LA CONSULTA SEMANAL

 

ABRIL 2001

 

 

CONSULTA

Ovarios Poliquísticos

BJOG 2000 Nov;107(11):1327-38 
The long term health consequences of polycystic ovary syndrome.
Kelly CJ, Connell JM, Cameron IT, Gould GW, Lyall H
University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow. 
Women with polycystic ovary syndrome have both insulin resistance and beta cell dysfunction. Consequently, they are at increased risk of developing diabetes and  cardiovascular disease. Women with polycystic ovary syndrome present to clinicians at a young age and as such offer a unique opportunity to identify insulin resistant patients at an early stage. This enables the modification of risk factors and diagnosis of diabetes before the onset of macro- and micro-vascular symptoms. Increased emphasis should thus be placed on long term risk management and diabetic screening with advice on smoking, exercise and, if appropriate, weight loss. Where possible drugs that exacerbate insulin resistance should be avoided and consideration should be given to the use of insulin sensitising agents, particularly in the obese. 
Publication Types:
Review 
Review, tutorial 


J Pediatr Endocrinol Metab 2000;13 Suppl 5:1311-3 
Searching for the polycystic ovary syndrome genes.
Urbanek M, Legro RS, Driscoll D, Strauss JF, Dunaif A, Spielman RS
National Cooperative Program in Infertility Research, Department of Genetics, University of Pennsylvania, Philadelphia, USA. 
PCOS is a common disorder of unknown etiology. Studies of first-degree relatives of women diagnosed with PCOS suggest familial clustering of the disease. A prospective study of first-degree female relatives of women with PCOS conducted by NCPIR found that 46% of ascertainable sisters of women with PCOS were hyperandrogenemic. NCPIR has conducted linkage and association studies using affected sibling-pair analysis and the transmission/disequilibrium test to explore candidate PCOS genes. These studies point a finger at a region 1 MB centromeric to the insulin receptor gene on chromosome 19. 
Publication Types:
Review 
Review, tutorial 


Am Fam Physician 2000 Sep 1;62(5):1079-88, 1090 [Texto completo]
Polycystic ovary syndrome: it's not just infertility.
Hunter MH, Sterrett JJ
Medical University of South Carolina, Charleston, USA. 
Recent diagnostic and pharmacologic developments have focused renewed attention on polycystic ovary syndrome. Clinical features of the syndrome include anovulation, hyperandrogenism and menstrual dysfunction, but several other abnormalities, including hyperinsulinemia, luteinizing hormone hypersecretion, elevated testosterone levels and acyclic estrogen production, have been documented. Accompanying obesity and lipid abnormalities compound the risk of developing diabetes mellitus or cardiovascular disease, and chronic anovulation increases the risk for endometrial cancer. A careful history and physical examination should guide diagnostic testing. Slowly progressive hyperandrogenic  symptoms with anovulation of peripubertal onset often represent polycystic ovary  syndrome. Treatment goals include symptom management and the identification and  prevention of potential cardiovascular risks. Treatment should take into account the patient's desire for fertility. Advances in transvaginal ultrasonography and infertility treatments, including newer medications, have facilitated assisted reproduction in patients with polycystic ovary syndrome. Ongoing pharmacologic research focusing on the treatment of insulin resistance appears promising in reversing the longterm complications of the syndrome. 
Publication Types:
Review 
Review, tutorial 


Obstet Gynecol Clin North Am 2000 Sep;27(3):583-95 
Insulin-lowering medications in polycystic ovary syndrome.
Taylor AE
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. 
Publication Types:
Review 
Review, tutorial 


Curr Opin Obstet Gynecol 2000 Jun;12(3):169-73 
Polycystic ovary syndrome: a single gene mutation or an evolving set of symptoms.
Ben-Rafael Z, Orvieto R
Department of Obstetrics and Gynecology, Rabin Medical Center, Tel Aviv University, Israel. brafael@internet-zahav.net 
Polycystic ovary syndrome is one of the most common endocrinopathies among women. Nevertheless, there is no one single acceptable definition for this syndrome, its pathophysiology is not completely understood and its etiology remains an enigma. Several studies have examined the genetic basis of polycystic ovary syndrome with varying results, probably caused by the different criteria used to define the syndrome. These studies, together with studies that deal with reclassification of polycystic ovary syndrome, are described in the following review. Furthermore, a simplified alternative approach to this symptom complex is proposed. 
Publication Types:
Review 
Review, tutorial 


