Dysmenorrhea

Sedighe Esmaeilzadeh et al. (2025) · Reproductive biology and endocrinology : RB&E

This systematic review and meta-analysis combined 17 randomized controlled trials (15 pooled, 996 women) to ask whether antioxidant supplements ease the pain of endometriosis, a chronic inflammatory condition in which tissue like the uterine lining grows outside the uterus. Oxidative stress (damage from unstable oxygen molecules called free radicals) is thought to feed the inflammation and pain, so antioxidants such as melatonin, vitamins C, D, and E, curcumin (from turmeric), garlic, silymarin (from milk thistle), and resveratrol have been tested. Results across individual trials have been inconsistent, and earlier reviews were narrower, so this one searched seven sources through January 2025 and graded the certainty of the evidence. Included trials enrolled women aged 18 to 49 with confirmed endometriosis, mostly in Iran, plus Egypt, Brazil, the United States, China, and Sweden. Women took an oral antioxidant or a comparator (placebo, standard care, or nothing) for 8 to 24 weeks. The review pooled three pain outcomes using standardized mean differences (a way to combine different pain scales into one measure): painful periods (dysmenorrhea), painful intercourse (dyspareunia), and chronic pelvic pain. Study quality was graded with Cochrane RoB 2, and evidence certainty with GRADE. For painful periods, 12 trials (706 women) showed lower pain with antioxidants (SMD -1.26; 95% CI -2.19 to -0.32, equal to about 3 points on a 0 to 10 scale), but results varied enormously between trials (I² = 90.1%), so the evidence was rated low certainty. Melatonin stood out (SMD -1.89; 95% CI -2.48 to -1.31), while vitamin D, vitamins C plus E, omega-3, resveratrol, and curcumin did not reach significance. Painful intercourse showed no significant effect (SMD -1.01; 95% CI -2.27 to 0.24). Chronic pelvic pain fell in the pooled analysis (SMD -1.07; 95% CI -1.71 to -0.42), but the evidence was very low certainty and the effect vanished when trials with conflicts of interest were removed. Single trials of garlic powder and silymarin reported lower pain, whereas curcumin did not. Only 7 of 17 trials had low risk of bias. The authors say the findings do not support routine antioxidant use for endometriosis pain, and describe melatonin as the most promising candidate for painful periods, pending confirmation. Limitations include very high heterogeneity, small trials, different antioxidants and doses, bigger effects in weaker studies, and little control of baseline vitamin levels or diet. The paper did not report adverse events. The garlic and silymarin findings come from single trials, and publication-bias testing found no small-study effects for chronic pelvic pain. The authors call for larger, standardized trials.

Sophia Tsokkou et al. (2026) · International journal of molecular sciences

This systematic review pulled together seven randomized controlled trials to ask whether vitamin D, vitamin C, and vitamin E supplements affect endometriosis, a long-term inflammatory condition in which tissue like the uterine lining grows outside the uterus and affects roughly 1 in 10 women of reproductive age. Common symptoms include painful periods (dysmenorrhea), chronic pelvic pain, pain during intercourse (dyspareunia), and difficulty conceiving. The vitamins were chosen because vitamin D helps regulate immune signaling, while vitamins C and E act as antioxidants that neutralize reactive oxygen species (unstable molecules that damage cells and add to inflammation). Both processes are central to how endometriosis develops and causes pain. The authors registered their protocol in PROSPERO and searched PubMed, Scopus, and ScienceDirect, screening 5,639 records down to seven eligible trials. Two reviewers screened independently, and trial quality was graded with the Jadad scale and the Cochrane RoB 2 tool. The trials varied widely: vitamin D doses ranged from 2000 IU daily to 50,000 IU weekly, vitamin C and E doses from 343 mg and 84 mg to 1000 mg and 800 IU daily, and treatment lasted from about 8 weeks to 6 months. Because of this variation, results were described narratively rather than pooled. High-dose vitamin D (50,000 IU every two weeks) cut pelvic pain scores by 1.12 points (95% CI -2.1 to -0.09; p = 0.03) and lowered hs-CRP, an inflammation marker, by 0.64 mg/L. A weekly 50,000 IU regimen lowered active β-catenin (a signaling protein linked to lesion invasion) in endometrial tissue. Lower daily doses did not clearly beat placebo, since both groups improved by similar amounts. Vitamin C plus E for eight weeks reduced oxidative stress markers, and one trial reported pain drops of 43% for daily pelvic pain, 37% for painful periods, and 24% for painful intercourse. Pregnancy rates did not rise in the trial that measured them. Side effects were generally minor, mostly occasional digestive upset. Three trials were rated low risk of bias and four had some concerns. The authors describe vitamins as a possible well-tolerated adjunct for pain and oxidative stress, though not for fertility. The evidence base is small, with only seven trials, English-language inclusion only, very different dosing across studies, and no trial using a publicly available preregistered protocol. Few trials checked participants' baseline vitamin levels, so it remains unclear whether any benefit depends on deficiency. The authors call for larger multicenter trials with standardized doses, longer follow-up, and fertility and lesion outcomes.

