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

Hum Reprod. 2015 Jul;30(7):1714-23. doi: 10.1093/humrep/dev099. Epub 2015 May 6.


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, 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.

Keywords: analgesics; over-the-counter drugs; ovulation; reproductive hormones.

Publication types

  • Observational Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Acetaminophen / adverse effects
  • Acetaminophen / pharmacology
  • Adolescent
  • Adult
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / pharmacology*
  • Anovulation / prevention & control
  • Aspirin / adverse effects
  • Aspirin / pharmacology
  • Female
  • Follicular Phase / drug effects*
  • Follow-Up Studies
  • Humans
  • Ibuprofen / adverse effects
  • Ibuprofen / pharmacology
  • Naproxen / adverse effects
  • Naproxen / pharmacology
  • New York
  • Ovulation / drug effects*
  • Premenopause / drug effects*
  • Progesterone / blood*
  • Young Adult


  • Analgesics, Non-Narcotic
  • Acetaminophen
  • Progesterone
  • Naproxen
  • Aspirin
  • Ibuprofen