PANDORATHE PCOS SOCIETY NEWSLETTER

Issue 2 | Pages 12 | June-September 2016

Registered AddressKwality House, 1st Floor,August Kranti Marg, Kemps Corner,Mumbai 400 026

Phone: 022 23802584, 022 23803965Fax: 022 23804839Email: thepcossociety@gmail.com

WHAT’S INSIDE■ New Patrons & Life Members

Page 02

■ Presidential MessagePage 03

■ Report of theInternational ConferencePage 04-06

www.pcosindia.org | www.pcosindia.com

■ Scientific Article – CurrentControversies & Consensusfor Adjuvants in PCOSPage 07

■ Scientific Article –Management of Acne inpatients of Polycystic OvarySyndrome (PCOS)Page 08

■ Systematic Reviews inPCOS – Abstracts &PCOS QuizPage 10

Dr. A. Bhagauathi AmmalDr. A. CharmilaDr. A. RajeswariDr. A. SasikalaDr. Abha SharmaDr. Abhijit DesaiDr. Abhijit S. DeodharDr. Aditi A. DaniDr. Aditi SomaniDr. Aditya Sanjeev KhurdDr. Ajay Laxmichand ShahDr. Ajit MopkarDr. Akshita R. ShethDr. Akula Swaroopa RaniDr. Alaka C. GodboleDr. Alka JainDr. Altamash M. ShaikhDr. Amandeep KaurDr. Amish R. DoshiDr. Amit Nihalchand BafnaDr. Amita A. MaratheDr. Amita Ashok SuchakDr. Ammini Veena JagaramDr. Amol Prakash PawarDr. Amrit N. GuptaDr. Amrita S. JaipuriarDr. AmuthaDr. Anagha Pradyumna PaiRaiturkerDr. Anand Murari NanavatiDr. Ananda ChattopadhyayDr. Anil JadhavDr. Anita Gajendra SinghDr. Anita RajurkarDr. Anita SobtiDr. Anita SoniDr. Anjali DevalDr. Anjan Kumar SarangiDr. Anjana SisodiaDr. Anju Mehta MittalDr. Anju RastogiDr. Anjula BhargavaDr. Anu VijDr. Anupama M.ShahDr. Anuradha V. RidhorkarDr. Aparna A. DewaikarDr. Archana A. PrabhuDr. Archana BasuDr. Archana R. GaikwadDr. Arti GuptaDr. Arun M.BoruahDr. Asalatha RayaDr. Asha Atul RajadhyakshaDr. Asha HansDr. Asha NagarkattiDr. Asha S. VijayDr. Ashima Rohit MalikDr. Ashvinikumar DeshmukhDr. Ashwini Bhalerao-GandhiDr. B. ThirupurasundariDr. Barkha Amit BafnaDr. Belinda VazDr. Belu SharmaDr. Bhairavi DeshmukhDr. Bharat NaikDr. Bharati A RathodDr. Bharati MishraDr. Bharti SaranDr. Binal D. ShahDr. Bindhu K. S.Dr. Bishnu Pada ChoudhuryDr. C. A. Rasheetha BanuDr. C. H. SheethalDr. C. Rathi LavnyaDr. Caroline F. Mary

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Welcoming....Our New Patrons

Dr. Sadhana Desai Dr. Gauri Karandikar Dr. Gayatri Suresh Thakkar Dr. K. S. Jeyarani Kamaraj Dr. Krishnendu Gupta Dr. Manjula Agnal

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Dr. Shilpa Joshi

Our Associate Members

2Dr. R. KumaraSwamy

www.pcosindia.org | www.pcosindia.com

Presidential Address at First International ConferenceJointly Organized by The PCOS Society (India) &The Androgen Excess & PCOS Society (International)

Dr. Duru ShahPresidentThe PCOS Society (India)

Editorial Team

Dr. Sabahat RasoolAssociate Editor

Ms. Rochelle LoboAdministrativeAssistant

3

Email: thepcossociety@gmail.comDisclaimer – Published by the The PCOS SOCIETY (INDIA). Contributions to the editor are assumedintended for this publication and are subject to editorial review and acceptance. PANDORA is notresponsible for articles submitted by any contributor. These contributions are presented for reviewand comment and not as a statement on the standard of care. All advertising material is expectedto conform to ethical medical standards, acceptance does not imply endorsement by PANDORA.

The first question asked by everyone around me was "Why another Society? Do we not have enough professional Societies forGynaecologists?

The symptoms of PCOS first show their ugly head in a young girl after she attains puberty and ameliorate as she reaches menopause,suggesting that these symptoms go hand in hand with her ovarian function. And during this period she faces various health relatedproblems which make her visit different specialists, depending on the problem she has – so she sees her Gynaec for her irregular andheavy periods or infertility, her dermatologist for cosmetic issues such as pigmentation, acne, facial hair, and the endocrinologist for herobesity, not really knowing that all her symptoms are woven together by a condition called "Polycystic Ovarian Syndrome" or "PCOS".Globally 2.2 to 26% of reproductive aged women have PCOS!.

An Indian prevalence study from the National Institute of Research in Reproductive Health (NIRRH) has recently reported a prevalence of22.5% based on a community based study in the age group of young girls between 15-24 years in Mumbai! That means, 1 out of every5 young girls in the city of Mumbai has PCOS! They reported that 50% of the girls had irregular periods, 30% were either overweightor obese, with higher chances of having raised male hormone levels, higher insulin and blood sugar levels. Hence these young girls areat a future risk of developing delayed periods followed by heavy bleeding and anaemia, infertility, diabetes, obesity, hypertensionleading to an increased risk of cardiac problems and uterine cancer.

Can we stop this progress? Yes we can, there is no specific cure for PCOS but simple life style changes with exercise and healthy eating,in order to maintain a normal/ low body weight, to keep this problem under control and prevent it from reaching alarming proportions!

Our country has been labeled as one of the leading Diabetes Centers of the World with 62 million diabetics existing today! with aprevalence of 15% of the PCOS group becoming diabetic in future, i.e. 1 out of 6 PCOS women will turn diabetic and these girls willraise these statistics further if we do not create this awareness today! Almost 25% of Indian PCOS are obese and the combinationof diabetes and obesity dramatically increases the risk of cardiac complications leading to fatal heart attacks between theages of 50-60 yrs in such women.

