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Polycystic Ovarian Syndrome - Gynecology
This is a draft cheat sheet. It is a work in progress and is not finished yet.
DEFINITION
- Syndrome consisting of amenorrhea, hirsutism, and obesity in association with enlarged polycystic ovaries |
- "Classic" features: signs of elevated androgens, such as hirsutism, and oligomenorrhea or amenorrhea |
- 3-7% |
Rotterdam criteria - two of these three criteria are required |
- Menstrual irregularity |
- Symptoms or findings of hyperandrogenism |
- Polycystic ovaries on US |
Phenotype C - hyperandrogenism and polycystic ovaries in ovulatory women |
Phenotype D - irregular cycles and polycystic ovaries in the absence of documented hyperandrogenism |
Phenotype A - includes all three criteria with US findings of polycystic ovaries |
Phenotype B - women with the NIH definition when there are no US findings |
AEPCOS - hyperandrogenism, polycystic ovaries on us or menstrual irregularity (anovulation) |
CRITERIA FOR DIAGNOSIS OF PCOS
OVARIAN MORPHOLOGY
- 12 or more peripherally oriented cystic structures (2-9 mm) |
- Total follicle count in each ovary - most diagnostic |
- Ovarian volume of 10 ml or more |
- Polycystic-appearing ovaries (PAO), polycystic ovarian morphology (PCOM), or simply PCO |
THE DIAGNOSIS IN ADOLESCENCE
- Rotterdam criteria should not be used. |
- All three criteria are firmly in place and at a minimum of 3 years postmenarche |
MENSTRUAL IRREGULARITY
- Oligomenorrhea (cycles longer than 35 days) |
- Menstrual frequency of every few months |
- Frank amenorrhea (longer than 6 months missed) |
- Best correlate of insulin resistance in women with PCOS. |
- Subfertility of women with PCOS |
ANDROGEN EXCESS OR HYPERANDROGENISM
- Ovary |
- Adrenal gland |
- Adrenal gland |
- Adipose tissues |
11-oxygenated androgens - most abundant androgens in women with PCOS |
CHARACTERISTIC ENDOCRINE FINDINGS
- Abnormal gonadotropin secretion |
- Increased gonadotropin-releasing hormone (GnRH) pulse amplitude |
- Increased pituitary sensitivity to GnRH |
- Elevated LH level or elevated LH/FSH ratio- not be used as diagnostic tools |
- Increased levels of biologically active (non-sex hormone-binding globulin [shbg]-bound) estradiol |
- Increase estrone → increased peripheral (adipose) conversion of androgen |
- Increased levels of biologically active estradiol → elevated LH levels and anovulation |
- Elevated androgens |
- Serum testosterone levels - 0.55 to 1.2 ng/ml |
- Androstenedione levels are usually from 3to5 ng/ml |
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INSULIN RERSISTANCE
- Insulin and insulin-like growth factor 1 (IGF-1) enhance ovarian androgen production |
- High levels of insulin bind to the receptor for IGF-1 |
- The granulosa cells also produce IGF-1 receptor and IGF-binding proteins (IGFBPs). |
- Paracrine control |
-Enhancement of LH stimulation |
-Production of androgens by the theca cells |
- Elevated insulin levels stimulate adipocyte production of adipokines interfere → with the metabolism and breakdown of adipose tissue and further enhance IR |
- Insulin resistance in peripheral tissues |
- Muscle |
- Adipose |
- Ovary or adrenal |
- Signaling abnormalities |
- Euglycemia with peripheral IR |
- Severe cases - beta cell (secretory) dysfunction |
- Testing should be directed at ruling out diabetes and glucose intolerance |
- Measurement of the level of hemoglobin A1C |
- Prediabetes greater than 5.8% |
- Frank diabetes greater than 6% |
- Clamp test |
- Intravenous frequent sampling glucose tolerance test, or insulin tolerance |
ACANTHOSIS NIGRICANS (AN) |
- 30% of hyperandrogenic women |
- 50% of women with PCOS who are hyperandrogenic and obese |
- Velvety hyperpigmentation |
- Nape of the neck |
- Axilla |
- Vulva regions |
Hyperandrogenism, IR, and AN (HAIR-AN syndrome) |
-Associated with insulin receptor antibodies |
-Very high insulin levels |
- Severe IR |
ANTIMÜLLERIAN HORMONE IN PCOS
Müllerian-inhibiting substance (MIS) or AMH |
-Glycoprotein produced by the granulosa cells of preantral follicles |
- Elevated in women with PCOS |
- Pathophysiology of anovulation in PCOS |
- Used as a blood test to substitute for US findings of a polycystic ovary |
>4.7 ng/mL → PCOS |
PATHOPHYSIOLOGIC CONSIDERATIONS
Genetic predisposition |
- Susceptibility genes |
- 2p16.3 |
- 2p21 |
- 9q33.3 |
- LH/human chorionic gonadotropic (HCG) receptor thyroid adenoma locus |
- DENND1A |
- Environmental factors |
PATHOPHYSIOLOGIC CONSIDERATIONS
PATHOPHYSIOLOGIC CONSIDERATIONS
- Genetic factors |
- Environmental factors |
- Endocrine disturbances |
