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You are here: Home > Blogs > Disease > Genes may trump hormones in treating endometriosis

Genes may trump hormones in treating endometriosis

March 12, 2019 | Disease

Melanie senior

Endometriosis affects about one in ten women of reproductive age, making it one of the most common gynaecological disorders in the US. Yet no one really knows what causes the condition, which is occurs when endometrial tissue – which normally lines the womb – starts to grow where it shouldn’t, such as in the ovaries, fallopian tubes, bowel or along the pelvis.

Endometriosis can be extremely painful and, occasionally, may lead to infertility.

Endometrial tissue naturally breaks down according to hormonally-controlled cycles; the result is menstruation. But such tissue-breakdown outside the womb can cause cysts, severe cramps and very heavy periods. To date, most treatments deal with the symptoms, not the causes of endometriosis – and that is only after the condition is diagnosed, which can take years. Hormone therapy is most common: endometrial tissue grows in response to estrogen, so blocking estrogen using the contraceptive pill or gonadotropin releasing hormone analogs (GnRH) like Zoladex (goserelin) can help. Neither is without side-effects, and neither offers a long-term solution.

In July 2018, AbbVie’s Orilissa (elagolix) became the first FDA-approved oral treatment for the management of moderate-to-severe endometrial pain. Orilissa is a GnRH antagonist, rather than agonist. This means it is faster at lowering hormone levels, and is not associated with an initial, temporary worsening of symptoms that requires add-back therapy, as is the case for the older GnRH agonist drugs. AbbVie and partner Neurocrine Biosciences hailed Orilissa as a “significant advance”, which it is. But it, too, only deals with symptoms, not causes.

Enter gene therapy. This newly-resurrected modality – injecting corrected or new versions of faulty or missing genes to address the root causes of disease – is already transforming the lives of patients with certain rare, usually inherited conditions. Manipulating genes may be the next-big-thing in endometriosis, too. Recent research suggests that the expression of certain genes may be repressed in some women with endometriosis. Scientists at Yale University are trying to uncover whether administering a gene-regulator molecule called let-7b (a small, non-coding functional RNA, or micro-RNA) could help to treat the disease.

For now, they’re still working with mice. But results are promising: two weeks after receiving an injection of let-7b, mice with the disease had smaller lesions than before, and reduced expression of certain genes known to promote the condition.

If the approach works in humans, it would provide a much-needed alternative to hormonal therapy (which isn’t suitable for women trying to conceive, and can lead to reduced bone density) and to excision surgery, which is invasive, expensive and typically only used for severe cases.

So it is way too early to say definitively whether genes have trumped hormones in treating endometriosis. In the meantime, a call-to-action paper in the January 2019 issue of the American Journal of Obstetrics and Gynecology makes a strong case for earlier diagnosis of endometriosis, driven by patient and physician education and timely referrals to specialist providers. The authors put forward a practical, step-wise checklist designed to support more rapid, accurate diagnosis and faster treatment. AbbVie provided funding for the manuscript.

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