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Genitourinary and Reproductive Function

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extent of the disease. Definitive diagnosis can be accom- plished only through laparoscopy. This minimally invasive surgery allows direct visualization of pelvic organs to determine the presence and extent of endo- metrial lesions. Imaging techniques, including ultraso- nography and magnetic resonance imaging (MRI), can be useful tools in evaluating endometriomas and deep endometriosis. 29,30 Serum cancer antigen 125 (CA-125), which is known for its use in diagnosis and monitor- ing of ovarian cancer, may be elevated in the presence of endometriosis. It has limitations as a screening tool, but can be useful in monitoring response to therapy and recurrence. Treatment modalities fall into three categories: pain relief, endometrial suppression, and surgery. 29,30 In young women, simple observation and analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs]) may be sufficient treatment. The use of hormones to induce physiologic amenorrhea is based on the observation that pregnancy and menopause afford pain relief by inducing atrophy of the endometrial tissue. This can be accom- plished through administration of oral contraceptives, continuous progestogen therapy, androgenic agents (danazol), or long-acting GnRH analogs that inhibit the pituitary gonadotropins and suppress ovulation. Surgery may offer more definitive therapy for women with large or symptomatic endometriomas (endometrial cysts) that do not respond to medical therapy because of the concentration of endometriosis within the cyst. 29,30 Laproscopic surgical options include the use of cautery, laser ablation, or excision techniques. Definitive surgi- cal treatment involves total hysterectomy and bilateral salpingo-oophorectomy (removal of the uterus, ovaries, and fallopian tubes) when the symptoms are unbearable or the woman’s childbearing is completed. Adenomyosis Adenomyosis is the condition in which endometrial glands and stroma are found within the myometrium, interspersed between the smooth muscle fibers. 6,7 In con- trast to endometriosis, which usually is a problem in young, infertile women, adenomyosis typically is found in multiparous women in their late fourth or fifth decade. It is thought that events associated with repeated preg- nancies, deliveries, and uterine involution may cause the endometrium to be displaced throughout the myo- metrium. Adenomyosis frequently coexists with uterine myomas or endometrial hyperplasia. Heavy, painful peri- ods with clots and dyspareunia are common complaints. Adenomyosis resolves with menopause. Conservative therapy using oral contraceptives or GnRH agonists is usually the first choice of treatment. Hysterectomy (with preservation of the ovaries in premenopausal women) is considered when this approach fails. Endometrial Cancer Endometrial cancer is the most frequent invasive cancer of the female reproductive tract and accounts for 7% of all invasive cancers in women. 6,7 It is typically a disease of postmenopausal women. Because endometrial cancer

usually causes abnormal (postmenopausal) bleeding, early detection and cures are possible. Epidemiology and Pathogenesis. Endometrial can- cer occurs most frequently in postmenopausal women (peak age of 55 to 65 years) and is uncommon in women younger than 40 years of age. 6 Two groups in which endometrial cancers arise are perimenopausal women with estrogen excess and older women with endome- trial atrophy. Endometrial cancers that arise in women with estrogen excess are described as type I or endome- trioid carcinoma, and those that arise in women with endometrial atrophy as type II or serous or clear-cell carcinoma. 6,7,31–34 The first group, or type I, is the most common type of endometrial cancer, accounting for 80% of cases. Most of these tumors are well differentiated and mimic pro- liferative endometrial glands, and as such are referred to as endometrioid carcinoma . Endometrioid carci- noma is associated with prolonged estrogen stimula- tion and mutations in PTEN, a tumor-suppressor gene. In addition to unopposed estrogen therapy, other risks for endometrioid carcinoma are obesity, diabetes, nul- liparity (having borne no children), early menarche, and late menopause. Many of these risk factors are the same as those for endometrial hyperplasia. Obesity pre- disposes to insulin resistance, ovarian androgen excess, anovulation, and chronic progesterone deficiency. These hormonal changes stimulate endometrial cell proliferation, inhibit apoptosis, and promote angiogen- esis. Progesterone counteracts the effects of estrogen. Pregnancy, with intense placental production of pro- gestins, protects against endometrial cancer. Thus, mul- tiparity protects against endometrial cancer, whereas nulliparity increases risk, especially when infertility is also present. Diabetes mellitus, hypertension, and poly- cystic ovary syndrome are conditions that also alter estrogen metabolism and elevate estrogen levels. Type II endometrial cancers occur in a small sub- set of women who do not exhibit increased estrogen levels. These women usually acquire the disease at an older age and in a setting of endometrial atrophy rather than hyperplasia. This type of endometrial cancer usu- ally is associated with a poorer prognosis than type I carcinomas. 7 Clinical Features. The major symptom of endome- trial hyperplasia or overt endometrial cancer is abnor- mal, painless bleeding. Abnormal bleeding is an early warning sign of endometrial cancer in up to 90% of women, and because endometrial cancer tends to be slow growing in its early stages, the chances of cure are good if prompt medical care is sought. 31 In menstruating women, this takes the form of bleeding between periods or excessive, prolonged menstrual flow. In postmeno- pausal women, any bleeding is abnormal and warrants investigation. Later signs of uterine cancer may include cramping, pelvic discomfort, postcoital bleeding, lower abdominal discomfort, and enlarged lymph nodes. Although Pap smear cytology can identify a small per- centage of endometrial cancers, it is not a good screening