WHAT`S INSIDE - The PCOS Society (India)

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THE PCOS SOCIETY NEWSLETTER
PANDORA
Issue 2 | Pages 12 | June-September 2016
WHAT’S INSIDE
■
New Patrons & Life Members
Page 02
■
Presidential Message
Page 03
■
Report of the
International Conference
Page 04-06
■
Scientific Article – Current
Controversies & Consensus
for Adjuvants in PCOS
Page 07
■
Scientific Article –
Management of Acne in
patients of Polycystic Ovary
Syndrome (PCOS)
Page 08
■
Systematic Reviews in
PCOS – Abstracts &
PCOS Quiz
Page 10
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Swapna
Presidential Address at First International Conference
Jointly Organized by The PCOS Society (India) &
The Androgen Excess & PCOS Society (International)
Editorial Team
Dr. Duru Shah
President
The PCOS Society (India)
The first question asked by everyone around me was "Why another Society? Do we not have enough professional Societies for
Gynaecologists?
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 related
problems which make her visit different specialists, depending on the problem she has – so she sees her Gynaec for her irregular and
heavy periods or infertility, her dermatologist for cosmetic issues such as pigmentation, acne, facial hair, and the endocrinologist for her
obesity, 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 of
22.5% based on a community based study in the age group of young girls between 15-24 years in Mumbai! That means, 1 out of every
5 young girls in the city of Mumbai has PCOS! They reported that 50% of the girls had irregular periods, 30% were either overweight
or obese, with higher chances of having raised male hormone levels, higher insulin and blood sugar levels. Hence these young girls are
at a future risk of developing delayed periods followed by heavy bleeding and anaemia, infertility, diabetes, obesity, hypertension
leading 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!
Dr. Sabahat Rasool
Associate Editor
Ms. Rochelle Lobo
Administrative
Assistant
Our country has been labeled as one of the leading Diabetes Centers of the World with 62 million diabetics existing today! with a
prevalence of 15% of the PCOS group becoming diabetic in future, i.e. 1 out of 6 PCOS women will turn diabetic and these girls will
raise these statistics further if we do not create this awareness today! Almost 25% of Indian PCOS are obese and the combination
of diabetes and obesity dramatically increases the risk of cardiac complications leading to fatal heart attacks between the
ages 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 lay
population and amongst the girls themselves, and by highlighting its complications, we could prevent such morbidities in
future. We needed to have a Professional Organization which would focus on this subject and involve all the specialists
who deal with it and its problems, and have a single point agenda of creating this awareness. The Gynecologist, who is the
primary 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 not
enough to only regularize her periods, or to treat her acne or to manage her obesity, it is important for us to put
a finger on what's ticking behind these symptoms.
Our Government is focusing on simple solutions such as sanitation and hygiene which will ultimately drastically
reduce deaths due to infectious diseases. Similarly a focus on PCOS will alert many young girls early in life, and
with simple solutions such as exercise, yoga and healthy eating, we will prevent unnecessary complications in
their 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 best
Universities 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 Society
has 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 meeting
together 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 forward
and contributed generously and our invited guests from the media and Society and last but not the least all the 650 delegates
present here today.
Dr. Duru Shah
Founder President, The PCOS Society, India
Email: [email protected]
Disclaimer – Published by the The PCOS SOCIETY (INDIA). Contributions to the editor are assumed
intended for this publication and are subject to editorial review and acceptance. PANDORA is not
responsible for articles submitted by any contributor. These contributions are presented for review
and comment and not as a statement on the standard of care. All advertising material is expected
to conform to ethical medical standards, acceptance does not imply endorsement by PANDORA.
www.pcosindia.org | www.pcosindia.com
3
Report of the International Conference
Dr. Duru Shah
Founder President
The PCOS Society (India)
The first International Conference of the PCOS
Society (India) entitled "PCOS – Understanding the
Science and Practice" was held from the 17th- 19th
June, 2016 at The Leela Hotel, Mumbai. It was jointly
organized by the PCOS Society (India) and the
Androgen Excess and PCOS Society (AE-PCOS
Society) an International Society of Androgen Excess
and PCOS, and endorsed by the Federation of
International Societies of Gynecological
Endocrinology (FISGE).
