Am J Physiol Endocrinol Metab. 2011 Jul; 301(1): E1E10.

PMCID: PMC4459923

Published online 2011 Apr 12. doi: 10.1152/ajpendo.00667.2010

The physiological basis of complementary and alternative medicines for

polycystic ovary syndrome
Nazia Raja-Khan, 1 Elisabet Stener-Victorin,2,3 XiaoKe Wu,3 and Richard S. Legro4
1

Division of Endocrinology, Diabetes, and Metabolism, Pennsylvania State University College of Medicine, M.S. Hershey Medical Center,

Hershey, Pennsylvania;
2
Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg,
Sweden;
3
Department of Obstetrics and Gynecology, National Key Discipline and Clinical Base, Heilongjiang University of Chinese Medicine, Harbin,
China; and
4
Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, M. S. Hershey Medical Center, Hershey,
Pennsylvania
Corresponding author.
Address for reprint requests and other correspondence: N. Raja-Khan, Division of Endocrinology, Diabetes, & Metabolism, Penn State Univ.
College of Medicine, M. S. Hershey Medical Center, 500 University Dr., H044, Hershey, PA 17033 (e-mail: nrajakhan@psu.edu).
Received 2010 Dec 6; Accepted 2011 Apr 7.
Copyright 2011 the American Physiological Society

Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by chronic
hyperandrogenic anovulation leading to symptoms of hirsutism, acne, irregular menses, and infertility.
Multiple metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance,
obesity, type 2 diabetes, hypertension, inflammation, and subclinical atherosclerosis. However, current
treatments for PCOS are only moderately effective at controlling symptoms and preventing complications.
This article describes how the physiological effects of major complementary and alternative medicine
(CAM) treatments could reduce the severity of PCOS and its complications. Acupuncture reduces
hyperandrogenism and improves menstrual frequency in PCOS. Acupuncture's clinical effects are
mediated via activation of somatic afferent nerves innervating the skin and muscle, which, via modulation
of the activity in the somatic and autonomic nervous system, may modulate endocrine and metabolic
functions in PCOS. Chinese herbal medicines and dietary supplements may also exert beneficial
physiological effects in PCOS, but there is minimal evidence that these CAM treatments are safe and
effective. Mindfulness has not been investigated in PCOS, but it has been shown to reduce psychological
distress and exert positive effects on the central and autonomic nervous systems, hypothalamic-pituitaryadrenal axis, and immune system, leading to reductions in blood pressure, glucose, and inflammation. In
conclusion, CAM treatments may have beneficial endocrine, cardiometabolic, and reproductive effects in
PCOS. However, most studies of CAM treatments for PCOS are small, nonrandomized, or uncontrolled.
Future well-designed studies are needed to further evaluate the safety, effectiveness, and mechanisms of
CAM treatments for PCOS.
Keywords: acupuncture, mindfulness meditation, herbs, dietary supplements, traditional Chinese
medicine

(PCOS), a common endocrine disorder that affects 510% of reproductiveage women, is characterized by chronic hyperandrogenic anovulation leading to symptoms of hirsutism,
acne, irregular menses, and infertility (86). The exact etiology of PCOS remains unclear, but it is believed
to result from complex interactions between genetic, behavioral, and environmental factors. Multiple
metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance (IR),
obesity, type 2 diabetes (DM-2), hypertension, dyslipidemia, inflammation, and subclinical cardiovascular
disease (32, 62, 63, 87, 107). Anxiety, depression, and reduced quality of life are also common in PCOS
(5, 19, 45, 107).
POLYCYSTIC OVARY SYNDROME

Current treatments for PCOS are only moderately effective at controlling symptoms and preventing
complications. In fact, when 648 women were asked, If your PCOS could be safely and effectively helped
by something else besides fertility drugs or birth control pills, would that interest you?, 99% responded
yes (95). Although the prevalence of complementary and alternative medicine (CAM) used by women
with PCOS is not known, a landmark study showed that one in three Americans use CAM (23). Recent
studies suggest that several CAM treatments could be beneficial as an adjunct to conventional medical
management of PCOS. This article describes how the physiological effects of CAM treatments could
reduce the severity of PCOS and its endocrine, cardiometabolic, and reproductive complications.
Acupuncture

