Polycystic ovary syndrome

Polycystic ovary syndrome is a condition in which there is an imbalance of a woman's female sex hormones. This
hormone imbalance may cause changes in the menstrual cycle, skin changes, small cysts in the ovaries, trouble
getting pregnant, and other problems.

Causes

Female sex hormones include estrogen and progesterone, as well as hormones called androgens. Androgens, often
called "male hormones," are also present in women, but in different amounts.

Hormones help regulate the normal development of eggs in the ovaries during each menstrual cycle. Polycystic
ovary syndrome is related to an imbalance in these female sex hormones. Too much androgen hormone is made,
along with changes in other hormone levels.

It is not completely understood why or how the changes in the hormone levels occur.

Follicles are sacs within the ovaries that contain eggs. Normally, one or more eggs are released during each
menstrual cycle. This is called ovulation. In polycystic ovary syndrome, the eggs in these follicles do not mature and
are not released from the ovaries. Instead, they can form very small cysts in the ovary.

These changes can contribute to infertility. The other symptoms of this disorder are due to the hormone imbalances.

Women are usually diagnosed when in their 20s or 30s, but polycystic ovary syndrome may also affect teenage girls.
The symptoms often begin when a girl's periods start. Women with this disorder often have a mother or sister who
has symptoms similar to those of polycystic ovary syndrome.

Symptoms

Changes in the menstrual cycle:

 Absent periods, usually with a history of having one or more normal menstrual periods during puberty
(secondary amenorrhea)
 Irregular menstrual periods, which may be more or less frequent, and may range from very light to very
heavy

Development of male sex characteristics (virilization):

 Decreased breast size

 Deepening of the voice
 Enlargement of the clitoris
 Increased body hair on the chest, abdomen, and face, as well as around the nipples (called hirsutism)
 Thinning of the hair on the head, called male-pattern baldness

Other skin changes:

 Acne that gets worse

 Dark or thick skin markings and creases around the armpits, groin, neck, and breasts due to insulin
sensitivity
 Exams and TestsDuring a pelvic examination, the health care provider may note an enlarged clitoris (very
rare finding) and enlarged ovaries.
Diabetes, high blood pressure, and high cholesterol are common findings, as are weight gain and obesity.

Weight, body mass index (BMI), and abdominal circumference are helpful in determining risk factors.

Levels of different hormones that may be tested include:

 Estrogen levels
 FSH levels
 LH levels
 Male hormone (testosterone) levels
 17-ketosteroids

Other blood tests that may be done include:

 Fasting glucose and other tests for glucose intolerance and insulin resistance
 Lipid levels
 Pregnancy test (serum HCG)
 Prolactin levels
 Thyroid function tests

Other tests may include:

 Vaginal ultrasound to look at the ovaries

 Pelvic laparoscopy to look more closely at, and possibly biopsy the ovaries

Treatment

Losing weight (which can be difficult) has been shown to help with diabetes, high blood pressure, and high
cholesterol. Even a weight loss of 5% of total body weight has been shown to help with the imbalance of hormones
and also with infertility.

Medications used to treat the abnormal hormones and menstrual cycles of polycystic ovary syndrome include:

 Birth control pills or progesterone pills, to help make menstrual cycles more regular
 Metformin, a medication that increases the body's sensitivity to insulin, can improve the symptoms of
PCOS and sometimes will cause the menstrual cycles to normalize. For some women, it can also help with
weight loss.
 LH-releasing hormone (LHRH) analogs

Treatment with clomiphene citrate causes the egg to mature and be released. Sometimes women need this or other
fertility drugs to get pregnant.

Medications or other treatments for abnormal hair growth include:

 Birth control pills. It may take several months to begin noticing a difference.
 Anti-androgen medications, such as spironolactone and flutamide may be tried if birth control pills do not
work.
 Eflornithine cream may slow the growth of unwanted facial hair in women.
 Hair removal using laser and nonlaser light sources damages individual hair follicles so they do not grow
back. This can be expensive and multiple treatments are needed. Laser removal can be combined with other
medicines and hormones.
Glucophage (Metformin), a medication that makes cells more sensitive to insulin, may help make ovulation and
menstrual cycles more regular, prevent type 2 diabetes, and add to weight loss when a diet is followed.

Pelvic laparoscopy to remove a section of the ovary or drill holes in the ovaries is sometimes done to treat the
absence of ovulation (anovulation) and infertility. The effects are temporary.

Outlook (Prognosis)

Women who have this condition can get pregnant with the right surgical or medical treatments. Pregnancies are
usually normal.

Possible Complications

 Increased risk of endometrial cancer

 Infertility (early treatment of polycystic ovary disease can help prevent infertility or increase the chance of
having a healthy pregnancy)
 Obesity-related (BMI over 30 and waist circumferance greater than 35) conditions, such as high blood
pressure, heart problems, and diabetes
 Possible increased risk of breast cancer

When to Contact a Medical Professional

Call for an appointment with your health care provider if you have symptoms of this disorder.

Alternative Names

Polycystic ovaries; Polycystic ovary disease; Stein-Leventhal syndrome; Polyfollicular ovarian disease

POLYCYSTIC OVARY SYNDROME

MAKING PCOS LESS CONFUSING

PCOS (polycystic ovary syndrome) is the commonest female hormonal disorder and affects at least 5 to 8% of women
– almost 10 million women in America alone. Yet common as it is, many with PCOS find it baffling – and so do many
doctors. This lack of information is regrettable and unnecessary. Though PCOS is a complex condition, it is
understandable!

PCOS should not be so hard to diagnose because many of its signs are visible: oily skin and acne, increased hair
growth on face and body (hirsutism) and loss of scalp hair (androgenic alopecia). Many women with PCOS have
difficulty controlling their weight; it is one of the major causes of obesity in women. PCOS can cause irregular
periods, infertility and even depression. One of the underlying factors is insulin resistance (IR), also called metabolic
or dysmetabolic syndrome.

