Adolescent PCO

Polycystic ovary  syndrome – A clinical  and public  health problem affecting up to one in five  women of reproductive age .

Basics:--Polycystic ovary   syndrome  is a frustrating  experience for women   often complex  for managing   clinicians and is  a scientific challenge for  researchers , PCOS  is a complex condition  with psychological   reproductive and metabolic    manifestations  that impacts on health across  the lifespan    PCOS is   one  of the most common hormonal disorders  affecting women . it  has   multiple   components  - reproductive metabolic  and cardiovascular – with  health    implications for the patient’s   entire life   span. PCOS has  a significant effect  on adult women  resulting in diminished quality  of life  altered  feminine  identity and dysfunction in the family  and work  environment .

Most  debated Topic

Part 1: The History & Geography:-PCOS  was   originally  described in 1935  by Stein  and Leventhal   who reported  a  group  of women with   amenorrhea   and polycystic  ovaries  of whom some  were hirsute and / or   obese   in 1990 a National Institutes of Health   consensus   conference defined  PCOS as a combination of hyperandrogenism  menstrual  dysfunction  and exclusion of known   disorders   such as  congenital adrenal  hyperplasia    leading to the above.

Part 2: A fight between almost all academic bodies,. Millions of dollars spent for Recommendations & committee Opinions  with level 1-4 evidences : As a result  We GP & pts too are frightened when diff  PCO societies fight with swords, daggers, canons, fighter planes , missile  for an uniform & exact defn which will encompass latent & overt PCO and pick up caxes which are destined to develop PCO or Metab syb vy one deacde .Till 2003  diagnostic  criteria for PCOS   were varied  and often   confusing  However   the joint  European  Society  of Human   Reproduction and Embryology and The American Society     for Reproductive Medicine   ESHRE/ ASRM sponsored  consensus  meeting in Rotterdam in 2003  accepted  that CPSO consists of the presence  of any 2 of the 3 criteria.

 Oligo and / or  anovulation

Clinical and / or  biochemical evidence of hyperandrogenism  and

The  presence  of polycystic ovaries  on ultrasound examination

Part 4: Orther etiogy?? Other etiologies like  congenital   adrenal hyperplasia  Cushing’s  syndrome  and androgen secreting tumours  need to be   excluded. Ultrasonographic scanning of women with  unexplained  hyperandrogenic  chronic  anovulation frequently  reveal  ovaries that  are polycystic    Sonography   shows ovarian enlargement multiple  small follicles at the periphery with increased echogenecity. 

Part 5: Prevalence L:: Incidence  :: How believable

The  incidence  is influenced by the nature  of the population being   assessed studies   in which ultrasound   examination   for presence   of polycystic  ovaries    were conducted reveal a   prevalence    rate of approximately    20 to 30%  in Caucasian  women in the  reproductive age There are    significant   racial  difference and  as  compared to  PCOS is found to be  higher  in the  ethnic groups  in the south  Asians living  in the UK the prevalence   reported was 52%  in Indian   the incidence  of adolescent  PCOS  were found to be 36%

Part 6::  Catch them young:-PCOS in adolescence – a future fertility problem

Polycystic  ovary  syndrome   is a common disorder  among reproductive age women yet the diagnosis may be overlooked  during adolescence Although   the clinical and metabolic features are similar   to those  found in adult women  it can be difficult to distinguish the young woman with  PCOS  from a normal     adolescent. Adolescent patients  with PCOS who  are at the height of identity   development  and awareness of body   image may  have  a more significant  disturbance  in quality  of life .

Adolescent girls with PCOS were 3.4 times  more lively to be worried  about their  ability to become  pregnant than   comparisons and concern about  future fertility was associated  with significant  reductions in quality  of life.

In addition polycystic ovary  morphology  affects  20-30 %  of reproductive aged  women and  10%  of regularly menstruating girls . As in  adults current  therapy of adolescent  PCOS focuses  primarily on symptomatic management of the reproductive metabolic and cosmetic  manifestations of the disorder

A cross sectional study    of adolescent girls   with PCOS and healthy   comparisons was conducted by Trent et al at an urban  hospital  based adolescent medicine  practice. Healthy subjects  were 2.8  times more   likely to have had  sexual  intercourse  than PCOS participants though the mean age at initiation of sexual intercourse   among sexually active girls   was not significantly  different between the two groups. Girls   with PCOS    were 3.4  times more likely to be worried   about their ability  to become pregnant  than comparisons and concern   about future fertility   was associated with significant   reductions  in quality  of life. Adolescents with PCOS are more concerned about fertility than  their  healthy  peers and this  concern  may affect their overall quality  of life.