So PCOS is one of the conditions which could be the beginning of long term non- communicable diseases such as diabetes,hypertension, obesity and cancer in our country. By raising this awareness amongst the medical fraternity, amongst the laypopulation and amongst the girls themselves, and by highlighting its complications, we could prevent such morbidities infuture. We needed to have a Professional Organization which would focus on this subject and involve all the specialistswho deal with it and its problems, and have a single point agenda of creating this awareness. The Gynecologist, who is theprimary care physician of women, is usually the first point of contact for these young girls. We need to make an early

diagnosis in every girl who comes to us with a history of irregular periods and its associated symptoms. It is notenough to only regularize her periods, or to treat her acne or to manage her obesity, it is important for us to puta finger on what's ticking behind these symptoms.

Our Government is focusing on simple solutions such as sanitation and hygiene which will ultimately drasticallyreduce deaths due to infectious diseases. Similarly a focus on PCOS will alert many young girls early in life, andwith simple solutions such as exercise, yoga and healthy eating, we will prevent unnecessary complications intheir later years.

Today,the PCOS Society has brought together all specialists who treat such women under one umbrella to share their experiences,which will ultimately assist us to look after our PCOS girls better! We have with us the most reputed specialists from the bestUniversities in the World to offer their expertise; we have our national experts consisting of cardiologists, bariatric surgeons,nutritionists, cosmetic surgeons, sleep apnoea specialists, besides many experts from the field of Endocrinology and Dermatology.

I do hope you all enjoy the academic exchange which will follow in this 3 days meeting, as much as the team at the PCOS Societyhas enjoyed putting it together!

I would personally like to convey my thanks to all the members of my team who have worked very hard to put this meetingtogether with a special thanks to Rochelle, a special thanks to ManjuBhargav for bringing in our Celebrity Chief Guest, Mrs.Amruta Fadnavis,our everygreen Guest of Honor Dr. Rustom Soonawala admired and loved by women all over our country,the experts from the Androgen Excess & PCOS Society, our national experts, all our esteemed sponsors who have come forwardand contributed generously and our invited guests from the media and Society and last but not the least all the 650 delegatespresent here today.

Dr. Duru ShahFounder President, The PCOS Society, India

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The first International Conference of the PCOSSociety (India) entitled "PCOS – Understanding theScience and Practice" was held from the 17th- 19th

June, 2016 at The Leela Hotel, Mumbai. It was jointlyorganized by the PCOS Society (India) and theAndrogen Excess and PCOS Society (AE-PCOS

Society) an International Society of Androgen Excessand PCOS, and endorsed by the Federation ofInternational Societies of Gynecological

Endocrinology (FISGE).

We had a galaxy of international speakers, whichincluded Anuja Dokras, President of the AE-PCOS

Society, Enrico Carmina, Executive Director and CEOof AE-PCOS Society along with Richard Legro, KathyHoeger and Maurizio Nordio.

The consequences of PCOS are seen across the entirelifespan of women requiring a multidisciplinaryapproach, hence faculty from various specialties such

as endocrinologists, obstetricians, gynecologists,fertility specialists, dermatologists, sonologists,pulmonologists, physicians, obesity surgeons,

nutritionists were all invited on the same platformto share their expertise. The Conference Sessionsdiscussed all areas of PCOS from puberty to

menopause, covering the entire lifespan of thewomen.

There were two Precongress Workshops, one on

"Impact of PCOS on pregnancy" and the otheron "Management of cosmetic concerns inPCOS". The Cosmetic Workshop was followed by a

live demonstration of laser therapies. Both theWorkshops were well attended and there was morethan sufficient time for interaction between the

delegates and the faculty at the end of the Session.

The Inaugural Function was preceded by twoexcellent Inaugural Lectures followed by a very

elegant Inaugural Function where the Chief Guestwas Mrs. Amruta Fadnavis the better half of theMaharashtra Chief Minister Shri. Devendra Fadnavis

and a woman of substance in her own right. OurGuest of Honour was Padmashree RustomSoonawalla, our respected senior gynaecologist,

and both lent charm and grace to the function, whichwas attended by a full house followed by theBanquet.

The total number of delegates who had registeredfor our meeting were 650 and it was good to seethat the majority of the delegates were present in

the "Single Hall only". This goes to show the highacademic standards maintained at this congress,which allowed a good 30 minutes interaction

between the delegates and the faculty after everysession. Overall this International Congress was wellappreciated by all the delegates who gave a very

positive feedback.

The evening Cocktails followed by Dinner was veryenjoyable with music and a wonderful

"Standup Comedy" show by Sahil Shah of theCanvas Club. Everyone had a totally relaxing time asthey were in splits of laughter. We also had a guitarist

and a violinist and all sang along with the musicians.

There were four Round Tables, which assisted indeveloping Algorithms on "Management of Ovarian

Hyper Stimulation Syndrome (OHSS), Obesity,Menstrual disorders and Metabolic syndrome". Each

table had an international expert and 10 nationalexperts. They brainstormed to arrive at a consensuson these topics, which will be published as algorithms

on the PCOS Society Website and Newsletter.

There was an excellent session by our scientists fromthe National Institute for Research in Reproductive

Health (NIRRH) to showcase their research in this fieldand appraise the delegates on the excellent workhappening in India. Their research involved

community based studies giving us the prevalenceof PCOS amongst young girls in Mumbai, along witha holistic approach of treating PCOS through

womens lives. They also showcased the researchwork done in their laboratory involving thepathophysiology of Folliculogenesis.

The Conference ended on Sunday afternoon after aValedictory function followed by lunch.

During the Valedictory Function, LifeMembership Awards of the PCOS Society weregiven to young delegates who presented freepapers.

The President also thanked the sponsors of thisConference for their magnanimous support,without which this conference would not havebeen possible. We offer our gratitude to thefollowing Sponsors –

Diamond Sponsor – USV Private Limited.

Ruby Sponsors – Abbott India Limited, AlembicPharmaceutical Limited.

Sapphire Sponsors – Metropolis HealthcareLimited, Lupin Limited, Torrent PharmaceuticalsLimited, Glaxosmithkline PharmaceuticalsLimited.

