current concepts in polycystic ovarian syndrome mark n. simon, md exempla uptown women’s...
TRANSCRIPT
![Page 1: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/1.jpg)
Current Concepts inPolycystic Ovarian Syndrome
Mark N. Simon, MD
Exempla Uptown Women’s
Healthcare Specialists
October 17, 2003
![Page 2: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/2.jpg)
Disclosure
Dr. Simon has no significant financial interests or other relationships with industry relative to the subject of this lecture.
![Page 3: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/3.jpg)
Objectives
Cite the physical manifestations of PCOS. Describe the pathophysiology of PCOS. Formulate a treatment plan for patients with
PCOS.
![Page 4: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/4.jpg)
Scope of the Problem
PCOS is the MOST common endocrine disorder of reproductive age women
Effects 5-10% of these women Commonly presents to primary care
providers
![Page 5: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/5.jpg)
Diagnosis
North America (NIH Consensus):– Menstrual Irregularity (oligo- or anovulation)– Hyperandrogenism
Clinical evidence OR Laboratory evidence
– Absence of other endocrine disorders Congenital Adrenal Hyperplasia Hyperprolactinemia Thyroid dysfunction
![Page 6: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/6.jpg)
Diagnosis
Europe:– Morphological features of polycystic ovaries– Menstrual disturbance AND/OR– Hyperandrogenism
Hirsuitism Acne Alopecia Laboratory data are not needed
![Page 7: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/7.jpg)
Ultrasound
Polycystic Ovaries– Found in around 20% of general population– May be a predictor of future development of
PCOS– Found in 80% of women with PCOS
Appearance– Many, peripheral, small follicles– Increased ovarian stroma
![Page 8: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/8.jpg)
European Diagnosis
Increases prevalence to about 15% Proposed unifying protocol:
1. Determine if symptoms are present
2. If present, proceed with ultrasound
3. If ultrasound positive – diagnosis confirmed
4. If ultrasound negative – check lab tests
Homberg, Human Reproduction, 2002
![Page 9: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/9.jpg)
Diagnosis
North America (NIH Consensus):– Menstrual Irregularity (oligo- or anovulation)– Hyperandrogenism
Clinical evidence OR Laboratory evidence
– Absence of other endocrine disorders Congenital Adrenal Hyperplasia Hyperprolactinemia Thyroid dysfunction
![Page 10: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/10.jpg)
Patient Presentation
Symptoms of hyperandrogenism Irregular menstrual cycles Infertility – Most Common Presentation
![Page 11: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/11.jpg)
Symptoms of Hyperandrogenism
Hirsutism Acne Rarely see Virilization
– Male pattern balding– Clitoromegaly– Deepening of voice– Increased muscle mass
![Page 12: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/12.jpg)
Hirsutism
Occurs in 80% of PCOS patients Excess terminal body hair
– Male Pattern Back, Sternum, Upper Abdomen, Shoulder
More common areas– Upper Lip, Around breast nipples, Linea alba– ¼ of women have hair in these areas
Excluding Scandinavian, Asian
![Page 13: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/13.jpg)
Hirsutism - DDx
Idiopathic PCOS Drugs (Danazol) Hyperthecosis Ovarian Tumors Adrenal Tumors CAH
![Page 14: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/14.jpg)
Ovarian Hyperthecosis
Ovary has nests of luteinized theca cells Signs and Symptoms
– Hirsutism, Alopecia, Obesity– HTN– Clitoromegaly– Markedly elevated testosterone
![Page 15: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/15.jpg)
Red Flags with Hirsutism
Rapid onset of hirsutism Rapid progression of hirsutism Late onset
– Outside of early reproductive years
Virilization
![Page 16: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/16.jpg)
Tumors
RED FLAGS Testosterone > 150ng/dL (> 200ng/dL) LH low DHES > 800mcg/dL Further investigation warranted
– MRI abdomen/pelvis
![Page 17: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/17.jpg)
Nonclassic Congenital Adrenal Hyperplasia
Partial deficiency of 21-hydroxylase Elevation of 17-hydroxyprogesterone
– Precursor of androgens
Rare Do NOT have adrenal insufficiency Treat with anti-androgen therapy
![Page 18: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/18.jpg)
Nonclassic Congenital Adrenal Hyperplasia
Consider in patients not responding to typical PCOS treatment
Measure 17-hydroxyprogesterone– Follicular phase– Morning– Levels > 2 ng/mL need to be tested further
Adrenal stimulation
![Page 19: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/19.jpg)
Acne
Common in adolescent girls (30-50%) Severe acne is uncommon (<1%) Severe acne is a predictor of PCOS
![Page 20: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/20.jpg)
Irregular Menses
Most common to have erratic menses– Due to Anovulation
Patients present with oligomenorrhea or amenorrhea
![Page 21: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/21.jpg)
PCOS with Regular Menses?
