Review Article The Complementary and Alternative Medicine for Polycystic Ovary Syndrome: A Review of Clinical Application and Mechanism
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Evidence-Based Complementary and Alternative Medicine
Volume 2021, Article ID 5555315, 12 pages
https://doi.org/10.1155/2021/5555315
Review Article
The Complementary and Alternative Medicine for Polycystic Ovary
Syndrome: A Review of Clinical Application and Mechanism
Li-Yan Jia ,1 Jia-Xing Feng,2 Juan-Li Li ,2 Fang-Yuan Liu ,2 Liang-zhen Xie ,1
Shou-Juan Luo ,3 and Feng-Juan Han 1
1
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,
Harbin, China
2
Heilongjiang University of Chinese Medicine, Harbin, China
3
Digestive Hospital of Heilongjiang Hospital, Harbin, China
Correspondence should be addressed to Shou-Juan Luo; luoshoujuan1978@163.com and Feng-Juan Han; hanfengjuan2004@
163.com
Received 6 January 2021; Revised 8 February 2021; Accepted 19 February 2021; Published 26 February 2021
Academic Editor: Yong Wang
Copyright © 2021 Li-Yan Jia et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
As a reproductive endocrine disease, polycystic ovary syndrome (PCOS) has influenced billions of women during childbearing age
worldwide. Owing to its complex etiology and ambiguous pathogenesis, there is still not a specific method to cure it. Clinical
treatments, such as hormone therapy and surgical treatment, have side effects. Therefore, it is essential and urgent to seek
alternative treatment to solve these problems. The satisfactory efficacy of complementary and alternative medicine (CAM), such as
traditional Chinese medicine (TCM), immunotherapy, medicinal foods, vitamin therapy, diet therapy, psychotherapy, spa, and
oxygen therapy, in treating PCOS, has aroused an increasing number of medical workers’ concern and gradually become the
mainstream. This paper reviews the application of CAM in the treatment of PCOS, especially from the perspective of TCM.
Meanwhile, the limitations of the literature about CAM in the treatment of PCOS are mentioned and analyzed as well.
1. Introduction compliance, poor efficacy, and even contraindications [5].
Therefore, it is urgent to find a more effective treatment for
Polycystic ovary syndrome (PCOS) is a reproductive en- PCOS.
docrine disease characterized by menstrual disorder, in- Complementary and alternative medicine (CAM), an
fertility, and obesity, usually accompanied by insulin alternative therapy independent of Western medicine, has
resistance and metabolic disorders [1]. Due to various been extensively used in health care systems around the
reasons such as bad eating habits and unprecedented psy- world. Numerous studies have indicated that using CAM
chological and social pressure, its incidence has gradually including acupuncture, Chinese herbal medicine, Tai Chi,
increased as high as 5%–10% [2, 3]. The pathogenesis of yoga, and Qigong can also effectively treat PCOS with fewer
PCOS is relatively complex, which may be closely related to adverse reactions. Based on this, the purpose of this review is
genetic factors, endocrine, and specific environment [4]. It is to provide more accurate evidence for the treatment of
usually diagnosed with the Rotterdam diagnostic criteria. PCOS by CAM and to analyze its underlying mechanisms.
According to the pathophysiology and clinical characteris-
tics of PCOS, the treatment of PCOS includes exercise to lose
weight, decrease androgen, and improve insulin resistance
2. Acupuncture
(IR), oral contraceptives to regulate the menstrual cycle, and Acupuncture, an indispensable part of CAM, has been used
ovulation induction. These conventional treatments, how- in China for more than 3000 years. With the modernization
ever, have problems such as adverse reactions, low of TCM, more and more Western countries have begun to2 Evidence-Based Complementary and Alternative Medicine
apply it for treating and preventing diseases. Due to its safety of the treatment. However, due to issues such as the
superiorities, namely, ease of operation, economical and quality of the literature, further researches are needed to
satisfactory effect, etc., acupuncture has gradually been used prove its effectiveness. Based on the data analysis, Yu et al.
in the treatment of PCOS. According to literature searched [19] outlined the rules of acupoint-selection for PCOS
at the database PubMed and CNKI, we concluded that after (Table 1)
thousands of years of development, acupuncture has not
only been limited to its original model but has gradually
2.2. Electroacupuncture (EA). With the increasing applica-
evolved into different forms such as acupuncture, electro-
tion of acupuncture in Western countries, EA, a derivative of
acupuncture, warm acupuncture, acupoint embedding, and
acupuncture, is gradually being used in the treatment of
auricular points [6, 7]. At present, there are different
PCOS. EA refers to the combination of electric current with
mechanisms of acupuncture for PCOS summarized through
acupuncture to achieve the purpose of strengthening the
considerable clinical and animal trials such as the fact that it
stimulus [20]. At present, the mechanism of EA on PCOS
can regulate the function of the hypothalamus-pituitary-
has not been clarified. Xu G conducted an animal experi-
ovarian axis (HPOA) and the metabolism, promote ovu-
ment showing that the number of immature follicles, the
lation, and improve insulin resistance (IR) and endometrial
FSH, the LH/FSH, and the serum anti-Müllerian hormone
receptivity (ER) [8, 9].
