Polycystic Ovarian Syndrome (PCOS)?
Polycystic ovary syndrome is characterized by anovulation (irregular or absent menstrual periods) and hyperandrogenism (elevated serum testosterone and androstenedione). Patients with this syndrome may complain of abnormal bleeding, infertility, obesity, excess hair growth, hair loss and acne. In addition to the clinical and hormonal changes associated with this condition, vaginal ultrasound shows enlarged ovaries with an increased number of small (6-10mm) follicles around the periphery (Polycystic Appearing Ovaries or PAO). While ultrasound reveals that polycystic appearing ovaries are commonly seen in up to 20% of women in the reproductive age range, PolyCystic Ovary Syndrome (PCOS) is a estimated to affect about half as many or approximately 6-10% of women. The condition appears to have a genetic component and those effected often have both male and female relatives with adult-onset diabetes, obesity, elevated blood triglycerides, high blood pressure and female relatives with infertility, hirsutism and menstrual problems.
Why do women with Polycystic Ovarian Syndrome (PCOS) have trouble with their menstrual cycle?
The ovaries are two small organs, one on each side of a woman's uterus. A woman's ovaries have follicles, which are tiny sacs filled with liquid that hold the eggs. These sacs are also called cysts. Each month about 20 eggs start to mature, but usually only one becomes dominant. As the one egg grows, the follicle accumulates fluid in it. When that egg matures, the follicle breaks open to release the egg so it can travel through the fallopian tube for fertilization. When the single egg leaves the follicle, ovulation takes place.
In women with PCOS, the ovary doesn't make all of the hormones it needs for any of the eggs to fully mature. They may start to grow and accumulate fluid. But no one egg becomes large enough. Instead, some may remain as cysts. Since no egg matures or is released, ovulation does not occur and the hormone progesterone is not made. Without progesterone, a woman’s menstrual cycle is irregular or absent. Also, the cysts produce male hormones, which continue to prevent ovulation.
What are the symptoms of
Polycystic Ovarian Syndrome (PCOS)?
HYPERINSULIN & PCOS?
Blood hormone levels of LH, FSH, androgens and SHBG
Ideally, these tests should be performed during the first four days of the cycle. If the women has no period, then the test can be performed anytime, and repeated if the results do not provide a clear picture.
FSH levels are low or normal, LH levels are often raised. However, a normal level does not exclude diagnosis of polycystic ovarian syndrome (PCOS). The levels of androgens and testosterone may be raised.
The American Society of Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) joint consensus meeting in November 2003 agreed that the diagnosis of PCOS should be made when two of the following three criteria are met:
Does PCOS cause long-term
NEWER METHODS OF TREATMENT
Because there is no cure for PCOS, it needs to be managed to prevent problems. Treatments are based on the symptoms each patient is having and whether she wants to conceive or needs contraception. Below are descriptions of treatments used for PCOS.
Birth control pills. For women who don’t want to become pregnant, birth control pills can regulate menstrual cycles, reduce male hormone levels, and help to clear acne. However, the birth control pill does not cure PCOS. The menstrual cycle will become abnormal again if the pill is stopped. Women may also think about taking a pill that only has progesterone, like Provera, to regulate the menstrual cycle and prevent endometrial problems. But progesterone alone does not help reduce acne and hair growth.
If irregular and/or infrequent
menstruation is a problem, birth control pills that typically contain estrogen
and progestin can generally regulate your cycles. Restoring regular periods is
essential since it insures that the lining of the uterus is shed, protecting
against uterine cancer.
Diabetes Medications. The medicine, Metformin, also called Glucophage, which is used to treat type 2 diabetes, also helps with PCOS symptoms. Metformin affects the way insulin regulates glucose and decreases the testosterone production. Abnormal hair growth will slow down and ovulation may return after a few months of use. These medications will not cause a person to become diabetic.
Fertility Medications. The main fertility problem for women with PCOS is the lack of ovulation. Even so, her husband’s sperm count should be checked and her tubes checked to make sure they are open before fertility medications are used. Clomiphene (pills) and Gonadotropins (shots) can be used to stimulate the ovary to ovulate. PCOS patients are at increased risk for multiple births when using these medications. In vitro Fertilization (IVF) is sometimes recommended to control the chance of having triplets or more. Metformin can be taken with fertility medications and helps to make PCOS women ovulate on lower doses of medication.
Medicine for increased hair growth or extra male hormones. If a woman is not trying to get pregnant there are some other medicines that may reduce hair growth. Spironolactone is a blood pressure medicine that has been shown to decrease the male hormone’s effect on hair. Both of these medicines can affect the development of a male fetus and should not be taken if pregnancy is possible. Other non-medical treatments such as electrolysis or laser hair removal are effective at getting rid of hair. A woman with PCOS can also take hormonal treatment to keep new hair from growing.
