While they’re sold as the fix, you’re not crazy if they don’t work
Are you told to “just take a painkiller” for your period pain by a healthcare professional, over and over again, but you’re fed up with trying to explain that it doesn't touch the sides? Well, you’re in the right place.
The Massive Body of Painkiller Research No One Talks About
A Cochrane review (the gold standard of evidence), of 80 randomised controlled trials involving 5,821 women evaluated 20 different non-steroidal anti-inflammatory drugs, or NSAIDS (1). NSAIDs are medications such as ibuprofen and naproxen, and they are the first-line medical treatment for period pain amongst clinical guidelines.
Researchers assessed how effective and safe NSAIDs are for primary dysmenorrhoea - this is the term for period pain that isn't caused by an underlying condition like endometriosis or adenomyosis.
For Half of Women, “Just Take Ibuprofen” Isn’t a Full Answer
The good news? NSAIDS worked for more people than placebo. Around 18% of women on placebo achieved pain relief versus 45-53% achieved relief on NSAIDs. However, NSAIDs caused more side effects than placebo, most commonly indigestion, headaches and drowsiness (1).
The bad news? Around 50% of women didn’t reach moderate-or-better pain relief from NSAIDs, the first line treatment for primary dysmenorrhea. That’s a problem.
We need to stop pretending painkillers fix period pain for everyone. It shouldn't be a throwaway response to someone’s pain - one that contributes to women being dismissed when they go back and ask for more help. It’s not you being difficult. It’s in the data.
Why Painkillers Only Solve Part of the Problem
There are good reasons why NSAIDs don’t work for everyone. Period pain comes from many different pathways converging together, amplifying the pain that you may feel.
Painkillers target one pathway: prostaglandins.
Just before your period, progesterone drops, triggering a rise in prostaglandins in the uterine lining (2). Prostaglandins drive the uterine contractions needed to shed the lining. Too many, and those contractions become intense and prolonged, squeezing the blood vessels that supply the uterus. That reduced blood flow (ischaemia) causes pain. Prostaglandins also sensitise nearby pain fibres, making them fire more easily (2).
Prostaglandins are made by COX enzymes, which is exactly what NSAIDs block. This is why they work for some people.
But prostaglandins aren't the whole story
Period pain also involves:
◉ Leukotrienes: another family of inflammatory chemicals, can also drive uterine muscle spasms and pain, and NSAIDs don't block them (3).
◉ Oxidative stress: a systematic review found higher markers of lipid peroxidation, a type of cell damage caused by free radicals, in women with period pain compared with those without (4).
◉ Changes in the brain: repeated, intense pain month after month can change how the nervous system processes pain, known as central sensitisation. In women with intense period pain, the nervous system can begin to amplify pain signals further, and there are differences in the brain regions that process and dampen those signals. NSAIDs can't reverse what's happening at the brain level. (5)
So it’s not just prostaglandins, and it’s not even just inflammation.
Nutrition Science and Pain Modulation
Everyone is unique and responds differently to medication. NSAIDs may work for some people, and not for others. Because period pain involves several pathways at once, some people may benefit from an approach that supports more than one of them.
Other non-pharmaceutical options can be useful. That's where nutrition comes in. DITTO's Premenstrual Daily combines nutrients that act on several of the pathways we've just covered, including inflammation, oxidative stress and muscle function. Importantly, this approach doesn't work "instantly" like a painkiller. The nutrients need to be taken every day so they can build up over time and support the body's natural pain buffering pathways. That way, when your period arrives, pain is less likely to develop anywhere near as intensely in the first place. While painkillers are reactive, nutrition can be proactive in preventing pain severity.
Vitamin D for Prostaglandins
A 2023 meta-analysis of 8 clinical trials including participants suffering from painful cramps found that vitamin D supplementation significantly reduced period pain scores compared to placebo (6). How?
1. Vitamin D lowers prostaglandins in the uterus by reducing the activity of the enzyme called COX2, which is needed to make prostaglandins.
2. It also increases the activity of the enzyme 15-PGDH which breaks prostaglandins down.
The result: your prostaglandins are being made slower and broken down faster.
