Anita K. Blanchard
History of present illness
A 25-year-old gravida 0, para 0 woman presents to the emer- gency department complaining of heavy vaginal bleeding. Her current menses began eight days ago preceded by a three-month absence of menses. She reports menarche at age 16 with irregu- lar cycle intervals. She notes an alternating pattern of absent menses for 6–12 weeks followed by heavy bleeding lasting up to 10 days. Currently she notes passage of quarter-sized clots and soaked pads every four hours. She complains of fatigue but denies any dizziness. She denies abdominal pain, nausea, vomiting, or diarrhea. She denies any history of blood dyscrasia, epistaxis, or bruising. She is sexually active with one male partner. They intermittently use male condoms for contracep- tion. No vulvar, vaginal, or abdominal trauma is reported. She is otherwise healthy and takes no other medications.
Physical examination
General appearance:A well-hydrated woman in no distress Vital signs:
Temperature: 37.1°C Pulse: 88 beats/min
Blood pressure: 102/64 mmHg Respiratory rate: 12 breaths/min BMI: 36 kg/m2
HEENT:No goiter or thyroid prominence
Cardiovascular:Regular rate and rhythm without murmur or gallop
Lungs:Clear to auscultation bilaterally Breasts:No discharge, no masses bilaterally
Abdomen:Soft, nondistended and nontender to palpation, bowel sounds present
Pelvic:Normal external genitalia, no clitoromegaly. Blood noted at the introitus. Approximately 7 cc of dark blood is seen in the vagina. Normal appearing cervix; no vaginal or cervical lacerations or lesions are noted. Normal-sized, anteverted uterus with no adnexal masses palpated
Neurologic:Alert and oriented, nonfocalfindings on exam Skin:No frontal balding, mild acne, mild hirsuitism with skinfindings notable for hair growth on upper lip, chin, mid-sternum, periaerolar region, and thighs
Laboratory studies:
Urine hCG test: Negative
A CBC is ordered: Hb was 9.4 mg/dL
Imaging:Transvaginal ultrasound images reveal a normal- sized anteverted uterus. Ovaries are normal size with 12–14 follicles noted on the periphery of each ovary (Fig. 68.1)
How would you manage this patient?
This patient has chronic anovulation as a result of polycystic ovary syndrome. She was treated with a combined oral contra- ceptive pills to regulate her cycle and was scheduled to return to the outpatient clinic for further evaluation of her androgen excess.
Anovulation and the differential diagnosis
Pregnancy and malignancy should be excluded in any reproductive-aged woman who presents with abnormal vaginal bleeding. The source of the bleeding should also be confirmed.
Abnormal uterine bleeding associated with ovulatory dysfunc- tion is characterized by irregular uterine bleeding in which uterine structural abnormalities have been ruled out by imaging, typically transvaginal ultrasonography. Irregular uterine bleeding can be ovulatory or anovulatory. Causes of anovulation include physiologic etiologies associated with adolescence, perimenopause, pregnancy, or lactation. With the onset of menstruation, anovulation is frequent. It is esti- mated that 85% of menstrual cycles are anovulatory in the 1st year after menarche. This percentage decreases to about 59%
by year 3 of menstruation [1]. Pathologic causes of anovula- tion include endocrine abnormalities such as hyperandrogenic disorders, hypothalamic dysfunction, pituitary and thyroid disorders, and premature ovarian failure. Iatrogenic causes include radiation and medications, particularly chemotherapy and exogenous hormones.
Chronic anovulation is common in reproductive-aged women and is often characterized by oligomenorrhea followed by heavy and or prolonged menses. In the absence of ovula- tion, the corpus luteum does not form and the ovary does not secrete progestin to stabilize and differentiate the endometrial lining. Unopposed estrogen promotes stimulation and prolif- eration of the endometrium, which continues without the progesterone withdrawal-induced menstrual shedding. The thickened endometrium is vascular and lacks stromal support [2]. When bleeding occurs there is irregular, unsynchronized shedding of the lining producing noncyclic, unpredictably heavy, and prolonged menses. Patterns of irregular bleeding from chronic anovulation may be reported as early as menar- che and can continue until menopause. In patients who
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
present with vaginal bleeding with chronic anovulation, urgent or long-term intervention strategies depend on the acuity of the bleeding episode including quantifying the amount of blood loss, assessing active bleeding and identifying symptom- atic anemia. A subset of patients with chronic anovulation have polycystic ovary syndrome.
Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) was first described by Irving Stein and Michael Leventhal in 1935 [3]. PCOS is a clinical diagnosis that may present with a spectrum of symp- toms. There are several classification systems that have been used to define PCOS (Table 68.1) [4,5,6,7]. The Rotterdam criteria revised in 2003 provide the most commonly used definition [5]. Menstrual irregularity, androgen excess and ovarian morphologic changes are defining characteristics of PCOS. The prevalence of PCOS is estimated at 5–8% in women [8]. It is the most common endocrine disorder in reproductive-aged women. The pathophysiology of the dis- order is not completely understood but the familial associ- ations imply a genetic component. The clinical presentation of PCOS including the symptoms and comorbidities can vary with a heterogeneous phenotypic expression.
Management of PCOS is based on symptoms. In the cur- rent clinical scenario, the patient presents with an eight-day history of menorrhagia. Acute management focuses on assess- ment of hemodynamic state and blood loss. She is not actively bleeding and her anemia is relatively asymptomatic. Chronic anovulatory bleeding in a nonacute setting can be managed on an outpatient basis with hormonal regulation of the cycle.
Treatment options include combined oral contraceptive pills and progestins, including medroxyprogesterone acetate or the levonorgestrel intrauterine device. If active hemorrhage is noted resulting in severe anemia, blood transfusion may be indicated with a short course of intravenous estrogen therapy until the bleeding subsides. Supplemental iron therapy should be initiated to replace depleted iron stores. Long-term hormo- nal interventions depend on patient history, contraceptive needs, and fertility planning.
After an acute assessment and plan, long-term follow-up addressing health implications of PCOS is imperative. In addition to menstrual irregularity, other potential sequelae of PCOS including androgen excess, obesity, insulin resistance, and infertility should be properly managed in an outpatient setting.
Patients with features of androgen excess should complete an endocrine evaluation to rule out alternative causes of
Fig. 68.1 Transvaginal ultrasound.
hirsuitism. A biochemical assessment of hyperandrogenism identifies other endocrinopathies, including late-onset con- genital adrenal hyperplasia and Cushing syndrome.
Androgen-secreting tumors of the ovary or adrenal are also excluded (Fig. 68.2). The clinical assessment of androgen excess is subjective, both age and ethnicity may contribute to
body hair distribution. The Ferriman Gallwey score is some- times used by clinicians as a standard method of documenting hirsutism. Approximately 5% of reproductive-aged women are hirsute as defined by a Ferriman Gallwey score above 8. PCOS is the most common endocrine disorder associated with hir- sutism. Oral contraceptive pills are thefirst line of treatment in
Table 68.1 Diagnostic criteria for PCOS
NIH 1990 [4] Chronic anovulation
Clinical and/or biochemical signs of hyperandrogenism (with exclusion of other etiologies; e.g., congenital adrenal hyperplasia)
(Both criteria needed)
Rotterdam criteria 2003 [4,5] Oligomenorrhea and/ or anovulation
Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries
(Two of three criteria needed)
AE-PCOS Society 2006 [4] Clinical and or biochemical signs of hyperandrogenism
Ovarian dysfunction (oligo-anovulation and/or polycystic ovarian morphology) (Both criteria needed)
NIH Methodology Workshop on
PCOS 2012 [6] Recommend maintaining the broad inclusionary diagnostic criteria of Rotterdam while specifically identifying the phenotype:
Androgen excess + ovulatory dysfunction Androgen excess + polycystic ovarian morphology Ovulatory dysfunction + polycystic ovarian morphology
Androgen excess + ovulatory dysfunction + polycystic ovarian morphology AE, Androgen excess; NIH, National Institutes of Health; PCOS, polycystic ovary syndrome.
