Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Polycystic ovary syndrome. 1037 Jul 13

Polycystic ovary syndrome has been viewed primarily as a gynecologic disorder requiring medical intervention to control irregular bleeding, relieve chronic anovulation, and facilitate pregnancy. A large body of evidence has demonstrated an association between insulin resistance and polycystic ovary syndrome. The former condition has an established link with long-term macrovascular diseases such as type 2 diabetes mellitus, hypertension, and atherosclerotic heart disease, consequences that also are observed in women with polycystic ovary syndrome. In addition, chronic anovulation predisposes women to endometrial hyperplasia and carcinoma. The purpose of this review is to examine the clinical course of this syndrome, which spans adolescence through menopause, and suggest a simple and cost-effective diagnostic evaluation to screen the large numbers of women who may be affected. Therapy, which should be individualized, should incorporate steroid hormones, antiandrogens, and insulin-sensitizing agents. Weight loss by way of reduced carbohydrate intake and gentle exercise is the most important intervention; this step alone can restore menstrual cyclicity and fertility, and provide long-term prevention against diabetes and heart disease. Treatment alternatives should be directed initially toward the most compelling symptom. Longitudinal care is of paramount importance to provide protection from long-term sequelae.
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PMID:Current perspectives in polycystic ovary syndrome. 1531 31

Polycystic ovary syndrome (PCOS) is a syndrome, which can be defined as a group of recognisable patterns of symptoms or abnormalities that indicate a particular medical situation. The current definition of PCOS requires the presence of two of the following three conditions: (i) oligo- and/or anovulation; (ii) clinical and/or biochemical signs of hyperandrogenism; and (iii) polycystic ovaries--and the exclusion of other aetiologies. It is generally accepted that the prevalence of PCOS is approximately 5-10%, and that of polycystic ovaries alone is 21-23%. Other features of PCOS are obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease, obstructive sleep apnoea and infertility. An approach to a patient with possible PCOS should be directed towards making a diagnosis and screening for associated endocrine abnormalities. Therapeutic interventions are directed towards addressing the needs of the patient at present and towards preventing long-term complications of the syndrome. Body mass index, which is a primary mediator in the relationship between PCOS and health-related quality of life in obese PCOS adolescents, may play a similar role in other PCOS patients. Any intervention directed at reducing central obesity will not only improve quality of life but also correct hyperinsulinism and improve fertility and lipid and androgen profiles. It is also the only currently available intervention that can have a lifelong impact on reducing possible long-term complications of the syndrome. Lifestyle modification is the cardinal intervention. Pharmacological treatments are available for specific indications. Infertility can be treated with clomifene (clomiphene citrate), metformin, gonadotropins or surgery to the ovaries. Cyproterone (alone or in combination with ethinylestradiol) and spironolactone are the main drugs used in the treatment of hirsutism. Other drugs that can be considered include flutamide, ketoconazole and finasteride. Women with PCOS require ongoing surveillance to detect impaired glucose tolerance, hyperlipidaemia, endometrial hyperplasia and consequent complications. Obese women, in particular, require regular glucose tolerance testing because of the potential for rapid progression from normal to impaired glucose tolerance and diabetes. The focus of this article is the epidemiology, diagnosis and management of this common endocrine disorder. Diagnostic and co-morbid features are discussed separately to facilitate understanding of PCOS. Symptom-directed strategies, as well as short- and long-term goals of treatment, are outlined.
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PMID:Diagnosis and management of polycystic ovary syndrome: a practical guide. 1674 5

Polycystic ovary syndrome (PCOS) is a complex, multifaceted, heterogeneous disorder that affects approximately 5 to 10% of women of reproductive age. It is characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance, hyperinsulinemia, abdominal obesity, hypertension, and dyslipidemia as frequent metabolic traits (metabolic syndrome) that culminate in serious long-term consequences such as type 2 diabetes mellitus, endometrial hyperplasia, and coronary artery disease. It is one of the most common causes of anovulatory infertility. However, the heterogeneous clinical features of PCOS may change throughout the life span, starting from adolescence to postmenopausal age, largely influenced by obesity and metabolic alterations, and the phenotype of women with PCOS is variable, depending on the ethnic background. The etiology of PCOS is yet to be elucidated; however, it is believed that in utero fetal programming may have a significant role in the development of PCOS phenotype in adult life. Though a woman may be genetically predisposed to developing PCOS, it is only the interaction of environmental factors (obesity) with the genetic factors that results in the characteristic metabolic and menstrual disturbances and the final expression of the PCOS phenotype. Irrespective of geographic locations, a rapidly increasing prevalence of polycystic ovarian insulin resistance syndrome, excess body fat, adverse body fat patterning, hypertriglyceridemia, and obesity-related disease, such as diabetes and cardiovascular disease, have been reported in Asian Indians, suggesting that primary prevention strategies should be initiated early in this ethnic group. In lieu of the epidemic increase in the prevalence of obesity and diabetes mellitus in most industrialized countries including China and India owing to Westernization, urbanization, and mechanization, and evidence suggesting a pathogenetic role of obesity in the development of PCOS and related infertility, active intervention to combat the malice of these disorders is warranted. Pharmacologic therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals, and studies in China and India have proved to be effective.
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PMID:Polycystic ovary syndrome in the Indian Subcontinent. 1818 Oct 79

