Suicide attempts among women during low estradiol/low progesterone states Enrique Baca-Garcia a,b,g , Carmen Diaz-Sastre c,g , Antonio Ceverino b,g , M. Mercedes Perez-Rodriguez c,d,g , Rocio Navarro-Jimenez b , Jorge Lopez-Castroman b , Jeronimo Saiz-Ruiz c,g,e , Jose de Leon f , Maria A. Oquendo a, * a Department of Psychiatry at the New York State Psychiatric Institute and Columbia University, NY, USA b Department of Psychiatry, Fundacion Jimenez Diaz Hospital, Autonoma University of Madrid, Spain c Department of Psychiatry, Ramon y Cajal Hospital, Madrid, Spain d Department of Psychiatry, Mount Sinai School of Medicine, New York, USA e Department of Psychiatry, University of Alcala, Madrid, Spain f Mental Health Research Center (MHRC) at Eastern State Hospital, Lexington, Kentucky, USA g Centro de Investigación Biomédica en Red en el área de Salud Mental (CIBERSAM), Madrid, Spain article info Article history: Received 11 May 2009 Received in revised form 29 July 2009 Accepted 4 August 2009 Keywords: Attempted suicide Menstrual cycle Gonadal steroid hormones Estrogen Progesterone Menstruation abstract The relationship between the menstrual cycle and risk for suicidal behaviors is not clear. The aim of this study is to determine whether perimenstrual phases in fertile women are associated with acute risk for suicide attempt and explore whether risk is elevated during low estradiol/low progesterone states. Women (N = 431) recruited within 24 h of a suicide attempt were assessed for psychopathology, suicidal behavior and LH, FSH, estradiol and progesterone blood levels. Among fertile women (N = 281/431), sui- cide attempts were more likely to occur during menses (26%, 72/281 observed vs. 15%, 43/281 expected attempts; p < 0.001). Compared to women whose attempts occurred during other phases, women who attempted suicide during low estradiol/low progesterone states (menstrual phase, amenorrhea and men- opause) reported severe suicide intent, a measure that may be predictive of eventual suicide death. Sui- cide attempts among women are more likely when estrogen and progesterone levels are low and attempts made under these conditions are associated with greater severity. Low gonadal hormone levels may constitute a key factor in the neurobiological basis of suicidal behavior among women, suggesting a novel, testable hypothesis regarding the underpinnings of suicidal acts. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Studies of the neurobiological basis of suicidal behavior have largely focused on the serotonergic system, but have also exam- ined the hypothalamic–pituitary–adrenal (HPA) axis, and GABAer- gic and glutamatergic systems. Fewer studies have examined the hypothalamic–pituitary–gonadal axis, despite the fact that as early as 1926, publications described an association between the men- strual cycle and suicide attempts (Baca-Garcia et al., 2003a; Saun- ders and Hawton, 2006). Saunders and Hawton (Saunders and Hawton, 2006) reviewed studies of suicidal behavior and the menstrual cycle and found that 15 of 23 studies reported that suicide attempts tended to cluster around the premenstrual and menstrual phases of the cycle. The other eight studies found no association. Among these studies, they noted considerable variation in terms of the methodology used to determine the participants’ menstrual phase at the time of suicide attempt. Four studies used hormonal assessment, and only two of them combined menstrual history, hormonal assessments and psy- chiatric evaluation within 24 h of the index suicide attempt. In this study, we tested the hypothesis that low estradiol/low progesterone states are associated with suicide attempts during the menstrual cycle. To achieve this goal, we used a comprehensive assessment of blood hormonal levels among women who had recently attempted suicide. We also sought to determine whether the association extends to all low estradiol/low progesterone states such as menopause and amenorrhea. Such an association would sug- gest a novel biological pathway leading to risk for suicidal behavior in women and stimulate further investigation of the role of the HPG axis in suicidal behavior. Moreover, it may serve to alert the clinician to potential elevation in risk for suicidal behavior during low estradiol/low progesterone states among vulnerable women. 2. Materials and methods Women who attempted suicide (n = 431) were recruited and interviewed in the Emergency Departments of two general 0022-3956/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2009.08.004 * Corresponding author. Address: Molecular Imaging and Neuropathology Divi- sion, NYS Psychiatric Institute and Columbia University, 1051 Riverside Drive, Office # 2725, 10032 New York, USA. Tel.: +1 212 543 5835; fax: +1 212 543 6017. E-mail address: mao4@columbia.edu (M.A. Oquendo). Journal of Psychiatric Research 44 (2010) 209–214 Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/jpsychires