Ann Intern Med 2000 Jun 20;132(12):989-93 [Texto completo]
The importance of diagnosing the polycystic ovary syndrome.
Lobo RA, Carmina E
Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. ral35@columbia.edu 
The polycystic ovary syndrome (PCOS) is an extremely common disorder that occurs in 4% to 7% of women of reproductive age. Although PCOS is known to be associated with reproductive morbidity and increased risk for endometrial cancer, diagnosis is especially important because PCOS is now thought to increase metabolic and cardiovascular risks. These risks are strongly linked to insulin resistance and are compounded by the common occurrence of obesity, although insulin resistance and its associated risks are also present in  nonobese women with PCOS. Women with PCOS are at increased risk for impaired  glucose tolerance, type 2 diabetes mellitus, and hypertension. Cardiovascular disease is believed to be more prevalent in women with PCOS, and it has been estimated that such women also have a significantly increased risk for myocardial infarction. Many lipid abnormalities (most notably low high-density lipoprotein cholesterol levels and elevated triglyceride levels) and impaired fibrinolysis are seen in women with PCOS. Early diagnosis of the syndrome and close long-term follow-up and screening for diabetes and cardiovascular disease are warranted. An opportunity exists for preventive therapy, which should improve the reproductive, metabolic, and cardiovascular risks. 
Publication Types:
Review 
Review, tutorial 


Drugs 1999;58 Suppl 1:41-6; discussion 75-82 
Insulin resistance, polycystic ovary syndrome and metformin.
Pugeat M, Ducluzeau PH
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. 
Publication Types:
Review 
Review literature 


Pediatr Clin North Am 1999 Jun;46(3):519-43 
Menstrual disorders in adolescents. Excess androgens and the polycystic ovary syndrome.
Gordon CM
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA. 
The fundamental clinical features of PCOS include hirsutism and menstrual irregularities from the time of menarche. Obesity is present in approximately 50% of these patients, some of whom also carry a diagnosis of NIDDM. The biochemical abnormalities associated with the clinical picture include LH hypersecretion, hyperandrogenism, acyclic estrogen production, subnormal SHBG levels, and hyperinsulinemia. Hirsutism usually progresses slowly in patients with PCOS; however, the clinical presentation can resemble virilizing tumors, late-onset CAH, or Cushing syndrome. Virilization or rapidly progressive hirsutism requires immediate investigation to rule out a virilizing tumor. Goals of therapy for teenage patients include decreasing levels of bioavailable androgen, blockade of androgen action at target tissues, stabilization of the endometrium, and reduction of insulin resistance. Although the original description of PCOS by Stein and Leventhal was published in 1935, the cause of PCOS remains unknown. This reason, coupled with the fact that PCOS-related insulin resistance is an important cause of NIDDM in women, has caused this disorder to become one of interest and active investigation. Future research will likely be able to delineate mechanisms behind the defects of carbohydrate metabolism and ascertain large multigeneration kindreds for linkage analyses to identify affected genes. Future studies are also likely to confirm whether young women with PCOS are at increased risk for cardiovascular disease and other long-term health complications. As new pathophysiologic mechanisms are identified, the promise of new therapies arises, including treatments that could potentially reduce the long-term incidence of adverse health consequences. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1999 Jun;28(2):439-58, viii 
Cardiovascular consequences of polycystic ovary syndrome.
Amowitz LL, Sobel BE
Division of Women's Health, Brigham and Women's Hospital, Boston, Massachusetts, USA. 
Polycystic ovary syndrome (PCOS), a syndrome of hyperandrogenism and anovulation with numerous associated derangements, is typified by a substantially increased incidence of type 2 diabetes mellitus and coronary disease in mid-adult life. A marker of the disorder, and a potential determinant of the macroangiopathy, is insulin resistance. Thus, in addition to altered lipid metabolism, hypertension, hormonal derangements, obesity, and altered coagulation--all of which may contribute to the development of vascular disease--the insulin resistance and dysinsulinemia may underlie impaired fibrinolysis and related derangements within the vessel walls that may be modifiable by attenuation of insulin resistance and amelioration of hyperinsulinemia. 
Publication Types:
Review 
Review, academic 


