Multimodal Care for Headaches, Lumbopelvic Pain, and Dysmenorrhea in a Woman With Endometriosis: A Case Report

Objective The purpose of this case report is to describe the conservative management of a patient with headaches, lumbopelvic pain, and dysmenorrhea. Clinical Features A 36-year-old woman presented with intense pelvic and daily lumbar pain. She had difficulty sleeping and focusing and had 3 to 4 headaches per week. Before, during, or after her menses, she would have migraine headaches. During her menses, she experienced severe lumbopelvic pain and dysmenorrhea with moderate bloating, constipation, nausea, and diarrhea. When she was 32 years old, her gynecologist diagnosed endometriosis and prescribed nonsteroidal anti-inflammatory drugs and hormonal oral contraceptives, which failed to alleviate her symptoms. She sought an alternative approach to help control her symptoms. Intervention and Outcome A multimodal approach was selected for this patient, which consisted of acupuncture combined with supplements of magnesium citrate, B-100 complex and botanicals turmeric (Curcuma longa/root extract), bromelain (Ananas comosus [pineapple stem]) and black cohosh (Cimicifuga racemosa). After an initial trial of care, her daily lumbopelvic pain was reduced, and she was sleeping better and feeling more focused and less fatigued. She rarely had tension headaches during the week or migraine headaches or dysmenorrhea before, during, or after menses. Her lumbopelvic pain and gastrointestinal symptoms were reduced.

A patient who was experiencing headaches, lumbopelvic pain, and dysmenorrhea responded favorably to a course of care that included a combination of botanicals, supplements, and acupuncture. Key Indexing Terms: Endometriosis, Acupuncture, Curcumin (Curcuma longa), Cimicifuga (Cimicifuga racemosa), Bromelains (Ananas comosus), Magnesium, Vitamin B Complex, Migraine Disorders, Headache, Dysmenorrhea

Endometriosis is associated with the formation of endometrial tissue outside the uterus, resulting in a chronic inflammatory state.1 The primary pathophysiologic explanation of this condition involves an imbalance between estrogen and progesterone.1 A consequence of the disequilibrium between these hormones results in an estrogen dominance and progesterone resistance.1 A progesterone resistance is characterized by the inability of progesterone to bind to and activate progesterone receptors found on endometrial tissue.1 Without the activation of these receptors, regulation of estrogen is compromised.1 A negative feedback signal is not sent to decrease the expression of transcription factors that control estrogen secretion, which creates the state of estrogen dominance.1 An estrogen dominance alters uterine function allowing for retrograde flow of menstrual blood into the oviducts, creating various ectopic lesions.1 The ectopic tissue tends to form on the ovaries, ligaments of the uterus, pouch of Douglas, and oviducts.2 However, it can travel and create lesions on the gastrointestinal (GI) tract, diaphragm, lungs, and pericardium.2 Although retrograde flow of the menses is believed to be a major component contributing to the development of endometriosis, not all women who experience retrograde flow have endometriosis.2 Consequently, other factors can influence the formation of symptomatic endometrial lesions. Higher levels of oxidative stress perpetuating inflammation have been positively correlated with the pathophysiology of endometriosis.3,4 Evidence supports this theory as individuals with endometriosis have been found to have higher levels of the prooxidant homocysteine.4 There is an inverse relationship between hyper-homocysteinemia and serum progesterone and estradiol levels, indicating that certain pro-oxidants might contribute to the disequilibrium of the hormones, resulting in resistance and dominance.5,6 In addition, endometriosis is a chronic inflammatory disorder characterized by the up-regulation of the transcription factor nuclear factor-κB (NF-κB), which can perpetuate the pathophysiology of the disease.7 Increasing the activity of NF-κB can exacerbate the inflammatory process.7 Women who have endometriosis tend to have higher levels of the inflammatory mediators tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8.8 As inflammation occurs naturally during the female menses, the inflammatory response associated with endometriosis might intensify the process exacerbating the symptoms experienced.9 The primary form of conventional medical therapy consists of long-term hormonal contraceptive medications in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs).10 This treatment approach is used to manage symptoms and to slow the progression of the disease.10 However, the use of these medications rarely resolves symptoms