We had a galaxy of international speakers, which
included Anuja Dokras, President of the AE-PCOS
Society, Enrico Carmina, Executive Director and CEO
of AE-PCOS Society along with Richard Legro, Kathy
Hoeger and Maurizio Nordio.
The consequences of PCOS are seen across the entire
lifespan of women requiring a multidisciplinary
approach, 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 platform
to share their expertise. The Conference Sessions
discussed all areas of PCOS from puberty to
menopause, covering the entire lifespan of the
women.
There were two Precongress Workshops, one on
"Impact of PCOS on pregnancy" and the other
on "Management of cosmetic concerns in
PCOS". The Cosmetic Workshop was followed by a
live demonstration of laser therapies. Both the
Workshops were well attended and there was more
than sufficient time for interaction between the
egnancy–
Impact of PCOS in pr
p
pre-congress Worksho
4
Dr. Madhuri Patil
Scientific Co-ordinator
The PCOS Society (India)
delegates and the faculty at the end of the Session.
The Inaugural Function was preceded by two
excellent Inaugural Lectures followed by a very
elegant Inaugural Function where the Chief Guest
was Mrs. Amruta Fadnavis the better half of the
Maharashtra Chief Minister Shri. Devendra Fadnavis
and a woman of substance in her own right. Our
Guest of Honour was Padmashree Rustom
Soonawalla, our respected senior gynaecologist,
and both lent charm and grace to the function, which
was attended by a full house followed by the
Banquet.
The total number of delegates who had registered
for our meeting were 650 and it was good to see
that the majority of the delegates were present in
the "Single Hall only". This goes to show the high
academic standards maintained at this congress,
which allowed a good 30 minutes interaction
between the delegates and the faculty after every
session. Overall this International Congress was well
appreciated by all the delegates who gave a very
positive feedback.
The evening Cocktails followed by Dinner was very
enjoyable with music and a wonderful
"Standup Comedy" show by Sahil Shah of the
Canvas Club. Everyone had a totally relaxing time as
they 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 in
developing Algorithms on "Management of Ovarian
Hyper Stimulation Syndrome (OHSS), Obesity,
Menstrual disorders and Metabolic syndrome". Each
The lectures slides, which have the consent
of the authors will be available free of cost
to all as Continuing Medical Education on
the PCOS Society Website.
table had an international expert and 10 national
experts. They brainstormed to arrive at a consensus
on these topics, which will be published as algorithms
on the PCOS Society Website and Newsletter.
There was an excellent session by our scientists from
the National Institute for Research in Reproductive
Health (NIRRH) to showcase their research in this field
and appraise the delegates on the excellent work
happening in India. Their research involved
community based studies giving us the prevalence
of PCOS amongst young girls in Mumbai, along with
a holistic approach of treating PCOS through
womens lives. They also showcased the research
work done in their laboratory involving the
pathophysiology of Folliculogenesis.
The Conference ended on Sunday afternoon after a
Valedictory function followed by lunch.
During the Valedictory Function, Life
Membership Awards of the PCOS Society were
given to young delegates who presented free
papers.
The President also thanked the sponsors of this
Conference for their magnanimous support,
without which this conference would not have
been possible. We offer our gratitude to the
following Sponsors –
Diamond Sponsor – USV Private Limited.
Ruby Sponsors – Abbott India Limited, Alembic
Pharmaceutical Limited.
Sapphire Sponsors – Metropolis Healthcare
Limited, Lupin Limited, Torrent Pharmaceuticals
Limited, Glaxosmithkline Pharmaceuticals
Limited.
Crystal Sponsors – Sanofi India Limited, Sun
Pharma Limited (Spectra), Bayer Zydus Pharma
Private Limited.
Management of Co
smetic Concer ns
in PCOS – Workshop
Live Worksh
op
Inaugural lectures
Book release
Selfie please...
Evening Banquet...
ogress – Round Tables
Scientific session in pr
Stand up comedian
Some laughter and m
usic....
orrow...