Acupuncture is a form of sensory stimulation in which thin needles are placed in the skin and muscles. It is
of great importance to describe the needling dose, because the intensity, frequency, and type of
stimulation, manual or electrical, with high or low frequency, and the interval between stimulations
directly influence the kind of receptors activated and thus the therapeutic effect (114). Patients'
expectations may also influence the results, as acupuncture may have strong psychological effects (94).
The primary mechanism for acupuncture's clinical effects is activation of somatic afferent nerves
innervating the skin and muscles, which may modulate somatic and autonomic nervous system activity
and endocrine and metabolic functions. The efficacy of acupuncture in treating pain and disease has been
studied from a Western scientific perspective. Systematic reviews have concluded that there is no evidence
for acupuncture point specificity and suggest that needles can be inserted anywhere in appropriate
segments (80, 122). Here, we will use a neurophysiological approach to describe how acupuncture,
specifically electro-acupuncture (EA), where needles are electrically stimulated, may work in women with
PCOS, because it has good support from experimental and clinical studies (36, 79).
Etiology of PCOS.

The etiology of PCOS is poorly understood (83). Ovarian hyperandrogenemia, the most consistent
endocrine feature, probably plays a key role (30), but hyperinsulinemia/insulin resistance and abdominal
obesity are also thought to be important (4). Whether hyperandrogenism results from the hyperinsulinemia
of IR or vice versa is unclear (91). Moreover, neuroendocrine defects can contribute to persistently rapid
luteinizing hormone (LH) pulsatility and increased amplitude, which further augment ovarian androgen
production (7). In addition, PCOS women have high sympathetic nervous system activity compared with
controls, and circulating testosterone is the strongest factor explaining the high activity (105).
Furthermore, high activity in the sympathetic neurons innervating the ovaries precedes the development of
ovarian cysts in rats (58), and women with PCOS may have increased ovarian nerve fiber density (37).
Clinical effects of acupuncture in PCOS.

The clinical effect of acupuncture on menstrual dysfunction in PCOS has been evaluated in several case
control studies (12, 29, 101, 117) and in one randomized controlled trial (RCT) (n = 84) (44). In the RCT,
women were randomized in a 2:2:1 ratio to receive 14 treatments with low-frequency EA (n = 33) for 16
wk or physical exercise (n = 34) at least three times per week for 16 wk, or no intervention during the
study period, which served as a control group (n = 17). This RCT demonstrated that low-frequency EA
was superior to physical exercise and improved hyperandrogenism and menstrual frequency more
effectively than no intervention (44). Whether the improved menstrual frequency reflected ovulation
induction remains to be elucidated.
The effect of acupuncture (manual or electrical stimulation) on metabolic variables in women with PCOS
has never been evaluated in clinical trials. Low-frequency EA, with repetitive muscle contraction, may
activate physiological processes similar to those resulting from physical exercise and could influence
metabolic variables. Experimental evidence is described below.
The effect of acupuncture on mental health and health-related quality of life in women with PCOS has not
been evaluated in clinical trials. Acupuncture has been used to treat depressive disorders, but its
effectiveness and safety are not well defined (124). Because women with PCOS are prone to develop
symptoms of anxiety and depression and decreased health-related quality of life, this is an important area
for exploration.
Placebo and limitations in acupuncture studies.

Acupuncture treatment is associated with particularly potent placebo effects, and there are indications that
acupuncture treatment may be associated with larger effects than pharmacological and other physical
placebos (52, 53, 67). The characteristics of acupuncture treatment are relevant in the context of placebo
effects, including frequent patient-practitioner contacts and the procedure of needling (51). Placebo effects
result in true psychobiological events and exist in clinical practice (27).
Acupuncture studies are difficult to design for many reasons, including the variety of sham procedures, the
number of acupuncture points used, the number and duration of acupuncture treatments, and differences in
stimulation techniques (114). Studies involving acupuncture in which both the patient and the therapist are
unaware of the treatment are practically impossible to conduct. Thus, many variables affect the outcome of
an acupuncture study. The so called placebo-acupuncture needle (102) has been used in many trials, and
most often it has similar effects to true acupuncture but is superior to no treatment if a no-treatment group
is included. Thus, the placebo-acupuncture needle is not inert and may not be used as a sham (72). Instead,
it is of importance to control for the increased amount of attention, and the control/comparison group
should meet with a therapist the same amount of times as in the acupuncture group.
With this in mind, standardized study protocols to increase the validity of acupuncture studies by following
the new revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA)
checklist in conjunction with CONSORT will improve critical appraisal, analysis, and replication of trials
(73). Furthermore, given the uncertainties about physiological effects of sham controls and the question of
enhanced placebo effects, it is crucial that direct, head-to-head comparisons of acupuncture and goldstandard treatment be conducted.
Physiological basis of acupuncture in PCOS: peripheral mechanisms.

