Period pain and PMS
Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Medication
PMS and PMDD
Shown to ease overall premenstrual symptoms more than placebo, mostly in women with PMDD on a drospirenone pill. Depressive symptoms alone did not clearly differ.
Compared with placebo or another combined pill [30][31]
The numbers and sources
- Effect
- In two placebo-controlled trials in women with PMDD, a pill with drospirenone 3 mg and ethinyl estradiol 20 µg lowered premenstrual symptom scores after 3 months (MD -7.92, 95% CI -11.16 to -4.67) and eased impairment of productivity, social activities and relationships. Nausea (OR 3.15), bleeding between periods (OR 4.92) and breast pain (OR 2.67) were more common. In a 2-year trial, symptoms on a drospirenone pill matched a desogestrel pill [30]. Across 9 trials (1,205 women), combined pills improved overall premenstrual symptoms more than placebo (SMD 0.41, 95% credible interval 0.17 to 0.67) but not depressive symptoms (SMD 0.22, -0.06 to 0.47), and no pill did better than another [31].
- Population
- 1,920 women in 5 trials [30]; 1,205 women with PMS or PMDD in 9 trials, mean ages 24.6 to 36.5 [31].
- Sources
- [30], [31]
- Caveats
- The placebo response was large, and the trials lasted 3 cycles, so longer effects are unknown [30]. Evidence for women with milder symptoms is thin [30].
Period pain
Shown to relieve period pain more than placebo, with moderate or excellent relief in 45% to 53% of women against 18% on placebo.
Compared with placebo [24][25]; paracetamol [24]; other NSAIDs and aspirin [24][25]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In primary dysmenorrhea, NSAIDs gave more pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09, 35 RCTs, low-quality evidence). If 18% of women on placebo got moderate or excellent relief, 45% to 53% on NSAIDs would. NSAIDs also relieved pain more than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, 3 RCTs). No single NSAID was shown to relieve pain more or cause fewer side effects than another [24]. A network meta-analysis of 13 drugs found most gave more pain relief than aspirin, and ketoprofen, naproxen, rofecoxib and ibuprofen scored higher than placebo on overall assessment [25].
- Population
- 80 RCTs with 5,820 women with primary dysmenorrhea, comparing 20 NSAIDs [24]; 72 RCTs with 5,723 patients [25].
- Sources
- [24], [25]
- Caveats
- The Cochrane authors rated most evidence low quality because study methods were poorly reported. 59% of trials were commercially funded and 31% did not state funding [24].
Period pain
Shown to reduce period pain in women more than placebo, with improvement in 37% to 60% against 28%, along with more irregular bleeding, headache and nausea.
Compared with placebo or no treatment [5]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Combined pills reduced pain more than placebo (SMD -0.58, 95% CI -0.74 to -0.41, high quality) and raised the chance of improvement (RR 1.65), from 28% to between 37% and 60%. Extra medication and missed work fell (RR 0.63 each). Continuous pill use may reduce pain more than the standard regimen [5].
- Population
- 3,723 women in 21 trials [5].
- Sources
- [5]
- Caveats
- The dichotomous pain result was low quality [5].
Premenstrual syndrome and PMDD
Shown to reduce premenstrual symptoms in women with PMS or PMDD by a moderate amount, more with daily dosing than with dosing in the luteal phase only.
The numbers and sources
- Effect
- SSRIs lowered overall self-rated premenstrual symptoms against placebo (SMD -0.57, 95% CI -0.72 to -0.42). The effect was larger with continuous dosing (SMD -0.69) than with luteal phase dosing (SMD -0.39). Nausea (OR 3.30), insomnia (OR 1.99) and sexual dysfunction or decreased libido (OR 2.32) were more frequent than on placebo [16]. The 2013 version of the same review reported numbers needed to harm of 7 for nausea and 14 for decreased libido at moderate doses [17].
- Population
- 1,742 women in 12 studies for the symptom outcome, within 34 RCTs of fluoxetine, paroxetine, sertraline, escitalopram and citalopram [16]; 31 RCTs [17].
- Sources
- [16], [17]
- Caveats
- Both sources are versions of one Cochrane review. 68% of the included studies were funded by drug companies, and the authors suspected publication bias in the response analysis [16].
Side effects when taken for period pain
Shown to raise side effects in women taking NSAIDs for period pain, from 10% on placebo to between 11% and 14%, mostly gut and nervous system effects.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Against placebo, overall adverse effects rose (OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, low-quality evidence), as did gastrointestinal effects (OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs) and neurological effects (OR 2.74, 95% CI 1.66 to 4.53, 7 RCTs). If 10% of women on placebo had side effects, 11% to 14% on NSAIDs would [24].
- Population
- Women with primary dysmenorrhea in RCTs of NSAIDs against placebo [24].
- Sources
- [24]
- Caveats
- Short courses taken during periods. Evidence quality was low [24].
Supplements
Period pain
Shown in two reviews to lower period pain more than controls in women with dysmenorrhea, at 300 to 1,800 mg a day for 2 to 3 months.
Compared with control groups the source abstracts do not describe [54][55]
The numbers and sources
- Effect
- Across 12 studies (881 women) giving 300 to 1,800 mg of long-chain omega-3 a day for 2 or 3 months, 8 pooled studies showed lower pain (Cohen's d -1.020, 95% CI -1.53 to -0.51). 86% of studies that measured pain medicine use found it fell, and few mild side effects were reported [54]. A second review of RCTs found lower primary dysmenorrhea severity (SMD -1.075, 95% CI -1.871 to -0.279), with smaller effects at higher daily intakes and in older women [55].
- Population
- 881 women with dysmenorrhea in 12 studies [54]; women with primary dysmenorrhea in RCTs [55].
- Sources
- [54], [55]
- Caveats
- Most studies were rated neutral in quality [54]. The trials were small and short, and the two reviews share many of them.
