Pathophysiology Behind PCOS
Polycystic ovary syndrome (PCOS) is a common endocrine disorder experienced by women of reproductive age. It is characterized by polycystic ovaries with small cysts on the outer edge. It is a heterogeneous disorder identified by hyperandrogenism and chronic anovulation. Symptoms of this disorder include hirsutism, menstrual cycle irregularities, hypothyroidism, and obesity.
The pathophysiology behind PCOS is very complex. PCOS is a multifactorial disorder which involves the pituitary, hypothalamus, ovary, adrenal, and peripheral adipose tissues, all of which are simultaneously involved in the pathogenesis of the syndrome.
What is the Pathophysiology Behind PCOS?
Several theories have been proposed recently to explain the pathophysiology behind the PCOS. Some of which include
Hyperinsulinemia and insulin resistance which results due to the defects in insulin action and its secretion.
Neuroendocrine factors which may alter the release of luteinizing hormone, its pulse, frequency and amplitude.
Increase in androgen levels due to possible defect in the synthesis of androgens.
Altered cortisol levels due to altered metabolism which in turn promotes excessive adrenal androgen production.
Let’s learn how these theories can give rise to PCOS:
Insulin Resistance and T2DM
Around 50-70% of women with PCOS exhibit metabolic abnormalities like diabetes, insulin resistance, poor glucose tolerance, CVD and hyperinsulinemia.
Insulin resistance is an impaired action of insulin in the uptake and metabolism of glucose. This can decrease the synthesis of sex hormone-binding globulin (SHBG) proteins which usually binds to androgen.
Hyperinsulinaemia augments androgen production in PCOS by stimulating ovarian receptors of insulin and insulin-like growth factors and directly augmenting gonadotrophin LH activity.
Also, excessive levels of insulin can indirectly enhance the amplitude of serum LH pulses and lead to PCOS.
PCOS symptoms include lower levels of the progesterone hormone for a long period of time. This may decrease the normal ovulatory movements and stimulate the hypothalamus to increase the pulsatility of the luteinizing hormone (LH).
Women with PCOS are observed with neuroendocrine abnormalities which lead to the enhanced pulse, frequency and amplitude of the luteinizing hormone.
The ration of LH/FSH is also found to be elevated in women with PCOS. This elevation may contribute to the ovarian excess of androgens when compared to estrogens.
PCOS is characterized by excessive adrenal androgen secretion. Altered steroidogenesis and factors like hyperinsulinemia may contribute to the excessive ovarian androgen production.
The “cysts” in polycystic ovaries are due to the arrested development of ovaries which are accumulated to form cysts.
This arrest in the development occurs when the granulosa cells of the ovaries begin to produce estrogen, and androgens in the ovaries inhibit the action of aromatase, therefore, reducing estradiol synthesis, which is required for further maturation of ovaries. This results in abnormal development of ovaries and formation of polycystic ovaries.
Altered Sympathetic Nerve Activity
Women with PCOS experience increased sympathetic activity which is further accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which leads to the development of polycystic ovaries.
Recent family studies suggest that hyperandrogenaemia and familial clustering of PCOS have been associated with genetic factors which can cause the development of the syndrome. However, a more clear pattern needs to be exhibited on this.