Veterinary Microbiology 89 (2002) 303–309Distribution and characterization of class 1 integronsin Salmonella enterica serotype GallinarumHyuk Joon KwonTae Eun Kim, Sun Hee ChoJae Goo SeolaInstitute of iNtRON Biotechnology, Seoul, 138-200, South KoreabDepartment of Microbiology, College of Medicine, Cheju National University,cDepartment of Biochemistry, College of Medicine, Cheju Nation
Management of pcosManagement of PCOS
Marja Ojaniemi and Päivi Tapanainen
Department of Pediatrics and Adolescence
University of Oulu
The Rotterdam 2004 Consensus Workshop (Revised 2003) proposed that PCOS is a
syndrome of ovarian dysfunction, and recommended that two of the following criteria
should be present to establish the diagnosis: 1) chronic oligo or anovulation
for more than 6 months 2) cinical and/or biochemical evidence of hyperandrogenism, and
3) polycystic ovaries in ultrasound. Other dirsorders that mimic PCOS phenotype should
be excluded (1).
The polycystic ovary syndrome (PCOS) in a teenager is characterized by irregular
menstrual cycles, generally less than six menses per year, and by clinical or biochemical
features of hyperandrogenism. More than 50 % of PCOS patients have the metabolic
syndrome, including obesity, insulin resistance and dyslipidemia (2). Although PCOS is
a common disorder, the diagnosis may be overlooked during adolescence, as irregular
menses with anovulatory cycles, obesity and acne are frequent in adolescent women.
According to the androgen overexposure hypothesis, PCOS may have its origin already
in fetal life, but becomes clinically manifest during adolescence with maturation of the
hypothalamic-pituitary-ovarian axis (3). The incidence of PCOS among adolescents is
estimated to be 11-26 % (4) and about 50 % of the patients are overweight. The
pathophysiology of PCOS is still uncertain, although there is evidence that both genetic
and environmental factors may play a role, resulting in ovarian hyperandrogenism and
impaired insulin sensitivity (5-9).
The spectrum of PCOS phenotype is wide, imcluding women with no evidence of
clinical and biochemical hyperandrogenism despite dysfunctional polycystic ovaries.
Some adolescent PCOS patients may have normal androgen levels (10) with moderate
hirsutism compared to adults (11). Insulin resistance plays an important role in PCOS
pathophysiology. During puberty, insulin sensitivity is decreased causing increased
secretion of insulin(4).
Treatment of PCOS is symptomatic. Lifestyle changes are a first-line intervention in
obese adolescents with PCOS (12). Glucose intolerance can be managed by diet and
exercise, and appropriate weight control. Metformin improves insulin sensitivity and
glucose metabolism (13), and ameliorates hyperandrogenism and irregular menses in
adolescents (14, 15). Metformin is also benificial in normalizing the lipid profile (16).
Metformin has been administered at doses varying from 1.5 mg to 2.5 mg/day and it is
generally divided into two to three doses. Mild side-effects such as gastrointestinal
symptoms (nausea, metallic taste in the mouth and changes in bowel movement frequency ) occur in about 5-10 % of cases, but the drug is well tolerated if the dose is increased gradually. Its most feared complication is lactic acidosis which is fortunately very rare and almost always related to coexistent hypoxic conditions, which are contraindications for metformin therapy (17-19). However, questions about how long the treatment should be continued and long-term safety remain to be answered. Ibanez et al. have reported that the beneficial effects are lost soon after treatment is discontinued (16). It is important to take care of contraception in metformin users because of improvement of ovulatory function (20). Other treatment options used in PCOS are spironolactone and contraceptive pills. Spironolactone is very rarely used in adolescence. PCOS patients with acne and hirsutism may benefit of combined contraceptive pills, especially those containing cyproterone acetate. (21). Insulin sensitizers, glitazones, improve insulin resistance, but their use and safety