Utilizing the DUTCH Test for PCOS
How to use the DUTCH Test for
PCOS
Carrie Jones, ND, FABNE, MPH
1
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Polycystic Ovary Disease (PCOS) Objectives:
2
1.
The specifics of the Rotterdam Criteria and the Phenotypes
2.
The 4 “sub-categories” of PCOS
3.
Common symptoms of PCOS at-large
4.
How to use the DUTCH Complete to evaluate Insulin,
inflammatory, and adrenal PCOS
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Quick PCOS Facts:
3
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
What is the Rotterdam Criteria?
4
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Rotterdam Criteria:
5
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
1.
Oligo or amenorrhea
2.
Hyperandrogenism – androgen labs and androgen symptoms
3.
Polycystic ovaries seen on ultrasound
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
What’s the issue?
6
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Rotterdam Criteria:
7
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
1.
Oligo or amenorrhea
2.
Hyperandrogenism – androgen labs and androgen symptoms
3.
Polycystic ovaries
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Rotterdam Criteria:
8
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
1.
Oligo or amenorrhea
2.
Hyperandrogenism – androgen labs and androgen symptoms
3.
Polycystic ovaries
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
9
https://emedicine.medscape.com/article/404754-overview
*Ultrasound:
Either 12 or more follicles measuring 2-9 mm in diameter and/or an increased ovarian volume >10 cm
3
Lee TT, Rausch ME. Polycystic Ovarian Syndrome: Role of Imaging in Diagnosis RadioGraphics. 2012; 32(6):1643-1657.
Rotterdam Criteria:
10
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
1.
Oligo or amenorrhea
2.
Hyperandrogenism – androgen labs and androgen symptoms
3.
Polycystic ovaries – U/S not recommended in young women
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Don’t automatically call all cysts PCOS
11
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Rotterdam Criteria:
12
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
1.
Oligo or amenorrhea
2.
Hyperandrogenism – androgen labs and androgen symptoms
3.
Polycystic ovaries
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
The 4 Phenotypes per the NIH,
Androgen Excess & PCOS Society
13
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
4 Phenotypes of PCOS:
14
•
PCOS – A = full blown PCOS, all 3 Rotterdam criteria
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
4 Phenotypes of PCOS:
15
•
PCOS – A = full blown PCOS, all 3 Rotterdam criteria
•
PCOS – B = non PCO PCOS = oligo/anovulation + hyperandrogen
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
4 Phenotypes of PCOS:
16
•
PCOS – A = full blown PCOS, all 3 Rotterdam criteria
•
PCOS – B = non PCO PCOS = oligo/anovulation + hyperandrogen
•
PCOS – C = ovulatory PCOS = PCO and hyperandrogenism
Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to
clomiphene Indian J Endocr Metab. 2019; 23(3):326-.
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
4 Phenotypes of PCOS:
17
•
PCOS – A = full blown PCOS, all 3 Rotterdam criteria
•
PCOS – B = non PCO PCOS = oligo/anovulation + hyperandrogen
•
PCOS – C = ovulatory PCOS = PCO and hyperandrogenism
•
PCOS – D = nonhyperandrogen = PCO and oligo/anovulation
Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to
clomiphene Indian J Endocr Metab. 2019; 23(3):326-.
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
4 Phenotypes of PCOS:
18
•
PCOS – A = full blown PCOS, all 3 Rotterdam criteria
•
PCOS – B = non PCO PCOS = oligo/anovulation + hyperandrogen
•
PCOS – C = ovulatory PCOS = PCO and hyperandrogenism
•
PCOS – D = nonhyperandrogen = PCO and oligo/anovulation
Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to
clomiphene Indian J Endocr Metab. 2019; 23(3):326-.
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
4 Phenotypes of PCOS:
19
•
PCOS – A = full blown PCOS, all 3 Rotterdam criteria
•
PCOS – B = non PCO PCOS = oligo/anovulation + hyperandrogen
•
PCOS – C = ovulatory PCOS = PCO and hyperandrogenism
•
PCOS – D = nonhyperandrogen = PCO and oligo/anovulation
Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to
clomiphene Indian J Endocr Metab. 2019; 23(3):326-.
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Hiam , Moreno-Asso , Teede , et al. The Genetics of Polycystic Ovary Syndrome: An Overview of Candidate Gene Systematic
Reviews and Genome-Wide Association Studies JCM. 2019; 8(10):1606-.