Part 7:--The dilemma & confusion is here.. Diagnosis of PCOS – The clinical features May or may not have symptoms in varying combination just bto beffol physician

Although  adolescent patients with PCOS   can present  with a range of  symptoms and laboratory  abnormalities typical   complaints are acne  hirsutism irregular  menses  and obesity

Irregular  menses

Ovarian dysfunction   usually manifests as oligomenorrhea / amenorrhoea   resulting from chronic oligo ovulation /  anovulation  . Oligomenorrhea  occurs usually in  adolescence  with onset  later   in life often associated  with weight  gain.

Menstrual irregularity is a common   features  of CPSO 995 of CPSO  patients  present  with menstrual disorders.

99%  of CPSO patients   present  with menstrual disorders

This  menstrual pattern can be  difficult to distinguish form anovulation  associated with puberty  because   the hypothalamicpituitary   - ovarian  axis matures  preogressively   over a period  of several years  after  menarche. Although   many adolescents establish regular   cycles  by 2 years  post menarche  irregularity may continued beyond  that time period often without   cause for   clinical  concern. Although   irregular menstrual cycles   cannot be the sole crieterion  for PCOS they  comprise an important   symptom  that should be followed  in the adolescent. When   oligomenorrhea is persistent or presents  in conjunction with  symptoms   of androgen   excess  further   evaluation for PCOS  in  recommended. `

 Amenorrheic women with PCOS  usually have the most  severe   hyperandrogenism and higher antral  follicle counts  as compared   with women   presenting   with oligomenorrhea or regular menstrual  cycles.

Acne  vulgaris

Patients with PCOS complain of inflammatory acne   minimally responsive   to  conventional  line of  treatment   . Even if responsive  lesions promptly recur on stopping  treatment  . An important   feature  seen is the  development of multiple closed  comedones which   rapidly  transform    into tender  lumpy nodules distributed   in the lower  half of face   ad jaw line A pre menstrual   flare is  also common . Acne lesions  may not only by localized  to the face  but may   also be present  on the chest  shoulders  and  back  prompt  relapse  after stopping the treatment   strongly  suggests a hormonal  basis . The   prevalence of  acne in women   with   PCOS has been estimated  to be  10-34% .

Hirsutism

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 .

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. 

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.

Growing  evidences  of Myo inositol in PCOS

Studies have   found that  deficiency of inositol which is  precursor for phosphatidylinositol  3 kinase contributes to the  insulin resistance  in pcos   women. The women   with PCOS  are characterized by abnormal   metabolism of inositol and have  diminished insulin stimulates  releases of the putative phsophatidylinositol mediator.

Myo inositol significantly improves  insulin activity and  reduces   glucose level  in PCOS  patient. It also reduces  total testosterone as a result it   improves  hormonal   balance and ovulation. Elevated  concentration of myo inositol  in human   follicular    fluid  appears to play  important   role in follicular   maturity  and provides  good quality  oocytes.

Myo  inositol besides  improving hormonal profile and restoring  ovulation  is also  able to induce regular  menses in PCOS patients  . Finally  in conclusion myo inositol   increases  implantation  and pregnancy rate in PCOS  patients.

Clinical  effects of myo inositol  supplementation can be  summarized as follows :

Reduces  insulin  resistance   and increases   insulin sensitivity

Increases  glucose  uptake

Lowers insulin  levels 

Lower total and  free testosterone

Improves  menstrual  cycle  frequency

Improves  pregnancy  rate  and live birth rate

Lowers  triglycerides  and improves  lipid  profile .

As per ped Health 2010; Adolesscent girls  with PCOS require a long  term committed treatment   . Therefore     alternative treatments may be possible  option for a subset of PCOS  adolescent females. Myo  inositol a component  of the vitamin B complex  has been shown  to improve  insulin signaling   thereby  restoring  normal   ovulatory   function  in PCOS  women.

Thus as Myo inositol takes care of the major  symptoms  associated with PCOS    Care  in established PCOS  cases and in adolescent  PCOS  cases .

Clinical  studies of Myo  inositol in PCOS

Myo inositol shows  56% reduction in HOMA  Index

P.G, Artini et al evaluated the   effects  the administration of myo  inositol  on hormonal  paratemeters  in a group of polycystic ovary  syndrome   patients  in a controlled clinical  study 50  overweight PCOS  patients   were enrolled after  informed   consent. All patients   underwent  hormonal   evaluations and  an oral glucose tolerance test  before and after 12  weeks of therapy    MYO 2 g plus folic  acid 200 mg every  day Group B  folic acid   200 mg Ultrasound examination  and Ferriman – gallwey score   were  also performed

Main outcome measures  were  plasma  LH, FSH, PRL , E2  17 OHP , A, T , glucose    insulin , c peptide concentrations , BMI, HOMA index  and glucose  to insulin  ratio.

