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Polycystic Ovary/Ovarian Syndrome

Zeynep Uraz, ND

Table of Contents
Definition, Epidemiology, Etiology................................................................................2
PCOS....................................................................................................................................2
Epidemiology ,.....................................................................................................................2
Pathophysiology...........................................................................................................3
Clinical Presentation.....................................................................................................3
Common presenting signs and symptoms:...........................................................................3
Phenotypes..........................................................................................................................3
Diagnosis......................................................................................................................4
Long-term Health Outcomes........................................................................................7
Patient Monitoring:......................................................................................................7
Treatment....................................................................................................................8
Conventional Treatment......................................................................................................8
Treatment Goals/Approach.................................................................................................8
Note: The following lists contain therapies in order of clinical relevance (most important,
impactful therapies listed near the top of each category). Clinical importance is determined
by research where possible, and by clinical judgment and experience..................................9
Diet and Lifestyle Interventions...........................................................................................9
Exercise..................................................................................................................................9
Weight Loss............................................................................................................................9
Diet/Calorie Restriction/Low Glycemic Index/Load...............................................................9
Soy.......................................................................................................................................10
Flax Seed..............................................................................................................................11
Almonds and Walnuts..........................................................................................................11
Foods that may potentially increase Sex Hormone Binding Globulin (SHBG)......................12
Exposure to Endocrine Disrupting Chemicals.......................................................................12
Patient Education/Counseling............................................................................................12
Counseling............................................................................................................................12
Nutritional Supplements....................................................................................................12
**Myo-Inositol.....................................................................................................................12
**Calcium and Vitamin D.....................................................................................................13
**N-Acetyl Cysteine.............................................................................................................13
**Fish Oil..............................................................................................................................14
Chromium............................................................................................................................14
Botanical Medicine............................................................................................................16
Vitex.....................................................................................................................................16
Cimicifuga racemosa..........................................................................................................17
Tribulus................................................................................................................................17
Maitake ,..............................................................................................................................18
Spearmint (Mentha spicata)................................................................................................18
Traditional Chinese Medicine.............................................................................................18
Acupuncture......................................................................................................................20
Discussion topics:...............................................................................................................20

Relevance to your Naturopathic Practice


PCOS is one of the most common endocrine disorders in menstruating individuals. The
prevalence is 6.5-8%. This means, that in the Canadian population, there are
approximately 1.4M individuals with this disorder.

Background Reading
If you plan on becoming well-versed in PCOS, this is essential reading:
https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS_Evidence-
Based-Guidelines_20181009.pdf

Definition, Epidemiology, Etiology

PCOS
 “A syndrome associated with a range of metabolic abnormalities which can lead
to long-term health problems
 A multifactorial endocrine disorder
 A constellation of signs and symptoms that present in a variable manner
 Most commonly: hirsutism (90%), menstrual irregularity - with anovulation
(90%) and infertility (75%) 1
 History: Used to be called Stein Leventhal syndrome. Named after two doctors
(in the 1920s) who reported the classic symptomatology in a group of women
who were obese, had amenorrhea, infertility, hirsutism.
 Surgical exploration of these women showed enlarged ovaries (2-4x the normal
size), with tiny fluid filled cysts. After taking biopsies, they noted that some
women menstruated. One even became pregnant after many years of infertility
2
.

1
Hacker et al. Essentials of Obstetrics and Gynaecology, 4th Ed. 2004. Elsevier.
2
http://medind.nic.in/jaq/t10/i2/jaqt10i2p121.pdf
Epidemiology 3,4
 Prevalence: 5-10% of reproductive age menstruators have PCOS
 The most common endocrine disorder in menstruators of reproductive age
 Most frequent cause of anovulatory infertility
 Most often spans menarche to menopause, but can be diagnosed anytime in the
reproductive years
 There is likely a genetic component, as there is an increased prevalence among
first-degree relatives of menstruators with PCOS (25-50%)

Pathophysiology
There is an overall “hormonal imbalance” in individuals with PCOS, but the underlying
cause or origin for this remains unknown.