(AMH) were decreased by EA stimulated on CV4, SP6, and
ST36 [21]. Similarly, some studies have shown that EA can
correct the imbalance of FSH and AMH in PCOS granulosa
2.1. Acupuncture. Acupuncture refers to using the needle
cells by inhibiting the excessive secretion of AMH, thus
inserted into the patient’s specific area of the body at a
improving hyperandrogenemia and follicular development
certain angle to cure diseases through the manipulations
stagnation [22]. Peng et al. concluded that EA can improve
such as twisting, lifting, and thrusting [10]. Several studies
IR, mitochondrial dysfunction, and ER by enhancing
have proven that acupuncture is beneficial in treating PCOS.
autophagy in PCOS-like rats [23].
A review summarized from limited evidence-based studies
Budihastuti UR randomized 44 PCOS patients into a
showed that acupuncture can be effective in improving
control group and an EA group. The EA group was treated
PCOS-related symptoms, including the induction of ovu-
for 15 minutes per time, twice a week, for six consecutive
lation and restoration of menstruation [11]. An animal
weeks. The results show that EA can promote the growth of
experiment conducted by Zhang showed that acupuncture
oocytes in PCOS patients [24]. Li [25] conducted a study on
could significantly reduce the number of cystic expanded
62 PCOS patients undergoing IVF-ET and found that EA
follicles and the rate of cystic expanded follicles, increase the
can improve the quality of oocytes. The mechanism may be
corpus luteum, and significantly improve the ovarian
as follows: EA acts on HPOA to regulate the secretion of
morphology [12]. In addition, other studies have shown that
gonadotropin-releasing hormone or increase the sensitivity
acupuncture can reduce the incidence of PCOS by changing
of the pituitary to gonadotropin, indirectly regulate the
the distribution of specific intestinal flora, increasing the
secretion of FSH, and then improve the quality of follicles
content of beneficial bacteria, and maintaining the balance
and embryos. Cui [26] also reached the same conclusion in
between the internal and external environment of the pa-
the RCT and proposed that its mechanism may be related to
tients [13]. Ee designed a protocol to verify their hypothesis
the changes of the ovarian microenvironment.
that the mechanism of acupuncture for obese PCOS patients
is improving IR [14].
Wu et al. [15] randomized 112 obese PCOS patients into 2.3. Acupoint Catgut Embedding. Acupoint catgut embed-
the treatment group and control group. The treatment group ding refers to using needles and absorbable catgut to
was administrated with metformin combined with acu- stimulate meridians, balance yin, and yang, reconcile qi, and
puncture Xiawan (CV10), Zhongwan (CV12), Guanyuan blood to achieve the purpose of curing diseases [27]. Acu-
(CV4), Qihai (CV6), Tianshu (ST25), Shuidao (ST28), and point catgut embedding not only has a function similar to
bilateral Liangmen (ST21), while the control group was acupuncture but can also stimulate continuous and spon-
merely given metformin. After 3 months, they found that, in taneous. The superiority of it lies in its remarkable and stable
obese PCOS patients, acupuncture can effectively improve efficacy in treating disease with fewer adverse reactions.
the ovarian function by regulating the luteinizing hormone Numerous researches have confirmed the effectiveness and
(LH), the follicle-stimulating hormone (FSH), and the tes- have elaborated the mechanism of acupoint catgut em-
tosterone (T) and reducing LH/FSH, leptin (LEP), and bedding in PCOS. Lin [28] conducted an animal experiment
obesity. Its mechanism may be related to the reduction of to explore the mechanism of acupoint catgut embedding in
LEP [16]. Jin et al. [17] summarized 52 articles on the rules of PCOS. They found that acupoint catgut embedding can
acupuncture in PCOS patients and concluded that the most significantly improve IR and increase the expression of MiR-
frequently used acupoints were Sanyinjiao (SP6), CV4, 125b in PCOS rats’ ovaries. MiR-125b can reduce the high
Zigong (EX-CA), Zhongji (CV3), and CV6. Ren [18] con- expression of ERK1 and ERK2, downregulate the abnormal
ducted a systematic review and meta-analysis on the activation of the MAPK/ERK pathway, restore the balance
treatment of PCOS with acupuncture and concluded that between proliferation and apoptosis of granulosa cells, and
acupuncture can reduce HOMA-IR and BMI, promote reduce the excessive synthesis of androgen by theca cells. It
ovulation, increase pregnancy rate, etc. while ensuring the may be the epigenetic posttranscriptional mechanism ofEvidence-Based Complementary and Alternative Medicine 3
Table 1: The rules of acupoint-selection of acupuncture for PCOS.