A major achievement from 500 million years of evolution is the establishment of a high secretion rate of dehydroepiandrosterone (DHEA) by the human adrenal glands coupled with the indroduction of menopause which stops secretion of estrogens by the ovary. Cessation of estrogen secretion at menopause eliminates the risks of endometrial hyperplasia and cancer which would result from non-opposed estrogen stimulation during the post-menopausal years. In fact, from the time of menopause, DHEA becomes the exclusive and tissue-specific source of sex steroids for all tissues except the uterus. Intracrinology, a term coined in 1988, describes the local formation, action and inactivation of sex steroids from the inactive sex steroid precursor DHEA. Over the past 25 years most, if not all, the genes encoding the human steroidogenic and steroid-inactivating enzymes have been cloned and sequenced and their enzymatic activity characterized. The problem with DHEA, however, is that its secretion decreases from the age of 30 years and is already decreased, on average, by 60% at time of menopause. In addition, there is a large variability in the circulating levels of DHEA with some post-menopausal women having barely detectable serum concentrations of the steroid while others have normal values. Since there is no feedback mechanism controlling DHEA secretion within 'normal' values, women with low DHEA will remain with such a deficit of sex steroids for their remaining lifetime. Since there is no other significant source of sex steroids after menopause, one can reasonably believe that low DHEA is involved, in association with the aging process, in a series of medical problems classically associated with post-menopause, namely osteoporosis, muscle loss, vaginal atrophy, fat accumulation, hot flashes, skin atrophy, type 2 diabetes, memory loss, cognition loss and possibly Alzheimer's disease. A recent randomized, placebo-controlled study has shown that all the signs and symptoms of vaginal atrophy, a classical problem recognized to be due to the hormone deficiency of menopause, can be rapidly improved or corrected by local administration of DHEA without systemic exposure to estrogens. In addition, the four domains of sexual dysfucntion are improved. For the other problems of menopause, although similar large scale, randomized and placebo-controlled studies usually remain to be performed, the available evidence already strongly suggests that they could be improved, corrected or even prevented by exogenous DHEA. In men, the contribution of adrenal DHEA to the total androgen pool has been measured at 40% in 65-75-year-old men. Such data stress the necessity of blocking both the testicular and adrenal sources of androgens in order to achieve optimal benefits in prostate cancer therapy. On the other hand, the comparable decrease in serum DHEA levels observed in both sexes has less consequence in men who continue to receive a practically constant supply of testicular sex steroids during their whole life. In fact, in men, the appearance of hormone-deficiency symptoms common to women is observed at a later age and with a lower degree of severity. Consequently, DHEA replacement has shown much more easily measurable beneficial effects in women. Most importantly, despite the non-scientific and unfortunate availability of DHEA as a food supplement in the United States, a situation that discourages rigorous clinical trials on the crucial physiological and therapeutic role of DHEA, no serious adverse event related to DHEA has ever been reported in the world literature (thousands of subjects exposed) or in the monitoring of adverse events by the FDA (millions of subjects exposed), thus indicating, as expected from its known physiology, the excellent safety profile of DHEA. With today's knowledge, one can reasonably suggest that DHEA offers the promise of a safe and efficient replacement therapy for the multiple problems related to hormone deficiency after menopause without the risks associated with estrogen-based or any other treatments.
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PMID:DHEA, important source of sex steroids in men and even more in women. 2054 62

