The effect of chronic sodium loading and sodium restriction on plasma prostaglandin A, E, and F concentrations in normal humans.

It has been suggested that prostaglandins may be involved in the control of sodium homeostasis. Prostaglandin A and prostaglandin E have been shown to increase renal blood flow and urinary sodium excretion and prostaglandin A has been shown to stimulate aldosterone release. The purpose of this study was to determine the effect of chronic sodium loading and sodium restriction on plasma prostaglandin A, E, and F concentrations. SEVEN NORMAL HUMAN VOLUNTEERS WERE PLACED ON THREE SODIUM INTAKE DIETS: (a) ad lib. sodium intake, (b) high sodium intake, and (c) low sodium intake. Plasma prostaglandin A, E, and F concentrations were measured by radioimmunoassay. Mean prostaglandin A levels on the ad lib. diet were 1.60 ng/ml. Prostaglandin A levels decreased 49% to 0.82 ng/ml on the high sodium intake and increased 34% to 2.14 ng/ml on the low sodium intake. Prostaglandin A levels increased 161% on the low sodium diet in comparison with levels on the high sodium diet. Plasma prostaglandin E and F concentrations did not change significantly during variation in sodium intake. These results show that dietary sodium content markedly effects plasma prostaglandin A levels and that prostaglandins may play a role in the physiologic mechanism of sodium homeostasis.

Hormone levels during prostaglandin F 2 infusions for therapeutic abortion.

PIP: This study determines the effect of prostaglandins (PGs) on fetal-placental hormone production or luteal steroidogenesis early in pregnancy by measuring plasma levels of unconjugated estrone, 17-beta estradiol, estriol, progesterone, 17-hydroxyprogesterone, human chorionic gonadotropin (HCG), and human chorionic somatomammotropin (HCS) in 7 healthy women aged 15-30 years receiving PGF2alpha for therapeutic abortion. The patients were 7-20 weeks pregnant and were all from the Clinical Research Unit of the Yale-New Haven Hospital. 5 patients participated in a dose-response tolerance study in which the drug was given over a 12-hour period at predetermined dose levels from 25-200 mcg/minute. The remaining 2 patients received 50 mcg for 12 consecutive hours, and 2 6-hour periods respectively. Heparinized blood samples were collected prior to the beginning of the infusion, at least hourly during the infusion, and also 24 hours after the beginning of the study. Transabdominal and transcervical catheters were used to monitor intrauterine pressures. A definite decline in estradiol levels (from 50-70% of initial levels) was observed during the PGF2alpha infusions. Plasma levels of unconjugated estriol were found to decline earlier and more markedly than the estradiol levels. 17-hydroxyprogesterone was undetectable in all but 1 patient who was 7 weeks pregnant. There were no significant changes in HCG levels in 4 patients until abortion and or curettage was performed. HCS levels gradually declined in 3 patients during the infusion process. This study shows that PGF2alpha does not exert a luteolytic effect in terminating pregnancy from 7-20 weeks gestation, confirming the study of Wiqvist et.al. Further study of the 1st few weeks of gestation should be done before ruling out the possibility of luteolysis in humans.^ieng

Treatment of seizures with medroxyprogesterone acetate: preliminary report.

Medroxyprogesterone acetate (MPA), a synthetic progesterone, was added to the antiepileptic drug regimen of 14 women who had uncontrolled seizures. Of the 11 women who developed amenorrhea, 7 reported fewer seizures during MPA therapy. Overall reductions in seizure frequency averaged 30% (n = 11), declining from a baseline 8.3 +/- 5.8 seizures per month to 5.1 +/- 4.1 seizures per month (p = 0.02). No serious side effects were encountered, but spotting was common. These preliminary data suggest further evaluation of MPA for catamenial seizures.