completely.10 In some cases, hormonal contraceptives and NSAIDs are ineffective and surgical intervention is necessitated.10 The surgical procedures for endometriosis consist of excising the lesions, ablation of the uterosacral nerves, a presacral neurectomy or a complete hysterectomy.10 Unfortunately, even with surgical intervention symptoms persist in 20% to 50% of patients and in 5% to 15% of cases endometriosis can reemerge.10 Traditional Chinese Medicine (TCM) therapy, supplements and botanicals could be effective adjuncts or alternatives to conventional medical treatment strategies. Unfortunately, research related to the treatment of endometriosis using natural remedies is limited. However, magnesium, B vitamins, turmeric (Curcuma longa), bromelain (Ananas comosus), black cohosh (Cimicifuga racemosa), and acupuncture can mitigate and control the symptoms associated with the chronic inflammatory state of endometriosis. Acupuncture, magnesium, multiple B vitamins, turmeric (C. longa) and bromelain (A. comosus) are capable of generating anti-inflammatory effects.11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 In addition, niacin and pyridoxal phosphate (PLP) are specifically used to treat chronic inflammatory conditions.18,21 Another consideration is that a hormonal imbalance is believed to be the primary manifestation contributing to the development of endometriosis.1 Acupuncture, turmeric (C. longa), black cohosh (C. racemosa), and a few B vitamins possess properties have been suggested to promote hormonal regulation, which could impede retrograde flow of uterine tissue during menses.26, 27, 28, 29 These effects can be bolstered by the spasmolytic activity of magnesium, which can further diminish retrograde flow and the potential to form endometrial lesions.14 There is a marginal amount of information in peer-reviewed studies pertaining to the effects of magnesium, B vitamins, bromelain (A. comosus), or black cohosh (C. racemosa) for the treatment of endometriosis in humans. A few studies have demonstrated the positive effects of acupuncture and turmeric (C. longa) on the symptomatology of endometriosis.30, 31, 32, 33, 34, 35 However, the experiments using acupuncture do not provide a mechanism of action for mitigation of symptoms, and the research with turmeric (C. longa) was performed in vitro or in animal studies. With the limited data available for the natural treatment of endometriosis, the purpose of this case report is to describe multimodal, conservative management using TCM-based acupuncture, supplements, and botanicals for the treatment of headaches, lumbopelvic pain, and dysmenorrhea in a patient with endometriosis. Case Report A 36-year-old woman presented with chronic pelvic pain from endometriosis. Her pelvic pain started when she was 17 years old; however, endometriosis was not detected by a gynecologist until she was 32 years old. The gynecologist performed a diagnostic ultrasound examination and identified endometriomas on the surface of her uterus. Following her diagnosis, she was prescribed a series of hormonal oral contraceptives and NSAIDs for management of her pain. Before the administration of these medications, her pain was an 8 out of 10 on a numeric scale ranging from 0 to 10, with 0 being the least intense and 10 being the most severe pain. When she began taking the oral contraceptive and NSAID, there was minimal improvement in her pain, which was measured at a 6 out of 10. Over the course of the next 3 years, she was prescribed 3 other types of oral contraceptives and received a second opinion from another gynecologist. With this treatment, she never experienced a reduction in pain below a 6 out of 10 on a numeric scale. The final recommendation from the gynecologist was surgery to excise the endometrial tissue or perform a hysterectomy. She declined both forms of treatment. She had stopped taking the oral contraceptive and NSAID a few months before her appointment, and she began to focus on exercise to control her symptoms. The primary symptom that she experienced was severe pain around her lumbar and sacral regions and the anterior superior, posterior superior, and posterior medial aspect of her thighs bilaterally. Her pain was rated as an 8 out of 10 on her first visit. The pain was a constant intense ache all day and night every day. The pain was interfering with her sleep. She estimated that she slept for 2 to 3 hours per night and woke up feeling unrefreshed and fatigued. Because of her inability to sleep, she was having difficulty concentrating. Exercise reduced the pain to a 5 or 6 out of 10. Unfortunately, her relief was transient, and her usual pain intensity returned after a few hours. She was a pescatarian who ate fish (which are high in omega 3 fatty acids) about 2 times per week, also