Although it is not recommended as the first course of treatment, surgery called ovarian drilling is available to induce ovulation. The doctor makes a very small incision above or below the navel, and inserts a small instrument that acts like a telescope into the abdomen. This is called laparoscopy. The doctor then punctures the ovary with a small needle carrying an electric current to destroy a small portion of the ovary. Case series studies of women with PCOS have reported that ovarian drilling results in an 80% ovulation rate and a 50% pregnancy rate. The advantage of laparoscopy is that tubal patency can be checked at the same time in a single procedure, and ovarian drilling of either one or both ovaries appears to restore ovulation in a substantial number of patients. Serum concentrations of LH and testosterone decrease rapidly after ovarian drilling with a sustained mid- and long-term effect. The proportion of women with regular menstrual cycles increases substantially after drilling and is sustained at long-term follow-up. Ovulation and pregnancy rates are substantially increased in the period after the operation and appear to be maintained. Resistance to the effects of ovarian drilling include marked obesity, very elevated levels of androgens, and long duration of infertility. Addition of other ovulating agents such as clomiphene citrate or FSH appears to improve the effectiveness of laparoscopic ovarian drilling
Summary of Ovarian Drilling:
A healthy weight. Maintaining a healthy weight is another way women can help manage PCOS. Since obesity is common with PCOS, a healthy diet and physical activity help maintain a healthy weight, which will help the body lower glucose levels, use insulin more efficiently, and may help restore a normal period. Even loss of 10% of her body weight can help make a woman's cycle more regular.
For women in the reproductive age range, polycystic ovary syndrome is a serious, common cause of infertility, because of the endocrine abnormalities which accompany elevated insulin levels. There is increasing evidence that this endocrine abnormality can be reversed by treatment with widely available standard medications which are leading medicines used in this country for the treatment of adult onset diabetes, metformin (Glucophage 500 or 850 mg three times per day or 1000mg twice daily with meals). These medications have been shown to reverse the endocrine abnormalities seen with polycystic ovary syndrome within two or three months. They can result in decreased hair loss, diminished facial and body hair growth, normalization of elevated blood pressure, regulation or menses, weight loss, reduction in cardiovascular risk factors, normal fertility, and a reduced risk of miscarriage. We have seen pregnancies result in less than two months in woman who conceived in their very first ovulatory menstrual cycle. By six months over 90% of women treated with insulin-lowering agents, diet and exercise will resume regular menses.
The medical literature suggests that the endocrinopathy in most patients with polycystic ovary syndrome can be resolved with insulin lowering therapy. This is clinically very important because the therapy reduces hirsutism, obesity, blood pressure, triglyceride levels, elevated blood clotting factors and facilitates reestablishment of the normal pituitary ovarian cycle, thus often allowing resumption of normal ovulatory cycles and pregnancy. We know the polycystic ovary syndrome is associated with increased risk of heart attack and stroke because of the associated heart attack and stroke risk factors, hypertension, obesity, hyperandrogenism, hypertriglyceridemia, and these are to a large degree resolved by therapy with these medications.
What is the most effective therapy for an anovulatory patient with PCOS who wishes to become pregnant? It is clear that lifestyle modification with caloric restriction and exercise is extremely important in the first stage of any intervention. This should be considered active medical therapy and not as an alternative to other medical intervention. Once the patient has established adequate lifestyle change, ovulations will either occur spontaneously with subsequent pregnancy or additional intervention will be required. Clomiphene citrate is still considered to be a cheap, safe, and easy alternative and would probably be the first-line therapy for anovulatory PCOS. It could be argued, however, that at this stage metformin is equally effective and is introduced initially at a low dose and subsequently building up to 1500–2500 mg/d. Metformin alone can be considered an effective form of therapy (Fig. 2Go). Failure to respond to clomiphene citrate offers the options of laparoscopic drilling, addition of metformin, or the use of gonadotropins.
ARE THESE MEDICATIONS SAFE?
HOW DO WE MONITOR THERAPY?
While the most prudent policy may be to avoid the use of these medications during pregnancy until more data on pregnancy outcome is available, the risk of miscarriage may be reduced by continuing metformin during the pregnancy.
MISCARRIAGE & PCOS
Hyperinsulinemia may be a contributing factor in the higher rate of miscarriage. Elevated levels of insulin interfere with the normal balance between factors promoting blood clotting and those promoting breakdown of the clots. There are no placebo-controlled clinical trials to indicate whether pregnancy outcomes are improved in pregnancies that result from the use of insulin-lowering medications or whether pregnancy outcomes are better in those who continue metformin throughout the pregnancy or those who discontinue.