PIP: In Connecticut, physicians followed 19 women with tractable epilepsy for 3-5 months to determine baseline seizure frequency. 14 women agreed to enter a clinical trial evaluating synthetic medroxyprogesterone acetate's (MPA) ability to reduce seizure frequency by adding MPA to the usual antiepileptic drug regimen. They all received 10 mg MPA pills 2-4 times each day. 6 women who did experience amenorrhea later received 120-150 mg intramuscular MPA injections (Depo-Provera) every 6-12 weeks instead of oral MPA. The physicians followed the women for 12 months. 11 women eventually experienced amenorrhea and always had low levels of serum progesterone ( or = ng/ml). Seizure frequency fell significantly from a mean of 8.3 seizures/month before MPA administration to 5.1 seizures/month after MPA administration, equaling 39% fewer seizures (p = .02). 7 women who experienced obvious improvement had 52% fewer seizures on average (25-71%) reduction. All women who had fewer seizures did experience partial seizures, however. MPA did not affect the steady state levels of antiepileptic drugs. MPA levels were higher in women receiving oral MPA than they were in those receiving MPA injections (5.2 ng/ml vs. 2.6 ng/ml). Most women had some spotting, particularly during the first few months of the study. Some of these women discontinued treatment because of this side effect, especially women who did not appear to benefit from the treatment. Menstruation returned in 6-12 months in women receiving MPA injections. Further research on MPA's effect on catamenial seizures is needed.

A method of screening for ectopic pregnancy and its indications.

The possibility of distinguishing between normal intrauterine and ectopic pregnancies by determining the lower limit of the rate of human chorionic gonadotropin (hCG) increased in early pregnancy was investigated. This can be expressed as the slope of the log hCG-time curve or as the percent increase in hCG over a given sampling interval. For practical purposes, the rate is most easily determined from 2 samples drawn 48 hours apart. The differences between the 2 hCG values obtained is expressed as a percentage of the initial value, and should be 66% or greater for this sampling interval. Approximately 15% of normal intrauterine pregnancies screened in this way will appear abnormal, and the diagnosis in 13% of ectopic pregnancies will be delayed beyond 48 hours.

Treating hypertension in the diabetic patient: therapeutic goals and the role of calcium channel blockers.

Although many drugs effectively control hypertension in patients with diabetes mellitus, the risk of aggravating the diabetic process and inducing new complications can negate the benefits of reduced blood pressure. This article discusses the current status of antihypertensive therapy in diabetic patients and focuses on the use of calcium channel blockers that safely reduce blood pressure while having a neutral or beneficial effect on the diabetic state and related medical complications. While both calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors are suitable agents for the primary treatment of diabetic hypertension, the beneficial effects of calcium channel blockers on glucose homeostasis, lipid metabolism, and renal function support their routine use as alternatives to ACE inhibitors. Among the three classes of calcium channel blockers, second-generation dihydropyridines offer advantages over older calcium channel blockers because the second-generation drugs provide greater vascular selectivity and less direct myocardial depression.

Abnormal ovarian cycles as diagnosed by ultrasound and serum estradiol levels.

A significant portion of human infertility is presumably due to defective ovulation, including patients who fail to conceive despite medical induction of ovulation, those who fail despite repeated timely donor inseminations, and those with "infertility of unknown etiology". All point out the inadequacy of standard criteria for normal ovulation. This investigation correlates preovulatory serum estradiol and gonadotropin concentrations with dominant follicle growth measured ultrasonographically and serum progesterone levels. The data indicate a 35% incidence of cycles with significantly abnormal serum estradiol levels, decreased dominant follicle size, and abnormal progesterone levels despite biphasic basal body temperature curves and normal cycle length. If these cycles represent inadequate or abnormal ovulation, they can be distinguished from adequate cycles prior to follicle rupture and may benefit the treatment of human infertility.

Monitoring gonadotropin therapy.

