Hysteria, Valium and Clinical Trials
An in-depth analysis of the under-representation of women in clinical trials and its effects on modern medicine
Bibliography
This page includes all of the works cited throughout the site, as well as a brief further reading list if you are interested in the concepts mentioned.
Further Reading
Background and Hysteria
**The pain and suffering experienced by women, including a history of hysteria, why medicine must change its perception of women and more:
Jackson, Gabrielle. 2019. Pain and Prejudice: A call to arms for women and their bodies. Piatkus.
A thorough history of hysteria:
Tasca, C., M. Rapetti, M. G. Carta, and B. Fadda. 2012. "Women and hysteria in the history of mental health." Clin Pract Epidemiol Ment Health 8: 110-9. https://doi.org/10.2174/1745017901208010110.
The lingering effects of hysteria:
Saramiento, Sofia. 2021. "The Lingering Effects of Female Hysteria in Medicine." Berkeley Political Review. Accessed 8th August. https://bpr.berkeley.edu/2021/08/10/the-lingering-effects-of-female-hysteria-in-medicine/.
Sex Differences
Sex differences in ADME, drug transporters and hormones :
Fadiran, Emmanuel O., and Lei Zhang. 2015. "Effects of Sex Differences in the Pharmacokinetics of Drugs and Their Impact on the Safety of Medicines in Women." In Medicines For Women, edited by Mira Harrison-Woolrych, 41-68. Cham: Springer International Publishing. https://doi.org/10.1007/978-3-319-12406-3_2
‘Gender’ differences in drug response, with reference to pharmacokinetics and pharmacodynamics:
Franconi, Flavia, Sandra Brunelleschi, Luca Steardo, and Vincenzo Cuomo. 2007. "Gender differences in drug responses." Pharmacological Research 55 (2): 81-95. https://doi.org/10.1016/j.phrs.2006.11.001.
https://www.sciencedirect.com/science/article/pii/S1043661806002040.
Sex differences in foetal and neonatal life:
Alur, Pradeep. 2019. "Sex Differences in Nutrition, Growth, and Metabolism in Preterm Infants." Frontiers in Pediatrics 7. https://doi.org/10.3389/fped.2019.00022.
https://www.frontiersin.org/articles/10.3389/fped.2019.00022.
The sexually dimorphic brain, sex hormones and clinical studies in relation to neuropharmacology:
Bale, T. L., and C. N. Epperson. 2017. "Sex as a Biological Variable: Who, What, When, Why, and How." Neuropsychopharmacology 42 (2): 386-396. https://doi.org/10.1038/npp.2016.215.
Sex and gender differences in addiction research:
Sanchis-Segura, Carla, and Jill B. Becker. 2016. "Why we should consider sex (and study sex differences) in addiction research." Addiction Biology 21 (5): 995-1006. https://doi.org//10.1111/adb.12382.
Valium
The side effects of Valium:
Meyler, L., and J. K. Aronson. 2016. "Diazepam." In Meyler's Side Effects of Drugs (Sixteenth Edition), edited by J. K. Aronson, 930-937. Oxford: Elsevier.
Other
Implications for sex differences in transgender medicine:
Cirrincione, Lauren R., and Kai J. Huang. 2021. "Sex and Gender Differences in Clinical Pharmacology: Implications for Transgender Medicine." Clinical Pharmacology & Therapeutics 110 (4): 897-908. https://doi.org/10.1002/cpt.2234.
https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.2234.
A European study that proposes AI to eliminate sex biases in the evaluation of acute coronary syndromes:
Wenzl, Florian A., Simon Kraler, Gareth Ambler, Clive Weston, Sereina A. Herzog, Lorenz Räber, Olivier Muller, Giovanni G. Camici, Marco Roffi, Hans Rickli, Keith A. A. Fox, Mark de Belder, Dragana Radovanovic, John Deanfield, and Thomas F. Lüscher. 2022. "Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation." The Lancet 400 (10354): 744-756. https://doi.org/10.1016/S0140-6736(22)01483-0.
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**Is Prozac a feminist drug?:
Hoffman, Ginger A., and Jennifer L. Hansen. 2011. "Is Prozac a feminist drug?" International Journal of Feminist Approaches to Bioethics 4 (1): 89-120. https://doi.org/10.2979/intjfemappbio.4.1.89.
