Review of acupuncture treatment for perimenopausal syndrome

Li Rui-li (李瑞丽), Fu Jin-ying (傅金英), Deng Ying-ying (邓迎莹), Shen Wen-juan (沈文娟), Ma Hong-li (马红丽), Li Wei (李威), Wu Xiao-ke (吴效科)

1 Department of Obstetrics and Gynecology, National Key Discipline and Clinical Base, Heilongjiang University of Chinese Medicine, Harbin150040, China

2 Department of Obstetrics & Gynecology, Henan University of Chinese Medicine, Zhengzhou 450008, China

Critical Review

Review of acupuncture treatment for perimenopausal syndrome

Li Rui-li (李瑞丽)1, Fu Jin-ying (傅金英)2, Deng Ying-ying (邓迎莹)1, Shen Wen-juan (沈文娟)1, Ma Hong-li (马红丽)1, Li Wei (李威)1, Wu Xiao-ke (吴效科)1

1 Department of Obstetrics and Gynecology, National Key Discipline and Clinical Base, Heilongjiang University of Chinese Medicine, Harbin150040, China

2 Department of Obstetrics & Gynecology, Henan University of Chinese Medicine, Zhengzhou 450008, China

Objective:To summarize the mechanism of acupuncture in treating perimenopausal syndrome (PMS) from the aspects of reproductive endocrinology, immune system, neuroendocrine, the metabolism of free radicals and bone, and the effect of lipid.

Methods:The databases including MEDLINE, EMBASE, CNKI, Wanfang, and CQVIP were searched from the launch of each database to June 2014 for relevant papers involving clinical and laboratory researches about PMS treated with acupuncture.Results:Acupuncture is a safe, effective, and scientific method in treating PMS, and the efficacy is significant.Conclusion:Considering the limits of previous studies, future research should use high technologies such as molecular biology and genetic testing, and adopt multicenter randomized controlled study method to evaluate the efficacy of acupuncture in treating female PMS, and to further explore the mechanism of acupuncture in treating PMS.

Acupuncture Therapy; Perimenopause; Climacteric; Women; Review

As an integral part of traditional Chinese medicine (TCM), acupuncture dates back about 3 000 years[1]. It has been accepted as a complementary and alternative medicine therapy in the United States[2]. The history of using acupuncture to treat female reproductive disorders lasts at least 2 000 years. Acupuncture has been known to regulate the nerve-endocrine-immunity network, free radical metabolism, blood lipid and bone metabolism[3-6], with the advantages of convenience, lower cost and safety.

Perimenopausal syndrome (PMS) is a female reproductive disorder, presenting a series of somatic and psychological symptoms, such as menstrual disorders, anxiety, change of blood pressure, hot flashes[7], depression and sweating, and insomnia. Hormone replacement therapy (HRT) is effective in treating PMS[8], but it has many side effects and increases the risks of cancer[9], pulmonary embolism, and cardiovascular disease[10]. That’s why it is not widely accepted by patients, about 10% in America and less than 1% in China[11]. However, it offers a good chance to acupuncture therapy and the efficacy of acupuncture in treating PMS has been confirmed by a large amount of studies. Therefore, researches on acupuncture in treating PMS have become a core issue.

We reviewed the experiments and clinical trials in which acupuncture was adopted to treat PMS by observing reproductive endocrinology, immune system, neuroendocrine, metabolism of free radicals, lipid, and the metabolism of bone.

1 Mechanism of Acupuncture in Treating PMS

1.1 Regulation of reproductive endocrine system

With gradual degradation of ovarian function andfemale hormone level[12], especially serum estradiol (E2), women in perimenopausal period easily suffer from dysfunction of hypothalamic-pituitary-ovarian axis (HPOA) and a series of clinical symptoms. It’s reported that acupuncture has a content effect in regulating HPOA[13-16]. Researchers have found that acupuncture can increase the level of serum E2, decrease the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH), and improve clinical symptoms, especially hot flashes[17-19].

Shang YJ, et al[20]believe that the combination of Yuan-Primary points and Back-Shu point can effectively regulate the levels of E2, FSH and LH in PMS, and the effect is more significant than that of conventional acupuncture. Jin H, et al[21]designed a clinical study on acupuncture at the Back-Shu points of the five Zang organs in the treatment of PMS, with a group of subjects treated with oral administration of Premarin tablets as the control. The results showed that the therapeutic efficacy of acupuncture at the Back-Shu points is higher than that of Premarin. Moreover, Qin ZY, et al[22]found that electroacupuncture (EA) at Sanyinjiao (SP 6) can modulate the function of reproductive endocrine in PMS patients. Li Y, et al[23]observed the effects of different acupoints combination in treating PMS. Eighty subjects with PMS were recruited and randomly allocated to a Guanyuan (CV 4) group [selecting Guanyuan (CV 4) and Sanyinjiao (SP 6)] and a Neiguan (PC 6) group [selecting Neiguan (PC 6) and Zusanli (ST 36)], and the results showed that the E2level increased in both groups. In 2009, Liu DH[24]discovered that acupuncture and moxibustion plus psychotherapy can produce an ideal therapeutic effect on female PMS without side effects and the efficacy was higher than acupuncture and moxibustion treatment. Other researchers also found this phenomenon[25-30].