20
“
The proposed pathophysiology of PCOS is a synergistic relationship
between perturbed gonadotrophin releasing hormones (GnRH)
pulsatility and hyperandrogenism probably accompanied by
hyperinsulinemia, insulin resistance, and inflammation.”
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Glucocorticoids can also disrupt GnRH to disrupt
the pulsatile nature of FSH and/or LH
from the pituitary
Find the root cause of the elevated cortisol
(Stress? Infection? Inflammation? Cushing's?)
24
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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2
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•
T
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s
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g
:
•
CYP21A2 genotyping
•
Elevated 17-hydroxyprogesterone (17-OHP)
•
Elevated androgens
•
Cortisol generally
low
•
ACTH generally
high
Papadakis G, Kandaraki EA, Tseniklidi E, Papalou O, Diamanti-Kandarakis E. Polycystic Ovary Syndrome and NC-
CAH: Distinct Characteristics and Common Findings. A Systematic Review Front. Endocrinol.. 2019; 10.
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•
Insulin receptor
•
Insulin gene variable number of tandem repeats (INS-
VNTR)
•
Insulin Receptor Substrate-1 and 2 (IRS-1 and IRS-2)
•
Transcription Factor 7-Like 2 (TCF7L2) (adipogenesis)
•
Calpain-10 (↑ risk type 2DM)
•
Adiponectin
•
CYP1A1
•
CYP11A1
•
DENN domain containing 1A (DENND1A)
•
Paraoxonase 1 (PON1) (↑ risk type 2DM & CVD)
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Hiam , Moreno-Asso , Teede , et al. The Genetics of Polycystic Ovary Syndrome: An Overview of Candidate Gene Systematic Reviews and Genome-Wide Association Studies JCM. 2019; 8(10):1606-.
•
Follicle Stimulating Hormone Receptor (FSHR)
•
Androgen Receptor (AR)
•
CYP17/HSD 17
•
HSD3B
•
Anti-müllerian hormone (AMH)
•
Anti-müllerian hormone receptor II (AMHRII)
•
TNF-a
•
IL-6
•
And more
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
27
Lin YC, Papadopoulos V. Neurosteroidogenic enzymes: CYP11A1 in the central nervous system Frontiers in Neuroendocrinology. 2021; 62:100925-.
PCOS and the DUTCH Test
28
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
18yo Case Study
29
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
•
Menarche at 15yo
•
Cycles mostly irregular ever since
•
Bleeds 5-7 days
•
Dysmenorrhea off and on days 1 and 2
•
PMS symptoms a full week leading up to her period (it’s how she knows her
period is coming)
•
Hyperandrogenic symptoms
•
Female pattern hair thinning
•
Cystic acne since 15yo especially along the jaw line and under chin
18yo Case Study
30
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
•
Gained about 30lbs the last 3 years
•
Height 5’4”, weight 175#, BMI 30
•
Not taking medication or supplements
•
Diet – fairly standard American diet, fast food, box foods, soda, energy drinks
•
Senior in high school
•
Very high stress, up late studying and being a typical teenager
•
Family history:
•
Mother has type 2 diabetes
•
Older 1
st
cousin diagnosed PCOS at 20yo
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
31
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Collected day 22
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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•
Progesterone is just above the luteal star
•
Indicates likely ovulation this month
Does she ovulate every month?
43
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Does she ovulate every month?
44
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
45
•
Estrone in range
•
Estradiol elevated
•
Estriol in range
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
46
Estrogen “dominance” in the luteal phase
relative to progesterone
What about Estrogen Metabolism?
47
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
S
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w
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Sewer line out
S
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Sewer line out
P
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.
2OH
4OH
16OH
S
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P
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D
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.
2OH
4OH
16OH
2methoxy
COMT + Mg
S
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w
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Sewer line out
P
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3
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D
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2OH
4OH
16OH
2methoxy
COMT + Mg
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P
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3
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2OH
4OH
16OH
2methoxy
COMT + Mg
T
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a
c
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:
S
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Sewer line out
P
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3
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.
P
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2OH
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16OH
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COMT + Mg
A
d
d
r
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s
s
i
t
:
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
54
Phase 1 Metabolism
:
•
2-OH low
•
4-OH high 23.2%
•
16-OH in range
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
55
Phase 2 Metabolism
•
2-Methoxy in range
How can you further evaluate phase 3?