Concerns of tom
NIRRH session
6
Valedictory
See page 9 for more pictures
Scientific Article – Current Controversies &
Consensus for Adjuvants in PCOS
Dr. Sujata Kar
KCHPL, Bhubaneswar
PCOS is the commonest multi-organ endocrinopathy
affecting women of reproductive age group. This
reproductive and cardiometabolic syndrome greatly
increasing a woman's life time risk of infertility,
menstrual abnormalities, type II Diabetes Mellitus and
cardio vascular diseases. A cure is being highly sought
after by researchers. But in the absence of a known
pathophysiologic mechanism, this appears to be
elusive. Currently, various investigational therapies,
targeting the many symptoms of PCOS are being
tried. Present article attempts to enumerate such
therapies and explore their current status.
Insulin sensitizing agents
PCOS women, both obese and normal weight, have
a very high prevalence of insulin resistance and
hyperinsulinemia. Thus, the rationale to use insulin
sensitizing agents in PCOS women is very strong.
Biguanides and Thiazolidiones have been used
extensively and large body of data exists on this
subject. Some other novel agents which likely affect
insulin resistance and metabolic profile of the PCOS
woman have been discussed in this article.
Somatostatin analogs
Somatostatin is an endogenous hypothalamic
peptide with 14 amino acids and a short half life. It
inhibits pancreatic insulin release, pituitary growth
hormone secretion and also LH release in response
of gonadotropin releasing hormone (GnRH)1,2,3. This
property therefore should be useful in PCOS
management. Somatostatin analogue, octreotide,
has been shown in few studies to improve pulsatile
gonadotropin patterns, reduce LH, androgen and
IGF- I levels and improve ovulation 4-13. Octreotide
(LAR) long acting Somatostatin analog formulation,
has also to been tried and shown to directly influence
insulin secretion 3,14,15,16. Thus, this drug has potential
role as insulin sensitizing agent, improve
hyperinsulinemia, as well as have direct effect on
the ovaries, as suggested by recent discovery of
somatostatin receptors at ovarian levels17.
Inositols
"Inositol" is a group of naturally occurring
carbohydrate compounds, which plays a small but
significant role in "insulin" signaling. Many studies
have reported defective inositol signaling as likely
pathologic mechanism for insulin resistance of PCOS
women. Three inositol family members have been
tried in PCOS.
D-Chiro-inositol, Myoinositol and D-Pinitol. These
new molecules are thought to be having insulin
sensitizing properties, likely to improve metabolic,
cardiovascular and reproductive profile of PCOS
women. There are many studies reporting the use
of inositols in reducing insulin resistance and
dyslipidemias in PCOS women18.
In a recent paper, combination of myoinositol and
D-Chiro inositol, in a physiologic ratio of 40:1, was
shown to improve metabolic profile of PCOS
women19. Also, in another study this combination
therapy was shown to improve oocyte, embryo
quality and pregnancy rates in PCOS women
undergoing IVF-ET 20.
Artini et al studied 50 overweight PCOS women
before and after a 12 weeks course of myo-inositol
2 gms with folic acid 200 mg daily. Patients were
randomized to either the above combination or to
only folic acid 200 mg daily 21. They reported that
after 12 weeks of myo-inositol administration,
plasma LH, prolactin, testosterone, insulin levels and
LH / FSH were significantly reduced. Insulin sensitivity,
expressed as glucose to insulin ratio and HOMA
index, significantly improved. Menstrual cyclicity was
restored in all amenorrheic and oligomenorrheic
subjects. No such improvement was seen in "Folic
acid only" group. A systematic review published in
2011, looked into the effects of D-chiro-inositol on
ovulation and insulin resistance in women with
PCOS22. All studies published on PCOS and D-Chiro
inositol (DCI) upto 2010 were included. Patients were
women with PCOS receiving D-chiro inositol or where
the relationship between insulin resistance and DCI
had been investigated. Ovulation rates and insulin
resistance were the main out come measures. They
concluded that heterogeneity in study
methodologies and small sample size used prohibit
reliable conclusions to be drawn. More studies are
needed to evaluate accurately the effects of DCI in
PCOS. The inositols have potential to improve
reproductive axis functioning by reducing hyperinsulinemia.
