**6. Conclusions**

Perihematomal edema (PHE) formation after ICH may affect mortality and long-term neuro‐ logical function in this patient population. Wagner et al. [39] looked at the role of gender in perihematomal edema in cases of primary ICH. PHE development was assessed over a 14-day period on follow-up CT scans in 387 subjects and was compared between men and women. The investigators found that starting at days 2-4, women showed lower PHE values (P<0.05; days 2-4 and 8-11). The mechanism and ultimate effect on outcome of these findings is unclear.

To further support the neuroprotective role of female sex hormones, menopause may alter the risk of primary ICH in women. Feldman et al. [40] carried out a prospective observational study of 1714 patients with a diagnosis of ICH, and evaluated various risk factors for devel‐ oping primary ICH. The investigators found that post-menopausal women had signifcantly higer incidence of ICH as compared to premenopausal women. Thus, menopause was significantly associated with development of primary ICH (adjusted OR, 2.50; 95% CI, 1.06 to 5.88). This observation may support role of female sex hormones in modifying the risk of

Five studies provide information about the fatality of ICH in both genders. In a cross sectional study done by Kimura et al. [41], investigators found no difference in ICH mortality in men vs. women at 28 days. The case fatality was 17.6% overall, with 18.8% in men and 16.2% in women. These findings were similar to subsequent studies. Data from the Arcadia stroke registry [16] showed a slightly higher rate of case fatality in women (51.8%) as compared to men (44%) at 4 weeks after ICH. There was no difference in the case fatality rates in men as compared to women from the observations in STROMA study. [29] The investigators found that case fatality rate was 23.9% in men and 22.7% in women at 4 weeks after UCG. These findings were supported by a large multicenter study from China, where the case fatality rate was 48.4 percent in men, similar to 50.7 percent in women at 4 weeks after ICH. [24] Strikingly different were the observations made by Thrift et al. [30] from Australia. The investigators found that case fatality was higher in women (50.6%) as compared to men (29.2%). Finally, women had better survival than men after first-ever primary ICH in a prospective stroke register from Sweden, largely explained by a higher 28-day mortality in male patients over 75

Data from preclinical models of ICH suggest response to the estrogen therapy. Nakamura et al. [43] studied sex differences in rat model of ICH. They observed that brain edema and neurological deficits at 24 hours after ICH were less in female rats as compared to male rats. The investigators then studied the role of an estrogen derivative on edema as well as functional outcome in male and female rats. They observed that administration of exogenous estrogen decreased edema as well as neurological deficits in male rats, but made no difference in female rats. Other studies support these findings. [44,45] These observations may also extend to pretreatment. Auriat et al. [46] found that estrogen pretreatment significantly reduced hemorrhagic blood volume at 12 hours after ICH in male rats; however estrogen did not lessen

developing ICH. Clearly, more studies are necessary in this regard.

**5. Preclinical observations of the role of sex in ICH**

years. [42]

16 Intracerebral Hemorrhage

Several general conclusions can be made from the above observations. Gender differences in incidence of ICH appear to exist in Asian and South American populations, where men seem to suffer a higher incidence. Gender differences in incidence of ICH are not as obvious in Northern America, European, or Australian-New Zealand populations. Interestingly, there appears to be an interaction between age and gender in many of these populations, with ICH occurring at a younger age in men. Differences in access to preventative treatment, prevalence of known risk factors (e.g., hypertension, alcohol consumption, use of sympathomimetic drugs), and genetic variance may explain some of these disparities.

Less clear is the existence of gender differences in pathophysiology and outcomes after ICH. While preclinical data support the role of gonadal hormones influencing hemostatic and neuroinflammatory modulation after ICH, their effects on recovery in humans are unknown.

**No. Author Study details Year/s Observations**

<sup>19</sup> Fogelholm (2005) [52] Finland 1985-1991 Higher incidence of ICH related

Gender Differences in Incidence, Pathophysiology, and Outcome of Primary Intracerebral Hemorrhage

20 Khan (2005) [29] Sweden 1989-1999 Higher incidence of ICH in men <sup>21</sup> Labovitz (2005) [25] Manhattan, USA 1993-1996 Higher incidence of ICH in men of

22 Lavados (2005) [53] Iquique, Chile 2000-2002 Higher incidence of ICH in men <sup>23</sup> Benatru (2006) [7] Dijon, France 1985 to 2004Same incidence of ICH over years

26 Minelli (2007) [28] Matão, Brazil 2003-2004 Higher incidence of ICH in men

28 Thrift (2009) [31] Melbourne, Australia 1997-1999 Higher incidence of ICH in men

1 Department of Neurology and Anesthesiology, Duke University Hospital, Duke University

2 Department of Neurology, Duke University Hospital, Duke University School of Medicine,

[1] Flaherty ML, Woo D, Haverbusch M, et al. Racial variations in location and risk of intracerebral hemorrhage. *Stroke; a journal of cerebral circulation.* May 2005;36(5):

24 Feigin (2006) [33] Auckland, NZ 2002-2003 Same incidence of ICH across genders

No difference in incidence of ICH

http://dx.doi.org/10.5772/58469

19

across genders

mortality in men

across genders

genders over years

genders over years

African American ethnicity

Decrease in incidence of ICH across

Decrease in incidence of ICH across

The incidence of non-lobar ICH was high, most non-white populations

18 Anderson (2005) [34] Auckland, NZ 1981-2003

25 Lovelock (2007) [5] Oxford shire, UK 1981-2006

27 Islam (2008) [6] Perth, Australia 1989-2001

29 Lavados (2010) [54] Iquique, Chile 2000-2002

\*Address all correspondence to: Michael.james@duke.edu

**Author details**

NC, USA

**References**

934-937.

Michael James1\* and Sankalp Gokhale2

School of Medicine, NC, USA


