ENDOCRINE PERSPECTIVE OF

PCOS &

GROUND BREAKING STUDIES IN

REPRODUCTION

Robina Rana

PGY- 4 Endocrinology

February 1st , 2012

OBJECTIVE:

PCOS :Metabolic disease/ reproduction condition

Discuss the background, pathophysiology of PCOS and its impact on Reproductive Endocrinology.

To Review Journal Articles of particular importance to Reproductive Endocrine Practice

PCOS – HISTORICAL PERSPECTIVE:

1921 - ACHARD and THIERS reported the first observation of co-existing hirsutism and diabetes, and related this syndrome to hyperplasia of the adrenal cortex, detected at autopsy and was given the name,

“Diabetes in Bearded Women”(ACHARD – THIERS –SYNDROME)

PCOS – HISTORICAL PERSPECTIVE:

In 1935, Stein and Leventhal published a paper on their findings in seven women with amenorrhea hirsutism obesity a characteristic polycystic appearance

to their ovaries — one of the first descriptions of a complex phenotype today known as the “polycystic ovary syndrome.”

POLYCYSTIC OVARIAN SYNDROME:

The condition is now well recognized as having a major effect throughout life on the 1. reproductive, 2. metabolic, and 3. cardiovascular health of affected

women.

PCOS: CLINICAL FEATURES

ACNE

HIRSUTISM

ACANTHOSIS NIGRICANS

PCOS:SONOGRAPHIC AND HISTOLOGIC FEATURES

FACTORS CONTRIBUTING TO DIFFICULTIES IN DIAGNOSIS OF AND TREATMENT OF PCOS: Lack of precise and uniform definition of

PCOS Presenting signs and symptoms are; Heterogeneous Vary over time No Definite treatment is available.

Conditions for Exclusion in the Diagnosis of the Polycystic Ovary Syndrome.

Ehrmann DA. N Engl J Med 2005;352:1223-1236.

ESTROGEN BIOSYNTHESIS IN WOMEN

ANDROGEN BIOSYNTHESIS IN WOMEN:

EXTRAOVARIAN CONVERSION OF ANDROSTENEDIONE TO ANDROGEN AND ESTROGEN:

REGULATION OF (GNRH), (LH), AND (FSH) SECRETION:

The Hypothala

mic–Pituitary–Ovarian Axis and

the Role of Insulin.

Ehrmann DA. N Engl J Med 2005;352:1223-1236.

PATHOLOGIC MECHANISMS IN POLYCYSTIC OVARY SYNDROME :

HYPOTHESIS FOR PRENATAL ANDROGEN PROGRAMMING OF FEMALES FOR PCOS

PCOS HEALTH CONSEQUENCESReproductive

Infertility Increased risk of miscarriage Increased risk of gestational

diabetes/ preeclampsia Increased risk of

endometrial cancer(RR 3.1)

Psychosocial

Depression & anxiety Cosmetic concerns(hyperandrogenic symptoms)

Cardiometabolic:

Increased risk of type 2 Diabetes

Hypertension Dyslipidemia Increased inflammation Increased cardiovascular

disease risk Non-alcoholic

steatohepatitis (NASH) Sleep apnea

Figure 2. Pathophysiology of Polycystic Ovary Syndrome.

Legro, R. S. JAMA 2007;297:509-519

MANAGEMENT GOAL:

Overall goals of treatment are to: Restore appropriate Gonadotropin secretion Decrease androgen levels to prevent long-term

deleterious effects of PCOS Restore menstrual cyclicity Manage the cosmetic symptoms and signs Restore fertility if desired Long-term health - Chronic disease prevention

Diabetes prevention Cardiovascular disease risk reduction Cancer prevention

MANAGEMENT :1.Metabolic Management: Lifestyle management is the foundation of

treatment. Weight Reduction. Insulin Sensitizing agents.

Up to half of women with PCOS are overweight or obese

Abdominal obesity is typical Even lean women with PCOS tend to have increased

omental and visceral fat Modest weight loss of 5 – 10% can restore menstrual

cyclicity Healthy eating and exercise essential for management

of both hormonal and metabolic aspects of PCOS. Multidisciplinary approach to weight management.

