Mary T. Sale and Nancy A. Sokkary
History of present illness
A 26-year-old gravida 0 woman presents with complaint of 6 months of amenorrhea. She reports menarche at age 13 and describes her periods as having always been irregular. Over the last two years they have become increasingly less frequent. She has also experienced weight gain and increasingly troublesome facial hair growth. She denies any vaginal dryness, hotflashes, nipple discharge, or new headache.
She is sexually active with her long-term boyfriend. They use condoms for contraception. Her only prior surgery was a laparoscopic appendectomy. She has no other significant med- ical or family history. She takes no medications.
Physical examination
General appearance:Well-nourished woman in no acute distress
Vital signs:
Temperature: 37.0°C Pulse: 64 beats/min
Blood pressure: 142/88 mmHg Respiratory rate: 14 breaths/min Oxygen saturation: 98% on room air Weight: 224 lb
Height: 66 inches BMI: 36 kg/m2
Neck:Supple, no thyromegaly
Cardiovascular:Regular rate and rhythm Lungs:Clear to auscultation bilaterally
Breast:Symmetric, no nipple discharge, no lumps Abdomen:Soft, nondistended, nontender in all quadrants
Pelvic:
Normal appearing external female genitalia with excessive pubic hair extending to the inner thighs
Speculum exam: Well rugated, moist vaginal walls. No cervical discharge. Normal appearing nulliparous cervix without lesions
Bimanual exam: Small, anteverted uterus. No cervical motion tenderness. No adnexal masses
Extremities:No clubbing, cyanosis, or edema Neurologic:Nonfocal
Skin:Increased hair growth on chin, upper lip, abdomen, and chest. Moderate acne is present
Laboratory studies:
Urine pregnancy test: Negative
TSH: 3.2 àIU/mL (normal 0.50–4.70 àIU/mL) Serum prolactin: 16 ng/mL (normal for nonlactating women: 2–29 ng/mL)
Imaging:Endovaginal ultrasound was obtained (Figs 67.1 and67.2)
How would you manage this patient?
This patient has secondary amenorrhea due to polycystic ovarian syndrome (PCOS). She was counseled on lifestyle modifications and prescribed cyclical oral contraceptive pills. She began a vigorous exercise program and lost 35 lb.
Her acne improved. Nine months later, she discontinued her oral contraceptive pills and had spontaneous regular monthly cycles.
Secondary amenorrhea is defined as greater than three months without a period in a woman who has undergone menarche. In the acute setting it is sufficient to rule out common causes of amenorrhea: pregnancy, thyroid dysfunc- tion, and hyperprolactinemia. However, the evaluation (Table 67.1) may need to be more extensive depending on the symptoms associated with amenorrhea. If other symptoms such as hot flashes or vaginal dryness are present, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) should be tested to evaluate for primary ovarian insuffi- ciency (POI). If women are underweight or have other sys- temic illnesses, gonadotropin (FSH and LH) levels should also be evaluated to assess for hypogonadotropic hypogonadism.
Alternatively, a progestin challenge can be given to evaluate for endogenous estrogen production. If androgenic symptoms are present, like this case, PCOS should be considered. This patient has secondary amenorrhea with clinical symptoms of androgen excess including acne and increased hair growth.
Her initial laboratory evaluation was unremarkable, excluding other causes. Her endovaginal ultrasound demonstrated mul- tiple peripheral cysts (Fig. 67.1) and ovarian volume greater than 10 cm3(Fig. 67.2). She meets criteria for the diagnosis of PCOS.
Polycystic ovarian syndrome
Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that can present at any time during a woman’s repro- ductive years, and affects from 6 to 15% of women [1,2,3].
Woman with PCOS typically have a combination of irregular
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
Fig. 67.2 Endovaginal ultrasound demonstrating right ovary in 26-year-old woman with amenorrhea.
Fig. 67.1 Endovaginal ultrasound demonstrating left ovary in 26-year-old woman with
amenorrhea.
cycles or secondary amenorrhea, hyperandrogenism, and abnormal ovarian morphology [1]. Three different diagnostic criteria exist. They all require at least two of the following:
anovulation, clinical or laboratory evidence of hyperandrogen- ism, and polycystic ovaries on ultrasound. They also require exclusion of other diagnosis (Table 67.1) [2].
The pathophysiology of PCOS is complex and not entirely understood. Hyperandrogenism may be due to increased ovarian sensitivity to LH or abnormal gonadotropin-releasing hormone (GnRH) pulsatility resulting in increased circulating LH. Insulin resistance also plays a key role in increased andro- gen levels [2,4]. While the syndrome likely startsin uteroand has a heritable component, environmental factors such as obesity also contribute [4].
Evaluation of secondary amenorrhea includes a full history and physical examination to evaluate for symptoms of hypo- thyroidism, pregnancy, primary ovarian insufficiency, and hyperprolactinemia. When PCOS is considered as part of the differential, pelvic ultrasound should be considered. Polycystic ovaries on ultrasound are defined as the presence of 12 or more antral follicles measuring 2–9 mm in diameter (Fig. 67.1), or total ovarian volume greater than 10 mL (Fig. 67.2) [3]. Sonographicfindings of polycystic ovaries are observed in 20–30% of the general population and by them- selves are not diagnostic for PCOS [2]. Laboratory tests should be performed to rule out other etiologies of secondary amen- orrhea or oligomenorrhea. If androgen symptoms are severe, the differential diagnosis should be expanded to include an androgen-secreting tumor and if the patient is an adolescent, testing should be performed for late-onset congenital adrenal hyperplasia (Table 67.1).
