Endometriosis Breakthrough

Endometriosis is an estrogen dominant condition. Excessive estrogen activity induces excessive proliferation (growth) of tissue, excessive and bizarre endometrial tissue in the wrong places resulting in horrible menstrual cycle, irregular painful bleeding, scar tissue, adhesions and migraines. Often this leads to infertility and the usual treatment is to use oral contraceptive to manage at the same time as being re commended to fall pregnant to try to push it into remission and also get pregnant before infertile. Or get surgery to remove the scar tissue with side effect of the surgery being scar tissue. Systemic antiestrogen drugs are often used in extreme cases where the risk of the associated side effects is worth the benefit of blocking the hormone.
Endometriosis is cruel. It is not fair and the treatment options are not good enough. To think our women are going through monthly menses for the purpose of reproducing and this can be a consequence of that, man it is simply not fair to be a woman sometimes.

Now think about this. More than 10% of women suffer from endo and it is getting worse and creeping toward the 15% of women of reproductive age suffering from it. 40% of infertile women have endometriosis and 33% of laparoscopic surgeries are booked for endometrial scar tissue management (not cure). The global cost (investment into treating and loss of income etc.) is between $18 and $22 billion annually.

Over the last few decades there has been a fair bit of research looking into some of the more controversial and confusing findings with endometriosis and hormonal levels and 5this has led to a recent breakthrough. Not some miracle cure breakthrough but a scientific confirmation that there are many therapeutic targets that are not effective and not worth targeting. In regards to naturopathic treatment this will change a lot of things and refine the protocol to concentrate on the true therapeutic targets and forget about wasting time and money on the rest.

Estrogen excess or progesterone deficiency?

The answer is Yes. Can be either one or both. But this is where we went on a tangent.

Estrogen dominance is due to excessive production of oestradiol and is not related to the ratios between the good (2alpha hydroxyestrone), the bad (16 alpha hydroxyestrone) and the ugly (4 alpha hydroxy estrone) estrone metabolites. I need to explain this better.
Natural treatments and naturopaths have used a lot of detoxification support nutraceuticals (DIM, I-3-C, Sulforaphanes, broccoli sprout etc.) to manipulate the ratios of estrogen metabolites as this was claimed to be a major contributing factor to endo since the mid 80’s. The theory was that after estrogen has done its job to buyild period for example it is detoxified and eliminated from the body. Those that suffered estrogen dominance causing endo were believed to have a detox defect. Recent research shows this defect in detox is not consistent and not the driving factor. There is way too much estradiol being made and it is not clearing away to the deactivated metabolites via estrone. If we can stop the excessive stuff being made we can handle the detoxification and elimination, furthermore manipulating detox pathways to correct the ratio of metabolites doesn’t fix the problem.

Why so much estradiol (E2)?

– Aromatase is too fast and converts testosterone to estradiol (E2) and makes too much. Inflammation, arachidonic acid, PGE2, toxins, lipopolysaccharides and genetic polymorphisms (gene defect / variation to the norm) all contribute to the faster aromatase activity.
– The enzyme that deactivates the E2 to E1 (17BHSD2) is too slow causing the E2 to backlog
– The enzyme that recycles E1 back into the active E2 (17BHSD1) is too fast.
– The E1 conversion to the 2,4 and 16 alpha hydroxy forms don’t seem to be as relevant for this reason.
– Poor methylation (lack of folate, b12, C, B3, SAMe) results in estrogen receptor imbalances with too many beta estrogen receptors and not enough alpha.
– It is possible that the good clinical results using methylating agents in endometriosis is partly due to the manipulation of the 2 and 16 estrone metabolites but may in fact be more likely linked to supporting methylation processes to make receptors to correct the receptor imbalance.