**Key/recommended texts
Full Bibliography
Alur, Pradeep. 2019. "Sex Differences in Nutrition, Growth, and Metabolism in Preterm Infants." Frontiers in Pediatrics 7. https://doi.org/10.3389/fped.2019.00022.
https://www.frontiersin.org/articles/10.3389/fped.2019.00022.
Barsky, A. J., H. M. Peekna, and J. F. Borus. 2001. "Somatic symptom reporting in women and men." J Gen Intern Med 16 (4): 266-75. https://doi.org/10.1046/j.1525-1497.2001.00229.x.
Bhatt, A. 2010. "Evolution of clinical research: a history before and beyond james lind." Perspect Clin Res 1 (1): 6-10.
Bothwell, L. E., and S. H. Podolsky. 2016. "The Emergence of the Randomized, Controlled Trial." N Engl J Med 375 (6): 501-4. https://doi.org/10.1056/NEJMp1604635.
Chen, E. H., F. S. Shofer, A. J. Dean, J. E. Hollander, W. G. Baxt, J. L. Robey, K. L. Sease, and A. M. Mills. 2008. "Gender disparity in analgesic treatment of emergency department patients with acute abdominal pain." Acad Emerg Med 15 (5): 414-8. https://doi.org/10.1111/j.1553-2712.2008.00100.x.
Conrad, Nathalie, Andrew Judge, Dexter Canoy, Jenny Tran, Johanna O’Donnell, Milad Nazarzadeh, Gholamreza Salimi-Khorshidi, F. D. Richard Hobbs, John G. Cleland, John J. V. McMurray, and Kazem Rahimi. 2019. "Diagnostic tests, drug prescriptions, and follow-up patterns after incident heart failure: A cohort study of 93,000 UK patients." PLOS Medicine 16 (5): e1002805. https://doi.org/10.1371/journal.pmed.1002805.
https://doi.org/10.1371/journal.pmed.1002805.
Clarke, P. R. F., P. S. Eccersley, J. P. Frisby, and J. A. Thornton. 1970. "THE AMNESIC EFFECT OF DIAZEPAM (VALIUM)." British Journal of Anaesthesia 42 (8): 690-697. https://doi.org/10.1093/bja/42.8.690.
https://www.sciencedirect.com/science/article/pii/S0007091217504705.
Clayton, Janine A., and Francis S. Collins. 2014. "Policy: NIH to balance sex in cell and animal studies." Nature 509 (7500): 282-283. https://doi.org/10.1038/509282a.
Cooper, Ziva D., and Margaret Haney. 2016. "Sex-dependent effects of cannabis-induced analgesia." Drug and Alcohol Dependence 167: 112-120. https://doi.org/10.1016/j.drugalcdep.2016.08.001.
https://www.sciencedirect.com/science/article/pii/S037687161630223X.
Czeizel, A. E., B. A. Szegal, J. M. Joffe, and J. Rácz. 1999. "The Effect of Diazepam and Promethazine Treatment During Pregnancy on the Somatic Development of Human Offspring." Neurotoxicology and Teratology 21 (2): 157-167. https://doi.org/10.1016/S0892-0362(98)00043-9.
https://www.sciencedirect.com/science/article/pii/S0892036298000439.
Du, L., H. Bayir, Y. Lai, X. Zhang, P. M. Kochanek, S. C. Watkins, S. H. Graham, and R. S. Clark. 2004. "Innate gender-based proclivity in response to cytotoxicity and programmed cell death pathway." J Biol Chem 279 (37): 38563-70. https://doi.org/10.1074/jbc.M405461200.
Dodd-Butera, Teresa, and Molly Broderick. 2005. "Diazepam." In Encyclopedia of Toxicology (Second Edition), edited by Philip Wexler, 783-785. New York: Elsevier.
Fadiran, Emmanuel O., and Lei Zhang. 2015. "Effects of Sex Differences in the Pharmacokinetics of Drugs and Their Impact on the Safety of Medicines in Women." In Medicines For Women, edited by Mira Harrison-Woolrych, 41-68. Cham: Springer International Publishing. https://doi.org/10.1007/978-3-319-12406-3_2
Fox, Helen, Peter Morgan, and Rajita Sinha. 2014. "Sex Differences in Guanfacine Effects on Drug Craving and Stress Arousal in Cocaine-Dependent Individuals." Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39. https://doi.org/10.1038/npp.2014.1.
