多囊卵巢综合征的治疗——老问题新看法
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多囊卵巢综合征的治疗——老问题新看法
1.Title:Treatment of the adolescent patient with polycystic ovary syndrome.
Source:Obstet Gynecol Clin North Am. 2003 Jun;30(2):337-52.
Author:Pfeifer SM, Dayal M.
Author Address:Hospital of the University of Pennsylvania, 3400 Spruce Street, 106 Dulles Building, Philadelphia, PA 19104-4283, USA. spfeifer@obgyn.upenn.edu
Abstract:Frequently, a multidisciplinary approach is needed in the management of the adolescent with PCOS. Treatment must be provided in a supportive environment. Because adolescent females are concerned about their appearance any image, short-term treatment goals are usually directed toward the amelioration of hirsutism, acne, and irregular menstruation. Although not immediately concerning to the adolescent, the prevention of long-term sequelae from anovulation and hyperinsulinemia is also important. Multiple concomitant therapies are often necessary to address the variety of symptoms and achieve better results. Recent studies have investigated the role of the insulin-sensitizing agent, metformin, in the treatment of PCOS. Although most studies show a benefit, the conclusions are limited owing to the small numbers of select patients, observational designs, and short durations of follow-up. In addition, there are few data comparing insulin-sensitizing drugs with traditional therapies for PCOS. More long-term, randomized controlled trials are needed to determine the utility of insulin-sensitizing agents, their long-term benefits, and the ideal patient population for their use.
2.Title:Update: The pathogenesis and treatment of PCOS.
Source:Nurse Pract. 2003 Jul;28(7 Pt 1):8-17, 22-3, table of contents; quiz 23-5.
Author:Hill KM.
Irregular menstrual cycles, acne, and hirsutism often cause women to present to a primary care setting. This article demonstrates how to take a careful history, perform a physical examination, and order the laboratory tests necessary to diagnose polycystic ovary syndrome (PCOS). Managing PCOS complaints and maintaining important health issues are also addressed, as well as when to refer to a specialist.
3.Source:Ann N Y Acad Sci. 2003 Nov;997:49-55.
Title:Polycystic ovary syndrome in adolescence.
Author:Driscoll DA.
Author Address:Division of Reproductive Genetics, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, USA. ddriscoll@mail.obgyn.upenn.edu
Polycystic ovary syndrome (PCOS) 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. Irregular menses, anovulatory cycles, and acne are not uncommon in adolescent women. Adolescents with a history of premature pubarche, a family history of PCOS, Caribbean-Hispanic and African-American ancestry, and/or obesity are at risk for PCOS and deserve close surveillance. The laboratory evaluation of the adolescent with suspected PCOS or hyperandrogenism should be individualized based on the history, symptoms, and examination findings. The cornerstone of management of PCOS in adolescence includes either a combination oral contraceptive or progestin. Consideration of insulin-sensitizing agents, antiandrogens, topical treatments for acne, and various treatments for hair removal are dependent on the patient's symptoms and concerns. Healthy eating, regular exercise, and for the overweight adolescent, weight reduction, are encouraged to reduce the risk of cardiovascular disease and type II diabetes mellitus. Numerous studies have shown that weight loss and exercise decrease androgen levels, improve insulin sensitivity, and lead to the resumption of ovulation. Although initial studies suggest that Metformin may be particularly useful for treating the PCOS adolescent with insulin resistance and obesity, additional studies are needed to determine the efficacy and long-term outcome. Management of the adolescent with PCOS is challenging and requires a supportive, multidisciplinary team approach for optimal results.
4.Title：Polycystic ovary syndrome.
Source:Adolesc Med. 1999 Jun;10(2):321-36.
Author:Kahn JA, Gordon CM.
Author Address:Division of Adolescent/Young Adult Medicine, Children's Hospital, Boston, Massachusetts, USA.
Many adolescents present with hirsutism and irregular menses. The challenge for the clinician is to distinguish physiologic anovulatory cycles from true menstrual disorders such as PCOS, and to differentiate PCOS from other causes of hyperandrogenism in hirsute adolescents. Common clinical features seen in adolescents with PCOS include hirsutism, acne, menstrual irregularity, and obesity. Biochemical abnormalities include hyperandrogenism, acyclic estrogen production, LH hypersecretion, decreased levels of SHBG, and hyperinsulinemia. Management strategies for a patient with PCOS include treatment of features which may cause distress to the adolescent, such as hirsutism, acne, and irregular menses, and prevention of long-term sequelae. Oral contraceptive pills, antiandrogens, and cosmetic treatments are used to treat hirsutism, acne, and menstrual irregularity. Oral contraceptive pills or medroxyprogesterone acetate are given to prevent endometrial hyperplasia and carcinoma. Counseling about weight loss and nutrition are essential, as weight loss may improve signs of hyperandrogenism and menstrual irregularity and may prevent NIDDM and cardiovascular disease. Insulin-sensitizing agents show promise in terms of decreasing hyperandrogenism, restoring ovulatory cycles, treating infertility, and preventing long-term sequelae. Finally, it is important to recognize that adolescents with PCOS may experience psychological distress because of the clinical manifestations of hyperandrogenism or when confronted with the information that they have a chronic illness. Psychological support should be available for these young women. Future research is likely to further elucidate the pathophysiology of PCOS, identify candidate genes, and clarify which adolescents are at risk for long-term sequelae. Prospective studies are needed to identify which therapies could potentially reduce the risk of infertility, diabetes, cardiovascular disease, and endometrial carcinoma in young women with PCOS.
5.Title:Polycystic ovary syndrome: new perspective on an old problem.
Source:South Med J. 2001 Feb;94(2):190-6.
Author:Slowey MJ.
Author Address:The Fertility Center, NorthEast Medical Center, Concord, NC, USA.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. New treatment approaches resulting from a refined understanding of the pathophysiology are evolving. The literature shows that PCOS is an endocrinopathy resulting from insulin resistance and the compensatory hyperinsulinemia. This results in adverse effects on multiple organ systems and may result in alteration in serum lipids, anovulation, abnormal uterine bleeding, and infertility. In addition, PCOS may place the patient at long-term risk for the development of type 2 diabetes, hypertension, endometrial cancer, and cardiovascular disease. Oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies. However, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies. Early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.
6.Source:Drugs. 1999;58 Suppl 1:41-6; discussion 75-82.
Title:Insulin resistance, polycystic ovary syndrome and metformin.
Author:Pugeat M, Ducluzeau PH.
