Treatment of Tamoxifen-Induced Vasomotor Symptoms with Chinese Herbal Medicine and Acupuncture: A case study

Abstract

Background: Night sweats and hot flashes are two symptoms regularly experienced with the use of Tamoxifen; often severely affecting the quality of life. Tamoxifen is prescribed to treat and prevent breast cancer in both men and women.

Objective: To evaluate the response of acupuncture and Chinese herbal medicine in a female patient breast cancer survivor taking Tamoxifen.

Patient and setting: The patient is a forty-four-year-old female with complaints of night sweats and hot flashes. She has been prescribed Tamoxifen and is currently experiencing night sweats and hot flashes; the patient was seen in a private practice.

Intervention: The patient was treated using a combination of acupuncture and Chinese herbal medicine. The patient received 22 acupuncture treatments over the course of 6 months. She was also prescribed Chinese herbal prepared medicines in pill form.

Results: Upon the twenty-second visit the patient reported a complete absence of flushing or night sweats.

Conclusion: Traditional Chinese medicine (TCM) and acupuncture can be an effective way of mitigating the side effects commonly associated with the use of hormonal therapies, specifically Tamoxifen. Patients who experience night sweats and hot flashes as a side effect of the pharmaceutical Tamoxifen may benefit from TCM intervention.

Introduction

Biomedical Perspective

Menopause/ Hot Flashes

Menopause, which means the cessation of menses, is a natural transition for women consisting of three phases, i.e. perimenopause, menopause, and postmenopause. Menopausal genesis, from a biomedicine perspective, is described as a decline in ovarian follicles, which contributes to a lack of estrogen and thus results in amenorrhea.1,2 Menopause can occur naturally or as a result of medical intervention; including hysterectomies, chemotherapy, anti-estrogen hormone therapies and pelvic radiation. Menopause signs and symptoms; include observation of 12 consecutive months of amenorrhea, night sweats, vaginal dryness, and elevated follicle-stimulating hormone (FSH) (>40 IU/L).3,4 Age alone, however, can be a useful predictor in the diagnosis of menopause i.e., the average age for entering or completing menopause transition is 51.2,3 Comorbid symptoms of menopause, can severely affect a woman’s quality of life including mood swings, fluctuations in sexual desire (libido), forgetfulness, trouble sleeping, and fatigue. Menopausal symptoms, however, appear to be more robust in women who experience induced menopause.

Western biomedicine defines hot flashes as a common symptom experienced in menopause.1,2 Approximately 75% of women in the United States report experiencing hot flashes during menopause transition.1 Hot flashes, are described as a feeling of heat in the “face, neck and chest,” followed by sweating which affects the entire body.1 Hot flashes can be severe enough to affect one’s quality of life, presenting with co-symptoms including, “anxiety, nausea, tachycardia, and tachypnea.”5 The exact mechanisms involved in menopausal hot flashes are poorly understood. Current hypothesis suggest hot flashes occur due to a downshifting of the set point for the core body temperature in the thermoregulatory center, neuromodulators, peripheral vasculature and sweat glands.5 The thermoregulatory center is influenced by “sex steroids, β-endorphins, and central neurotransmitters.”5

Tamoxifen

Tamoxifen is one of several pharmaceuticals approved by the Food and Drug Administration (FDA) which are used for the prevention of breast cancer. Other pharmaceuticals include Evista (Raloxifene Hydrochloride), Keoxifene (Raloxifene Hydrochloride), Nolvadex (Tamoxifen Citrate), Raloxifene Hydrochloride and Tamoxifen Citrate.6 Hormonal therapies are used to either block or remove estrogen from the body, and thus prevent stimulation of estrogen receptive cancer cells from growing.6 Tamoxifen is used in the treatment of early stage and metastatic breast cancer.6 Another type of hormone therapy used in breast cancer prevention is aromatase inhibitors. Aromatase inhibitors block the production of estrogen by blocking the enzyme aromatase from turning androgen into estrogen.6

