Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed and over-the-counter (OTC) medications used for pain relief and to reduce inflammation. While most people are aware of their well-documented side effects on the gastrointestinal (GI), cardiovascular (CV), and renal systems, fewer know about a lesser-discussed but important concern: the potential link between NSAID use and reversible infertility in both men and women.
UNDERSTANDING INFERTILITY
Infertility is defined as the inability of a couple to conceive after 12 months of regular, unprotected sexual intercourse. It can be primary (when pregnancy has never occurred) or secondary (when conception fails after a previous pregnancy). Globally, infertility affects millions of couples, leading not only to medical challenges but also emotional stress, relationship strain, and social pressure. Any medication that interferes with reproductive hormones or ovulation can therefore have profound consequences on a couple’s physical and emotional well-being.
WHAT ARE NSAIDS?
NSAIDs are a diverse class of drugs that reduce pain, inflammation, and fever primarily by inhibiting cyclooxygenase (COX) enzymes, which are responsible for prostaglandin production. Prostaglandins are hormone-like substances that play key roles in pain signaling, inflammation, and even reproduction.
TYPES OF NSAIDS
NSAIDs can be broadly divided into:
• Nonselective COX inhibitors (e.g., ibuprofen, naproxen, diclofenac, aspirin) block both COX-1 and COX-2 enzymes.
• COX-2 selective inhibitors (e.g., celecoxib, etoricoxib) designed to reduce GI side effects by primarily targeting COX-2.
• Salicylates (e.g., aspirin) among the oldest NSAIDs with both anti-inflammatory and antiplatelet effects.
Despite their widespread use for headaches, arthritis, dysmenorrhea (menstrual pain), and fever, long-term or high-dose use raises concerns for reproductive health.
WELL-KNOWN ADVERSE EFFECTS OF NSAIDs
NSAIDs are notorious for their effects on:
• Gastrointestinal system: dyspepsia, erosions, heartburn, perforation, ulcers, and bleeding.
• Cardiovascular system: increased risk of myocardial infarction, stroke, heart failure, hypertension, venous thromboembolism, and atrial fibrillation.
• Renal system: acute kidney injury, electrolyte disturbances, acid-base imbalance, nephrotic syndrome, and interstitial nephritis.
In pregnancy, NSAID use near term can prolong labor, increase postpartum bleeding, and cause premature closure of the fetal ductus arteriosus. However, their lesser-known impact on fertility deserves equal attention.
HOW NSAIDs MAY CAUSE INFERTILITY IN WOMEN
Women of childbearing age often use NSAIDs such as naproxen, piroxicam, and diclofenac for conditions like arthritis or painful periods. NSAIDs exert their therapeutic effects by inhibiting COX-1 and COX-2 enzymes, blocking prostaglandin synthesis.
Prostaglandins, especially those induced by COX-2, are essential for normal ovulation, fertilization, and implantation. During follicular development, COX-2 activity triggers the rupture of mature ovarian follicles to release an egg. When COX-2 is inhibited, ovulation can occur without the actual release of the ovum, a condition known as Luteinized Unruptured Follicle Syndrome (LUFS).
SCIENTIFIC EVIDENCE
Several clinical and laboratory studies support this mechanism:
• In a study of 59 menstrual cycles in women with chronic inflammatory disorders, 35.6% of NSAID-exposed cycles showed LUFS compared to only 3.4% of untreated cycles (Akil et al., Ann Rheum Dis, 2002).
• A randomized trial presented at the European League Against Rheumatism (EULAR) 2015 reported that after 10 days of treatment with diclofenac, naproxen, or etoricoxib, ovulation rates dropped dramatically, with diclofenac reducing ovulation to just 6.3% of cycles.
• Experimental data from COX-2 deficient mice show complete failure of follicular rupture despite normal follicle development, highlighting the essential role of prostaglandins in ovulation.
These findings explain why chronic NSAID use can result in reversible infertility ovulation resumes once the drug is withdrawn.
HOW NSAIDs MAY AFFECT MALE FERTILITY
In men, NSAIDs such as ibuprofen, aspirin, and paracetamol have been shown to have anti-androgenic effects, influencing both semen quality and sperm parameters. Research suggests that NSAIDs may:
• Reduce the production of FSH (follicle-stimulating hormone) and LH (luteinizing hormone) from the pituitary gland, lowering testosterone levels and impairing sperm production.
• Cause abnormalities in sperm motility, shape, size, count, and DNA integrity.