Meridian Acupoints
Guan yuan (CV4), zhong ji (CV3), qi hai (CV6), zhong wan (CV12), shui fen (CV9), qu gu (CV2),
Ren meridian
dan zhong (CV17)
Spleen meridian of foot-Taiyin San yin jiao (SP6), xue hai (SP10), yin ling quan (SP9), da heng (SP15), di ji (SP8)
Stomach meridian of foot- zu san li (ST36), tian shu (ST25), gui lai (ST29), feng long (ST40), hua rou men (ST24), shui dao
Yangming (ST28)
Bladder meridian of foot-Taiyang Shen shu (BL23), pi shu (BL20), gan shu (BL18), ge shu (BL17), ci liao (BL32)
Extra points Zi gong (EX-CA1), luan chao (TF2)
Kidney meridian of foot-Shaoyin Tai xi (KI3), da he (KI12), heng gu (KI11), fu liu (KI7)
Liver meridian of foot-Jueyin Tai chong (LR3), xing jian (LR2)
Du meridian Bai hui (GV20), ming men (GV4), da zhui (GV14)
Large intestine meridian of hand-
he gu (LI4)
Taiyang
Pericardium meridian of hand-
Nei guan (PC6)
Jueyin
Gallbladder meridian of foot-
Dai mai (GB 26), xia xi (GB43)
Shaoyang
acupoint catgut embedding in improve IR and reproductive oxidative stress (OS) in PCOS patients. Through compari-
endocrine in PCOS. Wang [29] randomly divided 60 obese son, we found that warming acupuncture improves the OS
PCOS patients into acupoint catgut embedding group and level of obese PCOS patients more significantly than non-
acupuncture group. After treatment, hyperandrogenemia obese PCOS patients.
was significantly improved, and the total effective rates were
54% and 42%, respectively. There was no significant dif-
2.4.2. Auricular Points. When problems occur in certain
ference between the two groups, which indicates that acu-
parts of the body, it will react in the corresponding of the
point catgut embedding has the same effect as acupuncture.
auricle. These parts refer to the auricular point. Auricular
Because of its time-saving and low-cost characteristics, it is
point is mainly used to treat various diseases by stimulating
worthy of further promotion in clinical practice. Yu et al.
auricular point, which has been used as adjuvant therapy for
[30] analyzed the published literature and concluded that the
a long time in China. The main methods of stimulating
top 10 acupoints used in acupoint catgut embedding for
auricular point are acupuncture, embedding needle,
PCOS were ST25, CV4, ST40, SP6, GB26, BL23, CV12, ST36,
bloodletting, auricular point sticking, magnetic therapy,
CV6, and SP9. Due to the heterogeneity of the small sample
massage, etc. [34]. Gao [35] randomized 60 patients with
size and low quality of literature, more clinical trials are
PCOS infertility into a treatment group (30 participants) and
needed to verify its efficacy to promote the clinical
a control group (30 participants). The treatment group was
application.
given auricular points, and the control group was given oral
Chinese herb medicine (CHM). The total effective rate of
2.4. Other Acupuncture Therapies these two groups was 53.3% and 46.7%, respectively. There
was no difference between the two groups. It shows that
2.4.1. Warming Acupuncture. Warming acupuncture refers auricular points for PCOS infertility have an equal effect of
to the process of keeping the needle, twisting the moxa mass CHM. Studies have also reported that the mechanism of
around the needle handle to ignite, and transferring heat auricular points in PCOS is that it can regulate the functions
into the acupoints through the needle. Warming acu- of the anterior pituitary and ovaries [36]. Compared with
puncture is also a combination of acupuncture and mox- other CAMs, the auricular point is easy to operate and
ibustion. Lin et al. [31] randomized 58 PCOS patients into a inexpensive, so it has a high acceptance rate and is worthy of
control group (using acupuncture treatment) and a treat- promotion.
ment group (using warming acupuncture). After 3 sessions
of treatment, the effective rates of the two groups were 3. Chinese Herbal Medicine
66.67% and 44.43%, respectively. Xu’s clinical trials also
reached the same conclusion that warming acupuncture can As a part of CAM, CHM has saved thousands of Chinese
treat PCOS effectively. The results showed that after treat- people in the development of China. It started with Shen
ment, the observation group was better than the control Nong, a medical scientist in ancient China. After thousands
group in terms of ovarian volume, follicle number, ovulation of years’ exploration and practice, CHM has gradually be-
number, pregnancy rate, etc. (P < 0.05) [32]. Gu [33] divided come a major part of China’s medical system. The clinical
62 PCOS patients into the obese group and nonobese group efficacy of CHM is remarkable, especially for gynecological
according to BMI. Both groups were treated with warming diseases such as dysmenorrhea, infertility, and PCOS [37].
acupuncture for 3 cycles. The results show that warming The following content mainly focuses on the clinical efficacy
acupuncture can effectively reduce T, LH, and LH/FSH, and mechanism of TCM monomer and TCM compound in
increase SOD activity, reduce MDA level, and improve PCOS [38, 39].4 Evidence-Based Complementary and Alternative Medicine
3.1. Chinese Herbal Monomer Extracts (36 cases) and the control group (36 cases). The observation
group took Diane-35 combined with a Tanshinone capsule,
3.1.1. Berberine. Berberine is a quaternary ammonium salt while the control group was given Diane-35 merely. After
from the protoberberine group of isoquinoline alkaloids. It 3 months, TG, TC, LDL-C, TSH, LH, ACTH, β-EP, Cor, and
can be found in plants such as Berberis, Berberis aquifolium UFC were all improved. It is concluded that the Tanshinone
(Oregon grape), and Berberis vulgaris (barberry) [40, 41]. capsule could improve the lipid metabolism of PCOS pa-
Several studies have already reported about berberine on tients and regulate the function of the HPOA.
