The pathogenesis of dysmenorrhea is largely attributed to the excessive release of prostaglandins (PG), which leads to excessive uterine contractions, reduced uterine blood flow, and nerve hypersensitivity, thereby triggering dysmenorrhea. The synthesis of PG is limited by the availability of the free fatty acid precursor, arachidonic acid, which is regulated by cyclic adenosine monophosphate (cAMP). Through cAMP, the production of PG can be stimulated by substances such as adrenaline, peptide hormones, and steroid hormones, as well as by mechanical stimuli and tissue injury. Arachidonic acid is extracted from phospholipids by the lysosomal enzyme phospholipase A2. The large release of prostaglandins results in excessive uterine contractions, reduced uterine blood flow, and nerve hypersensitivity, all of which contribute to dysmenorrhea (4). Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate pain through a mechanism that involves the production of prostaglandins. Interestingly, many vitamins, such as vitamin D and vitamin E, are believed to participate in the molecular pathways of prostaglandins (5–7).

In recent years, herbs have commonly been used to treat primary dysmenorrhea. In traditional Chinese medicine, dysmenorrhea is believed to be caused by the stagnation of cold and dampness in the uterus due to drinking cold beverages, being exposed to rain, or coming into contact with water. Blood coagulates when exposed to cold, leading to a lack of smooth flow in the uterus, causing stagnation and resulting in pain. Therefore, the treatment principle for dysmenorrhea should focus on warming the meridians, dispersing the cold, and removing dampness. As commonly used natural products, cinnamon (Cinnamomum zeylanicum), fennel (Foeniculum vulgare), and ginger (Zingiber officinale) all warm the meridians, disperse cold, and remove dampness.

Diet and nutrition are crucial for maintaining overall health, including that of women. Gene-nutrient interactions play a significant role in health management and disease prevention. Previous studies have analyzed the potential impact of certain foods on dysmenorrhea, highlighting the protective effects of increasing the consumption of fruits, vegetables, fish, and dairy products on dysmenorrhea, while foods such as coffee, fats (42), and sugary foods are considered susceptible to primary dysmenorrhea (43, 44). The active ingredients in pomegranate juice can reduce uterine contractions and treat uterine tension disorders, with the potential to prevent preterm birth and dysmenorrhea. However, further research is needed to determine its mechanism of action (45). Honey and tryptophan capsules have been found to relieve the same level of pain in women with primary dysmenorrhea (46, 47). Moreover, honey has fewer side effects and pharmacological complications, so it is recommended for pain relief.

In fact, Barnard (48) found that women on a low-fat diet had a significantly reduced severity of primary dysmenorrhea. A Cochrane systematic review found that vitamins B1 and B6 and fish oil (omega-3 fatty acids) were more effective than placebos in reducing the severity of primary dysmenorrhea pain (49). In this study, the severity of dysmenorrhea in the diet and control groups was 7.14 ± 1.3 and 7.09 ± 1.4, respectively, before the treatment. After dietary treatment, the severity of dysmenorrhea in the diet group was significantly lower than that in the control group (control group: 6.74 ± 1.97, diet group: 5.15 ± 1.15). Research by Onieva-Zafra, MD et al. (50) found that women who ate fewer than two servings of fruit per day were more likely to experience dysmenorrhea. Similarly, women who enjoyed beans and ate them more than once a week were also more likely to experience dysmenorrhea. Compared to women with dysmenorrhea, those without dysmenorrhea had higher daily intakes of strawberries and olive oil, while women with dysmenorrhea who ate pickled ham at least once a week had slightly higher consumption and percentage. Zakaria IA et al. (51) confirmed that probiotics showed potential in reducing non-steroidal anti-inflammatory drug (NSAID) usage and improving pain and mental health. In a study conducted by Abu Helwa et al., skipping breakfast was identified as the strongest predictor of the severity of dysmenorrhea (43). Therefore, we can conclude that dietary interventions are an effective non-pharmacological treatment for young girls to alleviate the severity of primary dysmenorrhea symptoms. However, these studies have some limitations. The sample sizes are small, and thus, there is insufficient power to detect significant differences in outcomes such as inflammatory markers and the frequency of NSAID usage. The confounding effect of NSAID use was not considered, and although self-reports were used, they are susceptible to reporting bias. Table 1 summarizes the key clinical trials on ingestible substances for primary dysmenorrhea.