MANAGEMENT:

2. Symptomatic Management: Oral Contraceptives

Choose progestin with low androgenic potential Increases SHBG levels Suppresses androgen production Effective in reducing acne & hirsutism Cycle regulation and thus reducing risk of endometrial hyperplasia/cancer

Antiandrogens Spironolactone

PCOS – OTHER POTENTIAL DRUG TREATMENTS

Exenatide(Byetta): GLP-1 Analogue Exenatide restores

first- and secondphase insulin secretion which is attenuated in women with PCOS, as well as promote

weight loss, thereby potentially further improving insulin sensitivity

1. METFORMIN IN POLYCYSTICOVARY SYNDROME:

METFORMIN IN PCOS:SYSTEMATIC REVIEW AND META-ANALYSIS

Objective To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome.

Data sources Randomized controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent.

METFORMIN IN PCOS:

Selection of studies 13 trials were included for analysis,

including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence.

Main outcome measure Pregnancy and ovulation rates.Secondary outcomes of clinical and biochemical features of

polycystic ovary syndrome.

Metformin compared with placebo or no treatment:significant effect of metformin compared with placebo on ovulation

Lord J M et al. BMJ 2003;327:951©2003 by British Medical Journal Publishing

Group

Metformin combined with clomifene compared with clomifene alone–ovulation rate.effect for metformin and clomifene compared with clomifene alone

was significant

Lord J M et al. BMJ 2003;327:951©2003 by British Medical Journal Publishing Group

Metformin compared with placebo or no treatment–side effects.

Lord J M et al. BMJ 2003;327:951

©2003 by British Medical Journal Publishing Group

Lord J M et al. BMJ 2003;327:951

©2003 by British Medical Journal Publishing Group

Metformin compared with placebo or no treatment–fasting insulin:Metformin had a significant effect in reducing fasting insulin concentrations

RESULTS:Characteristics Metformin vs.

placeboClomiphene + Metformin vs. Clomiphene alone

Ovulation Effective with OR 3.88

Effective with OR 4.41

Pregnancy Rate Significant with combined Rx

Fasting Insulin Level

Reduced level reduced

Blood pressure Reduced reduced

LDL-C level Reduced level Reduced

BMI / Waist hip ratio

No effect ------

Adverse effectsNause/vomiting/GI

Higher incidence high

CONCLUSIONS: Metformin is an effective treatment for

anovulation in women with PCOS Can be used as first line agent There is some

evidence of benefit on variables of the metabolic syndrome.

It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.

Safety of Metformin No data for long term use in young women only limited data on in early pregnancy.

2. METFORMIN VERSUS ORAL CONTRACEPTIVE PILL IN

POLYCYSTIC OVARY SYNDROME:A COCHRANE REVIEW

HUMAN REPRODUCTION. 2007;22(5):1200-1209. © 2007 

ORAL CONTRACEPTIVES IN POLYCYSTIC OVARY SYNDROME: The OCPs are a key component of the

chronic treatment of PCOS addressing many of the goals of the reproductive-aged PCOS women not seeking pregnancy.

Earlier epidemiologic studies of OCPs in healthy women have raised concern regarding

potential adverse cardiometabolic effects increase the risk of diabetes particularly

in obese patients with severe insulin resistance.

OCPS VS INSULIN SENSITIZING DRUGS IN PCOS

ORAL CONTRACEPTIVES

INSULIN SENSITIZING DRUGS

Insulin Resistance

May Worsen Improves Insulin Sensitivity

Glucose Intolerance

May induce Improves Glucose tolerance

Serum TG May Increase May Reduce

Risk for Type 2 DM

May Increase Decrease

Risk for CVD May Increase Redcue dec. level of CRP, Edothelin levels

METFORMIN VS. OCP IN PCOS: (A COCHRANE REVIEW)

Background: The objective of this review was to compare metformin versus oral contraceptive pill (OCP) treatment in polycystic ovary syndrome.

