Stress (cortisol) causes pre-term birth by blocking progesterone


Mar 18, 2013
USA / Europe
If you ask a gynecologist what causes premature birth, the answer will usually be something along the lines of "insufficient progesterone" often accompanied by mumbling about "genetic predispositions". Yet, how exactly is insufficient progesterone responsible for premature birth has remained a mystery, at least for most practicing doctors. Back in the first half of the 20th century it was known that progesterone was the most potent endogenous antagonist at both the glucocorticoid and mineralocorticoid receptors (GR and MR). It is also well-known that just before onset of labor, progesterone levels rapidly drop and cortisol levels rise. So, the simplest explanation is that progesterone is able to maintain pregnancy by both increasing metabolism and blocking the effects of cortisol. Yet, medicine seems to have lost the knowledge on just how progesterone works and the focus nowadays is almost entirely on progesterone's effects through the eponymous receptor (PR). There are probably hundreds of synthetic PR agonists developed and approved for clinical use and medicine views them as equivalent (or superior) to bioidentical progesterone, despite the fact that almost none of them have the tocolytic (pregnancy-sparing) effects of progesterone. It just so happens that almost all of those synthetic progestins are agonists of either GR and/or MR, which immediately elucidates their inability to maintain pregnancy. The study below revitalizes the cortisol-progesterone interplay/antagonism (at least when it comes to pregnancy) and hopefully will lead to both more attention to the detrimental effect of stress for both mother and child, as well as the systemic protective/therapeutic effects progesterone could have in many conditions associated with cortisol/aldosterone excess.

Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth
Study reveals process to explain how maternal stress triggers idiopathic preterm birth
"...Preterm birth is a leading cause of infant deaths and illness in the U.S. -- yet its underlying molecular causes remain largely unclear. About 40 to 50% of preterm births, defined as births before 37 weeks of pregnancy, are estimated to be "idiopathic," meaning they arise from unexplained or spontaneous labor. And, maternal stress linked to depression and post-traumatic stress disorders as well as fetal stress have been strongly implicated in preterm births with no known cause. Now, for the first time, a University of South Florida Health (USF Health) preclinical study has uncovered a mechanism to help explain how psychological and/or physiological stress in pregnant women triggers idiopathic preterm birth. A research team at the USF Health Morsani College of Medicine Department of Obstetrics and Gynecology shows how cortisol -- the "fight-or-flight" hormone critical for regulating the body's response to stress -- acts through stress-responsive protein FKBP51 binding to progesterone receptors to inhibit progesterone receptor function in the uterus. This reduced progesterone receptor activity stimulates labor."
"...For the current study focused on maternal stress-induced idiopathic preterm birth, the researchers combined experiments in human maternal decidual cells and a mouse model in which FKBP5, the gene that makes FKBP51, had been removed, or "knocked out." Altogether, their results revealed a novel functional progesterone withdrawal mechanism, mediated by maternal stress-induced uterine FKBP51 overexpression and enhanced FKPB51-progesterone receptor binding, that decreased progestational effects and triggered preterm birth. The researchers found that Fkbp5 knockout mice (with depletion of the gene encoding for FKBP51) exhibit prolonged gestation and are completely resistant to maternal stress-induced preterm birth."


Jul 29, 2020
Interesting. My father was born at 7th month of pregnancy. To this day, age 70, he still remains the strongest man I know, with insane grip and reflexes, unmatcheable.

No matter how strong we think we are, the baby boomer generation of males; pre-xeno estrogens, who grew up drinking milk in glass bottles and where plastics were unheard of, with a kilo of bread a day (muh starch) and meat maybe once a week (lot more organs than todays) and spent 90% of their growing up outdoors, crafting stuff from the nature, in order to stimulate their huge imagination...They are reaaaally strong. No comparison.

That's why I think, even for seemingly "healthy" young males of today, it's wise to supplement stuff like Progesterone, occasional aspirin and stuff.

There's just so much stress going around that gets reduced by 80% by 10mg of Progestene, not even mentioning stuff like Androsterone.
I have a feeling there could be a nuclear war starting from tommorow and I'd stay perfectly calm, strong and keep my family and close ones safe.

Andro makes me protective of little kids, animals, my girlfriend, family, reaaaaally protective. Like the usual baseline mood that I have is just amplified, with zero side effects.

Anyways, a little derail of the original post. Progesterone is insanely protective stuff, it's really noticeable after you've gone through really stressful periods in life and get no break (no alcohol, no GABAergics, nothing). Plus it's insanely androgenic for me, like I don't even have to take it with DHEA at all. Mixed with T base is the best thing ever :)


Jul 29, 2020
@equipoise A really interesting post, so much thought and info condensed into a few paragraphs!

Do you use Progest-E?
I used Progestene by IdeaLabs. I think it's a very quality product, and if you read through my posts I left a review of it, kind of my 2c on Progesterone supplementation from a point of view of a 26 year old guy. Ray really was never lying to us when he said Progesterone is the most protective substance.


Jan 10, 2021
@haidut what is consider as high cortisol? I have morning cortisol who is pretty high but still in the range (top of the range) 623nmol. I suffer from bad anxiety and I insomina since PFS. Would be interested to know if my morning cortisol is to high and how to lower it.
Thanks for your help
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