Transcutaneous Electrical Nerve Stimulation (TENS) delivers pulsed electrical currents across the surface of the skin to stimulate peripheral nerves, thereby alleviating pain. The pain gate theory, proposed in 1965, suggests that large-diameter (Aβ) afferent fibers (which carry vibration, touch, etc.) reduce pain perception by inhibiting nociceptive activity in the dorsal horn of the spinal cord (52). TENS induces analgesia by stimulating large-diameter fibers. TENS produces pain relief at the spinal cord segment level and is considered to have an additional spinal segment effect. It can reduce dorsal horn neuronal sensitization (53) caused by inflammation, alter the levels of neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine, which are believed to participate in inhibiting pain transmission (54), and regulate the activity of glial cells that provide support and surround neurons in the spinal cord (55). Furthermore, TENS may influence endogenous analgesia. The descending activity transmitted through the periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) in the brainstem may exert inhibitory effects at the segmental level (56). This PAG-RVM relay segmental inhibition is partly mediated through opioid pathways (56, 57).

Clinical studies by Guy M et al. (58) have confirmed that, compared to the control group, the TENS group of primary dysmenorrhea patients experienced a 54% reduction in pain. Clinical reviews by Han S et al. (59) also confirmed that both high-frequency and low-frequency TENS can alleviate pain compared to a placebo or no treatment. Therefore, TENS is highly effective in treating primary dysmenorrhea. However, to achieve optimal TENS efficiency, the most important parameter is the intensity of the current. The intensity should continuously increase throughout the treatment to maintain a strong sensation and avoid habituation. Due to the risk of bias, the certainty of evidence is reduced. Future randomized controlled trials (RCTs) should focus more on secondary outcomes such as the need for additional analgesics, limitations on daily activities, or health-related quality of life, and ensure a low risk of bias.

Acupuncture has been practiced for thousands of years as a complementary and alternative therapy for treating primary dysmenorrhea. Previous acupuncture studies on dysmenorrhea have also found pain relief, which supports these research findings. The improvement of dysmenorrhea symptoms in primary dysmenorrhea patients may be attributed to acupuncture's central and peripheral analgesic effects, neuroendocrine activity, and the expression of related receptors.

First, from a central perspective, acupuncture stimulation of acupoints has been shown to trigger the release of endorphins in the periaqueductal gray (PAG), arcuate nucleus, and caudate nucleus (60). These structures send projections to the dorsal horn of the spinal cord via the dorsal column. Wang Y et al. (61) found in a comparison between true acupuncture and sham acupuncture that there were changes in resting-state functional connectivity (FC) between the rostral anterior cingulate cortex (rACC) and the left central anterior gyrus after treatment. Baseline rACC-left central anterior gyrus FC was negatively correlated with short-term pain relief, while changes in rACC-left central anterior gyrus FC were positively correlated with short-term pain relief after acupuncture treatment. These findings support the importance of rACC-left central anterior gyrus resting-state FC in modulating primary dysmenorrhea (PDM) pain intensity through acupuncture, which may clarify the central mechanism of acupuncture in treating PDM.

From a peripheral perspective, Pomeranz et al. proposed that acupuncture stimulation activates A-δ and C afferent fibers in muscles (62). During acupuncture at points such as SP6, SP8, and Ren 4, signals are transmitted to the spinal cord and then relayed to the midbrain via afferent pathways. It has been reported that acupuncture can stimulate nerves in local tissues, leading to the release of neuropeptides, which cause vasodilation and increase blood circulation in the target area. This increase in blood circulation dilutes pro-inflammatory molecules such as prostaglandins, kinins, and histamine (which trigger pain) within the vessels; enhances tissue oxygenation; promotes drainage and a “cleansing” effect; and clears tissue debris and byproducts of tissue damage.

