| Polycystic Ovarian Syndrome is common condition in women that wreaks havoc on hormones and causes physical and psychological damage. Polycystic ovarian syndrome (PCOS) is a complex hormonal disturbance that effects the entire body and has numerous implications for general health. Women with this syndrome have, over the course of their life, an increased risk of coronary disease, diabetes and endometrial cancer. PCOS was first diagnosed in 1935 as Stein-Leventhal syndrome. Between 5 and 30 percent of women have some characteristic of PCOS. The disorder is probably the most common hormonal abnormality in women of reproductive age and certainly is a leading cause of infertility. PCOS patients were once dismissed as “fat" women with no self-control. Doctors still can often miss, or dismiss, the diagnosis because they fail to recognize the diverse set of symptoms as being part of one medical condition. There are three broad reasons why PCOS patients seek medical care: 1) menstrual cycle disturbance and infertility 2) problems of appearance and self esteem arising from obesity and excessive hair growth, and 3) metabolic derangements, including abnormalities in blood fat (lipid) levels, insulin/glucose (sugar), and elevated blood pressure (hypertension). Often gynecologists, the health care provider to whom may women turn for help, have concerned themselves with only the first of these concerns and have been relatively insensitive to the latter two. Making the Diagnosis of PCOS In no other gynecological condition is the general medical history more important than in PCOS. There are 3 different ways to make the diagnosis of PCOS: 1) by symptoms and physical findings, 2) hormonal testing, and 3) ultrasound. Probably most individuals will have abnormalities in all three, some only in two, and possibly only in one. Some may argue that findings in only a single category may not constitute PCOS. But, until we have PCOS better characterized, or find a different diagnosis for these patients, the diagnosis of PCOS should remain and provides a good starting point for communication. Even the most minor of apparent problems may have significant implications for future general health and well-being. The classic findings of PCOS are: menstrual cycle abnormalities, increased sexual hair growth and obesity Menstrual Disturbance Often in PCOS patients, the menarche occurs at the usual age of 12-13 years. Some PCOS patients may start menstruating earlier. Not uncommonly, PCOS patients may first be seen by a physician for lack of menses. Any female who has not had menses by age 16 should be evaluated. The menstrual cycle may at first be regular, but by high school, cycles start to lengthen and may be skipped. Often during this time, oral contraceptives are started. The "pill" usually regulates the menstrual cycle and may give the false impression that all is well. Usually in the teenage years, the other symptoms of skin and weight problems also start to be seen. Some PCOS patients easily establish a pregnancy in these early years. Occasionally, birth control pills may even increase the chance of pregnancy by suppressing abnormal hormonal production. Often the PCOS patient is seen by a gynecologist when she is in her 20's after stopping the pill, and her periods. Some PCOS patients have quite regular 28 days cycles, but the diagnosis should be suspected in individuals with cycle length over 35 days. Some patients have no bleeding unless some form of medication, usually a progestin, is given. In some there is excessive bleeding, or long periods of spotting. It is thought that the age of menopause in individuals with PCOS is about the same, age 50, as other women. While virtually never mentioned in medical publications, or recognized by physicians, it seems that chronic pelvic pain and premenstrual (PMS) symptoms are quite common. Given the chronically abnormal hormonal patterns, the capacity of hormones to alter body fluid and even the enlarged cystic ovaries, these findings should not be surprising. Hair and Skin Problems The skin manifestations associated with PCOS are possibly more common than either menstrual cycle irregularity, or obesity. Disorders of the skin in PCOS patients are related to an increase in level of male hormones (hyperandrogenism). This may be due to an absolute increase in androgen level, or an alteration in ratio of hormone levels. A third possibility is an exaggerated response of the skin to relative normal androgen levels. The end result of all three of these possibilities is the same and includes: acne, seborrhea, balding, hidradenitis suppurtiva (inflammation of the specialized sweat glands in the arm pit and groin), acanthosis nigricans (see below) and hirsutism. Hirsutism is defined as an increase in amount and/or coarseness of hair distributed in the male pattern in a female. This is opposed to hypertrichosis, which is excessive growth of non-sexual hair. The issue of facial hair is usually self-evident, but a good screening test is the amount of hair