Marz Akyas Khusyatur Rehm (Polycystic Ovary Syndrome): An Overview

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1 International Journal of Advances in Health Sciences (IJHS) ISSN Vol 3, Issue 2, 2016, pp Research Article Marz Akyas Khusyatur Rehm (Polycystic Ovary Syndrome): An Overview Ayesha Fatema Syed* and Jaleel Ahmed** *Associate professor in Dept of Moalijat; ** Associate professor in Dept of Kulliyat ZVM unani medical college Pune. Id: [Received-10/06/2016, Accepted-20/06/2016, Published- 27/06/2016] ABSTRACT: The MARZ AKYAS KHUSYATUR REHM (polycystic ovary syndrome) (PCOS)is a common with an incidence varying from 5% to 10% and 9.13%. inindian population.it is a multispeciality disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism,often associated with psychological impairments, including depression and other mood disorders and metabolic derangements, chiefly insulin resistance and compensatory hyperinsulinemia, which is recognized as a major factor responsible for altered androgen production and metabolism.in Unani system of Medicine PCOS is mentioned under the headings of Amenorrhea, Obesity and other phlegmatic disorders. This disease is common in Balghami mizaj patients of reproductive age.on the basis of consistency one type is Balgham Mayi which is responsible for causing the Marz AkyasKhusyaturRehm (Polycystic Ovarian Syndrome). So it can be concluded that PCOS arise due to predominance of Balgham in the body which leads to the cyst formation in the ovaries, amenorrhea and obesity. Hirsutism has been mentioned as a complication of ehtebas tams associated with virilism, and other masculine features, like hoarseness of voice, male body contour, acne and clitoromegaly due to sue mizaj barid. Clinically, PCOS is made up of three characteristics: hyperandrogenic state, anovulation and insulin resistance.we can prevent or limit the complications from which PCOS patients suffer, such as cardiovascular disease, diabetes mellitus, and increased risk for unopposed estrogen, with using unani formulation having properties of antispasmodic and analgesic,emmenogogue (Mudir-e-haiz), diuretics (Mudir-e-boul), vasodialator (Mufatehsudad), specific drugs for liver to correct Ehtebase tams (amenorrhea) caused by liver disorders and Munzig Balgham and mushile balgham advia in single and compound form, along with ilajbittadbeerwatytaghziya. KEY WORDS: POLYCYSTIC OVARY SYNDROME, BALGHAMI MIZAJ, BALGHAM MAYI, EHTEBASE TAMS, ILAJBITTADBEER WATYTAGHZIYA, MUDIR-E-HAIZ INTRODUCTION: The MARZ AKYAS KHUSYATUR REHM (polycystic ovary syndrome) (PCOS) is a hyperandrogenic disorder associated with chronic oligo-anovulation and polycystic ovarian morphology1. It is often associated with psychological impairments, including depression and other mood disorders and metabolic derangements, chiefly insulin resistance and compensatory hyperinsulinemia, which is recognized as a major factor responsible for altered androgen production and metabolism 2. Most women with PCOS are also overweight or obese, further enhancing androgen secretion while impairing

2 metabolism and reproductive functions and possibly favoring the development of the PCOS phenotype. The definition of PCOS has led to an impressive increase of scientific interest in this disorder, which should be further directed to improve individualized clinical approaches and, consequently therapeutic strategies. 1 In 1935, Stein and Leventhal reported a series of 7 women who presented with oligo/amenorrhoea, hirsutism, obesity, infertility, and bilateral polycystic ovaries (Stein-Leventhal syndrome) 3, 4. To further dialogue and exchange ideas on PCOS an international group of PCOSresearchers, has gathered every other year to summarize the state of the field and stimulate further research.1, 5 Polycystic ovarian syndrome (PCOS) is a multispeciality disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosisnigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. 3 Bilateral wedge resection of the enlarged ovaries was therapeutic in normalizing the menses and fertility of the women studied. researchers concluded that there was a primary ovarian defect, and the disorder was known as polycystic ovarian disease (PCOD). Today, PCOD has been associated with various metabolic disorders, and is now known as polycystic ovarian syndrome (PCOS) 3. PCOS is a common disorder with an incidence varying from 5% to 10%. 6, 7, 8, 9. It is observed in women of child-bearing age across all cultures, and ethnicities 10. A prospective study of Indian adolescents reported an incidence of 9.13%. 