Endocrinol Metab Clin North Am 1999 Jun;28(2):423-38, viii 
Insulin-lowering therapeutic modalities for polycystic ovary syndrome.
Ehrmann DA
Department of Medicine, Pritzker School of Medicine, University of Chicago, Illinois, USA. 
This article summarizes the relationship between insulin and androgen excess, with a focus on what is known regarding two related issues in polycystic ovary syndrome: (1) defects in insulin secretion in PCOS and their role in the development of glucose intolerance in this population; and (2) pharmacologic interventions designed to attenuate hyperinsulinemia and its sequelae in PCOS. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1999 Jun;28(2):409-21 
Antiandrogen treatment of polycystic ovary syndrome.
Rittmaster RS
Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina, USA. rsr89794@glaxowellcome.com 
Although hirsutism and androgenetic alopecia are cosmetic problems, they can be psychologically devastating for women. Mechanical hair removal may control the cosmetic appearance of hirsutism, but the underlying problem usually continues to progress. Topical therapies for androgenetic alopecia provide for modest improvement at best, and no topical therapy has been shown to be effective for hirsutism. Antiandrogens, combined with ovarian suppression, offer the best hope for the improvement of hirsutism and androgenetic alopecia in women with PCOS. Improvement will occur in most women. Unless the underlying cause of the PCOS is corrected, medical therapy will need to be continued indefinitely. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1999 Jun;28(2):397-408, vii 
Diagnosis of polycystic ovary syndrome.
Chang RJ, Katz SE
Department of Reproductive Medicine, University of California, San Diego, La Jolla, USA. 
The clinical features of polycystic ovary syndrome (PCOS) include hirsutism and irregular menses, which are the results of ovarian hyperandrogenism and chronic, unopposed estrogen secretion. The discovery that most women with PCOS are insulin-resistant and have compensatory hyperinsulinemia, with increased risk for type 2 diabetes mellitus, designates this condition as a reproductive-metabolic disorder. That the symptoms of PCOS may be mimicked by other endocrine disorders of the ovary and adrenal glands warrants careful evaluation to exclude these associated conditions. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1999 Jun;28(2):379-96 
Polycystic ovary syndrome. Phenotype to genotype.
Legro RS
Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, USA. rsl1@psu.edu 
Available studies suggest there is a strong familial component to PCOS regardless of the diagnostic criteria used to ascertain probands and to assign affected status in kindreds. Investigation of all kindred members using the same systematic screen for metabolic and reproductive abnormalities strengthens the validity of conclusions. There is no substitute for direct biometric or biochemical proof of the phenotype. Initial studies by the author and his colleagues suggest that hyperandrogenemia in sisters is a valid phenotype characteristic. Further study is necessary to establish other phenotypes in the families. Large family clusterings of PCOS offer the best opportunity for identifying unique strains of PCOS. These families may represent a homogeneous etiology of the syndrome despite significant phenotypic heterogeneity within a given pedigree. Linkage analysis should be performed between polymorphic markers spaced at regular genetic intervals, and these familial traits may identify critical regions for further investigation. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1999 Jun;28(2):361-78 
Insulin action in the normal and polycystic ovary.
Franks S, Gilling-Smith C, Watson H, Willis D
Department of Reproductive Science and Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, United Kingdom. s.franks@ic.ac.uk 
Insulin has a stimulatory effect on steroidogenesis by granulosa cells of normal and polycystic ovaries and interacts with gonadotropins in an additive or, as in the case of LH, a synergistic manner. These actions seem to be mediated specifically by the insulin receptor rather than by cross-reaction with the type I IGF receptor, even in tissue obtained from women with PCOS with biochemical evidence of insulin resistance. The authors suggest that hyperinsulinemia makes a significant contribution to premature arrest of follicle growth, which is characteristic of anovulation in women with PCOS, and that the interaction of insulin with LH is a key element in this process. Insulin may also have a role in amplifying LH-induced androgen production by theca cells, which may help explain the prominence of symptoms of hyperandrogenism in obese subjects with PCOS. The results of recent clinical studies of insulin-sensitizing agents such as metformin and the thiazoladinedione troglitazone in PCOS have provided encouragement that improvement of insulin sensitivity and consequent lowering of circulating insulin levels by these agents may be of therapeutic value in the management of both anovulation and hirsutism. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1999 Jun;28(2):341-59 
Insulin action in the polycystic ovary syndrome.
Dunaif A
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. adunaif@bics.bwh.harvard.edu 
Research on insulin action in PCOS has been intensive after the identification of insulin resistance as a feature of the syndrome in 1980. It is now clear that PCOS is a metabolic as well as a reproductive disorder and an important cause of type 2 diabetes mellitus in women. The cellular and molecular mechanisms of insulin resistance in PCOS are distinct from those in other insulin resistance syndromes. Elucidating these mechanisms promises to provide considerable insight into insulin receptor signal specificity. Conversely, insulin resistance is now known to have an important role in the pathogenesis of the reproductive disturbances of PCOS. It is thought that one or several genetic defects may cause both the insulin resistance and reproductive abnormalities characteristic of PCOS. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1999 Jun;28(2):325-39, vi 
Growth factor action on ovarian function in polycystic ovary syndrome.
Giudice LC
Department of Gynecology and Obstetrics, Stanford University Medical Center, California, USA. 
Insulin-like growth factors, their receptors, binding proteins, and binding protein proteases are important in normal and abnormal ovarian follicle development. IGFs stimulate ovarian cellular mitosis and steroidogenesis and inhibit apoptosis. Patterns of expression of IGF family members are characteristic of whether follicles are estrogen- or androgen-dominant. The PCOS follicle is androgen-dominant but does not appear to be atretic and has characteristic IGF family expression. Available data strongly support an intraovarian, as opposed to endocrine, role for this growth factor family in ovarian follicle growth, steroidogenesis, and atresia. 
Publication Types:
Review 
Review, academic 