In order to explore the specific mechanisms of acupuncture therapy in treating female PMS, Chen BY, et al[31]designed a trial to study from the perspective of HPOA. The results showed that there was a decrease of blood E2and an increase of the expression of estrogen receptor protein and mRNA in the brain of ovariectomized (OVX) rats; while through stimulating the effective acupoints, EA increased the level of blood E2and suppressed the level of estrogen receptor, and consequently normalized the function of hypothalamicpituitary-ovarian axis. Ma S, et al[32]used quantitative real-time reverse transcription PCR (qRT-PCR) to detect the effects of EA on estrogen receptor alpha (ERα) and beta (ERβ) mRNA and protein expression in the hypothalamus of OVX rats. The results demonstrated that EA treatment could restrain the elevated mRNA and protein expression of ERα and ERβ in hypothalamus of the OVX rats, and also inhibited GnRH mRNA level in OVX rats. This should be a crucial mechanism of EA in treating PMS. This phenomenon had also been confirmed by Li XH, et al[33]. Yao X, et al[34]discovered that EA could increase the level of E2and the expression of prolactin-releasing peptide (PrRP) in the medulla oblongata of OVX rats. These results all suggest that EA can improve the reproductive disorders. Other researches[35-36]in China found that EA may increase E2level via promoting aromatase activity and mRNA expression in adipose and liver tissues, and transforming androgen into estrogen.

1.2 Regulation of immune system

Recently, the exploration of the relationship between menopause and immunity has attracted great attention. Wang WJ, et al[37]proved that splenic estrogen receptor (ER) and serum E2levels were generally down in the aging female rats. Therefore, it’s concluded that the function of immune system should be regulated by ER. In the aging rats, decreased serum E2level leads to the fading of ER in immune cells and then results in low immunity. With the arrival of aging, estrogen decreases because ovarian function declines and the immune function of perimenopausal women is consequently impaired. Li J, et al[38]believe that acupuncture can regulate cellular and humoral immune, and different acupoints can selectively activate different immune system. Chen JX, et al[39]discovered that acupuncture can increase the levels of interleukin (IL)-8, E-selectin and L-selectin, which may be one of the mechanisms that acupuncture regulates immune function. Liu HY, et al[40]reported that EA can improve the immunity of menopausal rats. In other reports, it’s found that EA can regulate estrogen receptor expression of immune cells and enhance immunity.

1.3 Regulation of neuroendocrine system

It’s confirmed that the changes of neurotransmitters should be related to menopause. The neurotransmitters include substance P (SP), β-endorphins (β-EP), 5-hydroxytryptamine (HT), dopamine (DA), epinephrine (E) and so on, which are important in regulating the secretion of Gonadotropin-releasing hormone (GnRH) and interacted with estrogen. The GnRH increases with the elevated SP, E and 5-HT; GnRH decreases with the elevated β-EP and DA. β-EP[41]and DA[42]are comparatively low in PMS patients, but SP, 5-HT and E are comparatively high in PMS patients. Researchers suggested that acupuncture can modulate the neurotransmitters in rats[43-44]. Therefore, acupuncture therapy is effective in improving the neurological disorders in PMS. Hao JW, et al[45]discovered that acupuncture can increase DA andγ-amino-butyric acid (GABA) which can inhibit the release of GnRH; while acupuncture also reduced aspartate (Asp), glutamate (Glu) and 5-HT which can promote the release of GnRH. Bao YX, et al[46]also proved that acupuncture can increase DA in brain issues of rats.

1.4 Regulating the metabolism of free radicals and anti-aging

Free radicals are one of the major causes of aging. They can react with substances such as nucleic acids, proteins and lipids in the body and change them into oxide or peroxide, and subsequently damage the body, resulting in aging and death. During the recent years, the relationship between the free radicals and menopause has attracted the attention of the medical researchers. With the decline of ovarian function and disorders of sex hormone in perimenopausal women, lipid peroxidation increases and the activity of free radical scavenging enzymes decreases[47]. It has been proven that acupuncture can postpone the aging process of cells by eliminating the free radicals and enhancing the activities of anti-oxidases[48].