lots of fruits and vegetables and whole grains, and avoided alcohol, caffeine, heat, and stress, as they exacerbate her symptoms. She had about 3 to 4 headaches per week. She described the headaches as a band wrapped around her head and rated them a 3 out of 10. Her menstrual cycle was well regulated for the past few years, but her cycle ranged from 24-30 days with 5 to 7 days of menses after she stopped taking the oral contraceptive. Her flow was very heavy and dark, but she did not experience any intermittent bleeding. Her low back pain level during her menses was a 10 out of 10. The other predominant symptom she experienced was dysmenorrhea, which she rated at an 8 out of 10. Concurrently, bloating, alternating bouts of constipation and diarrhea and nausea occurred during her menses. Her GI symptoms were rated at a 5 out of 10 collectively. Bowel movements and urination exacerbated her lumbosacral pain. Immediately before, at least 1 day during, and immediately after her menses she experienced unilateral migraine headaches on the right side of her head, which she rated at a 7 out of 10 for pain intensity. She began experiencing these migraine headaches during adolescence. Orthopedic tests (ie, Hibb test, Yeoman test, Erichsen test, Kemp test, straight leg raise, Mennell test, and Patrick FABERE test) failed to reproduce lumbopelvic symptoms. However, she noted soreness in her posterior superior iliac spine with a Mennell maneuver that did not change with inward or outward pressure and tightness in her iliopsoas muscles bilaterally during Patrick FABERE test. Palpation increased the pain in her sacroiliac joint, gluteus medius, and soft tissue and musculature immediately below her iliac crest, on either side of her sacrum from S1 to S4 and the anterior superior, posterior superior and posterior medial aspects of her thighs. The pain did not limit her active or passive range of motion, yet she noted low-grade discomfort with active extension and flexion of the lumbar spine. An abdominal examination revealed tenderness upon superficial and deep palpation of the hypogastric and inguinal regions bilaterally. Her history led to a Western medicine diagnosis of endometriosis. The symptoms related to her TCM diagnosis were a preference for cold drinks and feeling hot with mild night sweats. Her pulse was wiry bilaterally, and her tongue was swollen with a slight purple tint to the body and a red tip. Her TCM diagnosis considering her history and these additional symptoms with tongue and pulse diagnosis was spleen qi and kidney yin deficiency with yang heat rising. The treatment strategy was to fortify the spleen, nourish kidney yin and the mind, and dissipate heat. The points chosen were An Mian bilaterally, DU 4 (Yao Yang Guan), DU 16 (Feng Fu), UB 20 (Pi Shu) bilaterally, UB 23 (Shen Shu) bilaterally, KD 3 (Tai Xi) unilaterally, KD 6 (Zhao Hai) unilaterally, SP 3 (Tai Bai) unilaterally, SP 6 (San Yin Jiao) unilaterally, GB 34 (Yang Ling Quan) unilaterally, and 6 ashi points in the lumbosacral region and upper thigh. Financial constraints resulted in acupuncture treatment once every 7 to 14 days. In addition, 400 mg of magnesium citrate, a B-100 complex (100 mg thiamin HCl, 100 mg riboflavin, 100 mg niacinamide, 100 mg pyridoxine HCl, 100 mg calcium-D pantothenate, 100 μg folic acid, 100 μg cyanocobalamin, 100 μg biotin, 100 mg inositol, 100 mg para-aminobenzoic acid, and 100 mg choline bitartrate), 1000 mg of turmeric (C. longa [root extract]) with 3 mg black pepper extract (Piper nigrum) powdered capsules that are 95% standardized, 1000 mg bromelain (A. comosus [pineapple stem]) not standardized providing 1000 GDU, non-GMO maltodextrin with 141 mg calcium carbonate, and 540 mg of black cohosh (C. racemosa) nonstandardized from 135 mg 4:1 extract were prescribed 2 times per day. Three days before the onset of her menstrual period, it was recommended that she consume 400 mg of magnesium citrate, 1000 mg of turmeric, and 1000 mg of bromelain 3 times per day and 540 mg of black cohosh (C. racemosa) and the B-100 complex 2 times per day and continue to supplement with the primary regimen until after menstrual bleeding subsided. Outcome Two acupuncture sessions were administered over the course of 2 weeks, which might have helped to reduce her lumbopelvic pain level from an 8 to a 2. She began taking the supplements 3 days after her first treatment. With the combination of acupuncture and the supplements, she reported sleeping better, having more focus, and feeling less fatigued. After the second treatment session using acupuncture and taking the supplements, she no longer reported headaches. However, during her menses, her symptoms were exacerbated and she had severe lumbopelvic pain, dysmenorrhea, gastrointestinal symptoms, and a migraine