N Acetyl-Cysteine (NAC)
N-acetyl cysteine is a pharmaceutical drug and also
a nutritional supplement. Acetyl-cysteine is the Nacetyl derivative of amino acid L-Cysteine which
forms antioxidant glutathione in the body. This
compound is sold commonly as a dietary
supplement, claiming antioxidant and liver protecting
effects. Recent studies have shown beneficial effects
from the use of NAC for patients with PCOS. Oner
et al, reported clinical, endocrine and metabolic
effects of metformin and NAC in PCOS women23. In
this prospective trial, 100 women with PCOS were
randomly divided to receive metformin (1500 mg/
day) or NAC (1800 mg/day) for 24 weeks. Both
treatments resulted in a significant decrease in body
mass index, hirsutism score, fasting insulin, HOMA
index, free testosterone and menstrual irregularity,
compared with baseline values. Also both treatments
had equal efficacy. NAC reduced both total and low
density lipo-proteins, where as metformin only led
to a decrease in total cholesterol.
Badawy et al24 studied NAC as a novel adjuvant to
clomiphene citrate (CC) in clomiphene citrate
resistant PCOS women. One hundred and fifty
women diagnosed with CC resistant PCOS, aged 1839 years, undergoing infertility treatment were
included. The women were randomized to receive
either NAC (1.2 gm/day) or placebo with CC 100
mg/day. Ovulation rates and pregnancy rates were
reported. They concluded that NAC as an adjuvant
was more effective than placebo for CC resistant
PCOS women. Nasr, studied effect of NAC after
ovarian drilling in CC-resistant PCOS women. Sixty
CC-resistant women who had undergone unilateral
laparoscopic ovarian drilling were randomized to
receive placebo or NAC (1.2 gm/day) for 12
consecutive cycles. Ovulation rate, pregnancy rate
and live birth rate were all significantly higher in the
NAC group25. Thus, there is now a large body of
evidence to support use of NAC in women with
PCOS. It is likely to help to improve insulin sensitivity,
to restore fertility and also to tackle homocysteine
levels. It has been shown that many women with
PCOS have high homocysteine levels24. Elevated
homocysteine is associated with coronary artery
disease, heart attack, chronic fatigue, fibromyalgia
and cervical cancer. A 2009 study showed that
people taking NAC for two months had a significant
decrease in homocysteine levels26.
25-OH Vitamin D
Vitamin D deficiency has been shown to be prevalent
in PCOS women27. About 65-85% of women with
PCOS have serum concentration of 25-hydroxy
vitamin-D (25-0H vit D) < 20 ng/ml. Some
observational studies have shown that lower 25-0H
vitD levels are associated with insulin resistance,
ovulatory and menstrual irregularities, hirsutism,
hyper-androgenism, obesity and elevated cardio
vascular risk factors.
Pal et al28 studied 12 overweight, Vitamin-D deficient,
PCOS women. Blood pressure, plasma glucose, total
testosterone, serum sex hormone binding globulin,
2 hr oral glucose tolerance test, were assessed at
base line and after 3 months therapy with VitaminD and elemental calcium. Their results showed
improved androgen and blood pressure profile.
However, glucose and insulin resistance parameters
remained unchanged.
Wehr et al studied 57 PCOS women, who received
20,000 IU of cholecalciferol weekly for 24 weeks.
Anthropometric measures, oral glucose tolerance test
and blood analyses of endocrine parameters were
performed at baseline, after 12 weeks and after 24
weeks.
7
Scientific Article – Management of Acne in patients
of Polycystic Ovary Syndrome (PCOS)
Dr. Akshitha Shetty
Dermatologist
Introduction
Acne vulgaris is a common skin condition with 85%
lifetime prevalence. While acne is commonly viewed
as a disorder of adolescence, it may persist into
adulthood and often may present for the first time
in adulthood1. Adult acne is a common reason for
patients to present for dermatological evaluation,
and adults, in fact, make up a large portion of the
patient population seen by dermatologists for acne.
Pathogenesis of acne
Pathogenesis of acne in adult women is complex,
involving androgens in addition to other important
factors well accepted for their role in the
pathogenesis of acne: sebum production, follicular
plugging, genetics, Propionibacterium acnes, diet,
medications, innate immunity, and alterations in
follicular keratinization and differentiation2.
Dr. Rekha Sheth
MD, DVD
Dermatologist
Vice President
The PCOS Society (India)
ovaries, adrenal glands, and peripheral conversion.