Endocrinol Metab Clin North Am 1999 Jun;28(2):295-324 
Neuroendocrine aspects of polycystic ovary syndrome.
Marshall JC, Eagleson CA
Department of Medicine, University of Virginia, School of Medicine, Charlottesville, USA. 
A series of investigations have emphasized the heterogeneous nature of the clinical condition known as PCOS and have delineated several factors that may contribute to the hyperandrogenemia and anovulation in this condition. Currently, it remains unclear whether intrinsic abnormalities of ovarian steroidogenesis, the effects of hyperinsulinemia in augmenting LH stimulation of ovarian androgen production, and the persistent rapid frequency of LH/GnRH secretion are primary factors in all patients. Indeed, these factors may have variable roles in different patients, all of whom present with the clinical syndrome of PCOS. A consensus has emerged that abnormalities in the neuroendocrine control of GnRH secretion exist in a significant subset of patients and lead to persistent hypersecretion of LH, which seems to be an important component of the syndrome, particularly in nonobese patients. The relative frequency of primary abnormalities in the regulation of GnRH secretion versus secondary changes reflecting altered circulating concentrations of ovarian steroid remains uncertain. No clear evidence exists for an underlying neuroendocrine abnormality of GnRH regulation in all patients. The recent data showing insensitivity of the hypothalamic GnRH pulse generator to E2 progesterone feedback have suggested potential mechanisms that may explain the abnormalities of GnRH secretion seen in adolescent girls in whom the clinical syndrome of PCOS is destined to develop. Further studies are required in adolescents to establish whether GnRH regulation is impaired during puberty or whether data in adults simply reflect the long-term effects of elevated androgens, estrogens, or other hormones on the hypothalamus. Studies in carefully delineated subgroups of patients with PCOS are needed to establish these points, with a long-term goal of providing patients with improved methods of inducing ovulation and reducing hyperandrogenemia. 
Publication Types:
Review 
Review, academic 


