Excessive facial hair is a racial trait for the Indian sub continent running within families and especially strong in certain ethnic groups. This should be kept in mind while evaluating patients complaining of excessive facial / body hair. Androgens affect various aspects of follicular activity Acting via androgen receptors and secretory factors they increase the growth rate diameter and melanization of hair in androgen - sensitive areas. It is these thick coarse terminal hair in androgen dependent areas which are unsightly on a female and point to an underlying hyper androgenic state. Evaluation of the degree hirsutism is done by adopting a modified ferriman Galway score which evaluates 9 body areas on a scale of 1 to 4 . the total scores are significant if more than 6 to 8 . Overall 60-75% of patients with PCOS will have hirsutism.
Acanthosis nigricans
Typically thick dark velvety skin situated on the nape of the neck axillae groins and other frictional areas may often be the first clue of insulin resistance . The thickening occurs due to the stimulation of tyrosine kinase growth factor – signaling pathways in the epidermis . Insulin - kike growth factor receptor 1 is present in many tissues including the epidermis and ovary High levels of insulin directly or indirectly stimulate the IGF1R resulting in the skin changes . skin tags in the frictional areas like the neck axillae groins infra mammary or even under a pendulous abdominal fold are common especially in obese individuals.
Obesity
Obesity is a common finding in PCOS and aggravates many of its reproductive and metabolic features. In fact approximately 50% of PCOS women are overweight or obese and the history of the weight gain frequently precedes the onset of oligomenorrhea and hyperandrogenism suggesting a pathogenetic role of obesity in the subsequent development of the syndrome PCOS women are characterized by a high prevalence of several metabolic abnormalities which are strongly influenced by the presence of obesity. Adequate confirmation on the genuine role of obesity in determining hyperinsulinemia and insulin resistance in women with PCOS drives from studies comparing groups of normal weight and obese PCOS women . both festingand glucose stimulated insulin concentrations are in fact significantly higher in obese than in non obese PCOS subgroups.
It is well documented that women with PCOS have a high prevalence of abdominal body fat distribution even if they are normal weight . The impact of abdominal obesity on PCOS may be greater than expected since this phenotype is associated with a more pronounced hyperandrogenism and insulin resistance than the peripheral one .
Multiple therapies may be needed to address the variety of PCOS symptoms However it is important to address the common cause linked to these PCOS symptoms .
PCO & Its Etio pathogensis: This is the arena of battlefield:-Insulin Resistance – A pathophysiological contributor in 50-80% of the PCOS women
According to Indian journal of Endocrinology and metabolism , 2011 insulin resistance is a pathophysiologicla contributor in around 50-80 % of women with PCOS especially in those with more sevdere PCOS diagnosed on the basis of National institutes of health criteria and in women who are overweight.
Insulin resistance contributes not only to metabolic features but also to reproductive features through augmenting androgen production and increasing free androgens by reducing sex hormone binding globulin . Obesity increases hyperandrogenism hirsutism infertility and pregnancy complications both independently and by exacerbating PCOS. Further more women with PCOS have increased risk factors for T2DM cardiovascular disease impaired glucose tolerance.
Glucose metabolism in a normal cell includes several processes
• Insulin first binds to its receptor located on the cell wall forming a complex called insulin receptor substrate.
• This complex enters into the cell for stimulating the most vital messenger called phosphatidylinositol 3 kinase.
• Once PI 3 kinase is activated it causes translocations of glucose transport 4 to its cell membrane.
• Glucose is then taken by GLUT 4 through glucose channel for utilizing energy .
• Once energy is utilized through glucose the IRS complex breaks down releasing the receptor to relocate back to its original site.
• This is how glucose utilization takes place in the presence of normal insulin sensitive condition.
Phosphatidylinositol 3- Kinase – A key messenger in Insulin sensitivity
Phosphatidylinositol 3 kinase is a key messenger / enzyme responsible for activation of glucose transport so as to utilize glucose and liberating energy. It plays very important role in preserving insulin actions and thus improving insulin sensitivity. This enzyme plays a vital role in PCOS in which the most prominent cause is IR. Inositol acts as a precursor for the synthesis of phosphatidyl inositol . Inositol acts as a precursor for the synthesis of phosphatidyl inositol. Inositol plays an important role in the production of PI3 kinase. Hence inositol is an integral part of PI3 kinase.
Therory 2:-Inositol & PCO:_PCOS…characterized by reduced levels of inositol
Evidences suggest that a deficiency of inositol contribute to insulin resistance in PCOS individuals . It was observed that deficiency of inositol shows defective insulin signaling pathway in patients with PCOS. The women with PCOS and normal women were assessed for circulating inositol and 24 hr urinary clearance of inositol and insulin sensitivity . The findings indicated a marked alteration in inositol urinary clearance and deficient insulin stimulated PI 3 kinase release in PCOS women.
Plasma concentrations of inositol is significantly lower in PCOS women compared with normal control subjects consequently urinary clearance of Inositol was significantly higher in
CPOS women compared with normal control subjects .
