Abstract: Heavy menstrual bleeding (HMB) is a common and debilitating symptom but menstruation remains a taboo subject. Hence, it is rarely discussed, under-researched and sub-optimally managed. Many currently available medical treatments fail due to hormonal side effects and/or lack of effectiveness. We study endometrial physiology and pathology during menstrual breakdown and repair with the aim of developing better treatments for those suffering with HMB.

Over 80 years ago it was proposed that progesterone withdrawal caused intense vasoconstriction and transient endometrial hypoxia that resulted in menstruation. Subsequent research confirmed that inflammation initiates menstruation and disputed the presence and role of hypoxia in endometrial physiology. By studying human tissue and a mouse model of “simulated menstruation” we have shown that hypoxia is present in the menstrual endometrium. We also revealed that hypoxia is not necessary for endometrial breakdown at menstruation but is essential for timely repair of the denuded endometrial surface to limit menstrual blood loss.

This seminar will detail our work on the presence and role of hypoxia and hypoxia inducible factor (HIF, the master regulator of the cellular response to hypoxia) in the human endometrium using in vivo MRI techniques alongside ex vivo studies. In addition, the effects of pharmacological and genetic inhibition of hypoxia pathways in our mouse model of simulated menstruation will be described. Finally, evidence will be presented proposing HIF-1 stabilisers as a potential non-hormonal therapeutic strategy for women with HMB.

Biography: I am a Senior Clinical Research Fellow at the MRC Centre for Reproductive Health at the University of Edinburgh and an Honorary NHS Consultant in Gynaecology at the Royal Infirmary of Edinburgh. I run a specialist menstrual disorders service and offer medical treatments as well as surgical interventions, ranging from minimally invasive hysteroscopy and laparoscopy to open abdominal procedures. My research aims to develop better preventative and therapeutic strategies for abnormal uterine bleeding, a common and debilitating complaint. Specifically, I hold a Wellcome Trust Clinical Career Development Fellowship to investigate the role of hypoxia in menstrual physiology and pathology with the aim of developing more effective, acceptable treatments for heavy menstrual bleeding. I also have funding from the Royal Society of Edinburgh to examine the potential link between Long COVID and menstrual disturbance. I sit on the Editorial Board of Reproduction, Frontiers in Reproductive Health (Gynaecology) and Physiological Reviews and am a member of the RCOG Blair Bell committee.

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