Thread by @ErinSandersNP

Progesterone, contraception & chronic disease

Dovetailing off MMPs, for menstruating people, I am curious if the expected hormonal fluctuation and necessary cyclical tissue breakdown could be associated with a higher risk for barrier permeability and pathogen translocation?

https://twitter.com/ErinSandersNP/status/1580393867316056064

2/ Furthermore, if progesterone “PRO-Gestation” is a hormone that is able to trigger (red arrow) or prohibit the cyclical ischemia and breakdown of the endometrium to support a pregnancy, could it do that for other mucosal barriers as well?
cc: @DrJenGunter @doctorjenn @acweyand

3/ Some background: In a healthy menstrual cycle, the ovary makes multiple follicles. One follicle grows larger with the egg that will be released. After the egg is released by the follicle and out of the ovary, it travels down the fallopian tube to the uterus to implant.

4/ What is left of the egg’s follicle actually turns into something called the *corpus luteum* and this secretes progesterone as well as estrogen.

Corpus luteum —> LUTEAL phase
(also secretory phase of the menstrual cycle)

https://twitter.com/advreproduction/status/1584371898561220610

5/ Hormones secreted by the corpus luteum (progesterone and estrogen) support a pregnancy by preventing breakdown of the uterine lining while the fertilized embryo implants & the placenta grows into the endometrium until it is able to take over hormone production.

6/ If the egg IS NOT fertilized, or the embryo does not implant into the endometrium, the corpus luteum shrivels up & progesterone levels drop. The vessels cut off blood flow to the tissue, which becomes ischemic & the lining of the uterus starts to slough off resulting in menses

7/ Low levels of progesterone can be an issue for people who have difficulty conceiving or maintaining a pregnancy, so clinicians (OB/GYN and reproductive endocrinologists) can give you additional progesterone.

See: Endometrin, Crinone, Prochieve

accessdata.fda.gov/drugsatfda_doc…

8/ Lack of ovulation is one cause of low progesterone, which makes sense because if an egg is NEVER released from a follicle, there is nothing to turn into the corpus luteum and therefore nothing to secrete “pro-gestation” progesterone.

9/ Irregular cycles are a part of the diagnostic criteria for polycystic ovary syndrome (PCOS). Many small cystic follicles develop but don’t lead to an egg being released (ovulation), which then doesn’t trigger the follicle to turn into the corpus luteum & secrete progesterone.

10/ Interestingly, in PCOS, luteal phase progesterone deficiency is also commonly associated with hyperinsulinemia. And administration of metformin has actually been shown to increase levels of progesterone in females with PCOS.
scielo.br/j/bjmbr/a/CZKZ…

11/ A way to diagnose secondary amenorrhea (lack of menstruation) is the “progesterone challenge test”.

Oral Medroxyprogesterone acetate (Provera) 10 mg daily for 5-10 days or one intramuscular injection of 100-200 mg of progesterone in oil.

Provera: accessdata.fda.gov/drugsatfda_doc…

12/ About 2-7 days after the progestin is finished, withdrawal bleeding will usually occur.

A positive test response is any bleeding more than light spotting that occurs within 2 weeks after the progestin is given.

13/ This tells us 2 things:

1. That the person makes enough estrogen to develop a thickened uterine lining.

2. The problem is likely related to egg production and release (ovulation).

14/ In fact, if a person “fails” this test (no bleeding) the next step is usually to give them estrogen before giving the progesterone to see if the lining can be built up and shed when progesterone is stopped.

15/ If a person STILL doesn’t have bleeding, even after giving them estrogen, then you worry more about an anatomical issue, like cervical stenosis, where the blood cannot get out/escape the uterus.

16/ Long acting reversible contraception (LARC) and continuous cycling to suppress menstruation have been amazing revelations for patients who have chronic disease and symptoms that are exacerbated by hormonal fluctuations associated with their periods.

17/ Long term progesterone only birth control methods (localized hormonal IUD like Mirena/Skyla, systemic Nexplanon arm implant) prevent pregnancy by thickening cervical mucus (blocking sperm) but also stabilizing the uterine lining over time leading to lighter or no bleeding

18/ I am a huge proponent of continuous birth control methods to prevent pregnancy and reduce the risk associated with higher estrogen methods, specifically clotting in the setting of a pandemic that causes vascular disease & the political reduction of necessary reproductive care

19/ Oral progesterone is not well absorbed. Much is lost due to first pass effect from the liver and it is eliminated from the body quickly. This is one reason why progesterone only birth control pills (like the mini pill) are very unforgiving in terms of needing to be taken

20/ at the same time every day or there is loss of efficacy.

Mini pill: accessdata.fda.gov/drugsatfda_doc…

I am very curious if there is also a positive effect of progesterone itself on *systemic* inflammation/tissue stability with Nexplanon, oral progesterone only pills, or even creams.

21/ Notably, continuous cycling with birth control methods is different from ovarian suppression with a medication like Lupron (gonadotropin-releasing hormone agnost or GnRH agonist), which can induce a temporary & reversible menopausal state.

Lupron: accessdata.fda.gov/drugsatfda_doc…

22/ It is pretty well established that progesterone can down regulate MMP, an enzyme that helps to break down tissue (like for menses).

pubmed.ncbi.nlm.nih.gov/15536155/

pubmed.ncbi.nlm.nih.gov/11949963/

pubmed.ncbi.nlm.nih.gov/10770206/

23/ Since progesterone only medications and methods are utilized by a large subset of the population already it would be interesting to see how their use could influence chronic diseases presentation.

Cc: @organichemusic @ales_frost

24/ I haven’t attempted to make a thread on #Mastodon yet.

But Twitter has seemed increasingly caustic and volatile since Elno took over. So, I’m still unsure if this platform is still helpful for learning and teaching…I guess we’ll see…

@threadreaderapp please unroll.