PCOS and summarized its mechanism including lowering
blood glucose, improving IR, decreasing androgen, and
affecting lipid metabolism. Meanwhile, a meta-analysis drew 3.1.3. Other Chinese Medicine Monomers. The total flavo-
a conclusion that berberine showed a promising prospect in noids of Cuscuta are extracted from the herbal medicine
treating PCOS-IR [42]. Cuscuta. Studies have shown that the total flavonoids of
Animal experiments showed that berberine could reduce Cuscuta can reduce the ovarian index of PCOS-like rats and
blood glucose and improve IR by activating the PI3K/AKT alleviate the proliferation; meanwhile, it can also restore the
pathway and inhibiting the upregulation of the MAPK HPOA function by regulating the secretion of estrogen and
pathway and glucose transporter 4 (GLUT4) [43, 44]. Zhang androgen and inhibiting the expression of ovarian apoptotic
et al. [45] found that berberine could decrease the level of IR proteins [53, 54]. Glycyrrhetinic acid, a main component of
in PCOS-like rats by improving GLUT4, which can regulate the traditional Chinese medicine licorice, can treat PCOS
both the PI3K/AKT and MAPK pathways. Another animal due to its anti-inflammatory, analgesic, antiallergic, etc.
experiment conducted by Feng L et al. also confirmed that properties. Studies have indicated that the mechanism of
berberine could effectively decrease the blood supply and glycyrrhetinic acid in treating PCOS lies in the fact that it can
angiogenesis of ovarian tissue and improve the morphology enhance insulin sensitivity and reduce testosterone in PCOS
of ovarian tissue in PCOS rats [46]. Zhang et al. [47] made a patients. In addition, glycyrrhetinic acid can increase the
study on 20 rats to observe the mechanism of berberine on expression of AMPK mRNA in porcine ovarian granulosa
PCOS. The study confirmed that berberine could improve cells and reduce the androgen secretion capacity of insulin-
abnormal glucose and lipid metabolism in PCOS-like rats resistant granulosa cells and the level of CYP17 mRNA
and regulate the level of serum steroid hormones. Berberine [55, 56]. Silymarin is extracted from the dried fruits of the
plays a vital role in the treatment of PCOS-related repro- Compositae plant Silybum marianum. Studies have found
ductive disorders. Studies about the mechanism of berberine that both glycyrrhetinic acid and silibinin can increase the
pointed out that it could improve the gene level, upregulate expression level of AMPK mRNA and reduce the androgen
the expression of ovarian CYP19a1 gene and uterine Glut4 secretion capacity and CYP17 mRNA of insulin-resistant
gene, and downregulate the expression of ovarian CYP17a1 granule cells [57].
gene. In summary, considerable trials have verified the ef-
fectiveness of Chinese medicine monomers on PCOS and
concluded that its mechanism may be related to improving
3.1.2. Cryptotanshinone. Cryptotanshinone is extracted IR, reducing androgen level, regulating lipid metabolism,
from danshen root, a Chinese herb. Studies have shown that etc. However, the existing studies on PCOS by Chinese
it can significantly improve the abnormal glucose and lipid medicine monomers still lack persuasiveness due to some
metabolism and hyperandrogenemia and can reduce the inevitable factors. Therefore, more high-quality research
inhibitory effect of PI3K inhibitor LY294002 on the PI3K studies are needed to add weight to its efficacy in PCOS.
pathway in cerebral cortex nerve tissue, thereby protecting
the activity of nerve cells, which may be the mechanism of
cryptotanshinone in treating PCOS [48]. 3.2. Chinese Herbal Formulas. Compared with other CAMs,
An animal experiment conducted by Kuang HY showed formulas are the most commonly used in China. However,
that cryptotanshinone could significantly reduce the ca- compared with the remarkable efficacy of formulas, the
pability of PCOS mice to modulate glucose levels in re- explanation of its mechanism lacks unified evidence.