headache. After her menstrual period, her lumbopelvic pain returned to 8 out of 10 on a numeric scale. A third acupuncture session reduced her pain to a 5 out of 10. Unfortunately, after this last treatment, she explained that she was changing her career path and was going to be moving at the end of the month. Because of the expense of the move, she did not believe she would be able to continue acupuncture treatment; however, she would still take the supplements. Follow-up reports were collected via office visits and e-mails to determine the progression of her case. The course of her condition is outlined in Tables 1 and 2. After 14 weeks, she reported her lumbopelvic pain to be at a 1 out of 10 on a numeric scale and 3 out of 10 during menstruation. She still had not experienced a tension type headache since the second acupuncture treatment and she felt more focused, was sleeping better, and had more energy. In addition, she had not experienced dysmenorrhea for her last 2 menses and had not experienced a migraine headache with her past 3 menses. She still experienced bloating and alternating bouts of diarrhea, constipation, and nausea; however, these symptoms were rated a 2 out of 10 compared with a 5 out of 10 at the start of treatment. Table 1. | Time Point | Lumbopelvic Paina | Tension Headachesa | |---|---|---| | Before treatment | 8 | 3 | | First treatment, week 1 | 3 | 3 | | Second treatment, week 2 | 2 | 0 | | Third treatment, week 4 | 5 | 0 | | Follow-up visit, week 5 | 5 | 0 | | Follow-up visit, week 6 | 1 | 0 | | Follow-up visit, week 8 | 1 | 0 | | Follow-up visit, week 9 | 1 | 0 | | Follow-up visit, week 12 | 1 | 0 | Rated on a scale of 0 to 10, with 0 being the least intense and 10 being the most severe pain. Table 2. | Symptomsa | Before Treatment | Week 3 | Week 7 | Week 10 | Week 14 | |---|---|---|---|---|---| | Lumbopelvic Pain During Menses | 10 | 10 | 5 | 3 | 3 | | Dysmenorrhea | 8 | 8 | 3 | 0 | 0 | | Gastrointestinal Symptoms During Menses | 5 | 5 | 2 | 1 | 2 | | Unilateral Migraine Headache During Menses | 7 | 8 | 0 | 0 | 0 | Rated on a scale of 0 to 10, with 0 being the least intense and 10 being the most severe pain. The patient moved out of state. A follow-up was performed at 16 weeks after the first treatment via e-mail. At this time, her lumbopelvic pain was sustained at a 1 out of 10 on a numeric scale and she still had not experienced a tension or migraine headache. The patient gave permission for her health information to be included in this case report.

This case presentation reflects an atypical case of endometriosis that might have responded favorably to natural medicine therapies. This is a unique case as it describes a female patient who received minimal benefits from conventional medicine therapies that are considered the standard of care for endometriosis. Treatments using natural remedies are sometimes used as an alternative to conventional medicine. The dosages that can induce toxic states either have not been established or are extremely high.26,29 Of the vitamins and minerals used in this case, the upper limits have been set for niacin at 1000 mg, magnesium at 3000 mg, and folic acid at 15 mg.29 The dosages administered were well below these values. In addition, the amount of thiamin, riboflavin, pantothenic acid, and cobalamin that can cause undesired reactions with oral consumption has not been established as these vitamins are well tolerated. The daily doses of bromelain (A. comosus) and turmeric (C. longa) were within the parameters outline by the Physician's Desk Reference (PDR) for Herbal Medicine at 2000 mg and 3000 mg, respectively, with the exception of the quantity of bromelain (A. comosus) recommended 3 days before and during her menstrual period, which was 3000 mg daily.26 The PDR does not specify a daily capsular dose of black cohosh (C. racemosa).26 The maximum capsular dosage for single use is 545 mg and the amount prescribed was 540 mg.26 As the primary adverse effects of these botanicals are GI in nature to prevent irritation of the GI tract, the patient was advised to consume the supplements and botanicals with meals in the morning and evening. As the patient had endometriosis that did not respond to conventional therapy and her symptoms were severe, administering the dose 2 times per day and 3 times per day 3 days before and during menses with meals seemed appropriate to control her symptoms. Black cohosh (C. racemosa) was the only supplement used that might not have been safe for prolonged use; however, the PDR states that it is safe to use for up to 6 months.26 After this time, its safety is unknown. Consequently, if the patient were to continue with the treatment beyond 14 weeks, the approach would have been to prescribe black cohosh (C. racemosa) once per day for the remainder