Increased urinary clearance of inositol is an independent predictor of insulin resistance in PCOS patients
Consequently AUC inositol was significantly lower in PCOS women compared with normal control subjects
These findings strongly suggest a contribution of abnormal metabolism of inositol to the insulin resistance in PCOS patient which leads to a reduction in circulating inositol and its availability to the tissues . Finally in conclusion a defect in tissue availability of inositol in PCOS contributes to the insulin resistance leading to decreased cellular availability of the PI 3 kinase mediated insulin action.
Theroy 3: Altered insulin signaling and its relationship with IR and PCOS.
PI 3 kinase is a mediator for glucose metabolism and its utilization by the cell.
Deficiency of inositol alters activity of PI3 kinase.
Reduced activity of PI 3 kinase reduces translocation of GLUT 4 thereby causing hyperglycemia
This brings about altered insulin signaling causing hyperinsulinemia and thus IR . Insulin resistance thus is responsible for PCOS.
Pathway of inositol deficiency and PCOS
Metformin fails to manage Insulin Resistance in PCOS women
Metformin is the most commonly prescribed insulin senstising drug in the treatment of PCOS. It enhances insulin sensitivity by activating PI 3 kinase but it has been postulated that Metformin has a very restrictive mechanism of action due to which it is not a right treatment option for PCOS.How useful is metformin??Authentic journal statements on the use of metformin in PCOS
In the absence of large adequately powered placebo controlled trials it is difficult to provide useful answers about the longer term benefits of metformin in PCOS women. However there are more side effects with metformin like lactic acidosis and malabsorption including poor adsorption of vitamin B12
Thus there arises a therapy which cares for each and every symptom of PCOS along with documented safety.
Now coming back to efficacy of MI:-How important is MI?? Myo- inositol – The Ultimate Insulin Sensitizer
Myo- inositol a six carbon sugar alcohol present abundantly in the body. The chemical name of myo inositol is 1,2, 3,,5/4,6- Hexahydroxycyclohexane . It is a precursor of various cell membrane phospholipids.
Generally myo inositol is present in the cells. Serum concentrations are high during fetal life and later on falls However during certain conditions like polycystic ovary syndrome physiological requirements of myo inositol increased.
Myo inositol is an insulin sensitizing agent produced by the human body from glucose and is one of 9 distinct isomers of the nutrient inositol naturally produced by the human body. It is a vitamin B complex derived product that has been evaluated in a number of controlled studies looking at ovulation frequency , time to ovulation follicular maturation and the quality of oocyte production cell morphogenesis and cytogenesis lipid synthesis the structure of cell membranes and cell growth . Myo inositol plays an important role as the structural basis for a number of secondary messengers like to synthesise phosphatidylinositol 3 kinase a key messenger to improve insulin sensitivity and glucose utilization along with reduction of insulin resistance.
Acanthosis nigricans
Typically thick dark velvety skin situated on the nape of the neck axillae groins and other frictional areas may often be the first clue of insulin resistance . The thickening occurs due to the stimulation of tyrosine kinase growth factor – signaling pathways in the epidermis . Insulin - kike growth factor receptor 1 is present in many tissues including the epidermis and ovary High levels of insulin directly or indirectly stimulate the IGF1R resulting in the skin changes . skin tags in the frictional areas like the neck axillae groins infra mammary or even under a pendulous abdominal fold are common especially in obese individuals.
Obesity
Obesity is a common finding in PCOS and aggravates many of its reproductive and metabolic features. In fact approximately 50% of PCOS women are overweight or obese and the history of the weight gain frequently precedes the onset of oligomenorrhea and hyperandrogenism suggesting a pathogenetic role of obesity in the subsequent development of the syndrome PCOS women are characterized by a high prevalence of several metabolic abnormalities which are strongly influenced by the presence of obesity. Adequate confirmation on the genuine role of obesity in determining hyperinsulinemia and insulin resistance in women with PCOS drives from studies comparing groups of normal weight and obese PCOS women . both festingand glucose stimulated insulin concentrations are in fact significantly higher in obese than in non obese PCOS subgroups.
It is well documented that women with PCOS have a high prevalence of abdominal body fat distribution even if they are normal weight . The impact of abdominal obesity on PCOS may be greater than expected since this phenotype is associated with a more pronounced hyperandrogenism and insulin resistance than the peripheral one .
Multiple therapies may be needed to address the variety of PCOS symptoms However it is important to address the common cause linked to these PCOS symptoms .
PCO & Its Etio pathogensis: This is the arena of battlefield:-Insulin Resistance – A pathophysiological contributor in 50-80% of the PCOS women
According to Indian journal of Endocrinology and metabolism , 2011 insulin resistance is a pathophysiologicla contributor in around 50-80 % of women with PCOS especially in those with more sevdere PCOS diagnosed on the basis of National institutes of health criteria and in women who are overweight.
