Polycystic Ovary Syndrome

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POLYCYSTIC OVARY SYNDORME, ENDLESS STORY

Polycystic Ovary Syndrome (PCOS) is the second common pathology in women who admit to our Pediatric and Adolescent Polyclinic, Department of Obstetrics and Gynecology, Medicine Faculty of Istanbul University. According to some database in USA, one of every 10 young girls have Polycystic Ovary Syndrome. And this Syndrome has physiologically negative effect on patient and her family.

Dear reader, ıt would be better to clarify some points before explanation of details.

1. Polycystic Ovary Syndrome (PCOS) is a syndrome as its name. Do not confuse with diseases which depend on only one reason that can be treated. A syndrome is the collection of signs and symptoms and it is an endocrine disorder. Therefore, the clinician should evaluate the patients generally and treatment should be planned according to this evaluation. The treatment is special for every patient and prognosis depends on this.

2. Polycystic Ovary Syndrome is usually seen in adolescents and the disease in adolescents is different from the disease in adults. Polycystic Ovary Syndrome in adolescents has different processes and pathophysiology detailed below.

3. Answer to question that ‘’Can I overcome this syndrome’’ is ‘’Sorry, maybe’’. As I mentioned before, this is a syndrome and the clinician should examine every patient individually.

4. Word ‘’Cyst’’ doesn’t mean that it must be operated. Treatment of some cysts are non-operative. Cysts in PCOS are very small and actually they are ovaries that cannot develop due to hormonal problems.

5. Usually, women ask ‘’May my daughter get pregnant ’’, hidden from the girl. I know, you have read so much about PCOS on the internet but believe that a significant number of the PCOS patients can get pregnant the natural way. First of all, your daughter has a normal uterus and ovaries. Anovulation is due to hormonal changes. If she has difficulties in becoming pregnant in the future, there is a lot of treatment modalities. Do nr-t worry your daughter will certainly have a baby. Now, the main problem is long term effects of the syndrome.

What is Polycystic Ovarian Syndrome? How does the disease develop? How is it diagnosed?

In last 10 years, method has completely changed. This is closely related to obesity in adolescents and insulin resistance in low birth weight babies.

Some criteria has been used for diagnosis of Polycystic Ovary Syndrome (PCOS). First standardization was done in 1990. So many studies performed and knowledge has increased, in years. Although, some points are still discussed, diagnosis criteria closest to the ideal was established in 2003. It has been revised in 2004. The criteria is called ‘’Rotterdam Criteria’’ and PCOS is diagnosed with 2 of the 3 Rotterdam criteria.

A. Rotterdam Criteria
1. Oligo- or anovulation: menstrual cycles more than 35 days or absence of ovulation.
2. Clinical or biochemical signs of hyperandrogenism: Acne on face, excessive facial and body hair, oily skin and hair, high androgen levels in laboratory tests (testosterone and derivate).
3. Ovaries appear on USG
** All other etiologies must be eliminated (especially, congenital adrenal hyperplasia, Cushing’s syndrome androgen secreting tumors)

B. Basic pathophysiology of Polycystic Ovarian Syndrome (PCOS)

According to Speroff, PCOS does not develop due to only one local or general special disorder, it is a hormonal disorder that is related to many different factors.

Today, it is known that prenatal (during pregnancy) growth restriction, postnatal (after birth) insulin resistance, dyslipidemia, exaggerated adrenarche and gonadal dysfunction leads to PCOS development. Let’s clarify this. First, basic biology then answer of ‘’how PCOS develops’’.

1. As you know, there is an endocrine gland placed in brain and it secretes LH (luteinizing hormone) and FSH (follicle stimulating hormone that stimulates ovaries) hormones. Ovum develops in a structure called follicle. FSH stimulates follicles and of course ovum. When the ovum maturation is complete, ovulation occurs and it corresponds to 14th day of a regular menstrual cycle. Corpus luteum is the left of the follicle after ovulation and it secrets progesterone. These two hormones affects endometrium that is inner mucous membrane of the uterus and the endometrium begins to bleed.

2. We explained the women period shortly. Now, the second lesson: we all have heard that testosterone is a male hormone and estrogen is a female hormone. This is a lie  In fact, the woman is a very good testosterone producer and even she produces estrogen from testosterone. There are 2 different group of cells inside the follicle that embodies ovum. One of these groups is theca cells and other is granulose cells. Theca cells secretes androgens that means testosterone. Granulose cells takes this testosterone from theca cells and converts it to estrogen by an enzyme called aromatase. Isn’t it astonishing?

3. So, ‘’what is the relation between insulin resistance and ovulation’’: adipose tissue is not only adipose tissue for women. The adipose tissue is hormonally very active. When the adipose tissue increases, insulin resistance increases, too. Insulin is secreted from pancreas and leads to the body for using the energy consumed in food. Insulin resistance is increased in fat person and energy cannot be taken into the cell. Consequently, body stores the unused energy as fat. However, the person feels hungry because the energy is not used, it is stored. Now you can understand why people get fatter and try to eat less but still get fatter and fatter. Increased ınsulin level affects insulin like growth factor (IGF-1, IGF-2) and IGF-binding protein (IGFBP). It is getting complicated. I am sorry, basic of the PCOS is a complicated subject. As insulin increases, IGFBP decreases in bloodstream. Therefore, IGF-1 and IGF-2 cannot bind and free levels of IGF increases excessively. Increased IGF-1 and IGF-2 results with increased androgenic activity.