Known endocrine pathophysiology:


1. High LH:
- increase in GnRH secretion  increase LH  increase in ovarian androgen
production and arrest of follicular development (in an immature state) 
multiple cysts in the ovaries and anovulation
- increase LH:FSH ratio (>2) vs. the opposite (more FSH than LH)
- increased androgens lead to increased estrogens through aromatization
- Lack of ovulation exposes endometrium to unopposed estrogen, which can
result in endometrial hyperplasia
- Risk of endometrial hyperplasia is greatest in individuals who do no menstruate
at least every 3 months.... immediate referral required
2. Hyper-insulinemia:
- hyperinsulinemia is an independent contributory factor
- Insulin resistance can occur
- High insulin levels can increase androgen production of ovaries

Clinical Presentation

Common presenting signs and symptoms:


 Obesity in 40-50% of individuals with PCOS (but approx. 50% are normal weight)
o Normal weight individuals with PCOS can also have insulin resistance (but
often milder)
3
First consult. Polycystic ovarian syndrome. Accessed 2016.
4
Ferri’s Clinical Advisor. PCOS . Accessed 2016.
 ***Oligomenorrhea (cycle length greater than 35 days)
 ***Acne (especially past age 25, lower third of face, deep, cystic)
 ***Oily skin
 ***clitoral hypertrophy
 ***polycystic or enlarged ovaries
 Hirsutism
 Glucose intolerance
 Acanthosis nigricans - gray-brown velvety discoloration of the skin, usually at the
neck, groin, and axillae
 Mood disorders (anxiety, depression)

Diagnosis
 European Society for Human Reproduction and Embryology (ESHRE) and
American Society for Reproductive Medicine (ASRM) 2003 consensus (known as
the Rotterdam criteria):
 Diagnosis made with 2 of 3 criteria:
 1. Oligo/anovulation
 2. clinical and/or biochemical hyperandrogenism
 3. Polycystic ovaries on transvaginal US where possible

AND exclusion of other causes

How to assess ovulatory dysfunction:


If cycle length is longer than 35 days, it may be assumed that chronic anovulation is
present. No special tests are needed. (In adolescents, the threshold is higher – 40 days).
If cycle lengths vary from cycle to cycle, ovulation should be assessed.
- Mid-luteal progesterone (>3ng/mL/9.5nmol/L is adequate, but >7ng/mL /22.3
nmol/L is ideal).
In addition, those with hyperandrogenism, there is a 10-15% chance that normal cycles
are anovulatory.
Other tests:
- mid-cycle urinary LH
- Mid-luteal progesterone
- Cycle tracking (an app) can be important as a way to get a good history from
your patient

How to assess clinical hyper-androgenism:


- in adults: hirsutism, alopecia and acne.
- In adolescents: acne is more common (generally) and not a good indicator.
Alopecia is very uncommon and usually has other causes, so hirsutism is the only
true marker in this population 5.
- Hirsutism: certain patterns of hair growth are consistent with androgen excess.
The type of hair is coarse, dark, terminal hair (vs. vellus hair). Onset follows
menarche, and progresses slowly and increases with weight gain (compared to
hair growth with a virilizing tumour).
- Normally, 25-33% of Caucasians have terminal hairs on upper lip, around the
areola, on linea alba.
- In the case of PCOS, there are coarse hairs present on the chin, neck, lower face,
and sideburns, lower back, sternum, abdomen, shoulders, buttocks, perineal
area, and inner thighs.
- Ferriman-Gallwey score is a widely-used scale used to determine hirsutism, but is
limited by its subjectivity and fails to include some locations of androgen-related
hair growth (sideburns, perineum or buttocks). A score of 8 or more is
considered to indicate hirsutism.

How to assess PCO:


- transvaginal ultrasound (occasionally trans-abdominal in certain cases, but is less
accurate)
- rapid changes in US technology have improved the ability to view small follicles
- Existing Rotterdam criteria suggests more than 12 small follicles (2-9mm) in each
ovary or by a finding of increased ovarian volume >10mL (in the absence of a
dominant follicle)
- With newer technology the cut-off value is 25 per ovary (AES guidelines)
- Since we are not always aware of the type of ultrasound machine in use, it is
best to always confirm with clinical signs, although ovarian size is still an
appropriate measure

5
http://journals.aace.com/doi/pd f/10.4158/EP15748.DSC
***The following conditions should be excluded in ALL with a suspected diagnosis of
PCOS: ***

The following conditions should be suspected in some clinical presentations:


Source: Diagnosis and Treatment of PCOS: An Endocrine Society Clinical Practice
Guideline. J Clin Metab. Dec 2013.

Anti-mullerian hormone (AMH): in the near future, AMH will likely be a part of the
diagnostic work-up for PCOS. Currently, an elevated AMH level is suggestive of PCOS,
but there are no clearly defined cut off values.

