Adult pain higher after fetal exposure to estrogen in birth control pills.

Ceccarelli, I, P Fiorenzani, D Della Seta, C Massafra, G Cini, A Bocci and AM Aloisi. 2009. Perinatal exposure to xenoestrogens affects pain in adult female rats. Neurotoxicology and Teratology doi:10.1016/j.ntt.2009.02.004

Female rats exposed to estrogenic compounds through their mothers while in the womb had greater reactions to pain as adults, according to a study by Italian researchers.

The increased pain sensitivity may be due to permanent changes in how the nerves developed in the rats that were exposed before birth to either ethynylestradiol (EE), the most commonly used synthetic estrogen in birth control pills, or methoxychlor (MXC), a common insecticide long known to have estrogenic activity in mammals.

This is the first time researchers have linked pain perception in a grown animal to their early exposure to low levels of environmental estrogens. It is, however, another example of how chemical exposures during critical times of development before birth can have lifelong impacts.

Human exposure to EE in the womb is not uncommon. Many women who become pregnant may continue taking birth control pills for several weeks because they do not realize they are pregnant. The results from this study suggest the possibility that girls exposed to estrogens in the womb may be more sensitive to pain as adults.

People are also exposed to MXC and EE through the environment. EE is found in water supplies around the world because women excrete it in their urine.

Males and females perceive pain in different ways. Hormones play a role in how the neural pathways that regulate pain form.

To see if synthetic estrogenic compounds could do the same, researchers fed pregnant and nursing mother rats either EE or MXC at low doses considered relevant for humans. The dose of 400 ng/kg/day of EE is similar to what is found in a birth control pill. The dose of  20µg/kg/day for MXC is close to natural environmental exposures.

The adult females exposed either before birth or during nursing were tested for pain sensitivity.

In one of the tests, animals exposed to EE or MCX through gestation were more sensitive to pain than the control females and those exposed during nursing. Their estrogen levels, measured when they were adults, were also four times higher than the untreated females. This difference points to permanent changes in the hormone system.

The researchers hypothesize that the synthetic estrogens can affect and permanently change the developing nerves that regulate pain. They say the results "underline the importance of the prenatal period as a critical time" when synthetic estrogens "could have a strong impact on the physiological development of neural circuits."