Recently, more information about PCOS has become available. Unfortunately much of it is fragmented or even
contradictory. I wrote this article to put this information together so that it makes sense.

In writing about PCOS, I have to discuss the problems it causes but no reader should feel discouraged because, the
basic message is positive: PCOS can be understood and it can be treated.

THE FRUSTRATION OF PCOS

It is frustrating just to have symptoms and even more frustrating when you cannot find anyone who will explain
what they mean. Many of the women I see for PCOS at the Hormone Center of New York have been in just this
situation; they knew something was wrong but could not get their doctors to give them a clear explanation or,
sometimes, even to admit there was a problem.

Polycystic ovary syndrome (PCOS) has several features. Some of the confusion arises because different doctors focus
on different aspects. Some define PCOS by how the ovary looks on ultrasound, some by the LH to FSH ratio, some by
testosterone levels, and some by insulin levels, others by the menstrual pattern or the skin and hair changes. Which
of these is most important? The answer is simple: they all are.

 Actually PCOS is not one condition but a group of them. Your PCOS may be quite different from someone else’s
whom you know with the condition. So it is important not only to understand the condition in general but to
understand how it affects you.

THE FOUR (OR FIVE) FEATURES OF PCOS

A few years ago I was asked by a group of pharmaceutical scientists to help them devise a computer model for
PCOS. This led me to spend a lot of time thinking how PCOS can be broken down into separate features. Finally I
came up with a 4 +1 scheme which I believe helps clarify PCOS and make its individual variation easier to grasp.

Here are the 4+1 features of PCOS:

1) Skin and hair changes due to the action of testosterone. These are oily skin and acne, hirsutism (increased
facial and body hair), and androgenic alopecia (the female hair loss).

2) Changes in the menstrual cycle (irregular periods) and infertility due to hormone changes inside the ovary.

3) Obesity due to difficulty controlling weight. The extra weight tends to be in the upper body and often the legs
are quite thin. Often, standard diets don’t work.

4) Shifts in metabolism, principally insulin resistance (IR) and unfavorable cholesterol changes. High blood
pressure is not uncommon. All these can be risk factors for later heart disease. A skin change called ACN
(acanthosis nigricans) can be a sign of IR. 

5) The fifth feature is an indirect but very important one: the emotional stress of dealing these physical and
metabolic changes. Some speculate that PCOS may directly cause depression by an effect on brain chemistry.
This is not proven but is almost beside the point because the physical symptoms are discouraging enough in
themselves. PCOS does not diminish femininity but its effects -- weight gain, hirsutism (increased hair growth),
alopecia (hair loss), difficulty in getting pregnant -- can certainly make a woman insecure about herself.

WHO SHOULD HAVE A WORKUP FOR PCOS?

If you - or someone important to you - have some of the following, you should consider evaluation for PCOS. (This is
intended as general information only. Medical diagnosis must be done through consultation with a physician.)

Very oily skin

Persistent acne

Facial or body hair that requires more than occasional removal (hirsutism)

Loss of scalp hair (alopecia, sometimes called androgenic alopecia)  This is common with PCOS but many women
have hair loss without any of the other changes.

Darkening of the skin on the back of neck or underarms (Acanthosis nigricans)

Irregular periods (Periods usually more than 5 weeks apart or prolonged, or heavy bleeding.) This is usually because
the ovary does not produce an egg cell (ovum) every month, a situation called anovulation.
Difficulty controlling weight, especially if the extra weight is on the upper part of the body or the abdomen,
sometimes referred to as upper segment obesity

THERE ARE AS MANY FORMS OF PCOS AS THERE ARE WOMEN WITH THE CONDITION
If you have several of the features I have listed, you probably have PCOS. Unfortunately doctors tend to quibble
about the definition. Many women have only partial PCOS. Whether to call what you have PCOS or not is less important
than getting proper treatment directed at the aspects you do have.

 The approach I take is to work out an individual PCOS profile based on the extent to which each of the four features
is present. This gets to what is really important: what features of the condition are present and what treatment will
best help them.

If you think you have PCOS or have been told you do, don’t just settle for the diagnosis; find out what your PCOS is.

HOW BAD IS PCOS?

This is a question I hear frequently. Most of the time PCOS is not nearly as bad as it is made to sound. Medical texts
are often misleading because they describe only the most extreme form.

 All features of PCOS can be treated effectively. The more you know about PCOS, the more you will be able to be your
own advocate in getting treatment.

NOT EVERYONE WHO HAS BEEN TOLD SHE HAS PCOS REALLY HAS IT
While I see many women with PCOS who were never told what their problem was, I also see some who have been
told that they have PCOS but do not. The skin and hair changes in particular can occur without any of the other
features. If you have increased facial or body hair (hirsutism), or loss of hair from the scalp (alopecia) but no other
symptoms of PCOS, you may find the articles on acne, increased hair and alopecia helpful to you.

Labels are stereotypes and stereotyping tends to hide individual differences. With PCOS the differences between
women with the condition are as important as the similarities.

WHAT HAPPENS IN PCOS:

INSULIN RESISTANCE, THE NEWEST PIECE OF THE PUZZLE
I’ve already mentioned the four features of PCOS. You may be wondering, why do these things tend to happen
together? Here’s the story, as we understand it today. The basic problem seems to be that the body becomes resistant
to its own insulin, a situation called insulin resistance (IR). Too much insulin can be just as much a problem as too
little. In IR, the body has a sluggish response to its own insulin and compensates by making more and more.
Eventually, the IR gets worse and the pancreas cannot make enough insulin to overcome it. At this point blood
glucose levels start to go up.

WHAT DOES IR DO?

