At 18.30 on Monday 7 November Professor Jeremy Tomlinson is chairing a debate on the treatment of adrenal insufficiency at SfE BES 2016. Ahead of the debate, we asked Professors Stafford Lightman and Karim Meeran to give… More
Did you know that the thyroid gland, which regulates metabolism, “is often an area out of balance, and that [yoga] poses that stimulate the gland, such as shoulder stands, can help redress this”? Or that testosterone is the new botox? Neither did consultant endocrinologist Professor Maralyn Druce. Having had enough of the extraordinary claims echoed in the tabloids, she pens an open letter to the public in response.
Dear reader of newspapers, magazines and websites
Like you I am often interested in the latest developments in health and beauty; the many new things on the horizon that promise me happiness, youth or energy. Recently I have noticed a trend in the press for thinking about our hormones – our endocrine systems – as a route to improving our health and wellbeing.
I am a clinical endocrinologist, a doctor for people with health problems relating to the malfunctioning of hormone glands, and I can tell you that the many hormonal systems in the body are fascinating and complex. The complexity arises because these systems control and support functions for many different body functions, and they must be able to produce the correct amounts of the right hormones in response to the internal and external environment.
When you read some of these articles’ claims, you might be forgiven for thinking that your hormone glands are very fragile and that all sorts of measures need to be taken to ‘boost’ the production of certain hormones and support the limited supply of others. This is not true. Your thyroid gland in your neck produces thyroxine to control your metabolism, and it does so in response to another hormone called TSH. It does not need extra ‘boosting’ by complex poses in specially designed and costly yoga classes.
While yoga in general may be very positive for your health, mood, wellbeing or flexibility, there is no evidence that stretching the thyroid gland will change the amount of hormone it makes. Nor indeed is there any evidence, even if this were the case, that the proposed hormone boost would benefit you. Likewise, I’ve seen a lot of myths in the press concerning adrenal glands, which sit at the top of the kidneys and produce the hormone cortisol in response to both emotional and physical stress – helping the body to adjust and cope. Contrary to what you may read, your adrenal glands are not delicate bowls containing a small amount of precious cortisol that might run out. Different types of exercise will not cause your adrenal glands to ‘fatigue’ and run out of hormones – the adrenal glands are factories that make just the right amount of hormone to meet your body’s needs. There is also no evidence that you will benefit from special and often expensive supplements that are marketed to ‘support’ your hormones or your glands – a sensible diet and a healthy lifestyle are the only things that you need to do this, unless you have a specific illness that requires treatment.
We are also told that growth hormone is important for stronger bones and muscle growth, but there is no evidence that doing particular types of exercise to ‘boost’ levels has special benefits on bone strength or fitness over and above any other kind of fitness regime. In fact people with excessive levels of growth hormone actually suffer from a condition called acromegaly, which leads to a number of negative health effects. More is not always better.
For men who are healthy, the sex hormone testosterone varies across the day. Regular sleep results in regular cycles of hormonal change – and you don’t need special sleep products or sleep apps to help this happen, just some insight into how to live healthily.
If you are a woman trying to decide whether or not to use hormone replacement, for example when you reach the menopause, you should be able to weigh up the possible benefits against measured risks. Should you decide to opt for hormone replacement, this always needs to be discussed with your doctor. As yet there is no evidence that so-called ‘bioidentical’ or ‘natural’ hormone replacements are better for you, despite claims made to the contrary where potential profits are at stake. You should be very careful when you consider taking hormones that have not been properly safety-tested in clinical trials and whose long term side effects have not been measured or monitored. The risks are totally unknown.
Your hormones are doing a great job supporting the functions of your body, responding to your environment and coping with the effects of what is going on around and inside you. Our glands have been doing this for millennia. As yet there has been no evidence that the purchase of extra and expensive support systems – be they yoga poses, supplements or other interventions – will truly boost your hormone health.
Got an axe to grind with sensationalism about hormones in the media? Get in touch with your Society for Endocrinology press office and find out how we can support you.
Following the recent media coverage of Caster Semenya competing at the Rio Olympics 2016, we have republished an abridged version of Harriet Nerva’s essay on disorders of sexual development, which won the Society for Endocrinology Undergraduate Essay Prize in 2010. You can read the full version here.
