1036
U N I T 1 1
Genitourinary and Reproductive Function
Chronic anovulation, causing amenorrhea or irregu-
lar menses, is now thought to be the underlying cause of
the bilaterally enlarged “polycystic” ovaries. Hence, the
polycystic ovary is a sign of the disease, not the cause of
the disease. There is increasing evidence that the disor-
der may begin before adolescence and that many of the
manifestations of PCOS begin to make their appearance
at that time. Because many of the symptoms common
to PCOS, such as hirsutism, acne, and obesity, can be
detrimental to a teenage girl’s health and self-esteem,
early detection and treatment of PCOS in adolescents
are essential.
40
The underlying etiology of the disorder is unknown,
although most women have altered gonadotropin lev-
els.
4,40
This is manifested by increased release of LH
in relation to FSH release, with a resultant increase in
production of androstenedione and testosterone by the
theca cells of the ovary. Androstenedione, in turn, is con-
verted to estrone within adipocytes. Although estrone is
a weak estrogen, it stimulates LH release and suppresses
FSH release. The resultant decrease in FSH levels allows
for new follicular development, but full maturation is
not attained and ovulation does not occur. The elevated
LH levels result in increased androgen production,
which in turn, prevents normal follicular development
and contributes to a vicious cycle of anovulation and
multiple cyst formation. Increased androgen levels also
lead to the development of acne and hirsutism.
The typical woman with PCOS has hyperinsulinemia
and many of the signs of the metabolic syndrome (see
Chapter 33).
4
It has been shown that the cause of hyper-
insulinemia is insulin resistance. The frequency and
degree of hyperinsulinemia in women with PCOS is
often amplified by the presence of obesity. In addition
to its clinical manifestations, long-term health problems
linked to PCOS include cardiovascular disease and type
2 diabetes. Classic lipid abnormalities include elevated
triglyceride levels, low HDL levels, and elevated LDL
levels. Hypertension is also common in women with
PCOS. There is also concern that women with PCOS
who are anovulatory do not produce progesterone.
This, in turn, may subject the endometrium to an unop-
posed estrogen environment, which is a significant risk
factor for development of endometrial cancer.
4,40
The diagnosis of PCOS can be suspected from the
clinical presentation. Although there is no consensus as
to which tests should be used, laboratory evaluation to
exclude hyperprolactinemia, late-onset adrenal hyper-
plasia, and androgen-secreting tumors of the ovary and
adrenal gland are commonly done. Because of the high
risk of insulin resistance, a fasting blood glucose, 2-hour
oral glucose tolerance test, and insulin levels may be
done to evaluate for hyperinsulinemia. Confirmation
with ultrasonography or laparoscopic visualization of
the ovaries is often done, but not required.
38
The overall goal of treatment of PCOS should be
directed toward symptom relief, prevention of potential
malignant endometrial sequelae, and reduction in risk
for development of diabetes and cardiovascular disease.
The preferred and most effective treatment for PCOS
is lifestyle modification. Weight loss may be beneficial
in restoring normal ovulation when obesity is present.
Combined oral contraceptive agents ameliorate men-
strual irregularities and improve hirsutism and acne.
The addition of spironolactone, a mineralocorticoid
antagonist that inhibits the production of androgens
by the adrenal gland, may be beneficial to women with
severe hirsutism.
4
Insulin-sensitizing agents (e.g., metformin) alone or
with ovulation-inducing medications are emerging as an
important component of PCOS treatment.
40
In addition
to expected improvements in insulin sensitivity and glu-
cose metabolism, they have been associated with reduc-
tions in androgen and LH levels and are highly effective
in restoring normal menstrual regularity and ovulatory
cycles.
Ovarian Cancer
Ovarian cancer is the second most frequent gyneco-
logic malignancy after endometrial cancer in the United
States, and it carries the highest mortality rate of all gen-
ital cancers combined.
6
The incidence of ovarian cancer
and mortality rate increases with age, with most cases
occurring in women older than 50 years of age.
41
Malignant ovarian tumors are categorized accord-
ing to cell type of origin—epithelial cell tumors,
germ cell tumors, and gonadal stromal cell tumors
(see Fig. 40-16). Approximately 90% of ovarian can-
cers are of epithelial cell origin.
6,7
These tumors tend to
occur in older women, are usually discovered late in the
disease, and have a high mortality rate. The nonepithe-
lial ovarian cancers, which include germ cell tumors and
stromal cell tumors, tend to occur in a younger popula-
tion of women. They typically present with earlier signs
of disease and excellent survival potential when detected
early.
The most significant risk factor for ovarian cancer
appears to be ovulatory age—the length of time during
a woman’s life when her ovarian cycle is not suppressed
by pregnancy, lactation, or oral contraceptive use.
41–43
The incidence of ovarian cancer is much lower in coun-
tries where women bear numerous children. Epithelial
cancer of the ovaries derives from malignant transfor-
mation of the epithelium of the ovarian surface. When
these epithelial cells are situated over developing folli-
cles, they undergo metaplastic transformation whenever
ovulation occurs. It follows that repeated stimulation
of the epithelium of the ovarian surface, which occurs
with uninterrupted ovulation, may predispose the epi-
thelium to malignant transformation. Family history
also is a significant risk factor for ovarian cancer. The
breast cancer susceptibility genes,
BRCA1
and
BRCA2
mutations, which are tumor-suppressor genes, increase
the susceptibility to ovarian cancer
6,7,41–43
(see Chapter
7). The estimated lifetime risk of ovarian cancer in
women bearing the BRCA1 and BRCA2 mutations is
23% to 54%. A high-fat Western diet and use of pow-
ders containing talc in the genital area are other factors
that have been linked to the development of ovarian
cancer.