of the 6-month period. After this period, substituting black cohosh (C. racemosa) with another estrogenic botanical would have been considered. The possibility of an exacerbation of her GI symptoms was discussed with the patient, yet her GI symptoms during menses improved over the course of treatment. This result might indicate that the dosages were within a safe range. The only botanical that was not within the total daily dosage range recommended by the PDR was bromelain (A. comosus); however, it was divided into 3 separate doses of 1000 mg at least 6 hours apart and taken with meals, which should diminish the potential low-grade adverse effects of GI discomfort and diarrhea. It might also indicate that bromelain (A. comosus) can be used at a maximum daily dose of 3000 mg/day for short periods if the dosages are separated into smaller quantities and administered with enough time between dosing. As endometriosis is a chronic inflammatory disease and related to a hormonal imbalance, the combination of the therapeutic approaches might have generated synergistic effects responsible for the positive outcome observed in this case. It is important to note that synergism has not been demonstrated between acupuncture and any of the nutraceuticals used in this case, except for cobalamin. Han et al36 found that acupuncture enhanced the effects of a cobalamin derivative in a human trial; however, acupuncture has been shown to augment the effects of other herbs, indicating a potential for synergism to occur.37, 38, 39 Unfortunately, a hormonal panel was not performed to determine estrogen or progesterone levels, yet migraine headaches might have been an indication of a potential disequilibrium of estrogen and progesterone as they would occur before, during, or directly after her menses and rarely occurred any other time during the month. Fluctuations in estrogen are often a major contributor to the development of migraine headaches, and the onset of migraine headaches coincided with the onset of her endometriosis symptoms during adolescence.40 The patient experienced tension-type headaches throughout the month in addition to her endometriosis symptoms. Tension headaches are not a typical symptom that manifests in cases of endometriosis.10 The irregularities of vasomotor function might have been associated with low levels of vitamins and minerals in the patient's body. Low levels of thiamin, niacin, PLP, folic acid, cobalamin, and magnesium have been positively correlated with the manifestation of tension headaches.29,41, 42, 43 Consequently, headaches might indicate lower-than-optimal levels of these nutrients. The patient was taking exogenous hormonal oral contraceptives, which can reduce the levels of PLP, folic acid, cobalamin, and magnesium, for almost 4 years.44 Hormonal contraceptives do not directly lower niacin levels, yet PLP is required for conversion of tryptophan to niacin.29 Consequently, the overall biosynthetic process could be impeded by reducing niacin levels. This scenario is probable, as her tension headaches subsided within a few weeks after supplementation began. Unfortunately, the levels of the nutrients were not assessed with laboratory testing. During the treatment period, the patient received multiple therapeutic modalities, making it impossible to determine the effectiveness of any remedy administered. However, since the predominant pathophysiologic factor associated with endometriosis is assumed to be a hormonal imbalance, it is possible that black cohosh (C. racemosa) might have affected the outcome observed in this case. Black cohosh (C. racemosa) is an estrogenic botanical that might have the ability to bind to and regulate the activity of estrogen receptors.28 Wuttke et al28 observed a weak association between the administration of black cohosh (C. racemosa) and estrogen levels; however, the dosage was 40 mg over a 12-week period, whereas the dosage used in the present case was 540 mg twice daily.45 Consequently, a higher dose in combination with administering the botanical 2 times per day might have generated more pronounced effects, which could have been responsible for the improvement in her clinical condition. Without an estrogen panel, the potential change in her hormone levels cannot be determined. Although the effects of black cohosh (C. racemosa) in this case cannot be confirmed, this botanical has been used for the alleviation of symptoms connected to conditions that are associated with a disequilibrium of hormone levels. An experiment by Bai et al46 compared black cohosh (C. racemosa) to tibolone, which is a synthetic estrogenic steroid. Black cohosh (C. racemosa) and tibolone produced analogous effects mitigating the symptoms of climacteric disorders such as insomnia, night sweats, hot flashes, vaginal