Period pain
Shown in three reviews to lower period pain more than placebo in women with primary dysmenorrhea, by about 1.1 to 1.6 points on a 10-point scale.
Compared with placebo or standard care [63]; placebo, in trials that had a placebo group [64]; placebo [65]
The numbers and sources
- Effect
- Across 8 RCTs (695 participants), vitamin D lowered pain more than placebo (SMD -1.404, 95% CI -2.078 to -0.731), with relief at average weekly doses over 50,000 IU [63]. Across 11 studies (687 participants), pain intensity fell 1.64 points more than in controls (95% CI 1.00 to 2.27, I² 79%), with moderate certainty. Pain fell in primary dysmenorrhea (MD -1.90) but not in the 3 trials of secondary dysmenorrhea [64]. A review of registered trials found pain 1.12 points lower than placebo on a visual analogue scale (95% CI 0.07 to 2.16, 5 studies, 308 participants), in the primary dysmenorrhea trials only [65].
- Population
- Women with primary dysmenorrhea in 8 RCTs [63]; women with regular periods and primary or secondary dysmenorrhea in 11 RCTs, 7 of them in Iran [64]; 7 registered RCTs in primary dysmenorrhea or endometriosis [65].
- Sources
- [63], [64], [65]
- Caveats
- Heterogeneity was high [64][65]. Doses and schedules varied widely, and the registered trials had high or some concerns of risk of bias [65]. The three reviews share many trials.
PMS symptoms
Shown in two reviews to ease PMS symptoms more than placebo, with small to moderate drops in total, emotional and physical symptom scores.
Compared with placebo [20][21]; placebo across the zinc trials reviewed [22]
The numbers and sources
- Effect
- Across 4 pooled RCTs, zinc lowered total PMS scores (Hedges's g -0.384) and emotional symptoms (g -0.347) with moderate certainty, and physical symptoms (g -0.512) with low certainty [20]. A second review of 5 studies found better physical health (MD 3.69, 95% CI 1.65 to 5.74) and fewer physical symptoms (MD -0.79, 95% CI -1.39 to -0.20) than placebo, with lower anger, anxiety and tearfulness scores [21]. A narrative review of 31 RCTs found zinc consistently improved psychological PMS symptoms, at 30 mg a day in 60 students and 50 mg a day in 142 women for 3 months [22].
- Population
- 5 RCTs in women of reproductive age, 4 pooled [20]; 5 studies in young women with PMS [21]; 31 RCTs with 3,254 women aged 15 to 50 [22].
- Sources
- [20], [21], [22]
- Caveats
- All trials had some concerns for risk of bias, and the trials were few [20]. The two meta-analyses draw on largely the same small set of trials.
PMS symptoms
Shown in several trials to ease PMS symptoms more than placebo. In the largest, total symptom scores fell 48% on calcium and 30% on placebo.
Compared with placebo [21][22]; placebo or usual diet across the trials reviewed [23]
The numbers and sources
- Effect
- In a trial of 1,200 mg of calcium a day as carbonate for 3 cycles, luteal phase symptom scores were lower than on placebo in the second (P = .007) and third (P < .001) cycles. By the third cycle, total symptom scores had fallen 48% from baseline on calcium and 30% on placebo, and all 4 symptom groups (negative mood, water retention, food cravings, pain) were lower [21]. In college students, 500 mg twice a day for 3 months improved early tiredness, appetite changes and depressive symptoms more than placebo [22]. A review of 31 RCTs found that all 4 calcium trials (776 women) reported benefits on PMS symptoms, including a crossover trial of 2,000 mg a day and a trial of calcium-rich food against usual diet [23].
- Population
- 466 women aged 18 to 45 with moderate to severe PMS at 12 US centers [21]; female college students with PMS, mean age 21.4 [22]; 4 trials with 776 women within a review of 31 RCTs [23].
- Sources
- [21], [22], [23]
- Caveats
- Only 1 of the 31 trials in the review had a low risk of bias [23]. Trials lasted 2 to 3 cycles.
Period pain
Shown to lower period pain scores in women with primary dysmenorrhea when taken in the first 3 to 4 days of the cycle.
The numbers and sources
- Effect
- In 4 placebo-controlled RCTs, ginger during the first 3 to 4 days of the cycle lowered pain scores (reported as -1.85, 95% CI -2.87 to -0.84) [7].
- Population
- Women with primary dysmenorrhea in 7 RCTs, 4 pooled [7].
- Sources
- [7]
- Caveats
- Four pooled trials. The search included Korean, Chinese and Indian databases [7].
Premenstrual symptoms
Shown to lower PMS anxiety, depression, mood and behavioral symptoms modestly against placebo. One small trial found physical and behavioral gains but no mood change.
The numbers and sources
- Effect
- Across 9 RCTs, St. John's wort lowered PMS anxiety (SMD -0.21, 95% CI -0.37 to -0.05), depression (SMD -0.45, 95% CI -0.74 to -0.17), mood disturbance (SMD -0.36, 95% CI -0.66 to -0.06) and behavioral symptoms (SMD -0.43, 95% CI -0.68 to -0.19) against placebo [4]. In a crossover trial of 36 women with mild PMS, 900 mg a day for two cycles improved physical and behavioral symptoms more than placebo. Mood and pain symptoms, anxiety, depression, hormones and cytokines did not differ [5].
- Population
- 1,020 participants in 9 RCTs published from 2000 to 2023 [4]. 36 women aged 18 to 45 [5].
- Sources
- [4], [5]
- Caveats
- One meta-analysis, which searched Iranian regional databases alongside international ones. The authors note a lack of high-quality evidence for some outcomes [4]. The single crossover trial found no mood difference, unlike the pooled result [5].
Period pain
Shown to lower period pain against placebo or NSAIDs in women with primary dysmenorrhea, in few trials with high heterogeneity.