Methods: A systematic review and meta-analysis employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was undertaken.

Conclusions: Limited RCT evidence to date does not show adverse metabolic risk with the use of the OCP compared with metformin. Further long-term RCTs are required.

Michael F. Costello; Bhushan Shrestha; John Eden; Neil P. Johnson; Peter Sjoblom

Human Reproduction. 2007;22(5):1200-1209. © 2007 Oxford University Press

Study

Allocatio

n concealment

Blinding

Number

randomized

Number analysed (type of analysis)

Mean age

(years)

Mean BMI (kg m-2)

Duration of

treatment

(months)

Total daily metformin dose (mg)

Type of oral

contraceptive pill Notes

Harborne et al.

(2003b), Scotland

A No 52 34 (ACA) 31 32 12 1500 Diane 35 Recruited polycystic ovary syndrome

(PCOS) women whose primary complaint

was hirsutism

Morin-Papunen et al. (2000),

Finland

A No 32 18 (ACA) 30 35 6 1000 increasing

to 2000 after 3 months

Diane 35 Recruited obese women with PCOS

Morin-Papunen et al. (2003),

Finland

A No 20 17 (ACA) 28 22 6 1000 increasing

to 2000 after 3 months

Diane 35 Recruited non-obese women with PCOS

Rautio et al. (2005),

Finland

A No 52 35 (ACA) 29 29 6 1000 increasing

to 2000 after 3 months

Diane 35 Assessed lipid levels only. The patients

included the combined patients of Morin-Papunen et al.

(2000; 2003)

PRIMARY OUTCOME MEASURESCOMPARISON OF METFORMIN VS. OCP OUTCOME OF HIRSUTISM:

69 participants analyzed reported on hirsutism using either Ferriman-Gallway (FG) scoring system or a subjective (patient self-assessed) visual analogue scale from 0 to 10

Meta-analysis demonstrated no difference in effect on hirsutism between metformin and OCP

PRIMARY OUTCOME MEASURESCOMPARISON OF METFORMIN VERSUS OCP WITH OUTCOME OF ACNE.

There was a single trial comparing metformin versus OCP with 34 participants analyzed (52 participants randomized) reporting acne subjectively (patient self-assessed) using a visual analogue scale ranging from 0 to 10 (Harborne et al., 2003b).

This trial demonstrated no significant difference in acne scores between metformin and the OCP

PRIMARY OUTCOME MEASURESCOMPARISON OF METFORMIN VERSUS OCP WITH OUTCOME OF TYPE 2 DIABETES MELLITUS• One trial comparing metformin versus OCP with 18

participants analysed (32 participants randomized) reported diagnosis of T2DM (Morin-Papunen et al., 2000).

• No significant difference was seen in the development of T2DM between the metformin and OCP groups (Peto OR 0.17, P = 0.37, 95% CI 0.00 to 8.54)

PRIMARY OUTCOME MEASURES

Cardiovascular Disease. There were no trials comparing metformin versus OCP reporting the outcome measure of CVD (stroke or myocardial infarction).

Endometrial Cancer. There were no trials comparing metformin versus OCP reporting endometrial cancer as an outcome.

SECONDARY OUTCOMES MEASURESIMPROVED MENSTRUAL PATTERN.

There were two trials comparing metformin versus OCP with a total of 35 participants analysed (52 participants randomized) reporting on improvement in menstrual cyclicity (Morin-Papunen et al., 2000, 2003).

Eighteen of 21 participants on metformin and 20 of 24 participants on the OCP had either oligomenorrhoea or amenorrhoea at baseline.

Both trials reported menstrual pattern in terms of days between menses and metformin was significantly less effective in improving menstrual pattern Peto OR 0.08, P = 0.004, 95% CI 0.01-0.45)

SECONDARY OUTCOMES MEASURESHORMONAL: SERUM TOTAL TESTOSTERONE (NMOL L-1).

There were three trials comparing metformin versus OCP with a total of 69 participants analysed (104 participants randomized) reporting on total serum testosterone (Morin-Papunen et al., 2000, 2003; Harborne et al., 2003b).

