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Exposure to Small-Particle Air Pollution During Gestation Increases Risk of PCOS

Key findings

  • This nationwide U.S. study of 3,321 women examined whether exposure to particulate matter (PM) or nitrogen dioxide (NO2) during preconception, gestation, or childhood is associated with increased risk of polycystic ovary syndrome (PCOS)
  • Exposure to higher levels of PM with an aerodynamic diameter ≤2.5 micrometers (PM2.5) during the first trimester increased the risk of PCOS development (adjusted HR, 1.38 per 5.4 mcg/m3; 95% CI, 1.03–1.80)
  • Exposure to PM2.5-10, PM10, or NO2 showed little association with PCOS risk, except for a suggestive link between PCOS and higher PM10 exposure during the first trimester
  • Future studies should investigate additional pollutants, different levels of exposure, and different populations to determine whether the findings remain robust in preconception, gestation, childhood, and lifetime windows

Ovulation disorders, such as polycystic ovary syndrome (PCOS), confer major risks across the lifespan. Exposures thought to influence risk include toxicants and heavy metals. Such exposures can influence hormone imbalance, hyperandrogenism, and insulin resistance, the pathophysiological foundation of PCOS.

Air pollution exposure during vulnerable periods of development might also influence PCOS development. Shruthi Mahalingaiah, MD, MS, director of Clinical Research at the Massachusetts General Hospital Fertility Center, Elizabeth Peebles, a research assistant at the Harvard T.H. Chan School of Public Health, co-first author Makiko Mitsunami, a post-doctoral fellow at the Harvard T.H. Chan School of Public Health, and colleagues recently became the first to study this issue.

In Environment International, they describe a significant link between PCOS and particulate matter (PM; particles composed of sulphate, nitrates, ammonia, sodium chloride, black carbon, mineral dust or water) in U.S. women.

Methods

The research group analyzed health information reported by 3,321 women participating in the nationwide Growing Up Today Study 2 (GUTS2). Launched in 2004, this U.S. study enrolled children born between 1988 and 1996 to female nurses participating in the Nurses’ Health Study II (NHSII). GUTS2 participants complete questionnaires annually or biennially, and the researchers included responses received through 2023. In 2009, mothers of the GUTS2 participants reported their pregnancy history in NHSII and via a GUTS2 mothers’ questionnaire.

Time-varying spatio-temporal models were used to estimate monthly levels of four types of air pollution during the study period:

  • PM5—particulate matter with an aerodynamic diameter ≤2.5 micrometers; while particles of all size diameters can be inhaled, these small particles can cross into blood circulation
  • PM5–10—diameter between 2.5 and 10 micrometers
  • PM10—diameter ≤10 micrometers
  • Nitrogen dioxide (NO2), a gas produced from combustion processes such as heating, transportation, industry, and power generation

Exposure and PCOS

237 of the 3,321 participants (7%) reported having received a diagnosis of PCOS. In multivariable analysis, participants who had higher estimated exposure to certain forms of air pollution during their first trimester of development were more likely to report PCOS:

  • PM5—adjusted HR, 1.38 per 5.4 mcg/m3 (95% CI, 1.03–1.80)
  • PM10—aHR, 1.29 per 9.6 mcg/m3 (95% CI, 0.97–1.72; suggestive association)

In the main analysis, exposure to these sizes of particulate matter during preconception or childhood (defined as the period from birth to menarche) was not associated with the risk of PCOS. However, a sensitivity analysis suggested an association between PCOS and PM2.5 exposure during the 10 to 12 months before birth, which could make paternal exposure worth studying as well.

Potential Mechanism

Dr. Mahalingaiah’s group speculates that exposure to respirable PM influences PCOS development during gestation by threatening oogenesis and oocyte development. It may also impair signaling in the hypothalamic–pituitary–ovarian axis. Additional ambient air pollutants should be studied for their effect on PCOS, including sulfur dioxide, nitric oxide, and black carbon.

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