Androgens converted to estrogens– Peripheral conversion– Aromatase
Estrogens stimulate uterine lining Can have regular shedding of endometrial
lining despite anovulation
![Page 22: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/22.jpg)
PCOS with Regular Menses?
Hyperandrogenism does NOT automatically cause anovulation
Women with hyperandrogenism and polycystic ovaries may still ovulate regularly
Affect on fertility is unclear
![Page 23: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/23.jpg)
Infertility
Usually long-standing infertility PCOS typically develops in early
reproductive years Infertility usually due to anovulation
![Page 24: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/24.jpg)
Clinical Presentations
Hyperandrogenism– Hirsutism– Acne
Menstrual Irregularity Infertility
![Page 25: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/25.jpg)
Initial Evaulation
History to determine onset PCOS usually has long course
– Rapid onset of hirsutism – Red Flag
Usually develops early in reproductive years PCOS is diagnosis of exclusion Lab tests help to exclude other problems
![Page 26: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/26.jpg)
What tests to order
Prolactin– Rule out hyperprolactinemia– Cause of menstrual dysfunction– Little signs of hyperandrogenism– Lactotroph stimulation from estrogen
Testosterone DHEAS
![Page 27: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/27.jpg)
Laboratory Tests
17-Hydroxyprogesterone– In patients suspected of NCAH
TSH– When symptoms warrant
Glucose Tolerance Test Fasting Lipid Profile
![Page 28: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/28.jpg)
Laboratory Tests
LH, FSH– Little benefit
Insulin
![Page 29: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/29.jpg)
Pathophysiology
Exact problems have not been identified Hypothalamic-pituitary abnormalities
– Elevated LH Increased frequency and amplitude of pulses
– Low-normal FSH– LH:FSH ratio increased– GnRH pulse generator may be disrupted causing
the elevated LH
![Page 30: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/30.jpg)
Hyperandrogenism
Androstenedione– Produced in ovarian thecal cells– Production is stimulated by LH– Converted to estradiol by FSH-stimulated
aromatase– Excess is converted to estrone which suppresses
FSH and is tonic to LH
![Page 31: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/31.jpg)
LH
Ovary
Androstenedione
EstroneEstradiol
FSH
+
-
Hyperandrogenism
Testosterone
SHBG
-
![Page 32: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/32.jpg)
Insulin Resistance
Feature of PCOS Both obese and lean women are affected Affects a number of systems Reduction in tissue response to insulin
![Page 33: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/33.jpg)
Insulin Resistance
Insulin causes androgen production– In women with PCOS
Insulin– Amplifies LH response in granulosa cells– Arrest of follicular development
![Page 34: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/34.jpg)
Insulin Resistance
Insulin-like growth factor 1 (IGF-1)– Amplifies LH and androgen synthesis– Helps to regulate follicular maturation
Insulin-like growth factor binding protein 3 (IGFBP-3)– Decreased in patients with ovarian hirsuitism– When decreased, more bioavailability of IGF-1
Shobokshi, et al, J Soc Gynecol Investig, 2003
![Page 35: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/35.jpg)
Insulin
Insulin
Glycogenolysis
Gluconeogenesis
PeripheralGlucoseUptake
- +
-
![Page 36: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/36.jpg)
Insulin Resistance
Insulin
OvarianAndrogenSecretion
Anovulation
Granulosa Cells +
![Page 37: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/37.jpg)
Summary of Pathophysiology
Elevated LH Leads to elevated Androgens
– Hyperandrogen symptoms
Insulin Resistance
![Page 38: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/38.jpg)
Treatment
Depends on symptoms Depends on patient’s goals
![Page 39: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/39.jpg)
Lifestyle Modification
Exercise– 150 minutes per week– Moderate exertion
Diet Weight Loss Most effective with obese patients
![Page 40: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/40.jpg)
Weight Loss
Improves ovulatory and fertility rates– 5-7% loss– Restored ovulation in 75%
Decreases LH pulse amplitude– Decreases androgen production
Reduces insulin levels
Kiddy et al., Clin Endocrinol, 1992.
