Bridging Gaps in Women's Health Research: The ENIGMA Neuroendocrinology Working Group

COEX 

The persistent neglect of women’s health in research poses a significant barrier to effective diagnostic and treatment strategies1. Despite efforts to include sex as a biological variable (SABV) and integrate sex and gender based analysis (SGBA) into study designs, inequalities persist in both research and medical practice2. Notably, female patients are more likely to experience adverse drug effects compared to their male counterparts3. Moreover, only 5% of neuroscience and psychiatry studies in 2019 statistically examined the influence of sex and gender, emphasizing the ongoing gap in understanding these critical factors4. Additionally, a funding disparity in research exists between conditions that predominantly affect women, such as premenstrual dysphoric disorder, and those that affect both men and women (NIH reporter search).

Sex hormones such as estrogens, androgens, and progesterone play a crucial role in shaping the female brain throughout the lifespan. Important organizational effects occur during perinatal stages and transition phases such as puberty and pregnancy5. Hormonal fluctuations exert both short-term and long-lasting effects on brain structure and function, influencing mental health and contributing to mood disturbances, especially during those transition periods6.

The current state of research is at a pivotal crossroad, with advancements in technology and methods enabling researchers to investigate the biopsychological effects of sex hormones across a female’s lifespan. Recognizing the limitations of small, cross-sectional datasets in the past, the ENIGMA Neuroendocrinology Working Group emerges as a potent contributor to pool data from around the world, investigating the effects of hormones on the female brain in large datasets, particularly in under-studied conditions. The Lancet noted ENIGMA as an innovative model where “Crowdsourcing meets Neuroscience”7. By bridging historical data gaps and fostering collaboration, the scientific field moves closer to unlocking a deeper understanding of the biopsychological effects of hormones — a crucial step in promoting holistic healthcare for women across the lifespan.

References:
1. Mauvais-Jarvis, F. et al. Sex and gender: modifiers of health, disease, and medicine. Lancet 396, 565–582 (2020).
2. White, J., Tannenbaum, C., Klinge, I., Schiebinger, L. & Clayton, J. The Integration of Sex and Gender Considerations Into Biomedical Research: Lessons From International Funding Agencies. J. Clin. Endocrinol. Metab. 106, 3034 (2021).
3. Karlsson Lind, L., Rydberg, D. M. & Schenck-Gustafsson, K. Sex and gender differences in drug treatment: experiences from the knowledge database Janusmed Sex and Gender. Biol. Sex Differ. 14, 1–4 (2023).
4. Rechlin, R. K., Splinter, T. F. L., Hodges, T. E., Albert, A. Y. & Galea, L. A. M. An analysis of neuroscience and psychiatry papers published from 2009 and 2019 outlines opportunities for increasing discovery of sex differences. Nat. Commun. 2022 131 13, 1–14 (2022).
5. Rehbein, E., Hornung, J., Sundström Poromaa, I. & Derntl, B. Shaping of the Female Human Brain by Sex Hormones: A Review. Neuroendocrinology 111, 183–206 (2021).
6. Barth, C., Crestol, A., Lange, A.-M. G. de & Galea, L. A. M. Sex steroids and the female brain across the lifespan: insights into risk of depression and Alzheimer’s disease. Lancet Diabetes Endocrinol. 0, (2023).
7. Mohammadi, D. ENIGMA: crowdsourcing meets neuroscience. Lancet. Neurol. 14, 462–463 (2015).