Ovarian-derived androgens include androstenedione
and testosterone, whereas adrenal glands produce
dehydroepiandrosterone (DHEA), DHEA-S,
androstenedione, and testosterone. Peripheral
conversion of androstenedione and DHEA also
generates testosterone in women.
Androgen-stimulated sebum production contributes
to 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 metabolized
through a multi-step process from DHEA to 5-alphadihydrotestosterone, stimulating sebocyte
proliferation and activity7. Sebum production is also
regulated by other hormones, including estrogens,
growth hormone, insulin, insulin-like growth
factor-1, glucocorticoids, adrenocorticotropic
hormone, and melanocortins5.
Treatment of acne
In the treatment of adult female patients with acne,
it is important to treat the cause of acne; an
endocrinal evaluation can be helpful. A systematic
treatment algorithm for acne should be utilized8,9.
The role of androgens in adult women with acne
has been well supported in the literature3, and four
clinical observations highlight this important role.
First, androgen-insensitive individuals do not produce
sebum and do not develop acne. Second, conditions
of hyperandrogenism, such as polycystic ovary
syndrome (PCOS), are associated with acne that is
highly responsive to hormonal therapies 4. Third, even
in women with normal androgen levels, hormonalbased therapies such as oral contraceptives and antiandrogen medications are effective treatments for
acne. Fourth, rising levels of dehydroepiandrosterone
sulfate (DHEA-S) are associated with the onset of
acne in pre-menarcheal girls, and higher levels in
pre-menarche may predict the development of more
clinically severe acne in puberty. Elevated DHEA- S
also correlates with clinical acne in a subset of
patients with PCOS5.
Androgens in women derive from three sources: the
8
Women over the age of 25 years have higher rates
of treatment failure; 82% fail multiple courses of
systemic antibiotics, and 32% relapse after
isotretinoin9. Recurrence shortly after treatment with
isotretinoin should trigger suspicion for an underlying
hormonal disorder. A thorough review of systems
for an underlying endocrine disorder should be
performed prior to initiating isotretinoin10.
Isotretinoin
Isotretinoin remains a highly viable and important
non- hormonal treatment option for acne in adult
women8. In this patient population, there are special
considerations of teratogenicity, and individuals over
35 years old may have increased risk of adverse
skeletal side effects. Low-dose isotretinoin (10-20
mg/day) can be used to minimize side effects
associated with systemic retinoid therapy, and this is
an effective treatment of choice in this population9.
Hormones
Hormonal therapies, such as oral contraceptive pills
(OCPs) and anti-androgen therapy, also provide an
important and effective opportunity to increase
treatment options for acne. As many adult women
present with comedonal disease, hormonal therapies
can be utilized across the entire clinical spectrum of
acne, including mild and/or comedonal only
disease 11 . Evidence-based recommendations
supporting an algorithm for use of hormonal
therapies in acne are currently lacking. An important
goal of hormonal treatment is to reduce sebum
production. The mainstay of hormonal acne therapy
in the USA includes OCPs and spironolactone, other
treatment options include flutamide and
cyproterone4. Hormonal therapy provides an effective
adjunct to the current acne treatments or may serve
as primary therapy. Patients should be educated that
this 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 postmenarcheal females over the age of 14 years, even
in those with normal androgen levels.
Spironolactone
Spironolactone is a highly effective treatment for
acne in adult women and may surpass the efficacy
of 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. Drospirenone
is a synthetic progestin that is an analog to
spironolactone. In commonly-available OCP
preparations, the 3 mg drospirenone is estimated to
have anti-androgenic activity equivalent to 25 mg
of spironolactone. Spironolactone is not FDA
approved for the indication of acne, but
spironolactone 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 improves
seborrhea. Studies with lower dose spironolactone
(50-100 mg/day) demonstrate 33% improvement,
suggesting a dosage effect. Studies with a higher
dose of 100 mg plus drospirenone demonstrated
an 85% improvement in acne, suggesting a highly
effective combination treatment2,12,13 .
