The role of genetics in estrogen responses

The role of genetics in estrogen responses: a critical piece of an intricate puzzle – free full-text article /PMC4232287/ – Dec 2014

The estrogens are female sex hormones that are involved in a variety of physiological processes, including reproductive development and function, wound healing, and bone growth.

In addition to the role of estrogens in promoting tissue growth and development during normal physiological states, they have a well-established role in determining susceptibility to disease, particularly cancer, in reproductive tissues.

As with so many other biochemical components at work in our bodies, estrogen has both positive and negative effects and we each react differently depending on how the rest of our body is built. 

The responsiveness of various tissues to estrogen is genetically controlled, with marked quantitative variation observed across multiple species, including humans.

This variation presents both researchers and clinicians with a veritable physiological puzzle, the pieces of which—many of them unknown—are complex and difficult to fit together.

And not only is this variation between people, but also within people, and not just over the years of a life but even over the hours of a day. This is why it’s notoriously difficult to get a useful measure of estrogen levels.

Although genetics is known to play a major role in determining sensitivity to estrogens, there are other factors, including parent of origin and the maternal environment, that are intimately linked to heritable phenotypes but do not represent genotype, per se.


It is now accepted that estrogens have a vast array of functions across multiple tissues and that genetic factors play a highly significant role in the variation in tissue responses to estrogens.

For those of us with EDS, we often find our joint pains worsen during the times in a menstrual cycle when estrogen is low. This could be because estrogen has a role in the stiffness versus laxity of the ligaments that hold our joints together (since our pelvis mist split apart slightly when giving birth).

Finally, more work is needed to

  • clearly identify the critical windows wherein exposure to natural or environmental estrogens can permanently alter tissue physiology,
  • the mechanisms by which this occurs,
  • what genetic factors render an individual sensitive or resistant to exposure, and
  • how these processes can be manipulated to optimize development and prevent disease.


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