For menopausal women who have difficulty sleeping, it might be because of chemicals in the environment.
A new study based on data from the Midlife Women’s Health Study suggests that exposure to various chemicals, such as phthalates, found in hundreds of products used daily, is associated with sleep disruptions in midlife women.
Study results are published online today in Menopause.
Up to 60% of women in the menopause transition experience sleep difficulties. Women who have trouble falling asleep are at greater risk of developing persistent depression that can lead to worse health outcomes, may require more medical care, and increase absenteeism.
Earlier studies have shown that such sleep disruption is the result of decreasing hormone levels.
Exposure to endocrine-disrupting chemicals (EDCs), however, is one largely unexplored area that may help to explain the increased prevalence of sleep difficulties in midlife women.
Phthalates increase the performance of everything from food packaging and clothing to cosmetics and children’s toys.
Personal care products, in particular, represent a major area of exposure.
Although everyone is exposed to phthalates, they appear to concentrate more in women than men. A previous study suggested that increased exposure to phthalates from personal care products significantly increased the risk of hot flashes.
Other studies have demonstrated associations between phthalate exposure and the likelihood of waking up at night, as well as the risk of suffering from depression.
Since phthalates are known to modulate the hormones associated with sleep and depression, researchers in this latest study surmised that they may be directly or indirectly associated with sleep in midlife women.
This study, based on data gathered from more than 760 premenopausal and perimenopausal women, suggests that the frequency of sleep disruptions is associated with urinary concentrations of phthalates.
It is the first known study to document this association. The relationship, however, appears complex, because other variables, such as smoking status, have been shown to influence the effect.
More research is warranted to fully understand this association, as well as the underlying mechanisms of how hormones and EDC exposure influence sleep, particularly in midlife women.
Study results appear in the article “Associations of phthalate exposure and endogenous hormones with self-reported sleep disruptions: results from the Midlife Women’s Health Study.”
“This study raises concerns and additional questions about a possible contribution of phthalates to sleep disturbances in premenopausal and perimenopausal women.
Additional research into these endocrine-disrupting chemicals and their interactions with hormones, sleep, and mood in midlife women is needed,” says Dr. Stephanie Faubion, NAMS medical director.
Phthalates are a large class of ubiquitous synthetic chemicals, which are used as plasticizers and stabilizers in a myriad of consumer products, including shower curtains, children’s toys, cosmetics, and personal care products such as perfumes, nail polishes, deodorants, and lotions [1–3].
Phthalates are also used in pesticides, wood finishes, adhesives, solvents, lubricants, and in medical devices including tubing, blood bags, surgical gloves, and dialysis equipment .
The wide range of products in which phthalates are incorporated results in a global production and use of phthalates that is greater than 18 billion pounds per year .
The chemical structures of phthalates consist of esters of ortho-phthalic acid and are named based on the alcohol that generates the varying lengths of the alkyl chain in a linear or branched format. Phthalate esters with long alkyl chains (more than 6 carbons) have higher molecular weights and are likely to undergo chemical modifications for renal excretion.
At least six different parent phthalates are used in consumer products, including diethyl phthalate (DEP; short alkyl chain), di(2-ethylhexyl) phthalate (DEHP; long alkyl chain), dibutyl phthalate (DBP; short alkyl chain), diisobutyl phthalate (DiBP; short alkyl chain), diisononyl phthalate (DiNP; long alkyl chain), and butyl benzyl phthalate (BBzP; short alkyl chain) [1, 3].
The parent compounds can be converted mainly by the gastrointestinal tract or liver to various metabolites that can be more toxic than the parent compound [1, 3–5].
The ubiquity of phthalates and phthalate metabolites is further evidenced by their detection in nearly all tested human urine samples [6–10]. Interestingly, the measured levels of urinary phthalate metabolites are higher in women compared to men [1, 11].
This finding is possibly due to a greater use of personal care products by women compared to men.
Previous epidemiological studies indicate that phthalate metabolites can reach the reproductive tissues and adversely affect reproductive function [8, 12, 13]. For example, phthalate metabolites have been associated with an increased risk of endometriosis  and earlier age at menopause .
Further, animal studies indicate that exposure to phthalates inhibits ovarian synthesis of sex steroid hormones that are required for normal reproductive function [3, 4, 15–17], and epidemiological studies indicate that phthalate exposure is associated with reduced sex steroid hormone levels [8, 12, 18, 19].
It is not clear, however, whether and how phthalates impact reproductive function as women age and enter the menopausal transition.
During the menopausal transition, a woman’s reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases [20, 21]. Hot flashes are transient periods of intense heat in the upper parts of the body and are often followed by flushing of the skin, profuse sweating, chills, palpitations, and anxiety .
Despite the high prevalence of hot flashes among women undergoing the menopausal transition, little is known about the etiology or the risk factors for hot flashes. However, the predominant hypothesis is that drastic changes in estrogen levels lead to the onset of menopausal hot flashes [20, 22] and that low estradiol levels are associated with an increased risk of any, frequent, and severe hot flashes [20, 23–25].
With evidence from animal studies that phthalates reduce estradiol levels [3, 4, 15, 16], evidence from epidemiological studies that low estradiol levels are associated with an increased risk of hot flashes [20, 23, 25], and information that women commonly use personal care products containing phthalates [1, 2], we tested the hypothesis that higher urinary levels of phthalate metabolites, including those combinations of phthalate metabolites present in personal care products, are associated with an increased risk of midlife hot flashes.