• Increase oxidative stress, reduce nitric oxide and prostaglandin production, and interfere with zinc metabolism, leading to spermatocyte damage.
SCIENTIFIC EVIDENCE
• A controlled trial in healthy men found that ibuprofen at 600 mg twice daily for 6 weeks induced a state of compensated hypogonadism with elevated LH and relatively low testosterone (Kristensen et al., PNAS, 2018).
• A Taiwanese population-based study reported that long-term ibuprofen use (>60 days/year) was associated with a twofold increase in the risk of male infertility compared with acetaminophen (Lin et al., Andrology, 2024).
• Animal studies show consistent results: ibuprofen exposure in mice caused significant reductions in sperm motility, count, and DNA integrity (El-Sayed et al., Andrologia, 2016).
While most human data suggest these effects are reversible after discontinuing the drug, the threshold dose and duration for clinically significant changes remain unclear.
INFERTILITY’S IMPACT ON COUPLES
Infertility is more than a medical condition; it can deeply affect a couple’s emotional and psychological health. Couples may experience:
• Emotional stress and anxiety from repeated failed attempts to conceive.
• Relationship strain, including feelings of guilt, blame, or isolation.
• Social pressure and stigma, especially in cultures where fertility is closely linked to self-worth or family expectations.
If NSAID use is a contributing factor, identifying and stopping these medications can spare couples from unnecessary investigations, expensive fertility treatments, and prolonged emotional distress.
CONCLUSION
Without expensive fertility workups, simply discontinuing chronic NSAID use can sometimes resolve unexplained infertility especially in women with ovulatory dysfunction such as LUFS. For men, stopping irrational or long-term NSAID intake may reverse hormonal imbalances and improve sperm quality.
While occasional short-term NSAID use is unlikely to cause permanent reproductive harm, long-term or frequent use should be carefully evaluated in anyone trying to conceive. Healthcare professionals should always weigh the benefits of NSAID therapy against potential reproductive risks and explore safer alternatives when appropriate.
KEY TAKEAWAY
If you or your partner is facing unexplained infertility, reviewing medication history including regular NSAID use may provide an overlooked yet reversible solution.
FAQs
1. Can occasional NSAID use cause infertility?
Short-term or occasional use (for example, a few doses for a headache or fever) are unlikely to cause infertility. Most evidence links fertility issues to chronic or long-term NSAID use.
2. Is NSAID-related infertility permanent?
Current studies indicate the effect is usually reversible. Ovulation and sperm quality often return to normal once NSAIDs are discontinued.
3. Are all NSAIDs equally risky?
Both non-selective NSAIDs (like ibuprofen, naproxen, diclofenac) and COX-2 inhibitors (like celecoxib) can interfere with reproductive processes. Risk depends on dose, duration, and individual susceptibility.
4. How quickly can fertility recover after stopping NSAIDs?
Limited human data suggest that normal ovulation may resume within one or two menstrual cycles in women. In men, hormonal balance and sperm parameters typically improve within a few weeks to months.
5. Are there safer alternatives for chronic pain?
Paracetamol (acetaminophen) is often used as a first-line analgesic but also has some weak prostaglandin effects. Always consult a healthcare professional for personalized pain-management plans.
DISCLAIMER
This article is for educational purposes only and should not replace professional medical advice. If you are trying to conceive or have concerns about fertility, consult a qualified healthcare provider before starting or discontinuing any medication.
CALL TO ACTION
If you or your partner is experiencing unexplained fertility challenges, review your medication list with your doctor or pharmacist. A simple change such as reducing or stopping unnecessary NSAID use could make a significant difference.
REFERENCES
1. Akil M, Amos RS, Stewart P. Ann Rheum Dis. 2002;61(11):1070-1072.
2. Kristensen DM et al. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. PNAS. 2018;115(4): E715-E724.
3. Lin CY et al. Long-term ibuprofen use and male infertility risk: a population-based cohort study. Andrology. 2024;12(3):402-410.
4. El-Sayed EM et al. Ibuprofen exposure impairs sperm parameters and DNA integrity in mice. Andrologia. 2016;48(7):813-819.
5. European League Against Rheumatism (EULAR). NSAIDs inhibit ovulation after ten days of use. Abstract, 2015. 6. Lim H et al. Multiple female reproductive failures in cyclooxygenase 2 deficient mice. Endocrinology. 1997;138(7):2739-2747.