Patients with PCOS can experience secondary amenorrhea due to anovulation. The consequent unopposed estrogen can lead to endometrial hyperplasia which, if left untreated, can progress to uterine cancer [1,4]. In a patient with anovulation,
one goal of therapy is to prevent endometrial hyperplasia either through resumption of spontaneous cycles or adminis- tering progestin. In a woman presenting with history of prolonged anovulation due to PCOS, endometrial biopsy should be performed to evaluate for endometrial hyperplasia or cancer. Biopsy should be performed in women over age 45 who have bleeding from suspected ovulatory dysfunction.
The American College of Obstetricians and Gynecologists guidelines [5] recommend endometrial sampling in younger women if they have had“prolonged” periods of unopposed estrogen or have failed medical treatment. The guidelines do not define “prolonged” but a determination should be made based on length of unopposed estrogen in conjunction with other risk factors such as degree of obesity [5]. If abnormal- ities are diagnosed, they should be treated. If the biopsy shows no evidence of hyperplasia or cancer, multiple hormonal therapies exist for prevention of hyperplasia. Hormonal therapy requires the delivery of progestin, which can be administered through combined hormonal contraceptives (pills, patch, or ring), or cyclic or continuous progestin alone.
Frequently used progestins include oral medroxyprogesterone (10 mg PO for 10–14 days each month) or depot medroxy- progesterone acetate (150 mg IM every 3 months). The levonorgestrel intrauterine device is another convenient way of delivering continuous progestin. Combined hormonal con- traceptives have the added benefit of improving androgenic symptoms. While nearly all patients can be managed with medical therapy, hysterectomy is a potential option in women who have completed childbearing and do not tolerate or cannot comply with medical therapy [5].
Other treatment options can be used in combination.
Therapy for PCOS includes lifestyle modification, particularly weight reduction, metformin, and anti-androgens. Lifestyle modification including diet and cardiovascular exercise is first-line therapy for this patient because she is obese. A 5%
reduction in body mass index leads to resumption of spontan- eous menses in 60% of women with PCOS [6]. Weight loss can also decrease the risk of hyperplasia by decreasing peripheral estrogen production. Metformin improves metabolic param- eters and is also effective in decreasing serum androgens and promoting the return of spontaneous menstrual cycles. Some studies have found a resumption of regular cycles in 50% of women within 6 months of initiation of metformin [6]. Anti- androgens, including spironolactone,flutamide, andfinaster- ide have not been found to have an additional treatment benefit when used in combination with oral contraceptive pills [1]. Clomiphene citrate is effective for ovulation induction in women with PCOS-related infertility [6].
Key teaching points
Polycystic ovarian syndrome (PCOS) is a diagnosis of exclusion. Other causes of amenorrhea and excessive androgen syndromes must be excluded to make the diagnosis.
Table 67.1 Laboratory evaluation of oligoovulation/secondary amenorrhea
Differential diagnosis Laboratory test
Pregnancy Urine pregnancy test or
serum beta-hCG
Hypothyroidism TSH
Hyperprolactinemia Prolactin
Hypogonadotropic-hypogonadism/
primary ovarian insufficiency LH/FSH, estradiol Androgen-secreting tumor* Testosterone, DHEA-S Late-onset congenital adrenal
hyperplasia† 17-
Hydroxyprogesterone
* Significant signs of androgenization
†Adolescents
DHEA-S, dehydroepiandrosterone sulfate; FSH, follicle-stimulating hormone;
hCG, human chorionic gonadotropin (hCG); LH, luteinizing hormone; TSH, thyroid-stimulating hormone.
Case 67: A 26-year-old woman with secondary amenorrhea
Diagnostic criteria for PCOS include anovulation, clinical, or laboratory evidence of hyperandrogenism, and
sonographic evidence of abnormal ovaries (>12 follicles measuring 2–9 mm or total ovarian volume>10 mL).
Women with secondary amenorrhea from PCOS are at increased risk of endometrial hyperplasia and malignancy.
Cyclic or continuous progestin is effective for protecting the endometrium in women with anovulation or oligoovulation from PCOS. Progestin can be delivered through combined hormonal contraceptives, oral progestin, depot medroxyprogesterone, or the levonorgestrel intrauterine device.
References
1. Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/
ASRM-Sponsored 3rd PCOS Consensus Workshop Group.Fertil Steril2012;97(1):28–38.
2. Azziz R, Carmina E, Dewailly D, et al.
The Androgen Excess and PCOS Society criteria for the polycystic ovary
syndrome: The complete task force report.Fertil Steril2009;91(2):
456–88.
3. Hart R, Hickey M, Franks S.Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome.
Best Pract Res Clin Obstet Gynaecol 2004;18(5):671–83.
4. American College of Obstetricians and Gynecologists. Polycystic ovary syndrome. Practice Bulletin
No. 108.Obstet Gynecol2009;114:
936–49.
5. American College of Obstetricians and Gynecologists. Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No. 136.Obstet Gynecol2013;122:176–85.
6. Bates GW Jr., Propst AM. Polycystic ovarian syndrome management options.Obstet Gynecol Clin North Am 2012;39(4):495–506.