11 PATHOPHYSIOLOGY The endocrinologic abnormality of PCOS begins soon after menarche. Chronically elevated luteinizing hormone (LH) and insulin resistance are 2 of the most common endocrine aberrations seen in PCOS. The genetic cause of high LH is not known. It is interesting to note that neither an elevation in LH nor insulin resistance alone is enough to explain the pathogenesis of PCOS. 12, 13 In vitro and in vivo evidence offers support that high LH and hyperinsulinemia work synergistically, causing ovarian growth, androgen production, and ovarian cyst formation. 13 Obesity, which is seen in 50% to 65% of PCOS patients, may increase the insulin resistance and hyperinsulinemia. One important caution is that the correlation between hyperandrogenism and insulin resistance has been recognized in both obese and nonobese anovulatory women. Thus, it is important to realize that a nonobese patient may also have insulin resistance. However, the insulin levels in obese women are higher than their nonobese counterparts. Clinically, though, both groups will have evidence of hyperandrogenism and oligo-ovulation or anovulation. 14 Insulin resistance can be characterized as impaired action of insulin in the uptake and metabolism of glucose. Impaired insulin action leads to elevated insulin levels, which causes a decrease in the synthesis of 2 important binding proteins: insulin-like growth factor binding protein (IGFBP-I) and sex hormone binding globulin (SHBG). IGFBP-I binds to IGFBP-II and SHBG binds to sex steroids, especially androgens. The triad of hyperandrogenism, insulin resistance, and acanthosisnigricans (HAIR-AN) syndrome appears in a subgroup of patients with PCOS. 15, 16 Women who are hyperandrogenic and hyperinsulinemic are at increased risk for dyslipidemia, coronary artery disease, hypertension, and diabetesmellitus. 13 The most common lipid abnormalities found in obese PCOS patients are decreased highdensity lipoprotein and elevated triglycerides. In addition to the lipid abnormalities seen in women with PCOS, these patientsare 7 times more likely to have a myocardialinfarction. 17 Because cardiovascular disease is the leading cause of death of among women, prevention is essential. Women with PCOS are at higher risk of developing diabetes mellitus type 2 because of Ayesha Fatema Syed, et al. 120

3 the relative insulin resistance. Also, these women tend to develop diabetes earlier in life, around the third or fourth decade. It is generally recommended, because of the known long-term complications of diabetes, that these young women be tested early in life and followed closely. These women should be screened in early pregnancy, as they have an increased risk of developing gestational diabetes. 18 ETIOPATHOGENESIS Mahiyatul marz in Unani: In Unani system of Medicine MARZ AKYAS KHUSYATUR REHM (Polycystic Ovarian Syndrome) is mentioned under the headings of Amenorrhea, Obesity and other phlegmatic disorders. ZakariaRazi ( AD) described that women with PCOS can present with the clinical features of amenorrhea, hoarseness of 19, 20 voice and hirsutism. Unani physicians attributed Marz AkyasKhusyaturRehm (Polycystic Ovarian Syndrome) to dominance of Balgham (phelgm). Ibn-e-Rushed described that Marz AkyasKhusyaturRehm is a disease of cold and moist nature and arises due to change in quantity and quality of balgham. Buqrat (Hippocrates), Ibn-e- HabalBagdadi, Ali Ibn-e- Abas Majoosi, Rabban Tabri attributed PCOS due to pathology in liver (Sue Mizaj Kabid) liver dysfunction which may lead to abnormal 20, 21, 22, production of Balgham (phelgm) 23 Abnormal form of Balgham is divided on the basis of consistency and taste. On the basis of consistency one type is Balgham Mayi which is responsible for causing the Marz AkyasKhusyaturRehm (Polycystic Ovarian Syndrome). So it can be concluded that PCOS arise due to predominance of Balgham in the body which leads to the cyst formation in the ovaries, amenorrhea and obesity. 20 In one trial its revealed that this disease is common in Balghami mizaj patients of reproductive age. 20 In authentic Unani books hirsutism has been mentioned as a complication of ehtebas tams associated with virilism, and other masculine features, like hoarseness of voice, male body contour, acne and clitoromegaly due to sue mizaj barid. 20, 24 Hippocrates (Buqrat BC) first documented the affiliation of excess facial and body hair (hirsutism) in females with prolongedamenorrhoea, obesity and infertility and Similar observations were reported by Galen (Jalinoos AD). 