2. IntroductionIntroduction
Polycystic ovarian syndrome (PCOS) affectsPolycystic ovarian syndrome (PCOS) affects
4% to 12% of women of reproductive age.4% to 12% of women of reproductive age.
hallmarks of the disease arehallmarks of the disease are
hyperandrogenism and chronic anovulationhyperandrogenism and chronic anovulation
3. Changing ApproachChanging Approach
management not only toward treatingmanagement not only toward treating
infertility and improving the ofteninfertility and improving the often
troublesome hirsutism but also toward thetroublesome hirsutism but also toward the
long-term riskslong-term risks associated with IR.associated with IR.
4. MoreoverMoreover
Recent data suggest that women withRecent data suggest that women with
PCOS are at increased risk for pretermPCOS are at increased risk for preterm
labor, preeclampsia, and gestationallabor, preeclampsia, and gestational
diabetes, though the evidence fordiabetes, though the evidence for
increased miscarriage rates is less certainincreased miscarriage rates is less certain
(Legro , 2007)(Legro , 2007)
5. Ideal design to get best EvidenceIdeal design to get best Evidence
A randomised controlled trial (RCT) withA randomised controlled trial (RCT) with
large numbers and, ideally, three groups islarge numbers and, ideally, three groups is
needed:needed:
women with PCOS taking medication,women with PCOS taking medication,
women with PCOS taking no treatmentwomen with PCOS taking no treatment
non-PCOS womennon-PCOS women
6. metformin vs. both clomiphene andmetformin vs. both clomiphene and
combination therapycombination therapy
Metformin is not an effectiveMetformin is not an effective additionaddition
to clomifene citrate as the primary methodto clomifene citrate as the primary method
of inducing ovulation in women withof inducing ovulation in women with
polycystic ovary syndromepolycystic ovary syndrome
7. NEJM, 2007NEJM, 2007
The live-birth rate wasThe live-birth rate was 22.5%22.5% (47 of 209(47 of 209
subjects) in the clomiphene group, 7.2%subjects) in the clomiphene group, 7.2%
(15 of 208) in the metformin group, and(15 of 208) in the metformin group, and
26.8%26.8% (56 of 209) in the combination-(56 of 209) in the combination-
therapy grouptherapy group
(P<0.001 for metformin vs. both(P<0.001 for metformin vs. both
clomiphene and combination therapy;clomiphene and combination therapy;
P=0.31 for clomiphene vs. combinationP=0.31 for clomiphene vs. combination
therapy).therapy).
8. BMJ, 2007BMJ, 2007
Clomid alone vs clomid + metforminClomid alone vs clomid + metformin
no significant differences in either rate ofno significant differences in either rate of
ongoing pregnancy (40% v 46%)ongoing pregnancy (40% v 46%)
12. All women with polycystic ovary syndromeAll women with polycystic ovary syndrome
(PCOS) should be screened for glucose(PCOS) should be screened for glucose
intolerance with a 2-hour glucose levelintolerance with a 2-hour glucose level
after a 75-g fasting glucose challengeafter a 75-g fasting glucose challenge
13. All women with PCOS should be screenedAll women with PCOS should be screened
for dyslipidemia with a fasting lipoproteinfor dyslipidemia with a fasting lipoprotein
profile, including total cholesterol, low-profile, including total cholesterol, low-
density lipoprotein (LDL) cholesterol, high-density lipoprotein (LDL) cholesterol, high-
density lipoprotein (HDL) cholesterol, anddensity lipoprotein (HDL) cholesterol, and
triglyceride determinations.triglyceride determinations.
14. LIFESTYLE MODIFICATIONLIFESTYLE MODIFICATION
WEIGHT LOSSWEIGHT LOSS
A 3 to 6 month trial of aggressive lifestyleA 3 to 6 month trial of aggressive lifestyle
modification may be a prudent first stepmodification may be a prudent first step
before considering medications.before considering medications.
However, many patients will have difficultyHowever, many patients will have difficulty
in achieving weight lossin achieving weight loss
15. Use of clomiphene citrate is appropriateUse of clomiphene citrate is appropriate
because it effectively results in pregnancybecause it effectively results in pregnancy
in women with PCOS. (Hughes, 1997)in women with PCOS. (Hughes, 1997)
16. The following recommendations areThe following recommendations are
based on limited or inconsistentbased on limited or inconsistent
scientific evidence (Level B)scientific evidence (Level B)
17. Long termLong term
Improvements in insulin sensitivity, byImprovements in insulin sensitivity, by
weight loss may favorably improve manyweight loss may favorably improve many
risk factors for diabetes andrisk factors for diabetes and
cardiovascular disease in women withcardiovascular disease in women with
PCOS.PCOS.
