HOW ANTIDIABETIC DRUG METFORMIN WORKS IN POLY CYSTIC OVARY SYNDROME (PCOS)

WHAT IS POLY CYSTIC OVARY SYNDROME?

Poly cystic ovary is hormonal imbalance syndrome which is characterized by increase in male hormone androgen like testosterone. In this syndrome, sac or cyst are develops around the follicles (immature eggs) and there a is anovulation (absence of release of mature egg from ovary) due to this woman also faces the problem in conceiving. PCOS affects women menstrual cycle, skin, hairs, weight, fertility and blood pressure. PCOS women shows increase resistance to insulin also. Women with PCOS are more prone to obesity, diabetes, heart diseases, sleep apnea (temporarily cessation of breathing while sleeping) and endometrial hyperplasia (endometrium is the lining of uterus which shed off during period and hyperplasia refers as overgrowth of endometrium because, it is not properly shedding off in PCOS women. This endometrial hyperplasia can also subject patient to endometrial cancer).

HOW MANY HORMONES ARE ELEVATED IN PCOS?

In PCOS women, there is imbalance in hormone secretion. Follicle stimulating hormone (FSH), Luteinizing hormone (LH), estrogen, progesterone which release at different stages of menstrual cycles get disturb. Increase level of LH made the ovary to release increase quantity of male hormone like testosterone but in normal cycle, ovary releases only minimum amounts of testosterone. There is also increase in availability of insulin in blood in PCOS women.

HYPERINSULINEMIA AND METFORMIN USE IN PCOS. 

HYPERINSULINEMIA is condition in which there is increased level of insulin in blood. Why it happens? It is happened when blood glucose levels of blood do not respond to normal insulin concentration which is release by pancreas. In response of this resistance, pancreas release more insulin in blood to maintain normal blood glucose levels. This excess level of insulin in blood termed as HYPERINSULINEMIA. This insulin resistance can subject the patient to glucose intolerance (a condition in which blood glucose levels is not manageable to normal despite of increase insulin in blood) which is a prediabetic condition and prediabetic condition is the risk factor of type 2 diabetes. 

ROLE OF METORMIN IN PCOS AND OBESITY. 

There is a steady increase in prescribing METFORMIN for PCOS and obesity but use of METFORMIN for above mentioned indication is unlicensed. Further studies are required to investigate safety and efficacy of METFORMIN for the both indications. However, it is primarily indicated for type 2 diabetes mellitus which is it license indication. How metformin works in PCOS and obesity is controversial. Different studies show different theories but it’s improved syndrome symptoms that why it is frequently prescribed for both indications. Possible mechanism of action of METFORMIN may be as follow,

METFORMIN may work by reducing circulating levels of insulin or has direct effect on ovary steroidogenesis (formation of steroids i. e testosterone). It is still not clear but increase insulin level increase production of insulin like growth factor (IGF-1) from liver which in turn increase testosterone levels. METFORMIN by reducing insulin level in blood results in decreased IGF-1 level which resulted in decreased testosterone levels. Reduction in blood androgen level and LH stimulates ovulation which in turn improve menstrual cycle and decrease body mass index resulted in the decreased body weight. Restoring of ovulation reduces risk of miscarriage and gestational diabetes mellitus in PCOS woman during pregnancy.

However, it is unlicensed prescribing is increasing for PCOS and obesity and it is helpful in managing symptoms of PCOS in women and shows improvements despite the fact that its mechanism of action is unknown and its safe use required more research and investigations for both indications.