19 It was said that persistence of amenorrhoea for a longduration causes alterations in internal environment of female body and status of equilibrium is disturbed, leading to formation of some unwanted material which is being excreted through skin pores and participate in the formation of thick hair over the body. 24 It was observed by these physicians that development of masculine features are more common in obese females with robust body and broad prominent blood vessels, because obese women have almost similar temperament as 19,21,24,25,26, 27 males. Mahiyatul marz in modern medicine:although the exact etiology is unknown, PCOS is a multi-factorial disease with a strong genetic influence. It has been evaluated after research that intra-uterine fetal exposure to androgen excess is associated with development of PCOS in later life. 28 PCOS is likely due to a steady state of high estrogen, androgens, luteinizing hormone (LH) and insulin levels, High estrogen levels can cause suppression of pituitary FSH and relative increase in LH, Increased LH stimulates the ovary, which results in anovulation, multiple cysts and theca cell hyperplasia with excess androgen output and High insulin levels may also increase the production of testosterone by 29, 30, 31,32,33,34 the ovaries. Mechanism of Follicle Arrest:The finding that granulosa cells from anovulatory polycystic ovaries responded well to FSH in culture directed initial investigations into follicular arrest towards discovery of raised levels of a locally produced inhibitor. It is difficult to deduce cause and effect, however if the factor is causing follicular arrest, or did the follicular arrest elicit the production of the inhibitor. Androgens are an obvious candidate, but production is raised in theca from ovulatory PCO also. Insulin causes premature acquisition Ayesha Fatema Syed, et al. 121

4 of LH receptors possibly leading to early follicular luteinisation, but the insulin signalling defect in the polycystic ovary remains to be clarified. More comprehensive investigation of insulin/glucose interactions in these cells has been undertaken utilising a metabolomics approach. AntiMullerian Hormone (AMH) is raised in women with PCOS and granulosa cell production is considerably higher in anovulatory than ovulatory women with PCOS. AMH s suppressive effects on folliculogenesis may make this the sought-after local inhibitor. Recent data indicated that it is those women in whom AMH levels fall who have the best response to methods to induce ovulation. Interestingly, the incubation of cells with metformin inhibited AMH production suggesting that this may be one mechanism of 1, 35 the action of this drug in PCOS. SYMPTOMS Clinically, PCOS is made up of three characteristics: hyperandrogenic state, anovulation and insulin resistance. The accompanying insulin resistance and hyperinsulinemia mark PCOS as a prediabetic state, with high incidence of impaired glucose tolerance, gestational diabetes, and overt diabetes. In patients with PCOS, other metabolic and biochemical changes, such as hypertension and dyslipidemia, increase the risk of cardiovascular disease. 36 In addition to the three features used to diagnose PCOS (absence of ovulation, high levels of androgens, and 37, 38 ovarian cysts). PCOS has many signs and symptoms, some of 30, 39 which may not seem to be related. Following are list of symptoms: Menstrual irregularities: o No menstrual periods called amenorrhea o Frequently missed periods called oligomenorrhea o Very heavy periods o Bleeding but no ovulation called anovulatory periods Infertility Excess hair growth on the face, chest, belly, or upper thighs a condition called hirsutism. Hirsutism can be graded using the Ferriman-Gallowey scoring system. This scoring system evaluates 9 key anatomic sites. These sites can be graded from 0 (no terminal hair growth) to 4 (maximal growth). The maximum score is 36. A score of 8 or greater suggests an 40, 41 androgen excess. Severe, late-onset, or persistent acne that does not respond well to usual treatments Obesity, weight gain, or trouble losing weight, especially around the waist Pelvic pain Oily skin Patches of thickened, dark, velvety skin a condition called acanthosisnigricans. Because many women don't consider problems such as oily skin, extra hair growth, or acne to be symptoms of a serious health condition, they may not mention these things to their health care providers. As a result, many women aren't diagnosed with PCOS until they have trouble getting pregnant or if they have abnormal periods or missed periods. Although PCOS is a leading cause of infertility, many women with PCOS can and do get pregnant. Pregnant women who have PCOS, however, are at higher risk for certain problems, such as miscarriage. 