Polycystic Ovarian Syndrome Case File
Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD
CASE 52
A 23-year-old G0P0 woman presents to the office with complaints of irregular cycles since menarche. Upon further questioning, she has also noticed an increase in facial hair and acne for many years. She denies any history of medical problems and has a strong family medical history of diabetes. On examination, she is noted to have a normal blood pressure (BP), pulse, respiratory rate, and temperature. She is obese with a body mass index (BMI) of 34 kg/m2. She is noted to have some hirsutism and acanthosis nigricans (of neck and inner thighs). Her pelvic examination is limited by her obesity but normal. She does not desire pregnancy at this time. Her pregnancy test is negative.
» What is the most likely diagnosis?
» What complications is the patient at risk for?
» What is your next diagnostic step?
» What is your therapeutic plan for this patient?
ANSWER TO CASE 52:
Polycystic Ovarian Syndrome
Summary: A 23-year-old woman with a long-standing history of irregular cycles, obesity, hirsutism, and acne.
- Most likely diagnosis: Polycystic ovarian syndrome.
- Complications: Diabetes mellitus (DM), endometrial cancer, hyperlipidemia, metabolic syndrome, cardiovascular disease.
- Diagnostic steps: Thyroid-stimulating hormone (TSH), prolactin, serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxyprogesterone, pelvic ultrasound.
- Therapeutic plan: Regulate menstrual cycles with combination oral contraceptives and screen for metabolic abnormalities (diabetes, lipid panel, etc). Encourage diet and exercise.
ANALYSIS
Objectives
- Know the clinical presentation and diagnostic criteria of polycystic ovarian syndrome (PCOS).
- Understand the work-up needed for the diagnosis.
- Become familiar with basic management strategies.
Considerations
The patient is a 23-year-old G0P0 woman with classic presentation of PCOS. The diagnostic criteria require two out of the three following signs and symptoms: oligomenorrhea/ amenorrhea, hyperandrogenism (not otherwise explained), or evidence of small multiple ovarian cysts on transvaginal ultrasound. The ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH) is often cited as a supporting diagnostic factor; however, this lab finding is inconsistent and unreliable. She has chronic menstrual cycle irregularities, obesity, and signs of hyperandrogenism (acne, hirsutism). The presence of acanthosis is a sign of insulin resistance. After exclusion of secondary causes of hyperandrogenism (late onset congenital adrenal hyperplasia, hyperprolactinemia, adrenal/ ovarian tumors, Cushing syndrome, thyroid disorders), the diagnosis can be made. Management depends on fertility desires. When the patient does not desire a pregnancy, her menstrual cycles are best regulated with combined oral contraceptive pills. Diet and exercise are important in treating the patient. She should be assessed for metabolic abnormalities, as this patient is at high risk for chronic conditions such as type 2 diabetes and cardiovascular disease. Ovulation induction may be necessary if the patient desires a pregnancy.
APPROACH TO:
Polycystic Ovarian Syndrome
DEFINITIONS
POLYCYSTIC OVARIAN SYNDROME: A condition of unexplained hyperandrogenic chronic anovulation associated with excessive estrogen. Criteria for diagnosis: (need two out of three): (1) Hyperandrogenism, (2) oligomenorrhea or amenorrhea, and (3) polycystic ovaries by ultrasound.
HIRSUTISM: Excessive terminal hair growth in male pattern of distribution.
BMI: Statistical measurement used to identify obesity taking into account a person’s height and weight (weight in kg divided by height in m2). The normal BMI range is considered to be 18.5 to 24.9.
ACANTHOSIS NIGRICANS: Velvety, mossy, verrucous, hyperpigmented skin usually noted on the back of the neck, in the axilla, and under the breasts, usually a sign of insulin resistance.
CLINICAL APPROACH
One would think by the name PCOS, the development of polycystic ovaries is a central feature for the hyperandrogenic chronic anovulation state. However, the polycystic ovary can occur with any state of anovulation and should be viewed as a sign but not a disease. Consequences of persistent anovulation include infertility, menstrual irregularities, androgen excess (hirsutism, acne, and alopecia), and increased risk of endometrial cancer, cardiovascular disease, and diabetes mellitus. Hyperandrogenic anovulation is reported to occur in 4% to 6% of women.
When evaluating patients with suspected PCOS, a thorough history and physical should be performed. Other causes of hyperandrogenic anovulation should be excluded. Important information to obtain from the patient includes her menstrual history, onset, and duration of androgen excess, medications, family history (especially of diabetes and cardiovascular disease), and lifestyle factors (exercise, smoking, alcohol). The physical examination, should carefully evaluate the body hair distribution and other signs of androgen excess (acne, temporal balding). The presence of acanthosis should be noted, and a pelvic examination should be performed to assess for ovarian enlargement.
Laboratory studies which need to be considered are TSH, prolactin, lipid profile, glucose-intolerance screening, endometrial biopsy (in patients with long-standing anovulation and unopposed estrogen exposure), and 17-hydroxyprogesterone (congenital adrenal hyperplasia). Testosterone and DHEA-S levels can be assessed when clinical signs of excess androgen stimulation are present or if an androgen-secreting tumor is suspected. The majority of testosterone is produced by the ovary, whereas, DHEA-S is almost exclusively secreted by the adrenal gland.
Besides the clinical examination, pelvic sonography revealing multiple small follicles on the ovaries is often one of the diagnostic criteria. More specifically, usually the presence of 12 or more follicles in each ovary measuring 2 to 9 mm in diameter or increased ovarian volume > 10 mL is considered to be polycystic. It is called the “string of pearls” sign since the small follicles line the periphery of the ovary.