The numbers and sources
- Effect
- Across 5 controlled trials (201 women on valerian, 207 controls), valerian reduced primary dysmenorrhea pain against placebo or NSAIDs (SMD -1.03, 95% CI -1.74 to -0.33, I² 90.40%) [5].
- Population
- Women with primary dysmenorrhea in RCTs published from 2000 to 2023 [5].
- Sources
- [5]
- Caveats
- Heterogeneity was high, the trials were few, and the comparators mixed placebo and NSAIDs. Doses and trial designs varied [5].
Premenstrual syndrome
Shown to improve overall premenstrual symptoms and premenstrual depression over placebo in women with PMS, in mostly low-quality trials from a 1999 review.
The numbers and sources
- Effect
- Across 9 trials, women on vitamin B6 were more likely than on placebo to report better overall premenstrual symptoms (OR 2.32, 95% CI 1.95 to 2.54) and better premenstrual depression (OR 1.69, 95% CI 1.39 to 2.06, 4 trials) [4].
- Population
- 940 women with premenstrual syndrome in 9 published trials [4].
- Sources
- [4]
- Caveats
- The authors rated most trials low quality. Doses ran up to 100 mg a day [4]. The review is from 1999.
PMS symptoms
Shown in one review of 5 trials to lower overall PMS severity, physical symptoms and depression, at very low certainty. Anxiety, cravings and water retention did not change.
Compared with placebo or standard care [68]
The numbers and sources
- Effect
- Across 5 RCTs (436 participants), vitamin D lowered total PMS severity (SMD -0.78, 95% CI -1.30 to -0.26), physical symptoms (SMD -1.00, 95% CI -1.99 to -0.01) and depression (SMD -0.78, 95% CI -1.53 to -0.02). Anxiety, craving and water retention did not change, and no adverse events were reported [68].
- Population
- 5 RCTs with 436 women with PMS [68].
- Sources
- [68]
- Caveats
- Certainty was rated very low, and heterogeneity was substantial. Four of the five trials had some concerns for risk of bias [68].
Period pain
Shown in one meta-analysis of 6 trials to lower period pain more than placebo, with larger effects at 8 weeks or longer.
Compared with placebo [18]; placebo or no treatment [19]
The numbers and sources
- Effect
- Across 6 RCTs, zinc lowered pain severity more than placebo (Hedges's g -1.541, 95% CI -2.268 to -0.814). Longer treatment (8 weeks or more) gave larger reductions (p = 0.003), and higher doses added a small amount per milligram. Adverse events did not differ significantly from placebo (OR 2.54, 95% CI 0.78 to 8.26) [18]. In a Cochrane review, zinc sulfate lowered pain by 0.95 points on a 0 to 10 scale against placebo in one trial (95% CI 0.36 to 1.54, 99 women) [19].
- Population
- 6 RCTs with 739 women with primary dysmenorrhea [18]; one RCT of 99 women within a review of 27 RCTs [19].
- Sources
- [18], [19]
- Caveats
- The Cochrane review rated its evidence low or very low quality [19]. The effect size in [18] is a standardized difference, not points on a pain scale.
Period pain
One small trial found calcium alone lowered period pain 1.6 points on a 10-point scale more than placebo. Calcium with vitamin D did not differ significantly.
Compared with placebo [24]
The numbers and sources
- Effect
- Taken from day 15 of the cycle until pain ended in the next cycle, for 3 cycles, 1,000 mg of calcium lowered mean pain intensity by 1.6 points more than placebo (95% CI 0.6 to 2.6). Calcium with 5,000 IU of vitamin D3 lowered it by 0.7 points, which was not significant (95% CI -0.3 to 1.6). Menstrual blood loss did not differ from placebo in either group [24].
- Population
- 85 university students with moderate or severe primary dysmenorrhea in Iran [24].
- Sources
- [24]
- Caveats
- One small trial. Time and the interaction of time with group had no significant effect on pain [24].
PMS symptoms
One small trial found PMS symptom scores fell more on ginger than placebo over 3 cycles in female students.
Compared with placebo capsules [16]
The numbers and sources
- Effect
- Ginger 250 mg every 12 hours, from 7 days before to 3 days after the start of bleeding for 3 cycles, lowered PMS symptom scores more than placebo at 1, 2 and 3 months (P < 0.0001), across mood, physical and behavioral symptoms. Scores did not differ before treatment [16].
- Population
- 70 female university students with PMS in Tehran, 35 per group [16].
- Sources
- [16]
- Caveats
- One small trial. The abstract gives no effect size [16].
Period pain
Small trials found magnesium relieved period pain more than placebo and cut the need for extra pain medicine, in a 2001 review.
Compared with placebo [18]
The numbers and sources
- Effect
- In three small trials, magnesium gave more pain relief than placebo, and less additional pain medication was needed. The number of adverse effects did not differ [18].
- Population
- Women with primary dysmenorrhea in three small randomized trials [18].
- Sources
- [18]
- Caveats
- The review is from 2001 and its abstract gives no pooled size of the effect. Doses and schedules varied between trials, and the authors could not name a dose or schedule from them [18].
Period pain
Mixed results: two reviews found vitamin E lowered period pain more than placebo, while a Cochrane review of two trials found no difference.
Compared with placebo [16][17]; placebo or no treatment [18]
The numbers and sources
- Effect
- Across 8 RCTs, vitamin E lowered primary dysmenorrhea pain more than placebo in the first month (SMD -1.16, 95% CI -2.16 to -0.17) and the second month (SMD -1.83, 95% CI -2.90 to -0.77), with no serious side effects reported [16]. A review of micronutrients found lower pain on vitamin E than placebo (SMD -0.47, 95% CI -0.74 to -0.20) [17]. A Cochrane review found no difference on a 0 to 10 pain scale (MD 0.00 points, 95% CI -0.34 to 0.34, 2 RCTs, 135 women) [18].
