Polycystic ovary syndrome/PCOS, one of the most common endocrine diseases affecting 8-13% of women of reproductive age, Tedee et al. In 2018; It is a heterogeneous disease characterized by hyperandrogenism and chronic avulsion. PCOS symptoms usually appear in early adolescence, and it is difficult to distinguish between its complex pathophysiology and triggering causes. PCOS is a health problem that affects one in 10 women of childbearing age. Hormonal imbalance also affects the general health and appearance of women with this disease and metabolism problems. Contrary to what is known, it is a common and treatable cause of infertility because women with PCOS cannot have children.

PCOS PATHOPHYSIOLOGY
A self-made and tight hypothalamic network is reproduction. HPO hormones give internal signals (side and external signals) and external effects. At the same time, this function and microbe will be more (1,2). Typical clinical features include hair growth, irregular menses, chronic anovulation, and infertility. Persistent hyperandrogenism, hypothalamic-pituitary, LH hypersecretion, early granulosa cell luteinization, abnormal oocyte, and early active primary follicles(3). Various hypotheses have been proposed over the years. In patients with PCOS, a self-perpetuating vicious circle-like phenotype including neuroendocrine, metabolic, and ovarian dysfunction occurs. PCOS develops in early puberty(4). Recent clinical, experimental, and genetic data highlight neuroendocrine involvement in the pathophysiology of PCOS.

1.) Ovarian, Adrenal, and Androgen Excess
PCOS is characterized by excessive ovarian and/or adrenal androgen secretion. Intrinsic ovarian factors such as altered steroidogenesis and extra ovarian factors such as hyperinsulinemia contribute to excessive ovarian androgen production. Its features include premature growth arrest of antral follicles at 5 to 8 mm, with more growing follicles in women with PCOS compared to normal controls. The classical ovarian phenotype of enlarged ovaries with pearl floss morphology and theca interstitial hyperplasia reflects androgen exposure; this morphology has also been observed in women with congenital adrenal hyperplasia (CAD) and in female-to-male transgender individuals (1,5). Distorted interactions between endocrine, paracrine, and autocrine factors responsible for follicular maturation may contribute to ovarian dysregulation in PCOS.

Under normal conditions, the ovarian stroma provides a structural framework that undergoes dynamic changes to support follicular growth. However, the ovarian stroma of women with PCOS tends to be more rigid. The developing oocyte and its surrounding structure rely on endocrine, paracrine, and autocrine signaling mechanisms to maintain cell-to-cell communication and ensure synchronized developmental progression. Abnormal development during these earliest stages of follicular growth, possibly contributing to the ovarian aspects of PCOS. Another feature of PCOS ovaries is the accelerated transition from primordial to growing follicles, increasing their number by 2 to 3 mm and 3 to 4 mm (6,7). AMH concentrations correlate with the number of these small antral follicles [ 8 ]. The growing follicle is exposed to an atypical environment with increased concentrations of LH, insulin, androgen, and AMH accompanied by insufficient FSH concentrations (9). Additional differences in PCOS ovaries include factors that influence vascular function and immune response.

2.) Neuroendocrine Factors
Increased LH pulse frequency, LH pulse amplitude, and increased LH/FSH ratios have been described in women with PCOS. The first features of PCOS appear in the early pubertal years, with reactivation of the hypothalamic GnRH pulse generator, increased gonadotropin secretion, and subsequently increased ovarian estrogen production. Hypothalamic GnRH neurons secrete GnRH in separate pulses from the median dominance to the pituitary gonadotrophs, resulting in pulsatile LH and FSH secretion (1,10). The LH and FSH pulse frequencies are modulated by the GnRH pulse frequency. Increasing the GnRH pulse frequency increases the LH pulse frequency and decreases the FSH pulse frequency (11). The increased LH pulse amplitude and pulse frequency observed in PCOS are most likely governed by increased pulsatile GnRH secretion.

3.) Insulin Resistance and Hyperinsulinemia
The phenotype of female patients with insulin receptor gene mutations includes insulin resistance (IR), compensatory hyperinsulinemia, and hyperandrogenism (12). Although IR and hyperinsulinemia are commonly detected in women with PCOS, insulin receptor gene mutations are extremely rare among women with PCOS. Women with PCOS have intrinsic IR, independent of the extent of obesity and the magnitude of androgen concentrations (13). IR is observed even in thin women with PCOS; increased body mass index (BMI) exacerbates IR (14). Normal-weight adolescent girls with PCOS have peripheral IR, increased liver fat, and muscle mitochondrial dysfunction compared to normal-weight girls. The prevalence of metabolic syndrome, defined as obesity, hypertension, dyslipidemia, and hyperglycemia, is approximately three times higher in women with PCOS. In some studies, obesity, diabetes (especially Type 2 Diabetes Mellitus), and metabolic syndrome development have been found to aggravate PCOS symptoms.