Once diagnosed, there are parameters by which to evaluate PCOS to monitor:


- response to treatment
- risk of long-term health outcomes

Phenotypes
Due to the variety of clinical features of this syndrome, PCOS can be categorized into 4
“phenotypes”: 6
o Frank PCOS – all three clinical features (most common - 66%)
o Ovulatory PCOS – hyperandrogenism, PCO but regular menstrual cycles
(13%)
o Non PCO – PCOS – hyperandrogenism, oligomenorrhea, but normal
ovaries (11%)
o Mild or normoandrogenic PCOS – oligomenorrhea, PCO ovaries but
normal androgens (9%) – metabolic disturbances equal to controls in
this group

6
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126218/
Long-term Health Outcomes
Individuals with PCOS are at an increased risk of the following conditions:
 Acne
 Type II Diabetes mellitus
 Obesity
 Dyslipidemia
 Endometrial hyperplasia and cancer ***
 Infertility
 Hypertension
 Obstructive sleep apnea
 Mood disorders
 Gestational diabetes
 Pregnancy induced hypertension
 Autoimmune thyroid conditions
 Elevated liver enzymes (30%)
 Non-alcoholic liver disease
 Better bone density (!!)
 Cardiovascular disease ***

Patient Monitoring:
Endometrial hyperplasia and cancer***:
Those who experience extended periods of amenorrhea, especially in the presence of
adequate estrogen levels are at a higher risk for endometrial hyperplasia and cancer.
ESHRE and ASRM recommend induction of menses when there is an absence of
menses for longer than 3 months. The risk is particularly high in PCOS as estrogen is
unopposed for a prolonged period of time. Cyclic treatment with progestins or
combined oral contraceptives is recommended to induce endometrial shedding every 3-
4 months.

Tools, tests and exams for patient monitoring:


Ferriman-Gallway Score to assess androgen excess – yearly
Menses in last 3 months?
Waist to hip ratio (waist is measured between lowest rib and iliac crest, or one inch
above naval, hip measured at widest point below 0.7 is ideal but below 0.8-0.85 is
adequate) Indicator of fertility and cardiovascular disease. Or just waist circumference
Blood pressure – every 3-4 months.
Fasting lipids – at initial diagnosis.
Two-hour oral GTT and HbA1C – at initial diagnosis and then every two years or yearly if
impaired
Liver Enzymes – contentious but consider it if treatment warranted.
Mood, anxiety, depression – PHQ-9, GAD-7 (as needed).
Ask about restful sleep and screen for sleep apnea (STOP-BANG) – initially.

BBT and Cervical Fluid Monitoring/Cycle tracking apps:


- BBT – normally, see sustained rise between 0.2 C and 0.5 C in luteal due to
thermogenic effects of a metabolite of progesterone in normal cycle
- Non-invasive and relatively reliable if looking at the “big picture” vs. day to day
temperatures
- Involves the patient in their own care
- Inexpensive but not definitive
- IN PCOS with anovulation:
o BBT will be erratic with no biphasic temperatures
o Cervical fluid may also be misleading, as ongoing presence of estrogen
may cause cervical fluid to appear to be “fertile” even when an individual
is not ovulating
o Cervical mucous may not be accurate with PCOS:
o Ovulatory mucous changes may be present in the absence of ovulation
o Due to surges in estrogen that may not result in ovulation
- Cycle tracking apps are a simpler way to track cycles and regular cycles 36 days
and under have a high probability of being ovulatory

Urine LH strips:
- may not be accurate, as ongoing LH surge may yield false positive results

Treatment

Conventional Treatment
1. Hormonal Contraceptives (oral, patch, IUD or vaginal ring): First-line
management for menstrual abnormalities and hirsutism/acne.
2. Exercise: As a means to weight loss and to reduce cardiovascular risk factors and
risk of diabetes.
3. Weight Loss: Calorie-restriction diets, low simple-carbohydrate diets. Especially
in overweight individuals.
4. Metformin: Not used as first line treatment. Should be reserved for those with
T2DM who fail lifestyle modification, or in conjunction with Clomid to prevent
ovarian hyperstimulation syndrome (OHSS). Can also be used as second-line
therapy in individuals who do not tolerate hormonal contraceptives for
management of menstrual irregularity.
5. Clomiphine citrate (Clomid)/Letrozole: First-line treatment for ovulation
induction in infertility related to PCOS. Initial dosage is 50mg/day for five days
starting on days 3-5 of cycle.

Treatment Goals/Approach
As PCOS is a constellation of symptoms, each individual with this diagnosis should be
assessed and treated according to her individual presentation of sign, symptoms, serum
hormone levels and desire for fertility, as well as her own principles and preferences. All
individuals should be counseled about the increase risk of long-term health outcomes
and preventive measures should be discussed. There is a particular opportunity to
make a large impact on adolescents through the early adoption of positive lifestyle
modifications.