- Population
- 8 RCTs with 1,002 women with primary dysmenorrhea [16]; 16 trials with 1,871 participants aged 13 to 40, 4 of them of vitamin E [17]; 27 RCTs with 3,101 women, mostly students in their late teens or early twenties [18].
- Sources
- [16], [17], [18]
- Caveats
- Heterogeneity was high in the second month (I² 76%) [16]. The Cochrane review rated all its evidence low or very low quality, and most trials were from Iran [18]. The reviews included different trials.
PMS symptoms
Mixed results: in small trials, magnesium eased premenstrual fluid retention in the second month but did not change mood symptoms on its own.
Compared with placebo [19][20]; vitamin B6 [20]; placebo or other nutritional interventions across the trials reviewed [21]
The numbers and sources
- Effect
- In a crossover trial of 200 mg a day, no symptom group differed from placebo in the first month. In the second month, fluid retention symptoms (weight gain, swelling, breast tenderness, bloating) fell more than on placebo (p = 0.009) [19]. In a second crossover trial, magnesium, vitamin B6, both together and placebo did not differ overall, while magnesium plus vitamin B6 lowered anxiety-related symptoms (p = 0.040) [20]. A review of 31 RCTs found insufficient evidence for magnesium on psychological PMS symptoms, and a crossover trial of 54 women found no significant effect of 200 mg a day over 2 months [21].
- Population
- 38 women [19]; 44 women, mean age 32 [20]; 31 RCTs with 3,254 women aged 15 to 50 [21].
- Sources
- [19], [20], [21]
- Caveats
- Trials were small and lasted one or two cycles. Only 1 of the 31 trials in the review had a low risk of bias [21]. The authors of [20] judged absorption from magnesium oxide poor.
Premenstrual syndrome
Limited evidence: the two most tightly controlled of 7 small trials found no benefit for premenstrual syndrome.
The numbers and sources
PMS symptoms
One small trial found PMS scores on vitamin E did not differ from placebo after 2 months.
Compared with placebo [22]
The numbers and sources
- Effect
- On 100 mg of vitamin E a day for 2 months, PMS scores fell in all three groups (vitamin D, vitamin E and placebo), and the differences between groups were not significant (P > 0.05) [22]. A later review notes that only 36 of the 86 women completed the trial [23].
- Population
- 86 women with PMS randomized to vitamin D, vitamin E or placebo [22].
- Sources
- [22], [23]
- Caveats
- One small trial with many dropouts [23].
Therapies
Period pain, compared with no treatment or NSAIDs
Shown in low-quality trials to ease period pain more than no treatment or NSAIDs, comparisons in which no one could be blinded.
Compared with no treatment [28][29]; NSAIDs [28][29]
The numbers and sources
- Effect
- Against NSAIDs, more women had pain relief with acupuncture (OR 4.99, 95% CI 2.82 to 8.82, 4 RCTs, 352 women), and adverse events were less common (OR 0.10, 95% CI 0.02 to 0.44, 4 RCTs, 239 women). Against no treatment, pain scores were lower with acupuncture in all 6 trials that reported them [28]. At 3 cycles after treatment, pain on a visual analogue scale was 47.80 points lower than with no intervention and 29.89 points lower than with NSAIDs [29].
- Population
- Women with primary dysmenorrhea in 42 RCTs [28]; 14 RCTs with 970 women [29].
- Sources
- [28], [29]
- Caveats
- Evidence was low quality, and 7 trials against NSAIDs were too heterogeneous to pool (I² 94%) [28]. The later review rated the evidence low certainty with high risk of bias [29]. Against sham, no difference was found (see above).
PMS and PMDD, compared with waiting list or no treatment
Shown in several trials to ease PMS and PMDD symptoms more than a waiting list or no treatment. A 2009 review had found little evidence.
Compared with waiting list [20][22][23]; no intervention [21]
The numbers and sources
- Effect
- In women with PMDD, 8 weeks of therapist-guided internet CBT improved functional and psychological impairment, interference with everyday life, symptom intensity and symptom disability more than waiting, and the gains held at 6 months [20]. In university students with moderate to severe PMS, internet CBT over 2 cycles lowered total symptom scores to 10.4 against 20.2 with no intervention (adjusted difference -9.9, 95% CI -13.3 to -6.6) and raised quality of life around periods [21]. One-to-one and couple CBT lowered total premenstrual symptoms and distress more than a waiting list [22]. Twelve weekly sessions of cognitive therapy improved symptoms and functioning more than a waiting list [23]. A 2009 review of 7 reports, 3 of them RCTs, found few statistically significant effects [24], while a 2021 review of 32 studies reported symptom reductions in all of them [25].
- Population
- 174 women with PMDD [20]; 92 university students aged 18 to 35 [21]; 83 women with premenstrual disorders, 63 completing [22]; women with PMS referred by doctors [23]; 7 reports [24]; 32 studies [25].
- Sources
- [20], [21], [22], [23], [24], [25]
- Caveats
- Waiting-list and no-treatment controls can inflate effects, and no trial here compared CBT with an attention control or with medication. The 2021 review called for more high-quality research [25].
Period pain, compared with sham acupuncture
Not shown to ease period pain more than sham acupuncture in women with primary dysmenorrhea. The one trial at low risk of bias found no difference.
Compared with sham or placebo acupuncture [28][29]
The numbers and sources
- Effect
- Against sham or placebo, findings across 6 trials were inconsistent, and the only trial at low risk of bias in every domain found no difference at 3, 6 or 12 months [28]. A 2025 review of 14 trials found acupuncture did not ease pain more than sham at 3 cycles after treatment [29].
- Population
- 42 RCTs with 4,640 women with moderate to severe primary dysmenorrhea, 6 of them sham-controlled [28]; 14 RCTs with 970 women [29].
- Sources
- [28], [29]
- Caveats
- The Cochrane authors rated the evidence low quality, from risk of bias, poor reporting, inconsistency and possible publication bias. No sham-controlled trial reported adverse events [28].
