Persistent Organic Pollutants and Early Menopause in U.S. Women

Abstract

ObjectiveEndocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause.MethodsCross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45–55 years.FindingsThis analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of β-hexachlorocyclohexane, mirex, p,p’-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners −70, −99, −105, −118, −138, −153, −156, −170, and −183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women.ConclusionsThis study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman’s life and has profound implications for fertility, human reproduction, and our global society.

The impact of FMR1 gene mutations on human reproduction and development: a systematic review

“…With intermediate (45)(46)(47)(48)(49)(50)(51)(52)(53)(54) and premutation carriers (55-200 CGG repeats), we notice a translation fault which can be held accountable for mRNA production levels [93] not balanced through an equivalent rise in FMRP that frequently is normal or somewhat reduced. By consequence, the mRNA levels build-up in the cells where it is hypothesized to exert cytotoxic effects (RNA/protein toxic gain-of-function disorder).…”

“…This 'normal' range, however, may not in fact be a homogenous population. Gleicher et al reported the intermediate genotype (45)(46)(47)(48)(49)(50)(51)(52)(53)(54) repeats) expresses a minor instability unrelated to a definite phenotype or to the fragile X syndrome (FXS) within one generation, even though the risk is consistent in two generations [113]. These intermediate carriers, compared to 'normal', show a greater prevalence of subfertility, menstrual cycle anomalies, overall earlier than anticipated menopause (by ∼7 years), premature ovarian failure (32 vs 1 %), increased prevalence of osteoporosis, higher rate of aneuploidy, miscarriage and even perhaps non-identical twinning rates [85,94].…”

“…Normal ovarian function is, in fact, a continuum process that initiates early during intrauterine life and persists throughout reproductive life, up to menopause. Endocrinological [90], autoimmune [41] and iatrogenic factors [13], as well as genetic causes [72] and microenvironmental dynamics (i.e., endocrine disrupting chemicals) [45], are frequently described for their possible impact on the size and quality of the follicle and oocyte pool, and as potential causes of premature ovarian senescence. FMR1 is one of the most commonly described genetic factors.…”

Is in utero exposure to maternal socioeconomic disadvantage related to offspring ovarian reserve in adulthood?

“…With respect to ovarian aging outcomes in particular, a recent review [95] summarized relevant human and animal literatures, suggesting environmental toxicants accelerate folliculogenesis and follicular atresia, including in the primordial stage and extending across the spectrum of ovarian follicle development. Notably, in a large representative sample of US women (n = 31,575) EDCs (i.e., polychlorinated biphenyl [PCBs], pesticides, furans, and phthalates) were associated with earlier onset menopause up to 3.8 years earlier, following adjustment for covariates [96]. In addition, prospective studies showed higher urinary phthalate and BPA levels were related to decreases in ovarian reserve as marked by lower AFC, although participants were patients seeking infertility treatment [97,98].…”

Environmental sensitivity as a trigger of erythema nodosum and perimenopausal symptoms

“…The association between environmental chemical exposure and endocrine abnormalities, including early menopause, has previously been suggested 4. One presumptive trigger, BPA is a chemical used in the production of plastics and epoxy resin.…”