Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.     

Determination of menstrual prostaglandin levels in non-dysmenorrheic and dysmenorrheic subjects

We have developed a method which can measure the menstrual prostaglandin (PG) activity in a single tampon specimen by bioassays. This method makes it possible to monitor the menstrual PG activity continuously during menstruation. Using this technique, we determined the menstrual PG patterns of two normal non-dysmenorrheic subjects, one subject on oral contraceptives (OC) and one subject with moderate to severe dysmenorrhea. Two to four cycles were studied per subject. We observed three mentrual patterns among the four subjects studied. Compared to the two normal controls, the subject on OC had a significantly lower menstrual fluid total and menstrual PG activity. The mean values +/- S.E. per menstrual period were 33.4 g +/- 1.5 vs 21.5 g +/- 2.0 and 28.6 microgram (PGF2alpha equivalent) +/- 1.5 vs 11.3 microgram +/- 4.2 respectively (control vs OC). The dysmenorrheic subject had a menstrual fluid total of 37.0 g +/- 1.9 similar to the two normal controls. Her menstrual PG activity (49.8 microgram +/- 7.7), however, was nearly two times higher than the normal controls. In one cycle studied, the dysmenorrheic subject was treated with a PG synthetase inhibitor, ibuprofen (Motrin). Remarkable relief was achieved. The alleviation of symptoms was accompanied by a concomitant marked reduction in the menstrual PG activity.     

Determination of menstrual prostaglandin levels in non-dysmenorrheic and dysmenorrheic subjects

We have developed a method which can measure the menstrual prostaglandin (PG) activity in a single tampon specimen by bioassays. This method makes it possible to monitor the menstrual PG activity continuously during menstruation. Using this technique, we determined the menstrual PG patterns of two normal non-dysmenorrheic subjects, one subject on oral contraceptives (OC) and one subject with moderate to severe dysmenorrhea. Two to four cycles were studied per subject. We observed three menstrual patterns among the four subjects studied. Compared to the two normal controls, the subject on OC had a significantly lower menstrual fluid total and menstrual PG activity. The mean values ± S.E. per menstrual period were 33.4 g ± 1.5 vs 21.5 g ± 2.0 and 28.6 μg (PGF_2α equivalent) ± 1.5 vs 11.3 μg ± 4.2 respectively (control vs OC). The dysmenorrheic subject had a menstrual fluid total of 37.0 g ± 1.9 similar to the two normal controls. Her menstrual PG activity (49.8 μg ± 7.7), however, was nearly two times higher than the normal controls. In one cycle studied, the dysmenorrheic subject was treated with a PG synthetase inhibitor, ibuprofen (Motrin). Remarkable relief was achieved. The alleviation of symptoms was accompanied by a concomitant marked reduction in the menstrual PG activity.     

The effect of ibuprofen on the intrauterine pressure and menstrual pain of dysmenorrheic patients

In 12 dysmenorrheic patients we examined the therapeutic action of the Prostaglandin-synthesis inhibitor: Ibuprofen, a non-steroidal analgesic agent. Ibuprofen highly significantly reduced the resting pressure (P<0.001), active pressure (P<0.001) and frequency (P<0.05) of cyclic activity of the uterus, as well as menstrual pain (P<0.001). Since these effects occurred after a single oral dose of 800 mg Ibuprofen, without side effects or complications, extensive field trials are recommended with this and other PG-synthesis inhibitors, to assess their therapeutic benefits.     

The effect of ibuprofen on the intrauterine pressure and menstrual pain of dysmenorrheic patients.

In 12 dysmenorrheic patients we examined the therapeutic action of the Prostaglandin-synthesis inhibitor: Ibuprofen, a non-steroidal analgesic agent. Ibuprofen highly significantly reduced the resting pressure (P less than 0.001), active pressure (P less than 0.001) and frequency (P less than 0.05) of cyclic activity of the uterus, as well as menstrual pain (P less than 0.001). Since these effects occurred after a single oral dose of 800 mg Ibuprofen, without side effects or complications, extensive field trials are recommended with this and other PG-synthesis inhibitors, to assess their therapeutic benefits.     

Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis.

The role of prostaglandins (PGs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myometrium, adenomyosis, normal ovary and endometrial cyst were incubated. 6-Keto-PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha, and PGE2 concentrations of the incubation medium were measured by RIA. The results showed that 6-keto-PGF1 alpha production in adenomyosis and endometrial cyst were significantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PGs production in tissue in endometriosis was observed.     

Differential effects of ibuprofen and naproxen sodium on menstrual prostaglandin release and on prostaglandin production in the rat uterine homogenate

In two independent studies, ibuprofen and naproxen sodium were found to be equi-effective in alleviating dysmenorrheic symptoms. However, the effects of these drugs on menstrual PG release were found to be dissimilar. Ibuprofen primarily inhibited menstrual PGF_2α release with little effect on PGE release, whereas, naproxen sodium inhibited both PGF_2α and PGE₂ release equally. To verify these results, we determined the inhibitory potency, IC 50' of ibuprofen and naproxen sodium on PGF_2α and PGE₂ synthesis in the rat uterine homogenate system. The preferential PGF2a inhibitory activity of ibuprofen was confirmed.These findings suggest that ibuprofen may, in addition to inhibiting fatty acid cyclooxygenase, also inhibit PGF_2α reductase, or some other PG metabolic pathways which affect PGF a and PGE₂ synthesis differently. The significance of this differential PG synthesis inhibitory effect in dysmenorrheic therapy is discussed.     

The effects of estrogen and progesterone on blood glutamate levels: evidence from changes of blood glutamate levels during the menstrual cycle in women

The gonadal steroids estrogen and progesterone have been shown to have neuroprotective properties against various neurodegenerative conditions. Excessive concentrations of glutamate have been found to exert neurotoxic properties. We hypothesize that estrogen and progesterone provide neuroprotection by the autoregulation of blood and brain glutamate levels. Venous blood samples (10 ml) were taken from 31 men and 45 women to determine blood glutamate, estrogen, progesterone, glucose, glutamate-pyruvate transaminase (GPT), and glutamate-oxaloacetate transaminase (GOT) levels, collected on Days 1, 7, 12, and 21 of the female participants' menstrual cycle. Blood glutamate concentrations were higher in men than in women at the start of menstruation (P < 0.05). Blood glutamate levels in women decreased significantly on Days 7 (P < 0.01), 12 (P < 0.001), and 21 (P < 0.001) in comparison with blood glutamate levels on Day 1. There was a significant decrease in blood glutamate levels on Days 12 (P < 0.001) and 21 (P < 0.001) in comparison with blood glutamate levels on Day 7. Furthermore, there was an increase in blood glutamate levels on Day 21 compared with Day 12 (P < 0.05). In women, there were elevated levels of estrogen on Days 7 (P < 0.05), 12, and 21 (P < 0.001), and elevated levels of progesterone on Days 12 and 21 (P < 0.001). There were no differences between men and women with respect to blood glucose concentrations. Concentrations of GOT (P < 0.05) and GPT (P < 0.001) were significantly higher in men than in women during the entire cycle. The results of this study demonstrate that blood glutamate levels are inversely correlated to levels of plasma estrogen and progesterone.     

The effect of naproxen-sodium on the prostaglandin concentrations of the menstrual blood and uterine “jet-washings” in dysmenorrehic women

A group of dysmenorrheic women was treated during two consecutive menstrual bleedings, once with placebo and once with naproxen-sodium (naproxen-Na), a potent inhibitor of prostaglandin synthesis. Concentrations of prostaglandins F and E (PGF, PGE) were assayed in the menstrual blood collected into cervical cups, and in uterine “jet-wash” specimens.In the $\text{menstrual blood}$ the high PGF concentrations of patients receiving placebo were significantly reduced following treatment with naproxen-Na (from ± S.E. 227±78.9 ng/ml to 42±19.5 ng/ml; p=0.03). A significant decrease of PGE concentrations was also observed during naproxen-Na treatment (from 10.8±2.1 ng/ml to 3.4±1.7 ng/ml; p=0.03).In the $\text{uterine “jet washings”}$ naproxen-Na significantly reduced PGE concentrations (p=0.03) while the decrease of PGF concentrations was close to statistical signficance (p=0.06). These results strenthened the premise of causal relationships between naproxen-Na treatment, decreased uterine prostaglandins, reduction of intrauterine pressure, and relief from dysmenorrehic pain.     