Endocrinol Metab Clin North Am 1999 Jun;28(2):265-93 
Ovarian and adrenal function in polycystic ovary syndrome.
Rosenfield RL
Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Illinois. 
Androgens are secreted by both the ovaries and adrenal glands in response to their respective trophic hormones LH and ACTH. Androgens in women are not specifically under negative feedback control by these pituitary hormones because they are by-products of estradiol and cortisol secretion. Rather, androgen secretion seems to be regulated mostly by intraglandular mechanisms. Functional ovarian hyperandrogenism is found in about 70% of patients with PCOS. It is characterized by excessive secretion of 17-hydroxyprogesterone in response to GnRH agonist or hCG stimulation. Failure of dexamethasone to suppress plasma free testosterone normally in the presence of normal adrenocortical suppression is also typical. Functional adrenal hyperandrogenism is found in about half of patients with PCOS. It is most often characterized by moderately increased secretion of the 17-ketosteroid DHEA in response to ACTH. The most likely cause of the excessive androgen secretion by both glands seems to be abnormal regulation (dysregulation) of the 17-hydroxylase and 17,20-lyase activities of P-450c17, the rate-limiting step in androgen biosynthesis. There are also subtle generalized disturbances of steroid metabolism, including tendencies toward excessive estrogen and cortisol secretion. The cause of dysregulation of steroidogenesis is unknown. The hyperinsulinemia that is compensatory for resistance to the glucose-metabolic effect of insulin seems to have a role in many cases. In most cases, intrinsic intraovarian or intra-adrenal autocrine or paracrine regulatory mechanisms are most likely malfunctioning. 
Publication Types:
Review 
Review, academic 


Endocrinol Metab Clin North Am 1999 Jun;28(2):247-63 
The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks.
Solomon CG
Harvard Medical School, Boston, Massachusetts, USA. 
Polycystic ovary syndrome is a common problem affecting approximately 5% of women of reproductive age when defined by clinical features of anovulation and hyperandrogenism. Metabolic derangements associated with this condition may predispose to a range of diseases with attendant morbidity and mortality risks. In general, available data support significantly increased rates of type II diabetes mellitus, dyslipidemia, and endometrial cancer in PCOS that are not completely explained by obesity; data also suggest that rates of hypertension, gestational diabetes, and pregnancy-induced hypertension may likewise be increased, although the extent to which obesity mediates these risks is not clear. The increased prevalence of several cardiovascular risk factors in PCOS and limited cross-sectional data suggest that cardiovascular disease should be more likely in PCOS, but prospective data are lacking to confirm this supposition. Limited data have suggested an association between PCOS and ovarian cancer risk and require further study. The present data do not support an increased risk for breast cancer in this condition. Long-term prospective data are clearly needed to better delineate the nature and magnitude of disease risks associated with PCOS, with appropriate adjustment for associated obesity. Such information is a necessary background for understanding the role of established and emerging PCOS therapies, including oral contraceptives, intermittent progesterone, ovulation induction agents, and insulin sensitizers, in modifying such risks. In the meantime, close follow-up of women with PCOS and encouragement of lifestyle practices likely to reduce disease risks, such as regular exercise and weight control, should be standard practice. 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1998 Dec;27(4):877-902, ix 
Polycystic ovary syndrome.
Taylor AE
Harvard Medical School, Boston, Massachusetts, USA. 
Polycystic ovary syndrome is a syndrome and not a disease. It reflects multiple potential etiologies and variable clinical presentations that are reviewed in this article. In addition to menstrual dysfunction and hyperandrogenism, women with polycystic ovary syndrome also may have hypothalamic-pituitary abnormalities, polycystic ovaries on pelvic ultrasonography, infertility, obesity, and insulin resistance. A familial pattern occurs in some cases, suggesting a genetic component to the disorder. The three major pathophysiologic hypotheses that have been proposed to explain the clinical findings of the disorder as well as treatment options are reviewed in this article. 
Publication Types:
Review 
Review, academic 