Bowen Xu et al. (2026) · Frontiers in endocrinology

This open-label randomized trial at Shanghai East Hospital compared two approaches to primary dysmenorrhea (menstrual cramping without an underlying pelvic disease) in 80 women aged 15 to 46: a Traditional Chinese Medicine protocol called Cai's Gynecology Cyclical Therapy, paired with a specific formula called the Stasis-Clearing and Meridian-Warming Method, versus standard ibuprofen. The TCM approach is built on a century-old idea from a Shanghai medical lineage: that treatment should change across the four phases of the menstrual cycle rather than staying the same throughout. Forty women received ibuprofen (a common anti-inflammatory pain reliever) for two days during each period, while the other forty received herbal decoctions -- different formulas depending on the cycle phase -- for three full menstrual cycles. Researchers tracked pain on a 0-to-10 visual pain scale and a symptom-severity score, and checked whether pain returned in the month after treatment ended. People collecting the follow-up data did not know which treatment each woman had received. Both treatments worked well overall (97.5% of women improved in each group), but the pattern of improvement differed. Ibuprofen relieved pain faster in the first month, as expected for a direct pain reliever. The herbal treatment started more slowly but kept improving month after month, and by the third month the two treatments were statistically equivalent on both pain and symptom scores. The most striking difference came after treatment stopped: only about 13% of the herbal-treatment group had their pain return the following month, compared to about 90% of the ibuprofen group. No side effects were reported in either group throughout the study. The researchers suggest this gap in relapse rates may reflect a real difference in how the two approaches work -- ibuprofen blocks pain-causing chemicals only while it is being taken, whereas the herbal protocol may produce a more lasting change. However, because patients and treating doctors could not be kept unaware of which treatment they were giving or receiving (an inherent challenge when comparing herbal decoctions to a standard pill), and because the study involved one hospital and a single follow-up cycle, the authors call for larger, multi-site studies with longer follow-up to confirm these findings.

Jihye Seo et al. (2020) · Medicine

This systematic review and meta-analysis pooled 14 randomized controlled trials (1,215 women, mostly from China with one from Japan) exploring whether Dangguijagyag-san (DJS) - a traditional East Asian herbal formula also called Danggui Shaoyao San - helps primary dysmenorrhea (PD), the cramping menstrual pain that occurs without an underlying pelvic disease. PD is common, estimated to affect 16-91% of women of reproductive age, and is driven by elevated uterine prostaglandins causing muscle spasm; standard NSAID and hormonal treatments carry gastrointestinal and other side-effect risks, which is part of why researchers keep examining herbal alternatives. The review followed a pre-registered protocol and searched eight medical databases through April 2019. The included trials compared DJS - most often prepared as a decoction (a boiled herbal liquid), given over roughly three menstrual cycles - against NSAIDs (5 trials), a placebo (1 trial), other herbal formulas (6 trials), or NSAIDs with moxibustion added to DJS (2 trials). The main outcome tracked was the total effective rate, a practitioner-judged measure of symptom improvement, alongside pain scores on a visual analogue scale in some trials. Pooled results favored DJS across every comparison. Against NSAIDs, DJS produced a higher effective rate (relative risk 1.16, meaning about 16% more improvement events, 95% confidence interval 1.08-1.24, with no meaningful variation between trials). Against placebo, DJS reduced pain scores and cut how often women needed rescue pain medication during their period. Against other herbal formulas, DJS again showed a higher effective rate (RR 1.24), an advantage that held up most consistently when DJS was prepared as a decoction rather than a granule or capsule. Adding moxibustion (heated-herb therapy at acupuncture points) to DJS outperformed NSAIDs alone (RR 1.47). Side effects were reported in only a handful of trials and were mostly mild digestive complaints, less frequent in the DJS groups than the NSAID groups. The review's authors rated the overall certainty of this evidence as moderate to low: most trials did not clearly describe how they randomized or concealed group assignment, could not blind participants to which herbal or drug treatment they were taking, and were often small (many under 100 participants), all conducted in East Asia. The findings do not establish how DJS performs in other populations or over longer treatment periods, and the authors call for larger, more rigorously designed trials to confirm the effect.

