RELATIONSHIPS IN ENDOMETRIAL HYPERPLASIA
The cyclic changes of the endometrium are regulated and controlled, as described previously, by the hormonal secretions of the ovary. When ovulation fails to occur or an inadequate amount of progesterone is secreted, while estrogen secretion continues unabated, then endometrial changes recognized as the progestational or secretory phase of the cycle do not take place. Under the constant stimulus of estrogen, the proliferative phase persists, and this growth phase sometimes— but not always—becomes sufﬁciently exaggerated to result in endometrial hyperplasia. It is, however, well known that isolated anovulatory cycles often terminate at the expected time with normal ﬂows, even though here, too, the rearrangement of the endometrium in the secretory phase has failed to make its appearance. It appears that in such cases the unopposed estrogen stimulation has not been prolonged enough to fully produce the developed hyperplasia. Why in one case regular bleeding from a proliferative endometrium occurs in spite of an anovulatory cycle whereas in another case failure to ovulate leads to endometrial hyperplasia remains unknown.
Endometrial hyperplasia represents an abnormal proliferation of both the glandular and stromal elements of the endometrium with characteristic alteration in the histologic architecture of the tissues. It is this architectural change that differentiates hyperplasia from normal endometrial proliferation caused by estrogen stimulation early in the menstrual cycle. Simple hyperplasia represents the least signiﬁcant form of alteration, whereas complex hyperplasia represents the most signiﬁcant form of alteration. The most common cause of endometrial hyperplasia is unopposed estrogen stimulation of the endometrium (such as chronic anovulation, estrogen therapy [four-to eightfold risk], or obesity [threefold risk]); other causes include nulliparity (two-to threefold risk), diabetes (two-to threefold risk), polycystic ovarian syndrome, and tamoxifen use. Five percent of patients with postmenopausal bleeding have endometrial hyperplasia.
The most reliable means of detecting endometrial hyperplasia is by endometrial biopsy. Ultrasonography may detect thickening of the endometrial stripe, but no standard has emerged for a threshold of endometrial thickness that carries ideal positive and negative predictive values. Therefore, it does not take the place of histologic evaluation. Magnetic resonance imaging may also diagnose endometrial thickening, but cost and low speciﬁcity argue against its use as a diagnostic tool.
Endometrial hyperplasia is, however, by no means the only cause of abnormal regular or irregular uterine bleeding, which can occur in any stage of the mucosa, even from an atrophic organ. Without a more direct cause identiﬁed, the term dysfunctional uterine bleeding has been used to cover the variety of hemorrhages observed when no organic lesions were detectable.
Having established or excluded neoplasia—both malignant and benign—and hyperplasia by endometrial biopsy or hysteroscopy without biopsy, one still encounters a number of cases of abnormal bleeding without pathologic ﬁndings. Signiﬁcance has been attached to the temporal correlation between with-drawal of ovarian hormones and mucosal shrinkage, absorption of interstitial ﬂuid, increased coiling of the arteries, autolysis, and ischemia. The same events may be operative in both normal menstrual ﬂows and functional bleeding that can continue profusely for weeks.
In some cases, the histologic picture is mixed—some areas are typical of the proliferative phase and others show a characteristic secretory pattern, whereas still others may be necrotic and menstrual in type. The descriptive terms dyssynchronous endometrium or disordered proliferative endometrium have been applied to such ﬁndings, although the cause for this variation in endo-metrial development is not clear. When nuclear atypia is present, more than 40% of patients will have a coexisting endometrial cancer. Hormonal therapy, such as oral progestins or combined estrogens and progestins (oral contraceptives), is often the only therapy needed when simple hyperplasia is found.