 First of all in the MYO treated group  the duration    of stimulation  was lower  than  in control group   and also  r-FSH  units  used were fewer  in the MYO   treated group. The HOMA  index got  significantly reduced from 2.5 + 0.6 to 1.1 + 0.3   in the MYO group .However     in the control group  the HOMA  index  remained unchanged from 2.5 + 0.4  to 2.4 + 0.7

The   insulin levels  got significantly  reduced from  11.4 + 2.2  to 5.5 + 1.1  in the MYO  group However  in the control  group  the insulin   levels decreased  from 11.4  + 1.3  to 10+ 1.1

The  BMI  got reduced from 28+ 1.6 to 27.3 + 1.3 in the MYO  group  . However in the control  group  the insulin levels  increased from 26.6 + 2.1  to 27.5 + 1.7  

Menstrual   cyclicity was  restored in all amenorrheic  and oligomneorrheic   subjects  in the Myo  inositsol group No changes  occurred in the patients treated  with folic acid.

Pregnancy  rate   was considerably higher in the treated  group  . 10   clinical  pregnancies developed in Group  A and 4 in Group B   while the delivery     rate was  8 versus  3   respectively 

MYO supplementation is efficient in changing  many  of the hormonal  disturbances of PCOS improving    insulin sensitivity of target  tissues  and positively  affecting the hormonal  functions. 

Myo-  inositol shows  2  times  improvement   in insulin sensitivity

Forty   two women   with PCOS were treated in a double  blind  trial  with MYO   inositol plus folic acid or folic  acid alone as placebo

After  randomization  23 women   received  4 gm of Myo  inositol plus  400  mcg of folic acid and  19 women received   400 mcg folic acid  alone as   placebo. The treatement was given for 12-16 weeks. In  the group    treated with MYO  inositol  the serum total testosterone  decreased  from 99.5+ 7 tpo 34.8 + 4.3  ng/dl  and serum free testosterone   from 0.85  + 0.1  to 0.24  + 0.33 ng/dl  . The area  under the   plasma   insulin curve after   oral administration of glucose  decreased from 8.54 + 1.149  to 5.535 + 1.792 ug /ml/min   . Plasma  triglycerides decreased from 195+ 20  to 95+ 17  mg /dl   The index of  composite  whole  body  insulin sensitivity   increased from 2.80 + 0.35  to 5.05 + 0.59  mg 2/dl-2   16 out of  23  women of Myo  inositol group  ovulated and only 4   out of 19 women treated with folic  acid were ovulated .

In conclusion treatment  of PCOS   patients  with Myo inositol provided a    decreasing  of circulating  insulin and serum total testosterone as well as an  improvement  in metabolic  factors.

Myo inositol shows 16-30 5  reduction in Hirsutism and 21-53% reduction   in acne

Zacche et al in a randomized clinical  study  stated  that Myo  inositol  administration is a simple  and safe  treatment  that  amelionates the metabolic  profile of patients with PCOS reducing hirsutism and acne  . Fifty patients   with PCOS  were enrolled    in the study    Every  woman  presented signs  of hyperandrogenism   on the basis of the number of lesions on the face /chest  / bck  they were    distinguished as moderate form severe  acne also  using a modification of the ferriman   gallway  score that quantifies  hairs  in nine body  areas hirsutism  was classified in mild   moderate    , severe

All patients were  evaluated for testosterone and insulin resistance was   measured  using homeostasis model   assessment

Patients  were  treated  orally with Myo inositol 2 g plus folic  acid 200 mg as twice  daily continuously for 6 months. Significantly  changes  were observed in biochemical features of patients  with PCOS  as shown

Hormonal  and metabolic  profile at baseline and after 3 months of myo inositol treatment

Testosterone   basal insulin levels     and consequently    and HOMA   index  were significantly  decreased.

Number   of cases and severity  of acne at baseline and after 3 and 6 months  of treatement  with myo inositol

Also  clinical    features improved  after  myo inositol  treatment  of 3 and  6  months    . all   patients   of our  study presented hirsutism before getting Myo  inositol    During  the observational   period  the hirsutism  score   decreased  after 3 months    and after 6 months of myo  inositol  treatement    

After  3 months  of myo inositol administration  plasma  testosterone  free testosterone insulin and HOMA  index were significantly  reduced,. Both  hirsutism  and acne  decreased after  6 months  of therapy.