Author Address:Clinique Endocrinologique, Hopital de l'Antiquaille and INSERM U329, France. mrichard@cismsun.univ-lyon1.fr
Polycystic ovary syndrome (PCOS) is the most common disorder of ovarian function in premenopausal women. PCOS is characterised by chronic anovulation and androgen excess with clinical manifestation of irregular menstrual cycles, hirsutism and/or acne. Insulin resistance with resultant hyperinsulinaemia, irrespective of excess weight or frank obesity, has been reported in patients with PCOS, and, as insulin has a direct effect on ovarian androgen production in vitro, insulin resistance may play a crucial role in the physiopathology of PCOS. Although the molecular mechanism(s) of insulin resistance in PCOS is unclear, excessive insulin-independent serine phosphorylation of the beta subunit of the insulin receptor, as reported in some patients with PCOS, has been put forward as a new mechanism for insulin resistance. Insulin-sensitising agents have recently been investigated for their role in the short term treatment of insulin resistance in PCOS. Controlled studies have shown that metformin administration, by promoting bodyweight loss, can decrease fasting and stimulated plasma insulin levels. However, other studies have shown metformin 500 mg 3 times daily to decrease insulin secretion and to reduce ovarian production of 17alpha-hydroxyprogesterone with recovery of spontaneous or clomifene-induced ovulation, independently of weight loss. These findings suggest a new indication for metformin and present insulin-sensitising agents as a novel approach in the treatment of ovarian hyperandrogenism and abnormal ovulation in PCOS. They also suggest that long term administration of metformin might be helpful in treating insulin resistance, thus reducing risks of type 2 (non-insulin-dependent) diabetes and cardiovascular disease in these patients.
7.Source:Endocrinol Metab Clin North Am. 1988 Dec;17(4):785-813.
Title:Evaluation and therapy of polycystic ovarian syndrome.
Author:Loy R, Seibel MM.
Author Address:Department of Obstetrics and Gynecology, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts.
The amenorrhea associated with bilateral polycystic ovaries, described by Stein and Leventhal, actually represents a syndrome involving various organs and systems. Clinically, this symptom complex commonly presents as menstrual disturbances, infertility, excessive body weight, and hirsutism. An understanding of the pathophysiology that underlies these symptoms provides a logical basis for evaluation and treatment of the syndrome. The diagnostic approach may involve biochemical determinations (baseline, stimulated, and suppressed) and radiologic testing. Therapy is directed at chronic anovulation, the hyperandrogenism responsible for hirsutism and acne, and the prophylaxis against endometrial and breast carcinomas. Ovulation can be induced with various agents, many of which have a risk of ovarian hyperstimulation in the PCOD patient. The use of GnRH agonists with HMG or FSH for ovulation induction will probably increase in the future. Although classic wedge resection has little place in modern management of PCOD, the recent laparoscopic ovarian cautery remains largely unstudied with respect to long-term postoperative plasma androgen levels and pelvic adhesions. It is too premature to evaluate this new surgical therapy. Hirsutism is effectively treated with estrogen-progestin combinations, medroxyprogesterone acetate, androgen receptor blockers (spironolactone, cimetidine, cyproterone acetate, and cyproheptadine), and glucocorticoids. To date, the available GnRH agonists have not been found selective enough to be used in the treatment of hirsutism, owing to possible long-term complications. Most medical approaches should include electrolysis for permanent hair removal. At present, gynecologic surgery seems to have little place in the management of hirsutism.
8.Source:Obstet Gynecol Clin North Am. 2000 Sep;27(3):583-95.
Title:Insulin-lowering medications in polycystic ovary syndrome.
Author:Taylor AE.
Author Address:Harvard Medical School, Boston, Massachusetts, USA.
A growing body of evidence suggests that serum hyperinsulinemia contributes to the excess ovarian androgen secretion observed in women with PCOS. As a group, women with PCOS are hyperinsulinemic and insulin resistant when compared with weight-matched normal women, but not all PCOS subjects display clear metabolic defects. The small studies using insulin-sensitizing drugs have demonstrated conclusively that a reduction in serum insulin levels is associated with a reduction of ovarian androgen secretion in PCOS, providing further evidence that hyperinsulinemia contributes to hyperandrogenism by increasing ovarian androgen secretion and reducing SHBG. The improvement of serum androgen levels with multiple different drug classes with different mechanisms of actions suggests an effect mediated by reduction in circulating insulin levels rather than a direct ovarian effect of the drugs. Although the studies published to date have increased understanding of the pathophysiologic mechanisms of PCOS, before these drugs can be recommended as first-line therapy for women, longer term clinical trials are needed to compare their safety and efficacy with other established therapies, such as oral contraceptive pills and antiandrogens. Because of the potential direct and unique beneficial effects of these medications on metabolism, studies must be performed to evaluate their efficacy in combination with other therapies, especially oral contraceptives. It is likely that subsets of patients who cannot tolerate traditional medications will be better managed with insulin sensitizers as first-line therapy; however, to date, the optimal way to identify these subjects is unknown. Whether therapy should be limited to subjects with documented hyperinsulinemia also remains unknown.
9.Source:J Pediatr Endocrinol Metab. 2002 Dec;15 Suppl 5:1367-78.
Title:Detection of insulin resistance and its treatment in adolescents with polycystic ovary syndrome.
Author:Legro RS.
Author Address:Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, PA 17003, USA. rsl1@psu.edu
Polycystic ovary syndrome (PCOS) appears to be a lifelong disorder. The stigmata of insulin resistance, including obesity and premature adrenarche, may be early forms of its presentation. Girls with premature pubarche, characterized by elevated dehydroepiandrosterone levels and hyperinsulinemia, are at high risk for developing the full PCOS phenotype, including ovarian hyperandrogenism and chronic anovulation. Because PCOS is associated with a 40% prevalence of abnormal glucose tolerance, every adolescent patient should be evaluated regularly for glucose intolerance with a 2-hour oral glucose tolerance test and for lipid abnormalities with a fasting lipid profile. The role of insulin-sensitizing medications such as metformin in adolescents with PCOS is unclear; short-term studies suggest that these agents improve circulating androgens and ovulatory frequency. Primary prevention of diabetes mellitus and cardiovascular disease by lifestyle modification, including regular exercise and a balanced diet, is particularly important in adolescents, who have the opportunity to establish healthy habits before entering adulthood. The findings of diabetes prevention trials suggest that these interventions may be more efficacious than pharmacological therapy.
10.Source:Minerva Ginecol. 2002 Apr;54(2):97-114.
Title:Polycystic ovary syndrome. Long term sequelae and management.
Author:Legro RS.
Author Address:Department of Obstetrics and Gynaecology, M.S. Hershey Medical Center Pennsylvania State, University College of Medicine, Hershey, PA, USA. RSL1@psu.edu
Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women and is defined by hyperandrogenic chronic anovulation with the exclusion of secondary causes, such as congenital adrenal hyperplasia or an androgen secreting tumor. PCOS women are uniquely insulin resistant. It is estimated that 5% of the female population is affected. The underlying genetic defect in insulin action is unknown. Obesity aggravates the underlying predisposition to insulin resistance. Diagnostic criteria which focus on menstrual irregularity are more likely to identify insulin resistant women. About 40% of PCOS women display glucose intolerance (either impaired glucose tolerance or type 2 diabetes) in response to an oral glucose challenge. Additionally women display multiple other risk factors for cardiovascular disease including dyslipidemia and elevated circulating inflammatory markers. The lack of a clear etiologic mechanism to the syndrome has led in the past to a multitude of symptom-oriented treatments with few therapies improving all aspects of the endocrine syndrome of PCOS. Recently treatments resulting in improved insulin sensitivity, either through weight loss/exercise programs or pharmaceutical, have been shown to improve both the endocrine and metabolic abnormalities in the syndrome. Anti-diabetic agents in PCOS have been examined in a number of randomized studies which have shown a treatment benefit. Further indications for these agents such as the prevention of pregnancy loss or the conversion to type 2 diabetes still need to be investigated in properly designed studies.