Tamoxifen has been found to reduce the frequency of “invasive and noninvasive breast cancer.”7 Common side effects associated with Tamoxifen use include: hot flashes, night sweats, and vaginal dryness.7 Tamoxifen with long-term use may also decrease platelet and white blood cell counts (thrombocytopenia and leukopenia).8 Less common life threating side effects, include “stroke, pulmonary embolism, and deep-vein thrombosis.”7 Selective serotonin reuptake inhibitors (SSRIs) have been used to relieve the side effects of Tamoxifen; however SSRI’s have been found to impede cytochrome P4502D6 (CYP2D6) an essential isoenzyme for Tamoxifen metabolism in the liver.9

Tamoxifen is a selective estrogen receptor modulator (SERM) and is effective in preventing all stages of estrogen receptor (ER)-positive breast cancer.10 Tamoxifen acts as a receptor antagonist through its active metabolite (Z)-4-hydroxytamoxifen, which block estrogen receptors found in cancer cells located in breast tissue.11 Tamoxifen binds to estrogen receptors and produces estrogenic and anti-estrogenic properties.11 Tamoxifen minimizes “circulating insulin-like growth factor-1, inhibits angiogenesis, and induces apoptosis.”12 The use of Tamoxifen has proven to be beneficial in minimizing breast cancer recurrence by 50% (stages not stated) and breast cancer mortality by 33% with a 15-year follow-up.13

Breast Cancer

Ductal carcinoma is the most common type of breast cancer and can be either in situ (noninvasive) or invasive ductal carcinoma. Ductal carcinoma germinates in the lining of the milk ducts (thin tubes that carry milk from the lobules of the breast to the nipple).6 According to the Center for Disease Control (CDC), breast cancer is the most common form of cancer for women across all ethnicities and age groups.14

TCM (Traditional Chinese Medicine) Perspective

Menopause/ Hot Flashes

Hot flashes fall under the disease category of Pre- and Postmenopausal Patterns in traditional Chinese medicine.15 According to Maciocia, menopausal symptoms are primarily due to a waning of “Kidney-Essence” which can manifest as Kidney-yin or yang deficiency.16 Kidney-yin deficiencies give rise to empty heat, whereas Kidney-yang deficiencies are less straightforward, pertaining to hot flashes. Maciocia explains, when Kidney-yang is deficient Kidney-yin will be deficient as well.16

Estrogen is a yin hormone and from a Chinese medicine energetics perspective, Tamoxifen is drying to Yin. It is theorized from a TCM perspective an overabundance of estrogen can contribute to dampness and thus the genesis of phlegm which may settle in the channels. Tamoxifen blocks the production of yin and thereby prevents the formation of phlegm.17 The Kidneys and Spleen in accord, contribute to the formation of Yin in the body. The Kidney’s contribute Yuan qi (transformed from Kidney essence) and the Spleen Gu qi (acquired through food and drink). The combination of these factors produces the body’s yin. Diet, emotional stress, and overwork can as mentioned above cause qi to stagnate, which in turn diminishes the Spleens ability to perform Transformation and Transportation of food and drink.

The authors Lomax, Schonbaum, Rebar and Spitzer state, a reduction of estrogen as seen in menopause can deplete the amount of β-endorphins, which is associated with the symptoms of hot flashes.5,18 Acupuncture has been found to increase estrogen and central β-endorphin activity.19 Since acupuncture can increase β-endorphins, thermoregulation becomes stable and thus a reduction of vasomotor symptoms decrease.20,21

In a single-blind study Chai Hu (Radix Burpleuri) one of the major herbs in the formula Jia Wei Xiao Yao San, was found to elevate serum β-endorphins levels. In this study, the authors used radioimmunoassay to measure plasma β-endorphins, epinephrine, and dopamine. The authors reported the experimental group’s plasma β-endorphins were significantly increased (p < 0.01) while epinephrine and dopamine were markedly decreased (p < 0.01). It was concluded by the study Chai Hu (Radix Burpleuri) regulates the nervous and endocrine systems.22