Gender verification and sport are two terms which when put together provide a bang louder than any starting pistol. In August 2009, Caster Semenya an 18 year old South African female athlete won the 800m sprint in the World Championship in Athletics in a world-record time. Her muscular build and fast time fuelled rumours of hermaphroditism and levels of testosterone three times that of ‘normal’. She was ordered to take a gender verification test. The worldwide controversy that followed has forced athletic organisations to create new guidelines for intersexed athletes, also known as those with a disorder of sexual differentiation (DSD). These are still being decided as this essay is written.
So are you female or male? The answer may seem simple enough – except that is for the 1.7% of the population who are born intersexed, and, for any young budding intersexed athlete out there, the consequences may be far reaching.
Introduced in 1936, and used to catch male imposters in female sporting events, compulsory gender testing of female athletes was abolished in 1992, with organisations retaining the right to test anyone thought of as ‘suspicious’. Males and females have traditionally been separated in elite sport because of the competitive advantage that men are argued to possess. The advantage stems from biologically determined sex differences in physical characteristics such as height, body composition, muscle mass, endurance and cardiovascular capacity.
However gender testing was never meant to address the issue of intersexed athletes. There is no evidence that female athletes with DSDs have displayed any sport-relevant physical attributes which have not been seen in biologically normal female athletes. Why is Semenya being tested? The grounds for her testing and the test itself have not been clarified.
DSD or ‘intersex’ refers to the atypical appearance of the external genitalia at birth where they differ from the usual development of either sex and create difficulty in sex assignment. The DSDs can broadly be split into 3 groups. Firstly, disorders of chromosomal sex occur when there is nondisjunction of sex chromosomes during meiosis. Secondly in disorders of gonadal sex, chromosomal sex is normal but the differentiation of the gonads is abnormal.
Thirdly there are the disorders of phenotypic sex. Here the phenotypic sex is ambiguous or is completely in disagreement with chromosomal and gonadal sex. Female pseudohermaphrodites (virilised females) have a 46, XX karyotype and female gonads, but ambiguous or male external genetalia. Male pseuodohermaphrodites (undervirlised males) have a 46 XY karyotype and male gonads, but ambiguous or female external genetalia. A true hermaphrodite has both ovarian and testicular tissue, irrespective of karyotype. Internal genetalia may also be mixed and external genetalia may be male, female or ambiguous.
Methods of defining gender in sport have been notoriously controversial. In essence what gender verification tries to do is find a cut-off point between females and males. This is harder than it sounds – sex is not defined by one parameter, it is a complicated combination of many, but athletics bodies have broadly used chromosomal sex for differentiation. Do DSDs always result in competitive advantage and do they always affect chromosomal sex test results? What about all this testosterone rumoured to be flying around?
Whereas in men a testosterone dose-response relationship has been shown to exist in sport, in women this relationship has only been found in relation to ‘explosive performance’. This measurement of height and power output involves performing the lowering portion of a lift at normal speed while the lifting portion is performed as rapidly and forcefully as possible. The dose-response relationship found was weaker in women than in men. It has been argued that this is because of gender differences in skeletal muscle sensitivity to testosterone, but this has not been substantiated. Whether women show a dose response relationship across all sporting attributes (for example endurance) is unknown, possibly because there is a lack of data on the relationship between resting testosterone levels in elite competitors and neuromuscular performance. In 2006 Cardinal and Stone found that testosterone levels varied significantly in different athletic groups, with sprinters having the highest values for both men and women.
And what of Caster Semenya? If judged ineligible to compete as a woman, she would also be ineligible to compete as a man, and if she refuses to consent to treatment (and is not taking anabolic steroids), must she be allowed to compete as an intersexed athlete based in moral obligation of athletic organisations? Finally as these organisations move to open “centres of excellence” around the world that would be equipped to treat intersexed athletes with anything from hormone therapy to surgery (Handley, 2010), what is the role of endocrinologists? Torn between controlling athletic prowess and the best interest of the client, we have to ask how level the playing field can, and should, ever be.
This month, the Society for Endocrinology’s open-access journal, Endocrine Connections, is marking four years since the publication of its first issue.
To celebrate Endocrine Connections’s achievements, as well as the fourth anniversary of the first issue, you are invited to vote for your favourite article from the shortlist below. This list has been produced based on scientific quality, originality and level of interest among the wider scientific audience – as well as download numbers to date.
