Polycystic ovary syndrome (PCOS) and his treatment

Polycystic ovary syndrome (PCOS) is the most common endocrine disorders - endocrinopathies - in women of fertile age.

It is characterized by chronic anovulation, hyperandrogenism and polycystic ovarian. Often associated with hyperlipidemia, insulin resistance and type II diabetes, and therefore this multisystemic syndrome reproductive-metabolic disorder.

The incidence of the syndrome is 15-20% at a young age, something more common in adolescents and is 25%, and 10% of perimenopause.

In 80-90% of patients is associated with:

• * novulation

• * oligomenorrhea (extended cycle)

• * acne or hairiness

 In 30% of patients is associated with:

• * amenorrhea (absence of cycles)

• * a disorder of glucose metabolism.

And it's characterized by:

• * high frequency of infertility and spontaneous abortions

• * high incidence of pathological changes in pregnancy

• * high correlation with obesity.

The diagnosis of Polycystic ovary syndrome

Diagnosis is based on the existence two of the following three criteria (according to Consensus from Rotterdam):

1. Oligo / anovulation: ovulation rare or absent

2. Hyperandrogenism:

• * clinical or biochemical

• * elevated levels of hormones - androgens

• * signs - acne, hirsutism, etc.

3. Polycystic ovarian (ultrasound)

• * Increasing volume of ovarian ≥ 10 ml

• * numerous small follicles> 12

• * and the only one ovary

• * thick stromal ovarian follicles such as necklaces

Only polycystic ovarian not sufficient for the diagnosis of this syndrome.

Additional diagnostics PCOS includes:

1. Analysis of hormones:

a. Follicle-stimulating hormone (FSH)

b. luteinizing hormone (LH)

c. androgens (total and free testosterone, androstenedione)

d. dehidroepiandrostendion sulfate (DHEAS)

e. 17-hydroxyprogesterone (17-OHP)

f. Anti-Müllerian hormone (AMH)

2. Dynamic tests of hormones:

a. TSH, prolactin, cortisol
b. The insulin / glucose ratio - IR
c. Glucose tolerance test (GUK) - OGTT, HbA1c
d. Body weight and BMI (body mass index - BMI)

Dysfunction caused by Polycystic ovary syndrome

• * Neuroendocrine disorders

In the brain and pituitary gland disorder controller appetite and hunger and exaggerated controls and incentives for the pituitary gland. An imbalance in the production of hormones that control the ovaries (elevated luteinizing hormone - LH, low follicle stimulating hormone - FSH)

• * Ovarian dysfunction

Increased recruitment is antral follicle, elevated the Anti-Müllerian hormone, it is noticeable maturation of follicles, absence of ovulation, the abnormal production of steroid hormones, androgens are elevated-hyperandrogenemia (testosterone, androstenedione).

• * Impaired function of adipose tissue

Increased production of testosterone, estrogen, android obesity (abdominal).

• * Elevated androgen

Elevated androgen from the ovaries, adrenal glands and fat tissue enhancing insulin resistance (IR), affect the imbalance of lipids (fats) in the blood, arrest follicles, causing hyperandrogenism - seborrhea, oily skin and hair, increased hairiness, hair fall.

• * Insulin resistance (IR)

Insulin resistance is not a diagnostic criterion for PCOS, but it is extremely important because elevated insulin negatively affects the brain, ovary, coagulation and contributes to elevation of androgens and metabolic diseases.

Even 70% of women with PCOS is overweight and has insulin resistance, which means a reduced sensitivity of tissues to insulin action, usually in terms of reduced glucose utilization.

Understanding of insulin resistance in women with PCOS based on the assumption that certain tissues resistant to insulin, while the other at the same time sensitive. Women with PCOS are resistant to the action of insulin to a degree corresponding to that of type II diabetes.

Determining insulin resistance is carried out by:

Glucose tolerance test (OGTT)

Fasting insulin (I0)

The ratio of glucose and insulin (G / I ratio)

HOMA index

Other potential markers of insulin resistance (IR) for possible clinical use as homocysteine, plasminogen activator inhibitor-1 (PAI-1) binding globulin sex steroids (SHBG), and a protein that binds to insulin-like growth factor (IGFBP-1).

