Prolonged lifetime exposure to estrogens is linked to a lower risk of stroke

According to a study from Chinese researchers, prolonged lifetime exposure to cumulative estrogens is linked to a lower risk for stroke.

The central nervous system and the peripheral nervous system are important targets for sex steroids, which influence brain development and differentiation and neuronal functions. Steroids with paracrine and/or autocrine mechanisms of action (known as neurosteroids) are synthesized locally in the central nervous system and the peripheral nervous system, by myelinating glial cells.

Compared to men, women are less likely to have a stroke at an early age. However, production of estrogens ceases during the postmenopausal phase, and the postmenopausal status has been identified as an independent risk factor for stroke. The reduction of sexual hormones has been proposed as one of the driving factors of stroke.

In addition, other reproductive factors, such as young age at menarche and lack of lactation, have been demonstrated to contribute to the development of stroke.

The majority of the experimental studies have shown that female sex steroids progesterone and 17β-estradiol exert protective effects in the experimental models of stroke, although deleterious effects have also been reported. Neuroprotective activities of the female sexual steroids include stabilization of neurotransmission, inhibition of apoptosis, reduction of cerebral edema, anti-inflammatory and antioxidant activities.

The factors determining the balance between the neuroprotective and the deleterious effects of these hormones are unknown, although the balance has usually been shifted towards neuroprotection, particularly in models of focal infarct. However, it should be noted here that clinical data indicate that the functional outcome following the stroke is influenced by gender, and that women who survive a stroke experience less favorable outcome than men.

About the study

The present study is based on data from China Kadoorie Biobank longitudinal prospective cohort study that recruited 512,726 individuals aged 30 to 79 from 2004 to 2008. The study involved 122,939 postmenopausal women. All included participants did not have a stroke at the start of the study, and the median age was 58 years. Participants answered questions about reproductive health, including age at first menstruation and onset of the menopause, number of pregnancies and miscarriages and use of oral contraceptives.

Participants were divided into the groups according to the length of reproductive life, the number of years between first menstruation and menopause.

In a nine-year average follow-up period, 15139 participants suffered a stroke. Of these, 12,853 had an ischemic stroke, 2,580 had intracerebral hemorrhage and 269 had subarachnoid hemorrhage.

The results showed that participants in the longer group had slightly more strokes than those in the shorter group, 13.2% compared to 12.6%. After adjusting for other factors that may influence stroke risk, such as age, smoking, physical activity and hypertension, the results showed that women with the longest reproductive lifespan had a lower risk of all types of stroke of less than 5%. Women with the longest reproductive lifespan had a 5% lower ischemic stroke risk, and a 13% lower risk of intracerebral hemorrhage when compared to women with the shortest reproductive lifespan.

The authors concluded that their study suggests that a lifetime cumulative exposure to estrogens could be a useful indicator of stroke risk following menopause. However, the authors suggested that further research is necessary on the underlying biological, behavioral, and social mechanisms linking estrogen exposure to the risk of stroke.

This study was published in the scientific journal Neurology. Hou L et al. Lifetime cumulative effect od reproductive factors on stroke and its subtypes in postmenopausal Chinese: a prospective cohort study. Neurology, 2023, DOI: 10.1212/WNL.0000000000206863 (Open Access)