POLYCYSTIC OVARY SYNDROME

Introduction

In 1935, Stein and Leventhal reported a series of seven women with bilateral polycystic ovaries and thickened ovarian cortex accompanied by amenorrhoea, hirsutism, and infertility: a constellation of symptoms now known as polycystic ovarian syndrome (PCOS).

Polycystic ovarian syndrome also called as Stein-Leventhal syndrome, is an endocrine and metabolic disorder. It is considered as a genetic trait that can run through generations. It has several severe complications on women's health.

Most of the time PCOS remains undiagnosed unless it is being exhibiting certain symptoms. One of the characteristics of PCOS is hormonal imbalance. It is said to have long term consequences on women's health.

Symptoms of PCOS :

 • Oligomenorrhea or amenorrhea

 • Infertility due to chronic anovulation

 • Acne and Hirsutism due to high level of male hormones

 • Androgenic alopecia

 • metabolic syndrome associated with central   obesity, insulin resistance (IR) and high homocysteine level.

Hormones and Menstrual cycle :

AMH( anti Müllerian hormone) ,Luteinizing hormone(LH), Gonadotropin releasing hormone (GnRH), Progesterone and estrogen are the hormones that play vital role in the physiologic process of the ovaries. The normal physiology includes the transition of the ovarian follicles from primordial to primary, secondary, and  pre ovulatory phase . All these processes are aided by the low level of AMH . To be specific the serum AMH level is inversely related to the size of the follicles in the transition phase. Hence any increase in the serum AMH level is known to disrupt the normal physiology of the ovaries.

Anti-Müllerian hormone (AMH) is an important regulator of folliculogenesis in the ovaries. It is secreted by granulosa cells of the ovarian follicles and its serum levels are elevated 2- to 3- fold in women with PCOS in comparison with normo-ovulatory women, consistent with the increased number of small antral follicles in PCOS. Data suggests that it is not only the increased number of follicles, with resultant increased granulosa cell mass, but also greater production by individual granulosa cells that is underlying AMH overproduction in PCOS. Several studies have demonstrated that AMH is correlated with severity of PCOS manifestations, including oligo/amenorrhoea, hyperandrogenism and polycystic ovarian morphology.  Some researchers have suggested that PCOS can be divided into anovulatory and ovulatory based on the serum AMH concentrations as women with anovulatory PCOS were found to have 18 times higher AMH concentrations than the women with ovulatory PCOS with no overlapping areas. AMH is not only a biomarker of disease but actually contributes to PCOS pathogenesis.

Women with PCOS are observed to have increased concentrations and frequency of secretion of LH and GnRH, which leads to dysfunction in HPO Axis (Hypothalamic-Pituitary-Ovarian Axis).

Lets understand this in the process of folliculogenesis, after first few stages of primordial, primary and secondary, there will be pre ovulatory phase and then ovulation occurs in graffian follicle,after ovulation it gets converted to Corpus luteum which produces progesterone which sends signal for the production of normal GnRH, which stimulates production of LH and FSH in proper ratio. This is the normal process.

But in the women who has PCOS ovulation doesn't take place and inturn there will be no progesterone and there will not be normal GnRH production (increased frequency of GnRH secretion). LH producing cells are more frequently sensitive to GnRH  than FSH producing cells , hence there will more production of LH than FSH. If LH production is increased ,it inturn stimulates androgen synthesis in theca cells of ovaries and so hyperandrogenism is caused.

High levels of LH is also responsible for the  decrease in the feedback sensitivity to progesterone and estradiol (type of estrogen), further reinforcing the LH and GnRH hypersecretion. Elevated serum AMH concentration in PCOS has been shown to be positively associated with androgen levels such as serum testosterone and androstenedione.

Coming to the insulin resistance, Due to the reduced absorption of glucose in gut , there will be reduced glucose assimilation. Liver glucose output is further reduced , thereby reducing ratio of insulin synthesis. This decreases glucose disposal and peripheral glucose utilisation is reduced causing insulin resistance. There are other possibilities like, due to hormonal imbalance in HPO axis insulin sensitivity is reduced (-ve feedback from steroidogenesis)and insulin resistance is seen.

Like ways many of the hypothesis have been said for the easy understanding of the pathogenesis, but still many researches are still going on ,on the same.

Common complications :

1. Pregnancy related

 • misscarriage - because of IR, hyperandrogenemia, and hyperinsulinemia or beacuse of abnormal endometrium,deficient progesterone secretion, elevated LH level and abnormal embryos from atretic oocytes

 • gestational diabetes

 • pre-eclampsia 

 • eclampsia  

2. Infertility - because of high AMH concentrations,weight gain due to IR, hyperandrogenism ,and reduced no.of ovulations that occur in the life span of a women

 • congenital anomalies

✓strictly speaking not every women who has PCOS is infertile

3. Cancer :

 • endometrial cancer- factors such as hypertension, diabetes,nulliparity, infertility and obesity associated with PCOS can cause endometrial cancer and prolonged anovulation results in unopposed secretion of estrogen which increases risk of developing endometrial cancer 

 • ovarian cancer - increased androgens and presence of androgen receptors on the borderline and benign tumors on normal cells of ovary indicate association between androgens and ovarian cancer

 • breast cancer - hyperandrogenism, infertility and obesity with ,PCOS and  family history of breast cancer are also believed to have positive association.

Association of PCOS with psychology :

 The characteristics features and negative consequences of PCOS negatively affect the psychologic health of women with PCOS.

commonly it includes psychologic distress, anxiety, depressive emotions, body dissatisfaction,body image disturbances, eating disorders ( esply bulimia nervosa) and social fears .

Borderline personality disorders : 

Both PCOS and BPDs result in highly prevalent negative health consequences such as obesity, cardiovascular diseases, abd type 2 diabetes.

It is because of high serum androgen level and polycystic ovaries.

Management strategies for PCOS : 

Multipronged treatment approach targeting the physical, metabolic, and  psychologic aspects of PCOS could help in the all-round management.

 • regulation of menstrual cycle

 • lifestyle changes that include following healthy diet and performing physical activity such as walking, yoga and pranayam

 • dietary modifications and weight loss in turn lower blood glucose levels and rectify IR in women woth PCOS

 • managing associated risk factors such as IR, hyperandrogenism, obesity with proper diet and weight management regimen.

References:

• Himalaya published article on eveforte.

• Research articles on PCOS from google.

• DC dutta textbook for gynecology .