? Link Between PCOS and endometriosis

Old (from 1989): "Pelvic endometriosis was observed in 15 of 91 women (16.5%) with laparoscopically confirmed polycystic ovary syndrome. There were no significant clinical differences among those with and those without endometriosis. The groups were of similar age, parity, and ponderal indices and had similar incidences of oligomenorrhea, hirsutism, and infertility; the serum concentrations of LH, FSH, LH/FSH, prolactin, testosterone, and dehydroepiandrosterone sulfate were also similar in each group. However, women with polycystic ovaries and endometriosis presented more frequently with regular menses (40 versus 14.5%; P = .05) and less frequently with secondary amenorrhea (0 versus 38.2%; P = .05) and galactorrhea (0 versus 9.2%; P = .05) than the women with polycystic ovaries alone. Endometriosis appears to be a coincidental finding in polycystic ovary syndrome, and its development does not modify significantly the clinical picture or biochemical profiles of these patients. However, menstrual patterns seem to be affected." http://www.ncbi.nlm.nih.gov/pubmed/2797642

2011: "The endocrinologic and metabolic abnormalities of women with polycystic ovary syndrome (PCOS) can result in a series of endometrial diseases. Abnormalities of hyperandrogenism and hyperinsulinemia that may be found in PCOS can elevate the levels of E2 indirectly, reduce progesterone secretion and induce some growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factors (IGFs) over expression, which may have a major impact on endometriosis occurrence and development. We suppose that there is a possible connection between PCOS and endometriosis." http://www.sciencedirect.com/.../pii/S1001784412600133

Surgical Technique and "microscopic" endo

"Occult or microscopic lesions have been reported as early as 1986 from laparotomy procedures. Hopton and Redwine {7} have shown a linear inverse relationship between the distance of the viewing lens from the peritoneal surface and the incidence of OME; these authors claim that OME almost ceases to exist with close contact laparoscopy with less than 1cm separation of the laparoscope tip from the peritoneal surface (and with direct visualisation laparoscopy, suggesting that the use of video-assisted laparoscopy may impair visualisation) with incidences of OME ranging from 0% to 25% in various studies {1-7}. 

 

"Hopton and Redwine {7} have also highlighted the key factors that are likely to be influential on whether OME is diagnosed: the definition of normal peritoneum, the size and location of biopsies of 'normal peritoneum', the histological definition of endometriosis, and whether women undergoing laparoscopic assessment have recently been using hormonal suppressive therapy....

 

"The more careful the search for endometriosis – and the closer the laparoscope tip is applied to the peritoneal surface – the less chance of missing any endometriosis. - There is a strong place for clear definitions to standardise laparoscopy performed by all gynaecological surgeons in relation to (a) viewing distance from the laparoscope tip and (b) definitions of what constitutes abnormal peritoneum, particularly the subtle abnormalities highlighted by Redwine {5} and Redwine and Yocom {6}. The more meticulous the search for endometriosis and the combination of this search with meticulous excision of all lesions, the more likely endometriosis is to be eradicated through laparoscopic surgery."

http://f1000.com/prime/718213409

Epigenetics in endo

Here is an interesting article discussing epigenetics in endometriosis. While they do assimilate epigenetics with pathogenesis of endo (since endo has been seen in fetuses, it is still more plausible that it is laid down embryonically), the incidence of epigenetics playing a role in how the disease presents itself and is influenced is interesting to consider.

 

 

http://molehr.oxfordjournals.org/content/15/10/587.long

 

 

Here's a tidbit:

 

"Endometriosis has been regarded as an ultimate hormonal disease, owing much to its estrogen-dependency and aberrations in estrogen production and metabolism (Bulun et al., 2002; Kitawaki et al., 2002; Gurates and Bulun, 2003). It also has been viewed as an immunological disease due to a myriad immunological aberration in endometriosis (Paul Dmowski and Braun, 2004; Ulukus and Arici, 2005). In addition, it has been thought of a disease caused by exposure to environmental pollution and toxins (Rier et al., 1993; Rier, 2002) although so far there are no solid human data (Guo, 2004). Finally, it has been regarded as a genetic disease (Simpson et al., 2003; Barlow and Kennedy, 2005), due, apparently, to its reported familial aggregation. Yet even the reported familial aggregation, when examined closely, may be debatable (Di and Guo, 2007), and there has been little progress regarding the identification of genetic variants that predispose women to endometriosis (Di and Guo, 2007; Falconer et al., 2007; Guo, 2009b)."