4.) Obesity
Overweight and obesity are common problems in women with PCOS. In response to overeating, adipocytes may hypertrophy or form new adipocytes with hyperplasia. A study of women with PCOS showed an increase in total abdominal fat mass due to preferential accumulation of intra-abdominal fat, with an increased population of small subcutaneous abdominal adipocytes, however, an increased risk of dysglycemia and cardiovascular disease. It has been demonstrated in studies carried out so far (1).

5.) Genetics
Twin studies show heritability to be approximately 70%.112 In a meta-analysis, loci (where a gene, one of its alleles, or a DNA sequence are thought to be on the chromosome or its physical specific location on DNA) are associated with genes plausibly related to the metabolic and reproductive properties of PCOS. showed that (15).

SYMPTOMS OF PCOS IN ADULT AND ADOLESCENT PERIOD
Symptoms seen in PCOS vary according to the age of women. Generally, young women complain of reproductive and psychological problems, while older women complain of metabolic problems. It has been reported that to diagnose PCOS in adolescents, they must meet the Rotterdam criteria as in adults. Normal pubertal events in adolescents and children PCOS It is difficult to make a definitive diagnosis as it tends to mimic the signs and symptoms.

Hyperandrogenism:
Hirsutism, which is defined as male pattern hair growth in women, is the primary clinical sign of hyperandrogenism and genetic and ethnic variations affect its development. The modified Ferriman-Gallwey scoring system is widely used in hirsutism. According to this scoring, a score of ≥4 to 6 points to hirsutism(16,17)
Other cutaneous symptoms of androgen excess are; severe cystic acne and male pattern baldness. Biochemical hyperandrogenism is confirmed by high serum androgen concentrations(1,18)

Since puberty is characterized by physiological hyperandrogenism, reference values for androgen levels in female adolescents are not well defined, and reference values do not take into account ethnic differences to detect hirsutism, it can be confused with pathological hyperandrogenism and the PCOS image may be blurred(19,20).

 

Irregular period:
Increased gonadotropin secretion promotes ovarian swelling secretion and follicular. Estrogen; Teaching of endometrial proliferation from the cervix and the cervix will generally be applied from endometrial learning. (one).
Ergenof hypothalamus/HPO, 2 curves, and oligomenorrhea will be fully defined years after menarche. may not begin to occur (,21). This should be expected in adolescents with fewer menstrual years19.

Polycystic Ovaries in the US:
Enlarged ovaries with increased stroma and smaller peripheral cysts are present in PCOS morphology. The PCOS Society recommended the Task Force, transvaginal readability as a stand-alone follicle using transvaginal readability.
Adolescent ovaries’ volumes and sizes become normal sizes for diagnosis. For diagnostic purposes, adolescence periods were accepted as less than or equal to 10 ml of normal ovarian length(1,19).

DIAGNOSIS AND EVALUATION
To make the diagnosis, an evaluation begins with a comprehensive anamnesis, including a detailed family history of the patient and a complete physical examination. Laboratory tests including thyroid, prolactin, total testosterone, and AMH (egg reserve) concentrations are performed in the individual with symptoms suggestive of PCOS. For more accurate results It is recommended to discontinue spironolactone and oral contraceptive pills (OCP) one month before the test and to perform tests close to the luteal phase of the menstrual cycle. At the same time, body mass index (BMI), fasting cholesterol, and 2-hour glucose loading measurements should be performed in these patients. Increased insulin resistance, Hyperinsulinemia, and obesity are defined in women with PCOS.
Appropriate care for the patient should aim not only to treat current symptoms but also to prevent any morbidity that may develop later in the future. For this, patients should be evaluated in terms of Type 2 Diabetes Mellitus, Cardiovascular Diseases, and Psychological Well-being at regular intervals (1,19).

1.)National Health Criteria/NIH》Hyperandrogenism and Menstrual Irregularity (2 criteria)
2.)PCOS Society Criteria》Hyperandrogenism and Menstrual Irregularity or Polycystic Ovaries on US (2 criteria)
3.) Rotterdam Criteria》Hyperandrogenism, Menstrual Irregularity and Polycystic Ovaries in the US (two out of 3 criteria)

It is evident in women with PCOS and women (Rotterdam, 2004; Chhabra et al., 2005; Legro et al., 2013) as follows (19,22,23,24).

