When visiting a doctor's office, most people expect that the drugs that are prescribed have been tested and are effective for their condition. But for many women, this fundamental belief is not true. Most drugs have been developed through a pipeline that does not include cells that are from an XX background. Researchers have a propensity to use largely male animals and forgo the examination of sex as a variable in clinical studies, thereby neglecting the assessment of the drug's efficacy on males vs. females. This relatively shocking reality has persisted over time in part because of the fear that tests on females might impact a pregnancy and that female menstrual cycles would confound biological outcomes. There is also a persistent misconception that there are no relative differences between males and females beyond the reproductive system and that including males and females would duplicate scientific effort and make the studies more expensive. Perhaps more fundamentally, many people fear the word sex, finding it to be 'dirty' or somehow related to 'having sex.' The word 'gender' is sometimes used to 'soften' the concept of sex-inclusive science, yet gender refers to characteristics pertaining to masculinity and femininity and therefore inadequately defines biological differences in the sex of the studied subject. Finally, many people, scientists, clinicans, and lay public alike, don't understand the role of hormones in their lives--the menstural cycle seems like a crazy set of chemical factors that go up and down and drive biology in sometimes random ways. All of these misconceptiosn and knowledge gaps are driving a drug pipeline that does not always meet the needs of the patient. Addressing sex as part of the research pipeline and becoming more aware of the biolgoy of sex as part of health and disease will not only improve health for women, but for all of us in profound ways.
In October 2015, the Women's Health Research Institute partnered with Northwestern Medicine to provide overviews on sex-inclusive medicine in specific clinical areas. Please follow the links below to watch these videos and learn about sex differences in these specific clinical areas:
The articles listed below focus on sex differences by discipline.
- Voskuhl, R. Sex differences in autoimmune disease. Biol Sex Diff. 2011; 2:1.
- Whitacre CC: Sex differences in autoimmune disease. Nat Immunol 2(9), 777-780 (2001).
Perhaps the earliest discovery of profound sex and gender differences in health and disease was associated with cardiovascular disease. In the 1980's and 1990's women were dying of heart attack and stroke at higher levels than males, and the eventual culprit was the sex differences in the vessels that feed the heart. Male heart blockage occurs in the major vessels that feed the heart and an angiogram easily detects these clots. In the female, it is the small vessels tat are generally affected which are not easily identified by angiogram, so many women would be sent home from the emergency room, only to regurn or die of their symptoms later. In addition to the anatomic difference in presentation, there was a gendered difference in the way men and women presented their symptoms when arriving in the emergency room. Men, in general, would be more demonstrative about a constricting of the chest muscles and doctors would immediately suspect heart attach. Women would have more diffuse pain or general tiredness and would be less demanding about the necessity of treatment. So both sex and gender were both to blame for the disparities between males and females and many physicians now know to treat males and females in ways that are appropriate to their symptoms.
- 10Q Report: Advancing Women's Heart Health through Improved Research, Diagnosis and Treatment. The Society for Women’s Health Research (SWHR) and WomenHeart: The National Coalition for Women with Heart Disease released the long awaited 2011 10Q Report that is an update to their 2006 10Q Report that identified the top 10 unanswered research questions concerning heart disease in women. Many of these questions have yet to be answered and this report serves as a recommendation to research who are designing new projects.
- Hogg ME, Varu VN, et al. Effect of Nitric Oxide on Neointimal Hyperplasia based on Sex and Hormone Status. Free Radic Biol Med. 2011 Jan 20. [Epub ahead of print] PubMed PMID: 21256959. This research was funding in part from the Institute for Women's Health Research!
- Hsia J, Rodabough R, Manson J, Liu S, Freiberg M, Graettinger W, Rosal M, Cochrane B, Lloyd-Jones D, Robinson J, Howard B: Evaluation of the American Heart Association cardiovascular disease prevention guideline for women. Circ Cardiovasc Qual Outcomes Feb 16. [Epub ahead of print] (2010).