Meta-analysis demonstrated a significantly higher serum total testosterone with metformin compared with the OCP

SECONDARY OUTCOMES MEASURESMETABOLIC: FASTING GLUCOSE (MMOL L-1).

Three trials comparing metformin versus OCP with a total of 69 participants analysed (104 participants randomized) reported on fasting glucose levels(Morin-Papunen et al., 2000, 2003; Harborne et al., 2003b).

There was no significant difference in fasting glucose levels between the two interventions (WMD 0.13, P = 0.25, 95% CI -0.09 to 0.35)

SECONDARY OUTCOMES MEASURESMETABOLIC: FASTING TOTAL CHOLESTEROL (MMOL L-1).

There were two trials comparing metformin versus OCP with a total of 69 participants analysed (104 participants randomized) reporting on total cholesterol levels (Harborne et al., 2003b; Rautio et al., 2005).

Meta-analysis demonstrated no significant difference in total cholesterol levels between metformin and the OCP

SECONDARY OUTCOMES MEASURESMETABOLIC: FASTING TRIGLYCERIDES (MMOL L-1).

Two trials comparing metformin versus OCP with a total of 69 participants analysed (104 participants randomized) reported on triglyceride levels (Harborne et al., 2003b; Rautio et al., 2005).

Metformin resulted in a significantly lower triglyceride level than the OCP (WMD -0.48, P = 0.01, 95% CI -0.86 to -0.09

RESULTS: METFORMIN VS. OCP IN PCOS: CHARACTERISTIC METFORMIN OCP

HIRSUTISM No Difference No Difference

ACNE No Difference No Difference

TYPE 2 DM No Difference No Difference

FASTING GLUCOE No Difference No Difference

TOTAL CHOLESTEROL No Difference No Difference

SEVERE ADVERSE EFFECTS No Difference No Difference

CVS DISEASE --------------- ---------------

ENDOMET. CA --------------- ---------------

IMPROVED MENSTRUAL PATTERN

Less effective More effective

S. TESTOSTERONE LEVEL Less effective in decreasing levels

More effective in decreasing levels

FASTING S. INSULN LEVEL More effective in decreasing levels

Less effective in decreasing levels

FASTING TRIGLYCERIDE LEVEL

More effective not increasing level

Less effective

3. TROGLITAZONE IN WOMEN WITH PCOS:

IMPROVES DEFECTS IN INSULIN ACTION, INSULIN

SECRETION, OVARIAN STEROIDOGENESIS,

AND FIBRINOLYSIS

Troglitazone: PPAR gamma activator

TROGLITAZONE IN PCOS:

Insulin-sensitizing agent troglitazone was administered to 13 obese women with PCOS and impaired glucose tolerance to determine whether attenuation of hyperinsulinemia ameliorates ovarian steroidogenesis, and fibrinolysis.

All subjects had oligomenorrhea, hirsutism, polycystic ovaries, and hyperandrogenemia.

The Journal of Clinical Endocrinology & Metabolism July 1, 1997 vol. 82 no. 7 2108-2116

Before and after treatment with troglitazone (400 mg daily for 12 weeks), all had

1) a GnRH agonist (leuprolide) test, 2) a 75-g oral glucose tolerance test, 3) a frequently sampled iv glucose tolerance test

to determine the insulin sensitivity index and the acute insulin response to glucose,

4) an oscillatory glucose infusion to assess the ability of the β-cell to entrain to glucose as quantitated by the normalized spectral power for the insulin secretion rate, and

5) measures of fibrinolytic capacity [ plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator].

Glucose (top panel) and insulin (bottom panel) responses during the OGTT before (closed symbols) and after (open symbols) treatment with troglitazone.

Ehrmann D A et al. JCEM 1997;82:2108-2116

©1997 by Endocrine Society

Measures derived from the rapidly sampled iv glucose tolerance test before (solid) and after (hatched) treatment with troglitazone. (improved b-cell fucntion)

Ehrmann D A et al. JCEM 1997;82:2108-2116

©1997 by Endocrine Society

Profiles of the glucose concentrations and ISR in response to an oscillatory glucose infusion in one representative subject before (upper panel) and after (lower panel)

treatment with troglitazone.

