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Polycystic ovaries (PCO) & polycystic ovarian syndrome (PCOS) Prevalence
The incidence of PCO and PCOS depends very much on the population being surveyed and the criteria used to diagnose the condition. True Whilst polycystic ovaries (PCO) describes the population studies have been reported from hospital ultrasonic diagnosis, the term polycystic ovary employees, family planning clinics, volunteers and syndrome (PCOS) is used if the ultrasound from general practice registers. These have been appearance is combined with clinical symptoms excellently reviewed by Balen and Michelmore2 and of hyperandrogenemia, such as oligomenorrhea, vary between 17 and 22 per cent. We have carried a hirsutism acne, seborrhoea or obesity.
study of the wives of men who were referred for IVF The definition of PCOS—that any two out of three with obstructive azoospermia, with 23 out of 100 parameters (morphology, hyperandrogenism (clinical sequential referrals demonstrating polycystic ovaries or biochemical) and oligo/amenorrhoea) were on baseline ultrasound examination, and about half sufficient to diagnose PCOS—was universally agreed upon at the ESHRE ASRM Consensus Conference on Thus it appears that almost a quarter of the female population has the appearance of PCO on The ultrasound criteria were also clarified. The critical ultrasound, but the natural history of these women is finding to diagnose PCO in ultrasound examination of the ovaries is the presence of multiple peripheral Longitudinal studies of women who are diagnosed small cysts. The Consensus Conference concluded with PCO are required to evaluate the probability that the presence of 12 peripheral cysts in at least one ovary was sufficient for diagnosis. There is also abnormalities and to identify significant factors usually an increase in ovarian volume, and change that may precipitate the development of these in ovarian dimensions with the ovary being more spherical. The role of imaging can be read in detail in the chapter by Dewailly et al.1 Inheritance
It has been recognised that PCOS has a familial
tendency, suggesting a genetic basis for its
inheritance. It is likely that there is an interaction
of environmental factors with a small number of causative genes.4 A number of candidate genes have been investigated including genes coding for steroidogenic enzymes (CYP 11a, CYP 19, CYP 17) genes involved with insulin secretion and action (Insulin gene including VNTR, Insulin receptor gene and Glycogen synthetase gene) and Follistatin.5 Short term problems
The commonest presentation to gynaecologists is menstrual irregularities and infertility, with one study reporting more than 65 per cent of women presenting having PCO.2 Whilst other problems need to be considered, the primary treatment given by gynaecologists is ovulation induction.
Baseline Lipid studies (cholesterol and triglycerides) Vol 7 No 4 Summer 2005 O&G
Lifestyle changes
Laparoscopic ovarian drilling
It has been reported that if obese women with PCOS Although there have been sporadic reports of enter a lifestyle program consisting of exercise and laparoscopic ovarian surgery restoring ovulation, it weight reduction, ovulatory cycles can be restored. was not until the report of Gjonnaess that following The initial studies of Clarke and Norman of a ‘Lifestyle, the laparoscopic unipolar diathermy of the ovaries Fertility Fitness program’6 found that 90 per cent of in 8 to 15 areas 92 per cent of patients ovulated with participants lost 5 per cent body weight and 90 per an 80 per cent pregnancy rate10 that this treatment cent ovulated, with 60 per cent becoming pregnant achieved popularity. Many small series of successful within 18/12. Whilst lifestyle change to healthy living cases have been reported. The use of laser including is to be encouraged, other groups have not found the CO2, argon Nd-Yag and KTP have all been described, exercise/diet program as effective.
but show little advantage over unipolar diathermy.11 Clomiphene citrate
A Cochrane review of 14 trials of laparoscopic ‘drilling’ or laser for ovulation induction in anovulatory PCOS The first line of pharmacological treatment is compared to gonadotrophin ovulation induction probably still the use of clomiphene citrate. With was carried out by Farquhar et al in 2001.12 They careful administration of a slowly escalating dose, identified eight studies including seven randomised ovulation rates of 70-85 per cent and pregnancy controlled trials (RCT). The main outcomes measured rates of 40-50 per cent can be achieved7 with low included ovulation rate and pregnancy rate whereas multiple pregnancy rates. The minimal effective dose secondary outcomes were miscarriage rate, multiple should be used, starting with 25mg/day for five days, pregnancy, and OHSS. They concluded that the increasing incrementally, monitoring response by value of ovarian drilling as primary treatment is at least monthly luteal oestradiol and progesterone undetermined. For Clomiphene-resistant patients, there are insufficient numbers to show difference on Insulin-sensitising drugs
pregnancy rate or ovulation rate have been studied. None of the modalities of drilling showed any The most widely used insulin sensitising agent is advantage but multiple pregnancy rates are reduced Metformin. Metformin is administered in a dose in pregnancies after ovarian drilling.