Spironolactone is a safe and well-tolerated
medication, yet patients should be counseled on
potential side effects14. Side effects include breast
tenderness (17%), menstrual irregularities (22%),
headache (13%), fatigue (15%), blood pressure
reduction (with mean decrease of 5 mmHg systolic,
2.6 mmHg diastolic blood pressure), and a minimal
rise in serum potassium levels in 13% with no
cardiovascular or renal sequelae. The investigators
recommended checking potassium levels at baseline
and at 4 weeks in certain patient populations, like
patients over the age of 45 years, those with cardiac
or renal disease, or those on concomitant
drospirenone 15. Importantly, spironolactone is a
potential teratogen associated with hypospadias and
feminization of male fetuses and is not
recommended in pregnancy or in women
contemplating pregnancy1,15.
Flutamide
Flutamide is a non steroidal androgen-receptor
blocker used in prostate cancer and is effective in
the treatment of hirsutism and acne in women11,1.
Typical doses are 250- 500 mg/day. Due to its risk of
hepatotoxicity, it is rarely used in the management
of acne. Other side effects include gastrointestinal
upset, hot flashes, and decreased libido 2.
Cyproterone acetate (CPA)
CPA is a 17-hydroxyprogesterone derivative with
potent androgen blockade. CPA is available in two
forms: in combination with OCPs or in a non-OCP
form that can be used in combination with OCP or
spironolactone. As a non-OCP medication, CPA is
given on days 1-10 of the menstrual cycle (day 1
marking the first day of menstruation)2.
Conclusion
Acne is common in adults and especially in women.
Acne in adult women has significant psychosocial
co morbidity and may be challenging to treat. It may
also be a sign of an underlying systemic disorder
such as PCOS. Dermatologists likely play a critical
role in the diagnosis of PCOS, as acne is a common
cutaneous presenting sign. It is important to look
for and ask about potential symptoms and signs of
hyperandrogenism and to exclude an underlying
hormonal disorder by complete history and physical
examination. Isotretinoin remains a highly-viable
treatment option. Hormonal therapies are also safe
and effective, even when androgen levels are normal,
and they provide an important opportunity to better
treat this patient population. Hormonal therapies
such as spironolactone and flutamide are effective
even when other standard therapies for acne have
failed, including antibiotics and isotretinoin. A strong
therapeutic alliance with the patient is vital in this
patient population, to attempt different combinations
of therapies and to identify the best personalized
treatment for acne.
References
1.
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, Tollefson
MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM,
Bhushan R. Guidelines of care for the management of acne
vulgaris.J Am Acad Dermatol. 2016 May;74(5):945-973.
3.
Harper JC. Evaluating hyperandrogenism: a challenge in acne
management. 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 serum
dehydroepiandrosterone sulfate is associated with phenotypic
acne and a reduced risk of abdominal obesity in women with
polycystic ovary syndrome. Human Reprod 2011; 26: 227-234.
6.
Imperato-McGinley J, Gautier T, Cai LQ, et al. The androgen
control of sebum production. Studies of subjects with
dihydrotestosterone deficiency and complete androgen
insensitivity. J Clin Endocrinol Metab 1993; 76: 524-528.
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 dermatologic
manifestations of the polycystic ovary syndrome. Dermatol Ther
2006; 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 placebo
or in combination with steroids for hirsutism and/or acne.
Cochrane Database Syst Rev 2009
13. Shaw JC. Low-dose adjunctive spironolactone in the treatment
of acne in women: a retrospective analysis of 85 consecutively
treated patients. J Am Acad Dermatol 2000; 43: 498-502.
7.
George R, Clarke S, Thiboutot D. Hormonal therapy for acne.
Semin Cutan Med Surg 2008; 27: 188-196.
14. Friedman AJ. Spironolactone for Adult Female Acne.Cutis. 2015
Oct;96(4):216-7.
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Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the
management of acne: an update from the Global Alliance to
15. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA ?2004;
292: 726-735.
9
Systematic Reviews in PCOS – Abstracts
Abstract 1
Abstract 2
Abstract 3
Does Metformin help in assisted
reproduction in PCOS patients?
Letrozole Vs. Clomiphene citrate for
ovulation induction in PCOS –
Which is better?
In vitro maturation (IVM) in PCOS
& non-PCOS patients – Is it
comparable?
Nine randomized controlled trials, with 816 PCOS
women were included in this systematic review,
A systematic review & meta analysis was done on
In vitro maturation (IVM) was evaluated in sub fertile
where metformin was compared with placebo in
women undergoing IVF/ICSI.
the results of randomized controlled trials (RCTs)
which compared letrozole and clomiphene citrate
PCOS & non-PCOS women undergoing IVF.