Ehrmann D A et al. JCEM 1997;82:2108-2116©1997 by Endocrine Society

PAI-1 antigen and activity levels before (solid) and after (hatched) treatment with troglitazone.

Ehrmann D A et al. JCEM 1997;82:2108-2116©1997 by Endocrine Society

RESULTS OF TROGLITAZONE THERAPY IN PCOS :Characteristic Post Treatment with

Troglitazone

BMI No Change

Body Fat Distribution No Change

Glycated Heamoglobin Concordant Reduction6.1 ± 0.1% 5.7 ± 0.1 (P < 0.03).

Total & Free Testosterone level Significant Reduction

Luprolide Stimulation

17-Hydoxy progesterone level

Significant Reduction

Andreostenddione level Significant Reduction

Total Testosterone level Significant Reduction

Total Cholesterol No Significant change

LDL – C No Significant change

Triglyceride levels Declined ( not statically significant.)

CONCLUSION: Administration of troglitazone to women

with PCOS and IGT ameliorates each of the metabolic and hormonal derangements that characterize these women.

Troglitazone was removed from the market because it caused liver dysfunction and, in some patients, liver failure.

Thiazolidinedione therapy has been investigated for induction of ovulation, but routine use of these drugs has not been suggested secondary to side effect profile.

4.COMPARISON OF SINGLE AND COMBINED TREATMENT WITH EXENATIDE VS.METFORMIN ON MENSTRUAL CYCLICITY IN OVERWEIGHT WOMEN WITH PCOS:

METFORMIN VS. EXANETIDEIN POLYCYSTIC OVARIAN SYNDROME:

Objective: Evaluate effect of exenatide (EX) and metformin (MET), alone and in combination (COM) on ; menstrual cyclicity, hormonal parameters metabolic profiles inflammatory markers in overweight, insulin-resistant women with PCOS.

DESIGN, SETTING, AND PARTICIPANTS:

Sixty overweight oligo ovulatory women with PCOS (body mass index 27; 18–40 yr)were randomized to one of three treatment groups:

MET[1000mgtwice daily (BID)] EX (10 mcg BID) or COM (MET 1000 mg BID, EX 10 g BID) for 24

wk.

The primary outcome was menstrual frequency; Secondary outcome measures included

changes in ovulation rate, insulin action, anthropometric measures, androgen levels, and inflammatory markers.

Menstrual cycle frequency index at baseline and after 24 wk of treatment with EX, MET, or COM

Absolute body weight (kg) of women with PCOS at baseline and after 12 and 24 wk of treatment with EX, MET, or COM.

RESULTS:Forty-two (70%) patients completed the study. COM therapy was superior to EX or MET monotherapy in 1) improving

menstrual cyclicity ovulation rate free androgen index insulin sensitivity measures

2) reducing weight abdominal fat.

Both EX arms were more effective in promoting weight loss than MET (P 0.003).

CONCLUSIONS: COM appears better than either EX or MET alone

on menstrual cycle frequency and hormonal and metabolic derangements.

A marked decrease in central adiposity could partly explain the improvements in

reproductive function, insulin-glucose parameters, and adiponectin observed in these overweight

women with PCOS treated with COM therapy. Larger trials of longer duration are warranted to

assess the long-term efficacy and safety of combined EX-MET therapy in overweight women with PCOS.

(J Clin Endocrinol Metab 93: 2670–2678, 2008)

Table 2. Selected Randomized Trials of Common Medical Therapies in Women With Polycystic Ovary Syndrome With at Least 100 Participants According to Outcomes Assessed.

Legro, R. S. JAMA 2007;297:509-519

POLYCYSTIC OVARY SYNDROME ASSOCIATED WITH MORBID OBESITY RESOLVES AFTER WEIGHT LOSS ??

