New evidence backs safety of low-dose aspirin in women attempting pregnancy

Daily use of low-dose aspirin (LDA) among women of reproductive age appears to have no harmful effect on menstrual cycle length and hormone patterns, as shown in a study.

Given the potential uses of daily LDA in women—including reducing the risks of stroke and cardiovascular disease, colon cancer, and obstetrical complications such as pre-eclampsia, foetal growth restriction, pregnancy loss, and preterm birth—the present data reassure those wanting to get pregnant that “LDA is unlikely to adversely affect their menstrual cycles,” according to investigators.  

“LDA may have further benefits in human reproduction by improving uterine and ovarian blood flow, enhancing embryo implantation and placental invasion, and sustaining early pregnancy. Indeed, we previously observed in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial that preconception LDA [use] in women with a single recent pregnancy loss was associated with higher rate of live birth compared with placebo,” they added. [J Clin Endocrinol Metab 2017;102:86-92; Lancet 2014;384:29-36]

In the current study, the investigators performed a secondary analysis of the EAGeR trial, which included 915 women (mean age, 29 years; mean body mass index, 26 kg/m²) with regular periods who had been randomized to receive 81-mg aspirin (n=452) or placebo (n=463) daily in addition to 400 mg folic acid. Participants were followed for six menstrual cycles or through pregnancy.

There were no significant between-group differences observed in menstrual cycle length and follicular and luteal phases. LDA did not confer a greater risk of having a short (relative risk [RR], 1.02) or long follicular phase length (RR, 1.01), short (RR, 1.02) or long cycle length (RR, 0.97), and short (RR, 1.23) or long luteal phase length (RR, 1.03). [Fertil Steril 2020;doi:10.1016/j.fertnstert.2020.06.022]

Furthermore, hormone levels during the first two cycles were similar in the LDA and placebo groups.

“Our results are consistent with one study evaluating serum hormone concentrations that also found no association between over-the-counter aspirin taken for one or two menstrual cycles and E2, luteal progesterone, follicle-stimulating hormone, and luteinizing hormone,” the investigators noted. [Gynecol Obstet Invest 1985;19:32-37; Hum Reprod 2015;30:1714-1723]

Meanwhile, the discrepancies in menstrual cycle length seen in several other studies are likely related to differences in aspirin dose and duration of use, they added. [Contraception 1984;29:181-188; J Clin Endocrinol Metab 2017;102:86-92; Gynecol Obstet Invest 1985;19:32-37]

In an editorial piece, Dr Jennifer Eaton, of the Women and Infants Hospital and Warren Alpert Medical School of Brown University, Rhode Island, US, said that the study is strengthened by its randomized, placebo-controlled design and its large study population, and the findings may be used to counsel women on the use of LDA. [Fertil Steril 2020;doi:10.1016/j.fertnstert.2020.08.018]

Eaton emphasized that normal cycle parameters and hormone levels do not necessarily mean normal fertility. Therefore, couples who fail to conceive based on the duration of unprotected intercourse should still undergo the standard fertility evaluation.

“Finally, women who present with cycle irregularity while taking LDA should be evaluated to determine the aetiology. Despite biologic plausibility, the hypothetical impact of LDA on menstrual cyclicity is not supported by the data presented in this well-designed study,” she added.

Eaton also pointed out some important limitations to the study. Among these are the inclusion of only normally cycling women, which limits data extrapolation to women with short or long cycles, and the use of urinary samples rather than serum samples, which could have influenced the results.