The effect of naproxen-sodium on the intrauterine pressure and menstrual pain of dysmenorrheic patients

The Prostaglandin-synthesis inhibitor: Naproxen-Sodium (NS) (an analgesic agent) very significantly (P<0.001) reduced the “resting” and “active” pressures and the frequency of cyclic uterine activity of 10 dysmenorrheic patients. It also highly significantly reduced (P<0.001) menstrual pain. Since these effects were observed after a single oral dose of 1100 mg NS, without side effects or complications, extensive field trials are recommended for assessing therapeutic benefits of this treatment.     

The effect of naproxen-sodium on the intrauterine pressure and menstrual pain of dysmenorrheic patients.

The Prostaglandin-synthesis inhibitor: Naproxen-Sodium (NS) (an analgesic agent) very significantly (P less than 0.001) reduced the "resting" and "active" pressures and the frequency of cyclic uterine activity of 10 dysmenorrheic patients. It also highly significantly reduced (P less than 0.001) menstrual pain. Since these effects were observed after a single oral dose of 1100 mg NS, without side effects or complications, extensive field trials are recommended for assessing therapeutic benefits of this treatment.     

Effect of prostaglandin inhibition on caffeine-induced hypercalciuria in healthy women

Caffeine ingestion increases urinary calcium excretion. The mechanism is not known, but prostaglandin synthesis has been implicated. We hypothesized that administration of a prostaglandin inhibitor such as acetylsalicylic acid (aspirin) along with caffeine would prevent caffeine-induced hypercalciuria. We measured 3-hour excretion in fasting subjects who each randomly ingested four treatments on nonconcurrent mornings: no drug, caffeine (5 mg/kg body weight), acetylsalicylic acid (650 mg), or caffeine plus acetylsalicylic acid. In experiment 1, nine healthy premenopausal female subjects were studied; each treatment was taken with 200 ml of orange juice. Water was provided hourly to encourage urine flow. Urinary calcium excretion rose with caffeine treatment; mean 3-hour calcium (mmol/mmol creatinine) was 0.49 +/- 0.07 compared with 0.23 +/- 0.04 during the no-drug treatment. Acetylsalicylic acid caused a significant reduction in urinary calcium to 0.13 +/- 0.08; when it was combined with caffeine, caffeine-induced calcium excretion fell significantly to 0.35 +/- 0.08. Sodium excretion tended to reflect calcium excretion. Urinary prostaglandin E(2) fell significantly with acetylsalicylic acid, with and without caffeine. There were no significant changes in creatinine, water, or potassium excretion. Experiment 2 was similar, except that water was substituted for orange juice to test the possibility that acetylsalicylic acid affected elevated but not basal calcium excretion. Similar and even more pronounced results were obtained, with caffeine causing a threefold increase in urinary calcium, acetylsalicylic acid causing a decrease by half, and the combined drug treatment being greater than no drug but less than caffeine alone. Urinary phosphorus rose significantly with caffeine alone. Prostaglandin synthesis may not be directly involved in caffeine-induced hypercalciuria, as the magnitude of the caffeine-induced increase was similar when treatments given the acetylsalicylic acid were compared with those without a prostaglandin synthesis inhibitor.     