11.Source:Curr Womens Health Rep. 2001 Oct;1(2):124-30.
Title:Early diagnosis, presenting complaints, and management of hyperandrogenism in adolescents.
Author:Schroeder B.
Author Address:Allegheny General Hospital, Department of Obstetrics and Gynecology, 7th Floor South Tower, 320 E. North Avenue, Pittsburgh, PA 15212, USA. bschroed@wpahs.org
Hyperandrogenism in the adolescent is a common problem that may manifest in several ways, and may be the result of numerous underlying problems. This article reviews hirsutism, acne, adrenal hyperplasia, and polycystic ovarian syndrome. Presenting signs and symptoms, as well as underlying pathophysiology and treatment options, are discussed.
12.Source:Int J Clin Pract. 1999 Jul-Aug;53(5):359-62.
Title:Polycystic ovarian syndrome: is community care appropriate?
Author:Gupta S.
Author Address:Department of Gynaecology and Reproductive Health Care, University of Manchester, UK.
In recent years the complexities and heterogeneity of polycystic ovarian syndrome (PCOS) have been recognised. Most PCOS sufferers with amenorrhoea, menstrual dysfunction, hirsutism, acne and infertility can be evaluated and safely managed in primary care. It is prudent to remember that all women with PCOS are at risk of insulin resistance and the associated abnormalities of the insulin resistance syndrome--dyslipidaemia, hypertension, coronary artery disease and diabetes mellitus.
13.Source:Acta Obstet Gynecol Scand. 2001 Aug;80(8):689-96.
Title:Clinical management of PCOS.
Author:Tan WC, Yap C, Tan AS.
Author Address:Department of Obstetrics and Gynecology, Singapore General Hospital, Outram Road, Singapore 169608. aileen-tan@hotmail.com
The polycystic ovary syndrome (PCOS) is a heterogeneous condition with genetic predisposition. It is characterized by a myriad of symptoms including oligomenorrhea or amenorrhea, anovulation or infertility, hirsutism or acne. Insulin resistance appears to be an important factor in PCOS though the lack of an etiology has led to symptom oriented therapy which includes lifestyle modification, the use of cyclical progestagens and antiandrogens. Ovulation induction by drug therapy and ovarian drilling aims to treat subfertility in women with PCOS. Therapeutic approaches to PCOS remain an ongoing source of debate. Insulin sensitizing agents may bring new hope in therapy. Future research is aimed at shedding light on the pathophysiology so as to optimize treatment of women with PCOS.
14.Source:Gynecol Endocrinol. 2002 Aug;16(4):275-84.
Title:Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences.
Author:Falsetti L, Gambera A, Andrico S, Sartori E.
Author Address:Department of Gynecological Endocrinology, University of Brescia, Brescia, Italy.
The aim of this study was to investigate whether the absence or presence of acne or hirsutism in 248 women with polycystic ovary syndrome was associated with different clinical, endocrine, metabolic and ultrasonographic factors. Patients were divided into three groups: 96 (38.7%) without any androgenic symptoms; 94 (37.9%) with only hirsutism; and 58 (23.4%) with only acne. The cycle alterations (oligomenorrhea or amenorrhea) and the echographic ovarian morphology (polycystic or multifollicular ovaries) showed no significant differences between the three groups. Hirsutism was associated with a greater incidence of obesity and insulin resistance, with an increase of 17-hydroxyprogesterone, ovarian and adrenal androgens, 3alpha-androstanediol glucuronide, insulin, insulin-like growth factor-I and low luteinizing hormone, sex hormone binding globulins and insulin-like growth factor binding protein-1 levels. Acne was associated only with the lowest 3alpha-androstanediol glucuronide levels. Therefore, two different pathogenetic mechanisms may play a role in the onset of acne and hirsutism.
15.Source:Ann Pharmacother. 2001 Dec;35(12):1644-7.
Title:Use of metformin in polycystic ovary syndrome.
Author:De Sloover Koch Y, Ernst ME.
Author Address:Division of Clinical and Administrative Pharmacy, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
OBJECTIVE: To review the use of the insulin-sensitizing agent metformin in women with polycystic ovary syndrome (PCOS). DATA SOURCES: Biomedical literature was accessed through MEDLINE (1996-March 2001) and the Iowa Drug Information Service. Key terms included metformin and polycystic ovary syndrome. DATA SYNTHESIS: A number of small clinical studies have examined the use of metformin in the treatment of PCOS. Women treated with metformin demonstrated normalization of endocrine function with minimal adverse effects. CONCLUSIONS: Metformin can be beneficial in normalizing menstrual irregularities and stimulating ovulation in previously anovulatory women. Metformin therapy is well tolerated by the majority of patients and should be considered for use in women with PCOS.
16.Source:Coll Antropol. 2001 Dec;25(2):673-85.
Title:The polycystic ovary syndrome--a medical condition but also an important psychosocial problem.
Author:Eggers S, Kirchengast S.
Author Address:Laboratory of Biological Antropology, Centre of Human Genome Studies, Institute of Bioscience, University of Sao Paulo, Brasil.
PCOS, the leading cause of anovulatory infertility that affects up to one fifth of the female population, is a complex chronic disease of genetic as well as environmental determination, but still unclear etiology. Besides of infertility, PCOS leads to menstrual dysfunctions, hirsutism and obesity--symptoms that are known to cause profound psychosocial distress. The present paper review the problematic of etiology and symptom expression of PCOS, which is not only a disease needing medical treatment but also a psychosocial problem for the affected women. PCOS may not only coinduced by psychosocial factors, the main symptoms of PCOS such as infertility, menstrual dysfunctions, hirsutism and obesity cause by themselves increased psychosocial stress.
17.Source:Adolesc Med. 2002 Feb;13(1):73-88, vi.
Title:Polycystic ovary syndrome in adolescents.
Author:Kent SC, Legro RS.
Author Address:Pennsylvania State University College of Medicine, M S Hershey Medical Center, Hershey, 17003, USA.