Animal studies have shown that acupuncture may help alleviate dysmenorrhea symptoms by regulating the neuroendocrine activity of the hypothalamic-pituitary-ovarian (HPO) axis and the expression of related receptors (63). The role of vascular changes in the causality of dysmenorrhea is well-documented. Previous research has suggested that dysmenorrhea is caused by reduced blood flow due to excessive uterine activity. This occurs when uterine contractions decrease blood flow, which can be alleviated by increasing blood circulation and using antispasmodics (64). Acupuncture has been shown to increase nitric oxide levels, which relax smooth muscles and help inhibit uterine contractions, thereby reducing spasms and other dysmenorrhea symptoms (65). Acupuncture may also alter the metabolism of substrates involved in the ascending facilitation pathways, such as N-methyl-D-aspartate (NMDA) receptors (66), substance P (67), and interleukin-1 (68), as well as the descending inhibitory pain pathways, including endogenous opioids (69), serotonin (70), and norepinephrine (71).

These findings suggest that acupuncture is a safe and acceptable treatment for women. Acupuncture has long been used to manage various types of pain, with substantial evidence supporting its effectiveness in pain management (72). The World Health Organization (WHO) recommends acupuncture for several conditions, including primary dysmenorrhea (PD) (73). Acupuncture actively regulates kidney-chong-ren-intrauterine hormone levels, affects the neuroendocrine system of patients, increases prostaglandin E2 (PGE2) levels, decreases prostaglandin F2α (PGF2α) levels, and alleviates symptoms and pain in PD patients (74). Three high-quality randomized controlled trials (RCTs) indicate that those receiving acupuncture experience less pain than those receiving placebo treatments (75–77). Cho et al. (78) found that acupuncture was significantly associated with pain reduction compared to drug treatments or herbal therapies. Furthermore, one study found no differences in the reduction of average visual analog scale (VAS) scores among different acupuncture points (77). However, due to the study design, it only demonstrated the effects of different acupuncture points on primary dysmenorrhea, and the overall impact of acupuncture therapy on the condition could not be excluded. Additionally, the relatively small number of participants in these studies might reduce statistical power. Therefore, the potential effects of acupuncture-related therapies need to be validated through large, well-designed trials with randomization, blinding, and control groups.

Shiatsu is defined as a form of needleless acupuncture, primarily aimed at stimulating energy channels called meridians and specific areas associated with particular organs by applying pressure (79). This technique involves applying pressure, and it has been shown to reduce muscle tension and promote relaxation in various areas of the body. Shiatsu is also known as acupressure, and research indicates that acupressure can alleviate menstrual symptoms (80), reduce the severity and duration of menstrual pain, as well as alleviate distress and anxiety. Additionally, it helps improve the quality of life and well-being of patients, providing psychological support and promoting self-care (81). As pointed out in the Korakaba theory, dysmenorrhea is an issue affecting comfort needs on four levels—physical, psychological, social-cultural, and environmental. Shiatsu not only alleviates pain through its sedative and analgesic effects but also enhances comfort. Existing evidence suggests that acupressure increases the release of endogenous opioids, such as endorphins, as well as neurotransmitters, including serotonin, by stimulating free nerve endings, which provide analgesic and sedative effects (82, 83). Most studies have also shown that it can improve pain intensity in primary dysmenorrhea. Moreover, it has been demonstrated that shiatsu can stimulate the secretion of endorphins, which are neurochemicals that relieve pain, as well as enhance blood circulation and oxygen supply, thus promoting relaxation.

Various clinical studies have examined the impact of acupressure on menstrual discomfort. Two studies conducted in Taiwan showed that acupressure at the Sanyinjiao acupoint significantly reduced dysmenorrhea pain and distress in adolescent girls during a 3- to 6-month follow-up period (84, 85). Another Taiwanese study involving 134 girls with dysmenorrhea found that after 6 months of follow-up, participants who received acupressure at the Hegu and Sanyinjiao acupoints showed significant reductions in menstrual pain, menstrual distress, and anxiety during menstruation (86). A study by Chen H M et al. (87) demonstrated the short-term, medium-term, and long-term effects of acupressure on relieving menstrual distress and confirmed that acupressure can be a safe, simple, non-pharmacological treatment for menstrual discomfort and low back pain. Thus, we can conclude that acupressure is an effective method for managing primary dysmenorrhea and, as a low-cost, easy-to-use, and non-pharmacological treatment, women can apply this method anywhere. However, there is a need for higher-quality randomized controlled trials with larger sample sizes to validate our conclusions. Future studies should explore acupoint interventions targeting other dysmenorrhea symptoms to provide more comprehensive care for dysmenorrhea patients. Additionally, to determine the effectiveness of acupressure for pain relief, it is crucial to appropriately adjust the stimulation dose, including the frequency, duration, and intensity of application.