The clinical pregnancy rates in metformin group
compared to the placebo group were 32-49% and
(CC) for ovarian stimulation in women with Polycystic
Ovary Syndrome (PCOS).
patients undergoing IVM were included in the metaanalysis. A higher birth rate was observed among
31%, respectively.
Seven RCTs with 1833 patients (906 in the letrozole
group & 927 in the CC group) and 4999 ovulation
the PCOS patients who underwent IVM compared
to non-PCPS controls. Clinical pregnancy and
induction cycles were included in the review. Live
birth & pregnancy rates were statistically higher in
implantation rates were also higher , whereas
cancellation rates lower among PCOS vs. non-PCOS
the letrozole group, with no differences in the
multiple gestations and miscarriage rates among the
patients.
two groups.
Ref: Letrozole versus clomiphene citrate in polycystic
as far as maturation and miscarriage rates were
concerned.
and decreases risk of ovarian hyperstimulation.
ovary syndrome: systematic review and metaanalysisRoque M, Tostes AC, Valle M, Sampaio M,
Ref: Metformin treatment before and during IVF or
Ref: In Vitro Maturation in Women with vs. without
Polycystic Ovarian Syndrome: A Systematic Review
Geber S.
and Meta-Analysis.
Gynecol Endocrinol. 2015 Dec; 31(12):917-21.
Siristatidis C1, Sergentanis TN2, Vogiatzi P1,
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
ICSI in women with polycystic ovary syndrome.
Tso LO, Costello MF, Albuquerque LE, Andriolo RB,
Eleven studies with 268 PCOS & 440 non-PCOS
However, there was no difference in the two groups
Kanavidis P2, Chrelias C3, Papantoniou N3,
Psaltopoulou T2
Macedo CR.
Cochrane Database Syst Rev. 2014 Nov 18;11:
PLoS One. 2015 Aug 4;10(8):e0134696.
CD006105
PCOS Quiz
1. What percentage of PCOS patients has
elevated prolactin levels?
4. Which of the following adipocytokines is
not involved in pathogenesis of PCOS?
a. <5%
a. TNF-ALHPA
b. 5-10%
b. Retinol binding protein-4
c. 15%
c. Monocyte chemoattractant protein-1
d. 25%
d. None
2. Which among the following statements
is false?
5. Leptin intake is associated with which of
thefollowing options
a. Androgen levels are elevated in obese as
well as non obese PCOS patients
a. Decreased hypothalamic Neuropeptide Y
b. Hyperandrogenemism is amplified by
increasing obesity
c. Increase in thermogenesis
c. Hyperandrogenism is amplified by
increasing insulin resistance
d. Hyperandrogenemia occurs as a result of
decreased Cytochrome P450 alpha enzyme
activity
3. Which among the following statements
is false?
a. Gonatropins stimulate adrenal androgen
production directly
b. Prolactin can stimulate DHEA-S production
c. DHEA-S has low androgenic potential
d. DHEA-S is co-secreted with cortisol
from adrenals
b. Increased GnRH activity
d. All of the above
6. Which of the following does not
contribute to anovulation in POCS
patients?
a. Increased insulin levels
b. Deranged early follicular development
c. Hyperresponsiveness of granulose cells to
FSG in terms of estradiol production
d. None of the above
7. The risk of developing moderate to severe
OHSS in PCOS women undergoing
gonadotropin stimulation is
a. 5-8%
b. 8-12%
10
c. 10-18%
d. 15-21%
8. The unfavourable reproductive outcomes
in PCOS patients are related to all of these
except
a. High BMI
b. Increased waist to hip ratio
c. Insulin resistance
d. None of the above
9. Using the NCEP criteria, what is the
prevalence of Metabolic Syndrome in
PCOS patients?
a. <10%
b. 20%
c. 30%
d. 40%
10. What percentage of PCOS patients have
insulin resistance using the HOMA-IR
index?
a. 20%
b. 30-45%
c. 50-55%
d. 65-80%
Cussions et al published a study in 2009 that
examined the effects of omega-3 fatty acids on liver
fat in PCOS women. Twenty five PCOS women were
randomized to receive 4 gm per day of Omega-3
fatty acids or placebo for 8 weeks. They concluded
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29. Wehr E, Pieber TR, Obermayer-Pietsch B.Effect of vitamin D3
treatment on glucose metabolism and menstrual frequency in
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2011 Nov;34(10):757-63.