dryness, and sexual dysfunction, and they could be used interchangeably.46,47 Tibolone has been recommended as a medication for the treatment of endometriosis, which indicates that black cohosh (C. racemosa) could be a viable option.48 The vitamins, acupuncture, and other botanicals prescribed in this case might have correlated with the improvement in symptoms the patient experienced, possibly by influencing estrogen levels. The research available pertaining to the estrogenic activity of B vitamins is limited, yet riboflavin could have indirect estrogenic effects as it is required for the conversion of pyridoxamine and pyridoxine phosphate to PLP in the liver.29 PLP is capable of binding to steroid hormone receptors and modulating activity, which could influence the levels of estrogen and progesterone.29 Niacin can increase the expression of estrogen-related receptor-α (ERRα).49 EERα has binding sites for estrogen receptor α (ERα), and estrogen replacement therapies often target ERα, indicating that niacin could alter the physiological effects of estrogen.50,51 Another B vitamin that might have contributed to the positive outcome observed in this case is biotin. Although the research related to the effects of biotin on estrogen is marginal, a study by Báez-Saldaña52 emphasizes that it could possess estrogenic activity.52 In this study, female rats fed a biotin-deficient diet experienced a disruption of their menstrual cycles and morphologic abnormalities of their ovaries.52 Reintroducing biotin to the diet caused a 105.4% elevation in estradiol.52 The mechanism of this effect is not entirely understood; however, it is believed to be involved with the alteration of gene expression and promotion of cell signaling.53 The last two B vitamins that might have modified the patient's estrogen levels are folic acid and cobalamin. Existing data demonstrate a correlation between folic acid, cobalamin, estrogen, and homocysteine levels and endometriosis.4,5,-54 Individuals with endometriosis have higher levels of homocysteine and lower levels of estrogen and progesterone.4,5,54 Folic acid and cobalamin are involved in the conversion of homocysteine to methionine, reducing the concentration of homocysteine.29 Supplementation with folic acid has been shown to normalize estrogen levels.5 Unfortunately, no evidence exists verifying the estrogenic activity of cobalamin or the effects of folic acid on progesterone. However, hyper-homocysteinemia reduces the levels of both estrogen and progesterone, indicating that supplementation with folic acid and cobalamin might possess weak upregulatory activity.5,6 The influence of the other B vitamins and bromelain (A. comosus) on steroid hormone levels has not been determined, but the botanical turmeric (C. longa) has weak estrogenic activity. Turmeric (C. longa) contains multiple phytochemicals that act estrogenically. The primary active component curcumin can bind weakly to ERα, altering the activity of estrogen.55,56 Another element that might have contributed to the positive outcome observed in this case is the anti-inflammatory nature of the supplements. As endometriosis is a chronic inflammatory disorder, downregulating the transcription of NF-κB and quenching inflammatory mediators could have mitigated the patient's symptoms.15 Turmeric (C. longa), bromelain (A. comosus), PLP, folic acid, and magnesium can reduce the gene expression of NF-κB.8,24,57, 58, 59 In cases of endometriosis, deactivating NF-κB has been shown to reduce the activity of cystic fibrosis transmembrane conductance regulator (CFTR).35 It has been hypothesized that CFTR promotes the migration of endometrial tissue outside of the uterus, since ectopic endometrial tissue contains higher concentrations of CFTR.35 Consequently, decreasing the expression of NF-κB can reduce CFTR levels and potentially mitigate the inflammatory process by preventing the migration of endometrial tissue. The inflammatory mediators TNF-α, IL-1β, IL-6, and IL-8 have been positively correlated with the pathogenesis of endometriosis.9 TNF-α, IL-6, and IL-8 can be reduced by supplementing with black cohosh (C. racemosa) and turmeric (C. longa).9,60,61 Bromelain (A. comosus) is capable of attenuating the levels of TNF-α and IL-6.62 Niacin, PLP, and folic acid can downregulate TNF-α.63,64 Folic acid, PLP, and para-aminobenzoic acid can decrease IL-6, and folic acid can diminish the levels of IL-1β.57,64,65 The combination of these anti-inflammatory agents might have had a summative effect that assisted with the control of the patient's signs and symptoms. Higher levels of oxidative stress have been positively correlated with endometriosis.4 Pro-oxidants can exacerbate the inflammatory state of individuals with endometriosis.4 Free radicals and reactive oxygen species can