Sex bias exists in basic science and translational surgical research


      Although the Revitalization Act was passed in 1993 to increase enrollment of women in clinical trials, there has been little focus on sex disparity in basic and translational research. We hypothesize that sex bias exists in surgical biomedical research.


      Manuscripts from Annals of Surgery, American Journal of Surgery, JAMA Surgery, Journal of Surgical Research, and Surgery from 2011 to 2012 were reviewed. Data abstracted included study type, sex of the animal or cell studied, location, and presence of sex-based reporting of data.


      Of 2,347 articles reviewed, 618 included animals and/or cells. For animal research, 22% of the publications did not specify the sex of the animals. Of the reports that did specify the sex, 80% of publications included only males, 17% only females, and 3% both sexes. A greater disparity existed in the number of animals studied: 16,152 (84%) male and 3,173 (16%) female (P < .0001). For cell research, 76% of the publications did not specify the sex. Of the papers that did specify the sex, 71% of publications included only males, 21% only females, and 7% both sexes. Only 7 (1%) studies reported sex-based results. For publications on female-prevalent diseases, 44% did not report the sex studied. Of those reports that specified the sex, only 12% studied female animals. More international than national (ie, United States) publications studied only males (85% vs 71%, P = .004), whereas more national publications did not specify the sex (47% vs 20%, P < .0001). A subanalysis of a single journal showed that across three decades, the number of male-only studies and usage of male animals has become more disparate over time.


      Sex bias, be it overt, inadvertent, situational, financial, or ignorant, exists in surgical biomedical research. Because biomedical research serves as the foundation for subsequent clinical research and medical decision-making, it is imperative that this disparity be addressed because conclusions derived from such studies may be specific to only one sex.
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      1. Drugs can affect men and women differently. Aired on 60 Minutes February 7, 2014. Available from

      2. Rabin RC. Labs Are Told to Start Including a Neglected Variable: Females, NY Times, May 14, 2014. Available from

        • Clayton J.A.
        Policy: NIH to balance sex in cell and animal studies.
        Nature. 2014; 509: 282-283
        • Kim A.M.
        • Tingen C.M.
        • Woodruff T.K.
        Sex bias in trials and treatment must end.
        Nature. 2010; 465: 688-689
        • Woodruff T.K.
        • Kibbe M.R.
        • Paller A.S.
        • Turek F.W.
        • Woolley C.S.
        Commentary: “Leaning in” to support sex differences in basic science and clinical research.
        Endocrinology. 2014; 155: 1181-1183
        • Woodruff T.K.
        Sex, equality and science.
        Proc Natl Acad Sci U S A. 2014; 111: 5063-5064
        • Mostertz W.
        • Stevenson M.
        • Acharya C.
        • Chan I.
        • Walters K.
        • Lamlertthon W.
        • et al.
        Age- and sex-specific genomic profiles in non–small cell lung cancer.
        JAMA. 2010; 303: 535-543
        • Anderson G.D.
        Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics.
        J Womens Health (Larchmt). 2005; 14: 19-29
        • Zopf Y.
        • Rabe C.
        • Neubert A.
        • Gassmann K.G.
        • Rascher W.
        • Hahn E.G.
        • et al.
        Women encounter ADRs more often than do men.
        Eur J Clin Pharmacol. 2008; 64: 999-1004
        • Hughes R.N.
        Sex does matter: comments on the prevalence of male-only investigations of drug effects on rodent behaviour.
        Behav Pharmacol. 2007; 18: 583-589
        • Tharpe N.
        Adverse drug reactions in women's health care.
        J Midwifery Womens Health. 2011; 56: 205-213
      3. American Association for Justice 2013. Unequal harm: The disproportionate damage to women from dangerous drugs and medical devices. Available from

