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Auckland scientists seek to shed light upon endometriosis

Auckland scientists seek to shed light upon endometriosis

It affects at least one in ten New Zealand women, can cause severe abdominal pain and fertility problems, and costs the public health system an estimated $1 billion a year.

If you have endometriosis, or know someone who does, you will be familiar with its debilitating and distressing effects. March is Endometriosis Awareness month, but surprisingly little is known about the underlying causes of this chronic disease, in which pieces of endometrium, the innermost lining of the uterus, lodge and grow outside the uterus.

Treatments now in use are not effective for all women. Steroids, such as oral contraceptives, are the main treatment, but steroids are only successful for half of women who receive them, and those women generally develop resistance to their specific treatment.

Some women undergo laparoscopies (keyhole surgery) to remove the rogue endometrium and scar tissue, and some undergo entire removal of the uterus or ovaries. But even surgical treatments do not always prevent the tissue growing back elsewhere.

New Zealand research underway into the cause of endometriosis offers fresh hope for future treatments that target the disease at its roots.

Dr Anna Ponnampalam, a reproductive biologist at the Liggins Institute and the University of Auckland department of Obstetrics and Gynaecology, suspects the cause partially lies in chemical changes to DNA that may lead the uterus lining to respond abnormally to the hormone progesterone.

“If we can figure out the exact molecular pathway behind endometriosis, and what triggers it, we will have a good chance of developing effective treatments,” says Dr Ponnampalam, who is conducting the study with Professor Cindy Farquhar from the department of Obstetrics and Gynaecology.

Dr Ponnampalam explains that usually oestrogen and progesterone work together to regulate a woman’s menstrual cycle.

“In the first half of the cycle, oestrogen primes the uterus lining to receive the progesterone, which in turn prepares it to accept an embryo if the woman gets pregnant. During the second half, even though there’s still some oestrogen around, progesterone dominates and mitigates the action of oestrogen.”

If the woman does not get pregnant, levels of both hormones fall and the endometrium sheds as a period.

“But in women with endometriosis, the lining responds differently to oestrogen, and progesterone doesn’t take over as it should – this is known as ‘progesterone resistance’.”

The researchers want to uncover how this develops at the molecular level. Their focus is on groups of small hydrocarbon molecules, called methyl groups, which they suspect are binding to DNA in affected women and switching particular genes on and off in a way that leads to progesterone resistance.

“Early data from my research and others’ show that many of the genes through which the steroid hormones act are abnormally methylated in the endometrium of women with this disease,” says Dr Ponnampalam.

“Chemical modulation of DNA by methylation is an epigenetic effect. Epigenetic effects do not change the underlying DNA sequence, but can be heritable.”

Researchers will collect endometrial samples from women with and without endometriosis, and hope to have early results next summer. The study is supported by a grant from the Auckland Medical Research Foundation.

Dr Ponnampalam is also keen to do a separate study to develop a new way of diagnosing endometriosis, which can currently be diagnosed only by laparoscopy, a keyhole surgery to visualise the endometrial tissues inside the abdomen.

“Because this is invasive, it puts some girls and women off,” she says.

Instead, she wants to search for a biological marker of endometriosis – molecules present in the menstrual blood of only women with endometriosis.

Internationally, the average delay before diagnosis is 8-11 years, and experts believe the actual incidence of the disease is far higher than the numbers diagnosed – which are around 120,000 women in New Zealand, and 176 million worldwide.

“This is also partly because period pain is viewed as normal, and so girls and women who complain of it are often not taken seriously.”

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