Zinc for Oxidative Stress
A 2024 meta-analysis of 6 clinical trials found that zinc supplementation significantly reduced pain severity of menstrual cramps compared to a placebo (7).
How? Free radicals are created due to hormonal changes, which can then lead to increased oxidative stress, onward inflammation and discomfort (4). Zinc works as an antioxidant and can turn off these free radicals, reducing oxidative stress and preventing damage.
Magnesium for the Uterine Muscle
In a 2024 study, magnesium supplementation reduced moderate to severe cramps and abdominal pain compared to a placebo, after two menstrual cycles (8).
How? Magnesium is shown to relax the smooth muscles of the uterus. Calcium is the trigger for muscle contraction. Magnesium limits how much calcium flows into smooth muscle cells, which prevents “depolarization” of the cells - ultimately helping to reduce uterine contractions, easing cramps and discomfort. (9,10)
Takeaway
Painkillers have been handed out as the answer to period pain for decades, so when they don't work, it's easy to assume the problem is you. It isn't. Around half of women in clinical trials didn't get adequate relief from NSAIDs. Period pain is driven by several pathways at once, so a drug that targets only one of them was never going to work for everyone. "Just take a painkiller" shouldn't be where the conversation ends. If NSAIDs work for you, that's great. If they don't, you deserve to be listened to, not dismissed, and to have other options made known to you. Your pain deserves to be taken seriously while you find what works.
References:
1. Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev. 2015 Jul 30;2015(7):CD001751. doi: 10.1002/14651858.CD001751.pub3. PMID: 26224322; PMCID: PMC6953236.
2. Itani R, Soubra L, Karout S, Rahme D, Karout L, Khojah HMJ. Primary Dysmenorrhea: Pathophysiology, Diagnosis, and Treatment Updates. Korean J Fam Med. 2022 Mar;43(2):101-108. doi: 10.4082/kjfm.21.0103. Epub 2022 Mar 17. PMID: 35320895; PMCID: PMC8943241.
3. Oladosu FA, Tu FF, Hellman KM. Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment. Am J Obstet Gynecol. 2018 Apr;218(4):390-400. doi: 10.1016/j.ajog.2017.08.108. Epub 2017 Sep 6. PMID: 28888592; PMCID: PMC5839921.
4. Szmidt MK, Granda D, Sicinska E, Kaluza J. Primary Dysmenorrhea in Relation to Oxidative Stress and Antioxidant Status: A Systematic Review of Case-Control Studies. Antioxidants (Basel). 2020 Oct 15;9(10):994. doi: 10.3390/antiox9100994. PMID: 33076228; PMCID: PMC7602455.
5. Liu N, Huo J, Li Y, Hao Y, Dai N, Wu J, Liu Z, Zhang Y, Huang Y. Changes in brain structure and related functional connectivity during menstruation in women with primary dysmenorrhea. Quant Imaging Med Surg. 2023
6. Chen YC, Chiang YF, Lin YJ, et al. Effect of Vitamin D Supplementation on Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Nutrients. 2023;15(13):2830.
7. Hsu TJ, Hsieh RH, Huang CH, Chen CS, Lin WY, Huang YC, Lin JH, Huang KT, Liu YL, Tsai HM, Ho DR. Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis. Nutrients. 2024
8. Yaralizadeh M, Nezamivand-Chegini D , Najar S , Namjoyan F , Abedi . Effectiveness of magnesium on menstrual symptoms among dysmenorrheal college students: A randomized controlled trial. International Journal of Women's Health & Reproduction Sciences. 2024. 12(2)
9. Kantas E, Cetin A, Kaya T, Cetin M. Effect of magnesium sulfate, isradipine, and ritodrine on contractions of myometrium: pregnant human and rat. Acta Obstet Gynecol Scand. 2002;81(9):825-830. Na, H. S., Ryu, J.
10. H., & Do, S. H. The role of magnesium in pain. In R. Vink & M. Nechifor (Eds.), Magnesium in the Central Nervous System. University of Adelaide Press. 2011