In the private clinical setting the use of Pergonal or Metrodin is a safe and efficient method of inducing ovulation; however, the known risks of those agents must be kept in mind at all times. By adhering to the guidelines listed here and administering Pergonal and then human chorionic gonadotropin in the prescribed manner, an ovulation rate of greater than 90% should be achieved. A six-month course of therapy with Pergonal should yield a pregnancy rate of 60-70%, provided that the fallopian tubes are normal, the sperm count is adequate and cervical mucus function is intact. Patients who do not become pregnant in six to nine months should be referred to tertiary centers for other procedures, such as in vitro fertilization and/or gamete intrafallopian transfer.

Prostaglandins in the control of ovulation, corpus luteum function, and parturition.

PIP: Aspirin and indomethacin have been found to be potent inhibitors of (PG) prostaglandin synthesis. Recent observations show that it is possible to partially reverse the block of ovulation caused by indomethacin if exogenous PGs, especially PGF2alpha are given at the same time as indomethacin. Indomethacin blockage of ovulation produces corpus lutea in which the eggs have been entrapped. The follicles proceed to luteinize and produce progesterone in amounts which do not differ from the normal. The differences between the effects seen on ovulation and the lack of effect seen on steroidogenesis may be a factor of timing. Recent evidence continues to support the view that PGF2alpha is the luteolysin in many of the nonprimate mammalian species. The same type of experiments in the monkey and human have produced completely different results. It is possible that very high levels are needed to accomplish luteolysis in primates. 1 similarity of results in studies of both primates and nonprimates is that when estrogens are administered, there follows a rapid luteal regression and a concomitant rise in PGFalpha. In the process of parturition, the role of PGs remains unsubstantiated. It is possible to speculate that PGF2alpha is responsible for increased uterine activity.^ieng

The use of prostaglandins for the induction of labor.

PIP: This paper attempts to assess the present status of the use of prostaglandins (PGs) in induction of labor. According to the published literature over 1000 patients have been treated with intravenous administration of PGF2alpha, a method which seems to be at least as effective as oxytocin infusion. Some authors suggest that this mode of action may be more effective in patients with lower Bishop scores at start of infusion. Intravenous infusion of PGE2alpha has been found to be 10 times more potent than PGF2alpha, regardless of mode of administration; success rates and amount of side effects are similar. Oral administration of PGE2alpha has shown to be as effective as oxytocin in 786 elective inductions of labor; the oral way of administration is more effective in the latent and early active phase of labor. 15 methyl PGE, a chemically modified PG, is as effective as its parent compound, has the same side effects, can be used in smaller amounts, but does not have any major advantages over the natural compound. In general it takes less than 1/10 the dose of PG to initiate labor than it takes to induce abortion, and the side effects are reduced about the same degree; since PGs may cause hypertonus care should be taken in monitoring the fetal condition and in controlling the rate of PG administration. Considerable work is needed before the full value of PGs in induction of labor can be assessed.^ieng

Efficacy of fenoprofen in the treatment of primary dysmenorrhea.

We compared fenoprofen calcium, 200 mg; fenoprofen calcium, 400 mg; aspirin, 650 mg; and a placebo in 85 women for the relief of primary dysmenorrhea in a double-blind, clinical trial. The usefulness of these drugs was judged from data obtained over four consecutive menstrual periods on: restriction of daily activity, pain intensity scores, need for rescue analgesics, withdrawal due to lack of efficacy, and adverse events. Both fenoprofen, 200 mg, and fenoprofen, 400 mg, offered significant (P less than .01) pain relief when compared to placebo and aspirin. Analyses of data on 1, 2 and 3 indicated that aspirin was not significantly different from placebo. The aspirin-treated group reported the greatest number of adverse reactions, but the differences between the four groups were not statistically significant. Our study lends support to the concept of a "plateau analgesic effect" of nonsteroidal antiinflammatory drugs (NSAIDs): fenoprofen, 200 mg, appears to be as effective as fenoprofen, 400 mg. When this type of drug fails to provide relief for a woman suffering from primary dysmenorrhea, switching to another NSAID may be more appropriate than increasing the dosage and the probability of dosage-related side effects.