Polycystic Ovary Syndrome
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Ehrmann's review article on the polycystic ovary syndrome (March 24 issue)1 misses the liver issue. Alanine aminotransferase activity is abnormal in 30 percent of patients with the polycystic ovary syndrome in whom causes other than nonalcoholic fatty liver disease were excluded.2 The high rates of prevalence of impaired glucose tolerance and type 2 diabetes mellitus among patients with the polycystic ovary syndrome confirm that chronic nonalcoholic liver disease and its consequences are an important issue in these patients.3 Accordingly, the use of thiazolidinediones to treat patients with the polycystic ovary syndrome requires serious caution. The Food and Drug Administration recommends that liver enzymes be checked at the start of therapy, quarterly during the first year, and periodically thereafter. Moreover, even though the short-term studies presented look promising, caution would seem to be indicated because long-term therapy with thiazolidinediones in obese mice with diabetes results in severe hepatic centrilobular steatosis.4 Long-term data will be important to obtain from studies of patients with the polycystic ovary syndrome.
Alain Braillon, M.D.
Centre Hospitalier Universitaire
80000 Amiens, France
braillon.alain@chu-amiens.fr
References
Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005;352:1223-1236.
Schwimmer JB, Khorram O, Chiu V, Schwimmer WB. Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 2005;83:494-497.
El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 2004;126:460-468.
Boelsterli UA, Bedoucha M. Toxicological consequences of altered peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in the liver: insights from models of obesity and type 2 diabetes. Biochem Pharmacol 2002;63:1-10.
To the Editor: Autoimmune thyroiditis should be added to the group of disorders associated with the polycystic ovary syndrome. Sex steroid hormones appear to be the most important environmental factors contributing to the development of autoimmune thyroiditis.1 Furthermore, a recent prospective study demonstrated a high prevalence of autoimmune thyroiditis among women with the polycystic ovary syndrome.2 Since hypothyroidism has been shown to make the polycystic ovary syndrome worse,3 physicians should carefully check thyroid function and thyroid-specific autoantibodies in such patients.
Luca Mascitelli, M.D.
Comando Brigata Alpina Julia
33100 Udine, Italy
lumasci@libero.it
Francesca Pezzetta, M.D.
Ospedale di S. Vito al Tagliamento
33078 S. Vito al Tagliamento, Italy
References
Olsen NJ, Kovacs WJ. Gonadal steroids and immunity. Endocr Rev 1996;17:369-384.
Jannsen OE, Mehlmauer N, Hahn S, Offner AH, Gartner R. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol 2004;150:363-369.
Ghosh S, Kabir SN, Pakrashi A, Chatterjee S, Chakravarty B. Subclinical hypothyroidism: a determinant of polycystic ovary syndrome. Horm Res 1993;39:61-66.
To the Editor: We were concerned about Dr. Ehrmann's statement that "there is an increased prevalence of endometrial hyperplasia and carcinoma in women with the polycystic ovary syndrome." The common occurrence of risk factors for endometrial carcinoma, obesity, and type 2 diabetes in patients with the polycystic ovary syndrome does not necessarily suggest that the syndrome is associated with an increased prevalence of endometrial carcinoma. In fact, the recent review of the relevant literature by Hardiman et al.,1 which was mentioned by Dr. Ehrmann to support his statement, did not confirm such an association, and the authors concluded that the evidence of an increased risk of endometrial carcinoma in the polycystic ovary syndrome was incomplete and contradictory.1
Erian Mikhail, M.D.
Dennis Cope, M.D.
Olive View UCLA Medical Center
Sylmar, CA 91342
nmikhail@ladhs.org
References
Hardiman P, Pillay OS, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003;361:1810-1812.
Dr. Ehrmann replies: Dr. Braillon rightly calls attention to the increased prevalence of nonalcoholic steatohepatitis among women with the polycystic ovary syndrome1 and the importance of periodic assessment of hepatic function in women with this syndrome who are taking a thiazolidinedione. However, recent evidence suggests that the thiazolidinediones may attenuate, rather than exacerbate, the biochemical and histologic abnormalities of nonalcoholic steatohepatitis associated with insulin resistance.2 Thus, although the thiazolidinediones are not formally recommended for the treatment of nonalcoholic steatohepatitis associated with the polycystic ovary syndrome, neither are they necessarily contraindicated when nonalcoholic steatohepatitis is present. Prospective studies are needed to clarify the short-term and long-term effects of the thiazolidinediones when nonalcoholic steatohepatitis is present in women with the polycystic ovary syndrome.
Drs. Mascitelli and Pezzetta's assertion that thyroid dysfunction (i.e., autoimmune thyroid disease) and the polycystic ovary syndrome are causally linked must be viewed with caution. Although sex steroids (androgens, estrogens, and progestins) may modulate the immune response in humans,3 these effects are complex and often conflicting. In addition, because both autoimmune thyroid disease and the polycystic ovary syndrome occur commonly in women, a statistical association between these conditions may be evident, but this does not imply causality. Although it is reasonable to recommend the assessment of thyroid function in women with the polycystic ovary syndrome, there is little evidence of a pathogenetic link between these two disorders.
Finally, Drs. Mikhail and Cope are correct in remarking that on the basis of the review by Hardiman et al.,4 data on the risk of endometrial carcinoma among women with the polycystic ovary syndrome are incomplete and contradictory. Yet it must be acknowledged that Hardiman et al. go on to conclude that in the absence of data to confirm the contrary, "there is little choice other than to advise oligomenorrheic women with PCOS [polycystic ovary syndrome] that they may be at increased risk of developing endometrial cancer." I suspect that all would be in agreement with this recommendation.
