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P

olycystic

ovary

syndrome

:

controversies

and

challenges

R

ev

A

ssoc

M

ed

B

ras

2015; 61(6):485-487

485

EDITORIAL

Polycystic ovary syndrome: controversies and challenges

S

índrome

do

ovário

policístico

:

controvérsias

e

desafios

J

osé

M

aria

S

oares

J

únior

1

, M

aria

C

ândida

P. B

aracat

2

, G

ustavo

A

rantes

R

osa

M

aciel

3

, E

dmund

C

hada

B

aracat

4

1

Associate Professor, Division of Gynecology, Department of Obstetrics and Gynecology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil

2

Assistant, Division of Gynecology, Department of Obstetrics and Gynecology, FMUSP, São Paulo, SP, Brazil

3

Assistant, Habilitation (BR: Livre Docência, Division of Gynecology, Department of Obstetrics and Gynecology, FMUSP, São Paulo, SP, Brazil

4

Full Professor, Division of Gynecology, Department of Obstetrics and Gynecology, FMUSP, São Paulo, SP, Brazil

http://dx.doi.org/10.1590/1806-9282.61.06.485

One of the biggest challenges in medicine is that of poly-

cystic ovary syndrome (PCOS) because of its complexity,

its progression aspect and the consequences it entails for

women’s lives: from adolescence to post-menopause. It

affects a large number of women, ranging from 6% to 8%

of the population during the reproductive years. So this

condition is very important.

1-6

It is known that PCOS is not characterized by the as-

sociation of hyperandrogenism and chronic anovulation

only, but also involves disorders of carbohydrate metab-

olism, with a focus on insulin resistance and increased

risk of developing diabetes. The latter is higher with in-

creases in weight and ultimately the appearance of obe-

sity, leading to dyslipidemia, metabolic syndrome and in-

creased possibility of malignancies such as endometrial

carcinoma.

1-6

Although the description of the clinical picture had

been reported in the literature before the twentieth cen-

tury, this syndrome was recognized by the work of two

American surgeons, Stein e Leventhal, in 1935.

1

Since then,

several publications have been made looking for a single

agent to justify PCOS.

2-5

However, the interaction between

genetic, environmental, behavioral and psychological fac-

tors is, to date, the best way to understand this condition

and its various phenotypes.

Some researchers believe that PCOS is the result of a

disorder that begins during pregnancy, generating a low

birth weight (less than 2,500g or less than 10% of expect-

ed weight for gestational age) or macrosomic (weighing

over 3,800g) newborn. In both cases, there would be more

risk of developing the disease involving insulin metabo-

lism. Depending on the habits (sedentary lifestyle and

poor diet), there could be worsened hyperinsulinemia and

early pubarche, a clinical sign suggestive of greater chanc-

es of developing PCOS.

1-7

Other important factors are heredity (mothers with

PCOS) and genetics. There are several genes that can serve

as biomarkers, including

GTF2A1L

and

LHCGR

(plays a

crucial role in luteinizing hormone [LH] receptors).

8

Other

researchers believe that two polymorphisms of the

THADA

(thyroid adenoma associated) gene

,

follicle-stimulating

hormone (FSH) receptor and

DENND1A

gene

9

would of-

ten be found in PCOS women. However, many agree that

environmental, behavioral and psychological factors as-

sociated with genes would be essential for the emergence

of PCOS. It is also known that changes in life habits

per

se

could alleviate the symptoms associated with PCOS,

particularly improving the ovulation pattern and fertili-

ty in these women.

10

Insulin metabolism is also associated with higher

risks of developing cardiovascular disease and cancer, as

well as infertility. The main change would be a post-re-

ceptor defect involving reduced substrate for tyrosine and

increased phosphorylation of serine residues in the intra-

cellular signal from the insulin receptor. The end result

would be the collapse of GLUT-4 protein on the cell sur-

face and difficulty in glucose metabolism with subsequent

hyperinsulinism as a pancreatic response. This clinical

condition can also progress to glucose intolerance, which

would facilitate the emergence of

diabetes mellitus

11

and

increase the risk of cardiovascular disease.

Excessive insulin has a direct effect on the ovary, ex-

tending the action of LH on androgen production, and

also determines further degradation of the proteins car-

rying androgenic steroids and growth factors. There would

thus be the amplification of the effects of androgens and

of substances that can increase cell proliferation, increas-

ing the risk of cancer.

12,13

Although PCOS has hyperandrogenism as a central

feature, its diagnosis is also based on the exclusion of oth-

er conditions that may present similar clinical picture.

Thus, the diagnosis is based on expert consensuses. These

include panels promoted by the US National Institute of

Health (NIH) in 1990

14

and the Rotterdam consensus, or-

ganized by the American Society for Reproductive Med-

icine (ASRM) and the European Society of Human Re-

production and Embryology (ESHRE), in 2003.

15

The

latest and most accepted consensus is that issued by the

Androgen Excess and Polycystic Ovary Syndrome (AES-

-PCOS) Society, which recommends that women neces-