At birth, the ovaries are provided with thousands of eggs, each surrounded
by cells which develop into a small fluid filled blister known as a follicle.
Each month in women with regular periods (normal ovulation), one of these
follicles will develop and grow to about 20 mm in diameter and then release
a mature egg (ovulation), which passes into the fallopian tubes. The
fertilized egg (embryo) continues its course through the tube into the
uterus where it will implant in the lining (endometrium) and develop
as a pregnancy. If there is no fertilization, the endometrium is shed
asa menstrual period around 14 days after ovulation.
Three important groups of hormones - estrogens, androgens and progesterone
- are also produced in the ovary. These, in turn, are regulated by the
release of two additional hormones- follicle stimulating hormone (FSH)
and luteinizing hormone (LH) - from the pituitary gland which is located
at the base of the brain. These two "reproductive" hormones
influence the development of the follicle and the timing of ovulation.
ABNORMAL OVARIAN FUNCTION - PCOS
Women with PCOS have normal reproductive organs such as the uterus and
fallopian tubes. Their ovaries each usually contain about 10 or more
small cysts located at the periphery of the ovary. The size of these
cysts generally are less than 8 mm and can be detected by ultrasound
examination. These cysts do not appear to grow and usually remain small.
They do not require surgical removal. Additionally, these cysts do not
represent cancer and are not associated with an increased risk of ovarian
cancer.
The reason for multiple cyst development is not clear. It may be related
to the inability of ovulation in PCOS. In comparison to normal ovulation,
women with PCOS are unable to completely develop a fully mature egg (on
their own) due to abnormal pituitary FSH and LH secretion. As a result,
the ovulatory process is not completed and the partially stimulated follicle
becomes cystic followed by degeneration of the egg.
The problems of irregular or absent menstrual bleeding, excess hair
growth and infertility are a result of abnormal hormone secretion by
the pituitary gland (FSH and LH) and the ovaries (estrogen, androgen
and progesterone). Despite irregular ovulation in PCOS, the ovary continues
to be stimulated by FSH and LH in an uncoordinated manner, which leads
to a constant production of estrogen, excessive amounts of androgen,
and very little progesterone.
THE SYMPTOMS OF PCOS
Menstrual Irregularities
Constant estrogen production stimulates growth of the uterine lining, or endometrium.
As the lining grows and becomes abnormally thickened, there can be spontaneous
shedding of the endometrium. This process, together with the lack of regular
ovulation, leads to irregular and, sometimes, very heavy uterine bleeding.
The bleeding episodes may occur after long gaps of time (oligomenorrhea) or;
for some women, not at all (amenorrhea).
Impaired Fertility
Another consequence of incomplete follicular development is a lack of regular
ovulation. Irregular ovulation usually means that pregnancy is more difficult
to achieve. Similarly, if ovulation is not taking place, it is not possible
to conceive. In most instances of PCOS, some form of treatment is necessary
to reestablish predictable ovulation.
Miscarriage
While miscarriage seems an unfortunate chance event for most couples, it is now
known that women with PCOS who have high circulating levels of LH may be at
increased risk. A possible explanation is that levels of LH which are high
in PCOS may interfere with egg development within the follicle and/or disrupt
embryo implantation within the uterus.
Hair and Skin Problems
Androgen (male hormone) is produced by ovaries from both normal women and those
with PCOS. In PCOS the production of androgen, such as testosterone, is excessive,
which causes abnormally increased hair growth and contributes to acne formation.
Obesity
About 50 percent of women with PCOS are obese. Obesity tends to enhance abnormal
estrogen and androgen pro duction in this disorder; which only magnifies the
problems of irregular bleeding and excessive hair growth.
Abnormal Insulin Action
Recently, it has been discovered that in PCOS there is an abnormality of insulin
secretion. Women with PCOS are more resistant to the action of insulin than
normal women and, as a result, have a greater long-term risk of developing
diabetes mellitus.
Heart Disease
Another long-term concern is that of cardiovascular risk. Androgens are known
to induce an unfavorable lipid profile by increasing low density lipoprotein
and decreasing high density lipoprotein. Thus, the excessive production of
an-drogen in PCOS may place these women at an increased risk for heart disease.
MANAGEMENT OF PCOS
Menstrual irregularities
Irregular periods are a nuisance and suggest some hormonal disorder or risk of
endometrial thickening. Any irregular bleeding should be checked by a doctor
who may prescribe hormonal treatments to regulate the menstrual cycle.
Fertility Difficulty
In women with PCOS, failure to ovulate is the usual reason for not achieving
pregnancy. However, prior to initiating fertility treatment, it is recommended
that other factors which impact fertility should be evaluated. These factors
include tubal patency, pelvic anatomic relationships, and assessment of semen
and sperm function.
Monitoring Ovulation. In normal cycles, ovulation takes place
14 days before a period starts. For instance, if your cycle is 28 days,
ovulation will occur around day 14. If your cycle is 27 days, ovulation
will occur around day 13. If your cycle is 35 days, ovulation will
occur approximately on day 21. It is important to understand these
relationships for the purpose of timing sexual intercourse to coincide
with ovulation. An inexpensive and convenient means by which ovulation
may be detected is using the basal body temperature (BBT) chart. This
methodology is based on the knowledge that a temperature rise of approximately
0.5° F occurs following ovulation and lasts for approximately 12
days. If ovulation does not occur, or if the ovulation is faulty, then
a rise in temperature will not occur or the duration of any increase
in temperature will be less than 11 days. It must be emphasized that
prediction of ovulation can only occur after several cycles of BBT
have been recorded.
