Stephen Franks is Professor of Reproductive Endocrinology at Imperial College Faculty of Medicine and Consultant Endocrinologist at St Mary’s and Hammersmith Hospitals, London. Prof Franks’ clinical and laboratory research focuses on the hypothalamic-pituitary-ovarian axis, with a particular interest in polycystic ovary syndrome. In this interview, he tells us more about his research, current challenges in reproductive endocrinology and his role as a Reproductive Endocrinology and Biology Network convenor.
What inspired your passion for endocrinology, and reproductive endocrinology in particular?
As a young medical registrar with no experience of research, I was offered a research fellowship to study the physiology and pathology of prolactin (my supervisor and mentor was Howard Jacobs whose enthusiasm was contagious). It was an exciting time for prolactin research because measuring prolactin in blood was new. Radioimmunoassays for prolactin were problematic and I had to set one up from scratch that enabled us to show that hyperprolactinaemia was a common cause of amenorrhoea. The project got me hooked on endocrinology, and reproductive endocrinology in particular, so I carried on to train in internal medicine and endocrinology before finding the ideal clinical academic staff position, which I have held ever since.
Tell us a little more about your current position and work?
As Professor of Reproductive Endocrinology, my clinical practice focuses on reproductive endocrine problems with strong collaboration among my gynaecological colleagues. My main research goals for the last 30 years have focused on trying to unravel the complexities of both reproductive and metabolic problems of polycystic ovary syndrome (PCOS). This has involved clinic-based studies, epidemiological studies and lab-based studies, using human ovarian cells and animal models. My lab-based studies are jointly led with my colleague Professor Kate Hardy, a reproductive biologist.
Over the last decade, what do you think have been the most significant advances in reproductive endocrinology research or clinical practice?
There are many, including the discovery of the importance of the neuroendocrine signalling relay that impacts on gonadotropin secretion, notably the role of kisspeptin, neurokinin and dynorphin neurones. In the area of PCOS research, new data emerging from genome-wide association studies have given us clues to the genetic basis of this complex endocrine disorder.
What do you think has been the most surprising discovery in the field over the last decade?
Discovery, in the mouse at least, that anti-Mullerian hormone (AMH) has receptors in hypothalamic neurones, and can affect secretion of gonadotropin-releasing hormone (GnRH). For many years, it was thought that AMH was simply a local hormone, produced by the Sertoli cells of the testis, that played a key part in differentiation of the male reproductive tract. However, much more recently, AMH was also found to be synthesized and secreted by granulosa cells of the ovary, and has since been widely used as a clinical marker of ovarian follicular reserve. So, the report, by Dr Paolo Giacobini and colleagues in Lille, that this hormone has specific receptors in the mouse hypothalamus and that AMH has a profound effect on GnRH secretory activity was, to say the least, unexpected. The relevance of these findings to human physiology remains to be seen but perhaps we should not be too surprised, given that related gonadal growth factors, such as inhibins and activins, also have actions on the hypothalamic-pituitary axis.
What clinical advances do you think could make a difference for patients affected by reproductive health conditions in the near future?
I would hope that understanding more about the genetic basis of PCOS, particularly differences in genotype between individuals, will lead to more specific and effective ways of treating PCOS, rather than (the nevertheless important) management of symptoms.
What do you think are the main challenges faced by your clinical specialty?
There is a shortage of endocrinologists with a special interest in reproductive endocrinology. This is partly because not all endocrine training programmes offer sufficient experience of this sub-specialty.
Are there any major controversies in your practice area?
One good example is whether PCOS is a risk factor for cardiovascular events. Women with PCOS have risk markers for cardiovascular disease but do they actually have more heart attacks? We lack long-term, longitudinal studies on this, and therefore it would be wise to consider appropriate screening for cardiovascular risk factors in women with PCOS (including cholesterol, lipid and lipoprotein measurements), especially if they are obese. Despite the lack of definitive information about cardiovascular events in women with PCOS, it seems sensible to advise women with PCOS about the importance of diet and exercise to reduce the risk of cardiovascular disease.
What is the most unusual part of your work?
As a reproductive endocrinologist, much of my work and research centres around problems related to reproductive health and ovarian disorders. That naturally means that I have close links with my gynaecological colleagues and, for example, we ran a joint infertility clinic, albeit with a focus on induction of ovulation. Much of my research is laboratory based and, in that area, my long-term collaboration with my reproductive scientist colleague, Professor Kate Hardy, plays an important part. We jointly run our research group and the interaction between clinical and basic scientists is an important aspect in both research and training.
What do you enjoy about being a Reproductive Endocrinology and Biology Endocrine Network convenor, and how do you think the Network can benefit others?
The network facilitates interdisciplinary research through meetings in reproductive endocrinology and biology, using joint sponsorship from the Society for Endocrinology and the Society for Reproduction & Fertility (SRF), by providing a platform for collaborative research. Andy Childs and I (together with Kate Hardy) are currently putting together a programme of international speakers for a meeting on growth factor signaling in the ovary, to which the Society has contributed a meeting grant. An important feature of our Network is that it also involves input (both intellectual and financial) from the SRF, and we shall also be seeking involvement from them. Also, in planning, is another meeting of ReproSouth (again, jointly with SRF), an informal event where students and post-docs (from the Midlands and Wales, as well as London and the South) are encouraged to present work in progress (scheduled for June, this year). Ahead of our next Network meeting at SfE BES 2018 in November we will be canvassing topics for collaborative research across centres in the UK.
Further details on the ReproSouth meetings can be obtained from Stephen Franks and Andy Childs directly.
Do you have any words of wisdom for young endocrinologists out there?
Whether you are planning a career in academic endocrinology, clinical practice or related pathways, there is no substitute for the experience and excitement of being involved in a research project. My own experience of being introduced to research as a very junior physician is that it opened up a completely new way of thinking. So, whether you stay in research or not, it allows you to approach problems in a unique way. And, despite the trials and tribulations, the rewards of a career in academic endocrinology are many, including the privilege of being part of a national and international “family” of colleagues and friends.
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