56
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
57
DHEA-S in range – inflammation?
Inflammation can inhibit sulfation/SULT
Results?
Less DHEA-S
More downstream metabolites
58
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Mueller, J.W., et al., The Regulation of Steroid Action by Sulfation and Desulfation. Endocr Rev, 2015. 36(5): p. 526-63. Kim, M.S., et al., Suppression of DHEA sulfotransferase (Sult2A1)
during the acute-phase response. Am J Physiol Endocrinol Metab, 2004. 287(4): p. E731-8.
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
59
Testosterone elevated
Where is circulating testosterone
made in females?
60
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
https://www.bumc.bu.edu/sexualmedicine/publications/testosterone-insufficiency-in-women-fact-or-fiction/#:~:text=In%20women%2C%20testosterone%20is%20produced,the%20ovaries%20and%20adrenal%20gland.
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Where is circulating testosterone
made in females?
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
https://www.bumc.bu.edu/sexualmedicine/publications/testosterone-insufficiency-in-women-fact-or-fiction/#:~:text=In%20women%2C%20testosterone%20is%20produced,the%20ovaries%20and%20adrenal%20gland.
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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5a-preference = androgenic
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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What is 5a-Reductase
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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5a-DHT has a higher affinity to the androgen receptor, longer half life
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DHT can not aromatize into estrogen
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Biochemistry, Dihydrotestosteorne. Statpearls retrieved on March 3, 2022 from
https://www.ncbi.nlm.nih.gov/books/NBK557634/
•
Kayampilly PP, Wanamaker BL, Stewart JA, Wagner CL, Menon KMJ. Stimulatory Effect of Insulin on 5
α-
Reductase Type 1 (SRD5A1) Expression through an Akt-Dependent
Pathway in Ovarian Granulosa Cells . 2010; 151(10):5030-5037.
What is 5a-Reductase
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Insulin, inflammatory cytokines, elevated levels of testosterone
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Biochemistry, Dihydrotestosteorne. Statpearls retrieved on March 3, 2022 from
https://www.ncbi.nlm.nih.gov/books/NBK557634/
•
Kayampilly PP, Wanamaker BL, Stewart JA, Wagner CL, Menon KMJ. Stimulatory Effect of Insulin on 5
α-
Reductase Type 1 (SRD5A1) Expression through an Akt-Dependent
Pathway in Ovarian Granulosa Cells . 2010; 151(10):5030-5037.
Case: Sex Hormone Summary
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Progesterone on the low end of range
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Estradiol elevated
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Favors ‘more carcinogenic’ 4-OH estrogen metabolism pathway
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Elevated testosterone
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Elevated androgenic 5a-DHT
pathway
Rotterdam Criteria:
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
1.
Oligo or amenorrhea
2.
Hyperandrogenism – androgen labs and androgen symptoms
3.
Polycystic ovaries seen on ultrasound
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Rotterdam Criteria:
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Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and
Reproductive Biology: X. 2019; 3:100060-.
1.
Oligo or amenorrhea
2.
Hyperandrogenism – androgen labs and androgen symptoms
3.
Polycystic ovaries seen on ultrasound
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Remember, elevated glucocorticoids can disrupt HPO
signaling = cycle issues
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Remember, elevated glucocorticoids can disrupt HPO
signaling = cycle issues
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Elevated glucocorticoids = increased glucose through gluconeogenesis
and glycogenolysis
Other related tests to consider:
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Cardiometabolic testing
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Fasting glucose and insulin
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Lipid panel (advanced)
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Thyroid testing
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Prolactin
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FSH/LH and AMH
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Pelvic ultrasound
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Other related ‘functional’ testing as indicated
Addressing PCOS per the DUTCH Test
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Be mindful that she’s 18yo, impressionable and
struggling.
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While there is a genetic component you know that diet,
lifestyle,& environment influence DNA expression
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PCOS Treatment: Goals
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
1.
Normalize insulin/glucose
2.
Improve cardiovascular markers
3.
Reduce inflammatory cytokines
4.
Regulate ovulation/Improve luteal progesterone
5.
Improve estrogen metabolism
6.
Reduce androgens/5a-reductase
7.