Myo inositol is a  simple & safe  treatement  that ameliorates the metabolic  profile of patients   with  pcos  reducing  hirsutism & acne

 Myo inositol restores menstrual cycles in all amenorrheic  and  oligomenorrheic  patients   by reducing  insulin resistance

In a controlled  clinical study  20  overweight  PCOS patients    were  enrolled. All patients   underwent  hormonal  evaluations  and an oral   glucose  tolerance test before  and after 12 weeks of therapy  myo inositol 2 gm  plus  folic acid 200 ug every  day Group B    folic acid   200 ug every day    . PCOS    women treated with  myo inositol  for 3 months restores   menstrual cycle in all  amenorrheic  and oligomenorrheic  subjects . also  myo inositol   administration significantly reduced  insulin levels testosterone  levels   plasma  luteinizing hormone . Myo  inositol administration  significantly   reduce HOMA  index afer 3 months of therapy At baseline the HOMA  index  was 2.8  after treatment it came down  to 1.4

Myo inositol administration   positively affects  hyperinsulinemia  and hormonal  parameters in overweight  patients   with  polycystic ovary   syndrome. Myo  inositol  administration  improves  reproductive axis functioning in PCOS   patients reducing  the hyperinsulinemic  state that affects LH  secretion. Myo inositol  shows  62%  reduction  in free testosterone levels.

Papaleo  et al  in a randomized clinical  study  stated that myo inositol is a simple and safe treatment   that is capable of restoring  spontaneous   ovarian activity and consequently  fertility in most  patients  with PCOS

In this study these  researchers administered myo inositol combined with folic acid twice   a day for up to 6   months to 25  PCOS patients   of childbearing   age having age 28  to 38   years  with oligo or amenorrhea   hyperandrogenism   or hyperandrogenemia  .

While receiving myo   inositol  treatment   22 out of the 25   patients   had at least one  spontaneous    menstrual  cycle during  the 6 months treatment   period and 18 of these patients maintained  normal   ovulatory cycles  during the entire  6 months  study  period . All of them maintained spontaneous ovulation   activity  documented by follicular  growth   and increased   serum progesterone concentrations in the luteal  phase .

Furthermore after treatement   with MI  these women showed significantly decreased  concentrations of serum  total testosterone   and free  testosterone .

The length  of successive  cycles was improved to 31.7 + 3.2  days. Treatement   with Myo inositol in PCOS  patients   provided  decrease  in circulating  insulin and glucose  level  and serum total  testosterone  as well as an improvement    in metabolic factors. A total   of 10 singleton pregnancies    were  obtained. The  study  authors  concluded that  myoinositol  treatement is capable of restoring spontaneous ovarian activity  in most patients   with PCOS

Myo inositol restores ovulation improves lipid profile

Gerli et al assessed the effects of supplemental myo  inositol on ovarian  function in a randomized   double blind placebo controlled  trial  of oligomenorrheic  and polycystic   ovarian     women  Of the 92  subjects 45 were randomized to receive  myo inositol  plus  folic  acid / day   for 14 weeks  while  the remaining 47  received folic   acid per day  400 mcg folic   acid as a placebo Serum   samples  were obtained  twice weekly to assess   hormonal   concentrations  circulating   estradiol  concentrations increased  during  the  first week of treatment   only in the myo  inositol  group   indicating that there had  been a rapid  effect of myo inositol  on follicular   maturation . An improvement   in ovulation   frequency was  also observed between the women   receiving   myo  inositol    and those on placebo with  82%  of women on myo   inositol ovulating   at least  once during   the 14 week   period     and 63%   of women   on placebo   ovulating  at least  once during  the study period  . The  time to the first ovulation   was significantly  shorter  in  treated  patients    in these patients  the time  to first   ovulation   was   24.5  days   .

 Myo  inositol  treatment   also resulted in significantly increased  concentrations from baseline     in high   density  lipoprotein cholesterol no changes were  observed in he control group. Metabolic risk  factor benefits of inositol  treatement  were not observed   in  a morbidly obese   subgroup of patients  . The  authors  concluded   that supplemental myo inositol    improves  ovarian   function   in women   with  oligomenorrhea ad polycystic   ovaries.