        • Pinnow E.
        • Herz N.
        • Loyo-Berrios N.
        • Tarver M.
        Enrollment and monitoring of women in post-approval studies for medical devices mandated by the Food and Drug.
        J Womens Health (Larchmt). 2014; 23: 218-223
        • Hennekens C.H.
        • Eberlein K.
        A randomized trial of aspirin and beta-carotene among U.S. physicians.
        Prev Med. 1985; 14: 165-168
        • Zucker I.
        • Beery A.K.
        Males still dominate animal studies.
        Nature. 2010; 465: 690
        • Blauwet L.A.
        • Hayes S.N.
        • McManus D.
        • Redberg R.F.
        • Walsh M.N.
        Low rate of sex-specific result reporting in cardiovascular trials.
        Mayo Clin Proc. 2007; 82: 166-170
        • Prendergast B.J.
        • Onishi K.G.
        • Zucker I.
        Female mice liberated for inclusion in neuroscience and biomedical research.
        Neurosci Biobehav Rev. 2014; 40: 1-5
        • Arnold A.P.
        • Lusis A.J.
        Understanding the sexome: measuring and reporting sex differences in gene systems.
        Endocrinology. 2012; 153: 2551-2555
        • Beery A.K.
        • Zucker I.
        Sex bias in neuroscience and biomedical research.
        Neurosci Biobehav Rev. 2011; 35: 565-572
      4. Johnson PA, Fitzgerald T, Salganicoff A, Wood SF, Goldstein JM, Colson YL, et al. Sex-specific medical research: why women's health can't wait. A Report of the Mary Horrigan Connors Center for Women's Health & Gender Biology at Brigham and Women's Hospital, 2014, p. 32. Available from

        • Jochmann N.
        • Stangl K.
        • Garbe E.
        • Baumann G.
        • Stangl V.
        Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases.
        Eur Heart J. 2005; 26: 1585-1595
        • Mackay F.J.
        • Pearce G.L.
        • Mann R.D.
        Cough and angiotensin II receptor antagonists: cause or confounding?.
        Br J Clin Pharmacol. 1999; 47: 111-114
        • Wolbrette D.L.
        Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues.
        Am J Cardiol. 2003; 91: 39D-44D
        • Ridker P.M.
        • Cook N.R.
        • Lee I.M.
        • Gordon D.
        • Gaziano J.M.
        • Manson J.E.
        • et al.
        A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.
        N Engl J Med. 2005; 352: 1293-1304
        • Kindig D.A.
        • Cheng E.R.
        Even as mortality fell in most US counties, female mortality nonetheless rose in 42.8 percent of counties from 1992 to 2006.
        Health Aff (Millwood). 2013; 32: 451-458
        • Taylor K.E.
        • Vallejo-Giraldo C.
        • Schaible N.S.
        • Zakeri R.
        • Miller V.M.
        Reporting of sex as a variable in cardiovascular studies using cultured cells.
        Biol Sex Differ. 2011; 2: 11
        • Vidaver R.M.
        • Lafleur B.
        • Tong C.
        • Bradshaw R.
        • Marts S.A.
        Women subjects in NIH-funded clinical research literature: lack of progress in both representation and analysis by sex.
        J Womens Health Gend Based Med. 2000; 9: 495-504
        • Wang G.H.
        The relation between “spontaneous” activity and oestrous cycle in the rat.
        Comp Psychol Mon. 1923; 2: 1-27
        • Klinge I.
        Bringing gender expertise to biomedical and health-related research.
        Gend Med. 2007; 4: S59-S63
        • Klinge I.
        Gender perspectives in European research.
        Pharmacol Res. 2008; 58: 183-189
        • Mosca L.
        • Linfante A.H.
        • Benjamin E.J.
        • Berra K.
        • Hayes S.N.
        • Walsh B.W.
        • et al.
        National study of physician awareness and adherence to cardiovascular disease prevention guidelines.
        Circulation. 2005; 111: 499-510
        • Henrich J.B.
        • Viscoli C.M.
        What do medical schools teach about women's health and gender differences?.
        Acad Med. 2006; 81: 476-482

      Linked Article

      • Message from the Editors
        SurgeryVol. 156Issue 3
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        SurgeryVol. 156Issue 3
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      • Commentary on “Sex bias exists in basic science and translational surgical research”
        SurgeryVol. 157Issue 3
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