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Changes
in the uterine lining in response to estrogen and progesterone. |
A reasonably reliable way to predict ovulation is with an over-the-counter
urinary test kit. This measures the surge of LH which occurs around
the time of ovulation. Testing should begin a day or so before you
expect to ovulate. Intercourse should take place on the day when there
is a color change on the test, as well as on the following day.
Ovulation can be monitored by ultrasound, but this method is usually
reserved for women having more complicated treatments, and for those
who have difficulty with the urine test.
A blood test to measure circulating progesterone may be performed
7 days after presumed ovulation to determine whether ovulation has
taken place. Progesterone is produced by the ovary following normal
ovulation.
The efforts to monitor ovulation, whether simple or comp licated,
are intended to coordinate and time sexual intercourse with that of
ovulation. If there is a regular menstrual cycle and normal ovulation,
then intercourse two or three times a week should provide a sufficient
supply of sperm within the reproductive tract to maximize fertilization.
It has been noted among patients that intensive monitoring can remove
much of the spontaneity from their sex lives. Therefore, occasionally
a short break from treatment, perhaps a month or two, might be considered
to relieve the stress associated with this treatment.
Drugs to Induce Ovulation. In cases where ovulation is irregular
or absent, drugs can be used. The most common agent is clomiphene citrate,
which is taken as a tablet for five days from the third day of menstruation.
Results show that four out of five women given clomiphene do ovulate,
but only about one in three actually become pregnant. The starting
daily dose is usually 50 mg., which may be progressively increased
up to a dose of 150 mg.
While clomiphene is a useful drug for many women with anovulation
and infertility, there are patients who fail therapy. If clomiphene
has been unsuccessful in women over six months of treatment, then alternative
therapies are usually considered.
Side effects of clomiphene have been reported. These include stomach
and bowel upset, bloating, headache, sensitivity to bright light, dizziness,
hot flashes, depression, and breast discomfort. Mild to moderate cystic
enlargement of the ovary may occur with clomiphene which necessitates
discontinuance of the drug and observation. Multiple pregnancy is slightly
increased in women using this form of ovulation induction. There is
no increased risk of birth defects from clomiphene.
More complicated treatments. If clomiphene fails to successfully
induce ovulation, then a group of injectable hormone preparations,
known as gonadotropins, may be employed. There are two types of gonadotropin
preparations available. One contains both FSH and LH activities while
the other contains primarily FSH with a small amount of LH. Although
both types of gonadotropins work well in women with PCOS many programs
prefer to use the products which contain primarily FSH. Initial therapy
includes daily administration in small amounts with progressive increases
in dose until ovulation is achieved. Follicular development and growth
is carefully monitored by hormone measurements and ultrasound examinations.
If monitoring shows that too many follicles are developing, and the
risk of multiple pregnancy is high, then treatment will usually be
suspended and ovulation induction in that cycle canceled. When development
and growth of the follicle reaches optimum maturity, then human chorionic
gonadotropin (hCG) is administered by inlection to stimulate release
of the egg from the follicle.
Women with PCOS given gonadotropins are at an increased risk of a
rare but potentially serious condition known as Ovarian Hyperstimulation
Syndrome. This situation arises if an excessive number of follicles
are stimulated. The diagnosis is suspected when unusually large ovarian
cyst formation occurs. Avoidance of Ovarian Hyperstimulation Syndrome
is best achieved by careful monitoring of ovulation induction.
Ovarian Capsule Puncture. Recently, it has been shown that
in women with PCOS, penetration of the ovarian capsule by multiple
puncture results in resumption of regular ovulatory function. This
is usually performed through a laparoscope and puncture may be achieved
by either cautery or needle penetration at multiple sites. In some
cases, regular ovulation persists for some time, whereas in other patients,
after several spontaneous normal ovulations, irregular or absent menstrual
function recurs.
In Vitro Fertilization (IVF). The technique of IVF refers to the fertilization
of a woman's egg with her partner's sperm in the laboratory. Following
fertilization, the embryo is then placed in the woman's uterus in anticipation
of implantation and pregnancy. This pr~ cedure is recommended to women
who have blocked fallopian tubes, or men with poor quality sperm. IVF
is also offered to women with PCOS who wish to conceive after other
treatment strategies have failed. Since a part of the protocol for
IVF includes gonadotropin induction of ovulation, these patients must
be carefully monitored in an effort to avoid Ovarian Hyperstimulation
Syndrome.
SUMMARY
In summary, PCOS is the most common cause of menstrual irregularity
in reproductive-aged women and its occurrence may be associated with
a variety of clinical symptoms, including infertility. There are known
long-term health risks associated with PCOS. As a result, patients with
this condition are encouraged to seek medical assistance since current
therapies exist, which may prove to be extremely beneficial.