Improve cortisol markers
The PCOS Flow Summary
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Goal: Improving glucose/insulin sensitivity
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Address diet, lifestyle and exercise first!
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Address the reason why their cortisol is
elevated
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Glucophage/Metformin
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Myo and D- chiro inositol (2 grams BID)
Fenugreek seed extract (500mg BID)
Berberine (500mg TID)
Gymnema (100-400mg QD-BID)
Cinnamon (spice – pretty mild)
Citations:
•
Hassanzadeh Bashtian M, Emami SA, Mousavifar N, Esmaily HA, Mahmoudi M, Mohammad Poor AH.
Evaluation of Fenugreek (Trigonella foenum-graceum L.), Effects Seeds Extract on Insulin Resistance in
Women with Polycystic Ovarian Syndrome. Iran J Pharm Res. 2013; 12(2):475-81. [
]
•
Rondanelli M, Infantino V, Riva A, et al. Polycystic ovary syndrome management: a review of the possible
amazing role of berberine Arch Gynecol Obstet. 2020; 301(1):53-60.
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Roseff S, Montenegro M. Inositol Treatment for PCOS Should Be Science-Based and Not Arbitrary
International Journal of Endocrinology. 2020; 2020:1-8.
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Stracquadanio M, Ciotta L, Palumbo MA. Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary
syndrome patients Gynecological Endocrinology. 2017; 34(6):495-501.
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Goal: Reduce Androgens/5a-Reductase
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
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Address diet, lifestyle and androgens first!
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Identify and reduce inflammatory cytokines
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Identify and address the HPA axis
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C
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Finasteride/Propecia
Spironolactone
Minoxidil/Rogaine
Oral contraceptives
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Reishi mushroom
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Green tea (EGCG)
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Saw palmetto
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White Peony/licorice
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Spearmint tea (or oil topically)
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Rosemary oil topically
Goal: Reduce Androgens/5a-Reductase
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
C
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Reishi mushroom
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500-1500mg
Green tea (EGCG)
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500-1000mg
Saw palmetto
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500-2000mg
Stinging nettle root
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300-600mg
White Peony/licorice
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Common Chinese medicine
blend
Spearmint tea (or oil topically)
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1 cup tea twice/day
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Dilute oil, apply to scalp
Rosemary oil topically
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Dilute oil, apply to scalp
Citations:
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Arentz S, Abbott JA, Smith CA, Bensoussan A. Herbal medicine for the management of polycystic ovary
syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory
evidence for effects with corroborative clinical findings BMC Complement Altern Med. 2014; 14(1).
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Armanini D, Mattarello MJ, Fiore C, et al. Licorice reduces serum testosterone in healthy women Steroids.
2004; 69(11-12):763-766.
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Grant P, Ramasamy S. An Update on Plant Derived Anti-Androgens Int J Endocrinol Metab. 2012; 10(2):497-
502.
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Medical News Today. How to use rosemary oil for hair growth. Retrieved on March 5, 2022 from
https://www.medicalnewstoday.com/articles/319444
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Najafipour F, et al.
Therapeutic effects of stinging nettle (Urtica dioica) in women with Hyperandrogenism. Int
J Curr Res Aca Rev. 2014;2(7):153-160.
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PCOS Summary:
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1.
A thorough history is half the battle with PCOS
2.
Use the DUTCH test to evaluate androgens, progesterone,
estrogens, and cortisol.
3.
Insulin is the biggest player for most PCOS for a variety of
reasons and it has a massive effect on all the hormones
4.
Don’t forget about inflammation and the HPA axis though
5.
Want to learn even more?
Dr. Kalish x Rupa Bootcamp!
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Thank you for listening!
www.rupahealth.com
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Carrie Jones, ND, FABNE, MPH/Rupa Health 2022
Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder in females with various genetic, environmental, and lifestyle influences. The Rotterdam Criteria, involving oligo/amenorrhea, hyperandrogenism, and polycystic ovaries, is used for PCOS diagnosis. The DUTCH Complete test can assess insulin, inflammation, and adrenal functions related to PCOS. Long-term sequelae like cardiovascular disease and type 2 diabetes should be monitored. This article explores the Rotterdam Criteria, PCOS sub-categories, common symptoms, and provides quick facts about PCOS.