between the umbilicus and pubic hairline. Other areas of male pattern hair growth include 'sideburns,' lower neck, lower back and inner thighs. A faint moustache is quite common and may be more related to family trait and ethnic group than hormonal imbalance. The same can be said for occasional "stray" hair around the breasts. Outside hirsutism, other manifestations of hyperandrogenism are often dismissed, or not recorded in the gynecologist's evaluation. Acne and seborrhea occur quickly as androgens rise. Androgens increase sebum, which is a combination of skin oils and old skin tissue. Increased sebum causes plugging of skin pores. Bacteria that thrive on sebum are increased, resulting in inflammation. The inflamed skin pore is called a comedon. Closed comedones are "whiteheads," while "blackheads" are open comedones. The black color comes not from dirt, but from the breakdown of keratin, a natural skin product. Increased male hormone levels also cause seborrhea. A particularly common skin condition and one not usually associated with hormonal alterations is dandruff. Contrary to what is generally believed, dandruff is caused by oily, not dry skin and is a variety of seborrheic dermatitis. Many women complain of skin problems that wax and wane during the menstrual cycle. In regularly cycling women, the second half of the menstrual cycle is characterized by increased progesterone levels. Progesterone is a weak androgen and may create a situation of relative hyperandrogenism. Around the time of menstruation estradiol is decreased. Low levels of estrogen (hypoestrogenism) also creates a situation of relative increase in androgens with resultant increased oiliness and inflammation of the skin. One of the most distressing of hyperandrogenic skin disorders is alopecia (balding). The most androgen sensitive area of the scalp is the vertex, the highest point of the head. Frontal balding and anterior hairline recession is seen only in the more severe cases of androgen excess. As can be imagined, the mechanism for hair growth (and loss) has been extensively studied, but no unified theory has emerged. A search for acanthosis nigricans (AN) should be a part of every physical exam of the PCOS patient. AN is usually described as a velvety, raised, pigmented skin changes, most often seen on the back of the neck, axillae and beneath the breasts. AN is often seen in association with skin tags (acrochordons). Possibly the best description is that it looks like the affected area is 'dirty' and would benefit from scrubbing. Obviously this is not the case. There is an association of this finding with simple obesity as well as other endocrine disorders. AN should always alert the clinician to a risk of diabetes, major lipid abnormalities, and hypertension. Although less common, it may be a warning signal of cancer. Elevated androgen levels may be only a part of the problem. For androgens to have an effect on the skin they must bind together with an androgen receptor in the skin. There may little, or no, physical evidence of hyperandrogenism despite very high androgen levels, if the androgen receptor is lacking or present in relatively low numbers. The number of androgen receptors varies among different ethnic groups and individuals. Northern European women with PCOS are more likely to be hairier than Asian women. A third requirement for androgen action in the skin, besides androgens and receptors, is a specific enzyme called 5-alpha-reductase. Testosterone must be converted to dihydrotestosterone (DHT) by this enzyme to exert its effect. Only sexual hair follicles contain the necessary enzymatic machinery for conversion of circulating androgens to DHT. A fair skinned individual may have little excess hair growth despite high levels of testosterone, due to absence of the specific androgen receptor, or enzyme converting capacity, in the hair follicles. Another individual may be quite hirsute with no apparent abnormality in circulating hormones. Obesity Whether obesity is a cause of PCOS or obesity is a result of PCOS is unclear, but it seems that the latter is more likely. A distinction has been made between the "lean" and "obese" PCOS patient. The typical obesity of PCOS is described as "centripetal," related to fat distribution in the center of the body, as opposed to the thighs and hips. This "apple" opposed to a "pear" type of fat distribution clearly is associated with greater risk of hypertension, diabetes and lipid abnormalities. Certainly, many metabolic derangements improve with weight loss, but PCOS is not "cured" by weight reduction. Almost always, individuals with PCOS gain weight very easily and lose it only with great effort. Everyone knows that some individuals consume large quantities of food and never gain weight while others work hard just to stay "fat" instead of severely obese. Vanity keeps some from weighing much more than they might, if only they were less vigilant. When seeking medical help for weight control, too often, the obese patient has been told to