30, 39 Dokras et al. did a meta-analysis and systematic review of studies comparing anxiety symptoms in women with PCOS compared to normal, and concluded that all women with PCOS should be screened for anxiety symptoms. 42 DIAGNOSIS: APPROACH TO A PATIENT WITH PCOS:Suspect PCOS in women (obese/lean) with/without a history of irregular periods with one or more of the following complaints, namely, acne, hirsutism, alopecia, acanthosisnigricans and metabolic syndrome. Investigations both, hematological and imaging are geared to rule out other hyperandrogenic states as there is no single investigation to diagnose PCOS. Patients must be counseled about the long duration of treatment which Ayesha Fatema Syed, et al. 122

5 includes life-style modifications along with the systemic treatment. 3 History: A diagnosis of PCOS may often be made with a complete history. Pay particular attention to the onset of menstrual irregularities, as this will usually date back to menarche. Inquire about recent pregnancy status and other reproductive history such as miscarriages. In addition to obtaining a thorough medical and surgical history, elicit a completed menstrual history, including menarche and family history of PCOS. A history of hirsutism, acne, alopecia, menstrual irregularities, or infertility, especially in the patient's mother, is very important. 13 Medical history. A history of headaches or blurred vision (indicating pituitary tumor), any signs or symptoms of thyroid dysfunction (as a differential diagnosis of amenorrhea), or clinical signs of diabetes (indicating adrenal tumor) need to be elicited. Inquire about a history of acne, hirsutism, deepening of the voice, and increase in muscle mass (without exercise). If these symptoms have occurred, what has been tried to control them? It is imperative to know if the symptoms are recent or have occurred rapidly, either of which could indicate a virilizing syndrome or neoplasia. A rapid onset of these symptoms is rare in a PCOS patient, but if present, they suggest a need for an urgent work-up, as an ovarian tumor or adrenal tumor needs to be ruled out. Also, masculinization is uncommon with PCOS patients and is more suggestive of congenital adrenal hyperplasia 13. Family history. PCOS tends to run in families; it is important to ask about family history. Some believe that if a mother has PCOS and her daughter is showing signs of it, she should be evaluated by her pediatrician or by an endocrinologist. 43 Medications. In addition to asking about the patient's current medications it is important to remember that there are certain medications and classes of medications that can cause transient hirsutism. Examples of these are phenytoin (Dilantin),diazoxide, 13, 41, 44 glucocorticoids, and the phenothiazines. Physical examination: Central obesity with a hip ratio of > 0.85 is associated with cardiovascular disease and is a marker for PCOS. A "buffalo hump" on the back or purple striae on the abdomen might suggest Cushing's syndrome. During the pelvic examination, assess for clitoromegaly and pelvic masses. Bilateral pelvic masses would be more consistent with PCOS whereas a unilateral pelvic mass may be more consistent with a neoplasia. Remember, too, that the pelvic exam may not reveal any masses in a patient with PCOS. 13 Since 1990, various bodies have laid down criteria for the diagnosis of PCOS, based on oligo or anovulation, signs of hyperandrogenism, and ovarian sonography. 3, 30, 31 Table 1: Various diagnostic criteria defined for PCOS CRITERIA NIH 1990 ROTTERDAM 2003 ANDROGEN EXCESS SOCIETY 2006 Must include Two of following three Must include Diagnostic criteria Chronic anovulation Clinical and/or biochemical signs of hyperandrogenism 1. Oligo / anovulation 2. Clinical and/or biochemical signs of hyperandrogenism 3. Polycystic ovaries on USG 1.Ovarian dysfunction Oligo/anovulation Polycystic ovaries on USG 2. Androgen Excess Hirsutism hyperandrogenemia Ayesha Fatema Syed, et al. 123