Crystal Sponsors – Sanofi India Limited, SunPharma Limited (Spectra), Bayer Zydus PharmaPrivate Limited.

Dr. Duru ShahFounder PresidentThe PCOS Society (India)

Dr. Madhuri PatilScientific Co-ordinatorThe PCOS Society (India)

Report of the International Conference The lectures slides, which have the consentof the authors will be available free of costto all as Continuing Medical Education onthe PCOS Society Website.

Impact of PCOS in pregnancy–

pre-congress Workshop

Management of Cosmetic Concernsin PCOS – Workshop

Live Workshop

Selfie please...

Inaugural lectures

Evening Banquet...

Book release

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Scientific session in progress – Round Tables

Some laughter and music....

Valedictory

Concerns of tomorrow...

Stand up comedian

NIRRH session

See page 9 for more pictures

7

carbohydrate compounds, which plays a small butsignificant role in "insulin" signaling. Many studieshave reported defective inositol signaling as likelypathologic mechanism for insulin resistance of PCOSwomen. Three inositol family members have beentried in PCOS.

D-Chiro-inositol, Myoinositol and D-Pinitol. Thesenew molecules are thought to be having insulinsensitizing properties, likely to improve metabolic,cardiovascular and reproductive profile of PCOSwomen. There are many studies reporting the useof inositols in reducing insulin resistance anddyslipidemias in PCOS women18.

In a recent paper, combination of myoinositol andD-Chiro inositol, in a physiologic ratio of 40:1, wasshown to improve metabolic profile of PCOSwomen19. Also, in another study this combinationtherapy was shown to improve oocyte, embryoquality and pregnancy rates in PCOS womenundergoing IVF-ET20.

Artini et al studied 50 overweight PCOS womenbefore and after a 12 weeks course of myo-inositol2 gms with folic acid 200 mg daily. Patients wererandomized to either the above combination or toonly folic acid 200 mg daily21. They reported thatafter 12 weeks of myo-inositol administration,plasma LH, prolactin, testosterone, insulin levels andLH / FSH were significantly reduced. Insulin sensitivity,expressed as glucose to insulin ratio and HOMAindex, significantly improved. Menstrual cyclicity wasrestored in all amenorrheic and oligomenorrheicsubjects. No such improvement was seen in "Folicacid only" group. A systematic review published in2011, looked into the effects of D-chiro-inositol onovulation and insulin resistance in women withPCOS22. All studies published on PCOS and D-Chiroinositol (DCI) upto 2010 were included. Patients werewomen with PCOS receiving D-chiro inositol or wherethe relationship between insulin resistance and DCIhad been investigated. Ovulation rates and insulinresistance were the main out come measures. Theyconcluded that heterogeneity in studymethodologies and small sample size used prohibitreliable conclusions to be drawn. More studies areneeded to evaluate accurately the effects of DCI inPCOS. The inositols have potential to improvereproductive axis functioning by reducing hyper-insulinemia.

N Acetyl-Cysteine (NAC)N-acetyl cysteine is a pharmaceutical drug and alsoa nutritional supplement. Acetyl-cysteine is the N-acetyl derivative of amino acid L-Cysteine whichforms antioxidant glutathione in the body. Thiscompound is sold commonly as a dietarysupplement, claiming antioxidant and liver protectingeffects. Recent studies have shown beneficial effectsfrom the use of NAC for patients with PCOS. Oneret al, reported clinical, endocrine and metaboliceffects of metformin and NAC in PCOS women23. Inthis prospective trial, 100 women with PCOS wererandomly divided to receive metformin (1500 mg/

day) or NAC (1800 mg/day) for 24 weeks. Bothtreatments resulted in a significant decrease in bodymass index, hirsutism score, fasting insulin, HOMAindex, free testosterone and menstrual irregularity,compared with baseline values. Also both treatmentshad equal efficacy. NAC reduced both total and lowdensity lipo-proteins, where as metformin only ledto a decrease in total cholesterol.

Badawy et al24 studied NAC as a novel adjuvant toclomiphene citrate (CC) in clomiphene citrateresistant PCOS women. One hundred and fiftywomen diagnosed with CC resistant PCOS, aged 18-39 years, undergoing infertility treatment wereincluded. The women were randomized to receiveeither NAC (1.2 gm/day) or placebo with CC 100mg/day. Ovulation rates and pregnancy rates werereported. They concluded that NAC as an adjuvantwas more effective than placebo for CC resistantPCOS women. Nasr, studied effect of NAC afterovarian drilling in CC-resistant PCOS women. SixtyCC-resistant women who had undergone unilaterallaparoscopic ovarian drilling were randomized toreceive placebo or NAC (1.2 gm/day) for 12consecutive cycles. Ovulation rate, pregnancy rateand live birth rate were all significantly higher in theNAC group25. Thus, there is now a large body ofevidence to support use of NAC in women withPCOS. It is likely to help to improve insulin sensitivity,to restore fertility and also to tackle homocysteinelevels. It has been shown that many women withPCOS have high homocysteine levels24. Elevatedhomocysteine is associated with coronary arterydisease, heart attack, chronic fatigue, fibromyalgiaand cervical cancer. A 2009 study showed thatpeople taking NAC for two months had a significantdecrease in homocysteine levels26.

25-OH Vitamin DVitamin D deficiency has been shown to be prevalentin PCOS women27. About 65-85% of women withPCOS have serum concentration of 25-hydroxyvitamin-D (25-0H vit D) < 20 ng/ml. Someobservational studies have shown that lower 25-0HvitD levels are associated with insulin resistance,ovulatory and menstrual irregularities, hirsutism,hyper-androgenism, obesity and elevated cardiovascular risk factors.

Pal et al28 studied 12 overweight, Vitamin-D deficient,PCOS women. Blood pressure, plasma glucose, totaltestosterone, serum sex hormone binding globulin,2 hr oral glucose tolerance test, were assessed atbase line and after 3 months therapy with Vitamin-D and elemental calcium. Their results showedimproved androgen and blood pressure profile.However, glucose and insulin resistance parametersremained unchanged.

Wehr et al studied 57 PCOS women, who received20,000 IU of cholecalciferol weekly for 24 weeks.Anthropometric measures, oral glucose tolerance testand blood analyses of endocrine parameters wereperformed at baseline, after 12 weeks and after 24weeks.

