Aspirin versus placebo on estrogen levels in postmenopausal women: a double-blind randomized controlled clinical trial

Abstract

Background Estrogen is involved in the pathogenesis of breast and gynecological cancers. Regular use of aspirin reduces estrogen levels. The present study aimed to evaluate the effect of aspirin on estrogen levels in postmenopausal women. Methods This double-blind, placebo-controlled parallel-group trial was conducted on postmenopausal women referred to an outpatient clinic at a women’s hospital in Tehran. Volunteers were randomly assigned to receive aspirin 100 mg/day or placebo for 6 weeks. Estradiol, sex hormone-binding globulin (SHBG), and testosterone levels at baseline and at the end of the intervention were measured by ELISA. Data were analyzed using SPSS 20, Kolmogorov–Smirnov test, independent samples t-test, and Mann–Whitney U test. Results Twenty-seven and 28 participants were finally analyzed in the aspirin and placebo groups, respectively. There was no significant difference between the two groups in body mass index (BMI), age, or menopausal years. There was a statistically significant difference (p = 0.002) in the amount of change in estradiol levels of the intervention group (median=− 3.5 pg/ml) compared to the control group (median=1.5 pg/ml). In contrast, there were no significant differences between the two groups regarding testosterone and SHBG levels (p = 0.58, p = 0.32). Conclusions Since low doses of aspirin may decrease estradiol levels, it could be considered a promising adjunctive therapeutic candidate in postmenopausal women to decrease BC incidence. However, further studies with larger sample sizes, measurements of estrogen levels and its related compounds in different time points accompanied by long-term follow-ups are needed to better elucidate the potential mechanisms by which nonsteroidal anti-inflammatory drugs (NSAIDs) negatively affect breast cancer. Trial registration IRCT201012195397N1. Date of first registration: 03/01/2011.

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

“…Recent studies have found that in addition to its anti-inflammatory and cardioprotective characteristics, it serves a role in modulating BC risk [9] . Its ability to prevent cancer is mediated by its ability to reduce cell proliferation, induce apoptosis, and modify lymphangiogenesis [10] . Although the precise method by which aspirin exerts its protective effects on BC is not entirely understood the fundamental mechanism could be explained by suppressing cyclooxygenases (COXs), particularly COX-2, whose overexpression is associated with lymph node metastases, larger tumor sizes, and worse prognoses [10] .…”

“…Its ability to prevent cancer is mediated by its ability to reduce cell proliferation, induce apoptosis, and modify lymphangiogenesis [10] . Although the precise method by which aspirin exerts its protective effects on BC is not entirely understood the fundamental mechanism could be explained by suppressing cyclooxygenases (COXs), particularly COX-2, whose overexpression is associated with lymph node metastases, larger tumor sizes, and worse prognoses [10] . COX-2 suppression inhibits prostaglandin synthesis, which lowers estrogen levels.…”

“…COX-2 suppression inhibits prostaglandin synthesis, which lowers estrogen levels. Furthermore, cytochrome P450 aromatase, which is responsible for converting testosterone to estrogen, leading to increased estrogen synthesis in breast tissue adipose cells, is also blocked [10,11] .…”

“…A meta-analysis found that aspirin may reduce the overall risk of breast cancer in postmenopausal women, with data suggesting a significant reduction with relative risk of 0.92 (95% CI, 0.89-0.96; I 2 = 72%) [13] . Recent double-blind randomized controlled clinical research suggests that low-dose aspirin 100 mg/d may lower estrogen levels in postmenopausal women and may be a good candidate for adjuvant therapy to lower the incidence of BC [10] . However, in contrast to these results, a phase III randomized, controlled clinical study found that consuming 300 mg of aspirin daily does not help prevent recurrence in persons with HER2negative BC [14] .…”

“…The researchers anticipate that a satisfactory outcome from this trial will pave the way for novel therapeutic approaches [15] . Due to a limited follow-up period, a small sample size, and a lack of data on the precise frequency of usage or dose, it may not be feasible to evaluate an association between aspirin and a reduction in the risk of getting BC until more research has been conducted [10] .…”