The Bryan Hudson Clinical Endocrinology Award winner Lachlan Angus

2023 endocrinology award winner Lachlan Angus

2023 endocrinology award winner Lachlan Angus

The Bryan Hudson Clinical Endocrinology Award recognises the best presentation given to the Endocrine Society’s Annual Scientific Meeting by an early career researcher.

Lachlan became interested in sex and gender variation during his final years of medical school, when a patient with a rare intersex condition presented to his paediatric endocrinology clinic. While intersex and trans medicine isn’t exactly the same, intersex and trans people face some of the same social stigma and pressures. While gender and sex diversity are increasingly visible, people with atypical sex characteristics still face considerable discrimination in society and medical settings. And although the communities are small, the community of medical practitioners interested and knowledgable enough to treat them is even smaller.

Seeing that the area of gender medicine needed more trained doctors, Lachlan saw an opportunity to contribute to a field that was only just starting to be taken seriously. After spending his endocrinology training at several gender clinics in Adelaide, he moved to Melbourne to complete his PhD with Associate Professor Ada Cheung and the Trans Research Group at The University of Melbourne, and work at the Austin Gender Clinic.

Trans medicine has historically been a small, underfunded area of research. The research that exists is mostly focused on non-clinical outcomes rather than things that are meaningful to patients. This means there’s more papers about achieving the right blood hormone level than figuring out how to best grow facial hair or promote breast development.

One of the more common medical treatments for trans women are hormone blockers, which suppress testosterone production. The anti-androgens spironolactone and cyproterone have been thoroughly evaluated in terms of their ability to lower blood testosterone levels, but haven’t been directly compared to each other in terms of other transition effects. Since these drugs work in quite different ways, Lachlan and his supervisors saw potential in seeing how they stack up for various meaningful outcomes.

Spironolactone (Spiro) blocks the androgen receptors that testosterone usually attaches to. This means that testosterone can’t reach the cells it would usually reach, and the cells don’t receive the messages from testosterone that they would usually receive. In areas like breast tissue, blocking androgens means estrogen can be more active, resulting in breast growth. While Spiro works pretty well as an anti-androgen, that’s actually not what the drug was originally designed to do. Its main purpose is to block the receptors for mineralocorticoid hormones. These hormones regulate salt and fluid balances in the body, so Spiro is mostly prescribed to people with heart conditions and as a diuretic.

Cyproterone acetate (Cypro) is not an anti-mineralocorticoid but a powerful anti-androgen. Its main function is to block androgen receptors so testosterone and other androgens can’t get through. It also affects the production of androgens at their source, and mimics progesterone by activating the progesterone receptor. As it works much more effectively than Spiro, patients take much less of it.

Lachlan’s research compared the two drugs’ effects on breast development in trans women. In his double-blind, randomised controlled trial, fifty-five trans women were given either 100mg of spironolactone or 12.5mg of cyproterone acetate daily for six months. He measured breast development via breast-chest distance, estimated breast volume with 3D medical imaging scans using the BreastIdea Volume Estimator application, and monitored serum total testosterone.

His study found no statistically significant difference in breast size between the two groups. The results suggest no advantage or disadvantage to either drug in terms of breast development, which means that women who desire breast growth can consider both medications a viable option. The results were also extremely variable, with breast volume at the end of the study ranging from 20.27 to 787.77 mL. As baseline age, body mass index, breast indices, serum estradiol and serum total testosterone were comparable, this indicates other interesting factors are at play in breast growth.

Lachlan’s research is one of the first random controlled trials on breast development for transgender women. His winning the Bryan Hudson Clinical Endocrinology Award recognises not only the high quality of his research, but demonstrates that trans health research is increasingly respected and well regarded in the endocrinology community. While previously this kind of research would have been considered niche, or even taboo, receiving this award has meant that Lachlan feels supported in his research direction, acknowledged by his peers, and confidence in his field. Receiving this award also helps the publishability of this research, and Lachlan plans to present his findings at multiple overseas conferences.

Having moved back to Adelaide, Lachlan looks forward to being involved in South Australia’s new trans health centre, keeping in touch with his Melbourne colleagues, and being able to run clinical trials over multiple states. His research will continue to look at optimising hormones for trans people, with a particular interest in the promises of Bicalutamide, an anti-androgen that has only recently begun to be investigated for gender transition.

The Gail Risbridger Junior Scientist Award winner Georgia Cuffe

2023 endocrinology award winner Georgia Cuffe

2023 endocrinology award winner Georgia Cuffe

The Gail Risbridger Junior Scientist Award recognises the best science presentation at the Endocrine Society’s Annual Scientific Meeting by a postgraduate student or advanced trainee. In 2023, the award was presented to Georgia Cuffe, a third-year PhD student from the Prostate Cancer Research Group at Monash University.

Georgia first became interested in prostate cancer in the final year of her undergraduate degree, when a lecturer remarked that prostate cancer could be treated with high levels of hormones. This was intriguing, since it challenged the current treatment approach for advanced prostate cancer.

Advanced prostate cancer is typically treated using androgen deprivation therapy. This is because prostate cancer is a hormone-dependent cancer that relies heavily on hormones, such as androgens, for its growth. This is a well-established treatment that was first identified in 1941 by Dr Charles Huggins, who was later awarded the 1966 Nobel Prize for his discovery. Although advanced prostate cancer can be managed using androgen deprivation therapy for many years, it is not curative and can have unpleasant side effects for patients. The cancer itself can also develop resistance to androgen deprivation therapy by increasing its sensitivity to low levels of hormones, producing androgen receptor variants that can become activated without requiring hormones, or by bypassing the androgen receptor entirely.

Bipolar Androgen Therapy (BAT) is a potential new treatment that instead treats patients with alternating cycles of 1) very high levels of androgens, and 2) very low levels of androgens. This is achieved by treating patients with high-dose testosterone, alongside drugs that inhibit a patient’s own production of testosterone. This causes testosterone levels in the blood to rapidly spike, then gradually decline back to very low levels. With repeated cycles, BAT aims to overwhelm cancer cells, causing DNA damage that results in cell death, while also preventing the cancer from adapting to treatment. Although BAT has shown to be promising in several clinical trials, alongside improvements in quality of life, only ~30% of patients respond to this treatment. Georgia’s postgraduate mission is to discover why some patients respond to BAT while others do not.

To do this, Georgia took tissues from patients with advanced prostate cancer and grew them in the lab. In her study, Georgia treated tumours with either high-dose testosterone or a placebo. As the tumours grew, she measured differences in tumour growth between the two groups. The results show that BAT reduces tumour growth in some tumours, but not others. Georgia’s data suggests that this depends on the types of androgen receptors being expressed, such as the normal form of the androgen receptor as well as those androgen receptor variants.

A graph showing the BAT (Bipolar Androgen Therapy) cycle

A graph showing the BAT (Bipolar Androgen Therapy) cycle, during which testosterone rises and falls over time.

Georgia is currently in the final year of her PhD, which has been dedicated to working in the lab, finishing off her experiments, and writing her thesis. As her Honours year and early PhD career were impacted by pandemic lockdowns, she hopes to continue her research following submission. The award also offers Georgia one year of mentoring with Professor Risbridger, which will assist Georgia in planning the next stage of her scientific career.