6 Table 2: Important investigations to be done in suspect cases of PCOS 3 Name of Investigation Lipid profile Blood sugar (fasting) Blood sugar (post 75 gm glucose) Insulin (fasting) >12 miu/ml Insulin (Post 75 gm glucose) TSH FSH/LH ratio Total testosterone Significance May be deranged in metabolic syndrome May be deranged in metabolic syndrome May be deranged in metabolic syndrome suggestive of insulin resistance >25 miu/ml suggestive of insulin Resistance Hypothyroidism may cause oligo/ Amenorrhoea Normally FSH > 3 4 LH Reversal of ratio significant >3.6 ng/ml significant Androstenedione Elevated in ovarian pathology Prolactin May be raised in PCOS but very high levels indicate a pituitary tumor 17 hydroxy progesterone Elevated in late onset CAH DHEAS DHT Ultrasonography of pelvis Endometrial Aspiration Many PCOS patients have unopposed estrogen stimulation for prolonged periods of time and are thus at risk for endometrial hyperplasia or endometrial carcinoma. Any PCOS patient with prolonged oligomenorrhea or amenorrhea or a patient with PCOS who is older than aged 35 years and has irregular bleeding should have endometrial aspiration to rule out endometrial carcinoma. An important point to remember is that advancing age is not a factor in deciding to obtain endometrial aspiration in patients with PCOS as it is in non-pcos patients. 13,30,31 Radiologic Studies An enlarged uterus or enlarged ovaries palpated on pelvic examination suggests a need for a pelvic ultrasound to distinguish uterine fibroids from an adnexal mass. If a patient has elevated DHEAS, adrenal imaging is indicated. An important caveat to remember is that polycystic ovaries can been seen in a number of healthy women who do not have PCOS, and women with PCOS do not always have Elevated in adrenal pathology Indicative of peripheral conversion of Testosterone Volume of atleast 1 ovary more than 10 cc with string of pearl appearance radiographically demonstrated polycystic ovaries. Remember, by ultrasound, 25% of "normal" ovulating women would have polycystic-appearing ovaries. 13,45 A transvaginal ultrasound should be done, as 90% of virilizingtumors can be identified with this method. Polycystic ovaries are also better evaluated transvaginally than transabdominally. 13 Ovaries will have a typical appearance of enlarged subcapsular small follicles (> 10 mm) -- follicles are normally 2 mm to 10 mm in diameter. The ovarian volume in women with PCOS is > 10 cm 3 and the normal range is cm DIFFERENTIAL DIAGNOSIS Premature ovarian failure, rapid weight loss, extreme physical exertion, low body mass index (BMI) as in anorexia nervosa, and pregnancy will cause abnormal menstrual cycles. Discontinuation of oral contraceptives may also cause amenorrhea 13. The latter is called post-pill amenorrhea. A pituitary Ayesha Fatema Syed, et al. 124

7 adenoma, hyperthyroidism, or hypothyroidism will also cause a change in the menstrual cycle. Other important etiologies to consider include congenital adrenal hyperplasia, late-onset adrenal hyperplasia, and Cushing's syndrome. Tumors of the adrenal gland or the ovaries may also present with menstrual irregularities. 13,46 MANAGEMENT: In Unani medicines: 1). Ilaj bit-tadbeerwat-taghziya (Lifestyle Modifications): The American College of Obstetricians and Gynecologists (ACOG) and the Society of Obstetricians and Gynaecologists of Canada (SOGC) indicate that lifestyle modifications such as weight loss and increased exercise in conjunction with a change in diet consistently reduce the risk of diabetes. This approach has been found to be comparable to or better than treatment with medication and should therefore be considered first-line treatment in managing women with polycystic ovarian syndrome (PCOS). 47,48 These modifications have been effective in restoring ovulatory cycles and achieving pregnancy in obese women with PCOS. Weight loss in obese women with PCOS also improves hyperandrogenic features. 2). Ilajbid-dawa:To inducemenstruation and resolve the ovarian cyst following line of treatment can be used, due to its medicinal properties, in accordance to ibnebeetar and najmul ghani. 49,50 antispasmodic and analgesic : Suddab and Baranjasif, Afsanteen emmenogogue (Mudir-e-haiz): Abhal, Persishoyan diuretics (Mudir-e-boul) : tukhmekasnitukhmekhayarain vasodialator (Mufatehsudad): Kasni specific drugs for liver to correct Ehtebase tams (amenorrhea) caused by liver disorders: like Afsanteen, Darchini and Barinjasif Munzig Balgham and mushile balgham advia: Emmenogogue (Mudir-e-haiz), :Rhazes recommended regular induction of menstruation as one of treatment modality applied for hirsutism. He has also given a line of management for hirsutism based on correction of temperament and menstrual irregularity by use of emmenagogue single herbs or compound formulations and local application of herbs to reduce severity of hair growth. 