But what’s in it for you? As well as supporting your colleagues’ research, by voting for your favourite, you will be entered into a draw to win an endocrinology-themed plushie; a new mascot, perhaps, for you laboratory or office!
- Research paper: Efficacy of increased resistant starch consumption in human type 2 diabetes C L Bodinham et al.
- Research paper: Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis Liza Haqq et al.
- Review: The heart as an endocrine organ Tsuneo Ogawa and Adolfo J de Bold.
- Review: The appraisal of chronic stress and the development of the metabolic syndrome: a systematic review of prospective cohort studies N Bergmann et al.
- Review: Heroes in endocrinology: Nobel Prizes Wouter W de Herder.
- Research paper: Variation in the biochemical response to L-thyroxine therapy and relationship with peripheral thyroid hormone conversion John E M Midgley et al.
- Review: Mitochondrial dysfunction and insulin resistance: an updateby Magdalene K Montgomery and Nigel Turner.
- Review: Update on strategies limiting iatrogenic hypoglycemia Aldo Bonaventura et al.
- Research paper: Bone metastases and skeletal-related events from neuroendocrine tumours Katherine Van Loon et al.
- Review: Cardiac natriuretic peptides and obesity: perspectives from an endocrinologist and a cardiologist Hugo R Ramos et al.
This year, I was lucky enough to attend my first parliamentary links day. The largest science event in the Houses of Parliament, this day is held to promote dialogue between parliament and the scientific community. Given the vote to leave the EU less than a week earlier, it couldn’t have been a more interesting time to attend!
The scientific community directly benefit from the EU in terms of funding, collaboration and free movement of people. It was therefore no surprise that this year’s event saw the biggest attendance in history. The event, opened by John Bercow MP (Speaker of the House of Commons), involved opening remarks from Jo Johnson (Minister for Universities and Science) and Nicola Blackwood (Chair of the Science and Technology Select Committee). Two panels then followed, and then final speeches were given by Lord O’Neill of Gately, Sir Venki Ramakrishnan, and Stephen Metcalfe MP. Bewildered scientists filled the room, all anxious about their now uncertain future, and all speakers tried their best to reassure us.
‘Nothing has changed overnight in legal terms’ said Jo Johnson. MPs agreed that we have a strong country with a resilient history, and are able to pull through. Our science in particular they say is world class, and this can be used to help in our recovery. Many speakers told of reassurance from abroad, recognising the work we do and that they want to continue collaborating. These academic networks can therefore provide an alternative to the political networks, and help to smooth waters. So the message was one of hope and determination, despite the disappointment.
All emphasised that we now need to shout loud to ensure that science is prominent in the negotiations and in particular that the government maintain our overall investment in science. MPs assured us that they will do their best to fight for these things, and they said that we also need to send out the message to connections and networks across the world, that despite this decision Britain is a willing collaborator and welcoming society. Finally, they asked us to think about what we can learn. Although leaving the EU would clearly be bad for science, half of the public still responded with the leave vote. This suggests that science is not important to them, so what can we do now to convince people that science is worth investing in?
I will always remember this day at such an important time in British history. After all the hope given I look forward to seeing what the future holds for UK science!
Amber Abernethie is in the second year of her PhD in Cardiovascular Biology. She is based at the Queens Medical Research Centre (University of Edinburgh) but is originally from Cleethorpes, England.
Following the referendum result on the UK’s membership of the European Union (EU) the Society for Endocrinology urges the UK government to ensure that free movement of students, researchers and clinicians between the UK and other EU countries and full access to, and participation in, the EU research infrastructure is preserved. We strongly believe that the free movement of labour is essential to the delivery of care within the National Health Service (NHS) and to ensure that the UK continues to be a world leader in international scientific research. The full statement is available on our website.
The Society for Endocrinology provides early-career grants to support its members in a number of ways. In this article, Kerry McLaughlin explains how the grant helped her search for an elusive autoantigen, which made a splash on the BBC news page earlier this year.
People who have type-1 diabetes lose the ability to control blood sugar levels because of the destruction of insulin-producing cells in their Islets of Langerhans. We know this is because the immune response targets four specific proteins (known as autoantigens), and while the fifth major autoantigen has been known to exist for over 20 years its identity was unknown.
