Gender medicine

The “Gender Medicine” studies the differences between men and women, it analyses the different ways in which they develop and manifest the disease in the two genres and specific treatment options. These differences include those related to biological genes, both those arising from the complexity of the woman’s reproductive life (pregnancy, lactation, menstrual cycle, menopause, use of estrogen-progestogen combinations)

Initially, the only differences recognized were those affecting the sexual organs, the so called “Bikini Medicine”. Until the last decades of the last century, we had an androcentric medicine focused on Caucasian young adult. Today, we know that the differences between men and women and between boys and girls are significant and numerous, they influence the response to therapies. Although it was already known since 1932, the year in which it is reported the first indication on gender differences in the pharmacology of barbiturates in rats, a full awareness of the importance of the role of gender on the pharmacokinetics and pharmacodynamics came only at the end of the last century, when the medical community has realized that “women are not small men” and from the past decade, the awareness of this concept is greatly increased. In this regard, the United States Institute of Medicine declares that being a woman or a man significantly influences the prevention and course of diseases. Recently, the FDA has recommended a different dose of zolpidem, a hypnotic drug, for women and men. In Italy, it has begun to acknowledge the existence of the problem, so that, in 2005, was established at the Ministry of Health the Work Table “Women’s health and drugs for women.” In 2007, it was established by the then Health Minister Livia Turco, the Commission on Women’s Health. The commission’s work was completed with the publication of the report “Status of women’s health in Italy,” which is recommended to collect gender-specific data on health and propose methodological survey and statistical analysis, propose specific training courses at university level and for the operators of the National Health System and to promote research programs in a gender perspective. The AIFA, in three call for proposals in the years 2005 -2007, has funded a number of themes dedicated to research projects on medications that would provide significant contributions to the pharmacology of gender for both clinical disease characteristics of women, for clinical problems related to specific stages of the cycle woman’s life, such as pregnancy and menopause. The National Bioethics Committee has drafted, in 2008, a document entitled “The pharmacological experimentation on women”. Since then, it is to remember the consultation carried out by the 12th Standing Committee of the Senate (Health and Hygiene), chaired by Sen. Antonio Tomassini, that in many parts highlights the need to consider the determinant genre to program new health interventions. In order to train experts in the field, the University of Sassari, in 2006, established a doctorate “Pharmacology of Gender”, renamed in 2013 “Gender medicine of man, woman and child”. Finally, in 2010-2011, the Agenas has set up working groups to elaborate guidelines of gender in cardiovascular and respiratory diseases and, in 2011, the AIFA has established a Working Group “Drugs and Gender”. However, a clear understanding of the differences, including behavioural and social, and how these aspects are reflected on the development of the disease is yet to be explored and studied.

The work of INBB researchers involved in gender research has contributed in recent years to add new information on the topic. In particular, they studied differences in the expression of genes and proteins of oestrogen receptors and androgen and evaluation of their activity in monocytes, macrophages, endothelial cells, smooth muscle cells and human EPC in different experimental conditions in vitro and ex vivo. In addition, it was observed that cigarette smoking and oral contraceptive use influence, in a sex-gender matrix, specific endothelial function, cellular oxidative stress, DNA methylation and the function of macrophages in culture. It was also noted that the autophagy process, which is involved in the pathogenesis of many diseases, including cardiovascular disease, liver disease, diabetes mellitus and its complications, usually turns out to be sex-dependent and it presents also tissue-specific differences. Finally, whereas metabolomics is gaining more and more importance, in collaboration with Prof. Ruoppolo of INBB RU of Naples were measured amino acids, carnitine and acetilcarnitne which prove to be sexually dimorphic in an amino acid-specific and carnitine-specific . The commitment of INBB researchers in the specific area is also reported from the activity reports submitted as part of the INBB National Conferences, among which are mentioned the most recent ones related to INBB IX National Conference, held in Rome on 21-22 October 2010 and X INBB National Conference, held in Rome on 22-23 October 2012, whose detailed programs and abstracts of the reports are on the website www.inbb.it

