Evidence Based PCOsEvidence Based PCOs

IntroductionIntroduction

Polycystic ovarian syndrome (PCOS) Polycystic ovarian syndrome (PCOS) affects 4% to 12% of women of affects 4% to 12% of women of reproductive age. reproductive age.

hallmarks of the disease are hallmarks of the disease are hyperandrogenism and chronic hyperandrogenism and chronic anovulation anovulation

Changing ApproachChanging Approach

management not only toward management not only toward treating infertility and improving the treating infertility and improving the often troublesome hirsutism but also often troublesome hirsutism but also toward the toward the long-term riskslong-term risks associated with IR. associated with IR.

MoreoverMoreover

Recent data suggest that women Recent data suggest that women with PCOS are at increased risk for with PCOS are at increased risk for preterm labor, preeclampsia, and preterm labor, preeclampsia, and gestational diabetes, though the gestational diabetes, though the evidence for increased miscarriage evidence for increased miscarriage rates is less certain (Legro , 2007)rates is less certain (Legro , 2007)

Ideal design to get best Ideal design to get best EvidenceEvidence

A randomised controlled trial (RCT) A randomised controlled trial (RCT) with large numbers and, ideally, with large numbers and, ideally, three groups is needed:three groups is needed:

women with PCOS taking medication,women with PCOS taking medication, women with PCOS taking no women with PCOS taking no

treatmenttreatment non-PCOS womennon-PCOS women

metformin vs. both clomiphene metformin vs. both clomiphene and combination therapyand combination therapy

Metformin is not an effective Metformin is not an effective

additionaddition to clomifene citrate as to clomifene citrate as the primary method of inducing the primary method of inducing ovulation in women with polycystic ovulation in women with polycystic ovary syndrome ovary syndrome

NEJM, 2007NEJM, 2007

The live-birth rate was The live-birth rate was 22.5%22.5% (47 of (47 of 209 subjects) in the clomiphene 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the group, 7.2% (15 of 208) in the metformin group, and metformin group, and 26.8%26.8% (56 of (56 of 209) in the combination-therapy group 209) in the combination-therapy 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. P=0.31 for clomiphene vs. combination therapy). combination therapy).

BMJ, 2007BMJ, 2007

Clomid alone vs clomid + metforminClomid alone vs clomid + metformin no significant differences in either no significant differences in either

rate of ongoing pregnancy (40% v rate of ongoing pregnancy (40% v 46%) 46%)

HoweverHowever

gastrointestinal side effects were gastrointestinal side effects were more frequent with metformin armmore frequent with metformin arm

AccordinglyAccordingly

Addition of metformin to clomid is Addition of metformin to clomid is not recommendednot recommended

RecommendationsRecommendations

based on good and consistent based on good and consistent scientific evidence (Level A)scientific evidence (Level A)

All women with polycystic ovary All women with polycystic ovary syndrome (PCOS) should be screened syndrome (PCOS) should be screened for glucose intolerance with a 2-hour for glucose intolerance with a 2-hour glucose level after a 75-g fasting glucose level after a 75-g fasting glucose challenge glucose challenge

All women with PCOS should be All women with PCOS should be screened for dyslipidemia with a screened for dyslipidemia with a fasting lipoprotein profile, including fasting lipoprotein profile, including total cholesterol, low-density total cholesterol, low-density lipoprotein (LDL) cholesterol, high-lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, density lipoprotein (HDL) cholesterol, and triglyceride determinations. and triglyceride determinations.

LIFESTYLE MODIFICATION LIFESTYLE MODIFICATION WEIGHT LOSSWEIGHT LOSS

A 3 to 6 month trial of aggressive A 3 to 6 month trial of aggressive lifestyle modification may be a lifestyle modification may be a prudent first step before considering prudent first step before considering medications. medications.

However, many patients will have However, many patients will have difficulty in achieving weight loss difficulty in achieving weight loss

Use of clomiphene citrate is Use of clomiphene citrate is appropriate because it effectively appropriate because it effectively results in pregnancy in women with results in pregnancy in women with PCOS. (Hughes, 1997) PCOS. (Hughes, 1997)

The following recommendations The following recommendations are based on limited or are based on limited or inconsistent scientific evidence inconsistent scientific evidence (Level B)(Level B)

Long termLong term

Improvements in insulin sensitivity, Improvements in insulin sensitivity, by weight loss may favorably by weight loss may favorably improve many risk factors for improve many risk factors for diabetes and cardiovascular disease diabetes and cardiovascular disease in women with PCOS. in women with PCOS.