The next confusing bit was the progesterone deficiency

What screwed with our brains was that there were no signs of progesterone activity offsetting the estrogen; so, progesterone was often added in from creams or drugs but more often than not it didn’t work. There has been a lot of studies showing confusing results with some cases of low/ no progesterone and others had crazy high levels of progesterone. Some cases responded to contraceptives and progesterone treatment and others didn’t.
The most recent breakthrough here is that it has been shown that there is progesterone resistance at the receptor level. Meaning the antennas on the cells for progesterone don’t work or aren’t there. That’s why progesterone wasn’t working and that is also why some people have crazy high progesterone blood levels but no progesterone activity. Inflammation, excessive estrogen receptors and immune dysfunction have been associated with this defect. Progesterone helps to regulate estradiol (E2) levels by increasing its conversion to estrone (E1) and then detoxified and cleared away. Without it, the estrogen keeps building.

And surprise, surprise… inflammation and gut!!!

Inflammation and immune dysfunction are key features in all aspects of endometriosis. It is an inflammatory condition associated with autoimmunity. The immune system, in particular natural killer cells are used to break down the endometrial tissue and associated collagen and they create the scar tissue, adhesions and immune profile associated with endo pain and infertility.

Gut dysfunction, dysbiosis, and leaky gut wall contribute significant amounts of inflammation, immune cells, and lipopolysaccharide (bacterial cell fragment that is one of the most inflammatory triggers we can be exposed to) into the pelvic region. Furthermore the bugs in the guts especially if out of balance and overgrown can liberate and recycle estrogen that is on its way out in the poo and put it back in the body as biologically active estrogen.
The gut may be a causative factor in the following aspects of endo; autoimmunity, inflammation, progesterone resistance, estrogen dominance, scar tissue, adhesions, painful periods and clots and excessive aromatase activity.

So, with this in mind. The priorities for treatment that you want to discuss with your practitioner are as follows.

– Transdermal chrysin cream (e.g. Block e3 contains Chrysin) 2.5gm 2 x daily added to the vascular area of inguinal and groin as well as wrists. You can even do this with your Doctor and compounding chemist. Other natural aromatse inhibitors can struggle with oral absorption and systemic delivery but certain methoxylated isolflavones seem to be promising.
– Turmeric – anti-inflammatory, immune modulating as well as controls the essential fatty acid cascade to force omega oils down the correct pathways away from arachidonic acid and PGE2). Cort Rx contains a good dose of high quality turmeric) and NO black pepper. Black pepper contributes to leaky gut wall and intestinal inflammation and only helps absorption by blocking glucuronidation of our foods, drugs and toxins. Unfortunately, glucuronidation is an extremely important process for clearing away estrogen. So, regardless of what people say for turmeric in general and black pepper it’s not going to help you anymore and may make some things worse.
– Multifood contains essential cofactors; B12, folate, b6, b3, vitamin c as well as a hep of other cool stuff all in natural forms with proper doses and cofactors.
– AMP-V for essential fatty acids and combine with turmeric and Multifood to force away from AA and PGE2 pathways.
– Vitex agnus castus – 500mg to 1000mg daily (2 to 4 capsules with breakfast) for the progesterone support.

Read some of this stuff to find out more:
Christofolini DM, et al. CYP2C19 polymorphism increases the risk of endometriosis. J Assist Reprod Genet. 2015 Jan; 32(1):91-4
Al-Sabbagh M, et al. Mechanisms of endometrial progesterone resistance. Molecular and Cellular Endocrinology 358 (2012) 208-215
Bulun SE, et al. !7 Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis. Semin Reprod Med. 2010 Jan; 28(1):44-50
Pluchino N, et al. Innovations in classical hormonal targets for endometriosis. Expert Rev Clin Pharmacol. 2016;9(2):317-27
Parkin KL, et al. Uterine leukocyte function and dysfunction: a hypothesis on the impact of endometriosis. Am J Reprod Immunol. 2016 Mar; 75(3):411-7
Thiruchelvam U, et al. Natural Killer Cells: key Players in endometriosis. Am J reprod Immunol. 2015 Oct; 74(4):291-301