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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long-term (7-year) effects of oral contraceptive steroids including a combination of norethindrone and ethinyl estradiol, a sequential regimen of dimethisterone and ethinyl estradiol, and daily administration of megestrol acetate were studied in female beagle dogs at dose levels of 1, 10, or 25 times the projected human dose levels. The major findings included cystic endometrial hyperplasia and pyometra requiring hysterectomies and alopecia for the norethindrone-ethinyl estradiol and dimethisterone-ethinyl estradiol treated dogs. These groups did not have accentuated mammary development or treatment related hyperplastic or neoplastic changes. For dogs given dimethisterone-ethinylestradiol, numerous acnelike lesions occurred in the skin of the mammary areas. Dogs given the higher dose levels of megestrol acetate had marked mammary stimulation, hyperplastic and neoplastic changes in the mammary glands, and clinical and pathologic changes typical of diabetes mellitus. Mammary changes of nodular hyperplasia, benign tumor, and adenocarcinoma appeared as distinct entitles although constant and intense mammary stimulation may be a common denominator. The relevance of the canine mammary changes to projecting potential tumorigenisis in women is questioned.
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PMID:Problems in evaluating chronic toxicity of contraceptive steroids in dogs. 7 28

The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is the pineal gland involved in the pathogenesis of endometrial carcinoma. 134 18

This review of endometrial cancer summarizes the demographic characteristics of patients with the disease, their hormonal risk factors related to endogenous and exogenous estrogens and medical history, and other risk factors. Endometrial cancer increased in incidence in the US in the early 1970s, but then declined again in the last 2 decades. Possible reasons are classification including estrogen- induced hyperplasia, but also increased use of exogenous estrogens primarily in post-menopausal women, who are the predominant victims. Postmenopausal estrogen usage decreased at the same time. The highest incidence occurs in Polynesian women, although US Caucasians have more endometrial cancer then Blacks or European women. Endometrial cancer is common in women with estrogen-secreting ovarian cancer. Women with polycystic ovaries, where the steroid androstenedione is secreted and converted to estrone in peripheral tissues, but progesterone is lacking, are higher risk for endometrial hyperplasia and cancer. Obese women are also at risk (estimated 20-fold), as they have low sex binding globulin and higher estrogen levels. Any exogenous estrogen, by any route, even if stopped for a week per month confers higher risk for endometrial cancer, as shown by virtually all case control studies. Very little data exists on the actual effect of taking progestins with postmenopausal estrogens. These tumors are less invasive, more differentiated, and often detected earlier than non-estrogen dependent endometrial cancers. Other putative risk factors, e.g., diabetes, hypertension, gall bladder disease, radiation exposure, and family history of breast cancer have no solid evidence for association. Smoking, however, is associated with a lower risk of endometrial cancer.
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PMID:Epidemiology of endometrial cancer. 257 97

Endometrial carcinoma found in patients younger than 50 years of age were analyzed clinicopathologically in comparison with those of other age groups. The results were 1) Out of 150 patients with endometrial carcinoma, 44 (29.3%) were diagnosed in those younger than 50 years of age and 17(11.3%) were under the age of 40. The average age of endometrial cancer was 53.6 years and that of atypical endometrial hyperplasia was 49.2. 2) The majority of these patients (93.4%) had ever complained of vaginal bleeding, whereas those younger than 40 years of age had in 82.4%. 3) History of irregular menstrual cycle was only observed in 25.6% of the patients with the age 50 or older, whereas it was complained of in 61.5% of those among forties and in 56.3% of those younger than 40. 4) Nulliparity was found in 19.8% among 50 and older, whereas 70.4% and 64.7% were seen respectively in those among forties and younger than 40. 5) Hypertension was found more frequently in older patients, but diabetes mellitus and obesity did not correlate with age. 6) Seventy cases (46.7%) has history of receiving screening for cervical cancer without detecting endometrial cancer. 7) Well differentiated adenocarcinoma (G1) and adenoacanthoma was observed frequently in younger age group. Endometrial hyperplasia was often combined with cancer in young women. Having the data above mentioned, importance of screening for endometrial cancer in younger women is discussed.
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PMID:[Clinicopathological analysis of endometrial carcinoma in young women]. 261 74

The clinical and pathological characteristics of endometrial hyperplasia simulating or coexisting with secretory endometrium were studied in 35 cases of women with at least one biopsy diagnosed as secretory endometrium and another biopsy diagnosed as endometrial hyperplasia or neoplasia. The biopsy samples were examined histologically by semiquantitative methods to detect features that could aid in distinguishing secretory endometrium from hyperplastic endometrium existing focally in secretory endometrium or simulating secretory endometrium. Important histologic features were focal architectural abnormalities, epithelial pseudopalisading, a vesicular nuclear appearance, nuclear atypia, mitoses, the presence of metaplastic ciliated and "clear" cells, and a sharp luminal margin indicating absence of cytoplasmic secretion. The distribution of patients' ages fell between that of perimenopausal women with only secretory features on biopsy (curettage) and that of women with hyperplastic endometrium on biopsy. Twenty-nine per cent of the women in the study group had diabetes or hypertension, and 29 per cent had leiomyomata or adenomyosis at eventual hysterectomy. Patients followed up showed persistence of hyperplasia and progression to a more severe degree of cytologic atypia on later biopsy samples. Recommendations are made for improved detection of these hyperplastic changes and for careful follow-up of patients.
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PMID:The significance of secretory features and coincident hyperplastic changes in endometrial biopsy specimens. 361 Jan 33

