Doing everything right, and still hurting

Imagine following every instruction on the label. Right pill, right dose, right timing, exactly as a doctor recommended. And still, the pain doesn't go away.

That's the experience we set out to measure in this study. We targeted students who take it correctly and still don't get relief. It's a quieter, less-discussed problem, but it turns out to be a big one.

Why we needed to ask this question

Ibuprofen, naproxen, and similar anti-inflammatory painkillers (NSAIDs) are the global first-line treatment for period pain. They work by blocking the chemical signals (prostaglandins) that cause the uterus to cramp. For most people, this works well.

But a body of international research has quietly been pointing to something else: a meaningful chunk of women don't get adequate relief from NSAIDs even when they take them exactly as directed. Prior studies estimated this at roughly 18–25% globally. We set out to study it properly, at Afe Babalola University, using a stricter, more precise definition of what actually counts as medication resistance.

What we did differently

Rather than simply asking, "Does your period pain medication work?", a question that blends together people who don't take it correctly with people who genuinely don't respond to it, we asked a sequence of specific questions to isolate true treatment failure. A student only counted as having "NSAID-resistant dysmenorrhea" if she:

1. Actually experienced period pain,
2. Used NSAIDs specifically to manage it,
3. Took them at the dose and duration a healthcare professional would recommend, and
4. Still had inadequate pain relief despite all of that.

We surveyed 271 female undergraduates across all six colleges at Afe Babalola University, Ado-Ekiti, Nigeria, to answer this properly.

What we found

Period pain itself is nearly universal. 70.8% of students reported dysmenorrhea, and just over half of those (52.6%) described their pain as severe, not just "uncomfortable" but disruptive.

Roughly a third who used medication correctly still got no real relief. Among students who used NSAIDs, 75% said they took them at the right dose. But even among that adherent group, 69.2% still found the medication ineffective, and 81.7% felt it took too long to kick in. Altogether, 32.8% of all students with period pain and 52.5% of those who used NSAIDs met our definition of NSAID-resistant dysmenorrhea. That number is notably higher than earlier Nigerian estimates. We believe this isn't because more women are suddenly resistant to medication but because our stricter definition, requiring correct use and persistent pain, was better at catching real treatment failure rather than confusing it with simple non-adherence.

The biggest clue wasn't pain severity; it was how the medicine felt. Two things stood out as strong predictors of resistance: how effective a student rated the medication (lower ratings meant far higher odds of resistance), and whether she felt it was working too slowly. In fact, students who felt the medication was slow to act had roughly 17 times higher odds of being classified as NSAID-resistant, even after accounting for other factors. Interestingly, how severe someone's pain was didn't independently predict resistance once we accounted for these two factors. It came down to how the medication was actually performing for that individual.

When medication failed, students improvised, not always safely. Faced with pain that wouldn't budge, the most common responses were switching to another medication (25.4%) or simply taking more of the NSAID than recommended (23.8%). Antispasmodics, a different drug class that works by relaxing uterine muscle rather than blocking prostaglandins, was the most commonly used alternative medication (31.7%). Some turned to herbal remedies like clove or ginger, heat therapy, rest, or just "enduring" the pain by crying it out. Only 17.5% visited a hospital when medication failed them.

That last point matters more than it might seem. Persistent pain that doesn't respond well to standard treatment can sometimes be an early sign of an underlying condition like endometriosis, something that becomes harder to catch the longer a student assumes "the pill just isn't working for me" rather than seeking follow-up care.

Why this changes the picture

For years, if a young woman said period pain medication "just doesn't work" for her, it was easy for others, and sometimes for herself, to assume something else was going on: maybe she wasn't taking it right, maybe she was exaggerating, maybe it was "just in her head." Our findings push back on that. This is a real, measurable, and fairly common pharmacological phenomenon, not a communication or compliance problem.

That reframing matters. It shifts the conversation from "are you taking your medicine properly?" to "what do we do for the substantial group of young women for whom first-line treatment genuinely isn't enough?"

What needs to happen next

A few concrete implications fall out of this:

• Physicians and pharmacists should ask, specifically, about timing and effectiveness — not just "are you taking something for your period pain," but "is it actually working, and how fast."
• Dose escalation without guidance is a safety concern. Nearly a quarter of resistant students simply took more NSAIDs than recommended, a pattern that carries real risk of gastrointestinal and kidney side effects if it becomes routine and unsupervised.
• Second-line options need to be normalized and taught, not treated as a last resort discovered only through trial and error. Hormonal contraceptives, properly guided antispasmodic use, and evidence-based non-drug approaches all have a role when first-line treatment genuinely falls short.
• "It's not working" deserves a follow-up appointment, not a shrug. Persistent, treatment-resistant pain is exactly the kind of symptom that should prompt further evaluation, not just repeated self-medication.

Painful periods are common. What's less appreciated is that, for a real subset of young women, the standard first-line treatment for that pain simply isn't enough — and recognizing that is the first step toward actually helping them.

Read the full open-access paper here: https://doi.org/10.1186/s12978-026-02404-y