 

((((((NOTE: some of the references are dated- such as little progress to genetic variances when there have been such since then (2007).)))))

 

"Given the reported epigenetic aberrations in endometriosis, one question is whether these aberrations are the cause or merely the consequence of endometriosis. Since most, if not all, human studies reporting epigenetic aberrations in endometriosis are carried out cross-sectionally, the reported aberration may be a cause for, but also could be a consequence of, endometriosis.

 

"Aging (Wilson and Jones, 1983; Toyota and Issa, 1999; Richardson, 2002), diet (Jacob et al., 1998), chronic inflammation (Hsieh et al., 1998; Issa et al., 2001), prolonged transcriptional suppression (Song et al., 2002; Stirzaker et al., 2004) and even maternal care (Champagne et al., 2006). In endometriosis, it has been shown that prolonged stimulation of an endometriotic epithelial-like cell line by tumor necrosing factor (TNFα), which has been shown to have increased production in endometriosis, resulted in at least partial methylation in the PR-B promoter (Wu et al., 2008b). This provides evidence that certain phenotypic changes in endometriosis, such as increased production of proinflammatory cytokines, may also cause epigenetic aberrations, which in turn result in changes in gene expression and subsequently other phenotypic changes such as increased cellular proliferation (Wu et al., 2008a) and perhaps some phenotypic changes."

 

http://molehr.oxfordjournals.org/content/15/10/587.long

 

genotypes of GSTM1 and/or GSTT1 contribute to risk of endometriosis

"Endometriosis is one of the most frequent benign gynecological disorders. Numerous studies have shown an association between GSTM1 and/or GSTT1 polymorphisms and endometriosis susceptibility. However, these associations remain inconclusive. To derive a more precise estimation, we conducted a comprehensive search to identify all existing studies and then performed a meta-analysis. Electronic literature searches of the PubMed, Chinese Biomedical, and China National Knowledge Infrastructure databases were performed up to December 2013. GSTM1-, GSTT1-, and dual-null genotypes were analyzed independently, and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated by comparing the null genotype with other genotypes using the random-effects or fixed-effects model. Twenty-five and 16 independent studies on GSTM1 and GSTT1 polymorphisms, respectively, and five GSTM1-GSTT1 interaction analyses were identified and included in this meta-analysis. Both GSTM1- and GSTT1-null genotypes increased risk of endometriosis (OR = 1.54, 95% CI: 1.30–1.83, P<0.001; OR = 1.41, 95% CI: 1.10–1.82, P = 0.007; respectively). Moreover, we found a significant positive association between the dual null genotype GSTM1-GSTT1 and endometriosis susceptibility (OR = 1.33, 95% CI: 1.03–1.72, P = 0.027). This meta-analysis provides evidence that null genotypes of GSTM1 and/or GSTT1 contribute to risk of endometriosis. Further investigations are required to confirm these findings." http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106761

Links endo after ovary removal

http://www.ncbi.nlm.nih.gov/pubmed/8127534

http://www.ncbi.nlm.nih.gov/pubmed/7589631

http://link.springer.com/chapter/10.1007/978-1-4613-8404-5_18#page-1

http://www.ncbi.nlm.nih.gov/pubmed/11789754

http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.1999.tb08377.x/full

http://www.researchgate.net/publication/12870281_Recurrent_pain_after_hysterectomy_and_bilateral_salpingo-oophorectomy_for_endometriosis_evaluation_of_laparoscopic_excision_of_residual_endometriosis

http://endometriosis.org/treatments/hysterectomy/

Exercise and Endometriosis

Pain with exercise can be a symptom of endometriosis. The inflammation, the location of the lesions, the presence of adhesions, and other factors such as pelvic floor dysfunction (too tight muscles- http://endocomprehensive.blogspot.com/2014/01/pelvic-floor-spasm.html), trigger points, muscles spasms, etc can all factor into the pain felt. So how is exercise good for endometriosis?