When insulin goes up several things happen. It acts on the ovary to cause it to make too much testosterone. This may
stop ovulation, causing irregular periods and difficulty getting pregnant. Much of the testosterone goes into the
blood stream which carries it throughout the body. When it reaches the skin, the testosterone makes it oily and
stimulates hair follicles on the face and body. It also can cause scalp hair to thin.

Insulin causes the body to store energy in the form of fat and carbohydrate. This results in weight gain, especially on
the upper body and abdomen.

The most common cause of insulin resistance is being overweight. Weight gain increases IR and IR makes it harder to
lose weight. It’s not fair. Later I’ll discuss how IR can be overcome.

Studies have shown that nearly all women with PCOS have some insulin resistance. However slender women with
PCOS have only a minimal degree that can be detected only by a special research procedure.
Those of us with a long term interest in PCOS have known about the associated metabolic problems for more than a
decade. However they have only recently become more widely known.

LAB TESTS AND PCOS

As I have been emphasizing, PCOS is not really one condition but several and so there is no one test for PCOS.
However there are several tests which are important to characterize a particular woman’s PCOS.

Androgens are the so-called male hormones of which testosterone is the most familiar and important. Others often
measured are and androstenedione and DHEA-S. These do not have much effect on their own but can be converted
in the body to testosterone.

Some tests are not very useful: DHT (dihydrotestosterone) is the activated from of testosterone but blood levels do
not reflect what is happening in the skin or ovaries. 3 alpha diol G, was once thought to be an indirect measure of
tissue DHT but has not turned out to be useful.

Workup for PCOS should include testosterone and DHEA-S. However testosterone can be measured in two forms:
total testosterone and free testosterone. The second is the more useful. It is called “free” because it is not attached to
blood proteins and so is free to move into skin and other tissues where it causes its unwanted effects – acne,
hirsutism and alopecia, as well as anovulation. Best is to get both free and total testosterone measured at the same
time.

I WAS TOLD MY TESTS ARE NORMAL. WHAT DOES THAT MEAN?

Tests mean nothing until they are correctly interpreted. Even if a woman’s androgens are normal, they can still have
unwanted effects on skin and hair. This is because some women have skin which is much more sensitive to
testosterone than others. This skin over-reactivity can be the cause of acne, increased hair or alopecia when the blood
tests are normal.

The most important thing is this: There are treatments which work for acne, increased hair (hirsutism) and alopecia
even when all hormone levels are normal! Don’t feel discouraged if your tests are normal; help is still available.

LH/FSH   These are the pituitary hormones which regulate the ovary. In PCOS, LH is often higher than FSH. This test
is not much use though because results are too variable. FSH is important for any women whose periods are less than
every five weeks to be sure her ovaries are still able to function. A very high value of FSH, as happens after
menopause, suggests that the ovary can no longer make eggs and estrogen. However FSH is normally high just
before ovulation.

Prolactin This is another pituitary hormone; it helps the breast to make milk. High levels can stop menstruation so it
should also be measured when a woman is having infrequent periods. High prolactin is a different cause of lack of
periods than PCOS and treatment is quite different.

Ultrasound and the “cysts” of PCOS

One would think from the name, polycystic ovary syndrome that the cysts in the ovary are very important. Actually,
they are one of the least important features and this is often a point of confusion. There are many kinds of cysts
which can form in the body and they have quite different causes. With PCOS, the cysts are actually so tiny as to be
barely visible. (They have nothing to do with the usual ovarian cysts which many women have and which can cause
pain or bleeding and sometimes need to be removed. Those cysts generally occur one at a time and usually go away
in one or two cycles.)

The test used to look for cysts in the ovary is the ultrasound which can be done transabdominally or transvaginally.
Useful as this test can be, ultrasound is not the proper way to diagnose polycystic ovary syndrome. Some women
have many small cysts but regular periods and do not have the four features of PCOS. Others without cysts in their
ovaries do have the other features.

Tests for insulin resistance (IR)

The test for IR is a modification of the test for diabetes. For both, a standard 3 hour glucose tolerance test (GTT) is
done. Blood is taken for glucose, then a drink with 75 g of glucose is taken and more samples are taken at ½, 1, 2 and
3 hours. In looking for IR, insulin is measured either fasting or at each time period in addition to glucose. Labs are
still not used to doing the insulin levels, so if you have it done be sure to remind them that you need insulin done,
not just glucose.

The GTT is not particularly popular. It takes more than 3 hours, the glucose drink tastes bad and often does not sit
well on an empty stomach. However this is the best test available outside a research laboratory.

The idea has gotten around that diabetes can be diagnosed just with a simple fasting blood glucose level. This is
wrong. When diabetes is associated with PCOS, it is usually quite mild and will not show up with just a fasting level.
The GTT is so valuable precisely because it can pick up the tendency to diabetes much earlier. Not surprisingly
earlier diagnosis means more better treatment.

WHY IT IS IMPORTANT TO DETECT IR EARLY

Frequently, I make the initial diagnosis of diabetes in women with PCOS. Recognizing the signs of PCOS means
diabetes can be picked up at an earlier, milder stage. When diabetes is caught early, use of oral medication almost
always results in completely normal glucose levels. It is rare that the sort of diabetes associated with PCOS needs to
be treated with insulin injections, oral medication works better. So I have found it definitely worthwhile to test early
for diabetes in women who have PCOS. No one likes the thought that she might have diabetes but with early
recognition and much better medications, the outlook has changed dramatically for the better. (Not every woman
with PCOS needs to be tested for diabetes but most do. This depends on weight, other signs of PCOS and family
history.)

TREATING WHAT’S HAPPENING: THE INDIVIDUALIZED PCOS TREATMENT PLAN

I find that a comprehensive approach to treating PCOS is best. Each of the four possible features is assessed and
treatment planned accordingly. There is no one-size-fits-all treatment for PCOS.