Note: The following lists contain therapies in order of clinical relevance (most
important, impactful therapies listed near the top of each category). Clinical
importance is determined by research where possible, and by clinical judgment
and experience.
Diet and Lifestyle Interventions
Exercise

There is one systematic review on this topic. Outcomes measured included


cardiovascular risk factors [insulin resistance (IR), lipid profiles, blood pressure and
weight] and reproductive measures (ovulation, menstrual regularity and fertility
outcomes). Eight manuscripts were identified (five randomized controlled trials and
three cohort studies). All studies involved moderate intensity physical activity and most
were of either 12 or 24 weeks duration with frequency and duration of exercise sessions
ranging between studies. The most consistent improvements included improved
ovulation, reduced IR (9-30%) and weight loss (4.5-10%). Improvements were not
dependant on the type of exercise, frequency or length of exercise sessions. 7

Exercise is crucial for so many reasons, however, in those with PCOS, we see an increase
risk of cardiovascular disease, T2DM and psychological pathologies. Exercise may also
improve these long-term risks in these individuals.

7
https://www.ncbi.nlm.nih.gov/pubmed/20833639
What type of exercise would you recommend to your patients with PCOS?

Weight Loss

Approximately 50% of patients with PCOS are obese. Being overweight exerts and
additive effect on metabolic and hormonal imbalances of PCOS (cardiovascular risk,
oligomenorrhea, reduced insulin sensitivity, T2DM).

Individuals with PCOS often report that they find it very difficult to lose weight and very
easy to gain weight.

Individuals with PCOS who lose as little as 5-10% of their body weight report returning
to normal menstruation.

A combination of diet and exercise modifications has been shown to be the most
effective method of weight loss in folks with PCOS.

Please refer to comment on metformin above in the use of weight loss in PCOS.

Diet/Calorie Restriction/Low Glycemic Index/Load


-There is no agreement on what the best diet for those with PCOS is.
- based on clinical judgment, it makes sense to make the following recommendations:
- Eat a primarily Mediterranean-based diet
- Moderate consumption of carbohydrates (and low glycemic load
carbohydrates/whole grains/whole foods)
- Consume a high fiber diet
- approximately 30% of caloric intake from lean protein 8

This diet will serve to reduce long-term cardiovascular risk factors, reduce insulin
resistance, and potentially serum androgens and associated clinical signs. Can promote
weight loss and decrease abdominal obesity.

Dietary and Lifestyle Recommendations in individuals with Low/low-normal BMI


Individuals with low BMI and PCOS often still have significant metabolic dysfunction, and
at the very least are still prone to metabolic dysfunction. Reducing simple
carbohydrates, increased complex carbohydrates, and an overall healthy diet, will still
serve to improve health outcomes in these folks and can often help to restore menstrual
irregularity.

For a review of the joint guidelines regarding lifestyle published in 2018


8
https://www.ncbi.nlm.nih.gov/pubmed/22855917
https://www.monash.edu/__data/assets/pdf_file/0008/1411649/Algorithm-3.pdf

Soy

There are three small studies on the effects of soy/soy isoflavones on the metabolic
parameters of PCOS.
1. In this RCT 70 women with PCOS were allocated to two groups (50mg/day soy
isoflavones or placebo) for 12 weeks. Baseline evaluation of metabolic, endocrine,
inflammatory, and oxidative stress markers and then again at 12 weeks. After 12 weeks
of intervention, compared to the placebo group, soy isoflavone administration
significantly decreased circulating serum levels of insulin (-1.2 ± 4.0 vs +2.8 ± 4.7
μIU/mL; P < .001) and homeostasis model of assessment-estimated insulin resistance (-
0.3 ± 1.0 vs +0.6 ± 1.1; P < .001) and increased the quantitative insulin sensitivity check
index (+0.0009 ± 0.01 vs -0.01 ± 0.03; P = .01). Supplementation with soy isoflavones
resulted in significant reductions in free androgen index (-0.03 ± 0.04 vs +0.02 ± 0.03; P
< .001) and serum triglycerides (-13.3 ± 62.2 vs +10.3 ± 24.5 mg/dL; P = .04) compared to
the placebo group. There was a significant increase in plasma total glutathione (+96.0 ±
102.2 vs +22.7 ± 157.8 μmol/L; P = .04) and a significant decrease in malondialdehyde
levels (-0.7 ± 0.8 vs +0.8 ± 2.3 μmol/L; P = .001) by soy isoflavone intake compared with
the placebo group. We did not observe any significant effect of soy isoflavone intake on
other lipid profiles and inflammatory and oxidative stress markers. 9
2. Twelve Caucasian, obese women with hyperinsulinemia and dyslipidemia and PCOS.
Patients received 36 mg/d of genistein for 6 months. Ultrasonographic pelvic exams,
hormonal and lipid features, oral glucose tolerance test, and euglycemic
hyperinsulinemic clamp were performed at baseline and after 3 and 6 months of
treatment. Phytoestrogens supplementation significantly improved total cholesterol
levels, reducing low-density lipoprotein (LDL) cholesterol and resulting in a significant
decrease in the LDL-high-density lipoprotein ratio (LDL-HDL). Triglycerides showed a
trend toward decrease, whereas no changes were detected in very low-density
lipoprotein cholesterol plasma levels. Genistein treatment did not significantly affect
anthropometric features, the hormonal milieu, and menstrual cyclicity. No significant
changes occurred in glycoinsulinemic metabolism. 10
3. In this quasi-randomized trial, 146 subjects with PCOS were divided into two groups;
the experimental group who received Genistein (Bergamon, Italy) 18 mg twice a day
orally and the control group that received similar capsules with cellulose for 3 months.
Hormonal features and lipid profiles were measured before and after 3 months of
supplement therapy. After 3 months of supplement therapy there were no statistically
significant differences in high density lipoprotein cholesterol (HDL) and follicle