How to recognize Polycystic ovary syndrome, when the suspect?

The first possible sign is the absence of menstruation for a period of several months or long menstrual cycle and up to 6 weeks. Irregularities of the menstrual cycle may be manifested either by type of dysfunctional bleeding, either as oligo or amenorrhea.

In women with polycystic ovarian follicles do not mature enough to lead to the release of the egg, or ovulate. Therefore anovulatory polycystic ovary has a lot more small antral follicles than normal ovary and therefore specifically looks. Small antral follicles ultrasound appear as cystic structures that reflect stopped follicles in the middle phase of development.

But it can happen that the ovaries look healthy and PCOS is present. Often due to the male hormone testosterone appears excessive hairiness (hirsutism), and the male hair - hair patterns on the chest, abdomen, chin, toes, etc. Usually women suffering from PCOS suffer from being overweight, but not the rule. Fat accumulation is particularly pronounced at the waist, while the shoulders and arms thin. Not often there is the high blood pressure and high levels of LDL and decreased levels of HDL cholesterol, and elevated triglycerides. There are also cosmetic problems like oily skin, acne, seborrhea (dandruff), dark characters on the skin (especially on the neck, under the arms, on the knees, elbows, etc.). It can occur and male pattern baldness.

First time PCOS is most often detected because of infertility, when after 12 months of unprotected sexual intercourse there is no pregnancy, and not in terms of the so-called. male factor. Changes to the gynecological treatment of women. As there are various symptoms that may or may not be a sign of PCOS, is difficult to detect only one test. Ultrasound examination is not sufficient because some women have ovarian cysts.

Which doctor - a specialist can diagnose and treat PCOS?

Any doctor familiar with polycystic ovary syndrome can be diagnosed disease, or disorder is complicated and should be treated by a specialist. Women who have difficulty conceiving should go reproductive endocrinologist. The gynecologist may treat some women who have the syndrome, but a specialist endocrine disruption is more versed in treatment options in recent studies of polycystic ovary syndrome.

How to prepare for an initial discussion of PCOS with a doctor?

It is necessary to write down all the questions before the scheduled visit to the doctor, prepare family medical history, especially insulin resistance, diabetes, lipid abnormalities (high cholesterol), obesity, high blood pressure, heart disease and infertility. It is necessary to process information both partners and their families. Characteristics of PCOS can be inherited from any family party.

In addition, it is desirable to collect all the relevant medical data. The important thing is to inform about the symptoms of PCOS and discussed with your doctor.

Symptoms of Polycystic ovary syndrome

• * Amenorrhea (no menstrual period), infrequent menses, and / or oligomenorrhea (irregular bleeding) - cycles are often longer than six weeks, with eight or fewer periods per year. Irregular bleeding may be is lengthy bleeding episodes, scant or heavy periods, or frequent spotting (spotting)

• * Oligo or anovulation (infrequent or absent ovulation) - While women with PCOS produce follicles (fluid-filled bags on the ovary that contain an egg), the follicles often do not mature and release an egg that is necessary for ovulation.

• * Hyperandrogenism - elevated levels of male hormones, especially testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS).

• * Infertility - Infertility is the inability to get pregnant within 6-12 months of unprotected intercourse, depending on age. With PCOS, infertility is usually due to ovulatory dysfunction.

• * Cystic ovaries - Classic polycystic ovaries have a "string of pearls" or "pearl necklace" appearance with many cysts (fluid-filled bags).

• * Enlarged ovaries - Polycystic ovaries are often 1.5 to 3 times higher than normal

• * Chronic pain in the lower abdomen - the exact cause of this pain is not known, but it can be enlarged ovaries. Pain is considered chronic when it occurs more than six months.

• * Obesity or weight gain - often women with polycystic ovary syndrome are called. apple shape where the increase in weight is concentrated in the abdomen, similar to the way men often gain weight, along with narrower arms and legs. The ratio of waist: the waist is similar in women pear-shaped. It should be noted that in women with polycystic ovary syndrome often present obesity.