Multiple pieces of evidence suggest that aromatherapy is an effective intervention for reducing dysmenorrhea. Aromatherapy has historically been used for various purposes and forms, such as massage, inhalation, and bathing. Because these methods can be easily used in public by anyone, aromatherapy offers positive effects for users. It can enhance participants’ satisfaction, improve psychological stability (such as reducing depression, anxiety, and stress), and affect hormones, endocrine glands, and the circulatory system. Aromatherapy also promotes bodily functions, such as reducing pain and improving memory and concentration. Many types of essential oils used in aromatherapy have therapeutic functions for the body, mind, and spirit. Commonly used essential oils in aromatherapy include lavender, rose, geranium, and marjoram, with lavender being the most frequently used. All of these oils have antispasmodic and analgesic effects, making them beneficial for dysmenorrhea (88).

Furthermore, the effectiveness of aromatherapy essential oils may vary depending on the method of blending. By mixing oils together, a synergistic effect can be achieved (89). Therefore, it is necessary to determine standardized protocols through research on the selection of oils, their blending ratios, and the methods and duration of application. Additionally, the effectiveness of aromatherapy in antiviral, antimicrobial, and anti-inflammatory actions has been proven. Inhalation of aromatherapy can stimulate the olfactory system, increase parasympathetic nervous activity, reduce sympathetic nervous activity, and release neurotransmitters (such as endorphins), thereby effectively relieving pain and anxiety.

A study by Bakhtshirin F et al. (90) confirmed that, compared to placebo massage, lavender massage significantly reduced the VAS pain score. Statistically, lavender massage had a greater impact on the severity of primary dysmenorrhea than placebo massage. Raisi Dehkordi Z et al. (91) Conducted an experimental clinical trial with 96 female students living in dormitories at Tehran University of Medical Sciences in 2011. This study showed that inhaling lavender was effective in alleviating dysmenorrhea symptoms and could be safely used, as it had no side effects for all patients, being simple and cost-effective. However, there seems to be high heterogeneity among these studies, likely due to differences in the duration and timing of aromatherapy applications. Therefore, future research should compare the optimal application methods, cycles, and durations of aromatherapy. Studies must be rigorous, employing repeated research on the oils used during the intervention and experimental treatment periods, as well as strict control of external variables and study design, using standardized protocols to improve the quality of such evidence.

Exercise is widely used as a way to alleviate daily stress and control chemical changes in the immune system. Previous studies have shown that increasing progesterone levels through exercise can reduce the production of prostaglandins and pro-inflammatory cytokines, thereby decreasing pain (92, 93). Further research has indicated that exercise can reduce stress by decreasing sympathetic nervous system activity and increasing parasympathetic nervous system activity during rest, while also alleviating menstrual symptoms. Dysmenorrhea may be caused by increased uterine muscle contractions, which are mediated by the sympathetic nervous system (94). Stress contributes to increased sympathetic activity and may intensify uterine contractions, leading to greater pain during menstruation. Exercise that relieves stress can reduce sympathetic nervous system activity, thereby reducing menstrual symptoms.

Beta-endorphins, which act as natural painkillers, are released during exercise. Chantler et al. (95) suggested that exercise reduces the severity and duration of dysmenorrhea due to the release of endorphins, relaxation, stress relief, and improved blood flow. Mohammadi et al. concluded that regular and continuous aerobic exercise can control primary dysmenorrhea and heavy menstrual bleeding. Research by Aganoff and Boyle (96) indicated that regular aerobic exercise can improve mood and promote physical relaxation. Yoga is recommended as a generally safe intervention with almost no adverse side effects when practiced under the guidance of a trained instructor and has been proven to effectively alleviate primary dysmenorrhea.