 

"Regular physical exercise seems to have protective effects against diseases that involve inflammatory processes since it induces an increase in the systemic levels of cytokines with anti-inflammatory and antioxidant properties and also acts by reducing estrogen levels. Evidence has suggested that the symptoms associated with endometriosis result from a local inflammatory peritoneal reaction caused by ectopic endometrial implants....regular physical exercise seems to have protective effects against diseases that involve inflammatory processes since it induces an increase in the systemic levels of cytokines with anti-inflammatory properties [9]. In addition, regular physical exercise is associated with a cumulative effect of reduction of menstrual flow, of ovarian stimulation and of the action of estrogen [10]....Analysis of available literature data show that there are no controlled and randomized studies identifying whether physical exercise prevents the occurrence or progression of the endometriosis and how and to what extent physical exercise could be beneficial for women with endometriosis. The few existing studies are of an observational type, with little or no statistical significance, but that indicate an inverse relationship between the practice of physical exercise and the risk of endometriosis. These studies also drawing attention to the possibility that conclusions about non-protective effect of exercise in women with endometriosis can be due the discomfort experienced, what prevent the practice of physical exercise. Therefore, with the literature available it is not possible to point out the real role of physical exercise in endometriosis. Thus, until now we only have speculations about this topic. In this respect, we believe that studies well controlled, using validated instruments for evaluation and follow up, well- defined study groups and well established exercise protocol can demonstrate the real role of physical exercise on treatment of endometriosis. On this basis, experimental models of endometriosis would be justified because they would permit the characterization of the time course of the disease in order to elucidate whether physical exercise is indeed able to interfere with the development of the endometriosis injury. In addition, it would be possible to determine what intensity would be necessary for physical exercise to be used in both a preventive and curative manner regarding the disease." http://www.rbej.com/content/12/1/4

 

Exercise can be helpful for most chronic pain conditions:

 

 

"“Exercise improves your pain threshold,” says Trent Nessler, PT, DPT, MPT, a vice president with Champion Sports Medicine in Birmingham, Ala. “With chronic pain, your pain threshold drops -- in other words, it takes less pain to make you feel more uncomfortable. With cardiovascular, strengthening, and flexibility exercise, you can improve that pain threshold.”" http://www.webmd.com/pain-management/features/exercise-relief

 

"Dr Sluka concluded that these data suggest that regular exercise reduces pain by activation of opioid receptors in descending inhibitory pathways in the central nervous system. She further proposed that regular exercise could prevent the transition from acute to chronic pain through the release of regulatory macrophages and increased levels of IL-10, an anti-inflammatory cytokine which can reduce nociceptor sensitisation [2]." http://www.bodyinmind.org/physical-activity-chronic-pain/

 

"Exercise helps to alleviate pain related to nerve damage (neuropathic pain) by reducing levels of certain inflammation-promoting factors, suggests an experimental study in the June issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS)." http://www.eurekalert.org/pub.../2012-06/wkh-hde060112.php

 

 

But any exercise regimen should be tailored for your body and is best done under the guidance of a professional who is familiar with your condition.

"Exercise activates endogenous analgesia in healthy individuals. The increased pain threshold following exercise is due to the release of endogenous opioids and activation of (supra)spinal nociceptive inhibitory mechanisms orchestrated by the brain. Exercise triggers the release of beta-endorphins from the pituitary (peripherally) and the hypothalamus (centrally), which in turn enables analgesic effects by activating μ-opioid receptors peripherally and centrally, respectively. The hypothalamus, through its projections on the periaqueductal grey, has the capacity to activate descending nociceptive inhibitory mechanisms. However, several groups have shown dysfunctioning of endogenous analgesia in response to exercise in patients with chronic pain. Muscle contractions activate generalized endogenous analgesia in healthy, pain-free humans and patients with either osteoarthritis or rheumatoid arthritis, but result in increased generalised pain sensitivity in fibromyalgia patients. In patients having local muscular pain (e.g. shoulder myalgia), exercising non-painful muscles activates generalized endogenous analgesia. However, exercising painful muscles does not change pain sensitivity either in the exercising muscle or at distant locations. LIMITATIONS: The reviewed studies examined acute effects of exercise rather than long-term effects of exercise therapy. CONCLUSIONS: A dysfunctional response of patients with chronic pain and aberrations in central pain modulation to exercise has been shown, indicating that exercise therapy should be individually tailored with emphasis on prevention of symptom flares. The paper discusses the translation of these findings to rehabilitation practice together with future research avenues." http://www.ncbi.nlm.nih.gov/pubmed/22786458