damage the cell membrane, proteins, organelles, and the nucleus, thus contributing to the inflammatory cascade.29 Attenuating the generation of these prooxidants could diminish the inflammatory process. Multiple B vitamins and botanicals incorporated in this treatment can act as antioxidants. Thiamin, riboflavin, inositol, niacin, and cobalamin can reduce the production of free radicals and reactive oxygen species.29,53 Riboflavin, inositol, niacin, and cobalamin can regenerate the antioxidant agent glutathione.29,53 In addition, riboflavin and niacin can restore the levels of the antioxidant thioredoxin, and niacin can convert ascorbic acid back to its active form.18,29,53 PLP, turmeric (C. longa), bromelain (A. comosus), and black cohosh (C. racemosa) can increase superoxide dismutase (SOD) and glutathione peroxidase activity.66, 67, 68, 69 Folic acid can upregulate the antioxidant function of SOD and glutathione s-transferase.70 Turmeric (C. longa) potentiates the antioxidant effects of catalase.67 Although acupuncture was used for only a few treatments, it might have enhanced the physiologic activity of the supplements. Acupuncture seemed to assist with a reduction in her pain levels. After the first treatment, she experienced a reduction in lumbopelvic pain from 8 to 3, according to a numeric scale, before taking the supplements, and her pain level was a 2 after the second session with acupuncture in combination with the nutraceuticals. Her pain level increased during menstruation, but it was still lower than it had been at the beginning of her treatment. Several studies demonstrate the therapeutic value of acupuncture for the treatment of female reproductive issues. A systemic review and meta-analysis conducted by Mira et al71 concluded that acupuncture can improve symptoms in individuals with endometriosis.71 According to TCM theory, DU 4 (Yao Yang Guan), KD 3 (Tai Xi), KD 6 (Zhao Hai), UB 20 (Pi Shu), UB 23 (Shen Shu) and SP 6 (San Yin Jiao) can affect uterine function.72 The exact mechanism of these benefits has not been elucidated, but it may be through the regulatory mechanism of acupuncture on serum estradiol. In multiple studies, acupuncture therapy increased and decreased estradiol levels.27,28,73, 74, 75 Jeong et al27 found that certain acupuncture points had the ability to modulate estrogen levels and reduce hot flashes in women prescribed antiestrogenic therapy.27 Unfortunately, the study did not involve any of the points administered in this case.27 A few studies have demonstrated the efficacy of acupuncture for the treatment of endometriosis. One study by Xiang et al30 used abdominal points to attenuate localized endometrial pain. Another study by Sun et al administered a combination of local and distal points to diminish pain associated with endometriosis.31 Sun et al selected 3 of the acupuncture points used in the present case: UB 20 (Pi Shu), UB 23 (Shen Shu) and SP 6 (San Yin Jiao).31 In a study by Zhang et al,32 electroacupuncture demonstrated superior effects in a comparison with the medication group for controlling the symptomatology of endometriosis. The authors used SP 6 (San Yin Jiao) as part of their treatment strategy.32 Estrogen levels were not a primary outcome measured in this case, so if acupuncture had any effect on estrogen, it cannot be determined. However, several points administered during the treatment of this patient have been shown to reduce symptoms that might be associated with fluctuations in estrogen levels. Studies have found that DU 4 (Yao Yang Guan), UB 23 (Shen Shu), KD 3 (Tai Xi), KD 6 (Zhao Hai) and SP 6 (San Yin Jiao) used in combination with other points diminished the severity of hot flashes, which could be associated with altered levels of estrogen.76, 77, 78, 79, 80, 81, 82 In other studies, formulations using KD 3 (Tai Xi), KD 6 (Zhaohai), GB 34 (Yang Ling Quan), SP 6 (San Yin Jiao) and UB 23 (Shen Shu) attenuated symptoms of premenstrual syndrome.82, 83, 84 Because acupuncture was incorporated into the treatment strategy for about a month, if estrogenic effects were produced they were probably minimal, as it typically takes several weeks to balance hormone levels. Consequently, the positive effects observed might have been due to the ability of acupuncture to downregulate NF-κB expression, which can diminish CFTR activity and potentially prevent the migration of endometrial tissue.11 According to TCM theory, DU 4 (Yao Yang Guan), SP 3 (Tai Bai), SP 6 (San Yin Jiao), UB 20 (Pi Shu), UB 23 (Shen Shu), KD 3 (Tai Xi), KD 6 (Zhao Hai) and GB 34 (Yang Ling Quan) can be used for musculoskeletal pain in the lumbar spine or abdominopelvic region.72 Of the acupuncture points, only SP 6 (San Yin Jiao) and GB 34 (Yang Ling Quan) have been shown to reduce inflammatory mediators in the literature. In