• * Insulin resistance is a condition where the body is unable to use insulin. It is usually accompanied by compensatory hyperinsulinemia - an over-production of insulin. These conditions often occur with normal glucose levels and can lead to diabetes, in which glucose intolerance is further decreased and blood glucose levels may be elevated.

• * Dyslipidemia (lipid abnormalities) - Some women with PCOS have elevated LDL and decreased HDL - cholesterol levels, and high triglycerides.

• * Hypertension (high blood pressure) - blood pressure over 140/90.

• * Hirsutism (excess hair) - Excess hair growth on the face, chin, chest, abdomen, thumbs or toes.

• * Alopecia (male pattern baldness or thinning hair) - baldness is more common at the top of the head than on the temporal part.

• * Acne / Oily Skin / Seborrhea - Oil production is stimulated by overproduction of androgens.

• * Acanthosis nigricans (dark patches on the skin, which are brown, almost black) - often on the back of the neck, but also on the arm folds, breasts and between her thighs, sometimes on the hands, elbows and knees. Darker skin is often velvety or rough to the touch.

• * Akrohordoni (signs on the skin) - small signs on the skin that usually have no symptoms unless by rubbing.

What causes Polycystic ovary syndrome?

The exact cause of PCOS is unknown. There are studies to find the genetic code that tell how polycystic ovary syndrome in families. The genetic component of PCOS is still unknown with certainty but it is believed that the background of the syndrome interaction of multiple genes.

The consequences of Polycystic ovary syndrome?

1. The consequences that arise due to the changed relationship of hormones due to the permanent effects of estrogen and progesterone deficiencies - menorrhagia (heavy periods), hyperplasia and endometrial cancer (performance only estrogen, progesterone without oponirajućeg effect, creates a risk to the lining of the uterus)

2. Hyperandrogenism - anovulation, acne, hirsutism, alopecia, central obesity, insulin resistance

3. Infertility - anovulation, early miscarriages, pregnancy pathology

4. Metabolic syndrome - dyslipidemia (high total and LDL cholesterol, low HDL cholesterol and high triglycerides), hypertension, diabetes, cardiovascular diseases

Whether all women with PCOS have pronlems with infertility?

If the main criterion is anovulation, then by definition women with PCOS have problems with infertility. It is possible to have the appearance of polycystic ovaries and be fertile, but if its idiagnosed PCOS usually adversely affect fertility.

Is basal temperature reliable in women with PCOS?

For women with PCOS, whose cycles are often anovulatory, basal temperature is erratic nature. If a woman with PCOS has an ovulatory cycle, the BBT chart should show a thermal, but it is a bit harder to read. There are discrepancies about the interpretation of the chart, but it is important to follow the advice of your own doctor.

Are ovulation predictor kits reliable for women with PCOS?

Depends how women high LH levels. A woman with elevated LH may consistently get positive tests or get erratic readings. Most women will get some kind of line in the preview window with the result since LH is always present - it is important to note a positive result if is dark or darker than the control line. It is also important to check the doctor's suggestions on home monitoring.

Can weight loss restore fertility of women with PCOS?

It is possible, but not always. There are lean women with PCOS. Weight loss can reduce insulin resistance, resulting in spontaneous or improved ovulation. Quick weight loss may cause more harm than good so slow weight loss is best. Loss of 10% by weight should be sufficient to improve the symptoms.

Can drugs that increase insulin sensitivity (insulin sensitizers) used with ovulation stimulation drugs?

Yes. Use of these medicines while trying to conceive is becoming more common, and some doctors will include them with ovulation stimulation medications such as Clomiphene, injections of FSH or FSH / LH injection. Greater debate right now is when to stop with medication when pregnancy is achieved.

Additional data for woman which taking drugs while in  IVF / ET are limited. There are no controlled data that proves whether insulin levels important influence on oocyte quality, but some generalizations suggest on it. It seems that women who used metformin have a greater number of mature eggs retrieved.

Is the risk of miscarriage higher in PCOS?

