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Query: UMLS:C0011849 (diabetes)
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The use of the depot preparations medroxyprogesterone acetate (MPA) (Depo-provera) and norethindrone (Norigest) is discussed. MPA is administered in dosages of 150 mg every 3 months. It inhibits ovulation, probably by affecting cyclical gonadotropin secretion. It also causes atrophy of the endometrium, affects cervical secretions and ciliogenesis. MPA has a Pearl index of .348. Norethindrone works to inhibit ovulation, but its effectiveness is also dependant on changes in cervical secretions. Dosage is 200 mg every 84 days, and it is not as effective as MPA. MPA use usually causes oligoamenorrhea or amenorrhea. Gain in weight, headaches, and nervousness are side effects of MPA use, and it can also affect carbohydrate metabolism. The restoration of fertility after discontinuing MPA use generally takes a few months. MPA is counterindicated for women with unexplained vaginal bleeding, liver function disturbances, and diabetes mellitis. It can be used during the lactation period or in cases of endometriosis. MPA can often be used when the side effects of other contraceptive agents or methods are unacceptable.
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PMID:[Pharmacological and clinical application of progestational hormone depot preparations]. 56 21

The recent literature relating to the pathogenesis of diabetic retinopathy, with or without nephropathy, is critically reviewed. Particular attention is given to the (GH) growth hormone hypothesis. The various procedures of hypophysectomy are discussed including the possible ways of suppressing GH production or overproduction by drugs, especially with (MAP) medroxyprogesterone acetate. Personal results obtained with long-term administration of MAP in depot form on alternate days in 10 patients with advanced retinopathy are described. An inconstant and barely significant suppression of the GH response to insulin-induced hypoglycemia was noted in 6 cases showing that a complete pituitary inactivation had not been achieved. Therefore, the modifications observed in the fundus picture seem to have no relationship with such a condition. The features involved were Microaneurysms and Hemorrhages and Exudates. New vessels and retinitis proliterans were unaffected. Subjective improvement in visual acuity appeared to be more frequent with various possible explanations. MAP was without appreciable effect on the clinical and metabolic course of the diabetes or on renal function in cases of concomitant nephropathy. In light of these preliminary results, further investigation seems to be justified. (author's modified) (summary in ENG).
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PMID:[Trial treatment of diabetic retinopathy by inhibition of pituitary somatotropin secretion with MAP]. 112 48

We have analyzed the inheritance of maturity-onset diabetes of the young (MODY) on chromosome 20 in a large multigeneration family, the R.-W. family, and in two other MODY families. Of the four branches of the R.-W. pedigree which have been studied, two have documented early onset of non-insulin-dependent diabetes mellitus (NIDDM), while there is no evidence of early onset in the other two branches. The early-onset branches have apparently inherited the same D20S16 allele from the affected parent, while another D20S16 allele was inherited in the two branches without evidence of early onset. A test for homogeneity, the M-test, using the results of two-point linkage analysis with D20S16 indicates heterogeneity between early- and late-onset branches of the R.-W. family (P less than or equal to .014). In addition, analysis strongly suggests that MODY as expressed in the EDI and WIS families is unlinked to loci on chromosome 20 (P less than or equal to .018-.004). Comparable results are seen when the data are analyzed by the HOMOG program. Three polymorphic loci-D20S16, D20S17, and ADA--show no recombination with the MODY locus when two-point linkage analysis is used in the early-onset branches of the family. The multipoint lod score in the early-onset branches of the R.-W. family is 10.16, with the most likely location being between D20S4 and D20S17. Multipoint linkage analysis using the CHROMPICS option of the program CRI-MAP has been used to follow inheritance of the MODY disease locus. This analysis has identified two cases of possible nonpenetrance in the early-onset branches of the family (odds of at least 156:1), as determined by the appearance of apparent isolated double crossovers at the MODY locus in these unaffected individuals.
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PMID:Linkage analysis of maturity-onset diabetes of the young (MODY): genetic heterogeneity and nonpenetrance. 153 97

In this article, we analyze the blood pressure (BP) threshold for the start of antihypertensive treatment in insulin-dependent diabetes mellitus (IDDM) patients, with particular emphasis on those with persistent microalbuminuria or proteinuria (incipient and overt nephropathy, respectively). In such individuals, there is a clear increase in the prevalence of hypertension and in actual measured BP values that is not observed in normoalbuminuric patients. In 94 young healthy adults (less than 45 yr of age), average mean +/- SD arterial pressure (MAP; diastolic + 1/3 pulse pressure) was approximately 90.0 +/- 8.1 mmHg, closely corresponding to large population studies. In microalbuminuric IDDM patients, MAP values between approximately 105 and approximately 95 mmHg have been found in different studies, and the level has progressively decreased in various studies between 1984 and 1990 with similar BP-measuring techniques. Somewhat higher values are seen in patients with proteinuria, who are also consistently characterized by reduced glomerular filtration rate (GFR). A clear correlation is found between MAP plotted against the increased rate of microalbuminuria (%/yr) in incipient nephropathy and against fall rate of GFR (ml.min-1.mo-1) in proteinuric patients. In the natural history of renal disease, different cutoff points in MAP for start of progression are observed: greater than 95 mmHg for the start of progression of microalbuminuria and greater than 105 mmHg for the decrease in GFR. During antihypertensive treatment, there is reduction or no progression in microalbuminuria with MAP of approximately 90-95 mmHg and only a limited fall in GFR with MAP of approximately 100 mmHg. However, certain antihypertensive drugs (angiotensin-converting enzyme inhibitors) may have specific renoprotective actions, reducing microalbuminuria at rather low BP levels or even independent of BP reduction. The optimal way of monitoring BP may be by 24-h ambulatory recording.
Diabetes Care 1991 Nov
PMID:Renal factors influencing blood pressure threshold and choice of treatment for hypertension in IDDM. 174 53

