A daily pill to treat endometriosis has just been recommended by the National Institute for Health and Care Excellence (Nice).
Once available on the NHS, linzagolix will provide a new treatment option for those who have been unable to manage the condition using other standard treatments.
Endometriosis affects one in ten women of reproductive age. The condition causes the lining of the womb (the endometrium) to grow outside the uterus – most commonly in the pelvis, bladder and bowel.
This causes wide and varied symptoms, including heavy, painful periods, pelvic pain between periods, pain when using the toilet, painful sex, tiredness and difficulty getting pregnant. Up to half of women diagnosed with endometriosis experience infertility as a consequence of the condition.
Endometriosis currently has no cure. Available treatments include the use of painkillers, hormonal contraceptives and surgery to remove lesions. However, these treatment options are often inadequate and, in many cases, aren’t suitable for patients for many reasons – including existing medical conditions, pregnancy or because of the risk of side-effects or complications.
Endometrium growth (both inside and outside of the womb) is driven by the reproductive hormone oestrogen. As such, blocking oestrogen can help prevent or slow the growth of the abnormal endometrial tissue and help relieve symptoms in people with endometriosis.
This is what linzagolix aims to do. Linzagolix is a gonadotrophin releasing hormone (GnRH) antagonist, which works by suppressing oestrogen – inducing a “medical menopause”. Medical menopause refers to the cessation of periods as a result of a prescribed medical treatment. Menopausal symptoms are typically reversed as soon as the drug is no longer being used.
The hypothalamic-pituitary-ovarian axis is vital in women. It regulates the hormones involved in the menstrual cycle (including the release of oestrogen). GnRH is produced by a brain region called the hypothalamus. Usually, GnRH would bind to receptors in the pituitary gland (a small, pea-sized gland found at the base of the brain in line with the top of the nose) leading to the release of follicle stimulating hormone (FSH) and luteinising hormone (LH). FSH and LH then stimulate the ovaries to produce oestrogen and progesterone.
But linzagolix works by attaching to the pituitary gland GnRH receptors and preventing the GnRH from attaching. With no GnRH, FSH and LH are rapidly suppressed. This in turn leads to a decrease in oestrogen production from the ovary.
Linzagolix has been shown to cause a statistically significant reduction in painful periods and general pelvic pain in multiple trials. Patients saw the greatest benefits when taking a dose of 75mg or more. Significant relief from pelvic pain was noted by week 12 and maintained or even enhanced by weeks 24 and 52.
The side-effect from linzagolix that is most worrying is loss of bone mineral density due to the suppression of oestrogen. However, this was only really a concern when patients were taking doses of 200mg. In this instance, patients would need to be prescribed add-back hormone replacement therapy (HRT) – low doses of oestrogen and progesterone that help prevent the loss of bone mineral density while on a treatment that induces medical menopause. Add-back HRT can also help treat the crippling menopausal symptoms that women of reproductive age suffer with while in a medical menopause.
Unfortunately, add-back HRT is not suitable for all patients – especially those who have other medical conditions.
Take-at-home treatment
Linzagolix will be prescribed to those that have failed usual hormonal treatments (such as the combined pill, progesterone-only pill or hormonal coil) or surgery.
Linzagolix will be the second take-at-home pill to become available on the NHS for treating endometriosis in those that have failed other treatments.
In March, Nice also approved relugolix. This drug works similar to linzagolix, but has add-back HRT included in the prescription. Since add-back HRT isn’t suitable for everyone, linzagolix has the advantage of being a more tailored treatment option for women with endometriosis.
Linzagolix also offers multiple advantages over GnRH agonists, which are also used to manage endometriosis. GnRH agonists fully suppress the release of oestrogen. This can lead to many side-effects, including hot flushes, loss of libido, vaginal dryness and bone mineral density loss. But because linzagolix is a GnRH antagonist, this means it can be tailored to only partially suppress oestrogen, leading to fewer side effects.
Linzagolix is taken orally, whereas GnRH agonists need an injection every month or three months to work.
Linzagolix is also rapidly reversible, whereas GnRH agonists have unpredictable reversibility, it can take months for ovarian function to return to normal when using GnRH agonists. This is clearly a problem for those wishing to conceive or stop the treatment due to side-effects. Linzagolix has a short half life which means it does not stay in a person’s system for very long.
The most commonly reported side-effect of linzagolix are hot flushes – though this usually only occurs when a patient is taking a higher dose of the drug. Bone mineral density loss can also occur at higher doses, which is why add-back HRT will be needed in these instances.
Endometriosis affects millions of women. Current treatment options are limited – and with no cure in sight, any additional treatments offer new hope for those affected. Linzagolix may soon offer a lifeline to those with endometriosis who haven’t been able to find relief using other treatments.
Nicola Tempest is a Senior Lecturer, Subspecialist in Reproductive Medicine and Consultant Gynaecologist at the University of Liverpool. This article is republished from The Conversation under a Creative Commons license. Read the original article