- Melloni C, Berger J, Wang T, Gunes F, Stebbins A, Pieper K, Dolor R, Douglas P, Mark D, Newby K: Representation of women in randomized clinical trials of cardiovascular disease prevention. Circ Cardiovasc Qual Outcomes Feb 10. [Epub ahead of print] (2010)
- Mosca L, Mochari-Greenberger H, Dolor R, Newby K, Robb K: Twelve-year follow up of American women's awareness of cardiovascular disease risk and barriers to heart health. Circ Cardiovasc Qual Outcomes Feb 10. [Epub ahead of print] (2010).
- Vaccarino A: Ischemic heart disease in women: Many questions, few facts. Circ Cardiovasc Qual Outcomes Feb 16. [Epub ahead of print] (2010).
Eye Health (Opthamology)
- A special issue of Current Eye Research. Sex, Eyes, and Vision: Male/female Distinctions in Opthalmic Disorders Volume 40, Number 2 (February 2015)
- Clayton JA, Davis, AF. Sex/Gender Disparities and Women's Eye Health. Curr Eye Research. Feb 2015. Vol.40.
One of the interesting and unexpected ways that sex influeces biology is based on the bacteria that populate our intestines. Last year, in a blockbuster paper, Jayne Danska and colleagues found that the microbiome of male mice could eliminate disease in female mice. In a laboratory model of type 1 diabetes, female mice develop obesity related insulin resistance (type 1 diabetes) earlier than male mice. When female and male mice were depleted of their microbiome and male microbiota were transferred to the females, the animals were cured of their disease. Type 1 diabetes is an autoimmune disease and for reasons that are not clear, females are more affected than males in other autoimmune diseases as well. These diseases include lupus, MS, and even irritable bowel disease. The fact that gut microbiota may influence the sex-skewed incidence of disease opens a new area of research that may mitigate these intractable diseases.
New work on neural circuitry shows that the learning and memory region of the brain respond to drugs differently. Endocannabinoids are one of the most widely prescribed classes of drugs and is also the active ingredient in marijuana. There has been no study of male vs. female effects of these drugs even though scientists now believe there is a link that suggests that there are profound differences. Importantly, these effects are not regulated by the reproductive hormones. These studies are not about females or males being smarter or better than each other, it is about the fundamental mechanisms that drive normal function and how to better treat males and females with more specificity. If certain drug classes don't work in males, then they should not be treated with that group of drugs (Woolley et al, J. Neuroscience, 2015).
- Richardson J, Holdcroft A. Gender differences and pain medication. Women's Health (2009) 5, 79-90.
- Stening K, Eriksson O, Wahren L, Berg G, Hammar M, Blomqvist A: Pain sensations to the cold pressor test in normally menstruating women: Comparison with men and relation to menstrual phase and serum sex steroid levels.Am J Physiol Regul Integr Comp Physiol 293(4), R1711-1716 (2007).
Pharmacology (Drug Metabolism)
- Gelb K, Gelb A. Sex and Gender in the Perioperative Period: Wake Up to Reality. Anest & Analg. July 2008.
- Regitz-Zagrosek, Vera (ed). Sex and Gender Differences in Pharmacology. Springer-Verlag Berlin Heidelberg (2012).
- Paul KN, Laposky AD, Turek FW: Reproductive hormone replacement alters sleep in mice. Neuroscience Letters 463, 239–243 (2009).
- Paul KN, Losee-Olson S, Pickney L, Turek FW: The ability of stress to alter sleep in mice is sensitive to reproductive hormones. Brain Research 11 (1305) 74-85 (2009).
- The Substance Abuse & Mental Health Services Administration (SAMHSA) has just release a free publication called Treatment Improvement Protocol (TIP) 51, Substance Abuse Treatment: Adddressing the Specific Needs of Women, that will help professionals provide effective, up-to-date treatment to women with substance use disorders by taking into account their unique treatment needs. To order by phone call 1-877-726-4727 and ask for publication order number (SMA09-4426) or go to http://ncadistore.samhsa.gov/catalog/productDetails.aspx?ProductID=18244