Researchers followed 68 women who attended the Family Welfare Clinic at the Kenyatta National Hospital in Nairobi, Kenya to determine if the low estrogen combined oral contraceptive (OC) Microgynon, a progestogen only OC, and Depo-Provera induce changes in the oral glucose test. These women did not take any steroidal contraceptives before entry into the study. Blood glucose levels were significantly higher after 60, 90 and 120 minutes than the control levels for women taking Microgynon. In addition, the mean areas under the glucose curves were substantially elevated after 1, 3, and 6 months above the control (p.002, .005, and .01 respectively). The only significant change in blood glucose levels in women taking the progestogen only OC occurred at 30 minutes after 6 months. Yet the mean areas under the curve were significantly higher than the control after ,1 2, and 3 months (p.005, .05 and .002 respectively). As for Depo-Provera, significantly lowered blood glucose levels only occurred after 1 month at 30, 50, and 90 minutes although no significant changes occurred after 1, 3, and 6 months in the mean areas under the glucose curves. Metabolic change occurred earlier and more often in Microgynon users than progestogen only OC users. This could be due to the progestogen levonorgestrel which has been shown to interrupt glucose metabolism. These changes could possible adversely effect women who are predisposed to developing diabetes, since 1 woman did develop a diabetic curve after 1 month of using Microgynon. Nevertheless no pattern towards abnormal glucose tolerance existed. Standard deviations of areas under the curves indicated that the number of women who develop glucose intolerance may increase with duration of use.
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PMID:The effect of low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test. 214 46

The injection of 25 mg/kg i.p. cyclosporin (CsA) for 3 wk caused marked functional and morphological deteriorations of pancreatic islet cells in Wistar rats that were prevented by the combined administration of p-aminobenzoic acid-N-D-mannoside sodium salt (K-MAP). In this article, the toxic effect of CsA on pancreatic islet cells and the preventive effect of K-MAP on CsA-associated islet cell toxicity were investigated. Prolonged hyperglycemia and depressed insulin secretion after the glucose challenge observed in CsA-treated rats could be prevented by the combined administration of 300 and 900 mg/kg K-MAP. Cytoplasmic vacuolizations and a decrease in the number of mitochondria, intact endoplasmic reticula, secretory granules, and insulin-positive cells, as revealed by peroxidase-antiperoxidase staining, could also be prevented by the administration of 900 mg/kg K-MAP. This preventive effect of K-MAP on CsA-associated islet cell toxicity may suggest the combined use of K-MAP with CsA in pancreas transplantation and treatment of insulin-dependent diabetes.
Diabetes 1989 Jan
PMID:Modulation of prostaglandin metabolism by K-MAP and prevention of toxic effect of cyclosporin on pancreatic islet cells. 264 33

Patients with a history of recurrent candidiasis and who were using Depo-Provera (medroxyprogesterone acetate, DMPA) for contraception were reviewed in order to determine the time relationship between episodes of proven candidiasis, episodes of pruritus vulvae suggestive of this infection (but unproven), and injection of DMPA. Recently, patients were included in the study who had been given DMPA specifically to prevent recurrences of candidiasis even when the drug's contraceptive action was unnecessary, such as after sterilization. In all cases, the infection was initially treated with a vaginal candidacide, most commonly 1 week of an imidazole. The patients ranged in age from 19-37 years at the time of the 1st injection. Diabetes had been eliminated in all the cases. DMPA was given intramuscularly at a dose of 150 mg every 12 weeks. Prior to 1983, an estrogen supplement was prescribed in most cases in an effort to produce monthly menstrual periods. Estrogen supplementation is no longer used routinely, with amenorrhea the aim, although it is occasionally given to women who experience breakthrough bleeding. Candidal infection was considered proven when the branching filaments of the species were seen on a stained vaginal smear or when the species were cultured in a laboratory from a vaginal swab taken a symptomatic patient. With the exception of 2 patients, clinical candidiasis did not occur within the time in which 150 mg of intramuscular DMPA is known to suppress ovulation in all women, i.e., 12 weeks -- except in the presence of exogenous estrogen (cases 1, 2, and 14) and in one case (15) in which the patient had an unplanned conception prior to the injection. Both patients who experienced clinical despite the use of DMPA alone (cases 8 and 13) asked remain on the drug because believe it was responsible for their longest remissions in the past few years. The study seemed to provide evidence that DMPA will prevent a recurrence of clinical candidiasis in many women who are prone to this condition. The study further indicated that estrogens may predispose women to this infection.
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PMID:Depo-Provera in the treatment of recurrent vulvovaginal candidiasis. 294 26