PCOS ASSOCIATED WITH MORBID OBESITY MAY RESOLVE AFTER WEIGHT LOSS INDUCED BY BARIATRIC SURGERY

Objective: The objective of this study was to evaluate the response of PCOS to the sustained and marked weight loss achieved by bariatric surgery in morbidly obese women.

DESIGN: PATIENTS: This was a longitudinal prospective

nonrandomized evaluation. 36 consecutive premenopausal women

submitted to bariatric surgery were screened for PCOS, which was present in 17

Main Outcome Measures: Hyperandrogenism, menstrual function, and insulin resistance were estimated before and at least 6 months after bariatric surgery in 12 patients with PCOS

Clinical and biochemical characteristics of the morbidly obese PCOS patients submitted to bariatric surgery, before and after weight loss. ○, Individual values; ▪, mean ± sd.

Escobar-Morreale H F et al. JCEM 2005;90:6364-6369©2005 by Endocrine Society

RESULTS: Weight loss (41 ± 9 kg after 12 ± 5 months) Decreases in the hirsutism score (from 9.5 ± 6.8 to 4.9 ± 4.2; P = 0.001), Decrease in Total Testosterone (69 ± 32 to 42 ± 19 ng/dl; P < 0.02) Decrease in Free testosterone from 1.6 ± 0.7 to 0.6 ± 0.3 ng/dl; P < 0.005), Androstenedione level decrease (from 4.1 ± 1.5 to 3.0 ± 0.9 ng/ml; P < 0.02), Dehydroepiandrosterone sulfate level(from 2000 ± 1125 to 1353 ± 759 ng/ml; P < 0.005); Amelioration of insulin resistance (from 6.0 ± 3.0 to 1.6 ± 1.0; P < 0.001); Restoration of regular menstrual cycles and/or

ovulation in all patients

RESULTS: Regular menstrual cycles were restored in

the 12 PCOS patients after weight loss and 10 of these patients have confirmed ovulation.

Diabetes and dyslipidemia resolved in the PCOS patient presenting with both disorders.

In another patient, diabetes returned to glucose intolerance, whereas hypertension persisted.

In one of the two PCOS patients presenting with hypertension but no other metabolic complication, blood pressure returned to normal after weight loss.

CONCLUSIONS: The PCOS is a frequent finding in

women with morbid obesity and may resolve after weight loss induced by bariatric surgery.

EFFECTIVE TREATMENT OF POLYCYSTIC OVARIAN SYNDROME WITH ROUX-EN-YGASTRIC BYPASS

Surgery for Obesity and Related Diseases 1 (2005) 77–80

PURPOSE:

This study investigated the impact of weight loss surgery on the clinical manifestations of PCOS in morbidly obese women with PCOS

—a major risk factor for the development of heart disease, stroke, and type II diabetes.

METHODS:Reviewed the outcomes of women diagnosed with PCOS who had undergone weight loss surgery

at the University of Pittsburgh between July 1997 and November 2001.

Evaluated the changes in menstrual cycles, hirsutism, infertility, and type II diabetes.

PATIENT CHARACTERISTICS PRE- AND POST-GASTRIC BYPASS

Pre-Operative Post- Operative % change

AGE( yr) 34+/- 9.7 N/A N/A

WEIGHT( LB) 306 =/- 44 201 +/- 30 12-93%

BMI (Kg/m2) 50 +/- 7.5 30 +/- 4.5 25-38%

HTN 9 2 77

DM 11 0 100

HB A1C(%) only 5 pts who have preop

HBA1C

8.2 5.14 62

GERD 12 0 100

DYSLIPIDEMIA 12 1 92

HIRSUTISM 23 5 79

DEPRESSION 10 0 100

MENSTRUAL DYSFUNCTION

24 0 100

MEDS PER HYPERTENSIVE

1.3 (9 pt on 12 M)

0.67 (2 pt on 3 M)

N/A

DIABETIC MEDICATION 1.1( 11 pt on 12 M)

0 100

CONCLUSION:

Results suggest that obese patients with PCOS who undergo gastric bypass will experience a significant improvement in multiple clinical problems related to the disorder.

