I suggest the etiological mechanism underlying these findings is important.  I wish to suggest a mechanism, that is, that these effects of aspirin in men and women are the result of the effects of aspirin in reducing testosterone levels in both men and women.  Testosterone is the source of the problem.


Why Aspirin Affects Men and Women Differently Until Menopausal Age: Cardiopathy and Stroke


Copyright 2005, James Michael Howard, Fayetteville, Arkansas, U.S.A.


As women reach menopause, their estradiol decreases.  Therefore the ratio of testosterone may increase and the effects of testosterone increase accordingly.  (Just below is a citation regarding estradiol and testosterone in a group of postmenopausal women in which increased testosterone and decreased estradiol have been connected with increased cardiopathy.  I have not found this situation with stroke.)  However, briefly, "Spontaneous platelet aggregation" has been demonstrated to be greater in men and due to testosterone.  Aspirin antagonizes this effect.  I suggest the reason for the difference in the effects of aspirin in men and women, and which becomes similar in postmenopausal women, is testosterone.


"A number of clinical trials suggest that the antithrombotic effect of aspirin is limited to men. To test the possibility that this is due to a sex difference in the inhibitory effect of aspirin on platelet behavior, we studied whole-blood platelet aggregation in men and women and in male patients with carcinoma of the prostate receiving hormone therapy. The in vitro inhibitory effect of aspirin on so-called spontaneous platelet aggregation induced by stirring whole blood and monitored by the decrease in the number of singleton platelets was greater in men (mean +/- SD inhibitory ratio 1.54 +/- 0.30 in men, 1.23 +/- 0.22 in women; p less than 0.001). The inhibitory effect of aspirin was reduced in orchiectomized male patients and was restored by the addition of testosterone to blood samples. Estradiol had no detectable influence on the inhibitory effect of aspirin.  Testosterone thus seems to influence platelet aggregation and its inhibition by aspirin as assessed by whole-blood in vitro aggregometry. Possible mechanisms for this effect of testosterone and its relevance to the choice of antithrombotic therapy are discussed." (Stroke 1989; 20: 34-7).


This study reports an increase in the effectiveness of asprin in older women.  "Among the 4,097 women in the study over 64, regular aspirin use began to show a clear benefit, cutting the risk of ischemic stroke by 30 percent and the chance of heart attack by 34 percent." Yahoo News  This is from March 7 New England Journal of Medicine: "Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older."


In the following citation, increased cardiopathy was connected with increased testosterone and reduced estradiol in a group of older women.  I suggest the increased cardiopathy results from increased testosterone and reduced estradiol.  Since aspirin may reduce “spontaneous platelet aggregation” caused / increased by testosterone, I suggest the protective effects of aspirin in older women is also due to the same effect.  That is, aspirin reduces stroke and cardiopathy in older women.  A reduction of stroke in younger women may involve a group of women of higher testosterone.


Menopause. 2004 May-Jun;11(3):315-22


Association between hormonal changes at menopause and the risk of a coronary event: a longitudinal study.


Guthrie JR, Taffe JR, Lehert P, Burger HG, Dennerstein L.


OBJECTIVE: To investigate the association of hormone levels at menopause, lifestyle variables, and body composition with the predicted 10-year risk of a coronary event, calculated using the

PROCAM scoring system, in a population-based sample of Australian-born, middle-aged women. DESIGN: A 9-year prospective study of 438 Australian-born women, who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews, fasting blood, and physical measurements were taken annually. The risk of an acute coronary event was calculated using the PROCAM scoring system (includes: age, low-density lipoprotein cholesterol, smoking, high-density lipoprotein cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides). RESULTS: Retention rate after 8 years of follow-up was 88% (n = 387). In women not using hormone therapy (HT): higher than average body mass index (BMI) (P < 0.001), BMI that increased (P < 0.005), lower than average estradiol levels (P < 0.005), estradiol levels that decreased (P < 0.001), and high free testosterone levels

(P < 0.05) were associated with increased risk of a coronary event.  There was a trend for high exercise frequency to be associated with a decreased risk (P < 0.07). After BMI and lifestyle variables were taken into account, use of HT did not have a significant effect on risk of a coronary event. CONCLUSION: In this longitudinal observational study of middle-aged Australian-born women, high BMI, an increase in BMI, high free testosterone, low estradiol, and a decrease in estradiol levels were the main determinants of increased risk of an acute coronary event, based on the PROCAM scoring system calculation.  More frequent exercise tended to lower the risk.