exercise more, or to eat less. Clearly, this over-simplification fails to take into account the high likelihood that individuals vary in the way their body utilizes calories. Some use calories less effectively, or store fat more easily. A key to the way the body uses energy is insulin. Insulin is a hormone released by the pancreas in response to the breakdown of food into sugars, proteins and fats by the digestive system. Insulin promotes the storage of fat to ensure a constant source of fuel, calories, ensuring the body's most efficient operation. PCOS increasingly has been linked to abnormalities of insulin and glucose metabolism. In the past, this may have been an adaptive advantage allowing survival against cold, or famine. Now, in part a response to today's sedentary lifestyle, obesity has become a genetically related disease, which may treated, but only with great personal conviction and effort. Certainly, weight loss can only be achieved when caloric expenditure exceeds caloric intake, but genetic, metabolic and environmental alterations make this a much more complex equation. Hopefully in the future, there will be relief that is both more effective and less painful than our present treatment strategies. Obesity may be the single most important health issue in the United States today. Obese individuals have greater risk of hypertension, high blood pressure, diabetes, cancer, stroke, gall bladder disease, and uterine cancer. But obesity alone does not explain everything, possibly not anything. Laboratory Testing Virtually all patients with PCOS will have at least subtle laboratory abnormalities. The reported results may be only on the upper limits of the 'normal range,' showing only a tendency, not a discrete abnormality. Often a pattern will emerge after considering a group of tests together. These subtleties may reveal dysfunction in the control mechanisms of the hypothalamus, pituitary, ovary and adrenal (HPOA axis) working collectively. In distinction, serious pathology may be more evident by a marked elevation, or suppression of a single test. Though the value of repeated blood testing for the same hormones could be questioned, it is recommended that each PCOS patient have an initial, relatively comprehensive evaluation and interpretation by an individual familiar with this testing. Any level that is twice the upper or lower limit of normal, is particularly important and may indicate a serious problem. The marginally elevated test is almost always dysfunctional, rather than pathologic. As a rule, endocrine testing, other than a pregnancy test, is probably best performed in the morning, soon after a spontaneous, or induced menses. The days around ovulation or mid-cycle should be avoided. Hormonal evaluation in patients on oral contraceptive will often give misleading results with suppression of gonadotropin, ovarian steroid and SHBG levels. It is of limited value to determine these hormone levels in patients on the pill. Glucose and lipid evaluation should be in the morning after fasting (no food or drink after midnight the night before). Fasting insulin levels and a glucose tolerance test can be very important in the diagnosis of insulin resistance. Ultrasound Sonography of the pelvis is warranted in virtually every potential PCOS patient. Individuals experienced in judging ovarian and endometrial function should perform evaluation. The finding of greater than ten cystic structures less than 10 mm in either ovary, meets the generally established ultrasound criteria of PCOS. Often cysts of PCOS are located in a peripheral subcortical ring leading to the reference of a "string of pearls." The PCOS ovaries are typically 1.5 to three times normal size. In some cases the ovary is virtually filled with small cysts. In other cases, it is heterogeneously dense with hardly detectable microcystic changes. It must be remembered that any hyperandrogenic state may be manifested by the PCO-appearing ovary. Diffusely enlarged ovaries without discrete mass on ultrasound, in the absence of adrenal findings, are consistent with the diagnosis of hyperthecosis, which is probably a less common variant in the PCOS spectrum. Etiology The cause of PCOS is unknown. However, the story is starting to unravel and several important lines of evidence have emerged that offer clues about a central mechanism. Is there only one, or are there many causes of PCOS? PCOS is a "final common pathway" of a variety of disorders and the diagnosis PCOS itself remains one of exclusion. It is a near universal finding that PCOS is genetic, but the heritage is complex. This genetic predisposition is not as simple as brown eyes or blue, but has a complex heritage. The tendency to develop PCOS may be inherited from either the mother's side, (maternal origin), from the father's side (paternal origin), or from both sides. A paternal origin is equally likely, but often is overlooked. Also, various characteristic traits of PCOS may be passed down with varying degrees of severity. Insulin resistance may