In what follows you will find information about treatment of each of the four features of PCOS. I have tried to be
detailed and specific but only in consultation with a doctor can you determine which is right for you.

SKIN AND HAIR CHANGES:

CLEARING ACNE, DECREASING UNWANTED HAIR,
BRINGING BACK SCALP HAIR
The skin and hair changes are due to the effect of testosterone on the oil (sebaceous) glands and hair follicles. There
are two parts to this treatment: lowering testosterone and blocking its effects.

If testosterone levels are elevated, treatment usually includes lowering them. The best way to do this depends on
where the extra testosterone is coming from. When it comes from the ovary, oral contraceptives (OCs) usually lower
it by about half. It is important to use one of the several OCs which do not have testosterone-like activity. In rare
situations, other medications can be used to suppress the ovary more completely.

When the testosterone comes from the adrenal, a cortisone-like medication called dexamethasone can be used in low
doses to partially suppress the adrenal so that it makes less testosterone. This medication should be used only in
special circumstances and in very low doses.

Is lowering testosterone enough?

Treatments which lower testosterone include oral contraceptives and insulin sensitizers which are discussed in the
next section. While lowering testosterone can have some benefit on skin and hair changes, adding a testosterone
blocker often produces a much better result.

Blocking testosterone can be done with medications such as spironolactone (Aldactone®) and certain others which
are less commonly used. While these are not labeled for treatment of PCOS, they are used quite often. These help
clear acne, reduce facial and body hair and ameliorate alopecia. The section on increased hair (hirsutism) tells more
about these medications. Sometimes finasteride (Proscar® and Propecia®) is used to prevent the activation of
testosterone in the skin. With these as with any other medication which blocks testosterone, it is essential to avoid
pregnancy because there is worry that they might adversely affect development of a male fetus. However, they will
not affect pregnancy after they have been discontinued for an adequate interval. Any women who is on medication
should discuss with her physician ahead of time what to do about the medication when she is trying for pregnancy
or pregnant.

Does anything really help with hirsutism or alopecia?

Sadly, many women with PCOS are told nothing can be done. Generally this sort of advice is from physicians who do
not take these problems seriously or do not know how to treat them. Do not let yourself succumb to pessimism about
PCOS! Proper treatment usually can reduce facial and body hair and help scalp hair. Shedding in androgenic
alopecia can be slowed toward normal and many women get regrowth. Hair may not be restored to the fullest it ever
was but often there is enough improvement to reduce the terrible worry that goes with alopecia. Of course, as with
any medical treatment, results vary. Unfortunately, if left alone, alopecia and hirsutism often get worse over time. For
this reason, if you are distressed by them, its best to seek evaluation and treatment rather than waiting to see if they
will go away.

GETTING THE CYCLE BACK IN ORDER

Since periods are an inconvenience, some women ask, “what is wrong with not having them?” It is not that periods
are good in themselves but rather that regular menses are a sign that hormonal mechanisms are functioning properly.

Irregular periods occur commonly with PCOS because ovulation does not occur every month as it is supposed to.
The most common pattern is for periods to come infrequently. However some women with PCOS have prolonged
and heavy periods. When ovulation does not occur, the ovary does not make progesterone during the second half of
the cycle. Progesterone is necessary to prepare the uterus to have a normal period. When months go by with no
period, the endometrium (uterine lining) can get thicker and thicker. Then when a period does come, either on its
own or from medication, it is like having several at once: heavy, sometimes with clots and often crampy.

IRREGULAR PERIODS AND CANCER

There is a potentially serious issue with infrequent periods and PCOS. Progesterone protects the lining of the uterus
(endometrium) from overgrowth which can lead to cancer. It is very important that women with PCOS who have
irregular periods be treated with a form of progesterone to protect against cancer. This can either be an oral
contraceptive (all contain a form of progesterone) or a separate medication taken for at least twelve days every one or
two months. The various forms of progesterone are discussed in the article on menopausal hormone replacement.
The most commonly used is MPA (medroxyprogesterone acetate or Provera®) but natural progesterone
(Prometrium®) can also be used and tends to have fewer side effects.

Proper progesterone treatment can prevent most cases of endometrial cancer. Despite this, some women are still told
that not getting periods does not matter. Periods themselves may not matter but protecting the uterus against cancer
matters a lot.

TREATMENT OF INSULIN RESISTANCE

Having IR does not necessarily mean that someone has diabetes It does however, if a person is overweight, increase
the chance that she or he will develop diabetes, particularly if there is a family history. Over time, the resistance to
insulin tends to increase and when the pancreas can no longer keep up by making more insulin, glucose levels go up
in the blood and diabetes develops.

This is not inevitable however. Some simply luck out and do not develop diabetes at all. Losing weight, even as little
as 20 pounds is the best way to reduce the risk. Not everyone is able to accomplish this however. The unfair thing
about IR is that not only is it made worse by weight gain, it makes losing the weight harder. Fortunately we now
have medications which restore the body’s response to insulin. These medications can reduce IR considerably and
may even lessen the chances of going on the actual diabetes.

THE NEW MEDICATIONS FOR IR AND EARLY DIABETES

Older diabetes medications simply pushed the pancreas to release more insulin to overcome the IR. Rather than flog
the pancreas, it is better to restore the body’s response to insulin. Several new medications can do this. The one most
often used for IR in PCOS is metformin (Glucophage® and Glucophage XR®). One of the appeals of this medication
is that it often helps somewhat in losing weight. It can be unsafe in people with kidney disease and interacts with
certain things such as x-ray dye and general anesthesia, so if you are on metformin, be sure to tell any doctor or any
other health care provider you see that you are on it.
Two newer drugs which directly improve the body’s response to insulin are rosiglitazone (Avandia®) and
pioglitazone (Actos®). A similar medication, troglitazone (Rezulin®) was withdrawn because it could cause serious
liver problems. The two new ones are much safer for the liver but you should discuss the need for monitoring with
your doctor. Research on troglitazone in PCOS showed that it could improve IR and it is likely that the two newer
and safer ones have the same effect though so far as I know, they have not yet been studied with PCOS.