Asthma, high blood pressure and period pain
Not shown to treat asthma in children, high blood pressure or period pain. Every high- or acceptable-quality trial found manipulation no better than sham.
Compared with sham interventions [10]
The numbers and sources
- Effect
- All randomized trials of acceptable or high quality found spinal manipulation was not superior to sham for infantile colic, childhood asthma, hypertension, primary dysmenorrhea and migraine. No trial tested whether manipulation prevents any of these conditions [10].
- Population
- 6 randomized trials with 534 participants [10].
- Sources
- [10]
- Caveats
- Few trials for each condition. Six of the 50 researchers at the review summit did not approve the final report [10].
Practices
Period pain, compared with no treatment
Shown to ease period pain in women against no treatment, by about 1.9 cm on a 10 cm scale over 3 months of use, in pooled trials of low certainty.
Compared with no treatment [3][4]
The numbers and sources
- Effect
- Across 25 trials (2,393 women), pain after 3 months was lower with heat than with no treatment (WMD -1.85 cm, 95% CI -2.29 to -1.41). Within 24 hours of a painful period, the difference was larger (WMD -3.52 cm, 95% CI -5.01 to -2.02, 3 trials, 248 women) [3]. An earlier review found one trial of 132 women in which heat lowered pain against no treatment (MD -4.04, 95% CI -4.88 to -3.20) [4].
- Population
- 5,359 women with primary dysmenorrhea in 57 trials [3]. 6 trials [4].
- Sources
- [3], [4]
- Caveats
- Women knew whether they were using heat, so expectation can add to the effect. The reviewers judged the evidence low in certainty and write that heat "may" reduce pain [3]. The earlier review's comparison rests on one trial [4].
Period pain, compared with pain medicines
Shown to ease period pain in women as much as, or slightly more than, NSAIDs or acetaminophen, in two reviews of trials.
Compared with NSAIDs [3]; pain medicines [4]; ibuprofen 400 mg three times a day [5]; acetaminophen 1,000 mg [6]
The numbers and sources
- Effect
- After 3 months, pain was slightly lower with heat than with NSAIDs (WMD -1.10 cm, 95% CI -1.51 to -0.70, 22 trials, 1,938 women), and within 24 hours (WMD -1.50 cm, 95% CI -2.86 to -0.15, 2 trials, 167 women) [3]. Against pain medicines, heating pads lowered pain (SMD -0.72, 95% CI -0.97 to -0.48, 2 trials, 274 women) [4]. Heat with a placebo pill gave mean relief of 3.27 against 3.07 for ibuprofen with an unheated patch. Adding heat to ibuprofen did not raise relief (P = .096) but shortened the time to noticeable relief from 2.79 to 1.5 hours [5]. Against acetaminophen 1,000 mg, a heat wrap gave more relief over 8 hours (2.48 against 2.17, p = 0.015) and less cramping [6].
- Population
- Women with primary dysmenorrhea in 22 trials [3] and 2 trials [4]. 81 women [5]. 344 women [6].
- Sources
- [3], [4], [5], [6]
- Caveats
- The pooled certainty was low [3]. The single-day acetaminophen trial blinded only the investigator [6].
Period pain, compared with an unheated patch
Shown to ease period pain in women more than an unheated placebo patch, in two trials. Mean pain relief over 2 days was 3.27 with heat against 1.95 without.
Compared with an unheated patch with a placebo pill (sham) [4][5]
The numbers and sources
- Effect
- Over 2 days, mean pain relief scores were 3.27 with a heated patch and placebo pill, 3.07 with an unheated patch and ibuprofen, 3.55 with both, and 1.95 with an unheated patch and placebo pill (all P ≤ .001 against the sham) [5]. A review found two trials favoring heat over unheated placebo therapy [4].
- Population
- 84 women, 81 completing, in a double-dummy trial [5]. 6 trials [4].
- Sources
- [5], [4]
- Caveats
- A heated and an unheated patch feel different, so the blinding may be imperfect. The trials are small.
Period pain, compared with sham or no treatment pooled together
Shown to ease period pain in women by 1.39 points with high-frequency and 2.04 with low-frequency TENS, against sham or no treatment pooled together, at low certainty.
Compared with placebo TENS or no treatment, pooled together [5]
The numbers and sources
- Effect
- High-frequency TENS lowered pain against placebo or no treatment (MD -1.39, 95% CI -2.51 to -0.28, 10 trials, 345 women, I² 88%), as did low-frequency TENS (MD -2.04, 95% CI -2.95 to -1.14, 3 trials, I² 0%). High- and low-frequency TENS did not clearly differ (MD 0.89, 95% CI -0.19 to 1.96) [5].
- Population
- 585 women aged 12 to 49 with primary dysmenorrhea in 20 trials [5].
- Sources
- [5]
- Caveats
- The Cochrane review pools placebo and no-treatment arms, so blinded and unblinded comparisons are mixed. Certainty was downgraded for risk of bias [5].
Period pain
Shown in one meta-analysis of 4 small trials to lower period pain more than no yoga in women with primary dysmenorrhea, with a wide margin of uncertainty.
Compared with not doing yoga [19]
The numbers and sources
- Effect
- Across 4 trials, a yoga program lowered period pain more than no yoga (SMD -2.09, 95% CI -3.99 to -0.19) [19].
- Population
- 230 women with primary dysmenorrhea, 129 doing yoga and 101 not [19].
- Sources
- [19]
- Caveats
- Four small trials, with a confidence interval that runs from a very large to a small effect. No trial compared yoga with another exercise [19].
PMS symptoms
Shown in one review of 14 studies to ease overall PMS symptoms and most symptom areas except physical symptoms, in trials that varied widely.
Compared with control groups the source abstract does not describe [20]
The numbers and sources
- Effect
- Across 11 pooled studies, yoga eased total PMS scores, and each symptom area except the physical one [20].