Recent findings suggest substantial metabolic sequelae to polycystic ovary syndrome (PCOS), including risk of diabetes and cardiovascular disease. Primary treatment of the metabolic sequelae should be the focus of the clinician. The definition of PCOS has been expanded from a disorder that presents at menarche and ends at menopause to a disorder that may be present from birth to senescence. The earliest recognized PCOS phenotype to date is premature pubarche characterized by excessively elevated levels of dehydroepiandosterone sulfate and hyperinsulinemia. Such girls are at high risk to develop the full PCOS phenotype, including ovarian hyperandrogenism and chronic anovulation. A fasting glucose-to-insulin ratio of<7 is a useful index of insulin resistance in adolescents. However, each patient should be evaluated for glucose intolerance and lipid abnormalities on a regular basis by completing a 2-hour oral glucose tolerance test and a fasting lipid profile. Primary prevention of diabetes and cardiovascular disease by lifestyle modifications, regular exercise, and a balanced diet are of utmost importance, especially in adolescents who have the opportunity to establish healthy habits before entering adulthood. The role of insulin-sensitizing medications is still under study. Although no clinical trials over 6 months in duration have assessed the long-term efficacy of metformin use in adolescents, short-term trials have shown promising effects in lowering insulin secretion, improving insulin sensitivity, restoring normal menstrual cycles, and correcting lipid abnormalities.
18.Source:Hum Reprod. 2002 Apr;17(4):853-6.
Title:Should patients with polycystic ovarian syndrome be treated with metformin? A note of cautious optimism.
Author:Homburg R. Lis
Author Address:Maternity Hospital, Tel Aviv (Sourasky) Medical Centre, Tel Aviv 64239, Israel. homburg@netvision.net.il
Hyperinsulinaemia has proved to be a key link in the enigmatic generation of the symptoms of polycystic ovarian syndrome (PCOS), i.e. anovulatory infertility and the skin stigmata induced by hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinaemia. As obesity exaggerates the expression of the symptoms induced by hyperinsulinaemia, a low calorie diet and lifestyle change resulting in loss of weight for obese women with PCOS is capable of reversing these symptoms. Insulin-sensitizing agents, predominantly metformin, have been examined for their ability, in all patients with PCOS, to achieve similar beneficial changes to those induced by loss of weight in the obese. While the scientific value of many of these studies is questionable and solid evidence of efficiency and safety is not complete, the honourable intent of lowering high insulin levels in this way prompts the bottom line of this debate to strike a note of cautious optimism that insulin-sensitizing agents will be of some clinical usefulness both in the short-term aiding of infertility treatment and, possibly, in the prevention of the long-term sequelae for this troublesome and very prevalent condition.
19.Source:Hum Reprod. 2002 Aug;17(8):2035-42.
Title:Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome.
Author:Amer SA, Gopalan V, Li TC, Ledger WL, Cooke ID.
Author Address:Department of Obstetrics and Gynaecology, University of Sheffield, Jessop Wing, Sheffield Teaching Hospitals, Tree Root Walk, Sheffield S10 2SF, UK. s.amer@sheffield.ac.uk
BACKGROUND: Currently, there is an uncertainty about the impact of laparoscopic ovarian drilling (LOD) on the natural history of polycystic ovarian syndrome (PCOS). This longitudinal follow-up study was undertaken to investigate the long-term effects of LOD. METHODS: The study included 116 anovulatory PCOS women who underwent LOD between 1991 and 1999 (study group) and 34 anovulatory PCOS women diagnosed during the same period but who had not undergone LOD (comparison group). The hospital records were reviewed and questionnaires were sent to all the women. In addition, most women attended a follow-up interview. Clinical data recorded at different intervals of follow-up (short-term,<1 year; medium-term, 1-3 years; and long-term, 4-9 years) included: the menstrual pattern, symptoms relating to hyperandrogenaemia and reproductive history. RESULTS: The proportion of women with regular menstrual cycles increased significantly [relative risk (RR) = 1.6, 95% confidence interval (CI) = 1.4-1.9, P < 0.05] from 8% before LOD to 67% post-operatively. The proportion dropped to 37% (RR = 2.6, 95% CI = 1.8-3.8, P < 0.01) at medium-term follow-up and then increased again to 55% (RR = 2.2, 95% CI = 1.7-2.8, P < 0.01) at long-term follow-up. After LOD, 54/110 women (49%) conceived spontaneously during the first year and 42 (38%) during medium- and long-term follow-up. Among women with hirsutism (n = 43) and acne (n = 25), 10 (23%) and 10 (40%) respectively experienced long-term improvement after LOD. CONCLUSION: LOD produces long-term improvement in menstrual regularity and reproductive performance in about one-third of cases. A modest and sustained improvement in acne and hirsutism can be expected in approximately 40 and approximately 25% of patients respectively.
20.Source:J Obstet Gynaecol Can. 2002 May;24(5):393-401.
Title:Metformin and polycystic ovary syndrome: a literature review.
Author:Awartani KA, Cheung AP.
Author Address:Division of Reproductive Endocrinology and Infertility, University of British Columbia, Vancouver, BC, Canada.
Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects women of reproductive age. Anovulation, menstrual irregularities, hirsutism, and infertility are common clinical presentations. Long-term health concerns such as type II diabetes mellitus and, possibly, cardiovascular disease, have been linked to PCOS. Metformin, an oral hypoglycemic agent, has been recently advocated as treatment for some women with PCOS due to the association of PCOS with hyperinsulinemia. Metformin is utilized as sole therapy for ovulation induction as well as in combination with traditional ovulation-induction therapies. This review identified 23 prospective studies addressing the effects of metformin on PCOS. Because of the heterogeneity of the published reports, only a qualitative assessment of the data was possible. Review of this literature confirms a beneficial role of metformin in reducing insulin resistance in some women with PCOS. Other favourable biochemical effects include reduced free testosterone levels and increased sex hormone-binding globulin (SHBG). Metformin may improve menstrual regularity, leading to spontaneous ovulation, and improve ovarian response to conventional ovulation-induction therapies. There is, however, little evidence supporting the use of metformin to facilitate weight reduction, or improve serum lipids or hirsutism. Further evaluation is required to define the long-term effectiveness of metformin, who will benefit from metformin treatment, and the optimal duration of metformin therapy.
21.Source:Endocr Rev. 2003 Oct;24(5):633-67.
Title:Insulin-lowering agents in the management of polycystic ovary syndrome.
Author:De Leo V, la Marca A, Petraglia F.
Author Address:Department of Pediatrics, Obstetrics, and Reproductive Medicine, Institute of Obstetrics and Gynecology, University of Siena, 53100 Siena, Italy. deleo@unisi.it
Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple specialists together. Gynecologists, endocrinologists, cardiologists, pediatricians, and dermatologists are all concerned with PCOS patients and share research data and design clinical trials to learn more about the syndrome. Insulin resistance is a common feature of PCOS and is more marked in obese women, suggesting that PCOS and obesity have a synergistic effect on the magnitude of the insulin disorder. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism, and metabolic disturbances. Women with PCOS should be evaluated for cardiovascular risk factors, such as lipid profile and blood pressure. Modification of diet and lifestyle should be suggested to those who are obese. Several insulin-lowering agents have been tested in the management of PCOS. In particular, metformin is the only drug currently in widespread clinical use for treatment of PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of menstrual cycle, reduction in hyperandrogenism and in cardiovascular risk factors, and improvement in response to therapies for induction of ovulation.
