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/10.1590/1806-9282.61.06.485One 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-