Polycystic Ovary Syndrome (PCOS) is a medical condition in which women experience irregular or absent menstrual bleeding, increased hair growth, and difficulty becoming pregnant. In these women, the ovaries are slightly enlarged and contain multiple small cysts which have led to the descriptive term, polycystic ovaries. Thus, Polycystic Ovary Syndrome is comprised of several clinical features, each of which may be present to a greater or lesser degree. As a result, patients may seek medical advice to correct irregular menstruation, eradicate excessive hair growth, or achieve pregnancy.

Some women have been found to have polycystic ovaries without associated abnormalities of menstruation, hair growth or fertility. These women do not have Polycystic Ovary Syndrome. Thus, not all women with polycystic ovaries have PCOS, but all women with PCOS have polycystic ovaries.

NORMAL OVARIAN FUNCTION

Women have two ovaries; they are located in the pelvis alongside the uterus. Their main functions are to release eggs and produce hormones (illustration).

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.

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.


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