![Page 41: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/41.jpg)
Insulin Sensitizers
Metformin – Most extensively studied– Increases peripheral uptake of glucose– Decreases gluconeogenesis– Does not cause hypoglycemia– Relatively inexpensive
Generic 500mg, 60 tabs $33.99 (drugstore.com 10/15/03)
![Page 42: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/42.jpg)
Metformin
Side Effects– Gastrointestinal distress– Most common in first few weeks of use– Improves over time– Lactic acidosis
Dosage is 500mg TID or 875mg BID
![Page 43: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/43.jpg)
Metformin
Lactic Acidosis– Severe, potentially fatal– Concern with elevated creatinine (>1.4 mg/dL)
Contraindicated in – – CHF, Sepsis, Liver disease, history of lactic
acidosis
Surgery
![Page 44: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/44.jpg)
Rosiglitazone
Insulin-sensitizing agent Stimulate production of glucose transporter
proteins Few studies in PCOS Dosage is 4mg BID More expensive
– 4mg, 30 tabs cost $77.99 (drugstore.com, 10/15/03)
![Page 45: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/45.jpg)
Rosiglitazone
Improved clinical symptoms Corrects insulin resistance Improves ovulation rates Fewer side effects
– Especially GI
Fertility rates not studied Shobokshi, et al, J Soc Gynecol Investig, 2003 Ghazeeri, et al, Fertil Steril, 2003
![Page 46: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/46.jpg)
Treatment Algorithms
Path depends primarily on fertility desires Also depends on primary symptoms of
patient
![Page 47: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/47.jpg)
Desires Fertility
The Problem: Anovulation The Solution: Reestablish Ovulation Question for patient: Willingness to wait?
– Weight Loss– Insulin-sensitizers may take 3-5 months– Ovulation induction much quicker
Harborne et al, The Lancet, April 8, 2003.
![Page 48: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/48.jpg)
Weight Loss
Modest weight loss (5%) can help– Lower androgen levels– Induce regular cycles
Other health benefits for pregnancy– Diabetes– Hypertension
![Page 49: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/49.jpg)
Metformin
5 weeks of treatment Ovulation rate of 34 % vs. 4% in placebo No ovulation – Given Clomiphene citrate
– Increased ovulation rate to 90%
Nestler et al, NEJM, 1998
![Page 50: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/50.jpg)
Metformin and Pregnancy
Pregnancy Class B PCOS increases risk of miscarriage
– 30-50% higher
Plaminogen activator inhibitor (PAI)– Causes placental insufficiency– Increases with increased insulin levels
Kosasa, Contemporary OB/Gyn, March 2003
![Page 51: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/51.jpg)
Metformin and Pregnancy
Patients receiving 1.5g to 2.55g per day Decreased rate of miscarriage
– From 73% to 10%
Thought to be related to decrease PAI activity
Glueck et al, Fertil Steril, 2001.
![Page 52: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/52.jpg)
Metformin and Gestational Diabetes
PCOS increases risk of GDM Metformin treatment decreases development
of GDM– From 31% to 3%
Further studies are warranted
Glueck et al, Fertil Steril, 2002.