18. When using gonadotropins to induceWhen using gonadotropins to induce
ovulation, low-dose therapy isovulation, low-dose therapy is
recommended because it offers a highrecommended because it offers a high
rate of monofollicular development and arate of monofollicular development and a
significantly lower risk of ovariansignificantly lower risk of ovarian
hyperstimulation in women with PCOS.hyperstimulation in women with PCOS.
19. Ovarian drillingOvarian drilling
The clear benefit and role of surgicalThe clear benefit and role of surgical
therapy in ovulation induction in womentherapy in ovulation induction in women
with PCOS is uncertain.with PCOS is uncertain.
20. The following recommendations areThe following recommendations are
based primarily on consensus andbased primarily on consensus and
expert opinion (Level C)expert opinion (Level C)
21. HirsutismHirsutism
Combining medical interventions may beCombining medical interventions may be
the most effective way to treat hirsutism.the most effective way to treat hirsutism.
Combined therapy with an ovarianCombined therapy with an ovarian
suppression agent and an antiandrogensuppression agent and an antiandrogen
appears effective in treating hirsutism inappears effective in treating hirsutism in
women with PCOS. The best pill orwomen with PCOS. The best pill or
antiandrogen is unknown.antiandrogen is unknown.
22. Ablation techniquesAblation techniques
The ideal choice of ablative procedures forThe ideal choice of ablative procedures for
long-term management of hirsutism inlong-term management of hirsutism in
women with PCOS is unknown.women with PCOS is unknown.
23. During PregnancyDuring Pregnancy
The effects of insulin-sensitizing agents onThe effects of insulin-sensitizing agents on
early pregnancy are unknown; metforminearly pregnancy are unknown; metformin
appears safe, but any additional effect atappears safe, but any additional effect at
reducing pregnancy loss is uncertainreducing pregnancy loss is uncertain
24. Side Effects of MedicationSide Effects of Medication
ProgestinsProgestins. Use of medroxyprogesterone. Use of medroxyprogesterone
acetate is associated with decreases inacetate is associated with decreases in
sex hormone binding globulin (SHBG).sex hormone binding globulin (SHBG).
Progestin-only oral contraceptives areProgestin-only oral contraceptives are
associated with high incidence ofassociated with high incidence of
breakthrough bleeding.breakthrough bleeding.
25. GnGn
Use of gonadotrophins can result inUse of gonadotrophins can result in
ovarian hyperstimulation syndromeovarian hyperstimulation syndrome
26. Insulin-sensitizing agentsInsulin-sensitizing agents
The most common adverse reactions ofThe most common adverse reactions of
metformin are gastrointestinal symptomsmetformin are gastrointestinal symptoms
(diarrhea, nausea, vomiting, abdominal(diarrhea, nausea, vomiting, abdominal
bloating, flatulence, and anorexia).bloating, flatulence, and anorexia).
27. Troglitazone had been associated with anTroglitazone had been associated with an
increased risk of hepatotoxicity and wasincreased risk of hepatotoxicity and was
removed from the market.removed from the market.
28. Cosmetic management of hirsutismCosmetic management of hirsutism
Plucking can cause folliculitis,Plucking can cause folliculitis,
pigmentation, and scarring.pigmentation, and scarring.
Electrolysis is tedious, its success is highlyElectrolysis is tedious, its success is highly
operator-dependent, and it may beoperator-dependent, and it may be
impractical for treating large numbers ofimpractical for treating large numbers of
hairs.hairs.
Laser treatment is also operator-Laser treatment is also operator-
dependent and multiple treatments maydependent and multiple treatments may
be necessarybe necessary
29. FutureFuture
There are few data to support treatmentThere are few data to support treatment
during pregnancy with metformin induring pregnancy with metformin in
women with PCOS to prevent pregnancywomen with PCOS to prevent pregnancy
loss or pregnancy complications.loss or pregnancy complications.
(Legro, 2007)(Legro, 2007)
30. it may be time to takeit may be time to take
PCOS in pregnancyPCOS in pregnancy
seriouslyseriously