formulations, SP 6 (San Yin Jiao) can downregulate inflammatory ILs and NF-κB.85 In conjunction with other points, GB 34 (Yang Ling Quan) can reduce inflammatory ILs and TNF-α.86 Although DU 16 (Feng Fu) is not necessarily used for pain in the lumbar or abdominopelvic region, it is a point on the DU Mai, which is known as the Sea of Yang and can subdue yang energy that is associated with heat or inflammation according to TCM theory.72 Supporting research has shown that DU 16 (Feng Fu) has the ability to impede inflammatory ILs and TNF-α activity.87 In addition, DU 16 (Feng Fu) when used in conjunction with another point increased SOD activity, which could further abate the inflammatory process.87 The contribution of An Mian to the improvement in our patient's symptoms is unknown. An Mian is used to promote relaxation according to TCM theory.72 Collected data illustrate the sedative effects of AnMian,88 and other research has shown that chronic inflammatory conditions induce a stress response in the body.89 Consequently, An Mian might have produced positive effects through its sedative activity. As acupuncture was used for only the first month of treatment, it might have assisted with an initial reduction in signs and symptoms. A limited amount of research in humans has been conducted related to the therapeutic effects of natural remedies for the treatment of endometriosis. However, in this case, the combination of turmeric (C. longa), bromelain (A. comosus), black cohosh (C. racemosa), B vitamins, magnesium, and acupuncture appeared to improve the patient's symptoms. These effects might have been achieved by a single component or by the synergistic interactions of these agents. Unfortunately, this case report reflects only the potential effects of these remedies in a single case. Consequently, the true effectiveness of these natural therapies cannot be determined. Additional research is necessary to confirm the efficacy of each modality and the cumulative effects of the combination of these constituents.

The most apparent limitation for this case is that the improvements the patient experienced were based on a subjective numeric pain scale, which could have been attributed to a placebo effect. It is uncertain whether there was an effect on endometriosis. Having a second ultrasound examination might have given an indication of an improvement in physiology. In addition, a hormonal panel and tests assessing the levels of nutrients would have been beneficial, but they were not performed because of the patient's financial limitations. Another limitation was that there were multiple modalities administered in the treatment of this patient. Consequently, it is impossible to determine whether one or a combination of agents produced the desired effects. The therapeutic strategy also changed after the first month, and acupuncture was no longer performed. In addition, this is a report of the care of only 1 person; others might not respond in the same manner. Lastly, the long-term effectiveness of the treatment cannot be determined, because the patient moved out of state and her care was taken over by another physician; thus, long-term results are not known.

A patient with endometriosis who was experiencing headaches, lumbopelvic pain, and dysmenorrhea responded favorably to a multimodal approach including supplements, botanicals, and acupuncture. Acknowledgments Funding Sources and Potential Conflicts of Interest No funding sources or conflicts of interest were reported for this study. Contributorship Information Concept development (provided idea for the research): B.R.M. Design (planned the methods to generate the results): B.R.M. Supervision (provided oversight, responsible for organization and implementation, writing of the manuscript): B.R.M. Data collection/processing (responsible for experiments, patient management, organization, or reporting data): B.R.M. Analysis/interpretation (responsible for statistical analysis, evaluation, and presentation of the results): B.R.M. Literature search (performed the literature search): B.R.M. Writing (responsible for writing a substantive part of the manuscript): B.R.M. Critical review (revised manuscript for intellectual content, this does not relate to spelling and grammar checking): B.R.M. Other (list other specific novel contributions): B.R.M. Practical Applications. - • Acupuncture, turmeric (Curcuma longa), black cohosh (Cimicifuga racemosa), bromelain (Ananas comosus), magnesium, and B vitamins helped to reduce the symptoms of endometriosis, migraines, and dysmenorrhea. - • There is currently limited evidence that any of these modalities would be effective for the treatment of these conditions in human trials. Alt-text: Unlabelled box

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