1.Title:Treatment of the adolescent patient with polycystic ovary syndrome.
Source:Obstet Gynecol Clin North Am. 2003 Jun;30(2):337-52.
Author:Pfeifer SM, Dayal M.
Author Address:Hospital of the University of Pennsylvania, 3400 Spruce Street, 106 Dulles Building, Philadelphia, PA 19104-4283, USA. spfeifer@obgyn.upenn.edu
Abstract:Frequently, a multidisciplinary approach is needed in the management of the adolescent with PCOS. Treatment must be provided in a supportive environment. Because adolescent females are concerned about their appearance any image, short-term treatment goals are usually directed toward the amelioration of hirsutism, acne, and irregular menstruation. Although not immediately concerning to the adolescent, the prevention of long-term sequelae from anovulation and hyperinsulinemia is also important. Multiple concomitant therapies are often necessary to address the variety of symptoms and achieve better results. Recent studies have investigated the role of the insulin-sensitizing agent, metformin, in the treatment of PCOS. Although most studies show a benefit, the conclusions are limited owing to the small numbers of select patients, observational designs, and short durations of follow-up. In addition, there are few data comparing insulin-sensitizing drugs with traditional therapies for PCOS. More long-term, randomized controlled trials are needed to determine the utility of insulin-sensitizing agents, their long-term benefits, and the ideal patient population for their use.
2.Title:Update: The pathogenesis and treatment of PCOS.
Source:Nurse Pract. 2003 Jul;28(7 Pt 1):8-17, 22-3, table of contents; quiz 23-5.
Author:Hill KM.
Irregular menstrual cycles, acne, and hirsutism often cause women to present to a primary care setting. This article demonstrates how to take a careful history, perform a physical examination, and order the laboratory tests necessary to diagnose polycystic ovary syndrome (PCOS). Managing PCOS complaints and maintaining important health issues are also addressed, as well as when to refer to a specialist.
3.Source:Ann N Y Acad Sci. 2003 Nov;997:49-55.
Title:Polycystic ovary syndrome in adolescence.
Author:Driscoll DA.
Author Address:Division of Reproductive Genetics, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, USA. ddriscoll@mail.obgyn.upenn.edu
Polycystic ovary syndrome (PCOS) 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. Irregular menses, anovulatory cycles, and acne are not uncommon in adolescent women. Adolescents with a history of premature pubarche, a family history of PCOS, Caribbean-Hispanic and African-American ancestry, and/or obesity are at risk for PCOS and deserve close surveillance. The laboratory evaluation of the adolescent with suspected PCOS or hyperandrogenism should be individualized based on the history, symptoms, and examination findings. The cornerstone of management of PCOS in adolescence includes either a combination oral contraceptive or progestin. Consideration of insulin-sensitizing agents, antiandrogens, topical treatments for acne, and various treatments for hair removal are dependent on the patient's symptoms and concerns. Healthy eating, regular exercise, and for the overweight adolescent, weight reduction, are encouraged to reduce the risk of cardiovascular disease and type II diabetes mellitus. Numerous studies have shown that weight loss and exercise decrease androgen levels, improve insulin sensitivity, and lead to the resumption of ovulation. Although initial studies suggest that Metformin may be particularly useful for treating the PCOS adolescent with insulin resistance and obesity, additional studies are needed to determine the efficacy and long-term outcome. Management of the adolescent with PCOS is challenging and requires a supportive, multidisciplinary team approach for optimal results.
4.Title：Polycystic ovary syndrome.
Source:Adolesc Med. 1999 Jun;10(2):321-36.
Author:Kahn JA, Gordon CM.
Author Address:Division of Adolescent/Young Adult Medicine, Children's Hospital, Boston, Massachusetts, USA.
Many adolescents present with hirsutism and irregular menses. The challenge for the clinician is to distinguish physiologic anovulatory cycles from true menstrual disorders such as PCOS, and to differentiate PCOS from other causes of hyperandrogenism in hirsute adolescents. Common clinical features seen in adolescents with PCOS include hirsutism, acne, menstrual irregularity, and obesity. Biochemical abnormalities include hyperandrogenism, acyclic estrogen production, LH hypersecretion, decreased levels of SHBG, and hyperinsulinemia. Management strategies for a patient with PCOS include treatment of features which may cause distress to the adolescent, such as hirsutism, acne, and irregular menses, and prevention of long-term sequelae. Oral contraceptive pills, antiandrogens, and cosmetic treatments are used to treat hirsutism, acne, and menstrual irregularity. Oral contraceptive pills or medroxyprogesterone acetate are given to prevent endometrial hyperplasia and carcinoma. Counseling about weight loss and nutrition are essential, as weight loss may improve signs of hyperandrogenism and menstrual irregularity and may prevent NIDDM and cardiovascular disease. Insulin-sensitizing agents show promise in terms of decreasing hyperandrogenism, restoring ovulatory cycles, treating infertility, and preventing long-term sequelae. Finally, it is important to recognize that adolescents with PCOS may experience psychological distress because of the clinical manifestations of hyperandrogenism or when confronted with the information that they have a chronic illness. Psychological support should be available for these young women. Future research is likely to further elucidate the pathophysiology of PCOS, identify candidate genes, and clarify which adolescents are at risk for long-term sequelae. Prospective studies are needed to identify which therapies could potentially reduce the risk of infertility, diabetes, cardiovascular disease, and endometrial carcinoma in young women with PCOS.
5.Title:Polycystic ovary syndrome: new perspective on an old problem.
Source:South Med J. 2001 Feb;94(2):190-6.
Author:Slowey MJ.
Author Address:The Fertility Center, NorthEast Medical Center, Concord, NC, USA.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. New treatment approaches resulting from a refined understanding of the pathophysiology are evolving. The literature shows that PCOS is an endocrinopathy resulting from insulin resistance and the compensatory hyperinsulinemia. This results in adverse effects on multiple organ systems and may result in alteration in serum lipids, anovulation, abnormal uterine bleeding, and infertility. In addition, PCOS may place the patient at long-term risk for the development of type 2 diabetes, hypertension, endometrial cancer, and cardiovascular disease. Oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies. However, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies. Early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.
6.Source:Drugs. 1999;58 Suppl 1:41-6; discussion 75-82.
Title:Insulin resistance, polycystic ovary syndrome and metformin.
Author:Pugeat M, Ducluzeau PH.