When using gonadotropins to induce When using gonadotropins to induce ovulation, low-dose therapy is ovulation, low-dose therapy is recommended because it offers a recommended because it offers a high rate of monofollicular high rate of monofollicular development and a significantly development and a significantly lower risk of ovarian lower risk of ovarian hyperstimulation in women with hyperstimulation in women with PCOS. PCOS.

Ovarian drillingOvarian drilling

The clear benefit and role of surgical The clear benefit and role of surgical therapy in ovulation induction in therapy in ovulation induction in women with PCOS is uncertain. women with PCOS is uncertain.

The following recommendations The following recommendations are based primarily on are based primarily on consensus and expert opinion consensus and expert opinion (Level C)(Level C)

HirsutismHirsutism

Combining medical interventions Combining medical interventions may be the most effective way to may be the most effective way to treat hirsutism. Combined therapy treat hirsutism. Combined therapy with an ovarian suppression agent with an ovarian suppression agent and an antiandrogen appears and an antiandrogen appears effective in treating hirsutism in effective in treating hirsutism in women with PCOS. The best pill or women with PCOS. The best pill or antiandrogen is unknown. antiandrogen is unknown.

Ablation techniquesAblation techniques

The ideal choice of ablative The ideal choice of ablative procedures for long-term procedures for long-term management of hirsutism in women management of hirsutism in women with PCOS is unknown. with PCOS is unknown.

During PregnancyDuring Pregnancy

The effects of insulin-sensitizing The effects of insulin-sensitizing agents on early pregnancy are agents on early pregnancy are unknown; metformin appears safe, unknown; metformin appears safe, but any additional effect at reducing but any additional effect at reducing pregnancy loss is uncertain pregnancy loss is uncertain

Side Effects of Side Effects of MedicationMedication

ProgestinsProgestins. Use of . Use of medroxyprogesterone acetate is medroxyprogesterone acetate is associated with decreases in sex associated with decreases in sex hormone binding globulin (SHBG). hormone binding globulin (SHBG). Progestin-only oral contraceptives Progestin-only oral contraceptives are associated with high incidence of are associated with high incidence of breakthrough bleeding. breakthrough bleeding.

GnGn

Use of gonadotrophins can result in Use of gonadotrophins can result in ovarian hyperstimulation syndrome ovarian hyperstimulation syndrome

Insulin-sensitizing agentsInsulin-sensitizing agents

The most common adverse reactions The most common adverse reactions of metformin are gastrointestinal of metformin are gastrointestinal symptoms (diarrhea, nausea, symptoms (diarrhea, nausea, vomiting, abdominal bloating, vomiting, abdominal bloating, flatulence, and anorexia). flatulence, and anorexia).

Troglitazone had been associated Troglitazone had been associated with an increased risk of with an increased risk of hepatotoxicity and was removed hepatotoxicity and was removed from the market. from the market.

Cosmetic management of Cosmetic management of hirsutismhirsutism

Plucking can cause folliculitis, Plucking can cause folliculitis, pigmentation, and scarring. pigmentation, and scarring.

Electrolysis is tedious, its success is Electrolysis is tedious, its success is highly operator-dependent, and it highly operator-dependent, and it may be impractical for treating large may be impractical for treating large numbers of hairs. numbers of hairs.

Laser treatment is also operator-Laser treatment is also operator-dependent and multiple treatments dependent and multiple treatments may be necessary may be necessary

FutureFuture

There are few data to support There are few data to support treatment during pregnancy with treatment during pregnancy with metformin in women with PCOS to metformin in women with PCOS to prevent pregnancy loss or pregnancy prevent pregnancy loss or pregnancy complications.complications.(Legro, 2007)(Legro, 2007)

it may be time to take it may be time to take PCOS in pregnancy PCOS in pregnancy

seriouslyseriously

Thank YouThank You