Phthalates, oxidative stress, and hot flashes in aging women

Hot flashes are transient periods of intense heat in the upper body, arms, and face that are often followed by flushing of the skin, profuse sweating, chills, palpitations, and anxiety. Hot flashes pose a significant public health concern because they are the most common perimenopausal symptom reported by women in the U.S., affecting 4-5 million women each year. For more than half of these women, hot flashes last more than 7 years and some have hot flashes for up to 30 years. In addition, hot flashes negatively impact quality of life and lead to increased health care expenditures. Despite the importance of hot flashes in women's lives, little is known about their risk factors. Other than a few studies on cigarette smoking and one study on organic solvents, no studies examined the association between environmental chemical exposures and hot flashes in women. Thus, we conducted preliminary studies to examine whether exposure to phthalates is associated with an increased risk of hot flashes in a cohort of 782 midlife women. We focused on phthalates because they are one of the top contaminants present in human tissue and are used in a myriad of consumer products. Our data indicate that phthalate exposure is significantly associated with an increased risk of having recent and frequent hot flashes in midlife women. In fact, the degree of association is similar to that observed with cigarette smoking, one of the best known risk factors for hot flashes. Although our data clearly indicate that phthalate exposure is associated with a higher risk of hot flashes, we do not understand the underlying mechanisms. Published studies indicate that phthalate exposure increases oxidative stress in animal models and a few small epidemiological studies suggest that oxidative stress increases the risk of hot flashes. Thus, the overall goal of the proposed study is to test the hypothesis that a cumulative mixture of phthalates is associated with increased risk of hot flashes via oxidative stress pathways. We will test this hypothesis by completing the following specific aims: 1) prospectively determine if cumulative exposure to a mixture of phthalates is associated with validated biomarkers of oxidative stress in midlife women, 2) prospectively determine if validated biomarkers of oxidative stress are associated with hot flashes in midlife woman, and 3) explore whether observed associations between urinary phthalate metabolite concentrations and hot flashes are mediated by biomarkers of oxidative stress. This work may lead to the development of better strategies to prevent and treat perimenopausal hot flashes, a condition that goes untreated in the majority of women experiencing symptoms despite seeking medical treatment. Given the known risks associated with current treatments for hot flashes (e.g., cancer, blood clots, stroke), new treatments could be critical for this prevalent health outcome.