sponse to varying diets; meanwhile, it could increase the Therefore, the existing mechanisms of formulas in treating
phosphorylation level of key molecules in the PI3K signaling PCOS are still not convincing and need to be confirmed by
pathway of ovarian granulosa cells that reduced the ovarian further studies. A review about formulas in treating PCOS
volume of PCOS rats. The expression levels of steroid showed that several herbs were beneficial in improving
hormone synthase STAR and CYP17 in rat granulosa cells menstrual and ovulatory dysfunctions, obesity, IR, lipid
can improve hyperandrogenism [49]. Another rat experi- metabolism dysfunction, and androgen excess-related
ment showed that cryptotanshinone improved abnormal conditions [58]. Based on one study, the treatment of PCOS
glucose and lipid metabolism in PCOS rats and reduced LH with formulas may correct the abnormal secretion of en-
and T levels to restore the estrous cycle and ovulation of rats docrine hormones and improve glucose and lipid meta-
[50]. Studies have suggested that the effect of cryptotan- bolism, etc., thereby improving ovarian morphology and
shinone on PCOS may be achieved by downregulating the pregnancy outcome [59]. The usual clinical formulas mainly
expression of the CYP17 gene and IR [51]. Wu et al. [52] include Cangfu daotan Decoction, Xiaoyao San, Jiawei
randomized 72 PCOS patients into the observation group Xiaoyao San, and Danggui Shaoyao San. The composition ofEvidence-Based Complementary and Alternative Medicine 5
these formulas is listed in Table 2. The following content improved significantly in the treatment group. An animal
describes the treatment of PCOS individually [60]. experiment reached the same conclusion either.
3.2.1. Cangfu Daotan Decoction (CDD). Cangfu Daotan 3.2.4. Danggui Shaoyao San (DSS). Danggui Shaoyao San
decoction (CDD) is used for PCOS patients, especially the (DSS), created by Zhang Zhongjing, has been a common
patients who are the type of stagnation of phlegm and Chinese herbal formula, which was used since the Han
dampness. According to a rat trial conducted by Yi about dynasty. Jia and Nie [67] randomized 90 PCOS patients
CDD on obesity-type PCOS, the result showed that CDD into the treatment group (47 cases) and the control group
decreased the serum levels of TCHO, TG, LDL-c, LH, T, IL- (43 cases). DSS was prescribed to treatment group patients,
1β, IL-6, and TNF-α and increased the levels of HDL-c, FSH, while the control group was given gonadotropin. After
and E2 in a dose-dependent manner. Meanwhile, CDD 6 months, the total effective rate was 85.1% and 55.8%,
could induce the expression of OATP2B1 and OATP3A1 in respectively. The results of an RCT made by Chen and Xue
ovarian and uterine tissues. Therefore, CDD could improve [68] showed that DSS could improve the sex hormones
pregnancy outcomes [61]. Zhang and Wu [62] analyzed that (LH, FSH) and adjust the menstrual cycle.
the mechanism of CDD in the treatment of PCOS is to
improve IR. Fan and Ling [63] randomly assigned 60 cases of
obese PCOS infertility patients into two groups each of 30 3.2.5. Other Chinese Herbal Formulas. In addition to the
cases. Both groups were given oral letrozole and proges- commonly used Chinese herbal formula for treating PCOS
terone, and the treatment group was given CDD on this mentioned above, some other formulas have been reported
basis. The results showed that the pregnancy rates in the to be effective in PCOS. A rat study demonstrated that the
treatment group and control group were 53.33% and underlying mechanism of Guizhi Fuling Wan in improving
26.67%, respectively, with a significant difference (P < 0.05). IR in PCOS-like rats is to regulate intestinal flora to control
In addition, it also has obvious advantages in increasing the inflammation [69]. Heqi San, a traditional Chinese herbal
diameter of HCG follicles and the thickness of the formula, has been reported to regulate hormone levels in
endometrium. PCOS patients with metabolic disease, which may be an
alternative application for treating PCOS. Zhao et al. [70]
concluded through animal experiments that the beneficial
3.2.2. Xiao Yao San (XYS). Xiao Yao San (XYS) is a tra- effects of Heqi San on PCOS include altering serum hor-
ditional Chinese formula that is widely used for treating mone levels, recovering ovary morphological lesions, and
gynecological disease, especially for patients with liver improving IR, which are mediated through the PI3K/AKT
constraint type PCOS. The results of animal experiments by pathway. Besides, Bushen Culuan Decoction (CCBCD)
Sun et al. showed that the mechanism of XYS treatment of could effectively treat infertility patients with PCOS,
PCOS may ameliorate chronic unpredictable mild stress- according to a protocol of systematic review [71].