1.)Hyperandrogenism=
Clinical Examination》Hirsutism, acne, androgenetic alopecia, acanthosis nigricans.
Lab. Values》High circulating testosterone levels.
2.) Menstrual Irregularity=
Clinical Evaluation》Oligomenorrhea or amenorrhea.
Lab. Values》High Level LH.
3.)Polycystic Ovaries in US=
≥12 follicles in the ovary
The folic interval between 2-9 mm

 

According to the Rotterdam criteria, the disease is divided into four phenotypes;
1. ➢ Frank or classical polycystic ovaries PCOS (chronic anovulation, hyperandrogenism, and polycystic ovaries)

➢ Classical non-polycystic ovarian PCOS (chronic anovulation, hyperandrogenism, and normal ovaries)
➢ Non-classical ovulation PCOS (regular menstrual cycles, hyperandrogenism, and polycystic ovaries)
➢ Non-classical or normoandrogenic PCOS (chronic anovulation, normal androgens, and polycystic ovaries)(19).

 

Infertility in PCOS

Women with PCOS may have reduced fertility due to associated endocrine and gynecological abnormalities that affect ovarian quality and function. Persistent periods of anovulation associated with PCOS are positively associated with infertility. A 1995 study reported that 50% and 25% of women in the PCOS population suffered from primary and secondary infertility, respectively (Balen et al., 1995). More recently, a study by Hart and Doherty in 2015 showed that infertility is 10 times more common among women with PCOS compared to healthy controls. Various research data also show an increased risk of miscarriage in women with PCOS.

The effect of the classical or non-classical PCOS phenotype on female fertility is not yet fully understood. Data describing the effects of PCOS on pregnancy outcomes are also limited and based on small studies. Comprehensive studies are needed to evaluate the degree of infertility in various phenotypes of PCOS and to understand the reasons for the increased negative pregnancy outcomes in this group of women.

Regarding the effects on the embryo, women with PCOS have a 2.5 times higher risk of giving birth to children of gestational age compared to healthy women and show an increased morbidity and mortality compared to control.

PCOS and Cancer Relationship

Women with PCOS present many risk factors associated with the development of endometrial cancer, such as obesity, insulin resistance, type II diabetes mellitus, and anovulation. Anovulation triggers an unchallenged state of uterine estrogen exposure. This can then trigger the development of endometrial hyperplasia and eventually endometrial cancer. Some studies show that women with PCOS have a threefold increased risk of developing endometrial cancer (Chittenden et al., 2009; Fauser et al., 2012; Haoula et al., 2012; Dumesic and Lobo, 2013). ) This is often well differentiated with a good prognosis.

On the other hand, data supporting any association between PCOS and breast and ovarian cancer are limited. (Chittenden et al., 2009 ; Fauser et al., 2012 )

TREATMENT OPTIONS
PCOS treatment is managed by a multidisciplinary health team consisting of a gynecologist and endocrinologist, a dermatologist, a pediatric reporter, a physiotherapist, a dermatologist, a child registry, a physiotherapist, a specialist, and a psychologist. Treatment processes are generally managed by users for websites. anovulation, infertility, hirsutism.
1.) Lifestyle Intervention
Nowadays, pacing with PK is mainly used as a basic exercise therapy and a calorie-dense diet. It is chosen as a suitable choice for lifestyle(25,26). future detox) is recommended for adolescents (1,27). In addition, before going to WHO without considering the patient or in general, you can stay right on the news for 75 minutes in the middle or 150 minutes in the middle. Can you come in this one day. will be.

2.)Exercise
It is specially shaped for weight control or weight-oriented exercises for patients. Previously favored weight is associated with adverse metabolic evaluation and reproductive outcomes with PCOS. Numerous minor uncontrolled studies show that a 5% decrease in menstruation increases fertility and testosterone testing, laundering and hirsutism, and similarly, 30 unrated,32).
In PCOS it can be added additionally and has a good over anthropometric contours around the waist in addition to food such as visible, body mass appearance, upper part, insulin and lipid profile, and can also prolong tabular and other risk factors. It should be made suitable for application with PCOS.

Although the intensity and duration of the exercise is determined individually, it has been brought to the agenda in recent studies that low-intensity exercises are more beneficial than moderate-intensity exercises. As a type of exercise, but there is moderately conclusive evidence that aerobic exercise has a positive effect on body composition; exercise prescription and to guide clinical management. Longer-term and well-designed studies are needed to test the effect of specific exercise interventions on reproductive health outcomes.(19,28). A holistic twelve-week yoga program in adolescents with PCOS is highly effective in reducing anxiety symptoms.