Breast Cancer

The diagnosis of cancer has a rich history in China and can be traced back to the Shang Dynasty (16th-11th century B.C.). Chao Yuanfang, the author of the book Zhu Bing Yuan Hou Lun [A General Treatise on the Cause and Symptoms of Disease] (610 A.D.), wrote extensively on the subject of tumors. Chao Yuanfang dedicated two chapters to tumors and described two categories of tumors. The Liu tumor is characterized as a slow growing mass that does not become hard (similar to benign tumors) and Shi Yong, firm, stone-like mass, painful and hot (similar to malignant tumors). Chao Yuanfang described a Ru Shi Yong (breast stone yong abscess), similar to the symptoms of malignant breast cancer e.g., firm mass, painful, hot and when pulled appears to have a root and the skin nearest to the mass appears as “oxide hide.”23

Peiwen, author of the book [Management of Cancer with Chinese Medicine] attributes the etiology and pathology of breast cancer to external and internal factors. External factors include external pathogenic Wind-Cold, pathogenic Fire Toxins, and Pathogenic Dampness. He describes internal factors including the seven emotions, obstructions of spleen qi, and deficiency of liver and kidneys. Internal factors cause imbalances in the Chong and Ren vessels, which then cause the Zang-Fu organs to weaken. Once the Zang-Fu organs become debilitated the immune function becomes weakened, and qi, blood, and phlegm stagnate and congeal. The stagnation eventually can give rise to pathogenic toxins and thus breast tumors.23

Case History

A forty-four-year-old female presented with complaints of night sweats, multiple allergies, eczema, overweight, and constipation. She related her night sweat symptoms to the side effects from the hormone therapy for her previously diagnosed breast cancer. She mentioned she did not experience night sweats before she was prescribed Tamoxifen 20 mg, once per day. She also related her symptoms appear to be aggravated by stress. The above patient was diagnosed with breast cancer via mammogram and received a lumpectomy one year prior to her first visit. She had been prescribed Tamoxifen.

The patient’s cancer was an invasive ductal carcinoma and was estrogen-receptor-positive. The cancer was a stage 1, i.e., there was no evidence of it spreading to lymph nodes. The patient received a lumpectomy, followed by chemotherapy (5 sessions every three weeks). She also received radiation therapy (for two months weekly), followed by hormone therapy (Tamoxifen), which she will take for ten years. During the lumpectomy, some axillary lymph nodes were removed to test for cancer cells - the procedure is called sentinel node biopsy.

Previous to the diagnosis, the patient reported experiencing depression, feelings sadness, and loneliness. She mentioned she was sleep-deprived. She had a hectic schedule and poor eating habits, in terms of timing and of the quality of food. For example she mentioned she was eating refined sugar and prepackaged food.

Table 1: Current Lab results
Test CBC/ W/MAN Diff CPA Result Range
White Blood Count 3.22 low 4.5-11.0 K/µL
Hemoglobin 11.9 low 12.0-16.0 GM/DL
Mean Corpuscular HGB Conc. 30.4 low 31.0-37.0 g/dl
Eosinophils 9.0 high 0-7 %

Examination

Blood pressure 140/90 mm Hg (taken by Omron BP742 - Automatic Blood Pressure Monitor) on the left, pulse 56 bpm, respiration rate 12 bpm, temperature 98.6º Fahrenheit.

Tongue – Body: Red, stiff and red points-tip and sides. Coat: none too dry.

Pulses – Left wrist: Cun HT/SI (full); Guan LV/GB (wiry), Chi KD/UB (deep)
Right wrist: Cun LU/LI (full), Guan SP/ST (empty), Chi KD/PC/TH (deep)

The patient's lifestyle activities included a regular exercise program of weights and aerobics performed for one hour four times a week. Dietary information included having oatmeal, fruit, a snack, and usually cheese for breakfast. Lunch included a small carbohydrate, cheese, protein, vegetables, and her dinner was similar to her lunch. She reported having yogurt as a snack. She has one cup of coffee daily, and 4-5 8oz glasses of water daily. She stated her sugar intake was minimal.

Her general symptoms included a high appetite, recent weight gain, fatigue, sores on her tongue, night sweats and flushing with flushing also during the day. She has bloating with meals and tends toward constipation. She used a laxative on a daily basis and reported having one bowel movement daily. She stated she had occasional headaches, as well as pain in her ankles. She has been diagnosed with eczema, especially on her hands, which are dry, flaky, and itchy. She also has canker sores in her mouth. She reported having hypertension, and depression. She stated she is easily stressed and has had thought of suicide. She mentioned having decreased libido.