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How to use the DUTCH Test for PCOS Carrie Jones, ND, FABNE, MPH Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 1
Polycystic Ovary Disease (PCOS) Objectives: 1.The specifics of the Rotterdam Criteria and the Phenotypes 2.The 4 sub-categories of PCOS 3.Common symptoms of PCOS at-large 4.How to use the DUTCH Complete to evaluate Insulin, inflammatory, and adrenal PCOS Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 2
Quick PCOS Facts: 1.Number 1 endocrine disorder in females 2.It s a major reason for oligomenorrhea and fertility challenges 3.There are genetic, environmental, and lifestyle factors at play 4.Long term sequelae such as cardiovascular disease and type 2 diabetes must routinely be evaluated especially with hyperandrogenism 5.It is most commonly diagnosed by the Rotterdam Criteria Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and Reproductive Biology: X. 2019; 3:100060-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 3
What is the Rotterdam Criteria? Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 4
Rotterdam Criteria: Must be 2 out of 3 to be considered PCOS 1.Oligo or amenorrhea 2.Hyperandrogenism androgen labs and androgen symptoms 3.Polycystic ovaries seen on ultrasound Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and Reproductive Biology: X. 2019; 3:100060-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 5
Whats the issue? Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 6
Rotterdam Criteria: Must be 2 out of 3 to be considered PCOS 1.Oligo or amenorrhea 2.Hyperandrogenism androgen labs and androgen symptoms 3.Polycystic ovaries Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and Reproductive Biology: X. 2019; 3:100060-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 7
Rotterdam Criteria: Must be 2 out of 3 to be considered PCOS 1.Oligo or amenorrhea 2.Hyperandrogenism androgen labs and androgen symptoms 3.Polycystic ovaries Cysts on ovaries are VERY common While PCOS cysts are distinctive, many women have been told they have PCOS based on an ultrasound with cysts that should not qualify Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and Reproductive Biology: X. 2019; 3:100060-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 8
*Ultrasound: Either 12 or more follicles measuring 2-9 mm in diameter and/or an increased ovarian volume >10 cm3 Lee TT, Rausch ME. Polycystic Ovarian Syndrome: Role of Imaging in Diagnosis RadioGraphics. 2012; 32(6):1643-1657. https://emedicine.medscape.com/article/404754-overview Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 9
Rotterdam Criteria: Must be 2 out of 3 to be considered PCOS 1.Oligo or amenorrhea 2.Hyperandrogenism androgen labs and androgen symptoms 3.Polycystic ovaries U/S not recommended in young women Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and Reproductive Biology: X. 2019; 3:100060-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 10
Dont automatically call all cysts PCOS Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 11
Rotterdam Criteria: Must be 2 out of 3 to be considered PCOS 1.Oligo or amenorrhea 2.Hyperandrogenism androgen labs and androgen symptoms 3.Polycystic ovaries Hyperandrogenism has the highest risk for cardiovascular and metabolic disease due to the insulin link. Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article European Journal of Obstetrics & Gynecology and Reproductive Biology: X. 2019; 3:100060-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 12
The 4 Phenotypes per the NIH, Androgen Excess & PCOS Society Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 13
4 Phenotypes of PCOS: PCOS A = full blown PCOS, all 3 Rotterdam criteria Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 14
4 Phenotypes of PCOS: PCOS A = full blown PCOS, all 3 Rotterdam criteria PCOS B = non PCO PCOS = oligo/anovulation + hyperandrogen Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 15
4 Phenotypes of PCOS: PCOS A = full blown PCOS, all 3 Rotterdam criteria PCOS B = non PCO PCOS = oligo/anovulation + hyperandrogen PCOS C = ovulatory PCOS = PCO and hyperandrogenism Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to clomiphene Indian J Endocr Metab. 2019; 23(3):326-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 16
4 Phenotypes of PCOS: PCOS A = full blown PCOS, all 3 Rotterdam criteria PCOS B = non PCO PCOS = oligo/anovulation + hyperandrogen PCOS C = ovulatory PCOS = PCO and hyperandrogenism PCOS D = nonhyperandrogen = PCO and oligo/anovulation Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to clomiphene Indian J Endocr Metab. 2019; 23(3):326-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 17