Insertion and manual or electrical stimulation of needles in skin and muscle activates A, , , and C fibers
(49). In particular, activation of A and C fibers may be essential for modulating autonomic nervous
system activity (90). Manual and probably electrical stimulation causes release of neuropeptides from

peripheral nerve terminals into the area surrounding the needle, increasing blood flow (42). Low-frequency
(2 Hz) EA also increases skeletal muscle glucose uptake (39). In insulin-resistant rats with
dihydrotestosterone (DHT)-induced PCOS, peripheral insulin sensitivity is improved by low-frequency EA
for 45 wk with three treatments per week (75) and normalized by five treatments per week (47). This
normalization may reflect increased expression of soleus muscle glucose transporter (GLUT)4 protein,
including the plasma membrane of muscle cells (47). Moreover, there is a dose-response relationship
between the number of EA treatments and improvement in insulin sensitivity (74, 75). Similarly, in rats
with prednisolone-induced IR, low-frequency EA acutely increases protein expression of insulin receptor
substrate-1 and GLUT4 in skeletal muscle (65). Low-frequency EA improved insulin sensitivity in DM-2
db/db mice, and the effect was mediated, at least partly, via regulation of skeletal muscle Sirtuin-1 (SIRT1)
and peroxisome proliferator-activated receptor- coactivator-1 (PGC-1) (64). The increased peripheral
blood flow and glucose uptake in skeletal muscle are most likely mediated by a reflex response from
muscle twitches during manual or electrical stimulation, as the response is abolished after transection of
somatic afferent nerve fibers (38) (Fig. 1).
Segmental (spinal) mechanisms.

Needles in abdominal and leg muscles with somatic innervations corresponding to the sympathetic
innervations of the ovaries, so-called segmental acupuncture points, may alter ovarian function by
modulating sympathetic efferent activity (96, 98, 100). This is of particular interest since the PCOS ovary
has been shown to have denser innervation (37) and high concentrations of nerve growth factor (NGF), a
marker of sympathetic activity (20). Needles placed in the abdominal and hindlimb muscles of female rats
and stimulated with low-frequency EA modulate the activity of ovarian sympathetic nerves, as reflected by
increased ovarian blood flow (96, 98, 99). The response was demonstrated to be mediated by ovarian
sympathetic nerves as a reflex response and was controlled by supraspinal pathways [i.e., central nervous
system (CNS)] (96, 98). Further evidence that low-frequency EA modulates ovarian sympathetic nerve
activity comes from studies in estradiol valerate-induced PCOS. Gene and protein expression of markers
of sympathetic activity (1a-, 1b-, 1d-, and 2-adrenoceptors, NGF, the p75 neurotropin receptor, and
tyrosine hydroxylase) were normalized after 4 wk of low-frequency EA (76, 100). In rats with DHTinduced PCOS, ovarian morphology was improved by thrice weekly treatment for 45 wk, as reflected by
a higher proportion of healthy antral follicles and a thinner theca interna cell layer than in untreated PCOS
rats (74, 75). When treatment was increased to five times per week, low-frequency EA normalized estrus
cyclicity, indicating a clear dose-response relationship (25). It is not known whether manual stimulation of
acupuncture needles induces similar effects.
Central mechanisms of acupuncture.

When needles are placed, the peripheral nervous system transfers signals to the brain, which contributes to
the effect of acupuncture. Since the CNS regulates pituitary hormone release, acupuncture may also
modulate endocrine and metabolic function.
Many brain areas, especially the hypothalamic nucleus, are involved in the effect of acupuncture.
Acupuncture-induced release of CNS neuropeptides seems to be essential for inducing functional changes
in organ systems (36). The central hypothalamic -endorphin system is a key mediator of changes in
autonomic functions, such as effects on the vasomotor center, which decreases sympathetic tone and is
manifested as improved blood pressure regulation and decreased muscle sympathetic nerve activity (120).
Both exercise and low-frequency EA increase hypothalamic -endorphin secretion and decrease blood
pressure and sympathetic nerve activity; these effects are reversed by -opiod receptor antagonists (48).

