Progesterone and its effects? One minute it's clear, next it's gone.

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agranulocytosis

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I'm having a terribly difficult time understanding the physiology of progesterone. As I understand it, progesterone acts to promote the endometrium to become more glandular thereby making the endometrium suitable for implantation.

BUT...in endometrial hyperplasia where there is nearly constant estrogenic stimulation of the endometrium, progestins are given to decidualize the endometrial stroma, in effect thinning the endometrium. Progestins are also given as contraceptive pills, where they act by the same mechanism to prevent implantation, among other effects.

Got it.

Now, Mifeprostone acts as a progesterone receptor antagonist and used in medical abortions to block progesterone from making the endothelium suitable to maintain the pregnancy.

I thought I had it, but now it's gone. Does anyone have a reasonable explanation as to how progesterone acts to both make the endometrium suitable for implantation, yet not in certain cases?

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I'm having a terribly difficult time understanding the physiology of progesterone. As I understand it, progesterone acts to promote the endometrium to become more glandular thereby making the endometrium suitable for implantation.

BUT...in endometrial hyperplasia where there is nearly constant estrogenic stimulation of the endometrium, progestins are given to decidualize the endometrial stroma, in effect thinning the endometrium. Progestins are also given as contraceptive pills, where they act by the same mechanism to prevent implantation, among other effects.

Got it.

Now, Mifeprostone acts as a progesterone receptor antagonist and used in medical abortions to block progesterone from making the endothelium suitable to maintain the pregnancy.

I thought I had it, but now it's gone. Does anyone have a reasonable explanation as to how progesterone acts to both make the endometrium suitable for implantation, yet not in certain cases?

Progesterone is always "Progestational," remember it that way and you will be golden. As I understand it, the reason that it is in birth control pills isn't so that it prevents pregnancy. Birth control pills are a continual low dose of both estrogen and progesterone. This low dose of estrogen prevents the positive feedback loop that activates the LH surge that causes ovulation. So by taking that continual low dose it prevents ovulation. Also, because the estrogen stays so low, it doesn't build up the endometrium for implantation. And it doesn't decidualize (gain the glycgen secreting ability necessary for the secretive phase) because the progesterone levels don't jump up after ovulation.

The receptor antagonist means that it prevents the effect of progesterone. So, if you block the progestational effects of progesterone it would therefore abort.

Hope that helps.

PS. I won't swear by my description of how birth control works, I didn't research it just now, that is just what I understand at this point, so I apologize if there are any errors.
 
Mifepristone is a competitive antagonist to progesterone when it is present and a partial agonist when progesterone is not present. At low doses, it prevents ovulation much like endogenous progesterone. At higher doses, it prevents the decidualization of the endometrium, dilates the cervix, and releases prostaglandins (essentially causing abortion due to the blockade of progesterone). You can imagine a common adverse effect (or intended) is going to be cramping. All this can be understood in the action of prostaglandins on the uterus and cervix. (They are used to induce labor, contract the uterus with pitocin, soften, dilate, and efface the cervix for childbirth). Misoprostol is the abortifacent drug used in conjunction with mifepristone because the mifepristone sensitizes the uterus to the action of endogenous and exogenous prostaglandins.

(Guess I learned something in OB/GYN)

A side note on progesterone is that it is given to women who have menorrhagia or are at risk for endometrial hyperplasia and cancer because it reduces the proliferation caused by estrogen. Progesterone doesn't really block estrogen because it actually requires estrogen to function (estrogen priming in normal physiology to cause decidualization).
 
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