Gynecological history included having menarche at age 14. The normal length of her cycle was 28 days, with a duration of 5-7 days. Her periods were painful. She mentioned having PMS, clots, and breast lumps. She denied any pregnancies, and her menopause was induced at age 43 due to a diagnosis of breast cancer.

Her respiratory history included having asthma as a child.

Traditional Chinese Medical Diagnosis and Rational

Kidney yin deficiency with empty heat
Liver qi stagnation
Blood stagnation/ deficiency
Spleen qi deficiency

Table 2. Symptomatic support for TCM diagnosis
TCM diagnosis Signs/Symptoms
Kidney yin deficiency with empty heat Red/dry tongue, full pulse in the cun position; flushing with night sweats, constipation, decreased libido
Liver qi stagnation Breast cancer (lump found in the breast region); headaches, easily stressed and depression.
Blood stagnation/ deficiency Lumps in the breasts, eczema (dry/flakey/ itchy); joint pain (sharp/ ankle); history of painful periods and clots.
Spleen qi deficiency Empty pulse in the Guan SP/ST; bloating with meals and fatigue.

Etiology and Pathogenesis

According to Maciocia, emotional issues can contribute to the development of breast lumps. Various unwanted emotions including “worry, pensiveness, sadness, “bitter weeping,” anger, frustration, resentment, hatred, repressed anger and guilt,” contribute to the genesis of breast lumps. The mentioned emotions can cause the Qi to become stagnated, and eventually cause blood to stagnate. Maciocia mentions, the liver channel, is not the only channel to be involved in the stagnation of qi, the lungs and heart may be involved due to channel location.16

Irregular diet and overwork may also contribute to the genesis of breast lumps, for example, dairy foods, fats, and sweets may lead to phlegm and thus contribute to the formation of lumps.16 Overwork may deplete liver and kidney yin. Yin/blood are the mother of Qi, therefore if yin becomes deficient Qi can stagnate. Since the lump has been surgically removed, the actual diagnosis of the cancer via TCM is rendered impossible.

However, the patient’s primary signs and symptoms can be identified and explained from a TCM perspective. The patient’s hot flashes can be described via the various contributing factors mentioned above including improper diet, unwanted emotions, and overwork. What can be determined by the patients sign and symptoms are her specific patterns as mentioned above.

Treatment Principles, Rational, and Plan

Treatment principles focused on nourishing Kidney Yin and eliminating empty heat, strengthen Spleen qi and course Liver qi and blood.

The patient was seen weekly, for a total of 22 treatments. At each treatment, between 8 and 12 points were chosen from the following list, depending on the patient’s presentation that day.

Acupuncture treatment was delivered with (34) 0.22 x 1 (30mm) Mac-Pipe Needle.

Acupuncture point location, method of stimulation and rational

Posterior
UB 23 (bilateral), reinforcing method, strengthen Kidney yin.
UB 20 (bilateral) reinforcing method, Back Shu of the Spleen, strengthen Spleen qi.

Anterior
DU 20; even method, clear the head and calm the Shen.
REN 12; reinforcing method, Front Mu of the Stomach, digestive issues, strengthens Spleen.
Large Intestine 4 (bilateral); even method, 4 Gates along with Liver 3; regulates the sweat glands, clears stagnation.
SP 4 (right); reinforcing method; Chong Mai Master Point, coupled with PC 6; abdominal issues due to stagnation of Qi and Blood.
SP 6 (bilateral); reinforcing method, tonify Yin and Blood, digestive disorders, hypertension.
LV 3 (bilateral); reducing method, digestive issues from LV Qi stagnation, calming point, with LI 4, four gates treatment - effects the flow of Qi and Blood in the body.
ST 36 (bilateral); reinforcing method, tonify deficient Qi and Blood, constipation.
ST 25 (bilateral); all intestinal issues – constipation.
PC 6 (left); reinforcing method, Chong Mai Master Point couple with SP 4.

Herbal Formula Therapy

The patient took two pills 3 x/day of the following Golden Flower Chinese herbal formulas. Jia Jian Er Xian Tang was taken for the first seven weeks of treatment until the Kidney pulse was sufficiently improved. The patient was compliant in taking her prescription.