Am J Obstet Gynecol 1998 Dec;179(6 Pt 2):S109-S113 
The obstetrician-gynecologist's role in the practical management of polycystic ovary syndrome.
Berga SL
Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, The University of Pittsburgh, Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA. 
Women with polycystic ovary syndrome come to the gynecologist with a variety of symptoms, including menstrual irregularities, hirsutism, acne, weight gain, obesity, and infertility. An accurate diagnosis requires both confirmation of signs and symptoms of polycystic ovary syndrome and exclusion of other disorders. Once the diagnosis of polycystic ovary syndrome has been established, the presence of concomitant conditions, such as hypertension, dyslipidemia, and diabetes, must be assessed. Because the cause of polycystic ovary syndrome is not clear, treatment options have focused on symptom management. Such treatment options include oral contraceptives, gonadotropin-releasing hormone analogs with "add-back" hormone regimens, antiandrogens, ovulation-inducing agents, electrolysis, nutritional and weight loss counseling, exercise, laparoscopic ovarian drilling, and glucocorticoids. Pathogenic considerations, risk factor assessments, and treatment objectives combine to determine the choice of therapies. It is not clear whether insulin resistance is clinically important or causal in polycystic ovary syndrome symptom complex in all affected women. Polycystic ovary syndrome may be the final common expression of a variety of metabolic or neuroendocrine perturbations. If insulin resistance is a universal feature, it would make sense to treat with an insulin-sensitizing agent in the expectation that symptoms would resolve or improve. If insulin resistance is not the main etiologic factor, however, then insulin-sensitizing agents would be useful as adjunctive agents only for women with clinically important insulin resistance (eg, patients with polycystic ovary syndrome in whom insulin resistance causes hyperglycemia). In such cases an insulin-sensitizing agent could be instituted along with a program of weight loss and exercise. 
Publication Types:
Review 
Review, tutorial 


Am J Obstet Gynecol 1998 Dec;179(6 Pt 2):S101-S108 
Polycystic ovary syndrome: current and future treatment paradigms.
Legro RS
Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. 
Polycystic ovary syndrome is characterized by excess levels of circulating androgens and by chronic anovulation. Although the fundamental pathophysiologic defect has not been determined, women with polycystic ovary syndrome are known to be uniquely insulin resistant. Obesity in polycystic ovary syndrome aggravates the underlying predisposition towards insulin resistance. Diagnostic criteria that focus on menstrual irregularity are more likely to discriminate insulin-resistant women than are such criteria as abnormal gonadotropin secretion or ovarian morphologic characteristics. About 40% of patients with polycystic ovary syndrome demonstrate glucose intolerance (either impaired glucose tolerance or type 2 diabetes) in response to an oral glucose challenge. The lack of a clear causal mechanism in the syndrome has led to a multitude of symptom-oriented treatments, with few therapies improving all aspects of the endocrine abnormalities associated with polycystic ovary syndrome. Many of these therapies-such as ovulation induction with medical agents-hold increased risks for women with polycystic ovary syndrome, including ovarian hyperstimulation syndrome and multiple gestation. Empirical studies of interventions that improve insulin sensitivity in polycystic ovary syndrome (either weight loss and diet programs or pharmaceutical agents) have been shown to improve the endocrine abnormalities in the syndrome. Initial results with antidiabetic agents (specifically insulin-sensitizing agents) are promising but need to be confirmed with larger, randomized studies. 
Publication Types:
Review 
Review, tutorial 


Am J Obstet Gynecol 1998 Dec;179(6 Pt 2):S89-S93 
Polycystic ovary syndrome: symptomatology, pathophysiology, and epidemiology.
Guzick D
Department of Obstetrics and Gynecology, University of Rochester, Rochester, New York, USA. 
Women with polycystic ovary syndrome seek health care for 3 major reasons: infertility, menstrual irregularity, and androgen excess. The infertility is associated with anovulation. The menstrual irregularity is typically chronic, beginning with menarche. Although amenorrhea may sometimes occur, the more common presentation is irregular bleeding characteristic of anovulation. Androgen excess may be manifested by varying degrees of hirsutism. Patients may also report acne. The rapid development of virilizing signs, such as deepening of the voice, increased muscle mass, and temporal balding, should prompt a search for a tumor and lead one away from a diagnosis of polycystic ovary syndrome. Typically treatment is directed at alleviating the symptoms: ovulation induction for infertility, oral contraceptives or a progestin for menstrual irregularity, and oral contraceptives or spironolactone for hirsutism. On the basis of recent epidemiologic data suggestive of increased cardiovascular risk among women with polycystic ovary syndrome, such treatment might be complemented by a long-term approach that addresses the underlying pathophysiology of insulin resistance. 
Publication Types:
Review 
Review, tutorial 