Franconi, Flavia, Sandra Brunelleschi, Luca Steardo, and Vincenzo Cuomo. 2007. "Gender differences in drug responses." Pharmacological Research 55 (2): 81-95. https://doi.org/10.1016/j.phrs.2006.11.001.
https://www.sciencedirect.com/science/article/pii/S1043661806002040.
**Geller, Stacie E., Abigail R. Koch, Pamela Roesch, Amarette Filut, Emily Hallgren, and Molly Carnes. 2018. "The More Things Change, the More They Stay the Same: A Study to Evaluate Compliance With Inclusion and Assessment of Women and Minorities in Randomized Controlled Trials." Academic Medicine 93 (4): 630-635. https://doi.org/10.1097/acm.0000000000002027.
Harrison, Rick 2015. "Safety of Drinking with New Female Libido Drug Tested in Mostly Men." Addyi and Alcohol? Yale School of Medicine. Last Modified 21/06/2022. Accessed 15th July. https://medicine.yale.edu/news-article/addyi-and-alcohol/.
Herzberg, David. 2006. ""The Pill You Love Can Turn on You": Feminism, Tranquilizers, and the Valium Panic of the 1970s." American Quarterly 58 (1): 79-103. http://www.jstor.org/stable/40068349.
**Hoffmann, D. E., and A. J. Tarzian. 2001. "The girl who cried pain: a bias against women in the treatment of pain." J Law Med Ethics 29 (1): 13-27. https://doi.org/10.1111/j.1748-720x.2001.tb00037.x.
**Jackson, Gabrielle. 2019. Pain and Prejudice: A call to arms for women and their bodies. Piatkus.
Kaasinen, Valtteri, Juho Joutsa, Tommi Noponen, Jarkko Johansson, and Marko Seppänen. 2015. "Effects of aging and gender on striatal and extrastriatal [123I]FP-CIT binding in Parkinson's disease." Neurobiology of Aging 36 (4): 1757-1763. https://doi.org/10.1016/j.neurobiolaging.2015.01.016.
https://www.sciencedirect.com/science/article/pii/S0197458015000494.
Kim, J. H., and A. R. Scialli. 2011. "Thalidomide: the tragedy of birth defects and the effective treatment of disease." Toxicol Sci 122 (1): 1-6. https://doi.org/10.1093/toxsci/kfr088.
Koran, Mary Ellen I., Madison Wagener, Timothy J. Hohman, and Initiative for the Alzheimer’s Neuroimaging. 2017. "Sex differences in the association between AD biomarkers and cognitive decline." Brain Imaging and Behavior 11 (1): 205-213. https://doi.org/10.1007/s11682-016-9523-8.
**Labots, Geert, Aubrey Jones, Saco J. de Visser, Robert Rissmann, and Jacobus Burggraaf. 2018. "Gender differences in clinical registration trials: is there a real problem?" British Journal of Clinical Pharmacology 84 (4): 700-707. https://doi.org/10.1111/bcp.13497.
https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13497.
May, Mike. 2016. "Sex on the brain: Unraveling the differences between women and men in neurodegenerative disease." Nature Medicine 22 (12): 1370-1372. https://doi.org/10.1038/nm1216-1370.
McEvedy, C. P., and A. W. Beard. 1970. "Royal Free epidemic of 1955: a reconsideration." Br Med J 1 (5687): 7-11. https://doi.org/10.1136/bmj.1.5687.7.
National Institutes of Health. 2015. "Consideration of Sex as a Biological Variable in NIH-funded Research." National Institutes of Health. Accessed 12th August. https://grants.nih.gov/grants/guide/notice-files/not-od-15-102.html.
Merkatz, Ruth B., Robert Temple, Solomon Sobel, Karyn Feiden, and David A. Kessler. 1993. "Women in Clinical Trials of New Drugs -- A Change in Food and Drug Administration Policy." New England Journal of Medicine 329 (4): 292-296. https://doi.org/10.1056/nejm199307223290429.
https://www.nejm.org/doi/full/10.1056/NEJM199307223290429.
Pesce, Maria Ester, Ximena Acevedo, G. Pinardi, and H. F. Miranda. 1994. "Gender Differences in Diazepam Withdrawal Syndrome in Mice." Pharmacology & Toxicology 75 (6): 353-355. https://doi.org/10.1111/j.1600-0773.1994.tb00374.x.