Technical limitations at the time made it impossible to identify the fifth autoantigen, but we used a combination of biochemical techniques alongside high-tech mass spectrometry to discover that this fifth major autoantigen was tetraspanin-7, at last providing a complete picture of the immune targets in type-1 diabetes.
This discovery can now be used to help identify those at risk of future disease development through the detection of antibodies to tetraspanin-7, and to further research into strategies aimed at blocking the immune response to the major autoantigens in order to prevent the disease altogether.
This research came about as a result of work we were doing with a separate autoantigen (IA-2). My postdoctoral supervisor, Dr Michael Christie, was involved in earlier efforts to identify the fifth major autoantigen, and we realised that we could apply the technology developed for IA-2 for this purpose.
This was where the Early Career Grant from the Society for Endocrinology came in and provided some much needed resource to kick-start the project. While it took a little bit more time and effort to finally identify tetraspanin-7 as our elusive fifth autoantigen, this early funding was instrumental to the project’s successful completion.
I have since been awarded a 3-year fellowship by JDRF to continue my research into tetraspanin-7 in the laboratory of Professor Patrik Rorsman FRS, FMedSci at the University of Oxford. We published our study in Diabetes, and it was covered in the mainstream media by the BBC, at one point trending in the top 10 news articles, as well as by the Huffington Post. It was great to have the opportunity to share our research with the wider public, and I was very motivated to see how interested people were in hearing about scientific advances.
For young researchers, getting enough preliminary data to put together a competitive grant application for a major funding body can be tricky. The Early Career Grant from the Society for Endocrinology provides postdocs with the opportunity to explore a new avenue of research and can be used to provide that all-important first proof-of-concept.
The second advantage to this scheme is that it gives early-stage researchers a chance to go through the process of preparing an application for funding as well as managing an award, but on a much smaller scale and without the heavy administrative burden of larger grants. I would certainly recommend the scheme to those keen to take the first step towards an independent career in research.
Kerry McLaughlin, originally from Cape Town, South Africa, was awarded her PhD in Immunology from King’s College London in collaboration with The Pirbright Institute. She then spent six years as a postdoc in the laboratory of Dr Michael Christie at King’s College London before taking up a JDRF fellowship at the University of Oxford in 2016.
For details on how to apply for our Early Career Grant, visit our website. The next deadline for applications is 27 November 2016.
Next Tuesday, Liverpool John Moores University will host a public awareness day on anti-doping in sport, aimed predominantly at high school students, their teachers and practising coaches. In this post, Professor Graeme Close explains why it’s important to get an anti-doping message out to schools. The event is supported by a Society for Endocrinology public engagement grant.
Athletes who dope fall into two broad categories. Firstly, those who believe that it is not possible to be successful in their sport without using performance enhancing drugs and secondly those who accidentally take contaminated supplements or over-the-counter medication that contains prohibited substances. Without doubt, the best way to tackle both of these mistakes is by effectively educating athletes in schools before mistakes are made. In wake of recent doping scandals, this Society for Endocrinology sponsored event is not only timely but essential to promote clean sport.
We want attendees to think about why athletes do not need to dope in sport. We will cover the science of muscle mass and strength increases, which is very poorly understood. Many junior athletes believe that the only way to increase lean mass is to use sports supplements and/or take prohibited substances. In reality, this goal can be achieved through correct nutrition and optimisation of training plans. The problem is that many people do not understand how to eat and how to train to gain muscle mass and as such their training is often ineffective.
It is important to tell the truth about sports supplementation. There is currently a trend that you either have to join a “no-supplement” or “pro-supplement” team and there is no place for a balanced opinion. The reality is that there are a handful of supplements that may be beneficial if taken at the right time. If we are truthful with our education, athletes will come to qualified people for advice, such as nutritionists on the Sport and Exercise Nutrition register (SENr). In contrast, if we have a blanket no-supplement policy the danger is that athletes may take the matter into their own hands and take supplements that not only do not work but more worryingly have not been tested for contaminants.
As sport scientists, it is our moral and ethical duty to educate athletes on doping. It is crucial that respected practitioners and academics provide appropriate education with regards to anti-doping. As well as facing a potential lifetime ban from sport, there are many dangerous consequences of taking performance enhancing drugs such as cardiac damage and mental health problems. There are even fatalities following the misuse of drugs in sport.
