Low Dose Aspirin and the Menstrual Cycle
For anti-inflammatory effects and improved blood flow, many women use low dose aspirin (LDA) while trying to conceive. A study published in 2014, the EAGeR trial, showed that some women who were trying to conceive and who had recently lost a pregnancy had higher rates of giving birth if they were taking LDA compared to placebo. Today’s study came from data collected in the EAGeR trial, and this data attempts to answer if there will be menstrual side effects in women who take LDA while trying to conceive.
Study Background
WHAT
How does taking low dose aspirin (LDA) every day impact menstrual cycle length and hormones?
WHY
Women of reproductive age would value knowing if LDA impacts menstrual bleeding or other patterns in the menstrual cycle
WHEN/WHERE
2006-2012 at four medical centers (in CO, NY, PA, and UT)
WHO
1228 women, ages 18-40 years
All were trying to conceive
1-2 prior pregnancy losses
36% had lost one pregnancy
17% had lost two pregnancies
Had given birth no more than two times (53% of women had given birth previously)
Women were excluded if they experienced irregular periods (<21 days or > 42 days) or were known to have infertility or PCOS
HOW
Collected baseline laboratory samples and medical history questionnaires
Randomized to take LDA (aspirin 81 mg) or placebo - all participants took folic acid 400 ug daily
Follow up: six menstrual cycles (or 36 weeks if pregnancy occurred)
Menstrual cycles 1 & 2 - collected urine samples of hormones
hormones = pregnanediol glucuronide (PdG), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estrone-3-glucuronide (E1G)
patients collected at home and stored in freezer
Used Clearblue Easy Fertility Monitor to time provision of hormone samples, track ovulation
Results*
915 (75%) women completed the study, 452 taking LDA and 463 taking placebo
No statistically significant differences found in length of menstrual cycle, follicular phase, or luteal phase
No statistically significant differences found in hormone levels
* Analyzed intention-to-treat (ITT) populations, medication safety discussed in original EAGeR trial
“These data are reassuring for women of reproductive age using LDA, because all women studied in the EAGeR trial were attempting to become pregnant.”
Study Authors’ Thoughts:
Strengths
Design of study (randomized, double-blind, placebo-controlled)
Compared to past studies, women took LDA for longer period of time (more reflective of actual usage)
High participant retention
Limitations
Only included women with normal menstrual cycles
Used urinary vs. blood hormone levels (patients stored urine in freezer to eliminate inconvenience of multiple visits solely for bloodwork)
This Pharmacist’s Thoughts
Strengths
Detailed description of lab assays (allows replicability)
Strong placebo design enabled patients, investigators, and study personnel to remain blinded to treatment group
Authors attempted to account for confounding factors associated with missing data on cycle length, ovulation
Statistical methods and missing data explained
Limitations
95% White—> limited information on impact in other races
86% college education—> limited information on impact in women with limited education
Adherence measured by patient self-report and weight of pill bottles
Conclusions
The EAGeR trial was thoughtfully designed to minimize bias and reduce confounding variables. Women should not expect menstrual irregularities if taking low-dose aspirin while trying to conceive (caveat: these results are applicable only to women with regular menstrual cycles who do not have a diagnosis relating to infertility).
Resources
Evans MB, Nobles CJ, Kim K, et al. Low-dose aspirin in reproductive health: effects on menstrual cycle characteristics [published online ahead of print, 2020 Sep 4]. Fertil Steril. 2020;S0015-0282(20)30594-X. doi:10.1016/j.fertnstert.2020.06.022
Greer IA. Antithrombotic therapy for pregnancy complications: let's not throw the baby out with the bath water. Evid Based Med. 2015;20(1):10. doi:10.1136/ebmed-2014-110078
Schisterman EF, Silver RM, Lesher LL, et al. Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial. Lancet. 2014;384(9937):29-36. doi:10.1016/S0140-6736(14)60157-4