9
https://www.ncbi.nlm.nih.gov/pubmed/27490918
10
https://www.ncbi.nlm.nih.gov/pubmed/18166189
stimulating hormone (FSH) serum levels in Genistein and placebo group before and after
treatment; however serum levels of luteinizing hormone (LH), triglyceride (TG), low
density lipoprotein cholesterol (LDL), dehydroepiandrostrone sulfate (DHEAS) and
testosterone were significantly decreased after 3 months therapy in Genistein group. 11

Generally, soy phytoestrogens have a weak estrogenic effect in some parts of the body.
Early research shows that soy phytoestrogens (specifically genistein) may benefit lipid
parameter, decrease serum androgens, and may benefit glucose dysregulation.

Does soy work by increasing SHBG?


One of the mechanisms by which soy may work to decrease serum free T levels, is by
increasing SHBG. 12

Flax Seed

The effects of flax seed on PCOS are theoretical and there is one case study that
evaluates its use in PCOS.

This clinical case study describes the impact of flaxseed supplementation (30 g/day) on
hormonal levels in a 31-year old woman with PCOS. During a four-month period, the
patient consumed 83% of the flaxseed dose. Heights, weights, and fasting blood samples
taken at baseline and 4-month follow-up indicated the following values: BMI (36.0 vs.
35.7kg/m(2)); insulin (5.1 vs. 7.0 uIU/ml); total serum testosterone (150 ng/dl vs. 45
ng/dl); free serum testosterone (4.7 ng/dl vs. 0.5 ng/dl); and % free testosterone (3.1%
vs. 1.1%). The patient also reported a decrease in hirsutism at the completion of the
study period. The clinically-significant decrease in androgen levels with a concomitant
reduction in hirsutism reported in this case study demonstrates a need for further
research of flaxseed supplementation on hormonal levels and clinical symptoms
of PCOS. 13

Almonds and Walnuts


Speaker notes:
Read the underlined parts

A study of 31 women with PCOS were randomized to consume either almonds or


walnuts for 6 weeks. They were given a portion that contained 31g of total fat/day.

11
https://www.ncbi.nlm.nih.gov/pubmed/22091248
12
https://www.ncbi.nlm.nih.gov/pubmed/10946884
13
https://www.ncbi.nlm.nih.gov/pubmed/19789727
At the beginning and at the end, anthropometric parameters, fasting lipids,
phospholipid-fatty acids, inflammatory markers, androgens, oral glucose tolerance tests
(OGTT) and frequently sampled intravenous-GTT were obtained.
Weight remained stable. Within group, walnuts increased the n-3/n-6 essential PUFA in
the diet and plasma phospholipids. Walnuts decreased low-density lipoprotein-
cholesterol by 6% from 3.76 ± 0.27 to 3.38 ± 0.22 mmol/l (P = 0.05) and apoprotein B by
11% from 0.72 ± 0.04 to 0.64 ± 0.05 g/l (P < 0.03). Although almonds also reduced low-
density lipoprotein-cholesterol by 10% and apoprotein B by 9%, these were not
significant. Walnuts increased insulin response during OGTT by 26% (P < 0.02).
Both walnuts and almonds increased adiponectin (walnuts from 9.5 ± 1.6 to 11.3 ± 1.8
μg per 100 ml, P = 0.0241; almonds from 10.1 ± 1.5 to 12.2 ± 1.4 μg/dl, P =
0.0262). Walnuts decreased HgBA1C from 5.7 ± 0.1 to 5.5 ± 0.1% (P = 0.0006) with
significant intergroup difference from almonds (P=0.0470). Walnuts increased sex
hormone-binding globulin from 38.3 ± 4.1 to 43.1 ± 4.3 nmol/l (P=0.0038)
and almonds reduced free androgen index from 2.6 ± 0.4 to 1.8 ± 0.3 (P = 0.0470). 14
Overall nut intake exerted positive effects on plasma lipids and androgens in women
with PCOS.

