Polycystic Ovary Syndrome

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1 Polycystic Ovary Syndrome Kathleen Colleran, MD Professor of Medicine University of New Mexico HSC Presented for COMM-TC May 4, 2012 Objectives Understand the pathophysiology of PCOS Understand how to evaluate for PCOS Understand treatment options for PCOS 1

2 Thank you for attending this Envision NM webinar conference. We will begin shortly. To connect audio, please telephone Access code: # Please mute/un-mute your telephone line by pressing *6. You may also press your mute button on your headset or speakerphone during the webinar when you are not speaking. Do not place your phone on hold. If you wish to receive CME/CEU/ or an attendance certificate, you must announce your name when we ask who is participating both at the start and at the end of the session. This session is being recorded. If you are called on and do not wish to answer, feel free to say pass. Disclosure: UNM CME policy, in compliance with the ACCME Standards of Commercial Support, requires that anyone who is in a position to control the content of an activity disclose all relevant financial relationships they have had within the last 12 months with a commercial interest related to the content of this activity. The presenter discloses that he/she/they have no relevant financial relationships with any commercial interest. Accreditation: The University of New Mexico School of Medicine, Office of Continuing Medical Education is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Office of Continuing Medical Education designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity. Envision NM is a division of the UNM Department of Pediatrics and receives funding from the NM Department of Health and the NM Human Services Department. 2

3 Overview of PCOS Affects 5-10% of reproductive aged women Multi-system reproductive-metabolic disorder Hypothalamic-pituitary-ovarian axis Carbohydrate metabolism/insulin resistance Obesity Genetics 3

4 Risk Factors or Who Gets PCOS Overweight/obese reproductive aged women Women with insulin resistance (FH, GM, DM) Women with a family history of PCOS Women of color Native Americans Hispanic/Mexican Americans African Americans Clinical Features of PCOS Androgen excess (hirsutism, acne) Anovulation (irregular menses, infertility) Insulin resistance (diabetes) Polycystic ovaries 4

5 Normal Menstrual Cycle Hormone Level Estradiol Progesterone FSH LH Ovulation Endometrial Thickness Menstrual Cycle Day Anovulatory Bleeding in PCOS Hormone Level Estradiol Progesterone LH FSH Lower limit of normal Endometrial Thickness Breakthrough Withdrawal Weeks 5

6 Estimated Prevalence of Menstrual Patterns in PCOS Oligomenorrhea % Amenorrhea 20 % Regular cycles 5-10 % Obesity in PCOS 50-70% of PCOS Android distribution of fat Associated with insulin resistance Impaired glucose tolerance Diabetes Lowers SHBG- increases ratio of bioavailable T/E Adverse lipid profile Low HDL High TG Small dense LDL 6

Glucose Intolerance in PCOS n NGT IGT DM Legro et al (2005) Ehrmann et al (1999) Norman et al (2001) 71 39 (55%) 25 (35%) 7

7 Glucose Intolerance in PCOS n NGT IGT DM Legro et al (2005) Ehrmann et al (1999) Norman et al (2001) (55%) 25 (35%) 7 (10%) 16%/yr (55%) 43 (35%) 12 (10%) 50%/yr (81%) 13 (19%) 0 9%/yr 2%/yr 30%/yr 54%/yr Progression rates 9-50% 2-54% 7

for diagnosis 25% of women have PCO, but only 5% have PCOS PCO PCOS

8 Diagnosis: PCO on ultrasound At least 1 ovary with 12+ follicles 2-9mm &/or ovarian volume > 10mls US picture on 1 occasion suffices for diagnosis 25% of women have PCO, but only 5% have PCOS PCO PCOS ESHRE/ASRM PCOS Consensus Workshop May 2003 PCOS: Signs and Symptoms 8

9 Diagnostic Criteria NIH Rotterdam AES Others 2004 Consensus PCOS Definition 2 out of the following 3 features anovulation clinical and/or biochemical evidence of androgen excess polycystic ovaries on ultrasound 1 or more ovaries 10mls in size and 12 follicles 2004 Human Reproduction 9

