“A painful womb condition that affects around two million British women may be triggered by an out-of-control enzyme”, the Daily Mail reported. It said that scientists claim the findings of a study could be used to diagnose and treat endometriosis, a condition which causes pain, menstrual problems and can affect fertility. The enzyme, telomerase, aids the replication of DNA sequences, and is found in cells that divide frequently. The scientists said the telomerase-generating cells that line the uterus of women with endometriosis act like cancer cells, ‘dividing uncontrollably’ causing the cells to survive for longer and migrate outside of the uterus to other locations.
Although the newspapers said the findings may be used in the diagnosis and treatment of endometriosis, at the current time this is too early to say. The findings have shed some light on the possible pathological development of the condition, but this is preliminary research using laboratory samples from a few women. Whether this could lead to any diagnostic or treatment options is far from clear and has yet to be investigated.
Where did the story come from?
Dr D.K. Hapangama and colleagues from the School of Reproductive and Developmental Medicine at the University of Liverpool, and the Crucible Laboratory and Henry Wellcome Laboratory for Biogerontology Research at the University of Newcastle carried out the research. Funding was provided by the University of Liverpool and a Royal College of Obstetrics and Gynaecology grant to Dr Hapangama. The study was published in the peer-reviewed medical journal: Human Reproduction.
What kind of scientific study was this?
This was a case control study designed to investigate the theory that endometriosis is associated with abnormal expression of telomerase and telomere lengthening in the endometrium (lining of the uterus).
The researchers recruited a sample of 29 women with surgically diagnosed endometriosis (group one) and 27 women who were found not to have the condition during a routine surgical sterilisation procedure (group two). All women were between 18 and 46 years of age and had regular periods and were not taking any hormonal supplements, such as the contraceptive pill.
All women had biopsies taken of their endometrium (the lining of the uterus) during the second half of their menstrual cycle (the luteal phase). The biopsies were taken during the ‘window of implantation [of a fertilised egg]’ phase (between days 19 and 23) in 17 women from group one and 15 women from group two. The remaining 12 women in each group had biopsies in the last days of their cycle (days 24 to 28). Blood samples were also taken to assess levels of oestrogen and telomerase circulating in the blood.
In the laboratory, the tissue samples were examined for expression of telomerase and oestrogen receptor (ERß) using an antibody that would bind to telomerase and then be highlighted during staining. As positive controls (and so should show telomerase activity), the researchers also compared several different tissue types to the biopsies, including cancerous endometrial tissue, cancerous breast tissue, tonsillar tissue, and endometrial tissue taken during the early proliferative phase of the menstrual cycle. An antibody that would not bind to telomerase was used as a negative control. It is unclear where the comparison tissues came from, but presumably not from the same women. It was a blind study, so the researchers examining the samples were unaware of which samples they were examining.
Using another technique, the tissue and blood samples were used to examine the average length of the telomeres during cell division. Statistical tests were used to look at the differences in telomere length depending on when the biopsy was taken and whether or not the woman had endometriosis.
What were the results of the study?
Women in groups one and two were similar in age, height, weight, and usual menstrual cycle length; however, of the women biopsied in the late cycle days, those in group one were younger than those in group two. Half of the women with endometriosis had mild/moderate disease, and the other half had severe disease.
In the group two women without endometriosis, telomerase activity was weak or not apparent throughout the luteal phase of the menstrual cycle. In the women with endometriosis, staining for telomerase was significantly increased compared to the group two women at both the window of implantation and late, premenstrual phases. In healthy group two women, expression of telomerase and oestrogen receptor (ERß) was seen in the connective tissue (stroma) and cells surrounding the blood vessels during the luteal phase, but was significantly less in group one women. The researchers also found that the average telomere length was significantly longer during the window of implantation phase in women with endometriosis compared to those without it.
Telomere length was not affected by age, height, weight, or BMI. In the peripheral blood samples, oestrogen levels rose with increases in telomere length. There was no difference between the groups in circulating progesterone levels. The positive control samples showed telomerase activity, as expected.
What interpretations did the researchers draw from these results?
The researchers suggest that abnormal expression of telomerase in the endometrium enhances proliferation of the cells and may contribute to the pathogenesis (origin and development) of endometriosis.
What does the NHS Knowledge Service make of this study?
This carefully designed study has shed light on some cellular processes that might be responsible for the excess proliferation of endometrial tissue in endometriosis. However, as the researchers openly acknowledge, this is preliminary research. Tissue samples from only a small sample of women were studied and much larger numbers would be needed to confirm these results. Also, a case control study such as this cannot prove causation. As such, it is too early to suggest that this could lead to any diagnostic or treatment options for the conditions.
This study is a valuable first step in the further understanding of endometriosis, a condition which can be treated symptomatically but currently has no cure. More research is anticipated.
Sir Muir Gray adds...
Good to see some science on this much neglected and badly managed disease.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
Daily Mail, 6 August 2008
The Daily Telegraph, 6 August 2008
Links to the science
Cochrane Database Syst Rev 2007, Issue 3
Cochrane Database of Syst Rev 2004, Issue 3
Human Reproduction 2008 23:1511-1519