One of the best things about insulin sensitizers is that they often restore ovulation and may improve the odds of
getting pregnant. Many specialists feel they are the first thing to try, before more difficult and expensive treatments
such as hormone injections or IVF. While they have been used to help fertility, they are not FDA approved for this
indication, or specifically for PCOS. However they are widely used. Recent reports suggest that metformin can
reduce miscarriages in women with PCOS and may be safe throughout pregnancy. As stated before however, the
question of whether to continue medication when trying for pregnancy and when pregnant should be discussed in
advance with your physician.

WEIGHT LOSS AND PCOS

Weight is an important factor and in an unfair way because PCOS seems to make the pounds go too quickly and off
too slowly, if at all. And as weight is gained, the various symptoms may increase. Some women have few signs of
PCOS but develop them during a period of weight gain. IR promotes weight gain because the higher insulin levels
make it harder for the body to break down fat.

Two things can help with this frustrating situation. First, metformin helps somewhat with weight loss in people with
IR It is not a “diet pill” – all diet pills have harmful effects and are to be avoided. Second, a change in nutrition to
high protein, low carbohydrate has made a major difference for many women with PCOS. There are several books
about these diets but in my experience people do much better if they see a professional registered dietitian.
[www.thelowcarblife.com]  The dietary establishment is still skeptical about low carb diets – the American Dietetic
Association issued a position statement questioning them – but they clearly work for many women for whom
nothing else works. Low carb diets require eating meat or fish. If you are vegetarian, a different approach is needed –
and it is even harder to find a sympathetic nutritionist -- but veg diets can be good for PCOS too.

INFERTILITY AND PCOS

This is a whole subject by itself. The important thing is that treatment of women with PCOS who experience
difficulty getting pregnant is improving. Insulin sensitizers restore ovulation in many, though not all, women with
PCOS, although they are not FDA approved for this use at the present time.

One of the best things about insulin sensitizers is that they often restore ovulation and may improve the odds of
getting pregnant. Many specialists feel they are the first thing to try, before more difficult and expensive treatments
such as hormone injections or IVF. While they have been used to help fertility, they are not FDA approved for this
indication, or specifically for PCOS. However they are widely used. Recent reports suggest that metformin can
reduce miscarriages in women with PCOS and may be safe throughout pregnancy. As stated before however, the
question of whether to continue medication when trying for pregnancy and when pregnant should be discussed in
advance with your physician. 

Women with PCOS who have not conceived within a few months of trying should consult an infertility specialist.
How long to try before considering workup and treatment is individual.

While it is true that PCOS can cause infertility, it is important to realize that not all women with PCOS have
difficulty getting pregnant. Those with regular periods often can conceive without difficulty. A young woman with
PCOS should not assume she cannot become pregnant. Many do without any need for treatment and for those who
need treatment, it is often successful. Be careful to get reliable advice about this. The world is full of people whose
mothers were told they could not get pregnant!

Some specialists think that for women with PCOS, the use of birth control pills to rest the ovary may limit
progression of changes and is therefore a good idea in the years before pregnancy is desired. This is not proven but
seems sensible for women who have no contraindications for OC use. It is well established that taking the pill does
not reduce the chances of getting pregnant.
IS THERE A MALE PCOS?
PCOS is partly, though not entirely, genetic. One wonders then, what about males who inherit genes related to
PCOS? While there will probably be no absolute proof until the genes for PCOS have been completely identified, I
think the answer is right in front of us. Those men with substantial hair loss, who are overweight on the upper part of
their body and insulin resistant probably have the male equivalent of PCOS. Of course having facial and body hair is
normal for men so no one pays attention. Men cannot have irregular periods but they can have the metabolic
changes. I suspect that many men with adult onset diabetes actually have the equivalent of PCOS. I’ve noticed that
many of the women I see at the Hormone Center of New York have a family history of diabetes, often in male relatives.

Significantly, the treatment for IR or diabetes in men is the same as that for women with PCOS – insulin sensitizers.
Of course, many of the hormonal treatments I have discussed are suitable only for women.

A FINAL WORD OF ENCOURAGEMENT

PCOS can be a difficult condition: difficult to live with , difficult to understand and difficult to find treatment for.
There is help for all these difficulties however. The first step in making life with PCOS tolerable is being able to
understand what is happening. But the most important is finding a physician who is aware of recent research and
can properly apply the new treatments.

Things are getting better. The several year old Polycystic Ovary Syndrome Association is an effective advocacy
organization. The women’s media now recognizes the importance of the condition and carries more information
about it. But the most important thing is this: there are now enough options so that any woman with PCOS can find
treatment that will make a real difference for her.

Polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders affecting approximately 5%-10% of
women of reproductive age (12–45 years old) and is thought to be one of the leading causes of female subfertility.[1][2][3][4]

The principal features are obesity, anovulation (resulting in irregular menstruation) or amenorrhea, acne, and excessive amounts
or effects of androgenic (masculinizing) hormones. The symptoms and severity of the syndrome vary greatly among women.
While the causes are unknown, insulin resistance, diabetes, and obesity are all strongly correlated with PCOS.

[edit] Nomenclature

Other names for this syndrome include polycystic ovarian syndrome (also PCOS), polycystic ovary disease (PCOD), functional
ovarian hyperandrogenism, Stein-Leventhal syndrome (original name, not used in modern literature), ovarian hyperthecosis
and sclerocystic ovary syndrome.

[edit] Signs and symptoms

Common symptoms of PCOS include

 Oligomenorrhea, amenorrhea — irregular, few, or absent menstrual periods.

