CHAPTER 8: Abnormal Uterine Bleeding

PATHOPHYSIOLOGY

The endometrium is the source of most abnormal reproductive tract bleeding. It consists of two distinct zones, the functionalis layer and the basalis layer (Fig. 8-1). The basalis layer lies in direct contact with the myometrium and beneath the functionalis layer. The basalis serves as a reservoir for regeneration of the functionalis layer following menses. In contrast, the functionalis layer lines the uterine cavity and undergoes dramatic change throughout the menstrual cycle. It ultimately sloughs during menstruation. Histologically, the functionalis has a surface epithelium and underlying subepithelial capillary plexus. Beneath these are stroma, glands, and interspersed leukocytes (Fig. 33-1, p. 701).

Blood reaches the uterus via the uterine and ovarian arteries (see Fig. 8-1). From these, the arcuate arteries arise to supply the myometrium. These in turn branch into the radial arteries, which extend toward the endometrium at right angles from the arcuate arteries. At the endometrium-myometrium junction, the radial arteries bifurcate to create the basal and spiral arteries. The basal arteries serve the basalis layer of the endometrium and are relatively insensitive to hormonal changes. The spiral arteries stretch to supply the functionalis layer and end in a subepithelial capillary plexus.

In human menstruation, progesterone plays a critical role. Two progesterone receptors (PR) are found in the endometrium, PRA and PRB. In the secretory phase, PRB levels decline in the stromal and glandular epithelial cells of the functionalis layer. However, PRA expression in this layer persists in the stromal cells, which thus remain responsive to progesterone and to its withdrawal (Maybin, 2015).

In the absence of pregnancy, the corpus luteum regresses and curtails progesterone production. Progesterone acts as an antiinflammatory agent, and thus its withdrawal raises cytokine levels in the endometrium. Elevated concentrations of cytokines prompt an influx of leukocytes, which release lytic enzymes. These matrix metalloproteinases break down the stroma and vascular architecture of the functionalis layer (Critchley, 2011). Subsequent bleeding and sloughing of this layer constitute menstruation (Jabbour, 2006). Concurrently, endometrial levels of tissue factor and plasminogen activator inhibitor-1 drop with progesterone withdrawal. These two proteins foster hemostasis during the luteal phase, but their decline promotes an environment conducive to bleeding and fibrinolysis (Lockwood, 2011). Last, progesterone withdrawal raises concentrations of cyclooxygenase-2, a necessary enzyme in prostaglandin PG synthesis. As a result, levels of prostaglandin F_2α (PGF_2α) rise and cause intense spiral arteriole constriction. Explanations differ as to whether this vasoconstriction produces a hypoxia needed to prompt endometrial sloughing or whether it serves to minimizes menstrual blood loss (Maybin, 2015; Schatz, 2016).

Hemostasis and cessation of menstruation are dependent on the endometrial coagulation system. Initially, platelets aggregate and are activated in response to endothelial ...