So what causes AUB-O?

Blog Post  by Malcolm G. Munro MD, FACOG, FRCS(c), Professor, Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Director of Gynecologic Services, Kaiser Permanante, Los Angeles Medical Center, Los Angeles, CA, USA

In the reproductive years, many women with abnormal uterine bleeding (AUB) have a disorder of ovulation – a group of entities designated “AUB-O” in the new FIGO classification system for causes of AUB in the reproductive years.(1) But what are these ovulatory disorders, and how are they diagnosed and treated?

The only thing “typical” about women with ovulatory disorders is that they do not have the characteristics of normal ovulation – ie predictable menstrual bleeding, with a reliable cycle length of 22 to 35 days and duration and flow that is consistent from period to period.(2) Instead, these women are often plagued with uncertainty – uncertainty about the time of onset, and, frequently, the volume and duration of bleeding.  For “anovulatory” cycles, the timing of the periods may be intermittently frequent, with a cycle of less than 22 days, or may be infrequent – bordering on amenorrhea at times; bleeding volume also typically varies, being either very light, or very heavy.(3) The unpredictability can be very disconcerting for anyone, but especially for teens and women in the later reproductive years, the groups most often affected.  They face a life where uterine bleeding may occur at any time, a circumstance that dictates a purse full of menstrual pads and tampons, and a wardrobe that is designed to obscure unanticipated bleeding.

So what causes AUB-O? First it is important to understand that we are only recently learning more about the increasingly complicated pathogenesis of what seems to be a spectrum of clinical entities that collectively are called ovulatory disorders. The notion of chronic or intermittent anovulation is a concept that has been promulgated as being secondary to “immaturity” of the hypothalamic-pituitary-ovarian axis in the adolescent, and to evolving resistance of the ovary to gonatotropins in the woman of the late reproductive years. There are clearly disorders such as polycystic ovarian syndrome, hyperprolactinemia, hyperandrogenic states and, commonly, hypothyroidism, any of which can reflect disrupted endocrine communications among the hypothalamus, pituitary and ovary, and a number of pharmacologic agents, such as those that alter dopamine metabolism that may also interfere. More obscure but likely a related are obesity, stress, anorexia and relatively extreme exercise such as that of elite athletes, all of whom typically have ovulatory disorders, that in the instance of anorexia and the athletes, usually manifests in amenorrhea.(4) Another recently described mechanism is the luteal out of phase (LOOP) follicular event, found most commonly in the late reproductive years, where women persist with ovulatory function, but may have follicular development even in the context of the luteal phase. (5)These women typically have episodes of very heavy bleeding that in the past was likely ascribed to anovulatory cycles.

For the present, the diagnosis of disorders of ovulation is generally made by a careful history, evaluating patients for possible confounders such as focal lesions (eg endometrial polyps) using sonographic or hysteroscopic imaging, while maintaining skepticism over the role of potentially asymptomatic entities such as adenomyosis or intramural and subserosal leiomyomas. Most women with chronic AUB secondary to ovulatory disorders respond to appropriately selected gonadal steroid therapy, or, if a specific cause (such as hypothyroidism) is identified, treatment of that condition.  More about AUB-O can be found in the book Abnormal Uterine Bleeding, from Cambridge Medical Press.(6)

1.         Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113:3-13.

2.         Malcolm CE, Cumming DC. Does anovulation exist in eumenorrheic women? Obstet Gynecol. 2003;102:317-8.

3.         Van Voorhis BJ, Santoro N, Harlow S, Crawford SL, Randolph J. The relationship of bleeding patterns to daily reproductive hormones in women approaching menopause. Obstetrics and gynecology. 2008;112:101-8.

4.         De Souza MJ, Miller BE, Loucks AB, Luciano AA, Pescatello LS, Campbell CG, et al. High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition. The Journal of clinical endocrinology and metabolism. 1998;83:4220-32.

5.         Hale GE, Hughes CL, Burger HG, Robertson DM, Fraser IS. Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition. Menopause. 2009;16:50-9.

6.         Munro MG. Abnormal Uterine Bleeding. Cambridge: Cambridge University Press; 2010.

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