Age at Menopause: Do Chemical Exposures Play a Role?

By Schmidt, Charles W. | Environmental Health Perspectives, June 2017 | Go to article overview

Age at Menopause: Do Chemical Exposures Play a Role?


Schmidt, Charles W., Environmental Health Perspectives


With its associated hot flashes, mood swings, and insomnia, menopause can be a challenging period in a woman's life. But as much as it marks the end of her childbearing years, menopause-and more specifically the age at which it occurs--can also reflect on a woman's overall health. An older age at menopause typically reflects good health overall, whereas early menopause-generally defined as occurring before age 40--can reflect poorer health and a greater likelihood of premature mortality. (1)

Now, experts are taking a closer look at how environmental exposures may influence age at menopause and whether exposure-induced changes in menopausal timing put women at greater risk of associated health problems. These are early days in the field, but recent research suggesting a link between potential endocrine-disrupting compounds (EDCs) and early menopause (2,3) has raised concerns over how exposures might accelerate hormonal processes involved in female aging.

"We know that going through menopause early increases the risk of osteoporosis, heart disease, and other disorders," says Natalia Grindler, a reproductive and endocrinology fellow at the University of Colorado's Advanced Reproductive Medicine Division. "So the long-term health implications of early menopause are considerable."

There is still much to be learned about the toxicology underlying changes in age at menopause, and isolating chemical effects from the other varied influences that govern when a woman's reproductive years come to an end is challenging. Nevertheless, this area of study provides a new window on population-level effects from chemical exposures that could have wide-ranging consequences.

Mechanisms of Menopause

The fact that exogenous exposures can shorten the time to menopause first became evident during the 1970s, when research began linking early menopause with exposure to tobacco smoke. (4,5) Scientists have since reported associations with other environmental chemicals, including dioxins, polychlorinated biphenyls (PCBs), and phthalates. (1,3,6) To grasp how chemicals might hasten menopause, however, one first needs to understand the underlying hormonal system affected by exposure.

Healthy females are born with two ovaries, each filled with millions of immature eggs (oocytes) surrounded by specialized granulosa cells. By the time a girl reaches puberty, this number will have dwindled to approximately 400,000, of which just 400 or so eggs will become available for fertilization during the course of her life.

The menstrual cycle starts with the secretion of gonadropin-releasing hormone (GnRH) from the hypothalamus. GnRH triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH), which in turn initiates development of the follicle containing the oocyte, leading toward ovulation: the oocyte begins to mature, and the granulosa cells start secreting estrogen. When estrogen levels are sufficiently high, they cause the anterior pituitary to secrete luteinizing hormone (LH), which induces ovulation, or the release of the egg for fertilization.

The transition into natural menopause--as opposed to menopause caused by surgery (e.g., removal of the ovaries because of fibroids) or medication (e.g., chemotherapy)--is known as perimenopause. This transition typically begins in a woman's mid-40s, (7,8) when the functioning of the ovaries becomes inconsistent. "Perimenopausal women have irregular menstrual cycles, and it is not clearly understood if that has something to do with reduced function of the pituitary gland, or if it is because the ovarian follicles are not functioning adequately," says Patricia Hoyer, a professor of physiology and of pharmacology and toxicology at the University of Arizona College of Medicine.

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During perimenopause, declining estrogen output by the ovaries causes FSH and LH levels to remain elevated as the pituitary gland attempts to drive ovulation. …

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