Endometriosis lesions attract nerves and immune cells that relay pain signals to the brain, and a class of drugs originally developed for muscle wasting could block that process. Endometriosis affects roughly 1.5 million women in the UK, costs the economy £8.2 billion per year, and has no cure. Existing treatments—surgical removal of lesions or hormone-suppressing drugs—fail in up to 75% of women or cause intolerable side effects. The researchers have found that cells within endometriosis lesions carry androgen receptors, the same protein that mediates male hormone signals. Their pilot data suggest that selective androgen receptor modulators (SARMs), a class of drugs already in development for other conditions, could offer a new way to treat endometriosis pain without the side effects of current therapies. If the drugs work, women could have a medical alternative to surgery that directly targets the lesions themselves rather than shutting down the entire menstrual cycle. The work spans both fundamental science—understanding how androgens regulate the womb lining in health and disease—and translational testing of repurposed drugs in patient samples and animal models.
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Endometriosis is a chronic incurable disease that affects an estimated 176 million women worldwide, similar to the number of women affected by diabetes mellitus or asthma (approximately 1.5 million women in the UK). It is associated with debilitating pelvic pain, painful periods, pain with sexual intercourse and infertility. Endometriosis costs the UK economy £8.2 billion per year. The causes of endometriosis are not known but genetic, environmental and anatomical factors may all contribute. Up to 90% of patients with endometriosis suffer from 'peritoneal disease' caused by the presence of small pieces of tissue ('endometrium' or womb lining) that have 'escaped' into and stuck onto the wall of the pelvic cavity. Once embedded on the peritoneal wall these 'endometriosis lesions' attract nerves, and immune cells that interact with each other and relay 'pain' messages to the brain. Endometriosis is managed by surgical excision of lesions (with its inherent risks) or drugs, but symptoms recur after surgery in up to 75% of women and available medical treatments have undesirable side effects. There is an urgent need for new treatments for endometriosis. Whilst the type of sex steroid classed as 'androgens' are usually considered as 'male hormones', women also have significant amounts of androgens in their body. We have found that the protein that mediates the androgen signal to target tissues, the androgen 'receptor' is present not only in cells within the uterus but also in cells within endometriosis lesions. Our pilot data show that drugs capable of interacting with androgen receptors could offer a new way of treating women suffering from endometriosis and we believe that a newly developed class of drugs, termed selective androgen receptor modulators or SARMs, could be an effective, alternative novel therapeutic. Our overarching objective is gain a better understanding of the role played by androgens in the regulation of the endometrium, how this role may become disturbed in women with endometriosis and to test a new class of drugs - the selective androgen receptor modulators (SARMs), as a treatment for endometriosis-dependent pain. We will use samples from patients who attend our clinics, capitalise on other resources in our closely associated research environment (including new animal models) as well as using commercially available drugs that we can re-purpose to treat our patients. Our proven track record in women's health research and world-leading expertise in steroid hormone action will both ensure rapid progress and support a programme of work that spans both discovery science and translational medicine.
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