Scientific Article – Current Controversies &Consensus for Adjuvants in PCOS

Dr. Sujata KarKCHPL, Bhubaneswar

PCOS is the commonest multi-organ endocrinopathyaffecting women of reproductive age group. Thisreproductive and cardiometabolic syndrome greatlyincreasing a woman's life time risk of infertility,menstrual abnormalities, type II Diabetes Mellitus andcardio vascular diseases. A cure is being highly soughtafter by researchers. But in the absence of a knownpathophysiologic mechanism, this appears to beelusive. Currently, various investigational therapies,targeting the many symptoms of PCOS are beingtried. Present article attempts to enumerate suchtherapies and explore their current status.

Insulin sensitizing agentsPCOS women, both obese and normal weight, havea very high prevalence of insulin resistance andhyperinsulinemia. Thus, the rationale to use insulinsensitizing agents in PCOS women is very strong.Biguanides and Thiazolidiones have been usedextensively and large body of data exists on thissubject. Some other novel agents which likely affectinsulin resistance and metabolic profile of the PCOSwoman have been discussed in this article.

Somatostatin analogsSomatostatin is an endogenous hypothalamicpeptide with 14 amino acids and a short half life. Itinhibits pancreatic insulin release, pituitary growthhormone secretion and also LH release in responseof gonadotropin releasing hormone (GnRH)1,2,3. Thisproperty therefore should be useful in PCOSmanagement. Somatostatin analogue, octreotide,has been shown in few studies to improve pulsatilegonadotropin patterns, reduce LH, androgen andIGF- I levels and improve ovulation4-13. Octreotide(LAR) long acting Somatostatin analog formulation,has also to been tried and shown to directly influenceinsulin secretion3,14,15,16. Thus, this drug has potentialrole as insulin sensitizing agent, improvehyperinsulinemia, as well as have direct effect onthe ovaries, as suggested by recent discovery ofsomatostatin receptors at ovarian levels17.

Inositols"Inositol" is a group of naturally occurring

8

acne, including mild and/or comedonal only

disease11. Evidence-based recommendationssupporting an algorithm for use of hormonaltherapies in acne are currently lacking. An important

goal of hormonal treatment is to reduce sebumproduction. The mainstay of hormonal acne therapyin the USA includes OCPs and spironolactone, other

treatment options include flutamide andcyproterone4. Hormonal therapy provides an effectiveadjunct to the current acne treatments or may serve

as primary therapy. Patients should be educated thatthis strategy will require time, up to several months,to see results, and may require long-term systemic

treatment and ongoing monitoring for side effects.Hormonal therapy is safe and effective in post-menarcheal females over the age of 14 years, even

in those with normal androgen levels.

SpironolactoneSpironolactone is a highly effective treatment for

acne in adult women and may surpass the efficacyof OCPs. A potassium-sparing diuretic,spironolactone at low doses (25 mg /day) blocks

aldosterone and at higher doses (50-100 mg / day)blocks androgens at the receptor level. Drospirenoneis a synthetic progestin that is an analog to

spironolactone. In commonly-available OCPpreparations, the 3 mg drospirenone is estimated tohave anti-androgenic activity equivalent to 25 mg

of spironolactone. Spironolactone is not FDAapproved for the indication of acne, butspironolactone alone or combined with an OCPs at

a dose of 50-200 mg/day is effective in 33-85%reduction in acne lesion counts and also improvesseborrhea. Studies with lower dose spironolactone

(50-100 mg/day) demonstrate 33% improvement,suggesting a dosage effect. Studies with a higherdose of 100 mg plus drospirenone demonstrated

an 85% improvement in acne, suggesting a highlyeffective combination treatment2,12,13 .

Spironolactone is a safe and well-tolerated

medication, yet patients should be counseled onpotential side effects14. Side effects include breasttenderness (17%), menstrual irregularities (22%),

headache (13%), fatigue (15%), blood pressurereduction (with mean decrease of 5 mmHg systolic,2.6 mmHg diastolic blood pressure), and a minimal

rise in serum potassium levels in 13% with nocardiovascular or renal sequelae. The investigatorsrecommended checking potassium levels at baseline

and at 4 weeks in certain patient populations, likepatients over the age of 45 years, those with cardiacor renal disease, or those on concomitant

drospirenone15. Importantly, spironolactone is apotential teratogen associated with hypospadias andfeminization of male fetuses and is not

recommended in pregnancy or in womencontemplating pregnancy1,15.

Scientific Article – Management of Acne in patientsof Polycystic Ovary Syndrome (PCOS)

Dr. Akshitha ShettyDermatologist

Dr. Rekha ShethMD, DVDDermatologistVice PresidentThe PCOS Society (India)

ovaries, adrenal glands, and peripheral conversion.

Ovarian-derived androgens include androstenedioneand testosterone, whereas adrenal glands producedehydroepiandrosterone (DHEA), DHEA-S,

androstenedione, and testosterone. Peripheralconversion of androstenedione and DHEA alsogenerates testosterone in women.

Androgen-stimulated sebum production contributesto the pathophysiology of acne in women3. In skin,androgen receptors are located in sebaceous glands

and in the outer root sheath of the hair follicle6.Androgens in the sebaceous glands are metabolizedthrough a multi-step process from DHEA to 5-alpha-

dihydrotestosterone, stimulating sebocyteproliferation and activity7. Sebum production is alsoregulated by other hormones, including estrogens,

growth hormone, insulin, insulin-like growthfactor-1, glucocorticoids, adrenocorticotropichormone, and melanocortins5.

Treatment of acneIn the treatment of adult female patients with acne,it is important to treat the cause of acne; an

endocrinal evaluation can be helpful. A systematictreatment algorithm for acne should be utilized8,9.

Women over the age of 25 years have higher rates

of treatment failure; 82% fail multiple courses ofsystemic antibiotics, and 32% relapse afterisotretinoin9. Recurrence shortly after treatment with

isotretinoin should trigger suspicion for an underlyinghormonal disorder. A thorough review of systemsfor an underlying endocrine disorder should be

performed prior to initiating isotretinoin10.