induced irregular estrous cycles and follicles development
abnormalities, a decrease of estradiol and progesterone level 4. Dietary Supplements
as well as the increase of luteinizing hormone in serum,
reduce cystic follicles formation and the apoptosis and 4.1. Vitamin A. Vitamin A is a fat-soluble vitamin, also
autophagy of granulosa cells, and attenuate the increase in called retinol. Vitamin A-derived metabolites, such as ret-
dopamine beta-hydroxylase and c-fos level in locus coeru- inoic acid and retinol, contribute to antioxidant activity and
leus, the noradrenaline level in serum and ovarian tissue, and steroid metabolism, promote nuclear maturation of oocytes,
the expression of beta 2 adrenergic receptor in ovarian and inhibit cell apoptosis [72–74]. A study [75] has shown
tissue. Besides, XYS alleviated the reduction of phosphor- that genes related to retinoic acid synthesis are expressed
ylation of ribosomal protein S6 kinase polypeptide I and differently in intermembranous cells isolated from PCOS
protein kinase B, as well as the increase of microtubule- patients. A study made by Wickenheisser JK [76] showed
associated protein light chain 3-I to microtubule-associated that the use of retinol derivatives in the endometrial cells of
protein light chain 3-II conversion both in vivo and in vitro PCOM and healthy women found that all intermembranous
[64]. cells treated with trans-retinol increased dehydroepian-
drosterone expression. Meanwhile, obesity and abnormal
glucose metabolism are associated with retinol-binding
3.2.3. Jiawei Xiao Yao San (JWXYS). Jiawei Xiaoyao San protein 4 (rbp4) in overweight PCOS patients [77]. Another
(JWXYS), also called Danzhi Xiaoyao San, is composed of 10 study reported that rbp4 was expressed in PCOS subcuta-
herbs, which is the most common herbal formula used for neous and omental adipocytes, and the rbp4 gene was
PCOS [65]. Wang [66] made an RCT to observe the ef- upregulated, leading to changes in gonads and adrenal
fectiveness of JWXYS. 128 patients with PCOS were ran- steroids [78].
domly assigned into two groups with 64 cases in each group.
The control group received Ethinylestradiol cyproterone,
and the treatment group was combined with JWXYS based 4.2. Vitamin B. At present, many studies have found that
on it. The results showed that, compared with the control vitamin B6, vitamin B12, and folic acid, which are related to
group, the E2, LH, and endometrial thickness can be homocysteine, are expressed at higher levels in PCOS6 Evidence-Based Complementary and Alternative Medicine
Table 2: Ingredients of formula.
Formula Composition
Cangfu Daotan Decoction White atractylodes rhizome (12 g), cyperus (12 g), pinellia rhizome (6 g), citrus (9 g), medicated leaven (6 g),
(CDD) bile arisaema (6 g), poria (9 g), bitter orange (12 g), fresh ginger (6 g), licorice root (6 g)
Licorice root (15 g), Chinese angelica (30 g), poria (30 g), tree peony bark (30 g), white atractylodes rhizome
Xiao Yao San (XYS)
(30 g), bupleurum (30 g)
Jiawei Xiao Yao San Chinese angelica (3 g), white peony root (3 g), poria (3 g), white atractylodes rhizome (3 g), bupleurum (3 g),
(JWXYS) tree peony bark (1.5 g), gardenia (1.5 g), licorice root (1.5 g)
Chinese angelica (10 g), white peony root (30 g), Sichuan lovage root (15 g), white atractylodes rhizome
Danggui Shaoyao San (DSS)
(15 g), poria (15 g), water plantain rhizome (15 g)
patients. The reason is that homocysteine is a sulfhydryl of follicles to FSH [91]. However, there are some contro-
amino acid, mainly derived from dietary methionine. versial reports. After vitamin D treatment for 11 patients
Studies have pointed out that elevated HCY will increase the with PCOS for 3 weeks, there has a good effect on IR, but
risk of long-term complications such as cardiovascular and there is no significant change in the levels of dehy-
reproductive symptoms in patients with PCOS [79, 80]. Folic droepiandrosterone, total testosterone, free testosterone,
acid, vitamin B6, and vitamin B12 play an important role in and androstenedione [92]. Meanwhile, a recent study
regulating homocysteine. It has been reported that in the showed that [93] simultaneous vitamin D supplementation
pathophysiological study of PCOS, IR and HCY are posi- and low-calorie diet did not change androgen levels in
tively correlated [81, 82]. Kaya et al. [83] confirmed that the overweight and obese women with PCOS, but the menstrual
increase in IR, obesity, and HCY levels in PCOS patients is frequency was significantly improved.
related to the decrease of vitamin B12. Regular exercises can
reduce the concentration of HCY [84]. Metformin, a sen-
sitizer for IR, is a commonly used medicine for the treatment 4.4. Vitamin E. Vitamin E as a lipid-soluble substance with
of PCOS. Metformin has a good effect on regulating IR, and nonenzymatic antioxidant properties, also known as to-
it will reduce the levels of vitamin B12 and folic acid in the copherol, which can effectively reverse the adverse influence
body during the treatment [85]. The elevated homocysteine by oxidative stress brought to the reproductive system and
levels increase the risk of cardiovascular disease in patients endocrine system, is widely used in the field of reproductive
with PCOS. medicine [94, 95]. Vitamin E plays a vital role in the entire
Inositol, one of the B vitamins, is a water-soluble vita- reproductive process. It can antagonize the oxidative stress
min. Like choline, it is a lipophilic vitamin. An experiment caused by oxygen free radicals and antioxidation imbalance
conducted by Minozzi et al. suggested that combined and regulate the normal physiological functions of the re-
contraceptives and inositol may be more effective than OCP productive system [96]. The combined treatment of mag-
alone in controlling the endocrine, metabolism, and clinical nesium and vitamin E for PCOS for 12 weeks has benefits for
manifestations of patients with PCOS and may reduce in- hirsutism, serum hs-CRP, plasma NO, and TAC levels [97].