BMJ 1998 Aug 1;317(7154):329-32 [Texto completo]
Polycystic ovarian syndrome: the metabolic syndrome comes to gynaecology.
Hopkinson ZE, Sattar N, Fleming R, Greer IA
University Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary University NHS Trust, Glasgow G31 2ER. z.hopkinson@clinmed.gla.ac.uk 
Publication Types:
Review 
Review, tutorial 


Endocrinol Metab Clin North Am 1997 Dec;26(4):893-912 
Polycystic ovary syndrome.
Goudas VT, Dumesic DA
Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. 
The cardinal clinical features of PCOS are hirsutism and menstrual irregularity from anovulation. Obesity occurs in approximately 50% of hyperandrogenic anovulatory women, some of whom also have non-insulin-dependent diabetes mellitus. Underlying these clinical findings are several biochemical abnormalities, including LH hypersecretion, hyperandrogenism, acyclic estrogen production, decreased SHBG capacity, and hyperinsulinemia, all of which contribute to increased ovarian production of androgens, particularly T. A fundamental mechanism of ovarian hyperandrogenism in PCOS is LH hypersecretion. Whether the central nervous system is a possible locus for initiating LH hypersecretion remains unclear, because exaggerated LH secretion is temporarily reversed by induced ovulatory cycles or physiologic luteal concentrations of progesterone. On the other hand, desynchronization of pulsatile LH secretion from sleep in girls with PCOS and an exaggerated (e.g., masculinized) early LH response to GnRHa testing in women with hyperandrogenic anovulation and congenital adrenal virilizing disorders suggest that events occurring before puberty, perhaps during fetal life, may irreversibly alter neuroendocrine function. Hyperinsulinemia from insulin resistance is an important regulatory mechanism governing ovarian hyperandrogenism. Hyperinsulinemia in hyperandrogenic anovulatory women potentiates ovarian hyperandrogenism by enhancing LH secretion; potentiating 17-hydroxylase and, to a lesser extent, 17,20-lyase activity; and suppressing SHBG capacity. It is a key component of hyperandrogenic anovulation caused by a type of insulin resistance that in independent and additive to that of obesity alone. Although the mechanisms governing insulin action on ovarian steroidogenesis are unknown, abnormalities of intracellular insulin signaling or cytochrome P450c 17[alpha] activity may render the 17-hydroxylase/17,20-lyase enzyme complex more sensitive to insulin. Hyperinsulinemia in hyperandrogenic anovulatory women is accompanied by upper-body obesity characterized by an increased amount of abdominal fat. Upper-body obesity is an important independent risk factor for CVD and diabetes. Although genetic and environmental factors affect fat distribution, sex steroids, particularly androgens, regulate lipid metabolism, suggesting yet another link between the hormonal and metabolic abnormalities of hyperandrogenic anovulation. A careful history and physical examination guide the extent of diagnostic testing. Slowly progressive hirsutism with anovulation of peripubertal onset usually reflects hyperandrogenic anovulation. This type of clinical presentation requires an evaluation to rule out other endocrinopathies (e.g., virilizing tumors, adult-onset CAH, hyperprolactinemia, and Cushing's syndrome). Virilization or severe rapidly progressive hirsutism requires immediate investigation to rule out a possible virilizing tumor. The ultimate goals of therapy for hyperandrogenic anovulatory women are to normalize the endometrium, antagonize androgen action at target tissues, reduce insulin resistance, and correct anovulation, if necessary. 
Publication Types:
Review 
Review, tutorial 


N Engl J Med 1995 Sep 28;333(13):853-61 
Polycystic ovary syndrome.
Franks S
Department of Obstetrics and Gynaecology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, University of London, United Kingdom. 
Publication Types:
Review 
Review, tutorial

Envia tu Sugerencia