The event we are hosting at LJMU will include highly experienced researchers and practitioners who support some of the world’s greatest athletes, as well as top level athletes themselves. In addition, the Rugby Football Union and UK Anti-Doping will be present to help us reach out to kids more effectively.
We hope that this is the first of many such educational days and that the students, teachers and coaches will leave the event feeling inspired and motivated to commit to a future of clean sport.
Public engagement grants have been developed to help Society members and public engagement professionals (non-members) organise and deliver outreach activities, aimed at school children and/or the general public, to communicate the science of endocrinology. Find out how to apply for a public engagement grant on the Grants page of our website.
The annual Society conference, SfE BES, takes place this year in Brighton on 7-9 November 2016. It’s a great chance to network with colleagues, showcase your work and explore new research in your area of endocrinology. Our programme of events is varied yet specific – bringing together the best of basic science, clinical investigation and clinical practice, you have the chance to expand your horizons into other parts of the field whilst also attending those lectures which are really specific to you.
The submission system for abstracts is open until midnight on Wednesday 22nd June – so you have more than enough time to polish your final abstract and send it along. It’s not just a chance to show your colleagues across the whole field of endocrinology what you’ve been working on – it’s a chance to tell them why what you’ve been working on is important.
Last year at SfE BES, a great programme highlight was a session entitled ‘Evolving model systems for complex tissues’, which was chaired by Kevin Doherty and Shareen Forbes. In the ’90s, manipulation of human embryonic stem cells (hESCs) was something of a new thing. It was anticipated that the ability to grow human tissues in culture using hESCs would provide incredible model systems for drug development, toxicity testing and cell therapy.
However, it wasn’t until 2005 that reliable markers had been developed and a significant number of important signalling pathways had been elucidated in the path to differentiation. By this point, some ten years later, finally a tool box existed for nearly every tissue type. This lead to some of the first clinical trials, using pluripotent cells to treat age-related macular degeneration. However, liver disease, diabetes and neurodegeneration were still elusive and challenging goals.
By 2014, fully functional human beta cells has been generated, and they took only 45 days and 7 stages in culture. This was a hugely exciting moment for diabetologists and researchers across the world. But then, of course, the question sprang up: could they be used as a source of islet cells for replantation? Or would they merely serve as an invaluable model?
At Kevin and Shareen’s BES session, they gave a detailed overview of both the background to the field of complex tissue model systems, and the current state of basic science and clinical research, highlighting very recent advances, and discussing the potential future.
The stem cell field continues to expand rapidly. 2016 has already been the year that Chinese scientists grew functioning mouse spermatozoa from skin cells – these went on to fertilise egg which developed into embryos and grew to successful progeny. What will the second half of 2016 bring?
With over 1000 delegates, 100 abstract lectures, 10 plenary lectures, and an evening of awards and prizes, SfE BES is the best place for you to spread the word on your research, and meet the colleagues that you want to work with in future. Your lecture might be the one were talking about all the way into June 2017.
So submit your abstract now through our submission system. Submissions close on Wednesday 22nd June at midnight.
See you in November!
The syndromes associated with a dysfunctional thyroid gland can have severe impacts on an individual’s quality of life. Consequently, research aimed at understanding normal thyroid function and how this deteriorates through the pathologies of the various thyroid-related conditions is a high priority.
To support Thyroid Awareness Week on 23-29 May we have created a collection of recently published papers from Society for Endocrinology journals. They’ve all got a thyroid focus and they are all free to download until the end of the month.
- TERT promoter mutations in thyroid cancer Liu & Xing. Endocrine-Related Cancer (2016) 23 R143-R155.
- Variation in the biochemical response to L-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency Midgley et al. Endocrine Connections (2015) 4 196-205.
- Thyroid hormone and vitamin D regulate VGF expression and promoter activity Lewis et al. Journal of Molecular Endocrinology (2015) 56 123-134.
- Germline PARP4 mutations in patients with primary thyroid and breast cancers Ikeda et al. Endocrine-Related Cancer (2016) 23 171-179.
- Polymorphism of IL37 gene as a protective factor for autoimmune thyroid disease Yan et al. Journal of Molecular Endocrinology (2015) 55 209-218.
- A model for chronic, intrahypothalamic thyroid hormone administration in rats Zhang et al. Journal of Endocrinology (2016) 229 37-45.
