Anovulatory cycle

In most instances, dysfunctional bleeding is due to the occurrence of an anovulatory cycle. Anovulation results in excessive and prolonged estrogenic stimulation without the counteractive effect of the progestational phase that regularly follows ovulation. In most women anovulatory cycles have no obvious cause, occurring most likely due to subtle hormonal imbalances. Anovulatory cycles are most common at menarche and in the perimenopausal period. Less commonly, lack of ovulation is the result of (1) an endocrine disorder, such as thyroid disease, adrenal disease, or pituitary tumors; (2) a primary lesion of the ovary, such as a functioning ovarian tumor (granulosa-theca cell tumors) or polycystic ovaries (see "Ovaries"); or (3) a generalized metabolic disturbance, such as marked obesity, severe malnutrition, or any chronic systemic disease.

Failure of ovulation results in prolonged, excessive endometrial stimulation by estrogens. Under these circumstances the endometrial glands undergo mild architectural changes, including cystic dilation, that are usually self-limited by the occurrence of the next ovulatory cycle. Unscheduled breakdown of the stroma may also occur ("anovulatory menstruation"), with no evidence of endometrial secretory activity (see Fig. 22-23A). More severe consequences of repeated anovulation are discussed under "Endometrial Hyperplasia."

Inadequate luteal phase

This term refers to a condition that is thought to stem from inadequate corpus luteum function resulting in low progesterone output, with subsequent early menses. The condition often manifests clinically as infertility, with either increased bleeding or amenorrhea. Endometrial biopsy performed at an estimated postovulatory date shows secretory endometrium, which, however, lags in its secretory characteristics expected at that date.

Endometrial changes induced by oral contraceptives

As might be suspected, oral contraceptives containing synthetic or derivative ovarian steroids induce a wide variety of endometrial changes, depending on the steroids used, the method of administration (combined or sequential regimen), and the dose. A common response pattern is a discordant appearance between glands and stroma, usually with inactive glands amid a stroma showing large cells with abundant cytoplasm reminiscent of the decidua of pregnancy. When such therapy is discontinued, the endometrium reverts to normal. All these changes have been minimized with newer low-dose contraceptives.

Menopausal and postmenopausal changes

Because the menopause is characterized by anovulatory cycles, architectural alterations in the endometrial glands may be present transiently, followed by ovarian failure and atrophy of the endometrium. As discussed later in this chapter, anovulatory cycles and uninterrupted estrogen production can induce mild hyperplasias with cystic dilation of glands. If this is followed by complete ovarian atrophy and loss of stimulus, the cystic dilation may remain, while the ovarian stroma and gland epithelium undergo atrophy. In this case, so-called cystic atrophy results. Such cystic changes should not be confused with simple hyperplasia, which shows evidence of glandular and stromal proliferation.

Inflammation

The endometrium and myometrium are relatively resistant to infections, primarily because the endocervix normally forms a barrier to ascending infection. Thus, although chronic inflammation in the cervix is an expected and frequently insignificant finding, it is of concern in the endometrium, excluding the menstrual phase.