Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O)

Abnormal Uterine Bleeding associated with ovulatory dysfunction

What is Abnormal Uterine Bleeding (AUB) ?

Abnormal uterine bleeding (AUB) is a common condition affecting women of reproductive age that has significant social and economic impact. AUB may be defined as any variation from the normal menstrual cycle, and includes changes in regularity and frequency of menses, in duration of flow, or in amount of blood loss. 

What is “Abnormal Uterine Bleeding associated with ovulatory dysfunction” (AUB-O) ?

Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) is (i.e., oligo-ovulation or anovulation) is a spectrum of disorders most commonly associated with heavy, irregular uterine bleeding. Abnormal uterine bleeding occurs in the setting of ovulatory dysfunction because of the effects of chronic unopposed estrogen on the endometrium.

Is there a classification System for Abnormal Uterine Bleeding (AUB) in reproductive-aged women ? 

In an effort to create a universally accepted system of nomenclature to describe uterine bleeding abnormalities in reproductive-aged women, International Federation of Gynecology and Obstetrics (FIGO) working group on menstrual disorders developed a Classification System for Abnormal Uterine Bleeding in Reproductive-Aged Women  known by the acronym PALM–COEIN.

There are nine main categories, which are arranged according to the acronym PALM-COEIN: 

PALM: Structural Causes

  • Polyp (AUB-P)
  • Adenomyosis (AUB-A)
  • Leiomyoma (AUB-L)
  • Malignancy and Hyperplasia (AUB-M)

COEIN: Nonstructural Causes

  • Coagulopathy (AUB-C)
  • Ovulatory dysfunction (AUB-O)
  • Endometrial (AUB-E)
  • Iatrogenic (AUB-I)
  • Not yet classified (AUB-N)

The PALM– COEIN system classifies uterine bleeding abnormalities by bleeding pattern and etiology. According to this classification system, non-specific term like dysfunctional uterine bleeding should be abandoned to address a more specific etiology.

Understanding AUB-O: 

Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) is a condition for which women frequently seek gynecologic care. Anovulatory bleeding is common at the extremes of reproductive age. Abnormalities at any level of the hypothalamic–pituitary–ovarian axis can result in interruption of the ovulatory cycle.

In the absence of ovulation, a corpus luteum does not develop and the ovary fails to secrete progesterone. This results in continual endometrial proliferation without progesterone-withdrawal-induced shedding and bleeding. The clinical result is bleeding that is noncyclic, unpredictable, and inconsistent in volume. The endometrium that develops in the milieu of unopposed estrogen is fragile, vascular, and lacking sufficient stromal sup- port. As one area of bleeding begins to heal, another area begins to slough, which results in erratic bleeding patterns.

Puberty and the perimenopause typically are associated with AUB-O and are considered to be physiologic in these circumstances. In puberty, the immature hypothalamic–pituitary–ovarian axis does not develop the necessary hormonal feedback to result in ovulation and a subsequently stable endometrium. As the perimenopausal transition occurs, progressive oocyte depletion and abnormal follicular development lead to anovulatory cycles. 

Recognized causes of anovulation include;

  • Physiologic: Adolescence, Perimenopause, Lactation, Pregnancy
  • Pathologic: Hyperandrogenic anovulation (e.g., polycystic ovary syndrome, congenital adrenal hyperplasia, or androgen-producing tumors), Hypothalamic dysfunction (e.g., secondary to anorexia nervosa), Hyperprolactinemia, Thyroid disease, Primary pituitary disease, Premature ovarian failure, Iatrogenic (e.g., secondary to radiation or chemotherapy), Medications

Establishing the Diagnosis:

The evaluation of women with AUB includes a thorough medical history and physical examination, appropriate laboratory and imaging tests, and consideration of age-related factors. 

  • To establish the diagnosis of AUB-O, structural causes of abnormal bleeding must be excluded. Endometrial and structural uterine pathology therefore, should be ruled out. Pregnancy must be excluded during the evaluation. Pregnancies, although rare, may still occur until 1 full year without menses.
  • Recognized causes of anovulation should be considered when evaluating the medical history and physical examination. Patients with AUB-O typically do not experience the breast discomfort, increased mucoid vaginal discharge, or premenstrual cramping and bloating that are characteristic of ovulatory uterine bleeding. In addition, cycles that vary in length by more than 10 days from one cycle to another are likely anovulatory.
  • A thorough medical history and physical examination will guide the choice of appropriate laboratory studies, diagnostic or imaging tests, and tissue sampling methods. 

According to the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin “Management of Abnormal uterine bleeding associated with ovulatory dysfunction” (July 2013),  recommended assessments to establish the cause of AUB include the following :

  • Pregnancy testing for sexually active women (even those who have had a tubal ligation)
  • Sensitive β-hCG level testing to exclude trophoblastic disease in patients who were recently pregnant
  • Thyroid-stimulating hormone level assessment to exclude hypothyroidism or hyperthyroidism
  • Prolactin level testing (if the level is elevated, the test should be repeated in the fasting state.)
  • An endometrial biopsy in women with risk factors for for endometrial hyperplasia or malignancy
  • Saline infusion sonohysterography, hysteroscopy, or transvaginal ultrasonography may be necessary to rule out an anatomic abnormality

Endometrial evaluation in women of different ages with AUB-O:

Following are the recommendations for the endometrial evaluation in women of different ages with abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) from the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin “Management of Abnormal Uterine Bleeding Associated With Ovulatory Dysfunction” (July 2013),

Women aged 13-18 years:  

  • From 2005 to 2009, the incidence of endometrial cancer in women younger than 20 years was 0.2 per 100,000 women. In the rare case reports of adolescents with endometrial cancer, the clinical history typically includes 2–3 years of abnormal bleeding and obesity. 
  • Additional endometrial evaluation should be performed if medical treatment has failed after thorough investigation of all potential other causes and co-morbid disorders.

Women aged 19 – 39 years: 

  • The incidence of endometrial cancer increases with age. However, the incidence of endometrial carcinoma is still very low in women between the ages of 19 years and 39 years. The risk of endometrial cancer in women aged 20–34 years is 1.6%. In women aged 35–44 years, the rate increases to 6.2%.
  • Among women aged 40 years or younger, risk factors for endometrial cancer include nulliparity, hypertension, body mass index greater than 30, irregular menstruation, and family history. 
  • Although endometrial carcinoma is rare in women younger than 39 years, patients aged 19–39 years who do not respond to medical therapy or who have prolonged periods of unopposed estrogen stimulation are candidates for endometrial assessment. When endometrial biopsy is nondiagnostic, shows no evidence of hyperplasia or cancer, and the patients fail to respond to medical therapy, office hysteroscopy or saline infusion sonohysterography with further sampling may be appropriate.

Women aged 40 years to Menopause: 

  • Among women aged 40–50 years, the incidence of endometrial cancer ranges from 13.6 cases to 24 cases per 100,000 women-years and increases to 87.3 cases per 100,000 in women aged 70–74 years. 
  • Among women younger than 45 years, there is a lower rate of advanced-stage disease, a higher degree of tumor differentiation, and a better prognosis compared with patients older than 45 years. Therefore, all women older than 45 years who present with suspected anovulatory uterine bleeding should be evaluated with endometrial biopsy (after pregnancy has been excluded).