Two Immortals Formula (Jia Jian Er Xian Tang)
Ingredients
Salviae Miltiorrhizae Radix (Chinese Salvia Root / Dan Shen) 11.7%
Polygoni Multiflori Radix Preparata (Polygonum Root, Fo Ti / Zhi He Shou Wu) 11.7%
Epimedii Herba (Epimedium / Yin Yang Huo) 9.4%
Moutan Cortex (Tree Peony Root Bark / Mu Dan Pi) 9.4%
Angelicae Sinensis Radix (Dong Quai, Tang Kuei / Dang Gui) 9.4%
Morindae Officinalis Radix (Morinda / Ba Ji Tian) 9.4%
Cistanches Herba (Broomrape, Cistanches / Rou Cong Rong) 9.4%
Cuscutae Semen (Chinese Dodder Seed, Chinese Cuscuta / Tu Si Zi) 7.75%
Poria (Poria, Hoelen, Tuckahoe / Fu Ling) 7.75%
Curculiginis Rhizoma (Curculigo Rhizome / Xian Mao) 4.7%
Anemarrhenae Rhizoma (Anemarrhena Rhizome / Zhi Mu) 4.7%
Phellodendri Cortex (Phellodendron Bark / Huang Bai) 4.7%

Chinese Medical Actions
Replenishes kidney yin and yang, regulates the ren and chong channels, harmonizes the blood, and drains fire.

Free and Easy Wanderer Plus ( Jia Wei Xiao Yao San)
Ingredients
Bupleuri Radix (Bupleurum Root / Chai Hu) 12.5%
Angelicae Sinensis Radix (Dong Quai, Tang Kuei / Dang Gui) 12.5%
Paeoniae Radix, Alba (Chinese White Peony / Bai Shao) 12.5%
Atractylodis Macrocephalae Rhizoma (White Atractylodes Rhizome / Bai Zhu) 12.5%
Poria (Poria, Hoelen, Tuckahoe / Fu Ling) 12.5%
Glycyrrhizae Radix Preparata (Chinese Licorice Root, Honey-Fried / Zhi Gan Cao) 6.25%
Paeoniae Radix, Rubra (Chinese Red Peony / Chi Shao) 6.25%
Moutan Cortex (Tree Peony Root Bark / Mu Dan Pi) 6.25%
Gardeniae Fructus (Gardenia Fruit / Zhi Zi) 6.25%
Curcumae Radix (Turmeric, Curcuma Tuber / Yu Jin) 6.25%
Leonuri Herba (Chinese Motherwort / Yi Mu Cao) 6.25%

Chinese Medical Actions

Clears heat, cools blood, relaxes constrained liver qi, nourishes and circulates blood and disperses blood stasis, strengthens the spleen and transforms phlegm, harmonizes the relationship between the liver and spleen.

Results

The patient was seen a total of 22 times on a once a week basis. Upon the second visit the patient mentioned a reduction of night sweats and hot flashes from 2-3 a night and 2-3 a day to 3 total day/night, pertaining to frequency and intensity. Upon the third visit the patient mentioned her eczema was flaring up on her hands. Spring wind ointment from Golden Flower Chinese herbs was prescribed; Ingredients: Sesame Oil, Beeswax, Rehmannia, Arnebia, Coptis, Turmeric, Safflower, Tangkuei, Peach Pit, Licorice, Phellodendron. Indications: eczema, clears heat, nourishes skin and dispels dryness.

By the seventh visit hot flashes and night sweats had been reduced to 2 times a day/night, blood pressure normalized to 121/80 mmHg, eczema improved and bowel movements regular. Upon the thirteenth visit the patient mentioned her menstruation had returned after one year of amenorrhea. Upon the sixteenth visit, the patient mentioned she had been experiencing zero flushing during the day and night sweats were becoming infrequent. Upon the twenty-second visit the patient reported a complete absence of flushing or night sweats; the patient’s eczema was much improved.

After the 22 visit, the patient fell out of treatment, due to lack of symptoms. A follow up in November of 2014 revealed the patient is still taking Tamoxifen and will be continuing it for an additional three years. Since her last visit, she reported feeling much better pertaining to the side-effects from the Tamoxifen. She mentioned she still gets some hot flashes, but they are less frequent (about two a day at most), most occurring at night, and rarely during sleep. I recommended she return for a follow-up visit to address her current needs.