sulin levels and insulin resistance [86]. Another study car- Extensive research papers have proven that the treatment of
ried out by Genazzani et al. demonstrated that after 2 weeks vitamin E in patients with PCOS has a significant effect
of MYO administration in patients with PCOS, plasma LH, [98, 99]. It can significantly reduce TG and serum total
PRL, T, insulin, and LH/FSH levels were significantly re- cholesterol and improve IR, T, and free testosterone index in
duced. All subjects with amenorrhea and oligomenorrhea patients with PCOS. In addition, new evidence confirms that
resumed their menstrual cycle [87]. vitamin E can improve the endometrial thickness of patients
with unexplained infertility but does not support the hy-
pothesis that vitamin E can increase the ovulation rate and
4.3. Vitamin D. Vitamin D, apart from the most well-known pregnancy rate in PCOS [100].
nonskeletal functions, has a potential role in glucose ho-
meostasis which is connected with the secretion of insulin by 5. Tai Chi, Yoga, and Qigong
pancreatic beta cells, IR in different tissues, and its influence
on systemic inflammation [88]. Krul-Poel et al. [89] have Tai Chi, a unique Chinese exercise, combines physical ac-
confirmed that vitamin D is a significant and independent tivity and breathing organically, allowing people to enjoy a
factor predicting IR, and vitamin D status is closely related to pleasant mood while exercising. The key point of Tai Chi is
the metabolic disorder of PCOS. Other research studies concentration and slow movements. Therefore, it is suitable
showed that women with PCOS often lack vitamin D, and its for the elderly with a weak constitution and chronic diseases
concentration was lower in patients with abdominal obesity. [101]. In 2012, NEJM published an article on the treatment of
In overweight/obese people with PCOS, vitamin D is related Parkinson’s with Tai Chi. The results confirmed that Tai Chi
to fasting blood glucose and HOMA [90]. Vitamin D can alleviate the balance disorder of patients with mild to
supplementation can reduce abnormally elevated serum moderate Parkinson’s disease, improve functional ability,
AMH levels, and the reduction of serum AMH levels may and reduce falls [102]. Tai Chi can maintain the harmony of
improve follicular formation by reducing androgens in the qi and blood and regulate the balance of yin and yang, which
ovaries of women with PCOS and increasing the sensitivity can significantly reduce BMI; risk factors reduceEvidence-Based Complementary and Alternative Medicine 7
cardiovascular disease and improve psychological health 6. Meditation Stress Reduction
[103–105]. Studies have shown that Tai Chi is effective for
long-term complications such as obesity, cardiovascular Patients with PCOS are troubled by obesity, hirsutism, acne,
disease, diabetes, and psychological diseases caused by PCOS irregular menstruation, and infertility, which affects their
[106, 107]. Meng [108] summarized that Tai Chi can pro- psychological health, physical condition, and quality of life
mote the metabolism of cells and tissues, increase the body’s to varying degrees [121]. The risk of anxiety and depression
utilization of glucose, the responsiveness of target cells, and was significantly increased in patients with PCOS. Relevant
the body’s tolerance to glucose, prevent the composition of research showed that more than 60% of PCOS patients were
HbA1c, and accelerate the combination of hemoglobin and diagnosed with at least one kind of mental disorder [122].
oxygen to further control blood glucose, thereby reducing The severity of depression, anxiety, obsessive-compulsive
the levels of FBG, HbA1c, and 2hPBG. Paul-Labrador et al. disorder, and somatization disorder measured by different
[109] believed that Tai Chi can inhibit the activation of scales in PCOS patients was higher than that in women
sympathetic nerves to improve the neutral-mediated vaso- without PCOS [123].
constriction of blood glucose control and reduce the glucose Emotional depression activates the neuroendocrine
transport and uptake of skeletal muscle, while Tai Chi can stress response system and simultaneously alters the im-
reduce IR [110]. mune function, leading to changes in brain structure
Yoga, a form of holistic mind-body medicine developed [124, 125] and activity [126, 127]. Many people use medi-
thousands of years ago, is a low-impact exercise that can help tation to relieve stress and treat stress-related diseases.
people maintain balance among physical, psychological, Meditative stress reduction (MBSR) can help patients reduce
mental, sentimental, and spiritual aspects of life [111]. As a emotional symptoms (e.g., anxiety, depression, and stress)
branch of CAM, it is used to treat many different diseases, and improve physical symptoms (e.g., pain) to a certain
such as hypertension, asthma, low back pain, arthritis and extent [128]. In addition, MBSR can reduce blood pressure,
pain, stress management, and PCOS [112]. A study has blood glucose, and inflammation [129–131]. These changes
shown that yoga can help control endocrine function and were due to improved autonomic nervous system and
relieve symptoms of PCOS [113]. Compared with aerobic HPOA function after MBSR treatment [127, 132, 133].
exercise, yoga will not cause any harm to the female re- Through MBSR treatment, PCOS patients’ risk of diabetes
productive system, at the same time, with the low-cost and and cardiovascular disease will eventually be reduced.
