New research reveals endometriosis is a disorder of estrogen production on a cellular level. Endometriosis is caused by the presence of endometriosis implants, cells outside the uterus that normally live inside the uterus (the endometrium).
Evolution of the understanding of endometriosis offers hope for new treatments such as estrogen blockers and progesterone blockers.
In women with endometriosis, the processing of estrogen is abnormal, both within the cells lining the uterus (the endometrium), and in endometriosis implants outside the uterus.
Endometriosis implants have an abnormal amount of an enzyme called “aromatase”. This enzyme converts estrogen-precursor molecules to estrogen. Endometriosis implants also have high levels of estrogen receptors. Therefore endometriosis implants can both synthesize estrogen independent of the ovarian hormones; and they are more sensitive to estrogen.
Endometriosis implants are thus “self-perpetuating”. Endometriosis located outside the uterus can re-generate itself and spread through self-stimulation, whether or not the uterus and ovaries are present. This explains why some women who have hysterectomy for endometriosis have recurrent pain after total hysterectomy. Hysterectomy and oophorectomy (removal of ovaries) “debulks” endometriosis tissue present in the uterus and ovaries, but it does not remove endometriosis implants present outside the uterus.
Endometriosis implants outside the uterus and the endometrium produce high levels of inflammatory chemicals called “cytokines” and “prostaglandins”. By releasing prostaglandins and cytokines, molecules responsible for cramping during normal periods, endometriosis can inflame the nearby tissues and nerves, resulting in chronic pain at any time of the menstrual cycle.
“Location, Location, Location”: Endometriosis Resembles Real Estate
Location of endometriosis implants is key to their symptoms and other clinical manifestations.
Endometriosis is usually found in three places:
- the tissue lining the pelvis and ligaments that support the uterus (pelvic peritoneum, uterosacral ligaments)
- the ovary (a collection of endometriosis cells and fluid called an “endometrioma”)
- in the wall between the vagina and rectum (recto-vaginal septum)
Although these are the common locations of endometriosis can occur almost anywhere in the body. I have seen endometriosis on the intestines, and even had a patient with endometriosis in her lungs. Every time she menstruated she coughed up blood!
The location of endometriosis implants explain why some people with minimal endometriosis can have a lot of pain; while others with large cystic endometriosis can have no pain. For example, you can have a few small endometriosis implants on or near the pelvic nerves and have a great deal of pain; while another person can have a large cyst of endometriosis on the ovary and have no pain. The ovary has a different nerve supply and can apparently “tolerate” bulkier endometriosis.
Endometriosis that grows on and into the pelvic nerves can cause referred pain anywhere along the path the nerve innervates. For example, endometriosis on or near the obturator nerve, which supplies the inner thigh, can cause pain down the leg, and even in the groin/labial area. Endometriosis along the pudendal nerve, which innervates the lower vagina and external female genitalia, can cause pain anywhere along that nerve’s distribution. About 5-10 percent of women have symptomatic endometriosis, the most common cause of chronic pelvic pain.
Endometriosis in the ligaments supporting the uterus can be particularly troublesome because it can infiltrate the pelvic nerves, in close proximity.
Traditional Treatment for Endometriosis Focused on Suppressing the Growth of Endometriosis Implants
The main-stays of endometriosis treatment have been:
- suppression of menses with progesterone
- use of anti-inflammatory medications (e.g. ibuprofen) to reduce pain
- laparoscopic removal of endometriosis implants
- Use of Lupron (suppresses ovarian hormone production) to create a short-term “menopause” and withdraw hormonal support to endometriosis implants
- removal of uterus, tubes, and ovaries (total hysterectomy with bilateral salpingoophorectomy)
While each of these has their place in treating endometriosis, none of these is completely effective at eradicating endometriosis. (See the related post, Pros and Cons of “Traditional” Treatment for Endometriosis–not yet an active link).
In fact, endometriosis is now seen as a chronic disease. The goal of endometriosis treatment should be to control manifestation and progression of the disease, preferably without resorting to the extreme of hysterectomy.
For more information on managing endometriosis see the upcoming posts, to be published in June, 2009:
Exciting News for Endometriosis: Aromatase Inhibitors and Ablation (not yet an active link)
Pros and Cons of “Traditional” Treatment for Endometriosis (not yet an active link)
Questions:
- Do you have endometriosis?
- What treatments have worked for you, including “traditional” (allopathic)and complementary/alternative medicine?
- Have you tried yoga for treatment of chronic pain? If so, what has your experience been?
{ 15 comments… read them below or add one }
I have endometriosis and have undergone 4 laparoscopies to remove endometriosis implants and adhesions. Recently, I have started using progesterone cream from a compound pharmacy. The physician who prescribed it told me that my body would take some time to adjust, however I am on month 4 and every time I apply the cream I feel extreme pelvic pain. I use the cream primarily on cycle days 12 – 24. These 12 days are plagued with pain and tenderness. I know I have adhesions (as seen via transvaginal ultrasound by my RE) and it seems the progesterone cream makes the endo pain worse. Everything I’ve read however points to the contrary; progesterone cream improves endo symptoms. Can you explain this? Are my estrogen receptors still adjusting after 4 months of treatment? I appreciate your response.