Ángel Rodríguez-Ruiz et al. (2024) · Medicina (Kaunas, Lithuania)

This randomized controlled trial with 44 women explored whether a four-week "HAMMAM" program -- combining hydrotherapy (therapeutic water bathing at varying temperatures) and Swedish massage (a full-body technique using kneading, stroking, and tapping to relax muscle tissue and improve circulation) -- could ease pain in women with endometriosis-related chronic pelvic pain that had not improved with standard medical treatment. Endometriosis is a condition where tissue similar to the uterine lining grows outside the uterus, commonly causing pain during menstruation (dysmenorrhea, governing cyclical cramping) and intercourse (dyspareunia) that standard analgesics and hormonal therapy fail to relieve in roughly a third to half of patients. Women aged 20-50 with confirmed endometriosis and pelvic pain rated at least 4 out of 10 were randomly assigned to the HAMMAM group (21 women) or a control group continuing usual care (23 women) at a hospital in Granada, Spain. The HAMMAM group attended three 90-minute sessions over four weeks at a bathhouse: a 60-75 minute circuit of warm, hot, and cold water baths plus a steam room, then a 15-minute Swedish massage with essential oils; the last session added a traditional exfoliating scrub. Pain was measured on a 0-10 scale, and pressure sensitivity with a handheld algometer. The HAMMAM group reported significantly less menstrual pain (p = 0.035, a large effect) and pain during intercourse (p = 0.020, a moderate-to-large effect) after the program compared with the control group. Pain interfering with sleep also dropped notably (p = 0.018), and pressure pain thresholds in the pelvic region rose (p = 0.029, meaning the area became less sensitive to pressure -- a sign of reduced pain sensitization), with the strongest change at the left groin ligament (p = 0.006). Everyone attended all sessions (100% adherence) and rated satisfaction at 9.71 out of 10, with no adverse events. However, overall pelvic pain ratings, catastrophic thinking about pain, general subjective well-being, and endometriosis-specific quality of life did not change significantly, showing the benefits were concentrated in specific pain measures rather than global wellness. For women whose endometriosis pain persists despite conventional treatment, this suggests a short, low-intensity spa-style program combining water therapy and massage may meaningfully ease menstrual and intercourse pain and pain-disrupted sleep, with high satisfaction and no safety concerns. Because hydrotherapy and massage were only tested together, it is not yet known which component -- or their combination -- drives the benefit, and the small, single-site sample limits how broadly these results apply. Larger trials testing each therapy alone are needed before firm clinical recommendations can be made.