Irregular menses Exclude the following differenal diagnoses:
Pregnancy
Androgen-secreng tumor of adrenal origin Androgen-secreng tumor of ovarian origin
Hyperprolactemia Hypothyroidism
Nonclassical congenital adrenal hyperplasia Cushing syndrome
Acromegaly
PCOS confirmed by the following criteria:
Oligomenorrhea and/or anovulaon Clinical and/or biochemical signs of
Hyperandrogenism Polycysc ovaries (two of three criteria needed)
Assess for metabolic syndrome
Assess for glucose intolerance
Assess manifestaons of menstrual disorder
Hormonal intervenon Cycle regulaon Ovulaon inducon for ferlity
Long-term assessment of risk of endometrial pathology Assess for other phenotypic
sequelae including hirsusm, acne, obesity, sleep apnea
Fig.68.2 Algorithm for evaluation of irregular menses. (Adapted from [9].)
Case 68: Irregular bleeding in a 25-year-old woman
a patient without contraindications. Oral contraceptive pills increase the hepatic production of steroid hormone-binding globulin, which binds free circulating testosterone. Spironolac- tone, an aldosterone antagonist that inhibits dihydrotestoster- one binding and inhibits 5-α reductase, is a second-line therapy that decreases androgen production. Other oral anti- androgen medical therapies includeflutamide andfinasteride.
Cosmetic hair removal and topical eflornithine cream can also retard hair growth.
In addition to irregular bleeding, PCOS has other gyneco- logic impacts, including an increased risk of infertility and endometrial disorders. In evaluating a woman with PCOS who desires pregnancy, other health risks should be excluded.
Counseling and lifestyle modification with an improved diet and exercise regimen may be helpful in an overweight or obese patient. Ovulation induction can be achieved with clomiphene citrate. Successful therapy is noted with a reported cumulative singleton live-birth rate of 72% [10]. Second- and third-line therapy for clomiphene citrate-resistant anovulatory patients may include exogenous gonadotropins, laparoscopic ovarian surgery, or in-vitro fertilization [10]. Long-term anovulation and oligomenorrhea without hormonal regulation also increases the risk of endometrial hyperplasia and endometrial adenocarcinoma. An endometrial biopsy can exclude endo- metrial pathology and in chronic anovulation disordered pro- liferative endometrium is often found. Other assessment modalities include hysteroscopy with dilatation and curettage for individuals at risk.
Patients with PCOS are also at risk for chronic medical disorders including obesity, metabolic syndrome, and insulin insensitivity. These medical disorders can predispose affected patients with PCOS to dyslipidemia, cardiovascular disease, type 2 diabetes mellitus, and sleep apnea. Patients should be adequately screened and counseled about the potential seque- lae of PCOS. Individual risk assessments should be based on the phenotypic presentation.
Key teaching points
Anovulation is a common cause of abnormal uterine bleeding in patients who do not have structural uterine abnormalities.
Patients presenting with anovulation should be evaluated for physiologic and pathologic etiologies. Physiologic causes include adolescence, pregnancy, lactation, and perimenopause. Pathologic causes include
hyperandrogenic anovulation, hypothalamic dysfunction, hyperprolactinemia, thyroid disorder, primary pituitary disease, premature ovarian failure, and iatrogenic sources.
Polycystic ovary syndrome (PCOS) is a common cause of chronic anovulation and androgen excess.
Management of PCOS is based on presenting symptoms.
Minimizing long-time sequelae and comorbidities are optimal treatment strategies.
References
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2. American College of Obstetricians and Gynecologists. Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No. 136.Obstet Gynecol 2013;122:176–85.
3. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women.J Clin Endocrinol Metab 1961;21:1440–7.
4. National Institutes of Health.Evidence- based Methodology Workshop on
Polycystic Ovary Syndrome, December 3–5, 2012. Executive Summary.
Available athttps://prevention.nih.gov/
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5. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
Fertil Steril2004;81:19–25.
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