Key words: Polycystic Ovary Syndrome (PCOS), Complications, Insulin resistance, Amenorrhea,

International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html Issue 4, Vol. 3.May...
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International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html

Issue 4, Vol. 3.May-June 2014 ISSN 2249 – 5738

POLYCYSTIC OVARIAN SYNDROME: ITS IMPACT ON HEALTH Mrs. Bincy Varghese Department of Pharmacy Practice, Krupanidhi College of Pharmacy, Bangalore. Mobile: 9538309500.

ABSTRACT

Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. It affects multiple systems, and requires a comprehensive perspective on health care for effective treatment. Its metabolic derangements and associated complications include insulin resistance, diabetes, hyperlipidemia, hypertension, fatty liver, metabolic syndrome and sleep apnea. Reproductive complications are oligomenorrhea or amenorrhea, sub-fertility, endometrial hyperplasia and cancer. Cosmetic complications include acne & facial hair growth. Associated psychosocial concerns are depression and disordered eating. Anxiety, depression and reduced quality of life are also common in this condition. Diagnosis is clinical and is supported by lab findings. Regular exercise, healthy foods, and weight control are the key treatments for PCOS. Pharmacological treatments can reduce unpleasant symptoms and helps to prevent long-term health problems. Guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition.

Key words: Polycystic Ovary Syndrome (PCOS), Complications, Insulin resistance, Amenorrhea,

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International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html

Issue 4, Vol. 3.May-June 2014 ISSN 2249 – 5738

INTRODUCTION Polycystic Ovary Syndrome is one of the most common endocrine disorders among women of reproductive age. It is a problem in which a woman's hormones are out of balance. This is now a well-recognized condition affecting 6-25% of reproductive aged women; it affects multiple systems, and requires a comprehensive perspective on health care for effective treatment. [1] Metabolic derangements and associated complications include insulin resistance and diabetes, hyperlipidemia, hypertension, fatty liver, metabolic syndrome and sleep apnea. [2] Reproductive complications include oligomenorrhea or amenorrhea, sub-fertility, endometrial hyperplasia and cancer. Associated psychosocial concerns include depression and disordered eating. Cosmetic complications include acne & facial hair growth [3]

Symptoms of polycystic ovarian syndrome Menstrual disturbances [4]  Delay of normal menstruation (primary amenorrhea),  The presence of fewer than normal menstrual cycles (oligomenorrhea),  The absence of menstruation for more than three months (secondary amenorrhea ).  Menstrual cycle may not be connected with ovulation (anovulatory cycles) and may result in heavy bleeding. Elevated androgen levels  Acne R S. Publication, [email protected]

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 Excess hair growth on the body (hirsutism)  Male-pattern hair loss. Other signs and symptoms include  Obesity and weight gain  Elevated insulin levels and insulin resistance  Oily skin  Dandruff  Infertility  Skin discolorations  High cholesterol levels  Elevated Blood Pressure  Multiple, small cysts in the ovaries Above symptoms and signs may be absent in PCOS, with the exception of irregular and or no menstrual periods. All women with PCOS will have irregular or no menstrual periods. Women who have PCOS do not regularly ovulate; that is, they do not release an egg every month. This is why they do not have regular periods and typically have difficulty conceiving. Causes & Pathophysiology [5] The main causes are Genetic (Inherited) or Environmental factors. Genetic cause leads to hormonal variations; excessive production of male hormones in women may be a result of or related to the abnormalities in insulin production. A malfunction of the body's blood sugar control system (insulin system) is frequent in women with PCOS, who often have insulin resistance and elevated blood insulin levels. Another hormonal abnormality in women with PCOS is excessive production of the hormone LH, which is involved in stimulating the ovaries to produce hormones and is released from the pituitary gland in the brain.  Ovarian androgens are the main source of hyper androgenemia in PCOS. Hyper androgenemia has both a direct effect on the ovarian alterations. [6]  An increasing effect on pituitary LH (luteinizing hormone) pulse frequency and amplitude with relative low FSH (follicle stimulating hormone) secretion.  Further, adrenal androgens contribute to PCOS androgen excess.

