Polycystic ovary syndrome (PCOS) is a spectrum of symptoms due to elevated male hormones (androgens) in women. Signs and symptoms of PCOS include no menstruation or irregular menstruation and if regular is quite heavy, male pattern hair distribution on the chest, face and legs, pelvic pain, severe acne, infertility and acanthosis nigricans [ thickening and velvety appearance of skin folds. Associated symptoms include metabolic syndrome, cardiovascular diseases, hypertention, endometrial carcinoma after a while.

There have been disparities between authorities for the diagnostic criteria for polycystic ovarian syndrome, but the Rotterdam consensus of 2003 came up with the universal criteria for defining and diagnosing PCOS.

PCOS treatment is usually symptomatic.  Treatment usually involves lifestyle changes such as weight loss and exercise. Oral contraceptive pils may help with improving the regularity of periods, excess hair growth, and acne. Biguanides (metformin) and anti-androgens  can also be imployed. Other typical acne treatments and cosmetic hair removal techniques may be used. Improvement in fertility status may involve weight loss, clomiphene citrate, or metformin. In vitro fertilization is used by some as a last resort in fertility managemnent.

PCOS is the most common endocrine disorder among women between the ages of 18 and 44. It affects approximately 2% to 20% of this age group depending on how it is defined. It is one of the leading causes of female infertility. [1]


EPIDEMIOLOGY

Polycystic ovarian syndrome (PCOS) affects about 6–10% of women worldwide according to the 1990 NIH criteria7–11 and even more individuals according to the broader Rotterdam criteria. This makes it one of the most common human disorders and also the single most common endocrinopathy in women of reproductive age. Several types of women have an increased risk of PCOS, including those with clinical hyperandrogenism (namely, hirsutism, acne or alopecia), menstrual dysfunction, PCO, hyperinsulinemia from adiposity-dependent insulin resistance and a family history of PCOS.
 

PATHOPHYSIOLOGY

Although the real etiology of PCOS is not yet well defined, impaired functioning of the hypothalamo-pituitary-ovarian axis has been implicated.

The syndrome acquired its name due to the common sign on ultrasound examination of multiple ovarian cysts which represent immature follicles. The follicles have developed from primordial follicles but the development has stopped at an early antral stage due to the disturbed ovarian function. The follicles may be oriented along the ovarian periphery appearing as a ‘string of pearls’ on ultrasound examination. [2]

 Patients with PCOS have higher gonadotrophin releasing hormone (GnRH), which in turn results in an increase in LH/FSH ratio in females with PCOS. LH over FSH dominance, increased ovarian androgen production, decreased follicular maturation and decreased SHBG binding. All these factors contribute to the development of PCOS.The majority of patients with PCOS have insulin resistance and/or obesity. Study has shown that elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. Hyperinsulinemia increases GnRH pulse frequency.

There is some evidence that PCOS has some genetic links as to who can get it. Such evidence includes the familial clustering of cases, greater concordance in monozygotic compared with dizygotic twins and heritability of endocrine and metabolic features of PCOS. [3]

The genetic component appears to be inherited in an autosomal dominant fashion with high genetic penetrance but variable expressivity in females meaning that each child has a 50% chance of inheriting the predisposing genetic variant(s) from a parent, and, if a daughter receives the variant(s), the daughter will have the disease to some extent. The genetic variant(s) can be inherited from either the mother or the father, and can be passed along to both sons (who may be asymptomatic carriers or may have symptoms such as early male patern hair loss and/or excessive hair) and daughters, who will show signs of PCOS. The phenotype appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle theca cells from women with the allele.The exact gene affected has not yet been identified. [4]

Adipose tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese patients causes them to have both excess androgens (which are responsible for hirsutism and virilization) and estrogens (which inhibit FSH via negative feedback).

 Adipose tissue dysfunction has been implicated as a contributor to the insulin resistance observed in PCOS

The severity of PCOS symptoms appears to be largely determined by factors such as body weight.

PCOS has some aspects of a metabolic disorder, since its symptoms are partly reversible. Even though PCOS is considered as a gynecological problem, PCOS consists of 28 known clinical symptoms. [5]

Some symptoms of PCOS will persist even if both ovaries are removed meaning that ovarian cysts are part of the symptoms of PCOS rather than a cause; the disease can appear even if cysts are absent according to the Rotterdam criteria.. Gynecologists often see it as a gynecological problem, with the ovaries being the primary organ affected. However, recent insights show a multisystem disorder, with the primary problem lying in hormonal dysregulation in the hypothalamus, with the involvement of many organs thus the name PCOS is used when there is ultrasonographic evidence of multiple ovarian cysts. In PCOS cysts in the ovaries are seen only in 15% of people.

Environmental factors have been implicated in PCOS (especially industrial endocrine disruptors such as exposure to bisphenol A and certain drugs) and the increasing rates of obesity in the population. [6]

Advantages of the syndrome in ancient times, including smaller family sizes, reduced exposure to childbirth-related mortality, increased muscle mass and greater capacity to store energy. The diagnosis of PCOS hinges on establishing key features while ruling out other hyperandrogenic or oligo-ovulatory disorders. [7]


SIGNS AND SYMPTOMS

The most common symptoms of Polycystic ovarian syndrome include:

1.     Menstrual disorders such as oligomenorrhea or amenorrhea,

2.     Infertility, high levels of

3.     Masculinizing :manifested by acne and hirsutism

4.     Metabolic syndrome which appears as a tendency towards central obesity and other symptoms           associated with insulin resistance.