be a key player. Women with PCOS produce too much insulin, which in turn signals their bodies to release the male hormone testosterone. Too much testosterone creates facial hair, acne, weight gain and multiple cysts on the ovaries. Doctors believe the same insulin and testosterone overload that may cause PCOS in women may also be responsible for premature male-pattern balding in men. Several medications are on the market and clinical trials are now underway testing new medications that control the release of insulin. Therapy for PCOS Weight Loss With weight loss there is often an improvement in endocrine parameters and sometimes return of menses. Clearly important, but always much easier said than done. Progestins A progestin is a medication that mimics the action of progesterone. While progestins may be used to regulate the menstrual cycle and blood levels of LH may be reduced by progestins, they appear to be of little use in reduction of hair growth, or possibly metabolic derangements. Examples are Provera, Aygestin, and Cycrin. Oral Contraceptives Oral contraceptives (OC's) are a mainstay of treatment of PCOS in women who do not want to become pregnant. They increase the SHBG, which "traps" circulating androgens. The pill also reduces LH. Menses are often regulated and overall there are numerous positive health benefits. Corticosteroids Steroids have the ability to suppress adrenal androgen production and may be useful in treatment of PCOS with an adrenal component. Overall, their use is better in theory than practice and they are often discontinued by patients because of unwanted side effects. Anti-androgens This group of medications can be used only when not attempting a pregnancy or without some form of adequate birth control. There is, at least a theoretical, risk of feminizing the genitals of a male fetus. The value of the agents for PCOS patients is to improve the skin problems that occur with PCOS. None of these medications are approved for treatment of hirsutism or PCOS. Some may have potentially serious side effects. Examples are spironolactone (Aldactone), Flutamide, cyproterone acetate, and Finasteride. GnRH Analogs Gonadotropin releasing hormone (GnRH) is a hormone that is released from the hypothalamus and promotes production and release of the gonadotropins (LH and FSH) from the pituitary gland. While quite a good therapy for suppression of the ovary and its abnormal hormonal production of PCOS, the high cost and undesirable side-effects limits GnRH use. Fertility Therapy In PCOS, the normal mechanisms of hypothalamic-pituitary-ovarian (HPO) axis and therefore, follicle growth and ovulation are disturbed. "Fertility drugs" are commonly used in an attempt to temporarily override the problem and facilitate ovulation. Clomiphene (Clomid) is an oral fertility agent. There are also several injectable gonadotropin preparations that can be used when clomiphene fails. Surgical therapy In the past, ovarian wedge resection, a procedure whereby a portion of the ovary is removed and the ovary sewn back together, resulted in a significant reduction in LH and androgen production, reestablishment of regular menses in over 75% of patients and a pregnancy rate of about 60%. However, pelvic adhesive disease, which was often severe, occurred in about 30% of patients. There is probably no longer an indication for wedge resection by laparotomy, although electrosurgical incisions, or “ovarian drilling,” have become relatively commonplace. Success rates of microcautery vary by operator and, while adhesion formation may be considerably less, it is still common. Anti-diabetic agents By treating the insulin resistance, PCOS may be also treated, possibly reversed. It is still very unsettled which PCOS patient may derive benefit from these medications. With some PCOS patients these medications have successfully restored normal menstruation and fertility, even the absence of the insulin resistance. They may be a useful alternative when other therapies have failed, or benefit appears to exceed risk. These agent are: Metformin (Glucophage) An FDA advisory subcommittee voted unanimously in March 1994 that Metformin be approved for the treatment of insulin resistance and type 2 (insulin resistant) diabetes that cannot be controlled by diet alone. It had the strong endorsement of the American Diabetes Association and is presently used in over 80 countries. By September 1996 over one million U.S. patients had been prescribed the medication. Use is predicted to sharply rise. Metformin enhances the body's sensitivity to insulin and inhibits glucose production from the liver without the risk of hypoglycemia. It does not lower blood glucose levels, but acts to improve the body's sensitivity to insulin without affecting insulin secretion. Some patients have shown weight loss, improved lipid profiles, lowering of blood pressure, return of menstruation, and pregnancy. Metformin appears to have an excellent safety profile and is generally well tolerated. Gastrointestinal upset and a tendency toward looser stools, or more frequent bowel movements, are the most frequent side effects. These are common in the first month and can be reduced by starting at lower doses and increasing. These side effects are also more commonly experienced after a fatty meal, or dessert. Lactic acidosis, a rare and potentially fatal condition, has been associated with Metformin use. The reported incidence of lactic acidosis is 3 /100,000 patients using the drug for 1 year. Almost all cases occurred in older patients with other significant diseases and risk factors. A relative disadvantage of Metformin therapy may be the postponement of more aggressive fertility therapy. The usual dose is 500 mg. three times daily. |