of 500mg-1700mg daily. Side effects are mainly gastrointestinal including diarrhoea, nausea, Therefore the only conclusion that can be reached vomiting or abdominal bloating. In patients with is that there is no difference in terms of these impaired renal function, lactic acidosis can occur. clinical outcomes for the two treatment regimens, A systematic review of the use of Metformin for except for the reduction of multiple pregnancies ovulation induction for PCOS–up to 60 per cent of following surgical treatment. We have carried out women ovulate over 3-6 month period.8 A recent a cost comparison study of laparoscopic ovarian Cochrane review of insulin-sensitising drugs for cautery in the private hospital system in Australia, polycystic ovary syndrome concludes that metformin and ovulation induction using gonadotrophins.13 is an effective treatment for anovulation in women Costs included the cost of hormones, biochemistry with PCOS, either as a first agent, but it is more and medical/surgical costs. The cost of ovarian effective in combination with clomiphene citrate.9 cautery was $AU1180 whereas the cost of typical cycle ovulation induction with HMG was $AU1401 OI with gonadotrophins
and with recombinant FSH $AU1800. This means The use of daily follicle-stimulating hormone (FSH) that surgical treatment is slightly cheaper and injections to induce ovulation has been available also enables several cycles of ovulation to attempt since the 1960s. Although initial treatment involved pituitary gonadotrophins, this changed to the urinary preparation in 1985 with the diagnosis of CJD. These have now been superseded by the use of recombinant FSH. The principle of treatment has not changed, with incremental increase of FSH dose until there is a follicular response, as diagnosed by rising serum oestradiol and/or ultrasound. Special care needs to be taken with PCOS patients as they are at higher risk of Ovarian Hyperstimulation Syndrome (OHSS). It is therefore recommended that the dose of FSH is only increased by 30 per cent every 7-10 days. O&G
Insulin resistance
the community.20 This is thought to be associated with The basic biochemical abnormality in PCOS is both the raised levels of luteinising hormone (LH) associated insulin resistance and impaired pancreatic b cel with PCOS.21 Unfortunately, a randomised prospective function. This can lead hyperinsulinaemia and frank control ed study of 106 women with PCOS who have had at least three spontaneous abortions, using LH suppression with GnRH agonist did not improve Androgen excess
pregnancy outcome, the outcome having been The universal endocrine abnormality of polycystic ovary syndrome is the excessive circulation of androgens, and this is responsible for the symptoms References
and signs of polycystic ovary syndrome, such as 1. Robert Y, Ardaens Y, Dewailly D. Imaging polycystic ovaries. In: Kovacs G. (ed) Polycystic Ovary menstrual irregularities, hirsutism, acne and alopecia. Syndrome. Cambridge University Press 2000;56-69 Hyperangrogenemia may also be responsible for 2. Balen A, Mitcehlmore K. What is polycystic ovary syndrome? Human Reproduction 2002; weight gain in about 50 per cent of cases.14 It has also been shown that women who have polycystic ovaries 3. Lowe P, Kovacs G, Howlett D. Incidence of polycystic ovaries and polycystic ovarian syndrome on ovarian ultrasound, but have no overt symptoms amongst women in Melbourne, Australia. Aust NZ J Obstet Gynaecol 2005; 45:17-19 of PCOS, may stil have hyperandrogenemia on 4. Franks S, Cela E, Gharani N, Waterworth D, McCarthy M. The inheritance of polycystic ovary syndrome. In: Kovacs G. (ed) Polycystic Ovary Syndrome. Cambridge University Press 2000;23-34 5. Kao L, Urbanek M, Driscoll D, Legro R, Dunaif A, Spielman RS, Straus JFIII. The genetic basis of Long-term effects
polycystic ovary syndrome. In: Kovacs G. (ed) Polycystic Ovary Syndrome. Cambridge University Press 2000; 35-48 It is now widely accepted that women with PCOS have 6. Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJK. Weight loss in obese infertile a significantly increased risk of diabetes. There has also women results in improvement in reproductive outcome for all forms of fertility treatment. been concern that PCOS may contribute to the risk of developing cardiovascular disease (CVD). The reason for 7. Balen A, Jacobs H. Ovulation induction for women with polycystic ovary syndrome. In. Kovacs this is that many of the biochemical disturbances, such G. (ed), Polycystic Ovary Syndrome. Cambridge University Press, 2000; 117-143 as insulin resistance and hyperandrogenism and the 8. Costello M and Eden J, A systematic review of the reproductive sytem effects of metformin in patients with polycystic ovary syndrome. Fertil Steril. 