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International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html

Issue 4, Vol. 3.May-June 2014 ISSN 2249 – 5738

 Insulin resistance with compensatory hyper insulinemia enhances ovarian androgen production  Decreases production of SHBG (sex hormone binding globulin) in the liver, and both increase the pool of bioavailable androgens.  PCOS is also associated with increased muscle sympathetic nerve activity that is related to high testosterone, insulin resistance, and obesity.  Genetic defects probably contribute to the pathology of PCOS. Diagnosis [7, 8,9] The diagnosis is usually a clinical one based on the patient's history, physical examination, and laboratory testing. Serum levels of male hormones (Dehydroepiandrosterone - DHEA and testosterone) may be elevated. However, levels of testosterone that are highly elevated are not unusual with PCOS. Levels of a hormone released by the pituitary gland in the brain (LH) that involves in ovarian hormone production are elevated. The cysts (fluid filled sacs) in the ovaries can be identified with imaging technology. Computed tomography (CT scan) and magnetic resonance imaging (MRI) also can detect cysts, but they are generally reserved for situations in which other conditions that may cause related symptoms, such as ovarian or adrenal gland tumors are suspected. Complications Women with PCOS are at a higher risk for a number of illnesses, including high blood pressure, diabetes, heart disease, and cancer of the uterus (endometrial cancer). Infertility is common in women with PCOS. Because of the lack of ovulation, progesterone secretion in women with PCOS is diminished, leading to long-term unopposed estrogen stimulation of the uterine lining. This situation can lead to abnormal periods, breakthrough bleeding, or prolonged uterine bleeding in some women. Unopposed estrogen stimulation of the uterus is also a risk factor for the development of endometrial hyperplasia and cancer of the endometrium (uterine lining). However, medications can be given to induce regular periods and reduce the estrogenic stimulation of the endometrium.[10,11] Obesity is associated with PCOS. Obesity not only compounds the problem of insulin resistance and type 2 diabetes, but it also imparts cardiovascular risks. PCOS and obesity are associated with a higher risk of developing metabolic syndrome , a group of symptoms, including high R S. Publication, [email protected]

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International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html

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blood pressure, that increase the chances of developing cardiovascular disease. It has also been shown that levels of C-reactive protein (CRP), a biochemical marker that can predict the risk of developing cardiovascular disease, are elevated in women with PCOS. Reducing the medical risks from PCOS-associated obesity is possible.[12] The risk of developing pre diabetes and type 2diabetes is increased in women with PCOS, particularly if they have a family history of diabetes. Obesity and insulin resistance, both associated with PCOS, are significant risk factor for the development of type 2 diabetes. Several studies have shown that women with PCOS have abnormal levels of LDL cholesterol and lowered levels of HDL cholesterol in the blood. Elevated levels of blood triglycerides have also been described in women with PCOS.[13] Changes in skin pigmentation can also occur with PCOS. Some of the studies refers to the presence of velvety, brown to black pigmentation often seen on the neck, under the arms, or in the groin. This condition is associated with obesity and insulin resistance and occurs in some women with PCOS. Treatment Non Pharmacological Treatment Regular exercise, healthy foods, and weight control are the key treatments for PCOS. Treatment can reduce unpleasant symptoms and help prevent long-term health problems. 

Try to fit in moderate activity often.



Walking is a great exercise that most people can do.



Eat healthy foods. This includes lots of vegetables, fruits, nuts, beans, and whole grains. It limits foods that are high in saturated fat, such as meats, cheeses, and fried foods.



Most women who have PCOS can benefit from losing weight. Even losing 4.5 kg may help get your hormones in balance and regulate your menstrual cycle.



Women who smoke have higher androgen levels that may contribute to PCOS symptoms. So quit smoking.

Pharmacological Treatment [14, 15, 16, 17]  Treatment of PCOS depends partially on the woman's stage of life. For younger women who desire birth control, the birth control pill, especially those with low androgenic (male hormone-like) side effects can cause regular periods and prevent the risk of uterine cancer. R S. Publication, [email protected]

