Polycystic Ovarian Syndrome
Julie Adkins, Jill C. Cash, Mellisa A. Hall, Cheryl A. Glass, Angelito Tacderas, and Jenny Nelson Mullen
Definition
Polycystic ovarian syndrome (PCOS) is characterized by ovulatory dysfunction and hyperandrogenism. It was previously called Stein–Leventhal syndrome, and is a risk factor for metabolic syndrome, infertility, glucose intolerance, and type 2 diabetes mellitus (DM). PCOS itself is not considered a disease; instead, it is a syndrome of coexisting conditions (see Table 24.5).
The American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), and Androgen Excess and PCOS Society (AES) released new guidelines in the evaluation and treatment of PCOS. Highlights are as follows:
A.Diagnostic criteria must include two of the following three conditions: chronic anovulation, hyperandrogenism (clinical/biological) and polycystic ovaries.
B.Exclusion of other androgen excess or related disorders.
C.Although obesity is one of the hallmarks of PCOS, lean women may also have insulin resistance/PCOS. The diagnosis of PCOS is based on medical history, physical examination, and laboratory tests. Aggressive lifestyle modification is the mainstay of all women with PCOS.
Incidence
A.Five to ten percent of women between ages 15 and 44 will develop PCOS. It is the most common worldwide endocrinopathy in women, with five to six million women in the United States experiencing its effects. Up to 70% of PCOS remains undiagnosed.
B.Regarding non-Hispanic White, non-Hispanic Black, and Hispanic women: Hispanic women with PCOS have a higher prevalence of hyperandrogenism and metabolic syndrome; and non-Hispanic Black women have an overall phenotype (genetic makeup) for PCOS than Hispanics and non-Hispanic Whites.
Pathogenesis
A.The exact etiology is unknown; however, PCOS is noted to have insulin resistance and abnormal pituitary function, as well as abnormal steroidogenesis.
Predisposing Factors
A.Obesity.
B.Genetic predisposition, including Mexican American women.
C.Metabolic syndrome.
D.Women with oligo-ovulatory infertility.
E.Type 1, type 2, or gestational diabetes.
F.History of premature adrenarche.
TABLE 24.5 PCOS Associated Symptoms
| Cutaneous signs | Hirsutism Severe acne Alopecia |
| Menstrual irregularity | Oligomenorrhea Amenorrhea Dysfunctional uterine bleeding |
| Obesity | >35 inches (88 cm) waist circumference for women and adolescents >16 years. Standard deviation measurement is used for girls 10–16 years old, >90% |
| Polycystic ovaries | Noted on ultrasound |
PCOS, polycystic ovarian syndrome.
G.First-degree relatives with PCOS.
H.Antiepileptic medications.
Common Complaints
A.Hirsutism.
B.Menstrual problems.
C.Obesity.
D.Infertility.
Other Signs and Symptoms
A.Acne.
B.Alopecia (male pattern).
C.Hyperhidrosis.
D.Acanthosis nigricans.
E.Seborrhea.
Subjective Data
A.Review the patient’s menstruation history:
1.Premature puberty (younger than the age of 8).
2.Primary amenorrhea: Lack of menses by age 15.
3.Oligomenorrhea: Missing four periods per year.
4.Dysfunctional uterine bleeding (DUB): Bleeding at irregular intervals, heavy cycles, periods longer than 7 days.
5.Subfertility or infertility.
B.Review the patient’s history of weight gain, increased waist circumference, and obesity.
C.Review the patient’s history of any skin/hair changes.
D.Psychological: Depression, anxiety, psychosexual dysfunction, eating disorders.
E.Metabolic: Diabetes, dyslipidemia, hypertension (HTN).
F.Review the family history for the presence of diabetes, metabolic syndrome, obesity, and infertility.
Physical Examination
A.Check height, weight, waist circumference, blood pressure (blood pressure), pulse, and respirations.
B.Calculate the body mass index (BMI) and waist-to-hip measurement. Several Internet sites have BMI, body fat, and waist-to-hip ratio calculators.
C.Inspect:
1.Skin:
a.Evaluate hirsutism (upper lip, chin, nape of the neck, periareolar, abdomen-linea alba).
2.Observe fat distribution.
D.Perform pelvic examination to evaluate enlarged ovaries and pelvic masses.
Diagnostic Tests
A.Fasting glucose.
B.Oral Glucose Tolerance Test (OGTT) if fasting glucose is elevated between 100 and 125 mg/dL.
C.Thyroid function tests (thyroid-stimulating hormone [TSH], free T4).
D.Random serum cortisol to rule out Cushing syndrome.
E.Serum luteinizing hormone (LH) and prolactin to rule out hypothalamic and pituitary diseases.
F.Ultrasound to rule out ovarian pathology (as indicated: not required for definitive diagnosis). Ultrasound diagnosis: when 10 small antral follicles are seen bilateral ovaries; unilateral is rare yet clinically significant. For adolescents and young women, ultrasound is not a reliable diagnostic test secondary to studies indicating that up to 70% of very young women may display polycystic ovaries on ultrasound.
G.Insulin-like growth factor (IGF-I).
H.DHEA-S to rule out adrenal hyperandrogenism.