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31. Sharifi F, Mazloomi S, Hajihosseini R, Mazloomzadeh S.Serum
magnesium concentrations in polycystic ovary syndrome and its
association with insulin resistance.GynecolEndocrinol. 2012
Jan;28(1):7-11.
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K.Altered trace mineral milieu might play an aetiological role in the
pathogenesis of polycystic ovary syndrome.Biol Trace Elem Res. 2013
Apr;152(1):9-15.
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1;4(2):359-64.
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Answers for PCOS QUIZ
Omega-3 Fatty Acids
A link between PCOS and non-alcoholic fatty liver
disease (NAFLD) has been demonstrated for few
years now. Prevalence of NAFLD in women with
PCOS may be as high as 40-55%35, 36. NAFLD is
characterized by increased hepatic storage of
triglycerides and carries risk of cirrhosis. Very few
published studies have tested various treatment
options for NAFLD in association with PCOS. Animal
studies of marine derived omega-3 fatty acids have
demonstrated beneficial effects in NAFLD37.
1. Chiodera P, Volpi R, d'Amato L, Fatone M, Cigarini C, Fava A, Caiazza
A, Rossi G &Coiro V. Inhibition by somatostatin of LH-RH-induced LH
release in normal menstruating women. Gynecologic and Obstetric
Investigation 1986 22 17-21.
9. D
10. D
Lipoic Acid
Alpha lipoic acid is a potent antioxidant. We know
that oxidative stress is a likely mechanism leading
to insulin resistance in PCOS women. Controlledrelease alpha lipoic acid (CRLA) has been reported
to improve glucose control in Type 2 Diabetic
patients33. Masharane et al have reported the effects
of CRLA on the features of PCOS women. Six lean,
non diabetic PCOS women were given CRLA 600
mg twice daily for 16 weeks. Insulin sensitivity was
measured by euglycemic, hyperinsulenemic clamp.
Plasma lipids and serum oxidative markers were
measured. Results showed a significant
improvement in insulin sensitivity and a lowering of
triglyceride levels. This was, however, not associated
with increase in plasma antioxidant capacity34. They
concluded that CRLA has positive effects on PCOS
phenotype. This agent needs further studies to
substantiate its likely benefits.
References
7. C
8. D
Magnesium
There are some reports linking hypomagnesaemia
with PCOS. Whether serum magnesium
concentrations co-relate with insulin resistance,
hypertension, dyslipidemias of PCOS women is
currently unknown. Kauffmann et al, in 100 PCOS
women, could not find any co-relation between
PCOS and non PCOS women, in their magnesium
levels 30. Sharifi et al 31 too, could not find any
evidence to show that magnesium deficiency is
associated with insulin resistance of PCOS. However,
a very recent study reported in 2013 by Chakraborty
et al studied 132 PCOS women for multiple trace
elements including copper, magnesium, zinc,
manganese, chromium and calcium. They divided
PCOS women into insulin resistant and non-insulin
resistant. They found highly significant correlation
between low serum calcium and magnesium levels
with insulin resistance in PCOS women32.
Mohammads et al, in a double blind randomised
controlled trial conducted on 64 PCOS patients,
concluded that Omega-3 fatty acids had some
beneficial effects on serum adiponectin levels, insulin
resistance and lipid profile in PCOS patients and may
contribute to the improvement of metabolic
complications in these women39.
5. D
6. D
Their results showed improved glucose metabolism
and menstrual frequency in these women, but no
changes in androgens29 Thus, Vitamin-D deficiency
may play a role in exacerbating PCOS and there may
be a role for vitamin-D supplementation in the
management of this syndrome, but current evidence
is limited. Additional randomized controlled trials
are needed to confirm place of vitamin-D in
management of PCOS27
that Omega-3 fatty acid supplementation had a
beneficial effect on liver fat content and other
cardiovascular risk factors in women with PCOS,
including those with hepatic steatosis38.
3. A
4. D
Current Controversies &
Consensus for Adjuvants in PCOS
1. D
2. D
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