Hi Shannon,
Endometriosis implants are also known to process progesterone abnormally. However, estrogen and progesterone are produced by the body through similar metabolic pathways. While abnormal estrogen metabolism has been identified as a primary reason contributing to development of endometriosis, it is likely that in a percentage of people with endometriosis, the progesterone metabolism is the dominant abnormal process. People with endometriosis may actually have both, but one may manifest itself more than the other. For example, with your endometriosis implants you may have a progesterone dominant process. So taking progesterone may actually aggravate your endometriosis, instead of alleviate it. In fact, from what you’re describing, that is a likely possibility. You may want to consider discontinuing the progesterone and observe if your symptoms change. If you do this, let your doctor know; and it helps to track your symptoms using a daily diary, even if it’s a one-word entry. This allows you to retrospectively evaluate your response to a treatment in an objective manner.
You may benefit from treatment with a progesterone blocker such as mifepristone. Mifepristone is a SPRM (selective progesterone receptor modulator). It blocks the action of progesterone. It has been used in experimental trials to relieve or eliminate endometriosis symptoms. The dosing for endometriosis is 5-10 mg daily for 90 days. It can be extended to 180 days if it’s resulting in significant benefit; and in some people it may provide symptom relief for several years. Side effects of mifepristone would need to be discussed with your physician. I wish you the best and hope this helps. Thank you for reading the blog and sharing your experience.
Shelley,
Thank you for your timely response. I didn’t know that endometriosis implants can process progesterone abnormally. I will definitely discuss this with my doctor.
The reason I am using progesterone cream to begin with is that my progesterone levels (obtained via saliva testing) are extremely low. According to the endocrinologist I am seeing, my levels should be approximately 300 PG/ML and mine are 37 PG/ML. I was having symptoms of estrogen dominance, even though my estrogen levels are normal. The progesterone cream definitely helps with the hot flashes, mood swings, etc. of estrogen dominance, but I feel that my endometriosis pain is worse. Is this a case of choosing the lesser of two evils? If I get another laparoscopy (which I plan to do soon) to remove the adhesions and endo that I have, will the progesterone cream aggravate the endo and make it return faster? I know these questions may be hard to answer. I appreciate your time and knowledge.
Best regards,
Shannon
I have endo and have tried a number of treatments: continuous birth control (no break in between), 3 laps, two rounds of Lupron…the first round with add back and the second round without add back, and currently have a Mirena. My endo doc has said that I am not a good candidate for further laps (another doc performed each before I switched to an endo guy) as I do not have a good result and that it will only ad to the adhesions and scarring which he believes is adding to the extreme pain that I have been having. I had the Mirena fitted in Februaru 2008, the pain subsided a little about 4-6 months ago but in the past 2 months has become excruciating. I have an appointment with my endo doc July 28 and am looking for ANY other options as it is becoming quite unbearable. I have done a lot of research over the years and know that a hysterectomy may not be the cure. Id there anything else outside of the yoga etc. that I could try?
Thanks so much,
Nicole
I am having pain in the groin/liabal area along with leg pain. I currently have Mirena but am now having this pain worse than prior to the insertion of the Mirena. My doctor has placed me on anti-inflammatory for the pain. He has not tested me for endometriosis but has stated there may be a possibility I do have it. I believe there may be a good chance that I have it. Is this a normal are to be affected with endometriosis? The pain can be unbearable at times with no relief from pain medications. Do you suggest I continue to follow his orders and hope this subsides with more time?
I can’t make recommendations specific to your situation without doing a full history and physical. However, Mirena is a good option for some women with endometriosis. Other options include Lupron, aromatase inhibitors, and laparoscopy (surgical evaluation for diagnosis and treatment of pelvic pain). People who don’t respond to one treatment for endometriosis will often respond to another. Some women seem to have “progesterone dominant” endometriosis, and respond to Mirena well. However, other women seem to have “estrogen dominant” endometriosis; and they respond better to suppression of estrogen pathways with either Lupron or aromatase inhibitors. There is some scientific evidence to support this: biopsies of endometriosis implants from women with “estrogen dominant” endometriosis seem to have greater capacity to produce and respond to estrogen; while the complement is true in women with “progesterone dominant” endometriosis. If you’re not responding to a treatment within 3 months of using it, it may be beneficial to evaluate other options.
I am just finishing 6 months of Synarel and am scared to stop. For the first time in 20 years I have had no pain. I have stage IV endo in usual placves and on bowel nd diaphragm. Any ideas what I can take after Synarel? I love it. I had hot flushes, tiredness and a bit of nausea but no pain, clear skin and lost weight. Want to take it for ever!
