Heavy Metals and Trajectories of Anti-Mllerian Hormone During the Menopausal Transition

Background Experimental and epidemiological studies have linked metals with women's reproductive aging, but the mechanisms are not well understood. Disrupted ovarian folliculogenesis and diminished ovarian reserve could be a pathway through which metals impact reproductive hormones and outcomes.Objective The study aimed to evaluate the associations of heavy metals with anti-Mullerian hormone (AMH), a marker of ovarian reserve.Methods The study included 549 women from the Study of Women's Health Across the Nation with 2252 repeated AMH measurements from 10 to 0 years before the final menstrual period (FMP). Serum AMH concentrations were measured using picoAMH ELISA. Urinary concentrations of arsenic, cadmium, mercury, and lead were measured using high-resolution inductively coupled plasma mass spectrometry. Multivariable linear mixed regressions modeled AMH as a function of time before the FMP interaction terms between metals and time to the FMP were also included.Results Adjusting for confounders, compared with those in the lowest tertile, women in the highest tertile of urinary arsenic or mercury concentrations had lower AMH concentrations at the FMP (percent change: -32.1%; 95% CI, -52.9 to -2.2, P-trend = .03 for arsenic; percent change: -40.7%; 95% CI, -58.9 to -14.5, P-trend = .005 for mercury). Higher cadmium and mercury were also associated with accelerated rates of decline in AMH over time (percent change per year: -9.0%; 95% CI, -15.5 to -1.9, P-trend = .01 for cadmium; -7.3%; 95% CI, -14.0 to -0.1, P-trend = .04 for mercury).Conclusion Heavy metals including arsenic, cadmium, and mercury may act as ovarian toxicants by diminishing ovarian reserve in women approaching the FMP.