| What Is PCOS? |
| POLYCYSTIC OVARIAN SYNDROME A GUIDE FOR PATIENTS A glossary of underlined words is located at the end of this document. Introduction Polycystic ovarian syndrome (PCOS) is a common condition occurring in 1 out of every 9 women of the reproductive age group. It is characterized by an abnormal hormone function that leads to excessive androgen production by the ovaries. This result in abnormal ovarian function and various effects on other body systems. PCOS is a heterogeneous condition with some women presenting with severe symptoms and others only having minimal complaints. This disease cannot be cured but timely management can limit its implications. Many women with mild to moderate disease are not diagnosed and thus denied the opportunity to limit the short and long-term implications of PCOS. It is therefore important for all women to be aware of this condition and to seek medical advise. The cause and effect of PCOS A basic understanding of the mechanism and control of ovulation is essential in order to understand the nature of PCOS. The pituitary gland produces hormones called follicle stimulating hormone (FSH) and luteinising hormone (LH) which controls the ovulatory cycle. As the menstrual period begins, FSH stimulates the growth and development of a follicle. A midcycle rise in the LH matures the egg and leads to ovulation 24-36 hours later. This normally occurs 14 days before the onset of the next menstrual period in those women having regular menstrual cycles. The developing egg secretes oestrogen, which stimulate the lining of the womb (endometrium) to grow. The cells surrounding the follicle produce androgens in response to LH. These minimal amount of androgens are essential for normal egg development and ovulation. After ovulation, the remains of the follicle secretes progesterone, a hormone that finally prepares the womb for a possible pregnancy. If fertilisation does not occur, secretion of oestrogen and progesterone by the follicle ceases with a decline of hormonal support of the endometrium. This is followed by the onset of the menstrual period. A delicate interaction between the ovary and the pituitary gland controls the ovulatory and menstrual cycle. Although not yet well understood, research indicates that an abnormal function of the enzymes that control the ovarian hormone production leads to PCOS. A genetic link explains the clustering of PCOS in certain families. This enzyme abnormality results in a high concentration of androgens being produced in the ovary with resulting poor egg development and absence of ovulation. This disruption of the ovarian function leads to the formation of multiple small follicles in the ovary that fail to mature and ovulate. The androgens also enter the blood circulation with the following effects on the rest of the body. An abnormal feed back mechanism between the ovary and the pituitary gland leads to the excessive production of LH which in turn stimulates more androgen production in the ovaries initiating a vicious cycle of events. The androgens react with receptors in the skin resulting in male pattern hair growth, acne and in severe cases even male pattern baldness. Androgens are also converted to estrogens in fatty tissue resulting in high blood levels of oestrogens. Resistance of various body tissues to the effect of insulin is another important factor associated with PCOS. The resistance leads to high blood levels of insulin, which together with other related substances, stimulate the production of androgens in the ovaries. The resistance to insulin is enhanced and aggravated by obesity, which thus increases the signs and symptoms of PCOS. Symptoms of PCOS PCOS is a heterogeneous condition with some patients complaining of minimal symptoms while others present with severe disease. The following symptoms may be indicative of PCOS and should lead to further investigations: Menstrual irregularities are the most common symptom of PCOS. These can vary from mild irregularity of the periods, to excessive menses, to total absence of menstruation for prolonged periods of time. PCOS is inevitably associated with infertility because of the inefficiency and/or absence of the ovulatory process. A previous pregnancy does not exclude underlying PCOS, because the expression of PCOS may have