It is believed that PCOS increases the risk of early miscarriage. One possibility is that the early loss associated with increased levels of luteinizing hormone. Another possibility is increased levels of insulin and glucose, which can prevent implantation or cause problems in the developing embryo. There is a possibility that insulin resistance may reduce egg quality. This leads to other possibilities - late ovulation (after 16 days cycle) which is associated with underdevelopment of follicles and reduced quality of oocytes.

The initial way to reduce abortion-related PCOS is the normalization of hormone levels. Normalization of sugar and glucose in the blood can help and lead to reduced levels of androgens. It seems that the constant use of Metformin, at least through early pregnancy, can reduce the risk of miscarriage, especially in patients with repeated miscarriages. As with all other drugs in pregnancy, it must be assessed whether the benefit exceeds the potential risk.

Treatment of Polycystic ovary syndrome

Treatment of PCOS in adolescents

• * focused on the regulation of the menstrual cycle in order to protect the endometrium and correcting irregular bleeding

• * treatment of acne and hirsutism

• * Troubleshooting thickness and insulin resistance

In treatment are used:

• * Low-dose antiandrogen hormonal contraceptives (COCs, combined oral contraceptives - Diane 35, Yaz, Yasmin, Cilest - all kinds of acting anti-androgen)

• * progestins - Duphaston, Utrogestan

• * antiandrogens - cyproterone acetate, flutamide, finasteride

• * insulin sensitizing drugs - metformin and the like

• * hormonal contraception with the addition of low doses of anti-androgens and / or metformin

Treatment of Polycystic ovary syndrome in women of childbearing age

• * specificity with respect to the reproduction needs

• * protection of the endometrium

• * resolution of hyperandrogenism

• * reducing insulin resistance

• * solving infertility

Treatment of infertility in women with PCOS

1. Weight Loss - Diet / Exercise

2. Stimulation of ovulation:* Clomiphene citrate (CC), Letrozole table.

• Clomiphene citrate is an estrogen agonist / antagonist for the establishment of ovulatory cycles acting through competitive inhibition of estrogen binding to its receptor in the hypothalamus. This creates pseudohipoestrogeno condition, which results in the increase of FSH through feedback and progressive growth, the selection of the dominant follicle and ovulation in the establishment of an appropriate patient.

Letrozole belongs to aromatase inhibitors which block the conversion of testosterone and androstenedione into estrone and estradiol, which stop negative effect of estrogen on the hypothalamus and pituitary. Blockade of the conversion increases concentration of androgens. The higher local levels of androgens increases the sensitivity of follicles to FSH. Consequently, there is growth and development of ovarian follicles.

• * Gonadotropic hormones - Gonal F, Puregon, Menopur and others.

• Ovulation induction with gonadotropins is commonly used after the failure of applying Clomiphene citrate (which typically occurs in about 20% - 40%).

• Giving you clearer gonadotropins (Gonal F, Puregon, etc.) In women with PCOS certainly has an advantage over mixed gonadotropins (Menopur, Merional, etc.), and to determine exactly, should be done before stimulation extended hormonal treatment and proper interpret the observed findings on the basis of which later individualise and access.

• * Glucocorticoids - dexamethasone, prednisone

• Glucocorticoids (Dexamethasone, Decortin) feedback suppress levels of ACTH, hormones from the hypothalamus, which regulates the level of performance of the adrenal glands and thereby reduce the proportion of androgen hormones. DHEA and DHEA-S have inherently poor androgen action, or after metabolism in peripheral tissues obtained strong androgenic properties. The use of these drugs directly reduces the production of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S).

• * Metformin

• The use of metformin lowers blood sugar levels and, therefore, insulin levels; peripheral insulin resistance may reduce the ability of the drug that activates glucose transport in muscle and liver. Androgens profile is normalized to metformin wherein the total and free testosterone decrease while elevation of SHBG.

• * The combination of the above drugs

3. laparoscopic ovarian drilling - laparoscopic electrosurgery ovaries surgically principle of treating Polycystic ovary syndrome, intended to reduce the active ovarian tissue which consequently changes the endocrine mechanisms in the ovary