 

Pelvic physical therapy helped me get started by helping to retrain my pelvic muscles to relax and knowing what would trigger more pain (high impact exercises). (For some of the things pelvic PT can help with see http://www.pelvicpainrehab.com/female-pelvic-pain/674/how-pelvic-floor-pt-helps-endometriosis-4/ or watch this video: http://endocomprehensive.blogspot.com/2013/11/video-endometriosis-and-pelvic-physcial.html) After I had excision surgery, we were able to move on to rebalancing my muscle groups with a balance of strengthening and stretching exercises.

 

My mainstay throughout has been yoga. Many of the exercises I did in pelvic PT were what  I was doing in yoga. Yoga not only helped me manage pain but also manage the stress caused by the pain. For some of the poses that have helped me, see http://endocomprehensive.blogspot.com/2014/07/my-current-yoga-poses-that-help.html. Also here is a video that I come back to often: http://www.yogajournal.com/video/video/gentle-flow/

 

 

Why Some May Feel More Pain With Endometriosis

Differences that could influence pain levels:

"It's important to note that the amount of pain is not necessarily related to the extent or size of the growths. Tiny growths, called petechiae, have been found to be more active in producing prostaglandins, which may explain the significant symptoms that seem to occur with smaller growths." http://www.crat.org/Endometriosis_Info.html

"There was significantly different distribution of nerve fibers in multiple endometriosis lesions, which was correlated with dysmenorrhea, anus pain, dyspareunia and chronic pelvic pain, not with clinical staging." http://www.ncbi.nlm.nih.gov/pubmed/20646536

"The presence of endometriosis-associated nerve fibers appear to be related to both the pain experienced by women with endometriosis and the concentration of PF cytokines; however, this association varies with the lesion location."
http://www.ncbi.nlm.nih.gov/pubmed/22154765

"There was no difference in the density of nerve fibers across the menstrual cycle in peritoneal endometriotic lesions. These findings may explain why patients with peritoneal endometriosis often have painful symptoms throughout the menstrual cycle." http://www.ncbi.nlm.nih.gov/pubmed/21334610

"Initial work on mapping of pain associated with the endometriosis lesions resulted in some thought-provoking findings. The classic black lesions were found to be painful in only 11% of patients when the lesion was touched. Similarly, white lesions were painful in 20% of patients with red lesions at 37%, and clear lesions at 32% were the most painful (Table 1). These results added further reason as to why initial therapy had such poor results. Surgeons would only “see” the black lesions and removed them, but these were the least painful lesions. The most painful clear lesions were not “seen” at laparotomy and therefore remained, as did the pain. What became apparent next, while mapping the patient, was the fact that the pain extended 28 mm beyond the visible border of the lesion onto what looked like “normal” peritoneum ((Figure 1). Therefore, if the surgeon only removed the lesion at its border, the microscopic disease in the previously identified normal looking peritoneum was left, and persistence or recurrence of the symptoms was encountered." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3015350/

"Women with endometriosis and pelvic pain almost always have fine, unmyelinated nerve fibers present in the functional layer of endometrium, and these nerve fibers are also greatly increased in the myometrium. Women without endometriosis almost never have these nerve fibers. These nerve fibers may also play a role in pain generation."  http://www.livingwithendometriosis.org/2010/03/28/nerve-clusters-without-myelin-sheath-found-as-culprit-in-endometriosis/

"Hormones and chemicals released by endometriosis tissue also may irritate nearby tissue and cause the release of other chemicals known to cause pain....Some endometriosis lesions have nerves in them, tying the patches directly into the central nervous system. These nerves may be more sensitive to pain-causing chemicals released in the lesions and surrounding areas. Over time, they may be more easily activated by the chemicals than normal nerve cells are. Patches of endometriosis might also press against nearby nerve cells to cause pain."  https://www.nichd.nih.gov/health/topics/endometri/conditioninfo/Pages/symptoms.aspx
"Our group discovered that ectopic growths harvested from ENDO rats and women with established endometriosis develop their own C-fiber (sensory afferent) and sympathetic (autonomic efferent) nerve supply. The supply is derived from nerve fibers innervating nearby territories that sprout branches into the growths [10], [11]. This discovery suggests that, rather than the growths alone, it is the ectopic growth's own innervation that is a major contributor to the maintenance and modulation of pain in established endometriosis." http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0031758