Warm-up and Cool-down: It can be done for 5-10 minutes. While the main purpose of warming up is to slowly increase the heart rate, the purpose of cooling is the opposite, that is, slowly reducing the heart rate. Warming up and cooling down also reduces the risk of injury. Rom exercises or stretching involving large muscle groups such as hamstring, quadriceps, gastro-soleus, lumbar extensors can be performed. In cooling, stretching involving large muscle groups can be performed as in warming up. In some studies, it is said that stretching exercises will be more appropriate for cooling.

Aerobic Exercise: How to do it continuously for 5 days during 12-24 weeks.
Doing sports such as brisk walking, jogging, cycling or jumping rope between 20-60 minutes will not cause fatigue.

Resistance Exercises: It can be done 2-3 days a week for 12-24 weeks. More studies are needed for the effect of resistance training on PCOS treatment.
There should be a one-minute rest between sets and the valsalva maneuver should be avoided during the exercise. Core, pelvic floor muscle strengthening, squat and bridge exercises, hamstring and quadriceps strengthening, pilates band or dumbbell and strengthening exercises involving large muscle groups can be given individually (28).

 

Summary of international practice and activity recommendations in Evidence-Based Education for PCOS(33,34)

ADVICE OF RECOMMENDATION must purchase sufficient 75 for purchase and care and health advice (18 years old) within at least 150 minutes of visit or visit in the near or near future; In countries where two throws are not possible, muscle strengthening is included. 3 layers of final muscle and training for adolescents;

RECOMMENDATION2=Growth health and advice for health work, ideal weight final, weight gain progression and more benefits:
Less than 250 minutes of activity per week in secondary school or less than 150 minutes of activity in school and caste or school.
He said he trains major muscle groups two non-consecutive days a week.
Less inactivity, screen or sitting time.

RECOMMENDATION3=PCOS is a complex condition with multiple clinical features that place a significant burden on affected women. It is important for women with PCOS to include exercise and physical activity in the treatment plan and be supported by all members of the care team. The significant psychological burden associated with PCOS may affect the success of lifestyle therapy. Therefore, referral to a certified professional where appropriate should be considered as part of a chronic disease management plan. These certified exercise professionals must have higher education (university) training in developing personalized physical activity and formal exercise programs while addressing psychosocial barriers. Certified professionals are likely;
Certified Clinical Exercise Physiologist (ACSM; USA)
Accredited Exercise Physiologist (ESSA; Australia)
Certified Exercise Practitioner (BASES; UK)
Physiotherapist or Physical Therapist (Europe)

RECOMMENDATION4=Fitness trainers / personal trainers should be included after gaining confidence and proficiency in exercise programs.

RECOMMENDATION5=Fitness devices and technologies can be used as an aid to support and encourage active lifestyles and minimize sedentary behavior (step counts and active minutes).

Diet
With PCOS, weight and insulin resistance are faced for progression.
Positively designed in terms of high fiber spring break, the design consists of cruciferous vegetables such as broccoli and snow; cruciferous beliefs such as green and red, peppers, beans and lentils, almonds, strawberries, and zucchini.
In addition to diet therapy that reduces inflammation. These; tomatoes, cabbage, spinach, almonds and walnuts, olive oil, fruits such as blueberries and strawberries, fish rich in omega-3 fatty acids such as salmon and sardines.
In addition, those who are in good condition in terms of both the user and general health benefit. Among them, refined models such as white bread can be observed in shape and design. High-fiber vehicles such as broccoli, lean protein such as fish, lean proteins such as fish, turmeric, and spices can be preferred.

Medical Treatment
Lifestyle interventions to complement symptoms plan military to military to better manage shipboard referrals;
Oral contraceptive pills/OCP: Most commonly used for long-term with COS. OCP hypothalami-pituitary-ovary, suppress thinness, reduce LH secretions, purify sex pleasure globins content, and personal testosterone. It addresses acrobatic hirsutism, hyperandrogenism, and corrects menstrual minor mediation, provides a means of effective contraception. A minimum of 6 months of OCP is required to achieve subtle results against acne and hirsutism(19).
metformin
Thiazolidinediones (TZD): It represents a class of insulin-sensitizing drugs used in the treatment of type II diabetes.
inositol
Spironolactone: One study showed that spironolactone, a steroid chemically related to a mineralocorticoid, can exert the effect of insulin; It has been suggested to have detailed information about it (19).

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