been initiated by an increase in body weight after the pregnancy. Male pattern hair growth, acne and in severe cases male pattern baldness may be an expression of the high blood levels of androgens in patients with PCOS. These symptoms vary according to the individual sensitivity of the skin tissue to androgens. Genetic predisposition and the ethnic origin of the patient may influence this sensitivity to androgens. Women of Mediterranean origin tend to have a high skin sensitivity to androgens, whilst Asian and Scandinavian women might not have any symptoms in spite of high circulating androgen levels. Spontaneous miscarriage occurs more commonly in patients with PCOS, most probably due to high blood levels of LH and inadequate production of progesterone to support an early pregnancy. Obesity is a factor commonly associated with PCOS and it may aggravate the condition. It is however not a prerequisite for the diagnosis. These patients often experience difficulty in loosing weight in spite of dietary efforts. Long term implications of PCOS The abnormal blood lipid profile associated with PCOS as well as obesity and insulin resistance increases the risk for high blood pressure, heart vessel disease and diabetes. High circulating oestrogen concentrations over a prolonged period of time initiate excessive stimulation and growth of the endometrium. This growth is not opposed and balanced by progesterone on a regular basis because of the absence of ovulation and thus leads to proliferative growth of the endometrium and an increased risk of endometrial cancer. High oestrogen blood levels over a prolonged period of time may also increase the risk of developing breast cancer. What tests should be performed for patients with PCOS? Any women with symptoms mentioned above should undergo a thorough assessment by a gynaecologist. Women whose mothers had PCOS should carefully watch for these symptoms and seek help if they develop any of the signs or symptoms. PCOS patients with female children should inform their children that they are at risk and watch for symptoms. Menstrual irregularity after puberty could be an early indication of PCOS and intervention at this stage could prevent excessive male pattern hair growth and acne and thus avoiding these long term cosmetic effects. A thorough medical history and physical examination by a gynaecologist will indicate the extent of the disease and this baseline assessment is essential to monitor the response of treatment. Blood tests should be performed not only to diagnose PCOS, but also to exclude other hormonal problems that may mimic the symptoms of PCOS, like abnormal milk hormone (prolactin) production or a dysfunction of the adrenal gland. An increased LH/FSH hormone ratio as well as a raised free androgen level in the blood is suggestive and most often diagnostic of PCOS. In the setting of the symptoms of PCOS, the diagnosis can best be confirmed by the typical appearance of the ovaries on ultrasound. This diagnosis should only be made by transvaginal ultrasonography because of the superior imaging in comparison to abdominal ultrasound. The high incidence of insulin resistance and risk of developing frank diabetes necessitates testing of the fasting insulin and glucose level. After the menopause these women are still at increased risk of developing diabetes and heart vessel disease. Regular assessment of the blood pressure, fasting glucose and cholesterol will allow the early detection of disease and enable management that will contain progression of these problems. Sampling of the endometrium is indicated in patients with very few or absence of menstruation in order to exclude endometrial cancer. How should patients with PCOS be treated? No two women suffering from PCOS are affected the same way and treatment should therefore be tailored to the symptoms and needs of the specific patient. This is only possible after a thorough assessment by a gynaecologist. Weight loss Weight loss should always be the cornerstone of treatment because it is associated with decreased insulin resistance and less conversion of androgens to estrogens in fatty tissue. The binding substance of androgens in the blood also increases during weight loss. which thus ensures that more androgens are bound resulting in decreased activity on the body tissues. Weight loss improves most of the symptoms of PCOS over a period of time but it should go hand in hand with a long-term effort to maintain an ideal body weight. Weight gain after a period of time will lead to the resumption of all the symptoms of PCOS. These patients should preferably seek dietary advice from a registered nutritionist because merely following one of the conventional eating programmes may not be effective and might even be potentially harmful. Traditionally a low calorie and low fat diet is advised but this should be individualized and tailored according to the patients circumstances and needs. Hormone treatment If conception is not a priority, oral contraceptives are traditionally