- Effects of maternal nicoting exposure on thyroid hormone metabolism and function in adult rat progeny Lisboa et al. Journal of Endocrinology (2015) 224 315-325.
- Characterization of human follicular thyroid cancer cell lines in preclinical mouse models by Ashley N Reeb, Andrea Ziegler and Reigh-Yi Lin. Endocrine Connections (2016) 5 47-54.
If you’re a paid member of the Society for Endocrinology, you get free access to all journal content. So once you’ve read the papers above, just keep going. Remember to enter through the member section of our website to get access for free.
[And if you’re not a member, why not join us?]
In our last public engagement post, we shared a simple How-To graphic for one of our most successful public engagement activities. Now, it’s time to see another:
Introducing: The Hormone Card Game
This is a great (and simple!) activity to use at science fairs, open days or even careers fairs.
Create a set of 10 cards – 5 of them show the name of a hormone, and the other 5 show a description of the function of each hormone. We printed ours on A4 card. When the cards have then been shuffled, participants have the task of matching each hormone to its correct function. For extra help, you can add clues to the back of the hormone cards – if the participants are unsure, they can turn over for a helpful hint.
Finally, what’s really great about this activity is that it provides an easy and engaging springboard for discussing hormones in a little more detail. Have a look below to see how it works:
A recent case study in Endocrine-Related Cancer describes the case of a transgender woman developing breast cancer linked to a mutation in the BRCA2 gene. In this post Dr Adrian Daly talks about the potential implications of their findings – and what it could mean for screening techniques.
Few medical issues have seen greater changes in public awareness recently than those related to transgender individuals. Discussions around transgender identity were previously marginalized.
In contrast, today it is front and center in debates related to equality in many countries. Along with the work of activists, the arts and media have played a central role in this radical change in openness regarding transgendered people and their experiences. Leading characters in mainstream television drama are played by transgender actors such as Laverne Cox in Orange is the New Black, while popular series like Transparent have the transgender experience as the main theme of the show.
The real life experiences of gender transformation of the former Olympian and reality TV star Caitlyn (formerly Bruce) Jenner have been chronicled intimately. The upshot of this has been to dispel many taboos about discussing transgender related issues in the mainstream media. This, in turn, improves awareness around these issues and how transgender is managed.
Endocrinologists play a key role in this specialized area of medical care. Cross hormonal therapy is a cornerstone of gender transformation and is responsible for many desired changes sought by patients. For male to female transformation, this involves taking doses of female hormones like estrogens and blocking male hormones with anti-androgen therapy. This process leads to important physical changes like breast growth.
Hormonal therapy not only brings welcomed transformations but also changes in screening activities. Male to female transgender individuals should learn and adopt breast examination and routine mammography similar to genetic females. While male to female patients treated with hormones don’t appear to have an increased risk of breast cancer, there is a risk factor in this condition that might need better awareness in patients and doctors alike.
As published on 21 March 2016 in Endocrine-Related Cancer, a study involving the group of Prof. Albert Beckers at the University of Liège, Belgium described the case of a male to female transgender patient that developed breast cancer after 7 years of oestrogen and anti-androgen therapy. The patient had to stop their hormone therapy and undergo surgery, but despite this, the cancer recurred and required chemotherapy. Unbeknownst to the patient, multiple cousins had developed breast cancer and were found to have a mutation in the BRCA2 gene.
While the risks of cancer related to BRCA2 gene mutations have focused mainly on women, male mutation carriers are at greatly increased risk of male breast cancer and BRCA2 appears to act as a risk factor for prostate cancer, another hormone related tumor. Indeed multiple members of the family also had developed prostate cancer.
“This very difficult case highlights two important points.”, said Dr. Vinciane Corman a lead author of the study. “Firstly, the awareness of family cancer risk due to BRCA2 gene mutations needs to involve both males and females, and families need to be thoroughly informed. Information about a major risk factor like a BRCA2 mutation can lead to better decision making by potential carriers”.
She continued, “Secondly, the current cancer screening guidelines for BRCA2 mutation carriers have been written with the typical (or cisgendered) population in mind. Due to greater openness about discussing transgendered individuals, future iterations of these guidelines might need to consider how best to manage these rare but difficult cases of BRCA2 mutation carriers that are considering being treated with cross sex hormones.”