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Genitourinary and Reproductive Function
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