 Infertility, generally resulting from chronic anovulation (lack of ovulation).
 Hirsutism — excessive mild symptoms of hyperandrogenism, such as acne or hypermenorrhea,
are frequent in adolescent girls and are often associated with irregular menstrual cycles. In most
instances, these symptoms are transient and only reflect the immaturity of the hypothalamic-
pituitary-ovarian axis during the first years following menarche.[8] Approximately three-fourths
of patients with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of
hyperandrogenemia.[9]
PCOS can present in any age during the reproductive years. Due to its often vague presentation it
can take years to reach a diagnosis.

Serum insulin, insulin resistance and homocysteine levels are significantly higher in subjects
having PCOS but have no significant effect on fertility.[10]

[edit] Diagnosis
Not all women with PCOS have polycystic ovaries (PCO), nor do all women with ovarian cysts
have PCOS[citation needed]; although a pelvic ultrasound is a major diagnostic tool, it is not the only
one. The diagnosis is straightforward using the Rotterdam criteria, even when the syndrome is
associated with a wide range of symptoms.

 Standard diagnostic assessments:

o History-taking, specifically for menstrual pattern, obesity, hirsutism, and the absence of
breast development. A clinical prediction rule found that these four questions can
diagnose PCOS with a sensitivity of 77.1% (95% confidence interval [CI] 62.7%–88.0%)
and a specificity of 93.8% (95% CI 82.8%–98.7%).[11]
o Gynecologic ultrasonography, specifically looking for small ovarian follicles. These are
believed to be the result of disturbed ovarian function with failed ovulation, reflected by
the infrequent or absent menstruation that is typical of the condition. In normal
menstrual cycle, one egg is released from a dominant follicle - essentially a cyst that
bursts to release the egg. After ovulation the follicle remnant is transformed into a
progesterone producing corpus luteum, which shrinks and disappears after
approximately 12–14 days. In PCOS, there is a so called "follicular arrest", i.e., several
follicles develop to a size of 5–7 mm, but not further. No single follicle reach the
preovulatory size (16 mm or more). According to the Rotterdam criteria, 12 or more
small follicles should be seen in an ovary on ultrasound examination. The follicles may
be oriented in the periphery, giving the appearance of a 'string of pearls'. The numerous
follicles contribute to the increased size of the ovaries, that is, 1.5 to 3 times larger than
normal.
o Laparoscopic examination may reveal a thickened, smooth, pearl-white outer surface of
the ovary. (This would usually be an incidental finding if laparoscopy were performed for
some other reason, as it would not be routine to examine the ovaries in this way to
confirm a diagnosis of PCOS).
o Serum (blood) levels of androgens (male hormones), including androstenedione,
testosterone and Dehydroepiandrosterone sulfate may be elevated.[12] The free
testosterone level is thought to be the best measure, [13] with ~60% of PCOS patients
demonstrating supranormal levels.[9] The Free androgen index of the ratio of
testosterone to sex hormone-binding globulin (SHBG) is high, is meant to be a predictor
of free testosterone, but is a poor parameter for this and is no better than testosterone
alone as a marker for PCOS,[14] possibly because FAI is correlated with the degree of
obesity.[15]
o Some other blood tests are suggestive but not diagnostic. The ratio of LH (Luteinizing
hormone) to FSH (Follicle stimulating hormone) is greater than 1:1, as tested on Day 3 of
the menstrual cycle. The pattern is not very specific and was present in less than 50% in
 one study.[16] There are often low levels of sex hormone binding globulin, particularly
among obese women.

 Common assessments for associated conditions or risks

o Fasting biochemical screen and lipid profile
o 2-hour oral glucose tolerance test (GTT) in patients with risk factors (obesity, family
history, history of gestational diabetes) and may indicate impaired glucose tolerance
(insulin resistance) in 15-30% of women with PCOS. Frank diabetes can be seen in 65–
68% of women with this condition. Insulin resistance can be observed in both normal
weight and overweight patients.
 For exclusion of other disorders that may cause similar symptoms:
o Prolactin to rule out hyperprolactinemia
o TSH to rule out hypothyroidism
o 17-hydroxyprogesterone to rule out 21-hydroxylase deficiency (congenital adrenal
hyperplasia). Many such women may appear similar to PCOS and be made worse by
insulin resistance or obesity, but they can be greatly helped by adrenal suppression with
low-dose glucocorticoid therapy.

 Fasting insulin level or GTT with insulin levels (also called IGTT). Elevated insulin levels have been
helpful to predict response to medication and may indicate women who will need higher
dosages of metformin or the use of a second medication to significantly lower insulin levels.
Elevated blood sugar and insulin values do not predict who responds to an insulin-lowering
medication, low-glycemic diet, and exercise. Many women with normal levels may benefit from
combination therapy. A hypoglycemic response in which the two-hour insulin level is higher and
the blood sugar lower than fasting is consistent with insulin resistance. A mathematical
derivation known as the HOMAI, calculated from the fasting values in glucose and insulin
concentrations, allows a direct and moderately accurate measure of insulin sensitivity (glucose-
level x insulin-level/22.5).
 Glucose tolerance testing (GTT) instead of fasting glucose can increase diagnosis of increased
glucose tolerance and frank diabetes among patients with PCOS according to a prospective
controlled trial.[17] While fasting glucose levels may remain within normal limits, oral glucose
tests revealed that up to 38% of asymptomatic women with PCOS (versus 8.5% in the general
population) actually had impaired glucose tolerance, 7.5% of those with frank diabetes
according to ADA guidelines.[17]

[edit] Differential diagnosis

Other causes of irregular or absent menstruation and hirsutism, such as congenital adrenal
hyperplasia, Cushing's syndrome, hyperprolactinemia, androgen secreting neoplasms, and other
pituitary or adrenal disorders, should be investigated. PCOS has been reported in other insulin
resistant situations such as acromegaly.