in adolescents is not known. As a conclusion PCOS is common in adolescents and should be considered in an adolescent with irregular menses and excess weight. The metabolic syndrome is a common feature of PCOS. Testing for glucose intolerance and dyslipidemia is required, particularly in the presence of obesity. Lifestyle changes are the first line intervention in young overweight women with PCOS. Management of the PCOS adolescent with metformin is beneficial and well tolerated, but the longer term effects are not yet established. It appears that PCOS is a lifelong condition. Consequently, patients should be carefully monitored during adolescence and thereafter in adulthood (22). References 1. Consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reproduction 2004; 19: 41-47 2. Vural B, Caliskan E, Turkoz E et al. Evaluation of metabolic syndrome frequency and premature carotid atherosclerosis in young women with polycystic ovary syndrome. Human Reproduction 2005; 20: 2409-2413 3. Franks S. Adult polycystic ovary syndrome begins in childhood. Best Practice and Research. Clin Endocrinol Metab 2002; 16: 263-272 4. Driscoll DA. Polycystic ovary syndrome in adolescence. Ann New York Acad Sci 2003; 997: 49-55 5. Jahnafar S, Eden JA, Warren P et al. A twin study of polycystic ovary syndrome. Fertil Steril 1995; 63: 478-486 6. Legro RS, Driscoll D, Strauss JF et al. Evidence for genetic basis for hyperandro- genemia in polycystic ovary syndrome. PNAS 1998; 95: 14956-14960 7. Battaglia C, Regnani G, Mancini F et al. Polycystic ovaries in childhood: a common finding in daughters of PCOS patients. A pilot study. Human Reproduction 2002; 17: 771-776 8. Vink JM, Sadrzadeh S, Lambalk CB et al. Heritability of polycystic ovary syndrome (PCOS) in a Dutch Twin-Family Study. J Clin Endocrinol Metab 2005 9. Norman RJ, Wu R, Stankiewicz MT. Polycystic ovary syndrome. Med J Austral 2004; 180: 132-137 10. Pugeat M, Nicolas MH, Craves JC et al. Androgens in polycystic ovary syndrome. Ann New York Acad Sci 1993; 687: 124-135 11. Ruutiainen K, Erkkola R, Gronroos MA et al. Influence of body mass index and age on the grade of hair growth in hirsute women of reproductive ages. Fertil Steril 1988; 50: 260-265 12. Norman RJ, Davies MJ, Lord J et al. The role of lifestyle modification in polycystic ovary syndrome. Trends in Endocrinol Metab 2002; 13: 251-257 13. Arslanian SA, Lewy V, Danadian K et al. Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance: amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/ insulin resistance. J Clin Endocrinol Metab 2002; 87: 1555-1559 14. Glueck CJ, Wang P, Fontaine R et al. Metformin to restore normal menses in oligo- amenorrheic teenage girls with polycystic ovary syndrome (PCOS). J Adolesc Health 2001: 29: 160-169 15. Ibanez L, Valls C, Ferrrer A et al. Sensitization to insulin induces ovulation in non- obese adolescents with anovulatory hyperandrogenism. J Clin Endocrinol Metab 2001; 86: 3595-3598 16. Ibanez L, Valss C, Potau N et al. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious puparche. J Clin Endocrinol Metab 2000; 85: 3526-3530 17. Bailey CJ, Turner RC. Metformin. N Engl J Med 1996; 334: 574-9 18. Brown JB, Pedula K, Barzilay J et al. lactic acidosis rates in type 2 diabetics. Diabetes Care 1998; 21: 1659-63 19. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med 2002; 137: 25-33 20. Morin-Papunen LC, Koivunen RM, Ruokonen A et al. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil Steril 1998; 69: 691-696 21. Rittmaster RS. Antiandrogen treatment of polycystic ovary syndrome. Endocrinol Metab Clin 1999; 28: 409-421 22. Ojaniemi M. An adolescent with polycystic ovary syndrome. Eur J Endocrinol 2006; 155 Suppl. S1 49-52
Acarbose: an alternative to metformin for ﬁ rst-line treatment in type 2 diabetes? Most guidelines currently recommend metformin as and acarbose showed a signiﬁ cant rise in GLP-1 Published Online the ﬁ rst-line treatment for type 2 diabetes1–3 on the basis concentrations from 24 weeks onwards, although October 18, 2013of data mostly generated in European populations. the decrease