Discussion

Hot flashes and night sweats are a common side effect of taking SERM pharmaceuticals, such as Tamoxifen. Acupuncture and Chinese herbs offer a way to minimize the symptoms related, as demonstrated with this patient. The above patient when first seen was experiencing night sweats and hot flashes from 2-3 a night and 2-3 a day. After 16 visits, the patient reported a complete absence of symptoms, pertaining to night sweats and hot flashes. The patient was pleased with the results and mentioned her quality of life had improved.

From a TCM perspective, the Chinese herbs and acupuncture effectively countered the side effects of Tamoxifen. From TCM perspective Tamoxifen is depleting to Kidney Yin; as observed via its mechanism of lowering estrogen, a yin secretion, and its diuretic function.24 The vasomotor symptoms of night sweats and hot flashes are common symptoms seen in Pre- and Postmenopausal TCM Patterns, specifically, Kidney Yin deficiency with empty heat. The herbs and acupuncture points used with this patient corrected this pattern and thus facilitated a rebalancing of the body. In a balanced state of yin and yang, symptoms, e.g. night sweats, and hot flashes greatly diminish. From Western Biomedicine perspective’s, acupuncture, and Chinese herbs biochemically affected the body’s physiology, which had a meaningful and remarkable effect on the patient’s symptoms and quality of life, as self-reported by the patient. As mentioned above, studies have suggested acupuncture is effective in altering central opioid activity, one of the mechanisms involved in menopausal vasomotor symptoms, and thus reduce vasomotor symptoms.5,25,26 Acupuncture has shown to significantly affect hot flashes and sweating not only during the studies, but offered prolonged benefits up to 3 months follow-up.26

This is but one example of what acupuncture and Chinese herbs can offer patients dealing with the side effects of Aromatase inhibitors (AI’s); however, research using acupuncture to treat the side effects of AI’s are beginning to surface. Small studies are demonstrating acupuncture’s ability to be effective in the reduction of the symptoms associated with AI’s. For example, a study (n=47) showed significant improvement in patient-reported outcomes (PROs) pertaining to severity (P = .006), frequency (P = .011) of menopausal symptoms of hot flashes.27 Another small study also demonstrated acupuncture’s great potential in improving cancer survivors symptoms including pain, fatigue, and hot flashes.27

Acupuncture is well known for its ability to reduce inflammation and mitigate pain. Case studies such as this demonstrate how this ancient form of healthcare has more to offer than simply pain care. Good medicine is safe medicine; from an integrative perspective TCM can increase the safety index pertaining to the specific use of Tamoxifen. TCM is still relevant in our modern healthcare system, as seen in its ability to reduce the side effects of pharmaceuticals. Recent studies have shown acupuncture to be helpful in reducing several of the comorbid symptoms are commonly seen in cancer patients, e.g. pain, fatigue and hot flashes.28 This form of healthcare comes with few if any side effects and a low cost when compared to the standard care of treatment in the reduction of symptoms associated with AI’s. Hormonal therapy, a common therapy for treating vasomotor symptoms is being used less commonly due to an associated cardiovascular risk.29 Due to the obvious reasons, hormone replacement therapy is not an option for breast cancer survivors. Successful case studies and several small studies utilizing TCM in the reduction of symptoms of pharmaceuticals such as Tamoxifen warrant future larger studies.

Conclusion

In summary, the patient experienced remarkable improvement and sustained response to TCM in managing the problematic Tamoxifen induced symptoms of night sweats and hot flashes. By mitigating the night sweats and hot flashes, the patient’s sleep and quality of life improved greatly. Tamoxifen remains to be the pharmaceutical of choice in the treatment and prevention of cancer. TCM may offer a valuable and effective non-drug approach to reducing Tamoxifen induced symptoms, improving quality of life and should be considered as a therapeutic approach. Chinese medicine can be used to counteract adverse effects of biomedical therapies, and this is one way in which the two medicines can be used together advantageously. Future studies on the use of TCM and the mitigation of side effects associated with Tamoxifen use is warranted.

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