IsotretinoinIsotretinoin remains a highly viable and important

non- hormonal treatment option for acne in adultwomen8. In this patient population, there are specialconsiderations of teratogenicity, and individuals over

35 years old may have increased risk of adverseskeletal side effects. Low-dose isotretinoin (10-20mg/day) can be used to minimize side effects

associated with systemic retinoid therapy, and this isan effective treatment of choice in this population9.

HormonesHormonal therapies, such as oral contraceptive pills(OCPs) and anti-androgen therapy, also provide animportant and effective opportunity to increase

treatment options for acne. As many adult womenpresent with comedonal disease, hormonal therapiescan be utilized across the entire clinical spectrum of

IntroductionAcne vulgaris is a common skin condition with 85%lifetime prevalence. While acne is commonly viewedas a disorder of adolescence, it may persist into

adulthood and often may present for the first timein adulthood1. Adult acne is a common reason forpatients to present for dermatological evaluation,

and adults, in fact, make up a large portion of thepatient population seen by dermatologists for acne.

Pathogenesis of acnePathogenesis of acne in adult women is complex,involving androgens in addition to other importantfactors well accepted for their role in the

pathogenesis of acne: sebum production, follicularplugging, genetics, Propionibacterium acnes, diet,medications, innate immunity, and alterations in

follicular keratinization and differentiation2.

The role of androgens in adult women with acnehas been well supported in the literature3, and four

clinical observations highlight this important role.First, androgen-insensitive individuals do not producesebum and do not develop acne. Second, conditions

of hyperandrogenism, such as polycystic ovarysyndrome (PCOS), are associated with acne that ishighly responsive to hormonal therapies4. Third, even

in women with normal androgen levels, hormonal-based therapies such as oral contraceptives and anti-androgen medications are effective treatments for

acne. Fourth, rising levels of dehydroepiandrosteronesulfate (DHEA-S) are associated with the onset ofacne in pre-menarcheal girls, and higher levels in

pre-menarche may predict the development of moreclinically severe acne in puberty. Elevated DHEA- Salso correlates with clinical acne in a subset of

patients with PCOS5.

Androgens in women derive from three sources: the

99

FlutamideFlutamide is a non steroidal androgen-receptorblocker used in prostate cancer and is effective inthe treatment of hirsutism and acne in women11,1.

Typical doses are 250- 500 mg/day. Due to its risk ofhepatotoxicity, it is rarely used in the managementof acne. Other side effects include gastrointestinal

upset, hot flashes, and decreased libido2.

Cyproterone acetate (CPA)CPA is a 17-hydroxyprogesterone derivative with

potent androgen blockade. CPA is available in twoforms: in combination with OCPs or in a non-OCPform that can be used in combination with OCP or

spironolactone. As a non-OCP medication, CPA isgiven on days 1-10 of the menstrual cycle (day 1marking the first day of menstruation)2.

ConclusionAcne is common in adults and especially in women.Acne in adult women has significant psychosocial

co morbidity and may be challenging to treat. It mayalso be a sign of an underlying systemic disordersuch as PCOS. Dermatologists likely play a critical

role in the diagnosis of PCOS, as acne is a commoncutaneous presenting sign. It is important to lookfor and ask about potential symptoms and signs of

hyperandrogenism and to exclude an underlyinghormonal disorder by complete history and physicalexamination. Isotretinoin remains a highly-viable

treatment option. Hormonal therapies are also safeand effective, even when androgen levels are normal,and they provide an important opportunity to better

treat this patient population. Hormonal therapiessuch as spironolactone and flutamide are effectiveeven when other standard therapies for acne have

failed, including antibiotics and isotretinoin. A strongtherapeutic alliance with the patient is vital in thispatient population, to attempt different combinations

of therapies and to identify the best personalizedtreatment for acne.

References1. Kamangar F, Shinkai K. Acne in the adult female patient: a

practical approach. Int J Dermatol. 2012 Oct;51(10):1162-74.

2. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE,Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE,Leyden JJ,Reynolds RV, Silverberg NB, Stein Gold LF, TollefsonMM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM,Bhushan R. Guidelines of care for the management of acnevulgaris.J Am Acad Dermatol. 2016 May;74(5):945-973.

3. Harper JC. Evaluating hyperandrogenism: a challenge in acnemanagement. J Drugs Dermatol 2008; 7: 527-530.

4. Lolis MS, Bowe WP, Shalita AR. Acne and systemic disease.Med Clin North Am 2009; 93: 1161-1181.

5. Chen MJ, Chen CD, Yang JH, et al. High serumdehydroepiandrosterone sulfate is associated with phenotypicacne and a reduced risk of abdominal obesity in women withpolycystic ovary syndrome. Human Reprod 2011; 26: 227-234.

6. Imperato-McGinley J, Gautier T, Cai LQ, et al. The androgencontrol of sebum production. Studies of subjects withdihydrotestosterone deficiency and complete androgeninsensitivity. J Clin Endocrinol Metab 1993; 76: 524-528.

7. George R, Clarke S, Thiboutot D. Hormonal therapy for acne.Semin Cutan Med Surg 2008; 27: 188-196.

8. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into themanagement of acne: an update from the Global Alliance to

Improve Outcomes in Acne group. J Am Acad Dermatol 2009;60(5 Suppl): S1-S50.

9. Gollnick H, Cunliffe W, Berson D, et al. Management of acne:a report from a Global Alliance to Improve Outcomes in Acne.J Am Acad Dermatol 2003; 49(1 Suppl.): S1-S37.

10. Lowenstein EJ. Diagnosis and management of the dermatologicmanifestations of the polycystic ovary syndrome. Dermatol Ther2006; 19: 210-223.

11. George R, Clarke S, Thiboutot D. Hormonal therapy for acne.Semin Cutan Med Surg 2008; 27: 188-196.

12. Brown J, Farquhar C, Lee O, et al. Spironolactone versus placeboor in combination with steroids for hirsutism and/or acne.Cochrane Database Syst Rev 2009

13. Shaw JC. Low-dose adjunctive spironolactone in the treatmentof acne in women: a retrospective analysis of 85 consecutivelytreated patients. J Am Acad Dermatol 2000; 43: 498-502.

14. Friedman AJ. Spironolactone for Adult Female Acne.Cutis. 2015Oct;96(4):216-7.

15. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA ?2004;292: 726-735.