- PAO: normal menses, normal androgen levels, and normal ovulatory function and parity may develop a full-blown syndrome (PCOS) |
- Normal homeostatic factors → ward off stressors or insults |
- Homeostatic mechanisms → symptoms of PCOS to emerge with varying degrees of severity |
- 2 Major insults |
- Weight gain |
- Psychological stress |
PATHOPHYSIOLOGIC CONSIDERATIONS
CONSEQUENCES OF POLYCYSTIC OVARY SYNDROME
- Metabolic risk |
- Cardiovascular risks |
- Cancers risk with aging |
Multidisciplinary approach |
- With aging |
- Cardiovascular disease |
- Hypertension |
- Metabolic syndrome |
- Diabetes |
- Cancer (endometrial and ovarian) |
CONSEQUENCES OF POLYCYSTIC OVARY SYNDROME
WEIGHT GAIN/OBESITY AND METABOLIC SYNDROME
- Weight → major predictor of abnormal metabolic findings → cardiovascular (CV) disease risks |
- Increased abdominal and visceral fat in women with PCOS |
- Treatment: lifestyle management |
- Metabolic syndrome |
- Diabetes |
- CV disease (CVD) |
WEIGHT GAIN/OBESITY AND METABOLIC SYNDROME
Adult Treatment Panel III criteria (3 of 5) |
- Waist circumference >88cm |
- High-density lipoprotein |
- Triglycerides >150 mg/dl |
- Blood pressure >130/85 mmhg |
- Fasting blood sugar >110 mg/dl) |
DIABETES
- Type 2 diabetes mellitus is more prevalent (2-3 times higher) |
- Screen for diabetes in the overweight population with PCOS |
- Oral glucose tolerance test |
- Management |
- Diet and exercise |
- Metformin - doses of 1500 mg/day |
QUALITY-OF-LIFE ISSUES
Poor quality of life |
- Burden of being overweight |
- Having irregular cycles |
- Decreased fertility |
- Skin concerns such as acne and hirsutism |
- Depression |
- Anxiety disorder |
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CARDIOVASCULAR CONCERNS
- Lipid and lipoprotein abnormalities |
- Hypothetical scheme for increasing CV risk in women with PCOS with various phenotypes. |
- "Unless a woman with PCOS has "classic" features of PCOS and has diabetes and obesity, there is no evidence for increased CV morbidity and mortality in women with PCOS." |
CARDIOVASCULAR CONCERNS
CANCERS IN POLYCYSTIC OVARY SYNDROME
- Endometrial cancer can begin at a younger age |
- Long-term anovulation |
- Unopposed estrogen stimulation of the endometrium |
- Increased risk for endometrial and ovarian cancer |
- Milder phenotypes - little or no increased risk |
- Endometrial cancer - increased at least 2-3 fold |
- Ovarian cancer - 2.5 time increased |
- Use of oral contraceptives |
- Metformin - inhibitory effects on various cancers |
CANCERS IN POLYCYSTIC OVARY SYNDROME
OVARIAN AGING: PCOS AND MENOPAUSE
- Ovaries decrease in size and androgen levels decrease |
- As women with PCOS age |
- Become more regular and ovulatory |
- Decrease in the total follicular cohort |
- Lower levels of AMH |
-Preserved fertility in women with PCOS as they age |
Menopause |
- Hirsutism may still be prevalent T |
- Persistence of the metabolic issues |
- Continued vigilance in managing and following |
TREATMENT OF POLYCYSTIC OVARY SYNDROME
➤ Androgen excess and symptoms of hyperandrogenism |
➤Irregular bleeding and risks of endometrial disease as a result of unopposed estrogen stimulation from anovulation |
➤Fertility concerns and subfertility, mostly because of anovulation |
Lifestyle management |
- Use of an OC, with or without an antiandrogen - Androgen excess |
- OCS -> Reduce the risk of endometrial cancer |
- Supplying the missing progesterone in anovulatory - Irregular bleeding |
- Progestogen therapy |
- 2 to 3-month intervals |
- Medroxyprogesterone acetate (5-10mg) |
- Norethindrone acetate (2.5 to 10 mg) |
- Ovulation induction - subfertility |
TREATMENT OF SUBFERTILITY IN PCOS
Ovulation induction |
- Metformin |
- Clomiphene - after obtaining a semen analysis |
-Letrozole - 2.5 to 5 mg/day, 5 days; first-line treatment |
- Gonadotropins - Low-dose is highly effective as a second-line treatment |
- pulsatile GnRH - less effective |
- ovarian diathermy or drilling - second-line therapy, particularly in clomiphene failures |
Adjunctive measures |
-Dexamethasone |
- Dopamine agonists |
- Thiazolidinediones |
IVF - fail to conceive with ovulation induction over 6 cycles and with other infertility factors |
METABOLIC AND WEIGHT CONCERNS
Exercise regimens |
Metabolic syndrome (MBS) |
- Combination of diet and metformin |
- • Reduce weight by 5-7% |
- Reduce insulin resistance Improve metabolic parameters |
Bariatric surgery |
Antiandrogens (flutamide) |
Drospirenone and 17alpha- ethinylestradiol (EE2) with flutamine and metformin - adolescents |
METABOLIC AND WEIGHT CONCERNS
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