Shortly after moving to Canada's Okanagan Valley, Patricia Lee started experiencing severe irregularities in her menstrual cycle. She had one period that lasted two and a half months. The bleeding was so intense that at one point, doctors recommended a blood transfusion.
"I couldn't sleep--it was excruciatingly painful and I grew quite weak," said Lee, now 47. Her diagnosis: a fibroid, or benign tumor, the size of a ping-pong ball in her uterus, and two cysts in her ovaries.
At the time, Lee lived in a long, slender valley through the center of British Columbia that produces nearly all of the province's tree fruits and grapes. Agriculture is intensive there, as is pesticide use.
Lee will never know what role, if any, her environment played in causing her uterine fibroids. But scientists have long suspected a link between hormone-disrupting chemicals in the environment and gynecological diseases.
Research investigating these links has had mixed results. Now several new studies are adding to the evidence that some estrogen-mimicking pesticides and industrial chemicals may increase women's risk of uterine and ovarian diseases--helping to solidify a theory that emerged two decades ago.
"Our studies are beginning to corroborate the idea that environmental estrogen may be associated with endometriosis," said Germaine Buck-Louis, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development's epidemiology division in Maryland.
Back in 1993, a connection between endometriosis and environmental chemicals was discovered. Rhesus monkeys fed food contaminated with dioxins--hormone-disrupting pollutants created by waste incinerators and other industries--developed endometriosis 10 years later.
Endometriosis, when uterine tissue grows in the ovaries or other parts of the body, often causes pelvic pain and infertility. An estimated 10 to 20 percent of reproductive-age women in the United States suffer from it, according to the Endometriosis Foundation of America.
In a major new study, two groups of women in the Salt Lake City and San Francisco areas--one group with pelvic pain and the other with no symptoms--were more likely to be diagnosed with endometriosis if they had high blood levels of the estrogen-like pesticide hexachlorocyclohexane (HCH) than women with low levels. HCH has been banned as a crop pesticide in the United States but it builds up and persists in the environment, so it remains in some food supplies.
Calling the research "revolutionary," Buck-Louis said that finding the link in both groups of women "is a pretty strong signal" that the connection between endometriosis and the pesticide is real.
Also, women in the same group with the highest level of a sunscreen chemical, benzophenone, in their urine had a 19 percent higher risk of endometriosis than women with the lowest levels, according to research published in Environmental Science and Technology.
And in Italy, women had endometriosis more often if they had higher levels of two banned chlorinated chemicals that can disrupt hormones--polychlorinated biphenyls (PCBs) or residue of the insecticide DDT, according to a 2009 study of 158 women.
Recent research has uncovered links to other gynecological problems, too. Women in Greece diagnosed with polycystic ovary syndrome (PCOS)--which causes irregular menstrual periods, infertility, weight gain and excessive hair growth--were more likely to have higher blood levels of the estrogen-mimicking chemical bisphenol A than women without the disease, according to a study published last year.
"It's certainly plausible that any outside source that alters estrogen levels, even slightly, could contribute to gynecological diseases," said Dr. Megan Schwarzman, a family physician at San Francisco General Hospital and an environmental health scientist at the University of California, Berkeley.
Exposure to many hormone-disrupting chemicals starts in the womb, and some scientists suspect the timing may be important in determining reproductive disease risk later in life.
"We know from animal models that there are critical periods during early development when cells are rapidly dividing and forming the circuitry through which cells will communicate with each other to form various tissues of the body," said Retha Newbold, a reproductive biologist at the National Institute of Environmental Health Sciences in North Carolina. "When chemicals alter this set-up, the changes may not be reversible."
Future generations of females may be at risk, too, according to new animal research by Washington State University scientists.
Female rats exposed in the womb to high doses of several chemicals--including pesticides and plasticizers--developed cysts resembling human polycystic ovarian syndrome and premature menopause, according to the study published in PLoS One in July. Those changes were passed down through three generations--great-granddaughters of the exposed rats also developed cysts and other ovarian problems, even though they were not directly exposed.