Interestingly, repeated low-frequency EA plus physical exercise significantly decrease high sympathetic
nerve activity measured by microneurography in women with PCOS (97). Decreased sympathetic nerve
activity, possibly mediated by modulation of hypothalamic -endorphin secretion, may partly explain the
decrease in circulating testosterone and improved menstrual frequency after low-frequency EA plus
physical exercise in women with PCOS (44).
Hypothalamic -endorphin interacts with the hypothalamic-pituitary-ovarian axis by exerting a tonic
inhibitory effect on the gonadotropin-releasing hormone (GnRH) pulse generator and on pituitary LH
release (46). In PCOS, growing evidence suggests that the opioid system is dysregulated both centrally and
peripherally, with complex interactions (24). Indeed, opioid receptor antagonists improve menstrual
cyclicity, induce ovulation, and decrease testosterone, insulin, and LH levels and the LH/FSH ratio (1, 15,
28). Acupuncture might affect the hypothalamic-pituitary-ovarian axis by modulating central -endorphin
production and secretion, thereby influencing release of hypothalamic GnRH and pituitary secretion of
gonadotropins, as shown by the decrease in LH/FSH ratio after low-frequency EA (101). Furthermore, in
rats with DHT-induced PCOS, five low-frequency EA treatments per week for 45 wk restored high
hypothalamic androgen receptor and GnRH protein expression, which may help explain the beneficial
neuroendocrine effects of low-frequency EA in women with PCOS (25).
-Endorphin is also released into peripheral blood from the hypothalamus via the anterior pituitary, a
process regulated by CRF. Circulating -endorphin is thought to be related to the hyperinsulinemic
response (70). It may also decrease hyperinsulinemia by lowering high concentrations of circulating endorphin (101). Interestingly, low-frequency EA lowers high circulating -endorphin concentrations in
women with PCOS and may decrease hyperinsulinemia and increase insulin clearance or insulin
sensitivity (12, 101).
In sum, clinical and experimental evidence indicates that acupuncture with electrical muscle stimulation
may be a suitable alternative or complement to improving endocrine and reproductive function in women
with PCOS without adverse side effects. More experimental mechanistic studies and RCTs to further
explore the use of acupuncture to treat PCOS-related symptoms are warranted.
Chinese Herbal Medicine

Chinese herbal medicine (CHM) is an integral part of traditional Chinese medicine (TCM). In China today,
TCM is often administered as a complement to Western medicine. While TCM traces its roots back
thousands of years, it rests, from the view of evidence-based medicine, more on a philosophy than a
science. Much of the central philosophy involves maintaining the balanced flow of life energy (qi). TCM
views organ systems as contributing to mind-body states and tries to address imbalances of these organ
systems. TCM views PCOS as linked to disorders of the kidneys, liver, and spleen. Reproductive
abnormalities, especially anovulation, are believed to be linked to the kidney, and a deficit in kidney is
viewed as the primary problem in PCOS (82, 110).
Traditionally, CHMs are combined in varying preparations. Although some preparations are regulated by
the government, there remains concern about quality control of individual formulations, given the
variation in plant quality from harvest to harvest, and concerns about harmful supplements or byproducts
of preparation such as heavy metals, herbicides, pesticides, microorganisms, mycotoxins, insects,
pharmaceuticals, etc. (6, 68). The FDA has published guidelines to ensure better quality control of
manufactured products from plants, but many of these products fall outside of regulation by the FDA, as
they are not pharmaceuticals. CHMs also include many animal byproducts that we will not discuss in
detail in this review. For example, a common preparation used to induce ovulation in women with PCOS is

Di Long (Earth Dragon), which is made from abdominal extracts of the red earthworm Lumbricus
rubellus.
Safety and efficacy of CHMs.