feasible operation, so it is very promising to reduce the risk Takahashi et al. [134] conducted a study on quantitatively
of PCOS through yoga [114]. An RCT conducted by Nidhi analyzed changes in psychophysiological parameters during
et al. found that yoga was more effective than conventional Zen meditation. Their findings can be an important clue to
physical exercises in improving glucose, lipid, and insulin the efficient use of meditation as a therapeutic procedure.
values, including IR values, in adolescent girls with PCOS Since most of the current trials on meditation in the
[115]. Meanwhile, Patel et al. confirmed through RCT that treatment of PCOS are small-scale, nonrandomized studies,
regular yoga practice could reduce serum androgen in PCOS more large-scale trials are needed to prove its efficacy on
patients, which is a useful complementary therapy [112]. In PCOS [135].
addition, Ram Nidhi et al. found that a 12-week holistic yoga
program was significantly better than a physical exercise 7. Conclusions
program in reducing anxiety symptoms for adolescents with
PCOS [116]. Ratnakumari et al. also reached a similar PCOS is a reproductive endocrine disease closely related to
conclusion that yoga is efficient in bringing about beneficial infertility, obesity, diabetes, cardiovascular disease, and
changes in polycystic ovarian morphology and speculated other metabolic diseases, accompanied by different degrees
that a longer intervention might require to regulate men- of psychological disorders. CAM for PCOS mainly includes
struation [117]. acupuncture, Chinese medicine, diet and nutrition, Tai Chi,
Although Qigong existed for thousands of years, it has yoga, Qigong, and meditation. Through these therapies, the
never been widely adopted. In the early 1950s, Qigong incidence of cardiovascular disease and diabetes can be
became popular after Liu Guizhen advocated it. Medical reduced, and anxiety and depression can be relieved as well,
Qigong, a specific form of Qigong, may have the effects of therefore improving the quality of life. Although CAM has
decreasing blood glucose, triglycerides, total cholesterol, been used in some countries and regions, the globalization of
body weight, BMI, and IR in type 2 diabetes in empirical and CAM has been hindered due to the lack of more clear re-
randomized controlled pilot studies [118]. An RCT con- search on its safety and mechanism. The specific obstacles
ducted by Liu X has proved that after intervention by include the following: (1) there is a lack of a larger sample
Qigong, the weight, waist circumference, leg strength, and IR size and more structured methods to evaluate the safety and
improved which indicated weight reduction in the control of pharmacological mechanism of TCM; (2) there is not
diabetes. Besides, a meta-analysis by Meng suggested that enough convincing evidence to support the efficacy or safety
Qigong can improve the blood glucose of type 2 diabetes of dietary supplements; (3) there is a lack of verification of
patients and benefit the management of it [119]. Owing to Taijiquan, yoga, meditation, and other interventions; (4) the
the fact that PCOS has the risk of obesity and cardiovascular molecular mechanism of some CAM therapies remains to be
disease, etc., we speculate that Qigong also has a certain further studied and confirmed [136]. In the future, we need
effect in the treatment of PCOS [120]. larger samples and RCTs to confirm the efficacy and safety of8 Evidence-Based Complementary and Alternative Medicine
CAM in the treatment of PCOS to provide a new method for [12] L. Zhang, Therapeutic Effect and Mechanism of Acupuncture
PCOS. on Polycystic Ovary Syndrome in Rats, Huazhong University
of Science and Technology, Wuhan, China, 2010.
[13] Y. Peng, Y. Zhang, S. Wang et al., “Discussion on acu-
Conflicts of Interest
puncture treatment of polycystic ovary syndrome based on
The authors declare that there are no conflicts of interest intestinal flora,” Journal of Clinical Acupuncture and Mox-
regarding the publication of this paper. ibustion, vol. 35, no. 3, pp. 1–5, 2019.
[14] C. Ee, C. A. Smith, M. Costello et al., “Acupuncture or
auricular electro-acupuncture as adjuncts to lifestyle inter-
Authors’ Contributions ventions for weight management in PCOS: protocol for a
randomised controlled feasibility study,” Pilot Feasibility
Li-Yan Jia, Jia-Xing Feng, and Juan-Li Li contributed equally
Studies, vol. 6, p. 53, 2020.
to this work. [15] D. Wu, X. Wang, H. Cong, S. Liu, and Y. Liang, “The effect of
acupuncture on ovarian function in obese patients with
Acknowledgments polycystic ovary syndrome,” World Chinese Medicine,
vol. 15, no. 16, pp. 2482–2485, 2020.
The study was supported by the National Natural Science [16] R. Huang, X. Li, S. Xu et al., “Acupoint injection treatment
Foundation of China (grant no. 82074484) and the scientific for primary osteoporosis: a systematic review and meta-
research projects of the Heilongjiang Administration of analysis of randomized controlled trials,” Annals of Palliative
Traditional Chinese Medicine (grant no. ZHY2020-134). Medicine, vol. 8, no. 5, 2019.
[17] C. Jin, R. Pang, L. Xu, Z. Wu, and J. Zhao, “Acupuncture and
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