prescribed to ensure regular menstruation and prevent the long-term risk of endometrial cancer. The oral contraceptives also help to decrease the male pattern hair growth. Where excessive hair growth and acne are predominant symptoms, anti-androgen medication can be prescribed in conjunction with the oral contraceptive. These agents ensure that the effect of the androgens on the skin is blocked. It is important to realise that the effect of the anti-androgen treatment on the skin is only evident after 4-6 months. Infertility treatment Women with PCOS do not conceive because of the underlying ovulatory dysfunction. A complete assessment of the infertile couple is however essential before treatment to initiate ovulation is started. This will ensure that additional causes and factors that may contribute to the infertility are also detected and considered in the management. Only if this assessment is satisfactory, should specific treatment to initiate ovulation (ovulation induction) be undertaken. The aim of ovulation induction should be to initiate the development and maturation of a single egg in order to avoid the risk of multiple pregnancy. Ovulation induction should preferably be preceded by weight reduction because it improves the response of these women to ovulation induction. The response of patients with PCOS to ovulation induction is unpredictable and varies from patient to patient. Uncontrolled or poorly monitored induction of ovulation can result in potentially serious complications. These include ovarian hyperstimulation syndrome and multiple pregnancy. Ovulation induction in these patients should therefore be monitored very closely by vaginal ultrasound examination and should preferably be performed by a practitioner with a special interest in the management of infertility. Clomiphene tablets for ovulation induction are simple to use and relatively cost effective. These tablets are therefore still considered as the first line for ovulation induction in patients with PCOS. Clomiphene interacts with the brain and causes the pituitary to secrete FSH, which stimulates egg development. If egg development does not occur, the dosage of Clomiphene can be increased up to 150mg. Repeated and consecutive use of Clomiphene has a negative effect on the endometrium and it also makes the mucus around the mouth of the womb (cervical mucus) unfavourable for sperm penetration. Gonadotrophins as the next option for ovulation induction should be considered under the following circumstances: Poor egg development and absence of ovulation on Clomiphene. Unfavourable effect of Clomiphene on the endometrium and the cervical mucus. Development of multiple follicles on Clomiphene which increases the risk of multiple pregnancies. Ovarian cyst formation on Clomiphene. In patients with PCOS the gonadotrophin preparations which contain mostly FSH are recommended because additional LH might only compound the effect of the already high blood concentration of LH. Traditionally the low dose step up protocol with gonadotrophins is advised in order to initiate the growth of only one egg. During this protocol half an ampoule of gonadotrophins is injected daily from day 2 of the menstrual cycle. This dosage is only increased if no egg development is evident after one week of the treatment. In some patients egg development only becomes evident after more than a week of gonadotrophin injections and thus requires patience and perseverance. This protocol limits the risk of multiple pregnancies and ovarian hyperstimulation syndrome. In patients where ovulation induction with gonadotrophins does not lead to an egg development and ovulation, the in vitro fertilisation procedure (IVF) is ultimately indicated. Fortunately only very few patients with PCOS are resistant to ovulation induction and thus require IVF. In selected patients with PCOS where blood tests revealed excessive androgen production from the adrenal glands, the use of corticosteroids during ovulation induction is indicated. Surgical treatment should only be considered in severe cases that are resistant to ovulation induction as mentioned before. In the past an ovarian wedge resection was performed where a wedge of ovarian tissue was resected from each ovary. The aim of this procedure was to remove a part of the ovarian tissue that was thought to be the source of abnormal hormone production. Ovarian wedge resection leads to an improvement of the symptoms of PCOS but unfortunately requires major surgery and is associated with adhesion formation around the ovary. Both these drawbacks can be overcome by laparoscopic ovarian drilling (LOD). During this procedure the ovarian stromal tissue is destroyed by heat transmitted by a needle which is repeatedly inserted into the ovary. The ultimate result is a decrease in ovarian androgen production. LOD is a minor procedure, which enables discharge from hospital on the same day. LOD furthermore poses only a minimal risk of adhesion formation around the ovary. After LOD these patients must be