Unfortunately, there is minimal evidence that CHMs are safe and efficacious. Most of the trials have been
small and thus inadequately powered to detect true differences. Most, not surprisingly, have been
conducted mainly in Chinese populations and published in Chinese and thus are not easily accessible. The
studies have also tested a large number of varying preparations (most containing multiple components),
and thus there has been little to no replication for individual preparations. Above all, the studies have been
of poor methodological quality without adherence to CONSORT guidelines.
This is well illustrated by systematic reviews of CHM in subfertile women with PCOS (123) and patients
with impaired glucose tolerance (IGT) (34) and DM-2 (68), disorders related to PCOS because of the
common underlying link of IR (Table 1).
Here, we also review the evidence for CHM in IGT and DM-2 because women with PCOS are at markedly
increased risk for both IGT and DM-2 due to IR (63). Furthermore, these disorders of glucose
dysregulation may represent later stages in the pathophysiological progression of PCOS. Finally, many
drugs used to prevent or treat PCOS have been borrowed from DM-2, most notably metformin, but also
the thiazolidinediones, acarbose, but also newer agents such as incretin mimetics such as exenatide.
Similarly, many of the CHMs used to treat DM-2 may be useful for PCOS. However, the evidence for the
benefit of CHM in all three disorders is weak (Table 1).
There are the fewest articles for PCOS, which is perhaps understandable from a public health perspective,
as IGT and DM-2 are more prevalent than PCOS. The large drop-off from published articles to those
meeting the minimum quality standard for a systematic review is staggering. None of the studies
documented allocation concealment (the method by which the order of treatment assignment was
generated and implemented in the study) or blinding, none of the studies used an intention to treat method
analysis, a standard method to account for drop-out in a randomized trial (123).
The authors of the review of CHM in PCOS (123) did note that in two studies where multiple formulations
of Chinese herbs were given as adjuvant therapy to clomiphene, there was a significantly increased odds of
pregnancy with CHM (OR 2.97, 95% CI 1.71 to 5.17) (123). The reviews (34, 68, 123) share a common
theme, a hint of efficacy clouded by poor methodology and lack of replication. But all reviews were eager
to see larger better designed studies carried out.
There are multiple hurdles to adapting CHM into Western medicine. One is the lack of scientific
justification from a hypothesis-driven perspective for the use of these medications. Many herbs contain
multiple active substances, and combinations are exponentially more problematic for determining what is
doing what to what. Much research currently is focusing on compound analysis through such technologies
as high-performance liquid chromatography-mass spectrometry to identify specific bioactive agents.
Physiological mechanisms of CHMs.

Currently, the physiological mechanisms for efficacy of most CHMs are unknown in PCOS. Table 2 lists
several CHMs used in PCOS and their proposed mechanism of action. Many may have selective
estrogenic effects and function like clomiphene to induce ovulation. Risks, however, must be carefully
determined, and these have not been well delineated. Gancao or licorice, given chronically or in excess,
can cause an acquired form of apparent mineralocorticoid excess, as it is a potent inhibitor of 11-

hydroxysteroid dehydrogenease. This enzyme inactivates cortisol to cortisone, and decreased inactivation,
especially in the kidney, can lead to excess cortisol cross-reacting with the mineralocorticoid receptor,
which induces fluid retention, hypokalemia, and hypertension (66). In addition, CHMs may interfere with
the metabolism of other drugs used to treat PCOS. For example, plantain has been proposed to interfere
with many commonly prescribed medications such as digitoxin and tricyclic antidepressants, although at
least one study shows no clinical interactions (17).
Mechanisms of action should be explored in cell culture and animal models by basic scientists. For
example, Rhizoma alismatis has been found in an in vitro tissue model to inhibit intestinal glucose
absorption and stimulate glucose uptake in fibroblasts and adipocytes (59). Furthermore, in a
streptozotocin-induced diabetes mouse model, it lowers plasma glucose and triglycerides and improves
insulin levels (119). Other CHMs, such as Radix notoginseng, have been found to have similar antidiabetic
effects in mouse models, improving not only glucose tolerance and insulin action in a dose-response
fashion but also ameliorating obesity (13). Similarly, Salvia miltiorrhiza Bunge has been shown to
significantly improve glucose tolerance in a prenatally androgenized rat model of PCOS and to favorably
impact insulin signaling in treated animals (118). Berberine, a component of Rhizoma coptidis, has been
shown to improve glucose uptake and insuln action in human thecal cells with dexamethasone-induced
insulin resistance (125). These favorable changes in glucose metabolism have also been shown to
favorably alter sex steroid feedback or production, ameliorating hyperandrogenism in these models (22,
125). Additionally, antioxidant activity has been noted in vitro for a number of these substances (61, 116).
Furthermore, extensive investigation of promising drugs should be established in preliminary studies, first
exploring safety and secondarily exploring proof of concept through larger dose ranging studies. This is
certainly the FDA model for new drugs; i.e., begin with Phase I studies, progress to dose ranging and
further safety Phase II studies, and finally choose a dose and perform a large-scale, adequately powered
and designed Phase III efficacy study. Second, there remains, at least in the US, a great gulf between
practitioners of TCM and allopathic physicians and a general skepticism of the Weltanschauung of the
other. Along these lines, there is a lack of adequately trained investigators who are familiar both with
CHM and with the design and implementation of RCTs. This latter element is especially lacking in China,
where most of these trials are conducted, as the systematic reviews document.
A group of international authors has recognized the unique challenges of RCTs of CHMs and made the
following summary recommendations to improve the quality of these trials by ensuring the stability,
consistency, and purity of CHMs. These suggested guidelines, replicated here, are a positive step toward
the exploration of CHMs for the treatment of PCOS and related disorders. At present, their potential is
untapped, although this represents a tremendous opportunity for researchers on both sides of the ocean.
Dietary Supplements