So pain is influenced by several factors- the location of the endo, the "type" or "stage" (clear, black, red, etc) of lesions, how much innervation is there, how much inflammatory chemicals are being released, if adhesions are pulling on anatomy, if other conditions such as pelvic floor dysfunction, interstitial cystitis, or adenomyosis is present. Then add in other things that influence how any type of pain is felt and you can see there are many factors that come into play.

Endometriosis Persisting After Castration: Clinical Characteristics and Results of Surgical Management.

Endometriosis Persisting After Castration: Clinical Characteristics and Results of Surgical Management.
REDWINE, DAVID B. MD

Objective: To identify the clinical characteristics and response to surgical treatment of endometriosis-associated pain in castrated women.

Methods: In a prospective, longitudinal observational study, 75 patients with previous castration had biopsyproven endometriosis excised surgically. Anatomical characteristics of disease were studied using pelvic mapping and compared to the findings in non-castrated women with endometriosis. Preoperative and postoperative verbal analogue pain scales were used to gauge the response to excision of endometriosis.

Results: Patients treated surgically for endometriosis following castration were significantly older (37.8 +/- 8.1 versus 31.3 +/- 6.9 years, mean +/- standard deviation; 95% confidence interval [CI] 4.9-8.1) and slightly more likely to have intestinal involvement (risk ratio 1.3, 95% CI 0.94-1.8) than non-castrated endometriosis patients. Most had marked alleviation of pain after excision of endometriosis.

Conclusions: Endometriosis can remain symptomatic after castration, with or without estrogen therapy. In such patients, there is a 33% frequency of intestinal involvement. At castration, consideration should be given to removal of invasive peritoneal and intestinal disease. Symptom improvement occurs in most patients after excision of endometriosis.

(C) 1994 The American College of Obstetricians and Gynecologists
http://journals.lww.com/greenjournal/Abstract/1994/03000/Endometriosis_Persisting_After_Castration_.16.aspx

2 day old baby with endometriosis and endometrioma case report

Fertil Steril. 2015 Jan;103(1):160-2. doi: 10.1016/j.fertnstert.2014.09.045. Epub 2014 Oct 24.

Fetal endometriosis: a case report.

Schuster M¹, Mackeen DA².

Author information

• ¹Geisinger Medical Center, Danville, Pennsylvania. Electronic address: mschuster@geisinger.edu.
• ²Geisinger Medical Center, Danville, Pennsylvania.

Abstract

OBJECTIVE:

To report a case of a large fetal pelvic mass diagnosed at 35 weeks' gestation.

DESIGN:

Report of a unique case of a fetal abdominal mass, emphasizing the wide range of differential diagnoses. Although rare reports of fetal ovarian cysts exist, even fewer describe endometriosis or endometriomas in infants. As of 2014 there have not been any published reports of fetal endometriosis from the United States.

SETTING:

Large tertiary community hospital.

PATIENT(S):

An 18-year-old pregnant woman diagnosed with a large fetal pelvic mass at 35 weeks' gestation.

INTERVENTION(S):

Diagnosis of a fetal abdominal mass at 35 weeks with documented enlargement at 37 weeks leading to delivery, with subsequent removal of the mass on day of life 2.

MAIN OUTCOME MEASURE(S):

On day of life 2, a pediatric surgeon performed an exploratory laparotomy and left salpingo-oophorectomy.

RESULT(S):

Final pathology showed a 7.0 × 4.5 cm cyst-like structure consistent with hemorrhagic ovarian cyst wall and focal endometriosis.

CONCLUSION(S):

It can be very difficult to counsel patients regarding an abdominal mass in their unborn child. These difficulties stem from the large list of differential diagnoses and the range of prognoses they portend. As more and more of these cases appear in the literature, we are able to gain a better understanding of how each of these diagnoses present and appear on imaging, allowing us to provide a more accurate diagnosis and counseling antenatally.

Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
http://www.ncbi.nlm.nih.gov/pubmed/25450297