- Heudorf U, Mersch-Sundermann V, Angerer J. Phthalates: toxicology and exposure. Int J Hyg Environ Health. 2007; 210:623–634. [PubMed: 17889607]
- Koo HJ, Lee BM. Human monitoring of phthalates and risk assessment. J Toxicol Environ Health A. 2005; 68:1379–1392. [PubMed: 16009652]
- Hannon PR, Flaws JA. The effects of phthalates on the ovary. Front Endocrinol (Lausanne). 2015; 6:8. [PubMed: 25699018]
- Lovekamp TN, Davis BJ. Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells. Toxicol Appl Pharmacol. 2001; 172:217–224. [PubMed: 11312650]
- Wang W, Craig ZR, Basavarajappa MS, Hafner KS, Flaws JA. Mono-(2-ethylhexyl) phthalate induces oxidative stress and inhibits growth of mouse ovarian antral follicles. Biol Reprod. 2012; 87:152. [PubMed: 23077170]
- Hogberg J, Hanberg A, Berglund M, Skerfving S, Remberger M, Calafat AM, et al. Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ Health Perspect. 2008; 116:334–339. [PubMed: 18335100]
- James-Todd T, Stahlhut R, Meeker JD, Powell SG, Hauser R, Huang T, et al. Urinary phthalate metabolite concentrations and diabetes among women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008. Environ Health Perspect. 2012; 120:1307–1313. [PubMed: 22796563]
- Marsee K, Woodruff TJ, Axelrad DA, Calafat AM, Swan SH. Estimated daily phthalate exposures in a population of mothers of male infants exhibiting reduced anogenital distance. Environ Health Perspect. 2006; 114:805–809. [PubMed: 16759976]
- Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, et al. Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999–2000. Environ Health Perspect. 2004; 112:331–338. [PubMed: 14998749]
- Upson K, Sathyanarayana S, De Roos AJ, Thompson ML, Scholes D, Dills R, et al. Phthalates and risk of endometriosis. Environ Res. 2013; 126:91–97. [PubMed: 23890968]
- Hatch EE, Nelson JW, Qureshi MM, Weinberg J, Moore LL, Singer M, et al. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002. Environ Health. 2008; 7:27. [PubMed: 18522739]
- Hauser R, Skakkebaek NE, Hass U, Toppari J, Juul A, Andersson AM, et al. Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab. 2015; 100:1267–1277. [PubMed: 25742517]
- Adibi JJ, Hauser R, Williams PL, Whyatt RM, Calafat AM, Nelson H, et al. Maternal urinary metabolites of Di-(2-Ethylhexyl) phthalate in relation to the timing of labor in a US multicenter pregnancy cohort study. Am J Epidemiol. 2009; 169:1015–1024. [PubMed: 19251754]
- Grindler NM, Allsworth JE, Macones GA, Kannan K, Roehl KA, Cooper AR. Persistent organi c pollutants and early menopause in U.S. women. PLoS One. 2015; 10:e0116057. [PubMed: 25629726]
- Hannon PR, Brannick KE, Wang W, Flaws JA. Mono(2-ethylhexyl) phthalate accelerates early folliculogenesis and inhibits steroidogenesis in cultured mouse whole ovaries and antral follicles. Biol Reprod. 2015; 92:120. [PubMed: 25810477]
- Hannon PR, Brannick KE, Wang W, Gupta RK, Flaws JA. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles. Toxicol Appl Pharmacol. 2015; 284:42–53. [PubMed: 25701202]
- Gupta RK, Singh JM, Leslie TC, Meachum S, Flaws JA, Yao HH. Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro. Toxicol Appl Pharmacol. 2010; 242:224–230. [PubMed: 19874833]
- Meeker JD, Ferguson KK. Urinary phthalate metabolites are associated with decreased serum testosterone in men, women, and children from NHANES 2011–2012. J Clin Endocrinol Metab. 2014; 99:4346–4352. [PubMed: 25121464]
- Mendiola J, Meeker JD, Jorgensen N, Andersson AM, Liu F, Calafat AM, et al. Urinary concentrations of di(2-ethylhexyl) phthalate metabolites and serum reproductive hormones: pooled analysis of fertile and infertile men. J Androl. 2012; 33:488–498. [PubMed: 21597090]
- Ziv-Gal A, Flaws JA. Factors that ma y influence the experience of hot flushes by healthy middle- aged women. J Womens Health (Larchmt). 2010; 19:1905–1914. [PubMed: 20831431]
- Freeman EW, Sammel MD, Gracia CR, Kapoor S, Lin H, Liu L, et al. Follicular phase hormone levels and menstrual bleeding status in the approach to menopause. Fertil Steril. 2005; 83:383– 392. [PubMed: 15705379]
- Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci. 1990; 592:52–86. discussion 123–33. [PubMed: 2197954]
- Gallicchio L, Miller SR, Kiefer J, Greene T, Zacur HA, Flaws JA. Risk factors for ho t flashes among women undergoing the menopausal transition: baseline results from the Midlife Women’s Health Study. Menopause. 2015
- Gallicchio L, Miller SR, Visvanathan K, Lewis LM, Babus J, Zacur H, et al. Cigarette smoking, estrogen levels, and hot flashes in midlife women. Maturitas. 2006; 53:133–143. [PubMed: 16368467]
- Visvanathan K, Gallicchio L, Schilling C, Babus JK, Lewis LM, Miller SR, et al. Cytochrome gene polymorphisms, serum estrogens, and hot flushes in midlife women. Obstet Gynecol. 2005; 106:1372–1381. [PubMed: 16319265]