Several dietary supplements may have benefical effects on PCOS. However, most studies are small or
uncontrolled. Therefore, larger, better-designed studies are needed to further evaluate the risks and benefits
of these supplements in PCOS. In addition, it is important to note that the supplements discussed here are
not FDA approved for the treatment of PCOS.
Vitamin D.

Accumulating evidence suggests that vitamin D deficiency may be a causal factor in the pathogenesis of
IR and the metabolic syndrome in PCOS (35). Furthermore, 25-hydroxyvitamin D levels are closely
associated with impaired -cell function, IGT, and the metabolic syndrome in PCOS women (113). Two

small, uncontrolled studies demonstrate that vitamin D may improve IR and lipid profiles in PCOS
patients (56, 92). One of these studies demonstrated a significant reduction in homeostatic model
assessment of insulin resistance (HOMA-IR) 3 wk after a single oral vitamin D3 dose of 300,000 IU in 11
obese, insulin-resistant women with PCOS (56, 92). Moreover, vitamin D supplementation may also
improve anovulation in PCOS. A pilot RCT of 60 infertile PCOS patients showed that the number of
dominant follicles (14 mm) during 23 mo of follow-up was higher in the calcium (1,000 mg/day) plus
vitamin D (400/day) plus metformin (1,500 mg/day) group than in the calcium + vitamin D-only group or
the metformin-only group (88).
Vitamin B12 and folate.

Two recent studies suggest that B vitamins may be important in PCOS. In the first study, IR, obesity, and
elevated homocysteine were associated with lower serum vitamin B12 concentrations in PCOS patients
(55). The second study was a nonrandomized, placebo-controlled, double-blind trial that demonstrated that
supplementation with folate (400 g daily) for 6 mo increases the beneficial effect of metformin on the
vascular endothelium in women with PCOS (84). However, the mechanisms are still unclear.
Green tea and spearmint tea.

