Phthalate exposure is linked to sleep disruptions and insomnia in menopausal women


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 are common EDCs that are found in industrial plasticizers and chemical stabilizers.

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 [1].

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 [1].

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 [10] and earlier age at menopause [14].

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 [22].

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.


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