Overall treatment goals are to:
- Reduce circulating androgen levels
- Protect the endometrium from unopposed estrogen and reduce risk of endometrial cancer
- Encourage weight loss and healthy lifestyle changes
- Induce ovulation when pregnancy is desired
- Monitor for the development of diabetes and cardiovascular disease and modify risk factors if possible (smoking cessation, lipid-lowering agents, etc)
Combination oral contraceptives have been the primary management of longstanding PCOS. They are effective in regulating dysfunctional bleeding, limiting unopposed estrogen (thus reducing endometrial cancer risk), increasing the sex hormone-binding globulin (decreases free androgen levels), and suppressing ovarian androgen production. Weight loss can reduce both hyperinsulinemia and hyperandrogenism. These benefits can be seen with as little as 5% weight loss. Insulin-lowering agents, such as metformin can be helpful in reducing the hyperinsulinism and thus limiting the risk of developing cardiovascular disease and diabetes mellitus.
For patients desiring pregnancy with a BMI < 30, clomiphene citrate is the agent of choice; however, for those patients with a BMI >30, letrozole (aromatase inhibitor) is the first-line. Metformin should only be used for glucose intolerance.
|
CASE CORRELATION
|
COMPREHENSION QUESTIONS
52.1 A 32-year-old G0P0 woman is noted to have irregular menses and hirsutism. Which of the following is consistent with polycystic ovarian syndrome?
A. Elevated 17-hydroxyprogesterone levelB. Finding of a 9-cm right ovarian massC. Vaginal bleeding after a 5-day course of progesterone oral therapyD. DEXA scan showing osteopenia
52.2 A 29-year-old G0P0 woman with a diagnosis of PCOS is being counseled about the dangers of her condition. In particular, she is cautioned about the possibility of developing metabolic syndrome. Which of the following is the most significant consequence of metabolic syndrome?
A. HyperthyroidismB. Cardiovascular diseaseC. Breast cancerD. Renal insufficiency
52.3 A 28-year-old G0P0 woman has a chronic history of oligomenorrhea and amenorrhea. She undergoes an endometrial biopsy in light of her long history of anovulation, which returns as Grade 1 adenocarcinoma of the endometrium. Magnetic resonance imaging seems to indicate that the endometrial cancer is isolated to the uterus. The patient desires to have children if possible. Which of the following is the best therapy for this patient?
A. Endometrial ablationB. Radical hysterectomyC. Cervical conizationD. High-dose progestin therapyE. Oral contraceptive agent
ANSWERS
52.1 C. PCOS is characterized by obesity, anovulation, hyperandrogenism due to ovarian secretion of testosterone, after excluding other etiologies such as congenital adrenal hyperplasia (CAH), Sertoli– Leydig cell tumor, hypothyroidism and hyperprolactinemia. An elevated 17-hydroxyprogesterone level would indicate CAH. A 9-cm ovarian mass would suggest a Sertoli–Leydig cell tumor. With PCOS, the DEXA scan usually shows good bone density due to the excess estrogen environment. Women with PCOS usually will have a positive progestin challenge test; in other words, they have bleeding with a 5- to 10-day course of oral progestin.
52.2 B. Metabolic syndrome is characterized by hyperlipidemia, glucose intolerance, hypertension, and central obesity. Patients with metabolic syndrome are at greatly increased risk of cardiovascular disease, particularly when the glucose intolerance is present.
52.3 D. Young patients with chronic anovulation due to PCOS are at risk for endometrial cancer. The lesions are almost always Grade 1, and are usually treated with hysterectomy and surgical staging. In selected circumstances, high-dose progestin therapy and repeat of the endometrial sampling in 2 to 3 months is possible for those who desire a pregnancy. Hysterectomy is usually recommended after childbirth. The chronic estrogen exposure without progestin is the reason for development of endometrial cancer.
CLINICAL PEARLS
|
» Polycystic ovary syndrome is a common cause of chronic hyperandrogenic anovulation, and its diagnosis is made after other secondary causes have been ruled out. » Testosterone is largely secreted by the ovary whereas DHEA-S is secreted by the adrenal gland. » Patients with PCOS should be screened for glucose intolerance and lipid abnormalities. » Combined oral contraceptive pills are the primary management for irregular cycles and also decrease androgen levels. » An endometrial biopsy should be considered in patients with longstanding anovulation and unopposed estrogen. |
REFERENCES
Alexander CJ, Mathur R, Laufer LR, Aziz R. Amenorrhea, oligomenorrhea, and hyperandrogenic disorders. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 6th ed. Philadelphia, PA: Saunders; 2015:355-367.
American College of Obstetricians and Gynecologist. Polycystic ovary syndrome. ACOG Practice Bulletin 108. Washington, DC; 2009. (Reaffirmed 2013.)
Fritz M, Speroff L. Anovulation and the polycystic ovary. In: Clinical Gynecologic Endocrinology and Infertility. 8th ed. New York, NY: Lippincott Williams and Wilkins; 2010:465-498.
Legro, RS, Brzyski RG, Diamond MP, et al. Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome. N Engl J Med. 2014;371(2):119-129.
Lobo RA. H yperandrogenism. In: Katz VL, Lentz GM, Lobo RA, Gersenson DM, eds. Comprehensive Gynecology. 6th ed. Philadelphia, PA: Mosby-Year Book; 2012:849-867.
0 comments:
Post a Comment
Note: Only a member of this blog may post a comment.