Foods that may potentially increase Sex Hormone Binding Globulin (SHBG)
Green tea
Flax seed
Nettle root
Soy
Walnuts

Exposure to Endocrine Disrupting Chemicals


Vigilance about minimizing exposure to BPA, phthalates, and other environmental
plastics (and other endocrine disrupting chemicals). BPA levels are often significantly
higher in those with PCOS, and BPA can magnify the hormonal imbalances that are
common with PCOS.

Patient Education/Counseling
What are the potential opportunities for patient education?

Counseling
- Often ignored/medicated until desire to conceive
- Can take a number of months to return to normal cycle
- Hirsutism can also take 3-6 months to respond to treatment
- Loss of feminine identity (low fertility, male pattern hair growth, obesity)

14
https://www.ncbi.nlm.nih.gov/pubmed/21157477
- Effects on mood, sexual function, quality of life
- Should be recognized early (menarche) and educated about long term health
outcomes

Nutritional Supplements
**Myo-Inositol
Restores ovulation and improves egg quality in women with PCOS or insulin resistance.
May reduce miscarriage risk associated with insulin resistance. Use with caution in
bipolar, or schizophrenia as can exacerbate manic episodes. Titrate dose up slowly as
can cause gas, bloating and diarrhea. The higher the concentration of myo-inositol
inside the follicle, the better the embryo quality (observational). Higher insulin levels
cause infertility by increasing T in the ovaries. Myo-inositol works by increasing insulin
sensitivity. Therefor only see improvements in women with insulin resistance and PCOS.
In women undergoing IVF, when inositol was given at the start of stimulating drugs,
myo-inositol was found to increase the proportion mature eggs retrieved and decrease
number of immature eggs. Fewer cancelled cycles because of overstimulation of ovaries.
But probably better to start myo-inositol sooner. Even in individuals with PCOS who are
not displaying poor insulin sensitivity, it is still effective as treatment (improving egg and
embryo quality during IVF). May also reduce the risk of gestational diabetes. D-chiro-
inositol may have a negative effect on egg quality. Women given this had fewer eggs
and fewer good quality embryos.
Some studies are now looking at the benefits of combining myo-inositol with d-chrio-
inositol in a 40:1 ratio.
Can also be combined with COQ10 to support egg quality.
Myo-inositol also has anxiolytic properties, especially in higher doses.
Dose – 2g bid (total 4g). Can increase to 8-12g if necessary.

**Calcium and Vitamin D


It is most important to reach “optimal” serum vitamin D levels. Vitamin D:
- May improve insulin secretion and lipid parameters in obese individuals with
PCOS
- In individuals with PCOS à low serum 25-OH-Vit D levels are associated with
obesity, metabolic and endocrine disturbances, and supplementation may
improve menstrual frequency

A few studies exist looking at Ca and vit D in combination


- Improved menstrual regularity and more women had dominant follicle when
combined with metformin15 – hirsutism and acne were not improved

15
http://www.ncbi.nlm.nih.gov/pubmed/25535503
- Co-supplementation of both (in Vit D def women with PCOS) led to decreased
serum insulin level and HOMA-IR, and serum TG, and VLDL 16 (compared to
supplementation with either one alone and placebo). Dose was 1000mg Ca and
50000IU/week vit D3 for 8 weeks.
- Also see other studies to support the use of this combination, especially in
vitamin D deficient women with PCOS17.
- Some studies show reductions in testosterone, androstenedione, and decrease
in BP.