Larger prospective studies are needed to confirm further the benefit of surgically induced weight loss in the treatment of women with PCOS.

THE IMPACT OF BARIATRIC SURGERY ON MENSTRUAL PATTERNS

BACKGROUND:

Weight loss of at least 5% has been shown to reverse obesity-related anovulation.

The aim of this study was to assess the impact of bariatric surgery on infertility in morbidly obese women and to identify factors associated with return of normal menses following bariatric surgery.

METHODS:A survey of patients was collected fromthe bariatric surgery data-base at the Hospital of the University of Pennsylvania. 410 women under the age of 40 were sent

questionnaires. 195 patients completed the questionnaire,

resulting in a 51.2% response rate. Patients who reported menstrual cycle

lengths >35 days were considered abnormal.

92 of the 195 responders were considered anovulatory preoperatively, based on menstrual history.

RESULTS: Both groups had a decrease in BMI of

>18 kg/m2. The mean menstrual cycle length

preoperatively among those categorized as ovulatory and anovulatory was 27.3 and 127.5 days, respectively.

Of the 98 patients who were anovulatory preoperatively, 70 patients (71.4%)

regained normal menstrual cycles after surgery. Those patients who regained ovulation

had greater weight loss than those who remained anovulatory (61.4 kg vs 49.9 kg, P=0.02).

CONCLUSIONS: Anovulation resulting in abnormal menses is

a common problem in morbidly obese premenopausal women.

The menstrual cycle disorders may completely resolve after bariatric surgery.

Thus, infertility due to anovulation among morbidly obese women could potentially be viewed as an additional indication for bariatric surgery.

CONCEPTION RATE AFTER BARIATRIC SURGERY

PREGNANCY AND FERTILITY FOLLOWING BARIATRIC SURGERY:

Large numbers of women in their childbearing years may undergo bariatric surgery, which may change fertility following weight loss, alter nutritional requirements during

pregnancy, or impact contraception to prevent

pregnancy.

OBJECTIVES & EVIDENCE ACQUISITION To estimate bariatric surgery rates among

women aged 18 to 45 years and to assess the published literature on pregnancy outcomes and fertility after surgery.

Search of the Nationwide Inpatient Sample (1998-2005) and multiple electronic databases (Medline, EMBASE, Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness) to identify articles published between 1985 and February 2008 on bariatric surgery among women of reproductive age.

BARIATRIC SURGERY AND FERTILITY. 6 studies that addressed fertility

outcomes in patients after bariatric surgery and most of these compared pregnancy rates before and after surgery .

Three small studies reported improvements in fertility and 1 study

noted no change.

Six studies found evidence of normalization of hormones and menstrual cycles and lessening of polycystic ovarian syndrome following bariatric surgery.

CONCLUSION: Most observations on fertility following

bariatric surgery lack complete data on the total number of women attempting to get pregnant and pregnancy rates.

Most studies present convenience samples of women who were able to get pregnant, in whom pre surgery fertility histories were available.

With these significant limitations in mind, data suggest that surgery may have a beneficial influence on fertility, which is supported by the normalization of hormones in polycystic ovarian syndrome and correction of abnormal menstrual cycles.

PCOS: CLINICAL PEARLS

Most common endocrinopathy in reproductive age women(need early recognition of syndrome).

Clinical diagnosis: (irregular menses and hyperandrogenism)

Not only reproductive disorder! Need to address

metabolic defect and cardiometabolic risks. Evaluation:– hormonal parameters, fasting

glucose & OGTT (with insulin levels), lipids with other atherogenic markers; appropriate eval for sleep apnea and cardiovascular disease

PCOS: CLINICAL PEARLSManagement approach - aggressive reduction of CV risk factors Multidisciplinary team approach with support /

resources for patients Lifestyle management Diet, exercise, sleep, minimize exposure to environmental toxins. Pharmacologic treatment

First line medication - Metformin Use of OCPs with low androgenic progestin for

cycle regulation and symptomatic treatment of skin manifestations (acne, hirsutism, alopecia)

Clomiphene Citrate for ovulation Induction.

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