Ziqing Soh et al. (2025) · Journal of food and drug analysis

This double-blind, randomized, placebo-controlled trial with 30 young Malaysian women explored whether a beverage combining chamomile and l-theanine could ease primary dysmenorrhea - menstrual cramping that occurs without any underlying pelvic disease. Chamomile (Matricaria recutita) is a flowering herb long used as a calming remedy; the study intervention used a standardized flower extract of it. L-theanine is a non-protein amino acid concentrated in tea leaves (Camellia sinensis), used in supplements to support relaxation. The trial paired both in a functional beverage (CTT) and tested it against a chamomile-flavored placebo (non-CTT) to see whether the combination eased pain, mood, and sleep during menstruation. Thirty women aged 18-30 with primary dysmenorrhea (pain rated at least 4 of 10 on a visual scale across three cycles) were randomly split into a CTT group (480 mg chamomile extract plus 200 mg l-theanine daily) or a non-CTT control group, drinking two 240 mL packs daily - one on waking, one before bed - for five days spanning two days before their period through its third day. Pain was tracked with two 0-10 scales, symptoms with the 18-item Cox Menstrual Symptom Scale, sleep with the Pittsburgh Sleep Quality Index, and mood with the Profile of Mood States. Compared to their own baseline, women drinking CTT saw pain scores drop by roughly 57% on both pain scales (p<0.001), a large reduction over five days. Eight menstrual symptoms also eased significantly, including lower abdominal pain (down 53%), back pain (down 56%), and irritability (down 45%, all p<0.05). Mood shifted too: depression scores fell 12% and vigor (energy and alertness) rose 62% (p<0.05). On sleep, only "daytime dysfunction" - grogginess, poor concentration, and low energy during the day - improved (down 32%, p<0.05); overall sleep quality, how long it took to fall asleep, and total sleep time did not change significantly. Hemoglobin levels, checked with a finger-prick test, were unaffected in either group, likely because red blood cells take weeks to months to regenerate, too slow to show up in five days. Interestingly, the placebo group also felt calmer on a few measures, which the researchers link to the shared chamomile scent and flavor rather than to any active ingredient. For young women managing primary dysmenorrhea without relying on NSAIDs, a short course of this chamomile-l-theanine beverage appears to meaningfully ease pain and several physical and emotional symptoms, with no reported side effects. Because chamomile and l-theanine were only tested together, it is not yet clear how much each contributes individually, and the tiny sample (15 per group) and single five-day cycle mean the results are preliminary. Longer trials spanning multiple cycles, larger and more diverse groups, and a scent-neutral placebo are needed before firmer conclusions can be drawn.

Yincong Xu et al. (2020) · The Journal of international medical research

Painful periods are one of the most common health complaints among women of reproductive age — affecting anywhere from 16% to 91% — and the standard treatment, anti-inflammatory painkillers like ibuprofen, fails for roughly one in four women. This 2020 meta-analysis pooled the randomized trial evidence for three familiar kitchen herbs: cinnamon, fennel and ginger. In Traditional Chinese Medicine, menstrual pain is understood as cold dampness stagnating in the channels serving the uterus, and all three herbs are classically used to warm the meridians (the body's energy channels) and disperse that cold. The researchers combed four major research databases for randomized controlled trials — the strongest single-study design — where women with primary dysmenorrhea (period pain without an underlying pelvic condition) received one of the herbs or a placebo. Nine trials qualified, covering 647 women, most of them students aged 15 to 25. Seven of the nine trials rated as high quality on standard scoring. The herbs worked. Ginger showed the strongest effect, lowering pain scores by nearly 3 points on a 10-point scale compared with placebo (WMD = 2.902, p < 0.001 — a difference women would clearly feel). Cinnamon lowered pain by about 1.8 points (WMD = 1.815) and was the only herb that also shortened how long the pain lasted (by about 16 minutes per episode, WMD = 16.200). Fennel helped more modestly (WMD = 0.528, p = 0.011). The benefit held when only the highest-quality trials were analyzed, and earlier research has found ginger comparable to ibuprofen and mefenamic acid for this purpose. These effects have a known biological basis: compounds in these herbs (eugenol, gingerols) reduce prostaglandins — the chemicals that trigger the intense uterine cramping behind period pain. Typical study dosages were practical: ginger 250-500 mg capsules three times daily during the first 3-5 days of the period, and cinnamon around 1-3 grams daily for 3 days. The honest caveats: all nine trials were conducted in Iran, samples were small, and results varied considerably between studies — so larger, more diverse trials are needed before firm clinical recommendations. Still, for a low-cost, low-risk option with a plausible mechanism, this is among the better-supported uses of herbal medicine for a specific condition.