Tea, next only to water, is the most popularly consumed beverage in the world, with a per capita
consumption of 120 ml/day (78). Green tea has been shown to exert beneficial effects on glucose and lipid
metabolism (11, 21) and the hormonal system (26, 50) in rats and humans, which are all very relevant in
the management of PCOS patients. In addition, herbal tea reduces body weight and induced ovulation in
androgen-sterilized rats (103). However, there are only two RCTs of herbal tea in PCOS, one using green
tea (10) and the other spearmint tea (33).
The principal component of green tea, ()-epigallocatechin-3-gallate (EGCG), significantly reduced body
weight and circulating testosterone, estradiol, leptin, insulin, IGF-I, LH, glucose, cholesterol, and
triglyceride in Sprague-Dawley rats and lean and obese Zucker rats (50). In vitro studies demonstrate that
green tea extract and EGCG inhibit basal and stimulated testosterone production in rat Leydig cells. The
mechanisms underlying the effects of EGCG involve the in vitro inhibition of the PKA/PKC signaling
pathways as well as the inhibition of P-450 side-chain cleavage enzyme and 17-hydroxysteroid
dehydrogenase function during testicular steroidogenesis (26).
In an RCT of 34 obese Chinese women with PCOS, the body weight of the green tea capsule group (540
mg EGCG/day) decreased by a nonsignificant 2.4% after treatment, whereas the body weight, body mass
index (BMI), and body fat content of the control group were significantly higher after 3 mo (10). However,
there were no significant differences in glucose, lipid metabolism, or any of the hormone levels between
the two groups. The lack of a positive finding in this study may be due to an inadequate dose of green tea
and the small sample size of the study. Furthermore, the response to EGCG may be greater in other ethnic
groups, especially those groups who do not already have a strong habit of taking tea in their daily lives
(121).
In regard to spearmint tea, an RCT of 41 PCOS women showed that spearmint tea twice a day for 1 mo
significantly decreased free and total testosterone levels, improved patients' subjective assessments of their
hirsutism, and increased LH and FSH compared with a placebo herbal tea (33). Further studies are needed
to confirm these findings and further elucidate the mechanisms underlying the antiandrogenic effects of
spearmint tea.

Cinnamon extract.

Cinnamon extract (a traditional herb) has been shown to potentiate the insulin effect through upregulation
of glucose uptake in cultured adipocytes (3, 8, 43). Cinnamon extract also improves insulin action via
increasing glucose uptake in vivo, as it has been shown to enhance the insulin-signaling pathway in
skeletal muscle in rats (85). An RCT of 15 women with PCOS showed significant reductions in IR in the
cinnamon group (333 mg of cinnamon extract, 3 times a day) but not in the placebo group (111).
-3 and other polyunsaturated fatty acids.

A small RCT of 25 PCOS women demonstrated that dietary supplementation with -3 fatty acid 4 g/day
(4 1,000-mg capsules of 56% docosahexaenoic acid and 27% eicosapentaenoic acid; Ocean Nutrition,
Halifax, NS, Canada) for 8 wk has beneficial effects on liver fat content and other cardiovascular risk
factors in women with PCOS (16). Another small study, of 17 women with PCOS, showed that increased
dietary polyunsaturated fatty acid (PUFA) intake from walnuts (48 g walnuts per 800 kcal energy intake)
for 3 mo increased glucose levels in women with PCOS (54). Forty-eight grams of walnuts contain 311
kcal (70 kcal from 30 g fat, 28 kcal from 7 g protein, and 36 kcal from 9 g carbohydrates) and provide 19 g
of linolenic acid and 3.3 g of -linolenic acid. Further studies are needed to determine the risks and
benefits of -3 fatty acids and other PUFAs in PCOS.
Qi Gong and Tai Chi

Exercise is an important component of a healthy lifestyle, and it reduces metabolic and reproductive
disturbances in PCOS. Qi gong and Tai chi are the two most popular Chinese medical exercises
worldwide. Qi gong may be beneficial for individuals with DM-2 or metabolic syndrome, for its favorable
effects on hemoglobin (Hb) A1c, glucose levels, and insulin sensitivity, reported by several RCTs (69, 104,
109). Tai chi has been shown to have similar energy expenditure to other moderate-intensity activities,
such as walking at a speed of 6 km/h (2). It also has favorable effects on glucose control, lipid profile, and
anxiety in patients with DM-2 (41, 108, 112). Therefore, Qi gong and Tai chi may be effective adjunct
treatments for PCOS women. However, to date no studies have evaluated the effects of Qi gong or Tai chi
in PCOS.
Mindfulness Meditation

Mindfulness, a component of ancient meditative practices such as Vipassana meditation and Zen
meditation, is increasingly being applied to Western medicine to enhance psychological health and overall
well-being (14, 71). In contemporary Western psychology, mindfulness has been described as the
awareness that emerges through intentionally paying attention to one's present thoughts, emotions, and
bodily sensations moment to moment in a nonjudgmental manner (93). Mindfulness has not been
investigated in women with PCOS; however, studies in non-PCOS populations, including patients with
DM-2 (89), suggest that mindfulness has psychological and physiological effects that could be beneficial
in PCOS. Mindfulness-based stress reduction (MBSR), the most researched mindfulness-based program,
reduces psychological distress (71) and may also reduce blood pressure, glucose, and inflammation (9, 77,
89, 115). These physiological effects appear to be mediated by changes in brain activity (18, 31) and
structure (40, 60) leading to improvements in the autonomic nervous system (57, 81, 106) and
hypothalamic-pituitary-adrenal (HPA) axis (9, 77, 115). It is hypothesized that these beneficial effects of
mindfulness might ultimately lower the risk for diabetes and cardiovascular disease in PCOS. However,
most of the evidence comes from small, uncontrolled, nonrandomized studies in non-PCOS populations.
Therefore, well-designed RCTs of mindfulness in women with PCOS are needed before definitive