**N-Acetyl Cysteine
Precursor to glutathione, acts as an antioxidant. Improves insulin sensitivity. Most
study trials are 1500-1800 mg/day. Most products come in 500mg/capsule dosing.
Various trials show18,19,20,21:
- improvement in menstrual regularity
- reduction in hyper-insulinemia
- reduction in hyperandrogenism
- embryo quality in IVF with ICSI
- can improve ovulation rates in individuals who are resistant to clomid (when
combined with clomid) (but perhaps not as high as with clomid combined with
metformin)

**Fish Oil
Can improve metabolic pathways in PCOS. Has been shown to improve insulin
sensitivity, hirsutism (F-G score), BMI, and HOMA levels decreased. May improve lipid
profile. May improve liver fat content and reduce triglycerides.
Dose- 1500mg (omega 3) - 4000mg 22.

Chromium
Although the exact mechanism of action of chromium is still unknown, chromium has
been shown to enhance the effects of insulin on target tissues. Supplementing
chromium with 1000mg of vitamin C has been shown to increase its absorption
(increased serum levels). The studies on chromium are mixed. Some studies show a
benefit to serum insulin and glucose levels and others do not. The different outcomes
could potentially be accounted for by nutritional status of chromium (only those who
are deficient benefit from supplementation).

16
http://www.ncbi.nlm.nih.gov/pubmed/25300649
17
http://www.ncbi.nlm.nih.gov/pubmed/22780885
18
https://www.ncbi.nlm.nih.gov/pubmed/21831508
19
https://www.ncbi.nlm.nih.gov/pubmed/12057717
20
https://www.ncbi.nlm.nih.gov/pubmed/26654154
21
https://www.ncbi.nlm.nih.gov/pubmed/20939675
22
https://www.ncbi.nlm.nih.gov/pubmed/21270384
A typical prenatal vitamin contains 100mcg/dose.
A few studies have been conducted specifically in women with PCOS. Some studies
show that supplementation with approximately 1000mcg of chromium picolinate
improve insulin sensitivity23,24,25,26.

Dosages in the trials range from 200mcg to 1000 mcg.

How can we determine which individuals could benefit from chromium


supplementation?

Botanical Medicine
Vitex
- Lowers prolactin due to dopaminergic effects
- FSH – no change
- LH – lowered or no change

23
https://www.ncbi.nlm.nih.gov/pubmed/16730719
24
https://www.ncbi.nlm.nih.gov/pubmed/24639797
25
https://www.ncbi.nlm.nih.gov/pubmed/26663540
26
https://www.ncbi.nlm.nih.gov/pubmed/26613790
- Binds to ER-Beta
- Increased serum estradiol
- Increased serum progesterone
- Improved pregnancy rates

Cimicifuga racemosa
- Impacts of black cohosh on PCOS
- Binds with estrogen receptors in pituitary and decreases LH secretion
- Increases luteal progesterone secretion
- Improves endometrial thickness for infertile women with PCOS
- Lower LH for women with PCOS
- Improves LH:FSH ratio for women with PCOS
- Limits anti-estrogen effects when used with Clomiphene citrate for women with
PCOS
- 2014 RCT:
- Women <35 years of age presenting with PCOS and infertility
- 98 women received Clomiphene citrate (CC); 96 women received CC and
Cimicifuga racemosa
- Significant improvements were found in:
o Days to HCG injection (shorter time for follicular development)
o Endometrial thickness
o Serum levels of mid-luteal and midcycle estradiol
o Serum levels of mid-luteal progesterone
o Higher rates of pregnancy per cycle (17.2% for CC, 34.8% for CC+CR)

Tribulus
Impacts of Tribulus on PCOS
- Ovulation induction in polycystic ovaries
- No estrogenic effects
- Increased FSH in healthy women
- Equivalence for ovulation induction compared to CC for women with
oligo/anovular infertility
- In one study, suggested that use for 3 months may normalize ovulation and
result in pregnancy in women with endocrine infertility
- Standardized extract of 40% furostanol saponins
- Daily dose should be approximately 300-400mg/day from day 5 to ovulation
Maitake 27,28
- Maitake extract tablets containing 18mg of extract called SX-fraction (MSX) in
water soluble glycoprotein and 250mg of dried maitake mushroom powder.
Each patient given 3 tablets TID. 26 patients in maitake group.
- 31 patients in CC group – given 50 mg/day from days 5 to 9 of menses.
- Evaluated for ovulation with pelvic US. Ovulation rate for maitake was 76.9%
(20/26) and 93.5% (29/31) for CC.
- Combination group 7 of 7 patients who failed MSX monotherapy and 6 of 8 who
failed CC monotherapy demonstrated ovulation.