monitored closely to detect spontaneous ovulation and thus time sexual intercourse appropriately. Cosmetic treatment Excessive hair can be removed by various depilatory treatments with only short-term effects. Laser ablation is nowadays the recommended long-term solution to excessive hair growth. This treatment should however only be started after 4-6 months of anti-androgen treatment to limit failure with renewed growth of unwanted hair. Insulin sensitising agents In patients where clear insulin resistance can be demonstrated on the blood tests, insulin sensitising agents like metformin can contribute to the improvement of PCOS. After a few months of treatment, some of these women start to ovulate spontaneously. Hypoglycaemia does not occur if the patients have been selected properly. These agents should therefore only be prescribed selectively after clear insulin resistance has been demonstrated. New and more specific insulin sensitising agents which may improve the above mentioned effect even further, are being developed. Conclusion The implications of PCOS, a common condition in the female population, can be minimised if it is recognised early, investigated thoroughly and treated appropriately. Management of infertility in these patients is more complex and requires more specialised assessment and care. Glossary Adhesions: Bands of fibrous tissue that bind the abdominal or pelvic organs together. Adrenal: Glands situated on the upper pole of each kidney, consisting of an inner part, which secretes adrenaline, and an outer part, which secretes various hormones including sex hormones. Androgens: "Male hormones" responsible for encouraging masculine characteristics. Clomiphene: An anti-oestrogen drug used to induce ovulation. Follicle: A fluid filled cyst in the ovary, in which the developing egg growths and out of which it is ultimately released during ovulation. Follicle stimulating hormone (FSH): In women, FSH is the pituitary hormone responsible for stimulating follicular cells in the ovary to grow, triggering egg development and the production of the female hormone estrogen. In the male, FSH is the pituitary hormone that travels through the bloodstream to the testes and helps stimulate them to manufacture sperm. Gonadotrophins: This term includes both the FSH and LH hormone, which are secreted by the pituitary gland. Both these hormones are obtained from natural sources and processed into ampoules as injectable medication for ovulation induction. Hormones: Chemical substances formed in one organ or part of the body and carried to another organ. Depending on their composition they can change the function and sometimes the structure of one organ or a number of them. Hypoglycemia: An abnormally low concentration of glucose (sugar) in the blood, i.e. less than the minimum of the normal range. Insulin: This hormone secreted by the pancreas helps to control the glucose metabolism in the body. Luteinizing Hormone (LH): In women, the pituitary hormone that triggers ovulation and stimulates the corpus luteum of the ovary to secrete progesterone and trogens during the second half of the menstrual cycle. In the male, LH is the pituitary hormone which stimulates the testes to produce the male hormone testosterone. Oestrogen: The female sex hormones produced by the ovaries which are responsible for the development of female sex characteristics. Estrogens are largely responsible for stimulating the uterine lining to thicken during the first half of the menstrual cycle in preparation for ovulation and possible pregnancy. They are also important for healthy bones and overall health. A small amount of these hormones are also produced in the male when testosterone is converted to estrogen in fat cells. Ovarian hyperstimulation syndrome: During this complication of ovulation induction, the ovaries respond excessively to gonadotrophins with multiple follicle development, extreme enlargement of the ovaries and accumulation of fluid in the abdominal cavity. Ovaries: The two female glands in the pelvis that produce eggs, oestrogen and progesterone. Ovulation Induction: This is the process where medication is used to stimulate the development and maturation of an egg. Pituitary gland: A small hormone producing-gland beneath the hypothalamus in the brain which controls the ovaries, thyroid, and adrenal glands. Ovarian function is controlled through the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH). Disorders of this gland may lead to irregular or absent ovulation in the female and abnormal or absent production in the male. Progesterone: A female hormone secreted by the corpus luteum after ovulation during the second half of the menstrual cycle (luteal phase). It prepares the lining of the uterus (endometrium) for implantation of a fertilized egg and allows for complete shedding of the endometrium at the time of menstruation. In the event of pregnancy, the progesterone level remains stable beginning a week or so after conception. source: http://www.vitalab.com/pcos.htm |