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 Another option is intermittent therapy with the hormone progesterone. Progesterone therapy will induce menstrual periods and reduce the risk of uterine cancer, but will not provide contraceptive protection.  For acne or excess hair growth, a water pill (diuretic) called spironolactone (Aldactone) may be prescribed to help reverse these problems. The use of spironolactone requires occasional monitoring of blood tests because of its potential effect on the blood potassium levels and kidney function.  Eflornithine (Vaniqa) is a cream medication that can be used to slow facial hair growth in women. Electrolysis and over-the-counter depilatory creams are other options for controlling excess hair growth.  For women who desire pregnancy, a medication called clomiphene (Clomid) can be used to induce ovulation (cause egg production). In addition, weight loss can normalize menstrual cycles and often increases the possibility of pregnancy in women with PCOS. Other, more aggressive, treatments for infertility (including injection of gonadotropin hormones and assisted reproductive technologies) may also be required in women who desire pregnancy and do not become pregnant on Clomid therapy.  Metformin(Glucophage) is a medication used to treat type 2 diabetes. This drug affects the action of insulin and is useful in reducing a number of the symptoms and complications of PCOS. Metformin has been shown to be useful in the management of irregular periods, ovulation induction, weight loss, prevention of type 2diabetes, and prevention of gestational diabetes mellitus in women with PCOS.  Obesity that occurs with PCOS needs to be treated because it can cause numerous additional medical problems. The management of obesity in PCOS is similar to the management of obesity in general. Weight loss can help reduce or prevent many of the complications associated with PCOS, including type 2diabetes and heart disease. Consultation with a dietician on a frequent basis is helpful until just the right individualized program is established for each woman.  Finally, a surgical procedure known as ovarian drilling can help induce ovulation in some women who have not responded to other treatments for PCOS. In this procedure a small portion of ovarian tissue is destroyed by an electric current delivered through a needle inserted into the ovary. R S. Publication, [email protected]

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Complementary Therapy In Polycystic Ovary Syndrome [18]  Several studies confirmed that acupuncture, physical activity and (to a lesser extent) resveratrol (a natural polyphenol which can balances lipid profile, decreases adiposity and improves insulin sensitivity). may improve metabolic, hormonal and psychological profile of PCOS in women. Vitamin D - a potential contributor in endocrine diseases like PCOD [19]  Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships exist between not only blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also between 25-hydroxyvitamin D and risk of type 1 diabetes, type 2diabetes and polycystic ovary syndrome. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of type 2diabetes, but the available evidence is preliminary and not consistent. Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Randomized controlled trials are expected to provide insight into the efficacy and safety of vitamin D in the management of endocrine disease. KEY POINTS [20] Polycystic ovarian syndrome (PCOS) is a disorder of androgen excess and ovarian dysfunction. Young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function. [21] PCOS may represent the largest underappreciated segment of the female population at risk of cardiovascular disease. Treatment of the associated cardiovascular risk factors, including insulin resistance, hypertension, and dyslipidemia, should be incorporated. [22] Women with PCOS are at an increased risk for abnormal depression scores independent of BMI so we need to recommend routine screening in this population. [23, 24] High prevalence of mental disorders was observed, especially major depression and bipolar disorder.[25] There is an observed link between PCOS and bipolar screen-positivity and that is consistent with a possible shared hypothalamic-pituitary-gonadal axis abnormality.[26] Abdominal obesity may be co-responsible for the development of hyperandrogenism and associated chronic anovulation, through mechanisms primarily involving the insulin-mediated overstimulation of ovarian steroidogenesis and decreased sex hormoneR S. Publication, [email protected]

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binding globulin blood concentrations. By these mechanisms, obesity may also favour resistance to clomiphene and gonadotrophin-induced ovulation and reduce outcomes of IVF/ICSI procedures.

[27,

28,

29,

30]

Lifestyle

intervention

improves

body

composition,

hyperandrogenism (high male hormones and clinical effects) and insulin resistance in women with PCOS. [31]

CONCLUSION Accurate diagnosis and management of PCOS is essential and has many potential metabolic and cardiovascular risks if not managed appropriately. The underlying pathophysiology of PCOS is not fully understood. As a result, treatment is often focused on individual symptoms, not the syndrome. Treatment should be individualized; it should also focus on all metabolic consequences and decreasing future complications. Normal exercise, healthy food, and weight control are the key treatments for PCOS. Treatment can reduce disagreeable symptoms and help prevent long-term health problems. Guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. More widespread research and understanding of the pathophysiology of PCOS will improve treatment pattern and overall management of patients.

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