Previously
published as a commentary by Dr Thatcher in
The American Infertility Association Newsletter, February
2001
In my 25 years of reproductive medicine, I consider that there
have been three major clinical breakthroughs: laparoscopy,
IVF/ICSI and most recently, the bubbling to the surface of
polycystic ovary syndrome. The latter may, in the final analysis,
have the greatest impact of the three. But what is PCOS? One
presenter has compared PCOS to the familiar quote, “I
can’t define it, but I know it when I see it.”
Thus far, every definition is in some way lacking. In a 1990
NIH conference, the definition of PCOS was addressed and the
working definition of PCOS as hyperandrogenic chronic
anovulation was put forward. With all due respect to
this group, this definition is too limited to encompass the
boundaries of this complex hormonal disturbance. At another
NIH conference held in September 2000, the experts seem to
confirm that a clear definition for PCOS was lacking. This
time the experts seemed more comfortable with the lack of
a precise definition and agreed that this was a reasonable
position to hold until more and larger population based studies
are available. Certainly, PCOS is not just about fertility.
It is not about any single problem. As it is presently emerging,
it is about how long and how well a life is spent. Now, let's
look back to see how far we have come.
The earliest description of polycystic ovaries appears to
date from 1845 when “sclerocystic” changes of
the ovary were described in a French manuscript. The term
sclerocystic refers to the typical physical appearance of
the PCOS ovary, characterized by a tough thickened shinny
white covering, overlying a layer of multiple benign cysts.
The term cyst, a small fluid filled sac with a lining of cells,
raises fear in many. These cysts are neither cancerous, nor
are they likely to become so. They are also usually small,
with the average size that of a pencil eraser. Soon after
1900 there were isolated reports of "degenerating"
cystic changes of the ovary and treatment by the removal of
a portion of the ovary, a procedure called a wedge resection.
In 1935, Doctors Stein and Leventhal reported a triad of hirsutism,
obesity and menstrual cycle disturbances leading to infertility
and associated this with enlarged sclerocystic ovaries. They
also were impressed by the appearance of the ovaries and suggested
that the cysts arose from ovarian follicles and were actively
making hormones. Because of the appearance of the ovaries,
they designated this condition polycystic ovarian disease.
The earlier term of “disease” is not quite correct.
A disease indicates a specific and constant set of symptoms
and physical findings. Even in this first report of only seven
patients, not all women investigated had all three of the
above clinical features. The term disease has now been abandoned
in favor of syndrome to reflect a grouping of symptoms, physical
and laboratory findings. Perhaps the term syndrome is still
too restrictive and broad spectrum may be a better designation.
Polycystic ovary and ovarian syndrome can be used interchangeably.
However, "ovary" might be preferable to make the
distinction that it is not an "ovarian syndrome"
but a syndrome in which the ovary has a central role.
Can a woman who has had her ovaries removed, or is post-menopausal,
still have PCOS? Can women who have normal appearing ovaries,
or regular menses, have PCOS? I believe the answer to be a
resounding YES. Is PCOS a good name for this clustering of
problems? There have been many alternative designations proposed
for PCOS. Dr. Futterweit suggested that it be called "polyfollicular
syndrome" and most recently Dr. Orzeck has suggested
"ovarian dysmetabolic syndrome" to emphasize the
need to incorporate the components of metabolic syndrome --
hypertension, abnormal lipid levels and insulin resistance
into PCOS. The ovaries may, or may not, be the primary source
of the disorder, but they intractably related. At long last
PCOS is becoming a flag to rally around and while PCOS may
be an imperfect designation, it matters much less what the
disorder is called than that it is recognized, evaluated,
and treated. So, how do we arrive at a diagnosis?
Personally, I am very liberal about the diagnosis of PCOS
and more so than most. I see no stigma attached to the diagnosis
and all the better if it opens up treatment options, or leads
to positive lifestyle intervention. If asked "could I
have PCOS?" I uniformly answer yes. Still, to determine
proper short treatment strategy and predict its success, or
discuss long-term health consequences, individuals who have,
or may have PCOS should be thoroughly evaluated. As much information
as possible should be recorded. Only in this way can we gain
real insight.