Author Address:Clinique Endocrinologique, Hopital de l'Antiquaille and INSERM U329, France. mrichard@cismsun.univ-lyon1.fr
Polycystic ovary syndrome (PCOS) is the most common disorder of ovarian function in premenopausal women. PCOS is characterised by chronic anovulation and androgen excess with clinical manifestation of irregular menstrual cycles, hirsutism and/or acne. Insulin resistance with resultant hyperinsulinaemia, irrespective of excess weight or frank obesity, has been reported in patients with PCOS, and, as insulin has a direct effect on ovarian androgen production in vitro, insulin resistance may play a crucial role in the physiopathology of PCOS. Although the molecular mechanism(s) of insulin resistance in PCOS is unclear, excessive insulin-independent serine phosphorylation of the beta subunit of the insulin receptor, as reported in some patients with PCOS, has been put forward as a new mechanism for insulin resistance. Insulin-sensitising agents have recently been investigated for their role in the short term treatment of insulin resistance in PCOS. Controlled studies have shown that metformin administration, by promoting bodyweight loss, can decrease fasting and stimulated plasma insulin levels. However, other studies have shown metformin 500 mg 3 times daily to decrease insulin secretion and to reduce ovarian production of 17alpha-hydroxyprogesterone with recovery of spontaneous or clomifene-induced ovulation, independently of weight loss. These findings suggest a new indication for metformin and present insulin-sensitising agents as a novel approach in the treatment of ovarian hyperandrogenism and abnormal ovulation in PCOS. They also suggest that long term administration of metformin might be helpful in treating insulin resistance, thus reducing risks of type 2 (non-insulin-dependent) diabetes and cardiovascular disease in these patients.
7.Source:Endocrinol Metab Clin North Am. 1988 Dec;17(4):785-813.
Title:Evaluation and therapy of polycystic ovarian syndrome.
Author:Loy R, Seibel MM.
Author Address:Department of Obstetrics and Gynecology, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts.
The amenorrhea associated with bilateral polycystic ovaries, described by Stein and Leventhal, actually represents a syndrome involving various organs and systems. Clinically, this symptom complex commonly presents as menstrual disturbances, infertility, excessive body weight, and hirsutism. An understanding of the pathophysiology that underlies these symptoms provides a logical basis for evaluation and treatment of the syndrome. The diagnostic approach may involve biochemical determinations (baseline, stimulated, and suppressed) and radiologic testing. Therapy is directed at chronic anovulation, the hyperandrogenism responsible for hirsutism and acne, and the prophylaxis against endometrial and breast carcinomas. Ovulation can be induced with various agents, many of which have a risk of ovarian hyperstimulation in the PCOD patient. The use of GnRH agonists with HMG or FSH for ovulation induction will probably increase in the future. Although classic wedge resection has little place in modern management of PCOD, the recent laparoscopic ovarian cautery remains largely unstudied with respect to long-term postoperative plasma androgen levels and pelvic adhesions. It is too premature to evaluate this new surgical therapy. Hirsutism is effectively treated with estrogen-progestin combinations, medroxyprogesterone acetate, androgen receptor blockers (spironolactone, cimetidine, cyproterone acetate, and cyproheptadine), and glucocorticoids. To date, the available GnRH agonists have not been found selective enough to be used in the treatment of hirsutism, owing to possible long-term complications. Most medical approaches should include electrolysis for permanent hair removal. At present, gynecologic surgery seems to have little place in the management of hirsutism.
8.Source:Obstet Gynecol Clin North Am. 2000 Sep;27(3):583-95.
Title:Insulin-lowering medications in polycystic ovary syndrome.
Author:Taylor AE.
Author Address:Harvard Medical School, Boston, Massachusetts, USA.
A growing body of evidence suggests that serum hyperinsulinemia contributes to the excess ovarian androgen secretion observed in women with PCOS. As a group, women with PCOS are hyperinsulinemic and insulin resistant when compared with weight-matched normal women, but not all PCOS subjects display clear metabolic defects. The small studies using insulin-sensitizing drugs have demonstrated conclusively that a reduction in serum insulin levels is associated with a reduction of ovarian androgen secretion in PCOS, providing further evidence that hyperinsulinemia contributes to hyperandrogenism by increasing ovarian androgen secretion and reducing SHBG. The improvement of serum androgen levels with multiple different drug classes with different mechanisms of actions suggests an effect mediated by reduction in circulating insulin levels rather than a direct ovarian effect of the drugs. Although the studies published to date have increased understanding of the pathophysiologic mechanisms of PCOS, before these drugs can be recommended as first-line therapy for women, longer term clinical trials are needed to compare their safety and efficacy with other established therapies, such as oral contraceptive pills and antiandrogens. Because of the potential direct and unique beneficial effects of these medications on metabolism, studies must be performed to evaluate their efficacy in combination with other therapies, especially oral contraceptives. It is likely that subsets of patients who cannot tolerate traditional medications will be better managed with insulin sensitizers as first-line therapy; however, to date, the optimal way to identify these subjects is unknown. Whether therapy should be limited to subjects with documented hyperinsulinemia also remains unknown.
9.Source:J Pediatr Endocrinol Metab. 2002 Dec;15 Suppl 5:1367-78.
Title:Detection of insulin resistance and its treatment in adolescents with polycystic ovary syndrome.
Author:Legro RS.
Author Address:Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, PA 17003, USA. rsl1@psu.edu
Polycystic ovary syndrome (PCOS) appears to be a lifelong disorder. The stigmata of insulin resistance, including obesity and premature adrenarche, may be early forms of its presentation. Girls with premature pubarche, characterized by elevated dehydroepiandrosterone levels and hyperinsulinemia, are at high risk for developing the full PCOS phenotype, including ovarian hyperandrogenism and chronic anovulation. Because PCOS is associated with a 40% prevalence of abnormal glucose tolerance, every adolescent patient should be evaluated regularly for glucose intolerance with a 2-hour oral glucose tolerance test and for lipid abnormalities with a fasting lipid profile. The role of insulin-sensitizing medications such as metformin in adolescents with PCOS is unclear; short-term studies suggest that these agents improve circulating androgens and ovulatory frequency. Primary prevention of diabetes mellitus and cardiovascular disease by lifestyle modification, including regular exercise and a balanced diet, is particularly important in adolescents, who have the opportunity to establish healthy habits before entering adulthood. The findings of diabetes prevention trials suggest that these interventions may be more efficacious than pharmacological therapy.
10.Source:Minerva Ginecol. 2002 Apr;54(2):97-114.
Title:Polycystic ovary syndrome. Long term sequelae and management.
Author:Legro RS.
Author Address:Department of Obstetrics and Gynaecology, M.S. Hershey Medical Center Pennsylvania State, University College of Medicine, Hershey, PA, USA. RSL1@psu.edu
Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women and is defined by hyperandrogenic chronic anovulation with the exclusion of secondary causes, such as congenital adrenal hyperplasia or an androgen secreting tumor. PCOS women are uniquely insulin resistant. It is estimated that 5% of the female population is affected. The underlying genetic defect in insulin action is unknown. Obesity aggravates the underlying predisposition to insulin resistance. Diagnostic criteria which focus on menstrual irregularity are more likely to identify insulin resistant women. About 40% of PCOS women display glucose intolerance (either impaired glucose tolerance or type 2 diabetes) in response to an oral glucose challenge. Additionally women display multiple other risk factors for cardiovascular disease including dyslipidemia and elevated circulating inflammatory markers. The lack of a clear etiologic mechanism to the syndrome has led in the past to a multitude of symptom-oriented treatments with few therapies improving all aspects of the endocrine syndrome of PCOS. Recently treatments resulting in improved insulin sensitivity, either through weight loss/exercise programs or pharmaceutical, have been shown to improve both the endocrine and metabolic abnormalities in the syndrome. Anti-diabetic agents in PCOS have been examined in a number of randomized studies which have shown a treatment benefit. Further indications for these agents such as the prevention of pregnancy loss or the conversion to type 2 diabetes still need to be investigated in properly designed studies.