4 Phenotypes of PCOS: Most Common PCOS A = full blown PCOS, all 3 Rotterdam criteria PCOS B = non PCO PCOS = oligo/anovulation + hyperandrogen PCOS C = ovulatory PCOS = PCO and hyperandrogenism PCOS D = nonhyperandrogen = PCO and oligo/anovulation Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to clomiphene Indian J Endocr Metab. 2019; 23(3):326-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 18
4 Phenotypes of PCOS: PCOS A = full blown PCOS, all 3 Rotterdam criteria PCOS B = non PCO PCOS = oligo/anovulation + hyperandrogen Least PCOS C = ovulatory PCOS = PCO and hyperandrogenism Common PCOS D = nonhyperandrogen = PCO and oligo/anovulation Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to clomiphene Indian J Endocr Metab. 2019; 23(3):326-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 19
Hiam , Moreno-Asso , Teede , et al. The Genetics of Polycystic Ovary Syndrome: An Overview of Candidate Gene Systematic Reviews and Genome-Wide Association Studies JCM. 2019; 8(10):1606-. The proposed pathophysiology of PCOS is a synergistic relationship between perturbed gonadotrophin releasing hormones (GnRH) pulsatility and hyperandrogenism probably accompanied by hyperinsulinemia, insulin resistance, and inflammation. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 20
Glucocorticoids can also disrupt GnRH to disrupt the pulsatile nature of FSH and/or LH from the pituitary Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 23
Find the root cause of the elevated cortisol (Stress? Infection? Inflammation? Cushing's?) Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 24
21-hydroxylase deficient non-classical congenital adrenal hyperplasia Testing: CYP21A2 genotyping Elevated 17-hydroxyprogesterone (17-OHP) Elevated androgens Cortisol generally low ACTH generally high Papadakis G, Kandaraki EA, Tseniklidi E, Papalou O, Diamanti-Kandarakis E. Polycystic Ovary Syndrome and NC- CAH: Distinct Characteristics and Common Findings. A Systematic Review Front. Endocrinol.. 2019; 10. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 25
SNPS being studied with PCOS Insulin receptor Follicle Stimulating Hormone Receptor (FSHR) Insulin gene variable number of tandem repeats (INS- Androgen Receptor (AR) VNTR) CYP17/HSD 17 Insulin Receptor Substrate-1 and 2 (IRS-1 and IRS-2) HSD3B Transcription Factor 7-Like 2 (TCF7L2) (adipogenesis) Anti-m llerian hormone (AMH) Calpain-10 ( risk type 2DM) Anti-m llerian hormone receptor II (AMHRII) Adiponectin TNF-a CYP1A1 IL-6 CYP11A1 And more DENN domain containing 1A (DENND1A) Paraoxonase 1 (PON1) ( risk type 2DM & CVD) Hiam , Moreno-Asso , Teede , et al. The Genetics of Polycystic Ovary Syndrome: An Overview of Candidate Gene Systematic Reviews and Genome-Wide Association Studies JCM. 2019; 8(10):1606-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 26
Lin YC, Papadopoulos V. Neurosteroidogenic enzymes: CYP11A1 in the central nervous system Frontiers in Neuroendocrinology. 2021; 62:100925-. Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 27
PCOS and the DUTCH Test Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 28
18yo Case Study Menarche at 15yo Cycles mostly irregular ever since Bleeds 5-7 days Dysmenorrhea off and on days 1 and 2 PMS symptoms a full week leading up to her period (it s how she knows her period is coming) Hyperandrogenic symptoms Female pattern hair thinning Cystic acne since 15yo especially along the jaw line and under chin Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 29
18yo Case Study Gained about 30lbs the last 3 years Height 5 4 , weight 175#, BMI 30 Not taking medication or supplements Diet fairly standard American diet, fast food, box foods, soda, energy drinks Senior in high school Very high stress, up late studying and being a typical teenager Family history: Mother has type 2 diabetes Older 1st cousin diagnosed PCOS at 20yo Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 30
Collected day 22 Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 34
Progesterone is just above the luteal star Indicates likely ovulation this month Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 42
Does she ovulate every month? Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 43
Does she ovulate every month? Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 44
Estrone in range Estradiol elevated Estriol in range Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 45
Estrogen dominance in the luteal phase relative to progesterone Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 46
What about Estrogen Metabolism? Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 47
Sewer line out Sewer
Phase 1 Estrogen Detox. 2OH 4OH 16OH Sewer line out Sewer
Phase 1 Estrogen Detox. 2OH 4OH 16OH Phase 2 Estrogen Detox. 2methoxy COMT + Mg Sewer line out Sewer
