Understanding and Utilizing the DUTCH Test for PCOS

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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

Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 21

Carrie Jones, ND, FABNE, MPH/Rupa Health 2022 22

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