Li M, et al[49]observed the effects of EA at Yongquan (KI 1) acupoint on the expression of p53 and bcl-2 in the aging rats. The results showed that the p53 gene expression in aging rats was suppressed by EA at Yongquan (KI 1). Cong SY, et al[50]adopted EA to stimulate Zusanli (ST 6) and Guanyuan (CV4) acupoints in the aged female rats, and the results indicated that acupuncture can enhance the level of nitric oxide (NO) and the activity of superoxide dismutase (SOD), and decrease the level of malondialdehyde (MDA) in the rats’ brain, and there was a significant difference compared with the control group. The results were then confirmed by Bai W, et al[51].

1.5 The effects on lipid metabolism

With the decline of ovarian function, the estrogen level also drops in the perimenopausal women. Korljan B, et al[52]believe that the decline of estrogen concentration should be associated with a number of changes in perimenopause: increase of total cholesterol (TC), triglycerides, and low density lipoprotein cholesterol (LDL-C). Therefore, menopause is a process closely related to cardiovascular risk factors[53]. Cai H, et al[54]observed the effect of acupuncture on serum NO content and activity of myeloperoidase in rats with hyperlipoidemia. They concluded that acupuncture can reduce blood lipid, and the mechanism may be related to the inhibition of oxidative state. Li CJ, et al[55]found that acupuncture at Fenglong (ST 40) effectively stopped the increase of blood lipids. Other studies also obtained similar results[56-57]. Another interesting experiment performed in China by Xu TS[58]discovered that acupuncture could decrease the level of TC and LDL-C, and increase the level of high-density lipoprotein cholesterol (HDL-C) in patients with PMS.

1.6 Effects on bone metabolism

Postmenopausal osteoporosis stems from estrogen deficiency, which is because estrogen insufficiency stimulates the formation of both osteoblasts and osteoclasts[59-60]. When osteoblasts become active, osteoblasts will secrete a large amount of alkaline phosphatase (ALP) and deoxypyridinoline (DPD), which is an important part of type I bone collagen matrix. When the bone matrix is dissolved, bone collagen protein will hydrolyze to be DPD, which will then come into blood. DPD can be also discharged directly from the kidney in the form of prototype, which reflects the situation of bone resorption. One experiment was done by Li J, et al[61], showing that acupuncture improves the level of serum ALP and reduces the level of DPD in the osteoporosis rats, consequently promoting bone formation and inhibiting bone resorption, thus preventing the occurrence of osteoporosis in ovariectomized rats. Other researchers in China[62]had also achieved the similar results.

2 Summary and Future Directions

Recent clinical and experimental studies have confirmed that acupuncture therapy is effective in treating PMS by improving clinical symptoms such as menstrual disorders, hot flashes, sweating, insomnia, and mood disorders. The mechanism of acupuncture in treating PMS includes the following aspects: regulation of reproductive endocrine system, i.e. increasing the level of estrogen, decreasing the levels of FSH and LH, increasing the expression of estrogen receptor protein, inhibiting the release of GnRH, and transforming androgen into estrogen; regulation of immune system, i.e. increasing the levels of E-selectin and L-selectin, regulating estrogen receptor expression in immune cells; regulation of neuroendocrine system, i.e. increasing DA and GABA, decreasing Asp and Glu; modulation of free radicals, i.e. enhancing the content of NO and the activity of SOD; modulation of blood lipids, i.e. suppressing oxidative stress state of organism; regulation of bone metabolism, i.e. increasing the level of serum ALP and reducing the level of DPD. Therefore, acupuncture now has been widely accepted as an effective treatment for PMS by many countries.

These trials are the bases for further researches on the mechanism and action pathways of acupuncture therapy in treating PMS. They also offer an innovative treatment approach for perimenopausal women rather than using herbal medicine or Western medicine alone. However, to improve the quality of acupuncture researches, future clinical and experimental studies should have a rigorous and standard design, such as increasing the sample size, employing the methods of blinding (i.e. blinding to observer and patient), paying attention to the details of acupuncture, and the training of acupuncturists.

Conflict of Interest

There was no conflict of interest in this article.

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针刺治疗围绝经期综合征的研究进展

目的：从生殖内分泌、免疫系统、神经内分泌、自由基和骨的新陈代谢、血脂改变的角度，总结针刺治疗围绝经期综合征的机制。方法：检索了截止到2014年6月发表的临床和实验的针刺治疗围绝经期的研究，检索数据库包括MEDLINE，EMBASE，CNKI，万方和重庆维普。结果：针刺治疗围绝经期综合征是安全的、有效的、科学的，疗效是显著的。结论：以前的研究存在一定的局限性，以后再开展研究时，应采用诸如分子生物学、基因检测等高科技，也应开展更多的随机对照临床试验来评估针刺治疗围绝经期综合征的疗效，进一步探讨针刺治疗围绝经期综合征的机制。

针刺疗法; 围绝经期; 更年期; 妇女; 综述

R246.3 【

】A

27 August 2014/Accepted: 15 October 2014

Author: Li Rui-li, M.D. candidate

Wu Xiao-ke, professor.

E-mail: Email:xiaokewu2002@vip.sina.com