Insulin resistance contributes not only to metabolic features but also to reproductive features through augmenting androgen production and increasing free androgens by reducing sex hormone binding globulin . Obesity increases hyperandrogenism hirsutism infertility and pregnancy complications both independently and by exacerbating PCOS. Further more women with PCOS have increased risk factors for T2DM cardiovascular disease impaired glucose tolerance.
Glucose metabolism in a normal cell includes several processes
• Insulin first binds to its receptor located on the cell wall forming a complex called insulin receptor substrate.
• This complex enters into the cell for stimulating the most vital messenger called phosphatidylinositol 3 kinase.
• Once PI 3 kinase is activated it causes translocations of glucose transport 4 to its cell membrane.
• Glucose is then taken by GLUT 4 through glucose channel for utilizing energy .
• Once energy is utilized through glucose the IRS complex breaks down releasing the receptor to relocate back to its original site.
• This is how glucose utilization takes place in the presence of normal insulin sensitive condition.
Phosphatidylinositol 3- Kinase – A key messenger in Insulin sensitivity
Phosphatidylinositol 3 kinase is a key messenger / enzyme responsible for activation of glucose transport so as to utilize glucose and liberating energy. It plays very important role in preserving insulin actions and thus improving insulin sensitivity. This enzyme plays a vital role in PCOS in which the most prominent cause is IR. Inositol acts as a precursor for the synthesis of phosphatidyl inositol . Inositol acts as a precursor for the synthesis of phosphatidyl inositol. Inositol plays an important role in the production of PI3 kinase. Hence inositol is an integral part of PI3 kinase.
Therory 2:-Inositol & PCO:_PCOS…characterized by reduced levels of inositol
Evidences suggest that a deficiency of inositol contribute to insulin resistance in PCOS individuals . It was observed that deficiency of inositol shows defective insulin signaling pathway in patients with PCOS. The women with PCOS and normal women were assessed for circulating inositol and 24 hr urinary clearance of inositol and insulin sensitivity . The findings indicated a marked alteration in inositol urinary clearance and deficient insulin stimulated PI 3 kinase release in PCOS women.
Plasma concentrations of inositol is significantly lower in PCOS women compared with normal control subjects consequently urinary clearance of Inositol was significantly higher in
CPOS women compared with normal control subjects .
Increased urinary clearance of inositol is an independent predictor of insulin resistance in PCOS patients
Consequently AUC inositol was significantly lower in PCOS women compared with normal control subjects
These findings strongly suggest a contribution of abnormal metabolism of inositol to the insulin resistance in PCOS patient which leads to a reduction in circulating inositol and its availability to the tissues . Finally in conclusion a defect in tissue availability of inositol in PCOS contributes to the insulin resistance leading to decreased cellular availability of the PI 3 kinase mediated insulin action.
Theroy 3: Altered insulin signaling and its relationship with IR and PCOS.
PI 3 kinase is a mediator for glucose metabolism and its utilization by the cell.
Deficiency of inositol alters activity of PI3 kinase.
Reduced activity of PI 3 kinase reduces translocation of GLUT 4 thereby causing hyperglycemia
This brings about altered insulin signaling causing hyperinsulinemia and thus IR . Insulin resistance thus is responsible for PCOS.
Pathway of inositol deficiency and PCOS
Metformin fails to manage Insulin Resistance in PCOS women
Metformin is the most commonly prescribed insulin senstising drug in the treatment of PCOS. It enhances insulin sensitivity by activating PI 3 kinase but it has been postulated that Metformin has a very restrictive mechanism of action due to which it is not a right treatment option for PCOS.How useful is metformin??Authentic journal statements on the use of metformin in PCOS
In the absence of large adequately powered placebo controlled trials it is difficult to provide useful answers about the longer term benefits of metformin in PCOS women. However there are more side effects with metformin like lactic acidosis and malabsorption including poor adsorption of vitamin B12
Thus there arises a therapy which cares for each and every symptom of PCOS along with documented safety.
Now coming back to efficacy of MI:-How important is MI?? Myo- inositol – The Ultimate Insulin Sensitizer
Myo- inositol a six carbon sugar alcohol present abundantly in the body. The chemical name of myo inositol is 1,2, 3,,5/4,6- Hexahydroxycyclohexane . It is a precursor of various cell membrane phospholipids.
Generally myo inositol is present in the cells. Serum concentrations are high during fetal life and later on falls However during certain conditions like polycystic ovary syndrome physiological requirements of myo inositol increased.
Myo inositol is an insulin sensitizing agent produced by the human body from glucose and is one of 9 distinct isomers of the nutrient inositol naturally produced by the human body. It is a vitamin B complex derived product that has been evaluated in a number of controlled studies looking at ovulation frequency , time to ovulation follicular maturation and the quality of oocyte production cell morphogenesis and cytogenesis lipid synthesis the structure of cell membranes and cell growth . Myo inositol plays an important role as the structural basis for a number of secondary messengers like to synthesise phosphatidylinositol 3 kinase a key messenger to improve insulin sensitivity and glucose utilization along with reduction of insulin resistance.
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