Myo  inositol   provides follicular  maturity  and good   quality  oocytes

Unfer et al stated that  myo inositol  treatment    is able to improve oocyte   and embryo  quality during ovarian stimulation protocols. In this  study  Eighty  four euglycemic PCOS   patients undergoing   ovulation  induction  for ICSI were recruited Forty  three  participants  received  Myoinositol  2 g twice  a day and forty one patients   received  D chiro inositol  0.6  g twice  a   day , the number    of mature  oocytes was significantly  increased in the myo inositol     group compared to D chiro  inositol . Concurrently the number of   immature   oocytes   decreased  in myo  inositol  treated  patients . Furthermore    the myo inositol treated group  showed an increase in the mean number  of top quality   embryos   and in the total  number of pregnancies compared to  the D chiro  inositol  treated  group/ The presence  of high  concentrations   of myo inositol in the follicular  fluid has  become  a marker of good  quality oocytes it was observed  that high  concentrations of myo inositol in the follicular    fluid paly  in important   role in  follicular   maturation  and in embryonic  development   . In addition myo inositol decreases immature   oocytes  production

ESHRE 2008- Myo inositol , a simple  and safe first line treatment  in women  with  PCOS

Supplementation of myo inositol is positively related  to oocyte  maturity  in mouse while higher  concentrations  in human   follicular  fluids  are marker of  good  quality   oocytes . 75  infertile  women  with polycystic ovary  syndrome   to receive   continuously 4 g  myo inositol  plus 400  ug folic   acid orally  or 50 mg clomiphene   citrate daily   for 5 days eventually  increased to 100 mg if resistance occurred. During follow up period of 6  months ovulatory  activity  with ultrasound scan   and  hormonal   profile  ongoing pregnancy   and spontaneous abortion were  assessed.

Pregnancy  rate was 33.3%    in the myo  inositol group  ans 28.2 %    in clomiphene citrate group  among  pregnancies   the rate of multiple   pregnancy  was 18.1 %    in the clomiphene group  and 0%  in the   myo  inositol  group    . No side   effects were  reported with myo  inositol

Myo inositol is a simple and safe treatment   that is capable to restore a spontaneous  ovarian activity and consequently  fertility in most patients   with polycystic ovary    syndrome. This  therapy   did not cause multiple   pregnancy    and can be  evaluated  as primary  method  of inducing   ovulation  in PCO’s  women .

PCO  care  contains  Myo inositol  which takes care of the symptoms   of PCOS   and thus  provides a comprehensive  management  of PCOS

Composition

Each  tablet of PCO care contains  :

Myo inositol …. 1 gm

Myo inositol is an isomer of a  C6 sugar  alcohol that belongs  to the vitamin  B  complex group. The chemical   name of   myo  inositol is 1 R, 2R  , 3S  , 45  , 5R, 6S cyclohexane – 1,2,3,4,5,6- hexol

Clinical   pharmacology

Myo  inositol is metabolized to phosphatidylinositol which     acts as a precursor for phosphatidylinositol  3 kinases  a key  messenger responsible  for activation of glucose   transport so as to utilize glucose  and to liberate energy . It  helps  to improve insulin sensitivity in PCOS patient. Inositol deficiency is the basic pathophysiology for PCOS . Women   with PCOS  had a greater than  fivefold   increase  in urinary   clearance   of inositol  and circulating  plasma   concentration  of inositol  was reduced by half   in PCOS  women   as compared   to normal  women  . During  certain conditions  like polycystic   ovary syndrome  the physiological requirements of   myo inositol increases  The use of  myo inositol in PCOS patients   reduces insulin resistance   testosterone   levels and  improves    ovulation  Moreover   elevated  concentration of myoinositol  in human follicular   fluid  improves  follicular   maturity  and menstrual  frequency .

Pharmacokinetics

Myo  inositol  is absorbed from the  small intestine and is transported by the portal    circulation to the liver  and then by the systemic  circulation   to various  tissues   in the body  Within the  liver   and the  various tissues of the body myoinositol enters  into    a wide range  of biochemical   pathways   Myo  inositol reacts  with CDP  diacylglycerol  to form the   the phospholipid    phosphatidylinositol  which   can be   incorporated     into membrane   structure   .Phosphatidylinositol  via kinase  reactions  form phosphatidyl   4,5  bisphosphate  which  is the precursor to inositol -1,4,5- triphosphate diacylglycerol  phosphatidylinositol  -3,4,5- triphosphate  etc. The myo  inositol   phosphates  can be  dephosphorylated  via phosphatases. 

Indications

PCO care  is indicated  for the ultimate  management  of insulin  resistance  in PCOS and its associated  symptoms

Menstrual irregularities 

Hyperandrogenism 

Obesity  / Weight gain

Anovulation