10 Diagnosis of exclusion Work up for PCOS R/O other causes of hyperandrogenism R/O other endocrinopathies PCOS: Differential Dx Androgen secreting tumor Exogenous androgens Cushing s syndrome Nonclassical congenital adrenal hyperplasia Acromegaly Genetic defect in insulin metabolism Primary hypothalamic amenorrhea Primary ovarian failure Thyroid dz Prolactin dz 10

Investigations H & PE LH, FSH, E2, testosterone, DHEAS, 17-OHprogesterone, prolactin, TSH, T4, glucose, lipids, 24- hr urine cortisol Pelvic ultrasound Specific imaging procedures

11 Investigations H & PE LH, FSH, E2, testosterone, DHEAS, 17-OHprogesterone, prolactin, TSH, T4, glucose, lipids, 24- hr urine cortisol Pelvic ultrasound Specific imaging procedures to exclude adrenal tumors if indicated Acanthosis Nigricans Velvety plaques on nape of neck and intertriginous areas Epidermal hyperkeratosis Associated with insulin resistance 11

12 Laboratory Evaluation Total Testosterone (T) DHEA-S (DS) 17-hyroxyprogesterone (17-OHP) 24 hr Urine Cortisol T ± DS PCOS T & DS WNL Idiopathic/PCOS DS Adrenal 24 hr urine cortisol Suspect Cushings T > 200 ng/dl DS > 700 μg/dl Suspect Tumor 17-OHP > 2 ng/ml Suspect CAH PCOS: Consequences Diabetes/gestational diabetes Premature Cardiovascular disease Endometrial Cancer?? Ovarian cancer, breast cancer Risk in offspring if fertility is achieved Self Image/depression Infertility 12

13 Treatment Options: physical manifestations Lifestyle modification Androgen suppression Anti-androgens Insulin lowering agents/sensitizers Other Weight loss Weight loss Weight loss Obesity 7-10% weight loss significantly changes metabolism 13

14 Androgen Suppression improve signs and symptoms Estrogen/Progesterone Androgen blockade Oral Contraceptives Suppress ovarian androgen Increase SHBG Regular menstrual cyclicity Progestin opposition Contraception 14

15 OCPS in PCOS Yasmine Orthotricycline Anti-androgens Spironolactone Flutamide Finasteride 15

16 Spironolactone Androgen receptor blockade Steroid enzyme inhibition Aldosterone antagonism Lower blood pressure Potassium sparing Dose: mg/day Helps with hirsutism Cosmetic Shaving Waxing Laser treatment What Else: Hirsutism Vaniqa (eflornithine hydrochloride) 16

17 Insulin Sensitizing Agents Some reduced hair growth Improved glucose utilization Lowered serum insulin Lipid lowering properties Insulin Lowering Agents Metformin Thiazolidinediones Rosiglitazone Pioglitazone 17

18 Metformin Dosing Target mg per day Clinical response not regularly observed at doses less than 1000 mg per day Metformin Metformin Initiation Metformin 500 mg once a day with meals for 4 days (or 2-weeks) Metformin 500 mg twice a day with breakfast and dinner for 4 days (or 2-weeks) Metformin 500 mg with breakfast and 1,000 mg with dinner for 4 days (or 2-weeks) Metformin 1,000 mg twice daily 18

19 PCOS: Infertility DO not pursue in children Treatment X 19

20 Conclusions 1. PCOS is common 2. Always focus on presenting problem, but also educate patients about the long-term sequellae 3. Life-style modification is a very effective treatment option in PCOS 4. Do not be scared of using the OCP 5. Ongoing trials for metformin Rollcall If you wish to receive CME/CEU/ or an attendance certificate, please tell us your name. Please un-mute your telephone line by pressing *6. 20

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Polycystic Ovary Syndrome HEATHER BURKS, MD OU PHYSICIANS REPRODUCTIVE MEDICINE SEPTEMBER 21, 2018

Polycystic Ovary Syndrome HEATHER BURKS, MD OU PHYSICIANS REPRODUCTIVE MEDICINE SEPTEMBER 21, 2018 Learning Objectives At the conclusion of this lecture, learners should: 1) Know the various diagnostic