1010

Abstract 1

Does Metformin help in assistedreproduction in PCOS patients?Nine randomized controlled trials, with 816 PCOS

women were included in this systematic review,

where metformin was compared with placebo in

women undergoing IVF/ICSI.

The clinical pregnancy rates in metformin group

compared to the placebo group were 32-49% and

31%, respectively.

The risk of OHSS in metformin and placebo groups,

respectively, was 6-15% and 27%.

However, there was no conclusive evidence that

metformin improved live birth rates in women with

PCOS undergoing IVF/ICSI treatment.

Metformin treatment during or before IVF/ICSI in

women with PCOS increases clinical pregnancy rates

and decreases risk of ovarian hyperstimulation.

Ref: Metformin treatment before and during IVF or

ICSI in women with polycystic ovary syndrome.

Tso LO, Costello MF, Albuquerque LE, Andriolo RB,

Macedo CR.

Cochrane Database Syst Rev. 2014 Nov 18;11:

CD006105

Systematic Reviews in PCOS – AbstractsAbstract 2

Letrozole Vs. Clomiphene citrate forovulation induction in PCOS –Which is better?A systematic review & meta analysis was done on

the results of randomized controlled trials (RCTs)

which compared letrozole and clomiphene citrate

(CC) for ovarian stimulation in women with Polycystic

Ovary Syndrome (PCOS).

Seven RCTs with 1833 patients (906 in the letrozole

group & 927 in the CC group) and 4999 ovulation

induction cycles were included in the review. Live

birth & pregnancy rates were statistically higher in

the letrozole group, with no differences in the

multiple gestations and miscarriage rates among the

two groups.

Ref: Letrozole versus clomiphene citrate in polycystic

ovary syndrome: systematic review and meta-

analysisRoque M, Tostes AC, Valle M, Sampaio M,

Geber S.

Gynecol Endocrinol. 2015 Dec; 31(12):917-21.

Abstract 3

In vitro maturation (IVM) in PCOS& non-PCOS patients – Is itcomparable?In vitro maturation (IVM) was evaluated in sub fertile

PCOS & non-PCOS women undergoing IVF.

Eleven studies with 268 PCOS & 440 non-PCOS

patients undergoing IVM were included in the meta-

analysis. A higher birth rate was observed among

the PCOS patients who underwent IVM compared

to non-PCPS controls. Clinical pregnancy and

implantation rates were also higher , whereas

cancellation rates lower among PCOS vs. non-PCOS

patients.

However, there was no difference in the two groups

as far as maturation and miscarriage rates were

concerned.

Ref: In Vitro Maturation in Women with vs. without

Polycystic Ovarian Syndrome: A Systematic Review

and Meta-Analysis.

Siristatidis C1, Sergentanis TN2, Vogiatzi P1,

Kanavidis P2, Chrelias C3, Papantoniou N3,

Psaltopoulou T2

PLoS One. 2015 Aug 4;10(8):e0134696.

1. What percentage of PCOS patients haselevated prolactin levels?

a. <5%

b. 5-10%

c. 15%

d. 25%

2. Which among the following statementsis false?

a. Androgen levels are elevated in obese aswell as non obese PCOS patients

b. Hyperandrogenemism is amplified byincreasing obesity

c. Hyperandrogenism is amplified byincreasing insulin resistance

d. Hyperandrogenemia occurs as a result ofdecreased Cytochrome P450 alpha enzymeactivity

3. Which among the following statementsis false?

a. Gonatropins stimulate adrenal androgenproduction directly

b. Prolactin can stimulate DHEA-S production

c. DHEA-S has low androgenic potential

d. DHEA-S is co-secreted with cortisolfrom adrenals

PCOS Quiz4. Which of the following adipocytokines is

not involved in pathogenesis of PCOS?

a. TNF-ALHPA

b. Retinol binding protein-4

c. Monocyte chemoattractant protein-1

d. None

5. Leptin intake is associated with which ofthefollowing options

a. Decreased hypothalamic Neuropeptide Y

b. Increased GnRH activity

c. Increase in thermogenesis

d. All of the above

6. Which of the following does notcontribute to anovulation in POCSpatients?

a. Increased insulin levels

b. Deranged early follicular development

c. Hyperresponsiveness of granulose cells toFSG in terms of estradiol production

d. None of the above

7. The risk of developing moderate to severeOHSS in PCOS women undergoinggonadotropin stimulation is

a. 5-8%

b. 8-12%

c. 10-18%

d. 15-21%

8. The unfavourable reproductive outcomesin PCOS patients are related to all of theseexcept

a. High BMI

b. Increased waist to hip ratio

c. Insulin resistance

d. None of the above

9. Using the NCEP criteria, what is theprevalence of Metabolic Syndrome inPCOS patients?

a. <10%

b. 20%

c. 30%

d. 40%

10.What percentage of PCOS patients haveinsulin resistance using the HOMA-IRindex?

a. 20%

b. 30-45%

c. 50-55%

d. 65-80%

www.pcosindia.org | www.pcosindia.com11

Their results showed improved glucose metabolismand menstrual frequency in these women, but nochanges in androgens29 Thus, Vitamin-D deficiencymay play a role in exacerbating PCOS and there maybe a role for vitamin-D supplementation in themanagement of this syndrome, but current evidenceis limited. Additional randomized controlled trialsare needed to confirm place of vitamin-D inmanagement of PCOS27

MagnesiumThere are some reports linking hypomagnesaemiawith PCOS. Whether serum magnesiumconcentrations co-relate with insulin resistance,hypertension, dyslipidemias of PCOS women iscurrently unknown. Kauffmann et al, in 100 PCOSwomen, could not find any co-relation betweenPCOS and non PCOS women, in their magnesiumlevels30. Sharifi et al31 too, could not find anyevidence to show that magnesium deficiency isassociated with insulin resistance of PCOS. However,a very recent study reported in 2013 by Chakrabortyet al studied 132 PCOS women for multiple traceelements including copper, magnesium, zinc,manganese, chromium and calcium. They dividedPCOS women into insulin resistant and non-insulinresistant. They found highly significant correlationbetween low serum calcium and magnesium levelswith insulin resistance in PCOS women32.