[edit] Pathogenesis
Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of
male hormones (androgens), particularly testosterone, either through the release of excessive
luteinizing hormone (LH) by the anterior pituitary gland or through high levels of insulin in the
blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus.

The syndrome acquired its most widely used name due to the common sign on ultrasound
examination of multiple (poly) ovarian cysts. These "cysts" are actually immature follicles, not
cysts ("polyfollicular ovary syndrome" would have been a more accurate name). The follicles
have developed from primordial follicles, but the development has stopped ("arrested") at an
early antral stage due to the disturbed ovarian function. The follicles may be oriented along the
ovarian periphery, appearing as a 'string of pearls' on ultrasound examination. The condition was
first described in 1935 by Dr. Stein and Dr. Leventhal, hence its original name of Stein-
Leventhal syndrome.

PCOS is characterized by a complex set of symptoms, and the cause cannot be determined for all
patients. However, research to date suggests that insulin resistance could be a leading cause.
PCOS may also have a genetic predisposition, and further research into this possibility is taking
place. No specific gene has been identified, and it is thought that many genes could contribute to
the development of PCOS.

A majority of patients with PCOS have insulin resistance and/or are obese. Their elevated insulin
levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis
that lead to PCOS.

Adipose tissue possesses aromatase, an enzyme that converts androstenedione to estrone and
testosterone to estradiol. The excess of adipose tissue in obese patients creates the paradox of
having both excess androgens (which are responsible for hirsutism and virilization) and
estrogens (which inhibits FSH via negative feedback).[18]

Also, hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased
ovarian androgen production, decreased follicular maturation, and decreased SHBG binding; all
these steps lead to the development of PCOS. Insulin resistance is a common finding among
patients of normal weight as well as those overweight patients.

PCOS may be associated with chronic inflammation, with several investigators correlating
inflammatory mediators with anovulation and other PCOS symptoms.[19][20]

One study in the United Kingdom concluded that the risk of PCOS development was shown to
be higher in lesbian women than in heterosexuals.[21][22] It should be noted however that all the
participants in this study were referred after infertility was discovered or highly suspected and
conclusion made is purely conjecture. Until further studies have been conducted and the research
collaborated there is no assumption that female homosexuality will increase the occurrence of
PCOS.

[edit] Management
Medical treatment of PCOS is tailored to the patient's goals. Broadly, these may be considered
under four categories:

 Lowering of insulin levels

 Restoration of fertility
 Treatment of hirsutism or acne
 Restoration of regular menstruation, and prevention of endometrial hyperplasia and
endometrial cancer

In each of these areas, there is considerable debate as to the optimal treatment. One of the major
reasons for this is the lack of large scale clinical trials comparing different treatments. Smaller
trials tend to be less reliable and hence may produce conflicting results.

General interventions that help to reduce weight or insulin resistance can be beneficial for all
these aims, because they address what is believed to be the underlying cause of the syndrome.
Regular exercise and maintaining a healthy weight will help reduce the hormonal imbalance,
restore ovulation and fertility, and improve acne and hirsutism.[23]

[edit] Insulin lowering

[edit] Diet

Where PCOS is associated with overweight or obesity, successful weight loss is probably the
most effective method of restoring normal ovulation/menstruation, but many women find it very
difficult to achieve and sustain significant weight loss. Low-carbohydrate diets and sustained
regular exercise may help. Some experts recommend a low GI diet in which a significant part of
total carbohydrates are obtained from fruit, vegetables and whole grain sources.[24]

[edit] Medications

Reducing insulin resistance by improving insulin sensitivity through medications such as

metformin, and the newer thiazolidinedione (glitazones), have been an obvious approach and
initial studies seemed to show effectiveness.[25] Although metformin is not licensed for use in
PCOS, the United Kingdom's National Institute for Health and Clinical Excellence
recommended in 2004 that women with PCOS and a body mass index above 25 be given
metformin when other therapy has failed to produce results.[26] However subsequent reviews in
2008 and 2009 have noted that randomised control trials have in general not shown the promise
suggested by the early observational studies.[27][28]

[edit] Infertility

Not all women with PCOS have difficulty becoming pregnant. For those who do, anovulation is
a common cause. Ovulation may be predicted by the use of urine tests that detect the
preovulatory LH surge, called ovulation predictor kits (OPKs). However, OPKs are not always
accurate when testing on women with PCOS.[29] Charting of cervical mucus may also be used to
predict ovulation, or certain fertility monitors (those that track urinary hormones or changes in
saliva) may be used. Methods that predict ovulation may be used to time intercourse or
insemination appropriately.

While not useful for predicting ovulation,[30] basal body temperatures may be used to confirm
ovulation. Ovulation may also be confirmed by testing for serum progesterone in mid-luteal
phase, approximately seven days after ovulation (if ovulation occurred on the average cycle day
of fourteen, seven days later would be cycle day 21). A mid-luteal phase progesterone test may
also be used to diagnose luteal phase defect. Methods that confirm ovulation may be used to
evaluate the effectiveness of treatments to stimulate ovulation.