5.     Acanthosis nigricans  from increased serum insulin, insulin resistance also homocysteine levels are higher in females with PCOS than in the normal females. [8]


DIAGNOSIS

Not all women with PCOS have polycystic ovaries, nor do all women with ovarian cysts have PCOS. Although pelvic ultrasound is a major diagnostic tool, it is not the only one. Many definitions are used for diagnosis of PCOS such as National Institutes of Health (NIH) criteria, Rotterdam criteria and Androgen Excess PCOS Society criteria.

NIH criteria: In 1990, a workshop sponsored by the NIH suggested that a patient has PCOS if she has oligo-ovulation, signs of androgen excess (clinical or biochemical) and other entities are excluded that would cause polycystic ovaries.

 Rotterdam criteria: In 2003, a consensus workshop held in Rotterdam indicated PCOS to be present if any 2 out of 3 criteria are met including oligo-ovulation and/or anovulation, excess androgen activity clically and biochemically and polycystic ovaries >12 follicles ranging from 2-9mm and/or increased ovarian volume >10millilitres (By gynecologic ultrasound).

The Rotterdam definition is wider, including many more patients, most notably patients without androgen excess. Critics say that findings obtained from the study of patients with androgen excess cannot necessarily be extrapolated to patients without androgen excess.

Androgen excess PCOS Society criteria: In 2006, the Androgen Excess PCOS Society suggested a tightening of the diagnostic criteria to all of the following including excess androgen activity, oligoovulation/ anovulation, polycystic ovaries and other entities are excluded that would cause excess androgen activity. [9]

 

MANAGEMENT OF POLYCYSTIC OVARIAN SYNDROME

Management of PCOS is usually symptomatic.

1.     General interventions that help to reduce weight or insulin resistance can be beneficial for all these aims because they are believed to be the underlying causes.

2.     Biguanides ( metformin) or thiazolidinediones (troglitazone)can be used to assist in increasing insulin responsiveness.

3.     Clomiphene citrate can be used to stimulate ovulation

4.     Ovarian drilling can be used in ovaries resistant to clomiphene to further stimulate the ovaries.

5.     Spironolactone can be used to treat the hirsutism because it inhibits 5alpha-reductase in the hair follicle.

6.     Progesterone can used to stabilize the endometrium against the effects of estrogen. [10]


Alternative medicine

Acupuncture is one of the alternative medicine modalities that had been emerging as one of the commonly used methods for treatment of PCOS. Acupuncture may help PCOS patients to regulate and manage their periods. Moreover, it may help in decreasing body weight, reducing headache and improving patients’ mood. Also, placing acupuncture needles in the areas related to the reproductive system may improve blood supply to the reproductive area, normalize hormone levels and help the proper functioning of the reproductive system.

There is insufficient evidence to conclude an effect from D-chiro- inositol in PCOS. However, myo-inosiol appears to be effective. It is capable of restoring spontaneous ovarian activity and consequently fertility in most patients with PCOS.

SUMMARY

In summary, polycystic ovarian syndrome is a condition that arises as a result of dysfunction of the hypothalamo-pitutary-ovarian axis, leading to increased luitenizing hormone levels relative to follicle stimulating hormone, this in turn leads to increased testosterone and estrogen for peripheral fat, giving rise to symptoms of masculinization and irregular menstrual periods. It usually presents with infertility and obesity. Treatment is usually symptomatic and weight reduction is a major part of the management.


REFERRENCES

1.       Ehrmann David A (2005). "Polycystic Ovary Syndrome". N Engl J Med. 352: 1223–1236. doi:10.1056/NEJMra041536.

2.    Dunaif A, Fauser BC (2013). "Renaming PCOS--a two-state solution". J. Clin. Endocrinol. Metab. 98 (11): 4325–8. doi:10.1210/jc.2013-2040. PMC 3816269 . PMID 24009134.

3.   Palioura E, Diamanti-Kandarakis E (2013). "Industrial endocrine disruptors and polycystic ovary syndrome". J. Endocrinol. Invest. 36 (11): 1105–11. doi:10.1007/bf03346762. PMID 24445124.

4.   Hoeger KM (2014). "Developmental origins and future fate in PCOS". Semin. Reprod. Med. 32 (3): 157–158. doi:10.1055/s-0034-1371086. PMID 24715509

5.   Rutkowska A, RachoÅ„ D (2014). "Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS)". Gynecol. Endocrinol. 30 (4): 260–5. doi:10.3109/09513590.2013.871517. PMID 24397396.

6.    Lewandowski KC, Cajdler-Łuba A, Salata I, BieÅ„kiewicz M, LewiÅ„ski A (2011). "The utility of the gonadotrophin releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS)". Endokrynol Pol. 62 (2): 120–8. PMID 21528473.

7.    Munir, Iqbal; Yen, Hui-Wen; Geller, David H.; Torbati, Donna; Bierden, Rebecca M.; Weitsman, Stacy R.; Agarwal, Sanjay K.; Magoffin, Denis A. (January 2004). "Insulin Augmentation of 17α-Hydroxylase Activity Is Mediated by Phosphatidyl Inositol 3-Kinase But Not Extracellular Signal-Regulated Kinase-1/2 in Human Ovarian Theca Cells". Endocrinology. 145 (1): 175–183. doi:10.1210/en.2003-0329.

8.    Diamanti-Kandarakis, Evanthia; Dunaif, Andrea (December 2012). "Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications". Endocrine Reviews. 33 (6): 981–1030. doi:10.1210/er.2011-1034. PMID 23065822.

9.    Kumar Cotran Robbins: Basic Pathology 6th ed. / Saunders 1996

10.   Sathyapalan T, Atkin SL (2010). "Mediators of inflammation in polycystic ovary syndrome in relation to adiposity". Mediators Inflamm. 2010: 1–5. doi:10.1155/2010/758656. PMC 2852606 . PMID 20396393.