11.Source:Curr Womens Health Rep. 2001 Oct;1(2):124-30.
Title:Early diagnosis, presenting complaints, and management of hyperandrogenism in adolescents.
Author:Schroeder B.
Author Address:Allegheny General Hospital, Department of Obstetrics and Gynecology, 7th Floor South Tower, 320 E. North Avenue, Pittsburgh, PA 15212, USA. bschroed@wpahs.org
Hyperandrogenism in the adolescent is a common problem that may manifest in several ways, and may be the result of numerous underlying problems. This article reviews hirsutism, acne, adrenal hyperplasia, and polycystic ovarian syndrome. Presenting signs and symptoms, as well as underlying pathophysiology and treatment options, are discussed.
12.Source:Int J Clin Pract. 1999 Jul-Aug;53(5):359-62.
Title:Polycystic ovarian syndrome: is community care appropriate?
Author:Gupta S.
Author Address:Department of Gynaecology and Reproductive Health Care, University of Manchester, UK.
In recent years the complexities and heterogeneity of polycystic ovarian syndrome (PCOS) have been recognised. Most PCOS sufferers with amenorrhoea, menstrual dysfunction, hirsutism, acne and infertility can be evaluated and safely managed in primary care. It is prudent to remember that all women with PCOS are at risk of insulin resistance and the associated abnormalities of the insulin resistance syndrome--dyslipidaemia, hypertension, coronary artery disease and diabetes mellitus.
13.Source:Acta Obstet Gynecol Scand. 2001 Aug;80(8):689-96.
Title:Clinical management of PCOS.
Author:Tan WC, Yap C, Tan AS.
Author Address:Department of Obstetrics and Gynecology, Singapore General Hospital, Outram Road, Singapore 169608. aileen-tan@hotmail.com
The polycystic ovary syndrome (PCOS) is a heterogeneous condition with genetic predisposition. It is characterized by a myriad of symptoms including oligomenorrhea or amenorrhea, anovulation or infertility, hirsutism or acne. Insulin resistance appears to be an important factor in PCOS though the lack of an etiology has led to symptom oriented therapy which includes lifestyle modification, the use of cyclical progestagens and antiandrogens. Ovulation induction by drug therapy and ovarian drilling aims to treat subfertility in women with PCOS. Therapeutic approaches to PCOS remain an ongoing source of debate. Insulin sensitizing agents may bring new hope in therapy. Future research is aimed at shedding light on the pathophysiology so as to optimize treatment of women with PCOS.
14.Source:Gynecol Endocrinol. 2002 Aug;16(4):275-84.
Title:Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences.
Author:Falsetti L, Gambera A, Andrico S, Sartori E.
Author Address:Department of Gynecological Endocrinology, University of Brescia, Brescia, Italy.
The aim of this study was to investigate whether the absence or presence of acne or hirsutism in 248 women with polycystic ovary syndrome was associated with different clinical, endocrine, metabolic and ultrasonographic factors. Patients were divided into three groups: 96 (38.7%) without any androgenic symptoms; 94 (37.9%) with only hirsutism; and 58 (23.4%) with only acne. The cycle alterations (oligomenorrhea or amenorrhea) and the echographic ovarian morphology (polycystic or multifollicular ovaries) showed no significant differences between the three groups. Hirsutism was associated with a greater incidence of obesity and insulin resistance, with an increase of 17-hydroxyprogesterone, ovarian and adrenal androgens, 3alpha-androstanediol glucuronide, insulin, insulin-like growth factor-I and low luteinizing hormone, sex hormone binding globulins and insulin-like growth factor binding protein-1 levels. Acne was associated only with the lowest 3alpha-androstanediol glucuronide levels. Therefore, two different pathogenetic mechanisms may play a role in the onset of acne and hirsutism.
15.Source:Ann Pharmacother. 2001 Dec;35(12):1644-7.
Title:Use of metformin in polycystic ovary syndrome.
Author:De Sloover Koch Y, Ernst ME.
Author Address:Division of Clinical and Administrative Pharmacy, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
OBJECTIVE: To review the use of the insulin-sensitizing agent metformin in women with polycystic ovary syndrome (PCOS). DATA SOURCES: Biomedical literature was accessed through MEDLINE (1996-March 2001) and the Iowa Drug Information Service. Key terms included metformin and polycystic ovary syndrome. DATA SYNTHESIS: A number of small clinical studies have examined the use of metformin in the treatment of PCOS. Women treated with metformin demonstrated normalization of endocrine function with minimal adverse effects. CONCLUSIONS: Metformin can be beneficial in normalizing menstrual irregularities and stimulating ovulation in previously anovulatory women. Metformin therapy is well tolerated by the majority of patients and should be considered for use in women with PCOS.
16.Source:Coll Antropol. 2001 Dec;25(2):673-85.
Title:The polycystic ovary syndrome--a medical condition but also an important psychosocial problem.
Author:Eggers S, Kirchengast S.
Author Address:Laboratory of Biological Antropology, Centre of Human Genome Studies, Institute of Bioscience, University of Sao Paulo, Brasil.
PCOS, the leading cause of anovulatory infertility that affects up to one fifth of the female population, is a complex chronic disease of genetic as well as environmental determination, but still unclear etiology. Besides of infertility, PCOS leads to menstrual dysfunctions, hirsutism and obesity--symptoms that are known to cause profound psychosocial distress. The present paper review the problematic of etiology and symptom expression of PCOS, which is not only a disease needing medical treatment but also a psychosocial problem for the affected women. PCOS may not only coinduced by psychosocial factors, the main symptoms of PCOS such as infertility, menstrual dysfunctions, hirsutism and obesity cause by themselves increased psychosocial stress.
17.Source:Adolesc Med. 2002 Feb;13(1):73-88, vi.
Title:Polycystic ovary syndrome in adolescents.
Author:Kent SC, Legro RS.
Author Address:Pennsylvania State University College of Medicine, M S Hershey Medical Center, Hershey, 17003, USA.