David A. Ehrmann, M.D.
University of Chicago
Chicago, IL 60637
dehrmann@uchicago.edu
References
Schwimmer JB, Khorram O, Chiu V, Schwimmer WB. Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 2005;83:494-497.
Promrat K, Lutchman G, Uwaifo GI, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004;39:188-196.
Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Update (in press).
Hardiman P, Pillay OS, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003;361:1810-1812.
Alain Braillon, M.D.
Centre Hospitalier Universitaire
80000 Amiens, France
braillon.alain@chu-amiens.fr
References
Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005;352:1223-1236.
Schwimmer JB, Khorram O, Chiu V, Schwimmer WB. Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 2005;83:494-497.
El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 2004;126:460-468.
Boelsterli UA, Bedoucha M. Toxicological consequences of altered peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in the liver: insights from models of obesity and type 2 diabetes. Biochem Pharmacol 2002;63:1-10.
To the Editor: Autoimmune thyroiditis should be added to the group of disorders associated with the polycystic ovary syndrome. Sex steroid hormones appear to be the most important environmental factors contributing to the development of autoimmune thyroiditis.1 Furthermore, a recent prospective study demonstrated a high prevalence of autoimmune thyroiditis among women with the polycystic ovary syndrome.2 Since hypothyroidism has been shown to make the polycystic ovary syndrome worse,3 physicians should carefully check thyroid function and thyroid-specific autoantibodies in such patients.
Luca Mascitelli, M.D.
Comando Brigata Alpina Julia
33100 Udine, Italy
lumasci@libero.it
Francesca Pezzetta, M.D.
Ospedale di S. Vito al Tagliamento
33078 S. Vito al Tagliamento, Italy
References
Olsen NJ, Kovacs WJ. Gonadal steroids and immunity. Endocr Rev 1996;17:369-384.
Jannsen OE, Mehlmauer N, Hahn S, Offner AH, Gartner R. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol 2004;150:363-369.
Ghosh S, Kabir SN, Pakrashi A, Chatterjee S, Chakravarty B. Subclinical hypothyroidism: a determinant of polycystic ovary syndrome. Horm Res 1993;39:61-66.
To the Editor: We were concerned about Dr. Ehrmann's statement that "there is an increased prevalence of endometrial hyperplasia and carcinoma in women with the polycystic ovary syndrome." The common occurrence of risk factors for endometrial carcinoma, obesity, and type 2 diabetes in patients with the polycystic ovary syndrome does not necessarily suggest that the syndrome is associated with an increased prevalence of endometrial carcinoma. In fact, the recent review of the relevant literature by Hardiman et al.,1 which was mentioned by Dr. Ehrmann to support his statement, did not confirm such an association, and the authors concluded that the evidence of an increased risk of endometrial carcinoma in the polycystic ovary syndrome was incomplete and contradictory.1
Erian Mikhail, M.D.
Dennis Cope, M.D.
Olive View UCLA Medical Center
Sylmar, CA 91342
nmikhail@ladhs.org
References
Hardiman P, Pillay OS, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003;361:1810-1812.
Dr. Ehrmann replies: Dr. Braillon rightly calls attention to the increased prevalence of nonalcoholic steatohepatitis among women with the polycystic ovary syndrome1 and the importance of periodic assessment of hepatic function in women with this syndrome who are taking a thiazolidinedione. However, recent evidence suggests that the thiazolidinediones may attenuate, rather than exacerbate, the biochemical and histologic abnormalities of nonalcoholic steatohepatitis associated with insulin resistance.2 Thus, although the thiazolidinediones are not formally recommended for the treatment of nonalcoholic steatohepatitis associated with the polycystic ovary syndrome, neither are they necessarily contraindicated when nonalcoholic steatohepatitis is present. Prospective studies are needed to clarify the short-term and long-term effects of the thiazolidinediones when nonalcoholic steatohepatitis is present in women with the polycystic ovary syndrome.
Drs. Mascitelli and Pezzetta's assertion that thyroid dysfunction (i.e., autoimmune thyroid disease) and the polycystic ovary syndrome are causally linked must be viewed with caution. Although sex steroids (androgens, estrogens, and progestins) may modulate the immune response in humans,3 these effects are complex and often conflicting. In addition, because both autoimmune thyroid disease and the polycystic ovary syndrome occur commonly in women, a statistical association between these conditions may be evident, but this does not imply causality. Although it is reasonable to recommend the assessment of thyroid function in women with the polycystic ovary syndrome, there is little evidence of a pathogenetic link between these two disorders.
Finally, Drs. Mikhail and Cope are correct in remarking that on the basis of the review by Hardiman et al.,4 data on the risk of endometrial carcinoma among women with the polycystic ovary syndrome are incomplete and contradictory. Yet it must be acknowledged that Hardiman et al. go on to conclude that in the absence of data to confirm the contrary, "there is little choice other than to advise oligomenorrheic women with PCOS [polycystic ovary syndrome] that they may be at increased risk of developing endometrial cancer." I suspect that all would be in agreement with this recommendation.
David A. Ehrmann, M.D.
University of Chicago
Chicago, IL 60637
dehrmann@uchicago.edu
References
Schwimmer JB, Khorram O, Chiu V, Schwimmer WB. Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 2005;83:494-497.
Promrat K, Lutchman G, Uwaifo GI, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004;39:188-196.
Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Update (in press).
Hardiman P, Pillay OS, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003;361:1810-1812.