conclusions can be drawn regarding the effects and mechanisms of mindfulness in PCOS.
Conclusions

In conclusion, several CAM treatments may have beneficial endocrine, cardiometabolic, and reproductive
effects in women with PCOS. However, most studies are small, nonrandomized, or uncontrolled.
Therefore, larger, well-designed RCTs are needed to further evaluate the safety, effectiveness, and
mechanisms of CAM treatments for PCOS.
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
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Figures and Tables
Fig. 1.

Stimulation of needles activates A and C fibers and causes release of neuropeptides from peripheral nerve terminals,
increasing blood flow locally. Low-frequency electro-acupuncture (EA) caused muscle contraction and increased GLUT4
expression and most likely translocation to plasma membrane. Low-frequency EA also increased Sirtuin-1 (SIRT1) and
peroxisome proliferator-activated receptor- coactivator-1 (PGC-1).
Table 1.

List of systematic reviews of CHM for treatment of PCOS and disorders of glucose metabolism including
type 2 diabetes
Topic

Total No.

Total

Total

Total

Total No. of

of Studies

Studies

No. of

No. of

Preparations

Retrieved Included
in

Studies Subjects
in

in

Main Conclusions

Tested in
Trials

Cochrane Chinese Included

Review
Subfertile
PCOS (123)

267

Studies
4

334

Limited evidence that addition of CHM

to clomiphene is associated with
improved clinical pregnancy outcomes
and no other evidence of any other effect.
Methodology of RCTs was not
adequately reported.

Impaired

1,926

16

15

1,391

15

Some positive evidence favors CHM for

fasting

treatment of IGT or IFG. Limited by the

glucose (IFG)

following factors: lack of trials that tested

or impaired

the same herbal medicine, lack of details

glucose

on cointerventions, unclear methods of

tolerance

randomization, poor reporting, and other

(IGT) (34)

risks of bias

Type 2

713

66

61

8,302

69

diabetes (68)

Some herbal medicines show

hypoglycemic effect in type 2 diabetes.
However, these findings are limited by
low methodological quality, small sample
size, and limited number of trials.

PCOS, polycystic ovary syndrome; CHM, Chinese herbal medicine; RCT, randomized controlled trial.
Nos. in parentheses are references.
Table 2.

Partial list of CHMs used to treat PCOS, their proposed mechanisms of action, and their reported side
effects
Mechanism

Chinese

Latin Name

English Name

Adverse Effects

Name
Improve insulin sensitivity

Baishao

Radix paeoniae White peony

Uterine contractions, interfere with blood

Alba

root

clotting

Angelica

Uterine contractions

Red sage

May interact and potentiate effects of

Danggui Radix
angelicae
Sinensis
Danshen Salvia
miltiorrhiza

warfarin

Bunge

Induce ovulation (through

Huang

Rhizoma

Lian

coptidis

Luole

Ocimum

estrogenic effects)

Goldenthread

Hypertension, respiratory failure, paresthesias

Basil

Contains a chemical, estragole, which has

basilicum
Sanqi

caused liver cancer in mice

Radix no-

Panax

Dry mouth, flushed skin, nervousness, sleep

toginseng

pseudoginseng problems, nausea, and vomiting.

Zelan

Herba lycopi

Bugleweed

Zexie

Rhizoma

Water plantain Fresh rootstock may be poisonous

Enlarged thyroid gland, hypoglycemia

alismatis
Inhibit androgen synthesis

Gancao

Radix
glycytthizae

Licorice

Hypertension, fluid retention, hypokalemia,

exacerbate kidney disease

Articles from American Journal of Physiology - Endocrinology and Metabolism are provided here courtesy of

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