Issue 2 JANUARY 2012

Editorial
Dear All, Parakh Hospital has always been involved in imparting knowledge to doctors. With this in mind a CME was arranged on 22th December , 2012 at Parakh hospital. We have received an extremely positive feedback from all the attending doctors and in continuation with the knowledge series we have launched PARAKH NEWSLETTER from December 2011. Through this newsletter we hope that our association with the doctors would not only be maintained but will also increase manifold. This Month We have chosen a new topic From Gynaecology Our Aim is to present informative newsletters to the doctor in the field of medicine and also showcase special cases. We hope that you find the article interesting and informative. In case of any suggestions please feel free to write on info@parakhhospital.com There is also a short quiz at the end of the newsletter which can be answered on the same email address. The winners will receive a small token of appreciation from team Parakh

Parakh Newsletter

Patho-physiology of PCOS (Polycystic Ovarian Syndrome)

PCOS a complex disorder like cardiovascular and Type II diabetes wherein various genetic variants and environmental factors interact, combine and contribute to the pathophysiology. Azziz R, Carmina E, et al The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report, Fertil Steril 91:456, 2009.

Definition of PCOS
US National Institute of Child Health and Developement 1990 Classic PCOS means Chronic anovulation Clinical and/or biochemical signs of hyperandrogenism (with exclusion of other aetiologies, eg CAH) (both criteria needed)

Europe: Rotterdam 2003 (ESHRE & ASRM) Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries (2 of 3 criteria needed)

(One has to exclude other aetiologies of hyperandrogenism)

Message: It is not essential to have polycystic ovaries on sonography to diagnose PCOS.

Bisphenol A and PCOS ( Known environmental factor) BPA is a very common industrial compound used in food and drink packaging, plastic consumer products and dental materials It increases Estrogen as well as Androgens in both sexes. "Excessive secretion of androgens, as seen in PCOS, interfere with BPA detoxification by the liver, leading to accumulation of blood levels of BPA, "BPA also affects androgen metabolism, creating a vicious circle between androgens and BPA. E. Kandaraki ET AL Journal of Clinical Endocrinology & Metabolism, 2010

Clinical Hyperandrogenism
9% of young females have Hirsuitism 30% of young PCOS will have Acne

5% PCOS will have Acanthosis nigricans

LH/FSH ratio
Increase LH, Normal or low FSH, increase LH/FSH ratio Increase LH pulse frequency and amplitude Decrease FSH from increase negative feedback from chronically elevated estrone concentration by peripheral conversion of androstenedione and increased Inhibin B level from multiple small follicles. Now ratio 2:1 is not included in diagnostic criteria of PCOS as Laboratory Standards not well set.

Hyperinsulinemia
35% women with PCOS exhibit impaired GTT and 7-10 % meet criteria fro Type II diabetes. Coversely women with Type II diabetes have 6 fold more chances to have PCOS than non diabetic. Similarly 15% insulin resistant women will have PCOS Increased insulin stimulates increase ovarian androgen production from theca cells and by inhibiting hepatic SHBG increases FREE androgen in circulation. Insulin also potentiates action of LH and both synergistically stimulate androgen production

Hyperinsulinemia & Insulin Resistance Primary pathology and not result of Hyperandrogenism Present in 50-75% of PCOS ( more in obese PCOS and less in lean PCOS) Screening is recommended for premature adrenarche / menstrual irregularity 2 yrs after menarche Simple Test 75 gm GTT with 2 hours Glucose & Insulin Glucose normal <140 / impaired 140 199 / DM >200 Insulin normal < 80- 100 / Insulin resistance > 80 100 / Severe IR > 300 Fasting insulin more than 20-30 U/ml Fasting glucose/fasting insulin ratio 4.5 or less HOMA-IR criteria (Homeostatic Model of assessment) FBS (mg/ml) x F insulin (U/ml) / 405 value more than 3.2 3.9 generally indicate insulin resistance Better as includes fasting hyperglycemics QUICKI method (quantitative insulin sensitivity check index) 1 / log (glucose) + log (insulin) more than 0.33 suggest insulin resistance

Ovarian Hyperandrgenism
Higher local androgens results in reduced granulosa cells sensitivity to FSH Follicular arrests more small follilicles more leutinisation by LH more production of local androgens more follicular arrests self propagating cycle Large ovaries with more stroma and peripheral follicles. Surgical correction an option

Hyperandrgenism
OVARIAN ANDROGENS - Abnormal LH secretary dynamics, increased LH bioactivity ( more sensitive LH receptors in ovarian theca cells and interstitial stromal cells ) ADRENAL ANDROGENS (androstenideone, DHEA, DHEA-S) 50% PCOS have higher level of DHEA-S converted to Testosterone in periphery. DHEA 50% ovary 50% adrenal Adrostenideone 50% adrenal 25% ovary 25% periphery Testosterone 50% periphery 25% ovary 25% adrenal

Obesity and PCOS 60% PCOS women will be Obese or overweight Many of 40% lean PCOS will have higher visceral fat. Take care of these 60% w.r.t. metabolic syndrome and Diabetes Take care of these 60% w.r.t. complications during pregnancy

PATHO-PHYSIOLOGY OF PCOS

High LH

High Insulin

High/Low Chronic Anovulation Thyroid Obesity

High Prolactin

High Ovarian Androgen

High Adrenal

Mensrual Problems

Hirsuitism

Infertility

Endometrial cancer

Dyslipidemia

Cardiovascular Diseases

Diabetes

---------------------------------------------------------------------------------------------------------

Ratio of LH/FSH: 2-3/1 GnRH pulses

PUBERTY

LH
LH pulses > 25pulses /24h

INSULIN

ANDROGEN

ANOVULATION

HIRSUTISM ACNE ALOPECIA

INCREASE

Abnormal ovarian steroidogenesis due to abnormal hyperactivity of Enzyme P450c17, which has some genetic link. of autosomal recessive inheritance.

OVARIAN STEROIDOGENESIS

LH
Cholesterol 17 hydroxylase Pregnenolone 17 OH-Pregnenolone 17-20 Lyase DHEA T Progesterone 17 OH-Progesterone Androstenandion

Theca cell

Abnorm al hyperac tiv ity Enzyme P450c17 res pons ible for

Estrone

Granulosa cell

FSH
estradiol

This leads to abnormal hormonal feedback, thus creating triad of anovulation, hyperandrogenism and polycystic ovaries.

Abnormal hormonal feedback mechanisms

LH FSH

acyclic estrogen Extra glandular aromatization Adipose tissue Chronic anovulation follicular maturation Stim. Of stroma and theca Ovarian androgen

Cyclic estrogen

Androgen excess

Adrenal androgen

Healthcare Information:

Royal Flying Doctor Service of Australia A unique service in Australia It provides a 24-hours-a-day, 365-days-ayear aeromedical emergency The (RFDS, informally known as The Flying Doctor) is
an emergency and primary health care service for those living in rural, remote and regional areas of Australia. It is a not-for-profit organization which provides health care to people who are unable to access a hospital or general practice due to the vast distances of the Outback Dr.J.T.Shah and Dr.Sanjay Mehta Consulting Gynaeclogists Parakh Hospital.

JOKES
Certificate : Doctor: Please take your seat sir. what is your problem?? Patient: Hello Doctor please can you give me your certificate? Doctor: Why? Patient: I took 2 weeks leave in my office. They asked me to get an "Doctor Certificate"

QUIZ

"Triple test" include

A. MSAFP, estrogen HCO B. LH,FSH, estrogen C. HCG,LH,FSH D. Pregesterone, estrogen, prolactin

P A RA K H N EW SLE T TER