Effects of daily activities on ambulatory blood pressure during menstrual cycle in normotensive women

The purpose of this study was to determine whether (1) there is a menstrual phase effect on blood pressure (BP) and heart rate (HR), and (2) the effects of physical effort, posture, or moods on BP and HR is mediated by the menstrual phase. Twelve normotensive women, aged between 28 and 50, with normal menstrual cycles were studied. BP was measured at 30- to 60-min intervals during a 24-hr period using an ambulatory BP monitor on Days 1, 8, 15, and 22 of the menstrual cycle. Participants were asked to report their posture, physical effort, and mood (annoyed, tense, and happy) on 5-point Likert-type scales each time the ambulatory BP monitor took measurements. Systolic BP (SBP) was lower on Day 8 of the cycle. Diastolic BP (DBP) and HR were lower on Days 1 and 8. Daytime SBP was affected by the time of the day and posture, but not by moods, whereas daytime DBP was affected by posture and levels of tenseness. The level of physical effort only affected HR, not BP. The average daytime physical and emotional variables had little influence over the average daytime BP. In 1 normotensive women with a normal menstrual cycle, SBP was lower during the follicular phase and DBP and HR were lower during the follicular phase and menstruation even after controlling the effects of other factors. Physical activity or moods had only momentary effects on BP or HR. A cross-validation statistical method used is suggested to study how individuals are affected by various factors. With the use of this method, the inclusion of menstrual phase in the model improved the prediction of SBP for 5 out of the 12 women studied.     

Effect of honey bee venom on prostaglandin levels in mouse skin

The effects of honey bee venom on prostaglandin (PG) E levels were studied in mouse skin under and conditions. Levels of PGE were increased 10.8-fold after 15 minutes exposure to reconstituted bee venom and 3.8-fold 35 minutes after a bee sting . Phospholipase A₂ (PLA₂), a major component of bee venom, also caused a 10.9-fold increase in PGE levels and may be primarily responsbiel for this response of skin to bee venom.     

Dietary calcium and blood lead levels in women

Nutritional factors are known to influence metabolism and toxicity of several metals in animal experiments, but relevant human data are scarce and inconclusive. In this work, we tested the hypothesis that dietary calcium influences lead metabolism in humans. Blood lead concentrations were used as indicators of lead exposure and metabolism. Two groups of peasant women living in similar conditions in two different regions in Yugoslavia (100 in each) were chosen as subjects for this purpose. In region A, the dietary calcium intake was about 940 mg, and in region B about two times lower, i.e., 450 mg/day. The average blood lead concentration was significantly lower in women from region A (69 micrograms/L) than from region B (83 micrograms/L). Our results support the assumption that adequate calcium intake might be one of the preventive measures for decreasing lead absorption. This new evidence, sought for some time by nutritionists and toxicologists, needs further international confirmation.     

Effect of licorice on PTH levels in healthy women

Licorice has been considered a medicinal plant for thousands of years. Its most common side effect is hypokalemic hypertension, which is secondary to a block of 11beta-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid effect of cortisol. This effect is due to glycyrrhetinic acid, which is the main constituent of the root, but other components are also present, including isoflavans, which have estrogen-like activity, and are thus involved in the modulation of bone metabolism. We investigated nine healthy women 22-26 years old, in the luteal phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6%, w/w of glycyrrhizic acid) daily for 2 months. Plasma renin activity (PRA), aldosterone, cortisol, serum parathyroid hormone (PTH), 1,25-dihydroxy Vitamin D (1,25OHD), 25-hydroxycholecalciferol (25OHD), estradiol, FHS, LH, alkaline phosphatase (ALP), calcium, phosphate and creatinine, urinary calcium and phosphate and mineralometry were measured. PTH, 25OHD and urinary calcium increased significantly from baseline values after 2 months of therapy, while 1,25OHD and ALP did not change during treatment. All these parameters returned to pretreatment levels 1 month after discontinuation of licorice. PRA and aldosterone were depressed during therapy, while blood pressure and plasma cortisol remained unchanged. CONCLUSIONS: licorice can increase serum PTH and urinary calcium levels from baseline value in healthy women after only 2 months of treatment. The effect of licorice on calcium metabolism is probably influenced by several components of the root, which show aldosterone-like, estrogen-like and antiandrogen activity.     

Fluctuations of unbound whole blood polyamine levels during the menstrual cycle.

Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females.