I am 51 and had a hysterctomy and both ovaries removed 8 years ago. The surgery took 6 hours with several surgeons working to remove all the endo they could find. I started having pain about a year and a half ago saw several Drs. told them it felt like endo they told me not posssible. Six weeks ago I had severe abdominal pain for hours then I had a seizure. My husband called 911, when the paramedics arrived my blood pressure was 50/26. A CAT scan revealed a large abdominal mass (12x7x5)cm. It had been bleeding and this caused the pain and loss of conciousness. After several inconclusive biopsys a lap revealed that the large mass and several smaller ones are endo. The large mass is behind my stomach and surrounded by scar tissue. I have been in pain daily since this happened. I would like to have it surgically removed, but the GI Dr. says it is too risky. The Gyno Dr. says she can’t do surgery on that area. Waiting to see if my health insurance will approve Aromatase as a treatment. I am concerned about bleeding out again, and wondering how effective the Aromatase will be in shrinking the mass and helping to get rid of the pain.
Discovered aggressive endo at age 14 with two orange size endo cysts on ovaries and endo in various locations within abdominal cavity. Treatment included lap and birth control pills. Still on the pill 20 years later. This seems to have controlled the situation but I don’t live near my original doctor-he was a cutting edge endo doc at the time- Never had children. I’m very concerned about still being on the pill continuously and I’m eagerly awaiting any new treatments. I seem to do ok with “YAZ” although we are thinking I have chronic pancreatitis because of it. Not sure what to do.
Dana, have you been on continuous bc pills without a breakthrough bleed? I am diagnosed with stage 4 endo as well and am a bad case of the disease – 2 laps for large endometriomas on both ovaries with my left ovary stuck to the bowel and uterus. After a few months on Zoladex (GnRH agonist), I am to be on continuous bc pills back-to-back packs with no breakthrough bleed. Any idea how safe must this be?
This is a very interesting and useful website for us endometriosis sufferers. Dr Shelly, are the aromatase inhibitors already available for treatment? Thanks for all your help.
Dear friend,
My name is Diana….I have already been on this site, I am back.
I had 2 laparoscopic surgeries during last 5 years. I thought that I can beat the illness. Last month I tried FIV. Monday we got the result. Negative. No change. I thought I can win.
It was our last chance. I don’t know what to do know. I have a cyst o 6 cm. I should operate, but than I’ll never have babies again. And endometriosis can return, like before.
It is a hopples situation; I am so tired, because of pain, lack of hope, financial issues (in Romania FIV cost almost 5.000 euro.)
I don’t know what else to do, now one knows any treatment, I have tried everything: surgery, medicine- injection and FIV. Nothing works.
Thanks for reading my story.
Wish you all a great life!
AI’s can be used “off label” for treatment of endometriosis. In other words, they are FDA approved for one diagnosis (breast cancer), but can be used for other situations if the use is appropriate and scientifically based.
I had endo for many years up until twelve years ago when I had laser treatment and then very miraculously fell pregnant with my daughter. She is nearly eleven now, and the endo is back. For the last three years I have suffered with pain in my lower rib region, and have been hospitalised three times. I had thirteen attacks of this abdominal pain always during a period, and was diagnosed with idiopathic pancreatitis. Now there has been a question raised amongst my consultants that the endo could be causing the pancreatitis.. ( I have had scans and the docs say that my pancreas looks perfectly normal but the amalayse count after each attack is high). Is it possible that the endo is causing the pancreatitis? and if so what is the best treatment to erradicate the cause? This is really affecting my home and work life as I am almost totally incapacitated for maybe a week or more every month.. thanks for any comments
Hi everyone i need your suggestions this is my endo story. I am 19 right now and was diagnosed with endo at 11. I have had 2 surgeries for it in the past. i have tryed everything out there to start with birth control taken normally, birth control skipping placevos,and then taking the first three placevos and then another month only 2.i have tryed every kind of birth control on the market. when i was younger my periods were HORRIBLE i would where childs diapers as pads and would go through about 12-14 a day. Then i was put on a pill that quit your period with birth control. then i went to see this one of a kind specialist who put me on lupron then once it wore off my period started. went back on lupron and birth control at the same time so that when lupron quit birth control would work. nope didnt work. now im back on lupron for the last time with another birth control but i am not thinking it will work. along with it all i have severe back pain from endo i am on anti depressants for the back which helped but now quit so they up the dose and is ok but not working as well as hoped. Also i have interstital cystitis. please help me with all of this i am young and want to have kids someday!
thanks so much,
liz
Hi, I’m sorry the link is broken. I’ll try to get it fixed quickly. Aromatase inhibitors (e.g. anastrazole) block estrogen production at the cellular level. By blocking estrogen production within endometriosis implants, they may have value in reducing the size, number, and overall burden of the implants (e.g. production of inflammatory molecules). Some studies have shown 30-50% reductions in endometriosis symptoms with a 90-day trial of daily anastrazole. There are also more recent studies emerging on the use of progesterone-blocking chemicals to treat endometriosis, fibroids, and adenomyosis. I will try to put this information on the site as soon as I have the time to get it together and assemble it inot a coherent post. Thank you very much for your comment and for reading the blog. -SB