I.Free and total testosterone. Hormonal contraceptive use affects free testosterone; if appropriate reassess after contraceptive has been discontinued for 3 months. Discuss alternate contraception if
necessary.
J.Lipid profile.
K.Endometrial biopsy if indicated for women without menses for 1 year.
L.Pregnancy test prior to start of pharmaceutical therapy and history of an ovulation.
M.Serum 17-hydroxyprogesterone.
N.Positive for anti-Müllerian hormone.
Differential Diagnoses
A.PCOS:
B.Adrenal disorders:
1.Congenital adrenal hyperplasia (CAH).
2.Cushing syndrome.
3.Cortisol resistance.
C.Hyperprolactinemia.
D.Acromegaly.
E.Insulin resistance (types 1 and 2 diabetes).
F.Thyroid dysfunction.
G.Virilizing tumors.
H.Drug-induced:
1.Anabolic steroids.
2.Valproic acid.
Plan
A.General interventions:
1.Aggressive lifestyle modification focusing on increased physical activity and weight reduction is a cornerstone for treatment.
B.Patient education:
1.Exercise recommendations include a minimum of 30 minutes a day of walking at a brisk pace or other activity at a moderate intensity. Start by using a pedometer, walking at breaks, or household work.
2.Weight loss of 5% to 10% or more. Gradual weight loss of 1 to 2 kg per month. Even small amounts of loss are associated with health benefits.
3.Weight loss may cause a resumption of ovulation and the ability to get pregnant.
4.High-fiber, low-fat diet, and reduction of refined sugar.
5.Hair removal can be achieved with shaving, waxing, or use of depilatories. Electrolysis and laser treatment are more expensive therapies for hirsutism.
C.Pharmaceutical therapy:
1.Oral contraceptives (OCPs) are the most commonly used treatment for endometrial prevention and hirsutism:
a.Because of sodium and water retention, weight reduction while on OCPs is more difficult.
b.OCPs that contain 30 to 35 μ of ethinyl estradiol and progestins such as norethindrone (Ortho Micronor), norgestimate (Ortho-Tri-Cyclen), desogestrel (Desogen and Ortho-Cept), or drospirenone (Yasmin) are prescribed for PCOS.
2.Metformin (Glucophage) is used to manage oligomenorrhea, cause weight loss, lower insulin levels, and induce ovulation for women with PCOS:
a.Start metformin 500 mg at the evening meal. The dosage can be increased by 500 mg per week in divided doses up to the maximum of 2,000 mg/d.
b.Titrate slowly because of the GI side effects.
c.Check a metabolic panel before and every 3 to 6 months to evaluate for lactic acidosis.
d.Metformin is contraindicated in patients with renal impairment; assess renal function prior to instituting metformin and monitor regularly.
e.Metformin must be stopped prior to any procedure with radiographic dye.
3.Medroxyprogesterone acetate (Provera) is used for a withdrawal bleed 5 to 10 mg daily for 10 days every 1 to 2 months, or micronized progesterone (Prometrium) 100 to 200 mg by mouth at bedtime for 7 to 10 d/mo is used to protect the endometrium.
4.Spironolactone (Aldactone) 100 to 200 mg twice a day is utilized after a 4- to 6-month oral contraceptive trial as antiandrogen therapy:
a.Spironolactone is also a good alternative when OCPs are contraindicated. However, spironolactone can be used in combination with OCPs.
b.Alternative methods of birth control should be used when spironolactone is used alone secondary to abnormal development of the male fetus external genitalia.
c.Monitor potassium during spironolactone therapy.
5.Eflornithine (Vaniqa) topical may be prescribed to prevent facial hair regrowth.
6.Clomiphene citrate (Clomid) is used to induce ovulation. Weight loss should be attempted prior to starting ovulation induction treatment.
Follow-Up
A.Glucose tolerance needs to be evaluated regularly for patients diagnosed with type 2 DM who are also diagnosed with PCOS (see Table 24.6).
Consultation/Referral
A.Refer to an obstetrician/gynecologist or a reproductive endocrinologist for consultation and management of the following:
1.Infertility/pregnancy.
2.Menstrual bleeding that is not controlled despite OCPs.
B.An endocrinologist may be an appropriate consultation.
C.Consider a nutritional consultation.
Individual Considerations
A.Adults:
1.Women who use OCPs are at increased risk for venous thromboembolism (VTE). Obese patients using OCPs are also at increased risk for VTE. Educate all patients regarding this risk factor and monitor the patient closely for this risk.
2.Obese women older than 40 years of age are at greater risk for VTE. Precautions should be used when prescribing OCPs to this population.
3.Chronic conditions of the patient should also be considered before prescribing OCPs for PCOS. Contraindications to the use of OCPs include patients with a previous history of VTE, HTN, women 35 years or older who smoke 15 or more cigarettes per day, cardiovascular disease (CVD), recent surgery, diabetes, rheumatic diseases, and so forth. The patient’s medical history should be thoroughly evaluated.
B.Geriatrics:
1.Estrogen (oral/transdermal) with or without progestin increases risk for breast cancer, endometrial cancer, and worsening of incontinence, and lacks cognitive and cardiopulmonary protection.