Spearmint (Mentha spicata)


Spearmint consumed as a tea has been studied in two trials for anti-androgenic
properties.
1. Fourty two women with PCOS were randomized to consume two cups of
spearmint tea daily for 30 days, or placebo tea. At 0, 15 and 30 days, serum
gonadotropins and androgens were measured, as well as objective and
subjective measures of hirsutism. Free and total testosterone levels were
significantly reduced over the 30-day period in the spearmint tea group (p <
0.05). LH and FSH also increased (p < 0.05). Patient's subjective assessments of
their degree of hirsutism scored by the modified DQLI were significantly reduced
in the spearmint tea group (p < 0.05). There was, however, no significant
reduction in the objective Ferriman-Galwey ratings of hirsutism between the two
trial groups over the trial duration (p = 0.12). 29
2. Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9
with idiopathic hirsutism were included to the study. They were took a cup of
herbal tea which was steeped with M. spicata for 5 days twice a day in the
follicular phase of their menstrual cycles. After treatment with spearmint teas,
there was a significant decrease in free testosterone and increase in luteinizing
hormone, follicle-stimulating hormone and estradiol. 30

Traditional Chinese Medicine


PCOS is not it’s own disease state in TCM, but rather the unique phenotype of each
individuals is attributed to an appropriate TCM diagnosis. Often it is a result of a
deficiency of Kidney Yang and when deficient for a long time, it may fail to transform,
evaporate and transport fluids causing dampness in the lower burner, causing it to

27
J Altern Complement Med. 2010 Dec;16(12):1295-9. doi: 10.1089/acm.2009.0696.
Epub 2010 Oct 29.
28
PMID: 21034160
29
https://www.ncbi.nlm.nih.gov/pubmed/19585478
30
https://www.ncbi.nlm.nih.gov/pubmed/17310494
accumulate as Dampness/Phlegm. This can cause ovarian cysts to form. The deficiency
of Kidney Yang itself causes amenorrhea or infertility. There may also be blood stasis.
The difference between PCOS and ovarian cysts is that in PCOS there is a congenital
deficiency of Kidney Yang.

Treatment includes tonify Kidney Yang and resolve Dampness/Phlegm at the same time.
Resolve blood stasis if also an issue.

1. Deficiency of Kidney Yang with Dampness/Phlegm.


 No periods or scant periods
 History of infertility
 Feeling of oppression in the chest
 Feeling of heaviness of the abdomen
 Excessive vaginal discharge
 Tongue: Pale, swollen white with a sticky coating
 Pulse: Weak and slightly slippery
 Treatment principle: Tonify and warm Kidney-Yang, resolve Dampness and
phlegm.
Points:
 LU 7 on R and KI 6 on L – regulate the directing vessel and strengthen the
uterus, dissolve masses.
 Ren 3, ST 28, UB 32, 22 – resolve dampness from genital system.
 SP 9 and SP 6 – resolve dampness
 UB 23, KI 3, CV 4, KI 7 with moxa, tonify KD Yang.
 ST 36 and UB 20 – tonify spleen to resolve dampness.

2. Deficiency of Kidney Yang, Presence of Phlegm and stasis of the Blood.


 No periods or scant periods
 History of infertility
 Obesity
 Hirsutism
 Feeling of oppression in the chest
 Feeling of heaviness of the abdomen
 Excessive vaginal discharge
 Abdominal pain
 Tongue: Pale-purple or bluish-purple, swollen with a sticky white coating
 Pulse: Weak and slightly slippery
 Treatment principle: Tonify and warm Kindney-Yang, invigorate blood and
eliminate stasis, resolve Phlegm.
Points:
 LU 7 on R and KI 6 on L – regulate the directing vessel and strengthen the
uterus, dissolve masses.
 Ren 3, ST 28, UB 32, 22 – resolve dampness from genital system.
 ST 29, SP 10, UB 17 – invigorate blood and eliminate stasis.
 SP 9 and SP 6 – resolve dampness
 UB 23, KI 3, CV 4, KI 7 with moxa, tonify KD Yang.
 ST 36 and UB 20 – tonify spleen to resolve dampness.

Acupuncture
A recent Cochrane review showed that evidence quantity and quality is low and level of
effect is low31.

In many studies electro-acupuncture seems to help with inducing ovulation.

Best approach:
- address overall TCM picture (as above), while still doing local points to aid with
pelvic blood flow (CV3, CV4, Zigong)
- determine measurable outcomes to assess if treatment is having a positive
effect, and continue for a pre-determined amount of time.

Discussion topics:
When is conventional treatment warranted?
How would you approach the naturopathic treatment of a woman with PCOS?

Important Resources:
2018 International Guideline for Assessment and Management in PCOS.
https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS_Evidence-
Based-Guidelines_20181009.pdf

31
https://www.ncbi.nlm.nih.gov/pubmed/27136291

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