For overweight women with PCOS, who are anovulatory, diet adjustments and weight loss are
associated with resumption of spontaneous ovulation. For those who after weightloss still are
anovulatory or for anovulatory lean women, clomiphene citrate and FSH are the principal
treatments used to help infertility. Previously, even metformin was recommended treatment for
anovulation. But in the largest trial to date, comparing clomiphene with metformin, clomiphene
alone was the most effective.[31] In this trial, 626 women were randomized to three groups:
metformin alone, clomiphene alone, or both. The live-birth rates following 6 months of treatment
were 7.2% (metformin), 22.5% (clomiphene), and 26.8% (both). The major complication of
clomiphene was multiple pregnancy, affecting 0%, 6% and 3.1% of women respectively. The
overall success rates for live birth remained disappointing, even in women receiving combined
therapy, but it is important to consider that the women in this trial had already been attempting to
conceive for an average of 3.5 years, and over half had received previous treatment for infertility.
Thus, these were women with significant fertility problems, and the live-birth rates are probably
not representative of the typical PCOS woman. Following this study, the ESHRE/ASRM-
sponsored Consensus workshop do not recommend metformin for ovulation stimulation.[32]
Subsequent randomized studies have confirmed the lack of evidence for adding metformin to
clomiphene.[33]

The most drastic increase in ovulation rate occurs with a combination of diet modification,
weight loss, and treatment with metformin and clomiphene citrate.[34] It is currently unknown if
diet change and weight loss alone have an effect on live birth rates comparable to those reported
with clomiphene and metformin

For patients who do not respond to clomiphene, diet and lifestyle modification, there are options
available including assisted reproductive technology procedures such as controlled ovarian
hyperstimulation with FSH injections and in vitro fertilisation (IVF). Ovarian stimulation with
FSH followed by hCG has an associated risk in women with PCOS of ovarian hyperstimulation
syndrome — an uncomfortable and potentially dangerous condition with morbidity and rare
mortality. Thus recent developments have allowed the oocytes present in the multiple follicles to
be extracted in natural, unstimulated cycles and then matured in vitro, prior to IVF. This
technique is known as In vitro maturation (IVM).

The RCOG (The Royal College of Obstetricians and Gynaecologists) has recently published an
opinion paper on "Metformin therapy for the management of women with polycystic ovary
syndrome". The paper concluded that while initial studies appeared to be promising, more recent
large randomised controlled trials have not observed beneficial effects of metformin either as
first-line therapy or combined with clomifene citrate for the treatment of the anovulatory woman
with PCOS. Most work has been undertaken in the management of anovulatory infertility and
there are no good data from randomised controlled trials on the use of metformin in the
management of other manifestations of PCOS. It is clear that the first aim for women with PCOS
who are overweight is to make lifestyle changes with a combination of diet and exercise in order
to lose weight and improve ovarian function. The European Society for Human Reproduction
and Embryology and American Society for Reproductive Medicine consensus on infertility
treatment for PCOS concluded that there is no clear role for insulin sensitising and insulin
lowering drugs in the management of PCOS, and should be restricted to those patients with
glucose intolerance or type 2 diabetes rather than those with just insulin resistance. Therefore, on
current evidence metformin is not a first line treatment of choice in the management of
PCOS(RCOG December 2008)[1]

Though surgery is not commonly performed, the polycystic ovaries can be treated with a
laparoscopic procedure called "ovarian drilling" (puncture of 4-10 small follicles with
electrocautery), which often results in either resumption of spontaneous ovulations or ovulations
after adjuvant treatment with clomiphene or FSH.

[edit] Hirsutism and acne

When appropriate (e.g. in women of child-bearing age who require contraception), a standard
contraceptive pill may be effective in reducing hirsutism. A common choice of contraceptive pill
is one that contains cyproterone acetate; in the UK/US the available brands are Dianette/Diane.
Cyproterone acetate is a progestogen with anti-androgen effects that blocks the action of male
hormones that are believed to contribute to acne and the growth of unwanted facial and body
hair.

Other drugs with anti-androgen effects include flutamide and spironolactone, some improvement
in hirsutism. Spironolactone is probably the most-commonly used drug in the US. Metformin can
reduce hirsutism, perhaps by reducing insulin resistance, and is often used if there are other
features such as insulin resistance, diabetes or obesity that should also benefit from metformin.
Eflornithine (Vaniqa) is a drug which is applied to the skin in cream form, and acts directly on
the hair follicles to inhibit hair growth. It is usually applied to the face. Medications that reduce
acne by indirect hormonal effects also include ergot dopamine agonists such as bromocriptine.

Although all of these agents have shown some efficacy in clinical trials, the average reduction in
hair growth is generally in the region of 25%, which may not be enough to eliminate the social
embarrassment of hirsutism, or the inconvenience of plucking/shaving. Individuals may vary in
their response to different therapies, and it is usually worth trying other drug treatments if one
does not work, but drug treatments do not work well for all individuals. For removal of facial
hairs, electrolysis or laser treatments are faster and more efficient alternatives than the above
mentioned medical therapies.
[edit] Menstrual irregularity and endometrial hyperplasia

If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive
pill, though the effects are caused by substituted hormones that can easily cause more problems
if the pill is taken for a long period of time. The purpose of regulating menstruation is essentially
for the woman's convenience, and perhaps her sense of well-being; there is no medical
requirement for regular periods, so long as they occur sufficiently often (see below).

If a regular menstrual cycle is not desired, then therapy for an irregular cycle is not necessarily
required - most experts consider that if a menstrual bleed occurs at least every three months, then
the endometrium (womb lining) is being shed sufficiently often to prevent an increased risk of
endometrial abnormalities or cancer. If menstruation occurs less often or not at all, some form of
progestogen replacement is recommended. Some women prefer a uterine progestogen device
such as the intrauterine system (Mirena) or the progestin implant (Implanon), which provides
simultaneous contraception and endometrial protection for years. An alternative is oral
progestogen taken at intervals (e.g. every three months) to induce a predictable menstrual
bleeding.

[edit] Alternative approaches

D-chiro-inositol (DCI) offers a well-tolerated and effective alternative treatment for PCOS. It has
been evaluated in two peer-reviewed, double-blind studies and found to help both lean and obese
women with PCOS; diminishing many of the primary clinical presentations of PCOS.[35][36] It has
no documented side-effects and is a naturally occurring human metabolite known to be involved
in insulin metabolism.[37] DCI is regulated as a dietary supplement in the United States.