, respectively). On the contrary, considering NO2 quartiles, higher AMH levels were observed in third quartile compared to fourth quartile, even after adjustment for age (P = 0.028), indicating a stronger influence of NO2 exposure on AMH serum levels. Considering an AMH cut-off of 0.3 ng/ml, a significant higher frequency of women with severe ovarian reserve reduction in the fourth quartile was shown only for NO2 (P = 0.010). LIMITATIONS, REASONS FOR CAUTION Several limitations should be underlined, such as the lack of information about work and life habits of each patient and the retrospective nature of the analysis performed on real-world data. WIDER IMPLICATIONS OF THE FINDINGS Although the genetic component is highly predictive for defining the ovarian reserve at birth, potentially modifiable environmental factors could influence the rate of decline in AMH and ovarian reserve during adulthood. STUDY FUNDINGCOMPETING INTEREST(S) Authors have neither funding nor competing interests to declare. TRIAL REGISTRATION NUMBER N/A.

Using follicular fluid metabolomics to investigate the association between air pollution and oocyte quality

“…First, the follicular fluid is a distinct biological fluid from blood and may represent a more toxicologically relevant biofluid for investigating the impacts of air pollution on ovarian function. ( Qasemi and Amidi, 2020 ) Second, NO 2 exposure may have a specific negative impact on the ovary, ( Gregoire et al, 2021 ; La Marca et al, 2020 2020) which may be better captured by studying follicular fluid as opposed to blood.…”

Environmental Exposures and Anti-Müllerian Hormone: A Mixture Analysis in the Nurses’ Health Study II

“…So far, two studies reported inconsistent results for the association of PM with AMH. 12,14 Such inconsistency may be due to differences in the study population, exposure levels and time windows of exposures examined, and geographic characteristics.…”

“…So far, two studies reported inconsistent results for the association of PM with AMH. 12,14 Such inconsistency may be due to differences in the study population, exposure levels and time windows of exposures examined, and geographic characteristics. The observed associations in the main analysis were found in women above age 40, while there was less evidence of associations among younger women.…”

“…10,11 Several environmental factors, including particulate air pollution, traffic, ultraviolet (UV) radiation, and greenspace, have been linked with AMH and age at menopause. [12][13][14][15][16][17] However, these studies only examined the association of single exposure, without considering the complex mixture of exposures that is truly experienced. Additionally, other studies have linked impaired fertility and menstrual disorders, which are common consequences of reproductive aging, with occupational exposure to organic compounds that are also present in the ambient atmosphere.…”

Unraveling the Balance between Genes, Microbes, Lifestyle and the Environment to Improve Healthy Reproduction

“…The team found that AMH levels were lower in women who lived in areas with higher levels of pollution as assessed by measuring the daily values of fine particles (PM 2.5 and PM 10). When the team divided air pollution into four brackets, they found that three times as many women living in the lower bracket had lower levels of AMH than those in the higher brackets, referring to a level below 1 ng/mL, a value that correlates with a serious ovarian deficiency [122] (Figure 2).…”