This is not the first study to confirm the efficacy of acupuncture in reliving primary dysmenorrhea(23, 24). However, few studies have evaluated the efficacy of different doses of acupuncture or the use of more acupoints. Acupuncture has been widely applied to diverse conditions: pain, arthritis, neuropathy, insomnia, and even some cancer-related side effects(25, 26). However, scholars and clinical physicians have not yet reached consensus on the optimal acupuncture prescription, including the number of acupoints, the number of acupuncture sessions, or even the location of acupoints or the optimal total dose. A study by Sun et al. (2019) pointed out that a higher dosage of acupuncture might provide better treatment outcomes in terms of relief of pain and dysfunction in patients with knee osteoarthritis(27), but others consider that more acupuncture sessions will only relieve symptoms in those with chronic pain(28). In primary dysmenorrhea, only one previous study has demonstrated that the timing of the acupuncture treatment and the mode of needle stimulation were germane to menstrual pain outcomes, but even this study failed to identify the optimum dose parameters for this condition(29). From our study, we noted that, when the parameters of acupuncture timing and frequency were fixed, acupuncture with fewer acupoints (lower dose) was not inferior to higher dose, and even better in terms of dependence on analgesics (6 acupoints: 0.043; 12 acupoints: 0.056); dysmenorrhea symptom control (VMSS: 6 acupoints: p<0.001; 12 acupoints: p=0.007); and quality of life (SF-12 PCS: 6 acupoints: p<0.001; 12 acupoints: p=0.001). Therefore, the clinical physician should understand that clinical efficacy is not depend on the number of acupoints and should convey this concept to patients, to reduce the waste of medical resources(9). In quality of life assessment, we found that subjects had more improvement in mental quality of life than in physiological quality of life, so that the placebo effect should be considered a relevant psychological factor. In this regard, a study claimed that the correlation coefficients between de-qi and the therapeutic efficacy of acupuncture were greater than those between psychological factors and therapeutic efficacy in dysmenorrhea(30). Therefore, the mechanisms driving acupuncture efficacy are complex and extend beyond the simplistic “more is better” concept of treatment.
Relationship to autonomic activity adjustment
Some studies indicate that de-qi is the most important factor in making acupuncture effective(31). A study in 2017 revealed that patients with dysmenorrhea who experienced actual de-qi sensation had more pain relief and a greater analgesic effect(32). An interesting study revealed that de-qi elicited a significant response to acupuncture in specific brain regions, indicating that de-qi acupuncture triggers the neuroendocrine network to alleviate pain, but the mechanisms are not clear(22). In our study, we used HRV as an outcome measure, to check whether the acupuncture effect was correlated to autonomic change. HRV has long been recognized as a noninvasive indicator of autonomic nervous system activity(20, 33). Indeed, HRV coherence is related to many physiological benefits, including short-term improvement in cardiovascular and respiratory function, and an increase in vagal afferent activity, which converses pain signals and sympathetic outflow, and thereby promotes temporal synchronization of the body(34, 35). Accordingly, the improvement in autonomic dysfunction corresponds with the balance of yin/yang and implies the adjustment of neuroendocrine in the body microenvironment(20). In this study, we noted that acupuncture has only a short-term effect in adjusting the autonomic dysfunction within the acupuncture group; the benefit did not meaningfully outweigh that received by the medication (control) group (p>0.05). Nevertheless, inter-group analysis revealed that subjects in the high-dose group had greater HRV change, a result which can be interpreted two ways. First, the effect of acupuncture on the autonomic system is short-term rather than long-term. Second, the stimulation of more acupoints may lead to more change in HRV activity, but not greater efficacy in pain relief or symptom control. The mechanism by which acupuncture relieves dysmenorrhea may not directly derive from a change in autonomic nervous activity. We therefore wonder whether the effect of acupuncture in dysmenorrhea is correlated with alterations in serum cytokines, such prostaglandin E and prostaglandin F2 alpha, as has been revealed in previous literature(36). Further study to evaluate the role of serum cytokines is encouraged.
Potential mechanisms of pain reduction
The mechanism of pain associated with dysmenorrhea can be addressed in two aspects: the neuro-endocrine regulated and the neuro-physiologic related. As our study indicates that subjects who adopt acupuncture could use less analgesics, we suppose that acupuncture may have some neuro-endocrine effect(37, 38). In this regard, a previous study noted that acupuncture could have both an anti-inflammatory and an analgesic effect, which might be associated with its inhibition of spinal p38MAPK activation(39) or its regulation of serum prostaglandin E2 or F2 alpha(40). Because patients who used acupuncture required less NSAIDs, acupuncture may have a similar anti-inflammatory effect as NSAIDs, but without the side effects of gastrointestinal discomfort or ulcer stimulation.
On the other hand, some studies have noted that the shift in the estradiol/progesterone ratio in favor of estradiol seems to be the pathogenic principle behind dysmenorrhea(41, 42). We therefore suppose that acupuncture might somehow affect the related hormone balance. In animal models, acupuncture had been noted to regulate neuroendocrine activity and the related receptor expression of the hypothalamus-pituitary-ovary (HPO) axis(38, 43). Clinically, some gynecologist also use oral contraceptives or progestins (OCT) for primary dysmenorrhea(44). If acupuncture could adjust the HPO axis and thereby relieve the related symptoms, then patients can avoid taking OCTs which might have unwanted side effects such as increased risk of endometriosis, blood clot, stroke or cancer(45).
Holistic effect of acupuncture on dysmenorrhea
The results indicate that acupuncture could reduce subjects’ dependence on analgesics and improve their VAS and VMSS scores, which means increasing their ability to work and allowing them to resume more normal activity with fewer symptoms. Compared to the alternatives, acupuncture has fewer side effects and is more cost-effective, especially considering that the number of acupoints is not linearly related to outcomes.