2003;79:1-13 resultant unfavourable changes in blood lipids which are associated with PCOS, are recognised risk factors. 9. Lord JM, Flight IHK, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome (Cochrane Review) It has also been reported that women with PCOS have In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software increased atherosclerosis as diagnosed on ultrasound 10. Gjonnaess H. Polycystic ovarian syndrome treated by ovarian electrocautery through the measurement of the intima-media thickness of the laparoscope. Fertil Steril 1984;41:20-25 carotid arteries.16 However the Pierpoint study17 showed 11. Kovacs GT. Polycystic ovaries, surgical management in Endoscopic Surgery for Gynaecologists. no increase in deaths due to circulatory diseases or 2nd Edition. Sutton and Diamond (eds). 1998; Chapter 23:233–241 ischaemic heart disease in the PCOS group compared 12. Farquhar C, Vandekerchove P, Lilford R. Laparoscopic “drilling” by diathermy or laser for to the population as a whole. Consequently whilst ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev 2001;(4) CD 001122 there is a theoretical risk, there is little hard evidence 13. Kovacs G T, Clarke S, Burger H G, Healy D L, Vollenhoven B.Polycystic Ovary Syndrome (PCOS) that PCOS increases cardiovascular disease. The next – Surgical or Medical Treatment. A cost benefit analysis. Gynaecological Endocrinology2002; question is whether women with PCO on ultrasound but without biochemical or clinical changes have an 14. Goodarzi MO, Korenman SG. The importance of insulin resistance in polycystic ovary increased risk of long-term complications. This question syndrome. Fertil Steril 2003;80:255-8 15. Carmina E, Wong L, Chang L, Paulson RJ, Sauer MV, Stanczyk FZ et al, Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound, Hum Reprod 1997;12:905-9 Lipid abnormalities have long been recognised as a risk 16. Talbott EO, Guzick DS, Sutton-TyrellK, McHugh-Pemu KP, Zborowski JV, Remsberg KE et factor for CVD. The abnormalities reported in women al. Evidence for association between polycystic ovary syndrome and premature carotid with PCOS include depressed high density lipoprotein atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol 2000;20:2414-21 (HDL) Cholesterol, elevated low density lipoprotein 17. Pierpoint T, McKeigue P M, Isaacs A J, Wild S H, Jacobs H S. Mortality of women with (LDL) Cholesterol, and raised triglyceride levels. These polycystic ovary syndrome at long term follow-up. J Clin Epiodemiol 1998; 51:581-586 abnormalities are believed to be related to the insulin 18. Legro R, Kunselman AR, Dunaif A. Prevalance and predictors of dyslipidemiain women with resistance/hyperinsulinemia.18 It is also believed that polycystic ovary syndrome. Am J Med 2001;111:607-13 chronic inflammation is a predisposing factor for CVD. 19. Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N. Low grade chronic inflammation in It has been reported that C reactive protein levels are women with polycystic ovary syndrome. J Clin Endocrinol Metab 2001;86:2453-5 elevated in PCOS, which correlates with obesity and 20. Homburg R, Armar NA, Eshel A, Adams J, Jacobs HS. Influence of serum luteinizing hormone insulin resistance but not hyperandrogenemia.19 concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. BMJ 1988;297:1024-6 Early pregnancy loss and PCOS
21. Regan L, Owen EJ, Jacobs HS. Hypersecretion of luteinising hormone, infertility, and It has been reported that the chance of early pregnancy miscarriage. Lancet 1990;336:1141-4 loss in women with PCOS is significantly higher than 22. Clifford K, Rai R, Watson H, Franks S, Regan L. Does suppressing luteinising hormone secretion reduce miscarriage rate? Results of a randomised controlled trial. BMJ 1996; 312:1508-11 Vol 7 No 4 Summer 2005 O&G

Source: http://www.fssc.com.au/wp-content/uploads/2013/08/PCOS.pdf

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Dr. Mohammadreza Ghandforoush-Sattari Assistant Professor of Clinical Toxicology Personal Details Address: Dept. Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Email: mrgsuk@yahoo.com, ghandsat@gmail.com Phone No. +98-411-3341315, +98-914-4192704 Fax No. +98-411-3344798 Academic Qualifications PharmD: 1992, in Pharmacy, from

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