You can see my ‘’Polycystic Ovarian Syndrome in Adolescents’’ slide and also you can find a summary of this subject here PCOS –In Adolescents PCOS -Ergenlerde

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 Let’s get to the question of ‘’HOW PCOS DOES DEVELOP?’’

Recently, Ibanez, a Spanish investigator has performed some studies about PCOS in adolescents. Therefore, a theory called ONTOGENİC THEORY is proposed and a lot of factors is evaluated by the theory. Let’s describe item by item.

Prof. Dr. Süleyman Engin Akhan
DETAİLS OF THE ONTOGENİC THEORY REGARDING HOW THE POLYCYSTIC OVARY SYNDROME DEVELOP IN ADOLESCENTS
PROF.DR.SÜLEYMAN ENGİN AKHAN

1. At the beginning of the menstrual cycle, LH level is low. However, in patients with PCOS, LH level is high. Therefore, FSH tries to develop the ovaries but it cannot be successful. FSH cannot overcome LH level. And so, in ultrasound, there is follicles all around the ovaries like pearls. This is why the syndrome is called as ‘’polycystic’.! 

2. Intrauterine growth retardation is seen in adolescents with PCOS. Babies with intrauterine growth retardation gain weight rapidly after the birth and mothers feels happy about that. However, this case results with obesity in age of 5-8. So, obesity related mechanism explained above is activated. Insulin resistance of tissue and insulin levels increase. Increased insulin decreases IGFBP-1 levels. We have already explained that the IGF-1 and IGF-2 are secreted from the theca cells in ovaries and decreased IGFBP-1 level increases IGF-1 and IGF-2. As a result, the androgenic mechanism is activated very highly. In 40-50 year old patients increased IGF-1 levels triggers a process that can turn into cancer.
Also, in these children, there is usually problem in CYP-19 gene that is an insulin gene.

3. Theca and granulose cell proportion is unbalanced in long term, abnormally theca cells are very much. Testosterone and androgen hormones are produced very much in these patients.

Consequently, insulin metabolism and increased androgen trigger the process that begins with excessive hair growth.

4. Progesterone cannot be secreted due to anovulation. So, estrogen is high, relatively. The patient undergoes menstruation one of two or three months. And, endometrium, inner mucous membrane of the uterus is not ‘’stable’’ due to lack of progesterone hormone. So that, it begins to bleed easily and the patient undergoes menstruation with heavy bleeding.

 BASİC OF THE MECHANİSM İS AS DEFİNED. TREATMENT AND OF COURSE TREATMENT PLANS SHOULD BE PREPARED AS SPECİAL FOR EVERY PATİENT. 

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Clinical Findings of Polycystic Ovarian Syndrome

Clinically, a significant number of the adolescent girls with PCOS are overweight or obese that mean their weight is 85% more than peers. 35-60% of the PCOS cases have obesity. Most common endocrinological syndrome associated with obesity in adolescent girls is PCOS.

Acne and excessive hair growth is the most common clinical complaint, especially in young girls.

Significant problem in insulin metabolism may cause increased feelings of hunger and this feeling triggers overeating periods.

Evaluation of Laboratory Results

Laboratory findings are very important for PCOS diagnosis. Therefore, hormonal and biochemical tests on 2nd, 3rd or 4th day of the menstrual period are very important. Although, FSH and LH levels are not necessary according to Rotterdam Criteria, it is not acceptable for adolescent patients. So, FSH, LH, E2, Total Testosterone, Free Testosterone, SHBG, Total Cholesterol, HDL/LDL, fasting blood glucose and fasting insulin levels should be required. 17-OH progesterone and DHEA-SO4 may be additionally required.

Treatment of Polycystic Ovarian Syndrome in Adolescent Girls

1. Every patient should be evaluated especially on its own.

2. First and basic step of treatment of obesity related PCOS is losing weight. After weight loss, ovulation an menstrual cycle occurs again. Normal ovulation occurs in more than 60% of patients who lost weight.

3. Metformin is an insulin sensitizer and use of metformin in PCOS is increased in recent years. Metformin decreases basal and stimulated levels of LH, free testosterone and plasminogen activator inhibitor-1 levels.

4. Different agent can be used for excessive hair. Despite criticism of some professors, my favorite is ‘’finasterid’’. Unfortunately, use of some drugs are ‘’off-label use’’ in our country. So, clinician should talk to patient and her family and then treatment plan may be planned.

Weight loss and drugs results rapid improvement. Till now, only oral contraceptives were used for PCOS. Only ovaries were going to sleep with oral contraceptives and it didn’t affect basic pathology. When metformin and other similar drugs are used with oral contraceptives, results are much better.