Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women

Matyas RA; Mumford SL; Schliep KC; Ahrens KA; Sjaarda LA; Perkins NJ; Filiberto AC; Mattison D; Zarek SM; Wactawski-Wende J; Schisterman EF

doi:10.1093/humrep/dev099

Reproductive Endocrinology Ovulation Physiology

Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women

Matyas RA, Mumford SL, Schliep KC, Ahrens KA, Sjaarda LA, Perkins NJ, Filiberto AC, Mattison D, Zarek SM, Wactawski-Wende J, Schisterman EF

Published July 2015 Human reproduction (Oxford, England), 30(7), 1714-1723

DOI 10.1093/humrep/dev099 PMID 25954035 PMC PMC4472321

RRM Academy Synopsis

OTC analgesic use linked to fewer cycles without ovulation

In 259 women tracked for one or two menstrual cycles, those who used over-the-counter pain relievers early in the cycle were less likely to have a cycle without ovulation (adjusted odds ratio 0.36). Progesterone also trended higher, but not significantly. Follicular-phase use showed no link with estradiol, LH, or FSH.

About 7 in 10 women reported using over-the-counter pain relievers. Source: Matyas RA et al., 2015, PMID 25954035.

Study at a glance, prospective cohort of 259 healthy women: OTC analgesic use linked to fewer cycles without ovulation. Source: Matyas RA et al., 2015, PMID 25954035.

Key Findings

Among 509 cycles studied, 42 (8.3%) had no ovulation; women using OTC analgesics had fewer such cycles than non-users (4% versus 14%, P = 0.009).
Controlling for age, race, body-mass index, smoking status, stress level, and alcohol use, follicular-phase analgesic use remained linked to lower odds of a cycle with no ovulation (OR 0.36, 95% CI 0.17-0.75).
Luteal progesterone tended higher with follicular-phase analgesic use, though the difference wasn't statistically significant; estradiol, LH, and FSH showed no such association.
Among the 68% of women (175 of 259) who reported any OTC analgesic use, ibuprofen was most common (45%), followed by acetaminophen (33%), aspirin (10%), and naproxen (10%).
Analgesic use in the 5 days before a blood draw was linked to lower estradiol and higher FSH, compared with women who hadn't used analgesics in that window.

Interpretation

The BioCycle Study was a prospective cohort that followed 259 healthy women ages 18 to 44 in western New York State for one or two menstrual cycles. Women recorded their own medication use in daily diaries and gave blood samples several times per cycle, timed with fertility monitors. Women with known ovulation problems were excluded from the study. The authors note that self-reported diaries aren't a validated way to measure medication use. The findings support larger studies of over-the-counter analgesic use and ovulation.

RRM Context

Fertility awareness methods track the same signs measured here: the LH surge and the rise in progesterone after ovulation. The study used fertility monitors and frequent blood draws to time each visit. Close tracking like this can catch a pattern that one blood test would miss.

Our editorial summary of this paper, not the article's abstract.

Abstract

Study Question

Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women?

Summary Answer

Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders.

What Is Known Already

Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear.

Study Design, Size, Duration

The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles.

Participants/Materials, Setting, Methods

Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo.

Main Results and the Role of Chance

During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, -1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH.

Limitations, Reasons for Caution

Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women.

Wider Implications of the Findings

The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function.

Study Funding/Competing Interests

This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose.

Topics

Reproductive Endocrinology › Ovulation Physiology › Anovulation · Menstrual Cycle › Cycle Physiology › Ovulation

Sunni L Mumford, Karen C Schliep, Lindsey A Sjaarda, Neil J Perkins, Shvetha M Zarek, Enrique F Schisterman, Jean Wactawski-Wende

S Mumford, K Schliep, L Sjaarda, N Perkins, S Zarek, E Schisterman, J Wactawski-Wende

PMID 25954035 25954035 DOI 10.1093/humrep/dev099 10.1093/humrep/dev099 Matyas et al. 2015, Matyas 2015

Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women

OTC analgesic use linked to fewer cycles without ovulation

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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