Cancer of the endometrium is the most common type of gynecologic cancer in the United States. Vaginal bleeding is the presenting sign in more than 90% of postmenopausal women with endometrial carcinoma. Clinical risk factors for endometrial cancer, including but not limited to age, obesity, use of unopposed estrogen, specific medical comorbidities (eg, polycystic ovary syndrome, type 2 diabetes mellitus, atypical glandular cells on screening cervical cytology), and family history of gynecologic malignancy also should be considered when evaluating postmenopausal bleeding. The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose endometrial carcinoma and endometrial intraepithelial neoplasia. Transvaginal ultrasonography usually is sufficient for an initial evaluation of postmenopausal bleeding if the ultrasound images reveal a thin endometrial echo (less than or equal to 4 mm), given that an endometrial thickness of 4 mm or less has a greater than 99% negative predictive value for endometrial cancer. Transvaginal ultrasonography is a reasonable alternative to endometrial sampling as a first approach in evaluating a postmenopausal woman with an initial episode of bleeding. If blind sampling does not reveal endometrial hyperplasia or malignancy, further testing, such as hysteroscopy with dilation and curettage, is warranted in the evaluation of women with persistent or recurrent bleeding. An endometrial measurement greater than 4 mm that is incidentally discovered in a postmenopausal patient without bleeding need not routinely trigger evaluation, although an individualized assessment based on patient characteristics and risk factors is appropriate. Transvaginal ultrasonography is not an appropriate screening tool for endometrial cancer in postmenopausal women without bleeding.
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PMID:ACOG Committee Opinion No. 734 Summary: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding. 2968 4

Cancer of the endometrium is the most common type of gynecologic cancer in the United States. Vaginal bleeding is the presenting sign in more than 90% of postmenopausal women with endometrial carcinoma. Clinical risk factors for endometrial cancer, including but not limited to age, obesity, use of unopposed estrogen, specific medical comorbidities (eg, polycystic ovary syndrome, type 2 diabetes mellitus, atypical glandular cells on screening cervical cytology), and family history of gynecologic malignancy also should be considered when evaluating postmenopausal bleeding. The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose endometrial carcinoma and endometrial intraepithelial neoplasia. Transvaginal ultrasonography usually is sufficient for an initial evaluation of postmenopausal bleeding if the ultrasound images reveal a thin endometrial echo (less than or equal to 4 mm), given that an endometrial thickness of 4 mm or less has a greater than 99% negative predictive value for endometrial cancer. Transvaginal ultrasonography is a reasonable alternative to endometrial sampling as a first approach in evaluating a postmenopausal woman with an initial episode of bleeding. If blind sampling does not reveal endometrial hyperplasia or malignancy, further testing, such as hysteroscopy with dilation and curettage, is warranted in the evaluation of women with persistent or recurrent bleeding. An endometrial measurement greater than 4 mm that is incidentally discovered in a postmenopausal patient without bleeding need not routinely trigger evaluation, although an individualized assessment based on patient characteristics and risk factors is appropriate. Transvaginal ultrasonography is not an appropriate screening tool for endometrial cancer in postmenopausal women without bleeding.
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PMID:ACOG Committee Opinion No. 734: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding. 2968 9

This review seeks to describe new fertility-sparing endometrial cancer (EC) treatment strategies that take into consideration the medical and general health background of patients. We particularly focus on the application of metformin, which is a biguanide widely prescribed for treatment of type 2 diabetes mellitus. Fertility-sparing treatment using progestin is considered a standard treatment option for patients with atypical endometrial hyperplasia (AEH) and EC who desire to conceive. A previous meta-analysis of fertility-sparing treatments revealed a high remission rate; however, high rates of relapse persisted. Most young patients with AEH and EC who are subjected to fertility-sparing treatment have a background of obesity, insulin resistance and abnormal glucose tolerance complicated with polycystic ovary syndrome. Recently, metformin has been attracting more attention in the field of cancer research. Several in vitro and in vivo reports regarding the efficacy of metformin in EC management have accumulated. Thus far, the efficacy of combining metformin with progestin has been revealed in a single phase II study of medroxyprogesterone acetate in combination with metformin as a fertility-sparing treatment for patients with AEH or EC. In addition to improving the metabolic profile of patients with EC having metabolic disorders, metformin supplementation may improve the long-term oncological outcome of these patients. To date, many clinical trials employing progestin and metformin as a fertility-sparing treatment of AEH and EC are ongoing. In the near future, it is expected that the clinical advantage of metformin progestin combination therapy will be clarified.
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PMID:New therapeutic approaches for the fertility-sparing treatment of endometrial cancer. 3201 21