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0773.1994.tb00374.x.
Peters, Sanne A. E., Lisandro D. Colantonio, Hong Zhao, Vera Bittner, Yuling Dai, Michael E. Farkouh, Keri L. Monda, Monika M. Safford, Paul Muntner, and Mark Woodward. 2018. "Sex Differences in High-Intensity Statin Use Following Myocardial Infarction in the United States." Journal of the American College of Cardiology 71 (16): 1729-1737. https://doi.org/10.1016/j.jacc.2018.02.032.
https://www.sciencedirect.com/science/article/pii/S0735109718333102.
Prendergast, Brian J., Kenneth G. Onishi, and Irving Zucker. 2014. "Female mice liberated for inclusion in neuroscience and biomedical research." Neuroscience & Biobehavioral Reviews 40: 1-5. https://doi.org/10.1016/j.neubiorev.2014.01.001.
https://www.sciencedirect.com/science/article/pii/S0149763414000049.
Sanchis-Segura, Carla, and Jill B. Becker. 2016. "Why we should consider sex (and study sex differences) in addiction research." Addiction Biology 21 (5): 995-1006. https://doi.org//10.1111/adb.12382.
https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12382.
Silva, Anatildes Feitosa, Diego Silveira Sousa, André Macêdo Medeiros, Priscila Tavares Macêdo, Anderson Henrique Leão, Alessandra Mussi Ribeiro, Geison Souza Izídio, and Regina Helena Silva. 2016. "Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone." Progress in Neuro-Psychopharmacology and Biological Psychiatry 70: 68-76. https://doi.org/10.1016/j.pnpbp.2016.05.003.
https://www.sciencedirect.com/science/article/pii/S0278584616300756.
Sramek, J. J., M. F. Murphy, and N. R. Cutler. 2016. "Sex differences in the psychopharmacological treatment of depression." Dialogues Clin Neurosci 18 (4): 447-457. https://doi.org/10.31887/DCNS.2016.18.4/ncutler.
Swann, John. 2009. "The Pharmaceutical Industries." In The Cambridge History of Science: Volume 6: The Modern Biological and Earth Sciences, edited by John V. Pickstone and Peter J. Bowler, In The Cambridge History of Science, 126-140. Cambridge: Cambridge University Press.
Tabatadze, Nino, Guangzhe Huang, Renee M. May, Anant Jain, and Catherine S. Woolley. 2015. "Sex Differences in Molecular Signaling at Inhibitory Synapses in the Hippocampus." The Journal of Neuroscience 35 (32): 11252-11265. https://doi.org/10.1523/jneurosci.1067-15.2015.
https://www.jneurosci.org/content/jneuro/35/32/11252.full.pdf.
"The men’s health gap." 2020. Accessed 29 July 2022. https://www.manual.co/mens-health-gap/.
Villa, Alessandro, Elisabetta Vegeto, Angelo Poletti, and Adriana Maggi. 2016. "Estrogens, Neuroinflammation, and Neurodegeneration." Endocrine Reviews 37 (4): 372-402. https://doi.org/10.1210/er.2016-1007.
Wisdom, Amy J., Yuan Cao, Noriko Itoh, Rory D. Spence, and Rhonda R. Voskuhl. 2013. "Estrogen receptor-β ligand treatment after disease onset is neuroprotective in the multiple sclerosis model." Journal of Neuroscience Research 91 (7): 901-908. https://doi.org/10.1002/jnr.23219.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.23219.
World Health Organisation. 2018. The health and well-being of men in the WHO European Region: better health through a gender approach. https://www.euro.who.int/__data/assets/pdf_file/0007/380716/mhr-report-eng.pdf.
Zhao, Liqin, Zisu Mao, Sarah K. Woody, and Roberta D. Brinton. 2016. "Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease." Neurobiology of Aging 42: 69-79. https://doi.org/10.1016/j.neurobiolaging.2016.02.011.
https://www.sciencedirect.com/science/article/pii/S0197458016001548.
**Zucker, Irving, and Brian J. Prendergast. 2020. "Sex differences in pharmacokinetics predict adverse drug reactions in women." Biology of Sex Differences 11 (1): 32. https://doi.org/10.1186/s13293-020-00308-5.
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**Key/recommended texts