Recent findings suggest substantial metabolic sequelae to polycystic ovary syndrome (PCOS), including risk of diabetes and cardiovascular disease. Primary treatment of the metabolic sequelae should be the focus of the clinician. The definition of PCOS has been expanded from a disorder that presents at menarche and ends at menopause to a disorder that may be present from birth to senescence. The earliest recognized PCOS phenotype to date is premature pubarche characterized by excessively elevated levels of dehydroepiandosterone sulfate and hyperinsulinemia. Such girls are at high risk to develop the full PCOS phenotype, including ovarian hyperandrogenism and chronic anovulation. A fasting glucose-to-insulin ratio of<7 is a useful index of insulin resistance in adolescents. However, each patient should be evaluated for glucose intolerance and lipid abnormalities on a regular basis by completing a 2-hour oral glucose tolerance test and a fasting lipid profile. Primary prevention of diabetes and cardiovascular disease by lifestyle modifications, regular exercise, and a balanced diet are of utmost importance, especially in adolescents who have the opportunity to establish healthy habits before entering adulthood. The role of insulin-sensitizing medications is still under study. Although no clinical trials over 6 months in duration have assessed the long-term efficacy of metformin use in adolescents, short-term trials have shown promising effects in lowering insulin secretion, improving insulin sensitivity, restoring normal menstrual cycles, and correcting lipid abnormalities.
18.Source:Hum Reprod. 2002 Apr;17(4):853-6.
Title:Should patients with polycystic ovarian syndrome be treated with metformin? A note of cautious optimism.
Author:Homburg R. Lis
Author Address:Maternity Hospital, Tel Aviv (Sourasky) Medical Centre, Tel Aviv 64239, Israel. homburg@netvision.net.il
Hyperinsulinaemia has proved to be a key link in the enigmatic generation of the symptoms of polycystic ovarian syndrome (PCOS), i.e. anovulatory infertility and the skin stigmata induced by hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinaemia. As obesity exaggerates the expression of the symptoms induced by hyperinsulinaemia, a low calorie diet and lifestyle change resulting in loss of weight for obese women with PCOS is capable of reversing these symptoms. Insulin-sensitizing agents, predominantly metformin, have been examined for their ability, in all patients with PCOS, to achieve similar beneficial changes to those induced by loss of weight in the obese. While the scientific value of many of these studies is questionable and solid evidence of efficiency and safety is not complete, the honourable intent of lowering high insulin levels in this way prompts the bottom line of this debate to strike a note of cautious optimism that insulin-sensitizing agents will be of some clinical usefulness both in the short-term aiding of infertility treatment and, possibly, in the prevention of the long-term sequelae for this troublesome and very prevalent condition.
19.Source:Hum Reprod. 2002 Aug;17(8):2035-42.
Title:Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome.
Author:Amer SA, Gopalan V, Li TC, Ledger WL, Cooke ID.
Author Address:Department of Obstetrics and Gynaecology, University of Sheffield, Jessop Wing, Sheffield Teaching Hospitals, Tree Root Walk, Sheffield S10 2SF, UK. s.amer@sheffield.ac.uk
BACKGROUND: Currently, there is an uncertainty about the impact of laparoscopic ovarian drilling (LOD) on the natural history of polycystic ovarian syndrome (PCOS). This longitudinal follow-up study was undertaken to investigate the long-term effects of LOD. METHODS: The study included 116 anovulatory PCOS women who underwent LOD between 1991 and 1999 (study group) and 34 anovulatory PCOS women diagnosed during the same period but who had not undergone LOD (comparison group). The hospital records were reviewed and questionnaires were sent to all the women. In addition, most women attended a follow-up interview. Clinical data recorded at different intervals of follow-up (short-term,<1 year; medium-term, 1-3 years; and long-term, 4-9 years) included: the menstrual pattern, symptoms relating to hyperandrogenaemia and reproductive history. RESULTS: The proportion of women with regular menstrual cycles increased significantly [relative risk (RR) = 1.6, 95% confidence interval (CI) = 1.4-1.9, P < 0.05] from 8% before LOD to 67% post-operatively. The proportion dropped to 37% (RR = 2.6, 95% CI = 1.8-3.8, P < 0.01) at medium-term follow-up and then increased again to 55% (RR = 2.2, 95% CI = 1.7-2.8, P < 0.01) at long-term follow-up. After LOD, 54/110 women (49%) conceived spontaneously during the first year and 42 (38%) during medium- and long-term follow-up. Among women with hirsutism (n = 43) and acne (n = 25), 10 (23%) and 10 (40%) respectively experienced long-term improvement after LOD. CONCLUSION: LOD produces long-term improvement in menstrual regularity and reproductive performance in about one-third of cases. A modest and sustained improvement in acne and hirsutism can be expected in approximately 40 and approximately 25% of patients respectively.
20.Source:J Obstet Gynaecol Can. 2002 May;24(5):393-401.
Title:Metformin and polycystic ovary syndrome: a literature review.
Author:Awartani KA, Cheung AP.
Author Address:Division of Reproductive Endocrinology and Infertility, University of British Columbia, Vancouver, BC, Canada.
Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects women of reproductive age. Anovulation, menstrual irregularities, hirsutism, and infertility are common clinical presentations. Long-term health concerns such as type II diabetes mellitus and, possibly, cardiovascular disease, have been linked to PCOS. Metformin, an oral hypoglycemic agent, has been recently advocated as treatment for some women with PCOS due to the association of PCOS with hyperinsulinemia. Metformin is utilized as sole therapy for ovulation induction as well as in combination with traditional ovulation-induction therapies. This review identified 23 prospective studies addressing the effects of metformin on PCOS. Because of the heterogeneity of the published reports, only a qualitative assessment of the data was possible. Review of this literature confirms a beneficial role of metformin in reducing insulin resistance in some women with PCOS. Other favourable biochemical effects include reduced free testosterone levels and increased sex hormone-binding globulin (SHBG). Metformin may improve menstrual regularity, leading to spontaneous ovulation, and improve ovarian response to conventional ovulation-induction therapies. There is, however, little evidence supporting the use of metformin to facilitate weight reduction, or improve serum lipids or hirsutism. Further evaluation is required to define the long-term effectiveness of metformin, who will benefit from metformin treatment, and the optimal duration of metformin therapy.
21.Source:Endocr Rev. 2003 Oct;24(5):633-67.
Title:Insulin-lowering agents in the management of polycystic ovary syndrome.
Author:De Leo V, la Marca A, Petraglia F.
Author Address:Department of Pediatrics, Obstetrics, and Reproductive Medicine, Institute of Obstetrics and Gynecology, University of Siena, 53100 Siena, Italy. deleo@unisi.it
Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple specialists together. Gynecologists, endocrinologists, cardiologists, pediatricians, and dermatologists are all concerned with PCOS patients and share research data and design clinical trials to learn more about the syndrome. Insulin resistance is a common feature of PCOS and is more marked in obese women, suggesting that PCOS and obesity have a synergistic effect on the magnitude of the insulin disorder. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism, and metabolic disturbances. Women with PCOS should be evaluated for cardiovascular risk factors, such as lipid profile and blood pressure. Modification of diet and lifestyle should be suggested to those who are obese. Several insulin-lowering agents have been tested in the management of PCOS. In particular, metformin is the only drug currently in widespread clinical use for treatment of PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of menstrual cycle, reduction in hyperandrogenism and in cardiovascular risk factors, and improvement in response to therapies for induction of ovulation.
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