26 Mufradat: the herbs named Pudina, Daarchini, Neem, Kalonji, Saunf, Soy, Nut grass and Saw Palmetto may be beneficial in hirsutism due to polycystic ovarian syndrome. And may modulate the underlying endocrine and metabolic disturbances responsible for hirsutism directly or indirectly by antiandrogenic, estrogenic, hypolipidaemic, hypoglycemic and insulin sensitizing properties, but the evidences are weak. 51 Several single drugs and compound formulations for hirsutism were reported by ancientunani physicians for oral as well as topical use. These include oral use of Pudina (MenthaspicataLabiatae), Daarchini (Cinnamomumzeylanicum), Manjeeth (Rubiacordifolia Linn.), Neem (Azadirachtaindica), Kalonji (Nigella sativa Linn.), Afsanteen (Artemisia absinthium Linn.), Saunf (Foeniculumvulgare), Tukhmgazar (seeds of Daucuscarota Linn.), Anisoon(Pimpinellaanisum Linn.), Suddab (Rutagraveolens Linn), Zarawand (Aristolochia Rotunda), Irsaa (Iris ensata), Izkhar (Cymbopogonjwarancusa), Mur (Commiphoramyrrha), Baalchhar (Nardostachysjatamansi) and for local application Soyaa (Anethumsowa), Honey, Bargbhang (leaves of Cannabis sativa Linn.), Tukhmutangan (seeds of Blepharisedulis), Shookaran (Conium maculatum Linn.) etc 19,25,26,27,52 Murakkabat: Formulation 1: Unani formulation containing Barg-e-sudab (Rutagraveolans ), Abhal(Junipers communis), Parshiaushiaya (Adiatumcapillus), Afsanteen (Artemisia Ayesha Fatema Syed, et al. 125

8 abseinthium), Darchini (Cinnamomumzeyanicum), Brinjasif (Artemisiavulgaris), Methidana (Trrigonellafoenium), Charaita (Sweritacharasta) in the form of powder orally along with Arq-e-Kasni 25 ml twice daily after meal for three months. 53 Formulation 2: Tukhmekasni, tukhmekhayarain, parsiyawashan,mulaithimuqashar, gaozaban each 5gm and unnab 5 units. Make nuqu and consume after mixing and sieving it with 40 gmkhameerabanafsha. 54 Formulation 3 Dawa-ul-Qust 55 : Dar cheeni (Cinnamomumzelaynicum) 85 gm, Saleekha (Cinnamomumtamala) 85 gm, Qust (Saussurialappa ) 85 gm, Zafraan (Crocus sativous) 24 gm, Badiyan-e- Roomi (Foeniculumvulgare) 30 gm, Tukhm-e- Karafs (Apiumgraveolans) 30 gm, Tagar (Aquillariaagallocha) 4.5gm, RewandeCheeni (Rheum emodi) 30 gm, ShagoofaeIzkhar (Andropoganschaerranthus) 70 gm, Murmakki (Dendron myrrh) 70 gm In conventional medicine treatment of PCOS is modified according to a definite cause; aims of therapy comprisesamending hyperandrogenic symptoms by usage of anti-androgen drugs, persuading ovulation, regulating menstruation and preventing cardio-metabolic problems. 56 CONCLUSION: PCOS is much more than just oligomenorrhea, amenorrhea, or infertility. 13 PCOS encompasses many long-term health problems such as the development of cardiovascular disease, type2 diabetes mellitus, and prolonged exposure to unopposed estrogen, which can lead to endometrial hyperplasia and endometrial carcinoma. Clinicians need to be aware of the risk factors for PCOS and intervene with a preventive approach, which may restore normal menstrual function, ovulation, and fertility for those desiring it. We can also prevent or limit the complications from which PCOS patients suffer, such as cardiovascular disease, diabetes mellitus, and increased risk for unopposed estrogen, with using unani formulation along with ilajbittadbeerwatytaghziya. REFERENCES 1. Pasquali et al. PCOS Forum: Research in Polycystic Ovary Syndrome Today and Tomorrow. In: ClinEndocrinol (Oxf) April ; 74(4): doi: /j x ( PMC /pdf/nihms pdf on Monday, May 16, 2016) 2. Escobar-Morreale HF, Botella-Carretero JI, Alvarez-Blasco F, et al. The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery. Journal of Clinical Endocrinology & Metabolism. 2005; 90: [PubMed: ] 3. Madnani N, Khan K, Chauhan P, Parmar G. Polycystic ovarian syndrome. Indian J DermatolVenereolLeprol 2013;79: [Downloaded free from on Monday, May 16, 2016, IP: ] 4. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J ObstetGynecol 1935;29: ) 5. Dunaif, ACR.; Franks, S.; Legro, RS., editors. Polycystic Ovary Syndrome: Current Controversies, from the Ovary to the Pancreas. Humana Press; 2008.) 6. Slowey MJ. Polycystic ovary syndrome: new perspective on an old problem. South Med J. 2001;94: Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J ClinEndocrinolMetab 2004;89: Ahles BL. Toward a new approach: primary and preventive care of the woman with polycystic ovarian syndrome. Prim Care Update Ob/Gyns. 2000;7: Mac Pannill. Polycystic Ovary Syndrome: An Overview. Topics in Advanced Practice Nursing ejournal. 2002;2(3) 10. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected Ayesha Fatema Syed, et al. 126

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