- Population
- Women with PMS in 14 studies, 11 of them pooled [20].
- Sources
- [20]
- Caveats
- The studies differed in design, yoga regimen and outcome tools, publication bias was possible, and the abstract gives no effect sizes [20].
Period pain, compared with sham TENS
Mixed results: one review of sham-controlled trials found TENS eased period pain in women, while another found pain scores did not differ but fewer women needed pain pills.
Compared with sham TENS [2]; placebo TENS [3]; sham or placebo TENS in most trials, a placebo pill in one and usual NSAID use in one [4]
The numbers and sources
- Effect
- In 4 trials that all used sham TENS, pain was lower with TENS (SMD 1.384, 95% CI 0.505 to 2.262) [2]. In 9 trials against placebo, fewer women needed pain medicine (RR 0.43, 95% CI 0.30 to 0.63, moderate quality) and relief lasted longer, while pooled pain intensity did not differ (SMD -4.50, 95% CI -9.90 to 0.91) [3]. Across 13 trials, mostly against sham, pain scores were lower with TENS (MD -1.97, 95% CI -3.13 to -0.81, 8 trials, 398 women, I² 90%), fewer ibuprofen tablets were taken (MD -1.29, 95% CI -2.54 to -0.05), and scores for pain's effect on daily life did not differ (MD 0.01, 95% CI -0.37 to 0.40) [4].
- Population
- 260 women with primary dysmenorrhea in 4 trials [2]. 530 women in 9 trials [3]. 779 women and girls aged 15 to 29 in 13 trials [4].
- Sources
- [2], [3], [4]
- Caveats
- Trials were small, heterogeneity was very high, and the reviews included different trials [3][4]. TENS produces a tingling that a sham device does not fully copy, so blinding may be imperfect.
Period pain, compared with pain medicines and other treatments
Limited evidence: in single small trials, period pain did not differ between TENS and acetaminophen in women. Too few trials compared TENS with NSAIDs for pain.
Compared with acetaminophen [5]; acupressure [5]; interferential current therapy [5]
The numbers and sources
- Effect
- Pain did not differ between high-frequency TENS and acetaminophen (MD -0.98, 95% CI -3.30 to 1.34, 1 trial, 20 women) or low-frequency TENS and acetaminophen (MD -1.48, 95% CI -3.61 to 0.65). Nor did it differ against acupressure (MD -0.66, 18 women) or interferential current (MD -0.03, 95% CI -1.04 to 0.98, 2 trials, 62 women) [5].
- Population
- 18 to 62 women per comparison [5].
- Sources
- [5]
- Caveats
- Very low certainty, from one or two trials per comparison [5].
Daily life
Period pain in trials
Shown in two reviews of trials to lower period pain in women with primary dysmenorrhea, by about 2 to 2.5 cm on a 10 cm pain scale.
Compared with no treatment [23]; mefenamic acid in one trial [23]; comparators of any kind, not described in the source abstract [24]
The numbers and sources
- Effect
- Against no exercise, exercise lowered period pain (SMD -1.86, 95% CI -2.06 to -1.66, 9 RCTs, 632 women, low-quality evidence), about 25 mm on a 100 mm scale. Whether adverse events differed was uncertain [23]. A second review found pain intensity 1.89 cm lower on a visual analogue scale (95% CI 1.09 to 2.96) and pain lasting 3.92 hours less (95% CI 2.97 to 4.86), with moderate-quality evidence for intensity [24].
- Population
- 854 women with moderate to severe primary dysmenorrhea in 12 trials, 754 pooled [23]; 1,681 women in 15 RCTs, 11 pooled [24].
- Sources
- [23], [24]
- Caveats
- Heterogeneity was high in both reviews, and no trial compared exercise with an attention control [23][24]. Trials used stretching, core work, yoga, Zumba or aerobic training, about 45 to 60 minutes three or more times a week [23].
PMS symptoms in trials
Shown in one review of trials to lower overall PMS symptoms more than no exercise, along with psychological, physical and behavioral symptoms, in trials mostly at high risk of bias.
Compared with non-exercise comparator groups [25]
The numbers and sources
- Effect
- Across 7 pooled trials (265 women), exercise of at least 8 weeks lowered global PMS symptom scores (SMD -1.08, 95% CI -1.88 to -0.29, I² 87%). Psychological (SMD -1.67), physical (SMD -1.62) and behavioral (SMD -1.94) symptoms also fell [25].
- Population
- 717 women with PMS in 15 RCTs [25].
- Sources
- [25]
- Caveats
- 87% of trials were at high risk of bias, and heterogeneity was substantial [25].
Lab markers
Period pain
Small studies found slightly lower vitamin D in adolescents with period pain, 16.2 against 17.7 ng/mL in one, and more pain at lower levels.
The numbers and sources
- Effect
- In Asian adolescents, 25-hydroxyvitamin D was 16.17 ng/mL (SD 7.36) in those with primary dysmenorrhea and 17.65 (6.36) in matched controls (P = 0.01), and lower levels went with higher pain scores [29]. In 372 young women with period pain, lower 25-hydroxyvitamin D went with higher pain scores (P = 0.044) [30].
- Population
- 205 adolescents with primary dysmenorrhea and 210 controls [29]. 372 young women at one clinic in Tehran [30].
- Sources
- [29], [30]
- Caveats
- Observational and cross-sectional. The second study had no group without period pain. The gap in the first was 1.5 ng/mL, and both groups averaged below 20 ng/mL [29][30].
Premenstrual symptoms and period cramps
One cohort of midlife women linked hs-CRP above 3 mg/L to more premenstrual mood symptoms, cramps or back pain, bloating and breast pain, but not headaches.