This discussion identifies the risks and benefits of each of the hormonal methods of contraception -- combined estrogen-progesterone oral contraceptive (OCs), progestogen-only pills, and depot progestogen injections. It also explains the use of a profile of risk factors in considering the appropriate prescription for each individual in relation to her contraceptive needs. Information regarding medical risks has come from the consideration of mortality rates in large cohort studies. Looking at categories of the causes of 249 deaths in ever-users of the pill and controls, Layde and colleagues were able to show that there was an excess mortality in the pill group of 40% and that the extra risk was concentrated in cardiovascular causes: myocardial infarctions, cerebral thrombosis, and cerebral hemorrhage constituted the largest proportions. A small proportion of combined OC users may develop clinical hypertension but more suffer a reduction in the high-density lipoprotein (HDL) cholesterol fraction of the blood lipids. Both of these effects tend to increase the risk of cardiovascular complications and both are positively related to the dose of the progestogen components. In prescribing combined OCs, attention needs to be paid to further moves away from the norm towards the extremes: the presence of cardiovascular risk factors and the use of certain longterm medications or the presumptive designation as a "rapid metabolizer." An analysis of progestogen only pill (POP) users in the Oxford-Family Planning Association study confirmed the reasonably low rates of accidental pregnancy in POP users. There is a marked reduction with increasing age, and it is significant that many prescribers are now giving POP to older women for whom combined OCs are contraindicated because of cardiovascular risks. It also seems reasonable to use them in women with some medical disorders, for example, recurrent pulmonary embolism, hypertension, and diabetes. Initially, depot injections of progesterone were developed to provide a long-acting or sustained-release type of drug administration to assist users of the progestogen-only method which, unlike combined OCs, does not make use of regular drug-free intervals. In practice it has been found that the effectiveness against pregnancy is enhanced and the side-effects are increased in giving progestogen by depot injection. The 2 preparations currently licensed in Britain are Depo-Provera (medroxyprogesterone acetate) and Noristerat (norethisterone enanthate). In some cases proper and clear information may not have been given to the patient and proper consent not obtained before giving the drug. This problem is magnified because of the occurrence in some women of disturbed bleeding patterns, especially if given immediately after childbirth or an abortion. Also, in a small proportion of users anovulatory amenorrhea may supervene for some months or even as long as 2 years following depot injection.
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PMID:Hormonal contraceptive methods. 401 68

A follow-up study was conducted with 50 healthy parous volunteer women in India to ascertain the effect of a long-acting progestogen contraceptive on serum enzymes and hepatic function. The women received an intramuscular injection of a long-acting contraceptive, DMPA (depo-medroxyprogesterone acetate), in a dose of 150 mg every 3 months for 2 years. Women with a past history of jaundice, diabetes, hypertension, or eclampsia were excluded from the study. The activity of SGOT, SGPT, and AP (alkaline phosphatase) did not show any change during the longterm treatment. This result would indicate normal hepatic function and the absence of any damage or injury to the liver cells. Activity of serum ACP (acid phosphatase) and AChE (acetylcholinesterase) in red cells did show significant increase, which continued up to the end of the study. Results of the study indicate that DMPA is a suitable contraceptive for use in India, particularly since it does not cause the common side effects associated with oral contraceptives and does not affect liver function.
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PMID:Effect of medroxyprogesterone acetate contraception on human serum enzymes. 611 6

Epidemiologically, an inverse relation between serum HDL-C level (high density lipoprotein cholesterol) and risk for coronary heart disease has been reported. HDL has also been known to serve as a vehicle for transporting cholesterol from the arterial wall to the liver for excretion. However, there are no clinical data for the concept that a drug-decreased serum HDL-C is unfavorable with respect to atherosclerosis and myocardial infarction. This study compares the serum HDL-C level in 23 women who received depot medroxyprogesterone acetate (DMPA) as a 12-weekly injectable progestational contraceptive with that of a comparable control group of 23 IUD users. Both groups were selected on the basis of age, bodyweight, and alcohol consumption. HDL-C and serum triglyceride levels were measured by an enzymatic method. The serum HDL-C level was significantly lower in the DMPA group than in the IUD group (t=4.30, p= 0.001). The difference was attributed to the progestational effect of the DMPA. The lapse of time after a DMPA injection did not affect the serum HDL-C level, an unexpected finding as the average serum MPA level rises steeply during the 1st week after DMPA injection and then declines gradually to a relatively low value after 12 weeks. DMPA should not be prescribed to women with abnormally high risk for atherosclerosis (eg, heavy smokers, and women with adiposity and/or diabetes mellitus).
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PMID:Serum high density lipoprotein cholesterol levels in women using a contraceptive injection of depot-medroxyprogesterone acetate. 744 84


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