Seeking to learn how the chemicals were able to harm future generations, the Washington State researchers examined the DNA of the ones whose mothers were exposed to vinclozolin, an estrogenic fungicide commonly used in the wine industry. They found that the chemical had reprogrammed genes as the rat fetuses developed.
Other chemicals in the study that had the multi-generational effects were dioxins, a pesticide mixture including permethrin and DEET and a plastic mixture including BPA and two widely used phthalates.
"What we are seeing in animal models is sobering," said John McLachlan, a biomedical scientist at Tulane University in New Orleans. The gene mechanisms responsible for transmitting such harmful effects across generations are essentially the same in humans, he said.
In the case of uterine fibroids, the body's natural estrogens turn genes on and off in the smooth muscle of the uterus that allow the tumors to grow, according to research by McLachlan and colleagues. They are now investigating whether estrogen-mimicking chemicals in the environment affect these same genes.
The danger of estrogen-like chemicals already has been well-documented with DES, or diethylstilbestrol, a drug that was prescribed to millions of women at risk of miscarriages from 1940 through 1971. Daughters and granddaughters of the pregnant women who took the potent estrogenic drug had an increased risk of endometriosis, uterine fibroids and rare reproductive cancers.
But pesticides, sunscreen ingredients and PCBs are less potent hormone mimics than DES. The effects on women's health are not as clear.
Some studies have found no connection between women's exposure to environmental chemicals and gynecological diseases. For instance, among several hundred women in Italy highly exposed to dioxins from a 1976 factory explosion, UC Berkeley scientists found no significant increase in endometriosis linked to their contaminant levels. And in Japan, there was no increased rate of the disease among 139 infertile women with higher exposures to hormone-disrupting compounds including PCBs and dioxins, according to a 2005 study.
Newbold said because decades can pass between exposure during fetal development or early childhood and the manifestation of the disease in adult life, it can be difficult to nail down a link.
"Only recently are studies starting to focus on developmental risk factors in relation to adult disease," she said.
Endometriosis and fibroids are referred to as "benign uterine diseases," characterized mostly by painful periods, according to McLachlan. "Because these growths are not life-threatening or malignant, traditionally, these diseases haven't garnered the attention they should," he said.
But the disorders sometimes are linked to fertility problems, and researchers also are beginning to realize that such symptoms can be a sign of serious diseases to come.
"Gynecological problems during the reproductive years may be a predictor of diseases, such as cancer, later in life," said Barbara Cohn, a reproductive health scientist and director of Child Health and Development Studies at the Public Health Institute in Berkeley, Calif.
Endometriosis has been associated with an increased risk of some ovarian cancers. However, the risk remains small, according to a study published in Lancet Oncology in May. Women with endometriosis have a 1.5 percent lifetime chance of developing ovarian cancer compared with 1 percent in the general female population.
The research is less clear on a link between cancer and other gynecological diseases, such as uterine fibroids.
Lee was terrified that her fibroids and extreme menstrual periods were signs of cervical or ovarian cancer. Several doctors recommended that she have her uterus removed--standard treatment for severe fibroids. But she refused.
"You wouldn't cut your nose off because you got frequent nose bleeds," said Lee. "No one seemed concerned with trying to figure out why I was having such heavy periods."
Pesticides and other environmental chemicals may not have contributed to Lee's gynecological problems, since other factors, such as age and genetic predisposition, also increase a woman's risk.
Nevertheless, since leaving the Okanagan in 2010 and moving to Nova Scotia, Lee has seen a marked decrease in her symptoms. She now avoids processed foods and buys only organic produce. The fibroid is no longer growing. In fact, according to Lee, it has shrunk in size.
"I can no longer feel it, but I know it is still there," she said. "I worry constantly what the health effects will be down the road."
To read more about health risks, read "Bitter Taste."