There are three major ways to the diagnosis of PCOS.
- Clinical findings: These include menstrual disturbance,
hair and skin problems, and obesity. Many with PCOS have menstrual
cycle lengths greater than 35 days and this is often a key
to the diagnosis. Still, some with PCOS have regular cycles.
Probably 40-60% of PCOS patients are obese, but it is not
known what percentage of obese women have PCOS. It is very
possible that many with PCOS may maintain a near normal weight,
but only with a great effort. There is also a distinct group
of thin PCOS patients that may have even more firmly entrenched
hormonal and fertility problems than their obese counterparts.
Not all patients are excessively hairy, but may have other
skin problems, such as acne. Once someone is familiar with
the common symptoms and physical appearance of individuals
with PCOS, the diagnosis can be made in family members, coworkers
and perhaps even in the occasional passer-by. Despite this,
it is surprising how often health care providers miss this
diagnosis.
-
Laboratory testing: There is considerable disagreement
about which test to order. I recommend the following tests
be drawn in the morning of day 2-3 after fasting since midnight.
A comprehensive biochemical panel, lipid profile, FSH to exclude
compromise of egg stores, LH (a finding of LH higher than
FSH level is a good indicator of ovarian dysfunction), DHEAS
(helps exclude adrenal involvement and possibly permits better
therapy planning), total testosterone, sex hormone binding
globulin, prolactin, thyroid stimulating hormone, fasting
insulin and glucose. These are best obtained in the first
2-3 days after menses. A blood lipid profile should be a part
of every evaluation and many should have a glucose tolerance
test along with insulin levels. Again it’s a personal
belief, but I contend that this one-time panel of screening
tests has a value that far exceeds its cost.
-
Ultrasound scan: Transvaginal ultrasound is the most sensitive
marker for PCOS. There is a characteristic pattern of ovarian
enlargement to 1.5 to 3 times normal size and 8-10 small cystic
structures less than 10 mm, which are usually located in a
circle around the ovarian surface, the commonly called a "string
of pearls." In some there ovaries are more polycystic
and in others, stroma predominates (stroma is the hormone
secreting tissue that surrounds the follicles. There is considerable
debate about the distinction between “PCO-appearing”
ovaries on ultrasound and PCOS. With pelvic ultrasound it
has been found that approximately 20-30% of women of reproductive
age will have polycystic ovaries, some despite proven fertility
and lack of other characteristic findings. About half of these
will have the other signs or symptoms of PCOS. If this otherwise
"normal" group is examined closely, there may be
subtle hormonal changes that could have significant impact
on long-term health.
How all this fits together is really unknown. Is PCOS only
symptom of a variety of problems, much like a fever is a consequence
of a number of diseases? Certainly most of our therapy is
directed at the symptoms rather than a cause. Is there a central,
yet to be identified problem that may be the root of all PCOS?
We know that there is a very strong genetic and hereditary
basis of PCOS, but it is more complicated than brown eyes
or blue. But, even if two individuals have the same gene they
may express the gene differently depending on their environment
and lifestyle. The story is starting to unfold and breakthroughs
hopefully are at hand.
It is a sad reflection on the medical profession, but we have
not done a very good job of helping PCOS patients. We have
been able to help some establish a pregnancy with fertility
drugs and others to gain some semblance of normal menstrual
cycles with birth control pills. Too often there has been
a failure of perspective, possibly the reason a physician
was consulted in the first place. The average medical visit
lasts about 15 minutes, during which time a history must be
taken, an exam performed and a treatment plan given. Most
physicians know about PCOS, we hope. Unfortunately, there
isn’t the time for the complete history and thorough
discussion. It is a fact, not an excuse.
The evolution of PCOS is the evolution of modern medicine.
We are rapidly moving from treatment of disease to altering
risks of it. It will be interesting to see where PCOS will
go and who will be in the driver’s seat.
Sam Thatcher MD, PhD
Center for Applied Reproductive Science
Johnson City, Tennessee
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