The numbers and sources
- Effect
- Against hs-CRP of 3 mg/L or below, a level above 3 mg/L had adjusted odds ratios of 1.27 for premenstrual mood symptoms (95% CI 1.02 to 1.58), 1.40 for abdominal cramps or back pain (1.09 to 1.80), 1.41 for appetite cravings, weight gain or bloating (1.04 to 1.89) and 1.26 for breast pain (1.02 to 1.55). It was not associated with premenstrual headaches or with reporting three or more symptoms [25].
- Population
- 2,939 women aged 42 to 52, before or early in the menopausal transition, at the start of the Study of Women's Health Across the Nation, from several racial and ethnic groups [25].
- Sources
- [25]
- Caveats
- Cross-sectional, so it cannot show which came first. Covariates, body mass index among those tested, stayed in each model only if they were significant [25]. The women were in midlife, so the result may not describe younger women with period pain.
On a blood test: High-sensitivity C-reactive protein (hs-CRP)
Every finding in the library that measured this test, including studies that were mainly about something else (leaving out those done only in men or only in children).
Shown to lower it
- StrongThunder god vineCautionRheumatoid arthritis
Across 40 RCTs (3,092 patients), tripterygium glycosides added to DMARDs lowered morning stiffness, tender and swollen joint counts, pain scores, CRP, ESR and rheumatoid factor against DMARDs alone (all p < .001).
- StrongTurmericC-reactive protein and other inflammation markers
Shown to lower CRP and some other inflammation markers in adults with inflammatory conditions or diabetes. These are blood markers, not clinical outcomes.
- StrongTurmericRheumatoid arthritis
Across 7 RCTs, DAS28 fell by 1.47 (95% CI -1.68 to -1.26), with lower rheumatoid factor, ESR and CRP.
- ModerateOral corticosteroidsSevere COVID-19 and pneumonia in hospital
In severe community-acquired pneumonia, added corticosteroids lowered deaths (RR 0.47, 95% CI 0.3 to 0.74) and C-reactive protein on day 8 (SMD -0.8, 95% CI -1.11 to -0.5), with no difference in gastrointestinal bleeding or high blood sugar.
- ModerateBeta-sitosterolBlood pressure and other heart risk markers
Plant sterols and stanols lowered systolic blood pressure by 1.55 mmHg (95% CI 0.42 to 2.67), diastolic by 0.84 mmHg, apoB by 0.06 g/L and hs-CRP by 0.25 mg/L.
- ModerateFisetin and quercetin (senolytics)Liver enzymes and lipids in fatty liver disease (quercetin alone)
A 2025 meta-analysis of 7 RCTs (540 patients) with metabolic dysfunction-associated steatotic liver disease found that quercetin lowered ALT, AST, GGT, direct bilirubin and C-reactive protein, lowered total cholesterol, LDL and triglycerides, and raised HDL.
- ModerateGarlicInflammation markers
Shown to lower CRP by about 0.6 mg/L and lower TNF in adults. These are blood markers, and the reviews disagree on IL-6.
- ModerateGingerInflammation markers
Shown to lower CRP, TNF-α and IL-6 in adults, more in people with health conditions. These are blood markers, not clinical outcomes.
- ModerateProbioticsRheumatoid arthritis
Mixed results: reviews agree probiotics lower CRP or IL-6 in rheumatoid arthritis, but disagree on disease activity.
- ModerateTart cherryRecovery after strenuous exercise
A 2026 meta-analysis of 19 trials in trained athletes found faster recovery of maximal strength at every time point (ES 0.63 right after exercise to 4.82 at 96 hours) and lower CRP up to 48 hours (ES -0.46 to -0.73).
- ModerateVitamin DInflammatory bowel disease
In adults, the Harvey Bradshaw Index for Crohn's disease fell by 1.47 points (95% CI -2.47 to -0.47) and hs-CRP fell by 1.58 mg/L.
- ModerateZincBlood sugar
Across 32 placebo-controlled interventions (1,700 participants, 14 countries), zinc lowered fasting glucose by 14.15 mg/dL (95% CI -17.36 to -10.93), 2-hour glucose by 36.85 mg/dL, HbA1c by 0.55% (95% CI -0.84 to -0.27) and hs-CRP by 1.31 mg/L.
- ModerateRed light therapyWeight and waist size in obesity
Across 11 RCTs (569 patients), photobiomodulation improved waistline (mean difference -7.28, 95% CI -9.97 to -5.67), weight (-3.54, 95% CI -5.97 to -1.11) and BMI (-1.18, 95% CI -1.93 to -0.43), and lowered C-reactive protein, total cholesterol and HOMA-IR.
- ModeratePaleo dietInflammation markers
Shown in two reviews to lower CRP about 0.4 to 0.8 mg/L more than comparison diets in adults, with one result sensitive to single trials.
Compared with control diets the source does not describe; a control group the source does not describe
- LimitedBoronJoint pain and arthritis
In 60 adults with knee osteoarthritis, 15 days of calcium fructoborate improved C-reactive protein, fibrinogen and sedimentation rate against placebo, with no serious adverse events.
- LimitedGrape seed extractInflammation
Limited evidence: a 50-trial review found lower CRP, while an earlier review found no effect.
- LimitedTart cherryKnee osteoarthritis pain
One trial found knee pain scores did not differ significantly from placebo in adults with knee osteoarthritis, though CRP fell.
- LimitedUrolithin AMitochondrial and cellular markers
Acylcarnitines, ceramides and CRP fell more than on placebo in older adults over 4 months, and acylcarnitines and CRP fell in middle-aged adults.
- LimitedLymphatic drainage massageMuscle recovery after hard exercise
One trial of 36 combat athletes found drainage after jumping exercise raised pain thresholds and lowered creatine kinase and C-reactive protein more than passive rest.
Compared with passive rest; intense sports massage
- LimitedJuice cleanseStudied in womenInflammation
One trial found the inflammation marker hs-CRP fell on a 7-day lemon detox but not on a calorie-matched placebo juice, in overweight Korean women.