Yoga not only stimulates the release of beta-endorphins but may also promote physical and mental health by downregulating the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This effect has been shown to reverse the negative impact of stress on the immune system, reduce inflammatory markers, and lower stress, anxiety, heart rate, blood pressure, depression, and insomnia. Increasing evidence suggests that yoga can also improve quality of life by reducing pain through the release of pain-relieving endorphins. Low-quality evidence indicates that exercising for approximately 45–60 min, three times a week or more, regardless of intensity, may significantly reduce dysmenorrhea intensity by about 25 mm on a 100 mm VAS scale (97). Therefore, exercise is certainly effective in reducing the pain intensity of primary dysmenorrhea.

The association between smoking and dysmenorrhea is well-known, involving various physiological and psychosocial factors that can exacerbate menstrual pain. On one hand, smoking causes vasoconstriction, reducing blood flow to the uterus, and increases menstrual pain by enhancing uterine muscle contractions and reducing oxygen delivery (100). On the other hand, smoking directly affects the endocrine regulation of menstruation, leading to an increase in prostaglandins, which are associated with inflammation and pain, potentially worsening dysmenorrhea. Additionally, smoking may disrupt estrogen metabolism, resulting in menstrual irregularities and increased pain (101). This is related to the anti-estrogenic extra-ovarian effects of smoking, which alter estrogen binding through serum proteins or estrogen receptors, enhance the metabolism of exogenous estrogen, or reduce the conversion of circulating androgens into estrogen, thereby affecting estrogen activity (102). Furthermore, since ovarian atrophy has been observed in animals exposed to smoke, smoking may have a direct toxic effect on the ovaries, although the reversible effects observed after smoking cessation do not fully support this.

Finally, from a psychosocial perspective, smoking as a coping mechanism for stress profoundly impacts menstrual health (103, 104). Stress itself often amplifies menstrual discomfort. Moreover, smokers’ health awareness and behaviors can influence their pain perception and management methods, affecting the severity of dysmenorrhea (105, 106).

Epigallocatechin-3-gallate (EGCG) in green tea can limit the biosynthesis of prostaglandins, such as prostaglandin E2 (PGE2) (107). Currently, non-steroidal anti-inflammatory drugs (NSAIDs) target the COX pathway to reduce the accumulation of prostaglandins, thereby decreasing pain intensity. EGCG provides a natural alternative to NSAIDs, which may act through similar mechanisms. In a study on chronic inflammation and its association with cancer, it was found that EGCG can limit the synthesis of PGE2 in acellular and human whole blood assays, possibly by inhibiting microsomal prostaglandin E synthase-1 (mPGES-1), an enzyme important in catalyzing the COX pathway (108). This conclusion was further validated in subsequent studies on human monocytes (109). Overall, these preliminary data suggest that EGCG can modulate prostaglandin synthesis through the COX pathway, potentially alleviating dysmenorrhea in women.

Additionally, drinking thyme tea can reduce the production of prostaglandins (PGs) by inhibiting the COX-2 pathway (110) and prevent oxidative stress by clearing lipid peroxide free radicals (oxidative stress index) in women with dysmenorrhea. Several studies have shown that women with dysmenorrhea have higher levels of lipid peroxides compared to normal women. Excessive production and release of PGs, especially PGF2α, in the endometrium lead to excessive activation of the endometrium and subsequent uterine hypoxia and ischemia (111). This tissue damage in the uterus activates phospholipase A2, which hydrolyzes cell membrane phospholipids, further spreading lipid peroxide free radicals and the production of arachidonic acid (a precursor for prostaglandin synthesis), worsening the severity of primary dysmenorrhea. The phenolic compounds in thyme leaves may inhibit the activity of phospholipase A2 and the subsequent arachidonic acid pathway (112, 113).

