Progesterone Resistance and Endometriosis

The cause of endometriosis is unclear, and with an unclear reason for a pathology to be present, a targeted treatment becomes difficult – each women is going to respond to different therapies with variable outcomes. What is known about endometriosis though, is that there is significant disregulation with respect to the estrogen and progesterone receptors at the level of the endometrium.

Estrogen stimulates the proliferative component of the endometrial lining, stimulating it to grow more robust during the follicular phase of the cycle, and then progesterone comes in after ovulations to counter act the proliferation, and promote the secretory phase of the endometrial lining development, stopping growth but preparing the lining for potential implantation.

What can be seen in endometriosis, is a progesterone resistant endometrial lining. What does that mean? The progesterone receptors are not as responsive to the progesterone signals as they should be. This results in over stimulation of estrogen, because progesterone isn’t being received at the endometrium to counter balance it, causing the endometrial tissue to build and build – potentially in the wrong spaces too. This excess endometrial lining can result in increased cramping during menses to try and shed the extra tissue that has been built up, and if there is excess endometrial lining in an area it’s not supposed to be (ie outside of the uterus) that can be inflammatory to that environment.

So as well as progesterone resistance contributing to pain, this also plays a major role with respect to fertility. The uterine lining needs adequate progesterone exposure to go from proliferatory –> secretory after ovulation the menstrual cycle in order for a blastocyst to be able to implant properly. Queue up progesterone suppositories as a potential fertility treatment option in endometriosis!

If you’ve been following along on my  videos, where I’ve discussed the menstrual cycle, estrogen and progesterone, you’ll see that the whole cycle and the function of these hormones work in a fine dance with respect to each other, and endometriosis is an example of when that balance is off and a pathology can arise.

PMID: 31387263

3 thoughts on “Progesterone Resistance and Endometriosis

  1. Priscilla MacEachern June 30, 2021 — 7:27 pm

    What would it indicate about my potential progesterone resistance if when I take progesterone suppositories, I need to stop them in order for my period to start. I understand this isn’t the case for everyone and since I have endometriosis & am struggling with infertility, I want to make sure I’m doing everything I can to help my chances. I have only had my progesterone tested once on cycle day 21 & it came back in the low normal range. Thank You!

    1. User Avatar

      Thank you for your question! The fact that progesterone can hold your uterine lining until you stop the medication speaks to a good response to it, but progesterone resistance goes even deeper with endometriosis – it can be more about how progesterone converts the uterine lining at a cellular level to stimulate decidualization and enable implantation of the blastocyst. One blood measurement of progesterone also isn’t the be all end all. Progesterone is constantly in flux throughout the day from when its high to when it’s low, so potentially when you got your blood work done you hit it at a low that day. You’ll have to collect a few months worth of progesterone measurements done 1 week after ovulation to get a proper assessment of what your progesterone trends may be. Good luck, sending baby dust your way!

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