Case-Based Review

Abnormal Uterine Bleeding in Reproductive-Aged Women

Journal of Clinical Outcomes Management. 2015 February;22(2)

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Pathologic causes of anovulatory uterine bleeding include hypothalamic dysfunction (secondary to eating disorders, low BMI), primary pituitary disease, thyroid disease, diabetes, and hyperprolactinemia (not related to lactation). Hyperandrogenic anovulation is another subset of endocrine conditions and includes polycystic ovary syndrome (PCOS). Medications such as antiepileptics, typical and some atypical antipsychotics can contribute by causing weight gain, hyperandrogenism, and elevated prolactin [31,32] (Table 6).

Physical Examination

A thorough history will help to narrow the differential diagnosis. The physical exam can evaluate for other findings that indicate endocrine dysfunction such as low body weight, hirsutism, balding, acne, high blood pressure, obesity (especially centripetal fat distribution). Acanthosis nigricans is a sign of insulin resistance which is part of the pathophysiology of PCOS. The gynecologic exam is often unremarkable in AUB-O although a bimanual exam can reveal adnexal enlargement indicative of cystic ovaries. Of note, clitoromegally is not common in PCOS. This finding would increase the likelihood of other causes of hyperandrogenism [32].

What is the pathophysiologic basis for this patient’s bleeding pattern?

Pathophysiology of Anovulatory Bleeding

Anovulatory bleeding presumes that there is a normal anatomic and genetic makeup. For example, a woman without ovaries will be, by definition, anovulatory. Using current terminology anovulatory bleeding implies a disruption in the hypothalamic-pituitary-ovarian axis and is therefore primarily an endocrine disorder [31,33].

At the level of the ovary and uterus, anovulation results in prolonged estrogen effect on the endometrium. After ovulation, the corpus luteum produces progesterone which stops endometrial thickening and stabilizes the endometrium. Without ovulation, estrogen continues endometrial stimulation and excess proliferation of endometrial lining. The endometrium becomes unstable, undifferentiated, and sheds unpredictably. The blood vessels become larger, more tortuous and have increased fragility. The result is light or heavy menstrual bleeding, decreased frequency of periods but overall unpredictable menstrual bleeding [33].

Effects of Chronic Anovulation

Irregular cycles can be more than a mere inconvenience. Women who have anovulatory cycles associated with heavy menstrual bleeding are at risk for anemia. Anovulation that is a result of hyperandrogen state or other endocrine disorder has other health ramifications. Infertility and its treatment are common sequelae. Finally, over time, unopposed estrogen in anovulation increases the risk of endometrial hyperplasia, or cancer [7,34].

Case Continued

The patient reports menarche at age 12. Her periods were irregular for the first 1–2 years but became more regular after that. She has been taking combination oral contraceptives since the age of 20 to prevent pregnancy. She stopped this 1 year ago and she and her husband began actively trying to conceive 6 months ago. Her family history is notable for diabetes and hypertension in her father. Her mother had heavy periods leading up to menopause and had a hysterectomy with no malignancy at the age of 47. She has a BMI of 33; blood pressure is mildly elevated at 134/84 mm Hg. She has oily skin and acne along her chin and neck. She has mild hirsutism of her face. Otherwise her skin is normal appearing. She has an elevated waist circumference of 35 inches. The remainder of her exam is normal.