Alcohol has a significant impact on the hormonal balance in women, which is crucial for regulating the menstrual cycle. The disruption of hormonal levels caused by alcohol can exacerbate dysmenorrhea. In addition, alcohol stimulates the release of vasopressin, a hormone that constricts blood vessels, which may increase menstrual pain. Furthermore, alcohol is a diuretic, potentially leading to dehydration, which can worsen dysmenorrhea. Alcohol also lowers magnesium levels in the body, and magnesium is known to help relieve muscle spasms. Additionally, alcohol enhances the body's inflammatory response, which could intensify dysmenorrhea symptoms (114, 115).There is also evidence suggesting that alcohol may directly affect uterine muscles, increasing the severity of dysmenorrhea. However, individual responses to alcohol vary greatly and are influenced by factors such as alcohol consumption levels, overall health, and genetic predisposition. Therefore, while smoking or drinking alcohol alone may not have a substantial impact on the severity of dysmenorrhea, using both simultaneously can increase the risk of experiencing more severe menstrual pain.

Coffee, one of the most consumed beverages globally, has a controversial role in managing primary dysmenorrhea pain, with existing research showing conflicting results. Zeru A B et al. (116) observed a direct independent association between coffee consumption and primary dysmenorrhea in their final model. Compared to daily coffee drinkers, those who do not drink coffee or drink it infrequently (once a week or less) had an 88% and 86% lower likelihood of experiencing primary dysmenorrhea, respectively. Similarly, previous studies conducted in Ethiopia, Turkey (117), and Kuwait (110) have indicated that caffeinated beverages may increase the risk of primary dysmenorrhea.

Although the mechanism by which coffee exacerbates dysmenorrhea remains unclear, one possible explanation is the vasoconstrictive effect of caffeine, which reduces blood flow to the uterus, thus intensifying menstrual pain. However, coffee is one of the most widely consumed caffeinated beverages worldwide, and caffeine, a naturally occurring alkaloid (118), has been shown to help manage pain. Caffeine competitively binds to adenosine receptors, inhibiting their important role in pain modulation and signal transduction (119). Furthermore, decades of clinical research have evaluated and proven the adjuvant analgesic effect of caffeine (120), and many over-the-counter (OTC) pain relievers now include low doses of caffeine as an adjunct.

Research by Soler-Martínez R et al. (121) confirmed that coffee extracts could prevent neuropathic pain caused by spinal cord injury, with the major polyphenolic compounds in coffee reducing reflexive pain responses. For example, chlorogenic acid, the primary polyphenolic compound extracted from coffee, has anti-inflammatory properties, reducing oxidative stress and inflammatory mediators, thus alleviating pain (122).

The controversy likely arises because most of the current studies are small-sample, single-center observational trials. Future large-sample, multi-center clinical trials could enhance the credibility of the evidence. Additionally, further research into the underlying mechanisms is needed to address the gaps in the existing evidence.

The American Music Therapy Association (AMTA) defines music listening as a step in music therapy, a method aimed at protecting, maintaining, and improving individual physical and mental health (123). Listening to music has various positive attributes, including stress reduction and arousal, pain relief, promoting relaxation by affecting heart rate, blood pressure, and the release of endorphins, balancing emotional states, and treating anxiety and depression. Therefore, it can be used to alleviate dysmenorrhea (124). These positive outcomes can be explained by the characteristics and physiological effects of music. According to Western music theory, music is defined as “the art of organizing sound,” and its features are divided into two categories: the physical characteristics of sound (volume, pitch, and waveform) and the characteristics of the composition (melody, harmony, rhythm, and instrumentation). Rhythm is defined by the time signature and beat, with the beat indicating the temporal quality of the musical piece. Using these terms allows researchers to objectively categorize music and standardize interventions.Although the literature does not provide clear results on reducing dysmenorrhea in terms of rhythm, volume, or decibels, it is noted that in pain management, the sound level should not reach noise levels (51–75 decibels) (125). Recent neuroscientific research suggests that music can reduce physiological arousal and pain that increase during stress. Listening to music is associated with reduced physiological arousal and pain, as evidenced by decreases in cortisol levels, heart rate, and blood pressure (126–130). Therefore, many studies have investigated the effectiveness of art therapy in pain and anxiety management across various sample groups. However, more data is needed to determine the impact of art therapy on pain, perceived stress, and menstrual symptoms in women with dysmenorrhea. Table 2 summarizes the key clinical trials on non-ingestion interventions for primary dysmenorrhea.