Synthetic progestins derived from nortestosterone provide a promising contraceptive alternative for women with contraindications for estrogens. Progesterone and synthetic progestins reduce vasodilatation and edema induced by estrogens and stop estrogen-dependent cellular multiplication in target tissue. Progestins have 2 kinds of contraceptive affect: antigonadotropic action at sufficient doses, and peripheral action at lower doses. The cervical mucus is modified in composition and volume, becoming hostile to sperm; the endometrial mucus atrophies; and tubal motility is slowed. High dose progestins are administered from the 5th or 10th to the 25th cycle day, with the earlier date preferred for women with shorter cycles. They are an ideal method for women with endometrial hyperplasia or benign breast disease or histories of breast or uterine cancer, as well as for women over 40 with dysovulatory cycles. Contraindications to high dose progestins include obesity, hypertension, lipid metabolic anomalies, and diabetes. Low dose progestin-only pills are administered at the exact same time each day including during menstruation. They are attractive for some women because they contain no estrogen, a reduced progestin dose causing fewer headaches and less somnolence, and fewer metabolic effects. Low dose progestins are indicated for lactating women, those with contraindications to estrogens such as obesity, hypertension, hyperlipidemia, and diabetes, and those with renal or cardiac insufficiency with valvulopathy. Low dose progestins are also indicated for nulliparas and other women for whom IUDS are contraindicated. Women using low dose progestins should never take drugs that act as enzymatic inductors, which speed hepatic degradation of steroids and reduce their efficiency. A resulting pregnancy is likely to be extrauterine because of slowed tubal transport. The failure rate of low dose progestins ranges from .9-3%, with higher failure rates among younger women. About 30% of users initially experience spotting, which despite its usual disappearance after 2-3 months of use is the most common reason for discontinuing the method. Low dose progestins have no metabolic or vascular effects, but they may cause a relative hyperestrogenism is some users. Other modes of administration of progestin contraception include continuous high doses, never justified solely for contraception. Trimonthly injections of medroxyprogesterone acetate of norethindrone enanthate provide contraception through a long lasting antigonadotropic effect. Metrorrhagia and amenorrhea are among possible side effects. The method is used primarily in developing countries where its ease of use is a major advantage. Subcutaneous implants releasing continuous doses of levonorgestrel provide contraceptive protection for over 5 years. The cumulative failure rate is 1.7 at 5 years. Metabolic tolerance is good. The major side effect is menstrual irregularity.
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PMID:[Progestational contraception]. 365 94

The authors evaluated the diagnostic effectiveness of a triple specimen technique (cyto-histologic) performed by the Perma device. The incidence of endometrial hyperplasia (according to Dallenbach-Hellweg's classification) was estimated in 254 climacteric women selected from outpatients who come spontaneously to the Menopause Clinic of the Obstetrics and Gynecology Department (Bologna University). The selection criterion was the evidence of risk factors for endometrial carcinoma, climacteric bleedings (obesity, late menopause, high blood pressure, diabetes), or endometriotropic estrogen therapy in the postmenopause. Results showed that the cyto-histologic sampling is most useful for diagnosing endometrial hyperplasia and early carcinoma (diagnostic effectiveness: 89.0-93.8%). Also, endometrial hyperplasia was found to have a significant incidence in the group we examined. This incidence was highest in women with climacteric bleedings, secondly in women using high-dose estrogens, and thirdly in women with risk factors for endometrial carcinoma. When evaluating the different kinds of endometrial hyperplasia, we never found adenomatous hyperplasia in women on estrogen therapy. Affinity between histologic and cytologic classes was around 50% in endometrial hyperplasia and 100% in early carcinoma. This emphasizes that both samplings are needed to perform an accurate diagnosis.
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PMID:Cyto-histologic evaluation of the endometrium in climacteric women at risk for endometrial carcinoma. 376 24