The research future perspectives in the field of gender medicine are often bound to a more accurate analysis of the differences in both biological, behavioural and social fields in order to ensure, using appropriate methods in the field of prevention and clinical practice, the therapeutic appropriateness and therefore better health in all men and women, adults and children. The area is so vast and yet there is so much to explore, that it is necessary to start precise lines of preclinical and clinical research in order to adhere to the OMS recommendations. It is, therefore, appropriate to raise awareness in the pharmaceutical industry on gender issues, because at the moment the studies financed by public funds recruit more women compared to those financed by individuals, and the regulatory authorities in order to harmonize international standards.

In addition to the INBB National Laboratory of “Gender Medicine” active at the University of Sassari, different INBB RUs operate on the Platform on “gender medicine”: firstly the RU of the University of Naples Federico II and Roma Tre.

SOME RECENT PUBLICATIONS

• Franconi F, Campesi I. Pharmacogenomics, pharmacokinetics and pharmacodynamics: interaction with biological differences between men and women. Br J Pharmacol. 2013 Aug 27.
• Campesi I, Carru C, Zinellu A, Occhioni S, Sanna M, Palermo M, Tonolo G, Mercuro G, Franconi F. Regular cigarette smoking influences the transsulfuration pathway, endothelial function, and inflammation biomarkers in a sex-gender specific manner in healthy young humans. Am J Transl Res. 2013 Aug 15;5(5):497-509.
• Campesi I, Straface E, Occhioni S, Montella A, Franconi F. Protein oxidation seems to be linked to constitutive autophagy: a sex study. Life Sci. 2013 Aug 6;93(4):145-52.
• Anichini R, Cosimi S, Di Carlo A, Orsini P, De Bellis A, Seghieri G, Franconi F, Baccetti F. Gender difference in response predictors after 1-year exenatide therapy twice daily in type 2 diabetic patients: a real world experience. Diabetes Metab Syndr Obes. 2013 Apr 8;6:123-9.
• Campesi I, Galistu A, Carru C, Franconi F, Fois M, Zinellu A. Glutamyl cycle in the rat liver appears to be sex-gender specific. Exp Toxicol Pathol. 2013 Jul;65(5):585-9.
• Campesi I, Fois M, Franconi F. Sex and gender aspects in anesthetics and pain medication. Handb Exp Pharmacol. 2012;(214):265-78.
• Franconi F, Campesi I, Occhioni S, Antonini P, Murphy MF. Sex and gender in adverse drug events, addiction, and placebo. Handb Exp Pharmacol. 2012;(214):107-26.
• Campesi I, Sanna M, Zinellu A, Carru C, Rubattu L, Bulzomi P, Seghieri G, Tonolo G, Palermo M, Rosano G, Marino M, Franconi F. Oral contraceptives modify DNA methylation and monocyte-derived macrophage function. Biol Sex Differ. 2012 Jan 27;3:4.
• Franconi F, Campesi I, Occhioni S, Tonolo G. Sex-gender differences in diabetes vascular complications and treatment. Endocr Metab Immune Disord Drug Targets. 2012 Jun;12(2):179-96.
• Colasanti T, Maselli A, Conti F, Sanchez M, Alessandri C, Barbati C, Vacirca D, Tinari A, Chiarotti F, Giovannetti A, Franconi F, Valesini G, Malorni W, Pierdominici M, Ortona E. Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus. Arthritis Rheum. 2012 Mar;64(3):778-87.
• Seghieri C, Francesconi P, Cipriani S, Rapanà M, Anichini R, Franconi F, Del Prato S, Seghieri G. Gender effect on the relation between diabetes and hospitalization for heart failure. Exp Clin Endocrinol Diabetes. 2012 Jan;120(1):51-5.
• Bianchi L, Lari R, Anichini R, De Bellis A, Berti A, Napoli Z, Seghieri G, Franconi F. Taurine transporter gene expression in peripheral mononuclear blood cells of type 2 diabetic patients. Amino Acids. 2012 Jun;42(6):2267-74.