Impact of Aspirin on Estrogen Levels
The evidence shows that aspirin has minimal to no clinically significant effect on estrogen levels in most adults, though low-dose aspirin (100 mg/day) may modestly reduce estradiol levels in postmenopausal women by approximately 3.5 pg/ml after 6 weeks of use.
Evidence in Postmenopausal Women
The most recent and highest quality evidence comes from a 2022 randomized controlled trial that demonstrated a statistically significant reduction in estradiol levels with low-dose aspirin:
Low-dose aspirin (100 mg/day) for 6 weeks significantly decreased estradiol levels (median change: -3.5 pg/ml in aspirin group vs +1.5 pg/ml in placebo group, p=0.002) in postmenopausal women 1
No significant changes occurred in testosterone or sex hormone-binding globulin (SHBG) levels with low-dose aspirin 1
However, this finding contradicts an earlier 2014 trial using higher doses:
Higher-dose aspirin (325 mg/day) for 6 months showed no effect on serum estradiol, estrone, free estradiol, bioavailable estradiol, or SHBG in 144 postmenopausal women 2
Stratification by body mass index did not reveal any subgroup effects with the higher dose 2
Evidence in Premenopausal Women
The data in premenopausal women shows no meaningful impact on overall estrogen levels:
Aspirin use was not associated with changes in total estradiol, estrone, or major pathways of estrogen metabolism in 603 premenopausal women 3
More frequent aspirin use (2+ days/week) was associated with lower methylated 2-catechols (2-hydroxyestrone-3-methyl ether: 0.95 vs 1.21 pmol/mg creatinine, p=0.01), but this represents a minor metabolite rather than primary estrogen levels 3
Acetaminophen (not aspirin) showed positive associations with total estrogen metabolites and specific metabolites like 16α-hydroxyestrone 3
Evidence in Men
No direct evidence exists examining aspirin's effect on estrogen levels in men. The provided guidelines focus exclusively on cardiovascular outcomes and do not address hormonal effects in either sex 4.
Clinical Context and Mechanism
The proposed mechanism for aspirin's potential effect on estrogen involves:
Inhibition of cyclooxygenase activity, which reduces prostaglandin synthesis 5
Prostaglandins stimulate aromatase gene expression and estrogen biosynthesis 5
Reduction in inflammation in adipose tissues, including breast tissue, where estrogen synthesis occurs 2
Important Clinical Caveats
The clinical significance of the modest estradiol reduction seen with low-dose aspirin remains uncertain:
The 3.5 pg/ml reduction in estradiol is relatively small compared to normal postmenopausal estradiol ranges 1
The 2014 study suggests that either larger doses or longer duration may be needed to affect circulating estrogens, or that aspirin's effects on breast cancer risk (if present) may occur through direct tissue effects rather than systemic hormone changes 2
Epidemiologic data suggests aspirin use may reduce breast cancer risk, particularly for hormone receptor-positive tumors, but this may operate through mechanisms other than systemic estrogen reduction 5
One historical interaction to note: Oral contraceptives containing estrogen were shown to lower aspirin plasma levels and reduce its half-life, though this represents the opposite direction of effect (estrogen affecting aspirin, not aspirin affecting estrogen) 6
Practical Implications
For clinical decision-making regarding aspirin use:
Do not prescribe aspirin for the purpose of lowering estrogen levels - the effect is too modest and inconsistent to justify use for this indication alone
Aspirin prescribing should follow established cardiovascular prevention guidelines, which show sex-specific benefits: men benefit from myocardial infarction reduction, while women benefit from ischemic stroke reduction 4
Any potential hormonal effects of aspirin should be considered secondary to its established cardiovascular benefits and bleeding risks 4