Endometrial cancer is the cause of considerable morbidity among women, but the disease has been underrated and its management more casual than its virulence warrants. Endometrial carcinoma is the most frequently diagnosed invasive neoplasm of the female genital tract in the US, and is third in incidence after breast and colonic cancer. The white population of the US has the highest age standardized incidence of endometrial cancer in the world, India and Japan have the lowest, and the European countries occupy intermediate positions. Between 75% and 80% of women diagnosed with endometrial cancer are postmenopausal, and the mean age at diagnosis is about 60 years. In many cases endometrial hyperplasia is misdiagnosed as frank malignancy. The predisposing factors for endometrial cancer seem to be obesity, hypertension, diabetes mellitus or an abnormal glucose tolerance curve, and prolonged or unopposed estrogen stimulation. Raised estrogen levels may occur in the following situations: 1) women with functioning ovarian tumors that produce estrogen; 2) women with polycystic ovarian disease; 3) women with ovarian dysgensis (Turner's syndrome) managed with estrogen replacement therapy; 4) women taking high estrogen sequential oral contraceptives (OCs); and 5) women undergoing estrogen replacement therapy. There is an increased risk of endometrial carcinoma associated with nulliparity. Carcinoma of the endometrium occurs in a variety of subtypes, the most frequent being adenocarcinoma, followed by adenocanthoma, adenosquamous carcinoma, clear cell carcinoma, papillary adenocarcinoma, and secretory carcinoma. Overall 5-year survival rates are 72% for adenocarcinoma, 68% for adenocanthoma, and 26% for adenosquamous carcinoma. The true extent of endometrial cancer can be ascertained only after exploratory laparotomy and then various therapies may be used according to the stage of the disease.
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PMID:Carcinoma of the endometrium. 637 16

This review of the connection between unopposed estrogen therapy for climacteric symptoms and the development of endometrial hyperplasia briefly outlines the history of the association, and then concentrates on clinical classification problems which muddy the attempts to come to a clear understanding of the relationship between estrogen replacement therapy (ERT) and endometrial cancer. Little agreement exists about the definition of endometrial pathology and of the malignant potentials of different types of hyperplasia. This paper classifies 4 types of hyperplasia: 1) cystic hyperplasia, which has the risk of malignant change of less than 2%; 2) adenomatous hyperplasia, which has a risk of malignant change from 12-25%; 3) atypical hyperplasia, which has a malignancy potential of 45%; and 4) carcinoma in situ, which is malignant. The following conditions are discussed as they are associated with endometrial hyperplasia and adenocarcinoma: 1) obesity; 2) anovulation; 3) late menopause; 4) Stein-Leventhal syndrome; 5) functioning ovarian tumors; and 6) diabetes history. In addition hypertension and cancers of the breast and ovary occur more often with endometrial cancer than would be expected by chance. The remainder of the paper discusses the administration of exogenous estrogens unopposed, exogenous progestins, and their concurrent use, especially in controlling menopausal symptoms. Prevention, diagnosis, and treatment of hyperplasia are discussed. In terms of prevention, a study showed that low-dose cyclical Premarin (.625 mg) resulted in an incidence of hyperplasia of 7% and with higher doses (1.25 mg) rose to 15%. The addition of d-norgestrel for 7 days to the high dose of Premarin reduced incidences to 3%, whereas estrogen plus low-dose norethindrone resulted in 0% incidence of cystic hyperplasia. It is recommended that the unopposed use of estrogens be avoided if possible, although short-term therapy up to 6 months is probably safe. Longer term therapy must have added progestogen, and endometrial sampling in the form of Vabra curettage should be performed every year in patients taking unopposed estrogens and every 3 years in patients taking combined estrogen therapy.
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PMID:Oestrogens and endometrial hyperplasia. 699 95

During the past decade the World Health Organization (WHO) has embarked on a $17 million program to study different kinds of contraceptive methods and their effect on maternal health. More than 600 scientists from 85 countries are participating. These investigations have implicated abortion as a factor in miscarriage, perinatal morbidity, and perinatal mortality due to isthmus-cervical inadequacy. It is also implicated in sterility and extrauterine pregnancy, as well as other disorders of pregnancy. Hence WHO emphasizes other birth control methods, in particular the pill. But the birth control pill also has side effects, as this is the first time that hormones have been used not to treat some illness but in healthy women. Their incidence increases with age (after 30-35 years of age) and also is enhanced by smoking, high blood pressure, hyperlipoproteinemia, and diabetes. Oral contraceptives (OCs) also reduce the incidence of benign tumors of the breast, ovarian cysts, iron-deficiency anemia, and rheumatoid arthritis. They have a beneficial effect also in endometriosis, dysfunctional hemorrhages, polyposis and endometrial hyperplasia, ovulatory problems, and inflammatory conditions of the genitals. Many of the longterm effects of these contraceptives are still unknown, such as their influence on cancer or on the fetus. The WHO investigation has shown that 1/2 stop taking the birth control pill after 1 year, and 2/3 after 2 years. Another widespread technique is the IUD, used by over 60 million women. But this causes hemorrhage in some, especially the women of India, Pakistan, and other countries. Work is now being done on ways to minimize the hemorrhage associated with the IUD, to clarify its presence as a cause of inflammatory processes of the genitals, extrauterine pregnancies, and subsequent sterility. The WHO also studied the rhythm method of preventing conception and found that 35% of women ceased employing it after 13 months, while 20% became pregnant. It was decided to work on elucidating new methods of determining the onset of ovulation. The WHO is also studying the use of prostaglandins to interrupt pregnancy. A major task for the future is determining which women are at greatest risk from the various birth control techniques.
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PMID:[Modern methods of regulating generative function]. 733 55


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