![Page 53: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/53.jpg)
Ovulation Induction
Clomiphene citrate– Can start at 50mg/day on days 5-9– Up to 150mg/day
Some sources up to 200mg/day in morbidly obese
– Effective in about 85% of women with PCOS– Metformin-CC combination even more effective
90% in small study Further studies ongoing
Stovall, OBG Management, June 2003
![Page 54: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/54.jpg)
Other Induction Agents
Human menopausal gonadotropin Follicle-stimulating hormone Referral to specialist
![Page 55: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/55.jpg)
Fertility NOT Desired
Regulate Cycles– Hormonal Contraception
Oral Pills Patch Ring
– Progesterone withdrawal Every 3 months Monthly
![Page 56: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/56.jpg)
Hormonal Contraception
Reduces gonadotropin stimulation on ovary Reduces androgen production Can help with hirsutism, acne Increase SHBG Use newer progestins
– Desogestrel, Norgestimate
![Page 57: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/57.jpg)
Caution
Hormonal Contraception– Not as effective in morbidly obese– Increased risk of thrombotic event
![Page 58: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/58.jpg)
Hirsutism - Treatment
Reduce Androgens– Weight Loss– Hormonal Contraception– Anti-Androgens
Mechanical Treatment– Shaving– Electrolysis– Laser
![Page 59: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/59.jpg)
Hirsutism
Treatment takes a long time Spironolactone
– Binds to androgen receptor– Blocks 5α-Reductase– 25mg, 50mg,100mg, 200mg divided daily– Side effects
Light-headedness, lethargy, menstrual irregularity, mastodynia
![Page 60: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/60.jpg)
Spironolactone
Use with contraception Theoretical risk of teratogenicity Minimize menstrual irregularity
![Page 61: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/61.jpg)
Spironolactone
Effectiveness– 40-88% reduction in diameter of hair growth– 6-12 months of use
Futterweit, Obs and Gyn Survey, 1999.
![Page 62: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/62.jpg)
Other Antiandrogens
Flutamide– Blocks androgen binding to tissue– Rare fatal hepatotoxicity
Finasteride– 5α-reductase inhibitor– 5mg/day– Don’t use in pregnancy– As effective as Spironolactone
![Page 63: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/63.jpg)
Other treatments of hirsutism
Eflornithine– Topical agent– Slows hair growth– Apply twice a day– Mechanical hair removal is required– Hair will reappear 2 months after stopping tx
![Page 64: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/64.jpg)
Mechanical Treatment
Can be used after medical treatment Laser
– Most success in light skin, dark hair
Electrolysis– Long-term treatments
![Page 65: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/65.jpg)
Long-Term Consequences of PCOS
Endometrial Cancer Coronary Risk
![Page 66: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/66.jpg)
Endometrial Cancer
Most common invasive gyn cancer Risks include
– Unopposed estrogen– Obesity– High androstenedione levels– Risks that are common in PCOS patients
![Page 67: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/67.jpg)
Decreasing Endometrial Risk
Regulate menses Combination hormones Progesterone withdrawal
![Page 68: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/68.jpg)
Coronary Risk
Prediliction to Diabetes Dyslipidemia Obesity
![Page 69: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/69.jpg)
Diabetes Risk
Study of 122 obese women with PCOS Impaired Glucose Tolerance
– 30-40% Type 2 Diabetes
– 10%
Ehrmann, et al., Diabetes Care, 1999.
![Page 70: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/70.jpg)
Diabetes Risk
What screening test?– Fasting Glucose– 75 gram GTT
Risk of Diabetes with PCOS– 254 women with PCOS– 3.2% by fasting glucose alone– 7.5% with GTT
Legro, et al, J Clin Endocrinol Metab, 2002.
![Page 71: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/71.jpg)
Dyslipidemia
Elevated Triglycerides Decreased HDL Increased LDL/HDL ratio
![Page 72: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/72.jpg)
Overall Coronary Risk
Hard to determine Studies have been poorly defined
– Ovarian morphology– Oligomenorrhea
Can be confounded by other known risk factors– Diabetes, Obesity
![Page 73: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/73.jpg)
Long-Term Therapy
Cyclic Estrogen/Progesterone– Reduces risk of endometrial hyperplasia and
cancer
Insulin-sensitizers– Uncertain of long-term benefit– May reduce risk of diabetes
Need further studies
![Page 74: Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003](https://reader031.vdocuments.us/reader031/viewer/2022032312/56649de75503460f94ae06ad/html5/thumbnails/74.jpg)
Take Home
Treatment needs to be guided by patient desires and concerns
Lifestyle modification Protect the endometrium