Lipoic AcidAlpha lipoic acid is a potent antioxidant. We knowthat oxidative stress is a likely mechanism leadingto insulin resistance in PCOS women. Controlled-release alpha lipoic acid (CRLA) has been reportedto improve glucose control in Type 2 Diabeticpatients33. Masharane et al have reported the effectsof CRLA on the features of PCOS women. Six lean,non diabetic PCOS women were given CRLA 600mg twice daily for 16 weeks. Insulin sensitivity wasmeasured by euglycemic, hyperinsulenemic clamp.Plasma lipids and serum oxidative markers weremeasured. Results showed a significantimprovement in insulin sensitivity and a lowering oftriglyceride levels. This was, however, not associatedwith increase in plasma antioxidant capacity34. Theyconcluded that CRLA has positive effects on PCOSphenotype. This agent needs further studies tosubstantiate its likely benefits.

Omega-3 Fatty AcidsA link between PCOS and non-alcoholic fatty liverdisease (NAFLD) has been demonstrated for fewyears now. Prevalence of NAFLD in women withPCOS may be as high as 40-55%35, 36. NAFLD ischaracterized by increased hepatic storage oftriglycerides and carries risk of cirrhosis. Very fewpublished studies have tested various treatmentoptions for NAFLD in association with PCOS. Animalstudies of marine derived omega-3 fatty acids havedemonstrated beneficial effects in NAFLD37.

Cussions et al published a study in 2009 thatexamined the effects of omega-3 fatty acids on liverfat in PCOS women. Twenty five PCOS women wererandomized to receive 4 gm per day of Omega-3fatty acids or placebo for 8 weeks. They concluded

that Omega-3 fatty acid supplementation had abeneficial effect on liver fat content and othercardiovascular risk factors in women with PCOS,including those with hepatic steatosis38.

Mohammads et al, in a double blind randomisedcontrolled trial conducted on 64 PCOS patients,concluded that Omega-3 fatty acids had somebeneficial effects on serum adiponectin levels, insulinresistance and lipid profile in PCOS patients and maycontribute to the improvement of metaboliccomplications in these women39.

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A, Rossi G &Coiro V. Inhibition by somatostatin of LH-RH-induced LHrelease in normal menstruating women. Gynecologic and ObstetricInvestigation 1986 22 17-21.

2. Brazaan JC, Vale W, Burgus N, Lang N, Buteler M &Gullemin R.Hypothalamic polypeptide that inhibits the secretion of immuno-reactive pituitary growth hormone. Science 1973 179 77-79.

3. Hsu WH, Xiang HD, Rajan AS, Kunze DL & Boyd AE .Somatostatininhibits insulin secretion by a G-protein-mediated decrease in Ca2+entry through voltage-dependent Ca2+ channels in the beta-cell.Journal of Biological Chemistry 1991 266 837-843.

4. Prevelic GM, Wurzburger MI, Balin-Peric L &Nesic JS. Inhibitory effectof sandostatin on secretion of luteinizing hormone and ovariansteroids in polycystic ovary syndrome. Lancet 1990 336 900-903.

5. Prelevic GM, Wurzburger MI, Balint-Peric L, Hardiman P, Okolo S,Maletic D & Ginsburg J. Effects of the somatostatin analogue,octreotide, in polycystic ovary syndrome. Metabolism 1992 41 76-79.

6. Prelevic GM, Ginsburg J, Maletic D, Hardiman P, Okolo S, Balint-PericL, Thomas M &Orskov H. The effects of the somatostatin analogueoctreotide on ovulatory performance in women with polycysticovaries. Human Reproduction 1995 10 28-32.

7. Morris RS, Carmina E, Vijod MA, Stanczyk FZ & Lobo RA. Alterationsin the sensitivity of serum insulin-like growth factor 1 and insulin-likegrowth factor binding protein-3 to octreotide in polycystic ovarysyndrome. Fertility and Sterility 1995 63 742-746.

8. Fulghesu AM, Lanzone A, Andreani CL, Pierro E, Caruso A & MancusoS. Effectiveness of a somatostatin analogue in lowering luteinizinghormone and insulin stimulated secretion in hyperinsulinemic womenwith polycystic ovary disease. Fertility and Sterility 1995 64 703-708.

9. Morris RS, Karande VC, Dudkiewicz A, Morris JL &Gleicher N.Octreotide is not useful for clomiphene citrate resistance in patientswith polycystic ovary syndrome but may reduce the likelihood ofovarian hyperstimulation syndrome. Fertility and Sterility 1999 71452-456.

10. Lidor A, Soriano D, Seidman DS, Dor J, Mashiach S &Rabinovici J.Combined somatostatin analog and follicle-stimulating hormone forwomen with polycystic ovary syndrome resistant to conventionaltreatment. Gynecological Endocrinology 1998 12 97-101.

11. Ciotta L, De Leo V, Galvani F, La Marca A &Cianci A. Endocrine andmetabolic effects of octreotide, a somatostatin analogue, in leanPCOS patients with either hyperinsulinemia or normoinsulinemia.Human Reproduction 1999 14 2951-2958.

12. Wenzl R, Lehner R, Schurz B, Karas H & Huber JC. Successful ovulationinduction by sandostatin-therapy of polycystic ovariandisease.ActaObstetriciaetGynecologicaScandinavica 1996 75 298-299.

13. Prelevic GM, Wurzburger MI, Balint-Peric L, Hardiman P, Okolo S,Maletic D & Ginsburg J. Effects of the somatostatin analogue,octreotide, in polycystic ovary syndrome. Metabolism 1992 41 76-79.

14. Gambineri A, Patton L, De Iasio R, Cantelli B, Cognini GE, Filicori M,Barreca A, Diamanti-Kandarakis E, Pagotto U &Pasquali R. Efficacyof octreotide-LAR in dieting women with abdominal obesity andpolycystic ovary syndrome. Journal of Clinical Endocrinology andMetabolism 2005 90 3854-3862.

15. Gillis JC, Noble S & Goa KL. Octreotide long-acting release (LAR).Areview of its pharmacological properties and therapeutic use in themanagement of acromegaly. Drugs 1997 53 681-699.

16. Bertoli A, Magnaterra R, Borboni P, Marini MA, Barini A, Fusco A&Bollea MR. Dose-dependent effect of octreotide on insulin secretionafter OGTT in obesity. Hormone Research 1996 49 17-21.