Compared with before the diet, in the same people (overweight Korean women), with a calorie-matched placebo juice group measured the same way
Shown to raise it
- ModerateCLAInflammation and oxidative stress markers
Shown to raise CRP in adults across 14 studies. Sources disagree on oxidative stress, with one marker rising and another falling.
Studies disagree
- StrongDietary nitrateRecovery from muscle damage
Creatine kinase and oxidative stress did not change; C-reactive protein was higher than placebo at 48 hours (SMD 0.55). CRP, IL-6 and TNF-α did not change.
- StrongTart cherryBlood pressure and cardiometabolic markers
Across 21 trials, blood pressure, heart rate, hs-CRP and IL-6 did not change, while CRP fell by 0.39 mg/L (95% CI -0.74 to -0.05, moderate certainty).
- StrongVitamin DRheumatoid arthritis disease activity
Shown to lower disease activity modestly in adults with rheumatoid arthritis. Reviews disagree on CRP, ESR and pain.
- ModerateResveratrolInflammation and blood lipids
Mixed results: reviews disagree on whether CRP falls, and most found no change in LDL or triglycerides.
- ModerateFermented foodsInflammation and C-reactive protein
Mixed results: one meta-analysis found fermented dairy lowered C-reactive protein slightly, while two meta-analyses of kefir trials found no change.
Compared with control groups the abstract does not describe; people who did not drink kefir; control groups; a high-fiber diet, with changes measured over time in each group
- ModerateOlive oilInflammation
Mixed results: one pooled analysis found C-reactive protein fell 0.64 mg/L with olive oil, while a later one found no change in C-reactive protein or interleukin-6.
Compared with control groups, with control diets that varied; trials comparing olive oil or flaxseed oil with controls
- ModerateWhole grainsC-reactive protein and inflammation
Mixed results: two pooled analyses of trials found whole grains lowered C-reactive protein slightly, while a third found no significant change.
Compared with refined grains; refined grains or placebo; control diets low in or without whole grains
- ModerateKeto dietInflammation markers
Mixed results: CRP fell 0.62 mg/dL in one review of short and long trials, and a review of trials lasting a year or more found no CRP difference.
Compared with diets that did not restrict carbohydrates to the level of ketosis
- LimitedFish oilInflammation markers (CRP)
Limited evidence: CRP fell in hemodialysis patients but not with high-dose EPA, in knee osteoarthritis, or in most trials of trained people.
- LimitedPalmitoylethanolamideInflammation markers (CRP, IL-6)
Small trials found lower IL-6 and CRP in diabetic nerve pain, while a COVID-19 trial lowered other markers but not those two.
- LimitedMeditationInflammation and C-reactive protein
Mixed results: one meta-analysis found C-reactive protein fell against active controls, while a review of trials found a fall in three of six that measured it.
Compared with active control groups; waiting list, usual care and active control groups
Tested, and not shown to change it
- StrongTMGHigher cholesterol
Triglycerides, HDL, glucose, CRP, liver enzymes and blood pressure did not change.
- StrongVitamin DPsoriasis severity
Across 4 studies (333 patients), PASI, DLQI and CRP changes did not differ from control.
- StrongNutsInflammation and blood vessel function
Not shown to lower C-reactive protein in two meta-analyses of nut trials. Blood vessel widening, a measure of vessel function, improved in one.
Compared with control conditions the abstract does not describe; control arms without nuts
- ModerateAstaxanthinOxidative stress and inflammation
Shown to lower blood malondialdehyde, an oxidative stress marker, and IL-6 in type 2 diabetes. CRP and TNF-alpha did not change.
- ModerateFish oilCardiovascular outcomes with purified EPA (prescription)
Across 6 trials (42,738 adults) of 1.8 g a day or more of EPA-dominant omega-3, hospitalization for unstable angina fell (RR 0.75, 95% CI 0.66 to 0.87), while cardiovascular death, ischemic stroke and hs-CRP did not change significantly.
- ModerateFish oilRheumatoid arthritis
Across 18 RCTs (1,018 patients), tender joint count fell (SMD -0.59, 95% CI -0.79 to -0.39), while ESR, CRP and DAS28 did not change significantly.
- ModerateLactoferrinRespiratory infections
In adults, IL-6 fell by 24.9 pg/mL, while CRP and NK cell activity did not change.
- ModerateRhodiolaEndurance performance
Creatine kinase (ES -0.84) and lactate fell, and IL-6 and CRP did not change.
- ModerateCold water immersionInflammation
Not shown to lower inflammation. Inflammatory markers rose in the hour after immersion, and post-exercise reviews found no change in C-reactive protein or interleukin-6.
- ModerateWhole-body cryotherapyAnkylosing spondylitis
Shown to improve pain, function and disease activity scores in people with ankylosing spondylitis in a meta-analysis of 5 studies. C-reactive protein did not change.
- ModerateHigh-protein dietBlood pressure and triglycerides
Total and LDL cholesterol, C-reactive protein and HbA1c did not change.
Compared with diets with less protein
- ModerateNordic dietInflammation markers
Not shown to change CRP, IL-6 or TNF-alpha in adults in Nordic countries.
Compared with control groups the source does not describe
- LimitedDeer antler velvetArthritis
In 168 people with rheumatoid arthritis on standard treatment, 6 months of elk velvet antler did not differ from placebo on joint pain and swelling, disease activity, function, quality of life or CRP.
- LimitedGreen-lipped musselInflammation markers (CRP)
Small trials found no change in CRP in knee osteoarthritis, and lower airway inflammation markers in asthma.
- LimitedL-carnitineTMAO and cardiovascular markers
In healthy older women, 24 weeks of L-carnitine raised plasma TMAO tenfold but did not change CRP, IL-6, adhesion molecules or lipids.
- LimitedCuppingInflammation, wet cupping
One trial of 126 people with metabolic syndrome found wet cupping did not change high-sensitivity C-reactive protein over 12 weeks.
Compared with dietary advice alone