17. Strass MC, Seelig AS, Weiss JM, Diedrich K &Ortmenn O. Expressionof somatostatin and its receptors in human ovary 19th AnnualMeeting of the ESHRE 2003. Madrid, Spain, 2003.

18. Colazingari S, Treglia M, Najjar R, Bevilacqua A.The combined therapymyo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is ableto improve IVF outcomes: results from a randomized controlledtrial.Arch Gynecol Obstet. 2013 May 25.

19. Minozzi M, Nordio M, Pajalich R.The Combined therapy myo-inositolplus D-Chiro-inositol, in a physiological ratio, reduces thecardiovascular risk by improving the lipid profile in PCOS patients.EurRev Med Pharmacol Sci. 2013 Feb;17(4):537-40.

20. Colazingari S, Treglia M, Najjar R, Bevilacqua A.The combined therapymyo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is ableto improve IVF outcomes: results from a randomized controlledtrial.Arch Gynecol Obstet. 2013 May 25.

21. Artini PG, Di Berardino OM, Papini F, Genazzani AD, Simi G, RuggieroM, Cela V.Endocrine and clinical effects of myo-inositol administrationin polycystic ovary syndrome.A randomized study.GynecolEndocrinol.2013 Apr;29(4):375-9. doi: 10.3109/09513590.2012.743020. Epub2013 Jan 22.

22. Galazis N, Galazi M, AtiomoW.GynecolEndocrinol.D-Chiro-inositoland its significance in polycystic ovary syndrome: a systematicreview.2011 Apr; 27(4):256-62. Epub 2010 Dec 10.

23. Oner G, MuderrisII.Eur J ObstetGynecolReprod Biol.Clinical,endocrine and metabolic effects of metformin vs N-acetyl-cysteinein women with polycystic ovary syndrome.2011 Nov;159(1):127-31.

24. Rizk AY, Bedaiwy MA, Al-Inany HG.N-acetyl-cysteine is a noveladjuvant to clomiphene citrate in clomiphene citrate-resistant patientswith polycystic ovary syndrome.FertilSteril. 2005 Feb;83(2):367-70.

25. Nasr A.Effect of N-acetyl-cysteine after ovarian drilling in clomiphenecitrate-resistant PCOS women: a pilot study.Reprod Biomed Online.2010 Mar;20(3):403-9.

26. Rymarz A, Durlik M, Rydzewski A.Intravenous administration of N-acetylcysteine reduces plasma total homocysteine levels in renaltransplant recipients.Transplant. 2009 Oct-Dec;14(4):5-9.

27. Thomson RL, Spedding S, Buckley JD.Vitamin D in the aetiology andmanagement of polycystic ovary syndrome.ClinEndocrinol (Oxf).2012 Sep;77(3):343-50.

28. Pal L, Berry A, Coraluzzi L, Kustan E, Danton C, Shaw J, TaylorH.Therapeutic implications of vitamin D and calcium in overweightwomen with polycystic ovary syndrome.GynecolEndocrinol. 2012Dec;28(12):965-8.

29. Wehr E, Pieber TR, Obermayer-Pietsch B.Effect of vitamin D3treatment on glucose metabolism and menstrual frequency inpolycystic ovary syndrome women: a pilot study.J Endocrinol Invest.2011 Nov;34(10):757-63.

30. Kauffman RP, Tullar PE, Nipp RD, Castracane VD.Serum magnesiumconcentrations and metabolic variables in polycystic ovarysyndrome.ActaObstetGynecol Scand. 2011 May;90(5):452-8.

31. Sharifi F, Mazloomi S, Hajihosseini R, Mazloomzadeh S.Serummagnesium concentrations in polycystic ovary syndrome and itsassociation with insulin resistance.GynecolEndocrinol. 2012Jan;28(1):7-11.

32. Chakraborty P, Ghosh S, Goswami SK, Kabir SN, Chakravarty B, JanaK.Altered trace mineral milieu might play an aetiological role in thepathogenesis of polycystic ovary syndrome.Biol Trace Elem Res. 2013Apr;152(1):9-15.

33. Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics,tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid.EndocrPract. 2002;8(1):29-35.

34. Masharani U, Gjerde C, Evans JL, Youngren JF, Goldfine ID.Effects ofcontrolled-release alpha lipoic acid in lean, nondiabetic patients withpolycystic ovary syndrome.J Diabetes Sci Technol. 2010 Mar1;4(2):359-64.

35. Cerda C, Pérez-Ayuso RM, Riquelme A, Soza A, Villaseca P, Sir-Petermann T, Espinoza M, Pizarro M, Solis N, Miquel JF, Arrese M.2007 Nonalcoholic fatty liver disease in women with polycystic ovarysyndrome.J Hepatol 47:412-417 CrossRefMedline.

36. Gambarin-Gelwan M, Kinkhabwala SV, Schiano TD, Bodian C, YehHC, Futterweit W. 2007 Prevalence of nonalcoholic fatty liver diseasein women with polycystic ovary syndrome.ClinGastroenterolHepatol5:496-501 CrossRefMedline.

37. Alwayn IP, Andersson C, Zauscher B, Gura K, Nosé V, Puder M. 2005Omega-3 fatty acids improve hepatic steatosis in a murine model:potential implications for the marginal steatotic liverdonor.Transplantation 79:606-608 CrossRefMedline.

38. Cussons AJ, Watts GF, Mori TA, Stuckey BG.Omega-3 fatty acidsupplementation decreases liver fat content in polycystic ovarysyndrome: a randomized controlled trial employing proton magneticresonance spectroscopy.J ClinEndocrinolMetab. 2009Oct;94(10):3842-8. doi: 10.1210/jc.2009-0870.

39. Mohammadi E, Rafraf M, Farzadi L, Asghari-Jafarabadi M, SabourS.Effects of omega-3 fatty acids supplementation on serumadiponectin levels and some metabolic risk factors in women withpolycystic ovary syndrome.Asia Pac J ClinNutr. 2012;21(4):511-8.

Continued from page 04

Current Controversies &Consensus for Adjuvants in PCOS

Answers for PCOS QUIZ1.D2.D

3.A4.D

5.D6.D

7.C8.D

9.D10.D