The refief of primary dysmenorrhea by ketoprofen and indomethacin

The prostaglandin biosynthesis inhibitors ketoprofen and indomethacin were compared in the treatment of primary dysmenorrhea in a double-blind, cross-over trial involving 23 patients. Each drug was used for 2-4 days during 3 consecutive menstruations in randomized order. Good or moderate overall relief was obtained in 60 of the 68 ketoprofen-treated menstruations (88%). A dysmenorrhea score, based on subjective estimations of 8 symptoms, similarly decreased from a mean (+/- S.E.M.) basal level of 9.6 +/- 0.6 to 3.6 +/- 0.3 during ketoprofen treatment and to 4.0 +/- 0.3 during indomethacin. Both drugs relieved pelvic and lower back pains and eliminated vomiting and diarrhea in 82-97% of the cycles whereas headache, fatigue and nervousness were less frequently alleviated (40-67%). Eighteen of the 23 women (78%) had been unable to work during the first day of menstruation, the rate of working days lost was reduced to 4% with ketoprofen and 9 with indomethacin. Mild side-effects occurred during 12 ketoprofen and 14 indomethacin therapies. Ketoprofen thus seems to be as effective and tolerable as indomethacin in the treatment of primary dysmenorrhea.     

The relief of primary dysmenorrhea by ketoprofen and indomethacin

The prostaglandin biosynthesis inhibitors ketoprofen and indomethacin were compared in the treatment of primary dysmenorrhea in a double-blind, cross-over trial involving 23 patients. Each drug was used for 2–4 days during 3 consecutive menstruations in randomized order. Good or moderate overall relief was obtained in 60 of the 68 ketoprofen-treated menstruations (88 %) and in 60 of the indomethacin-treated cases (90 %). A dysmenorrhea score, based on subjective estimations of 8 symptoms, similarly decreased from a mean (±S.E.M.) basal level of 9.6 ± 0.6 to 3.6 ± 0.3 during ketoprofen treatment and to 4.0 ± 0.3 during indomethacin. Both drugs relieved pelvic and lower back pains and eliminated vomiting and diarrhea in 82–97 % of the cycles whereas headache, fatigue and nervousness were less frequently alleviated (40–67 %). Eighteen of the 23 women (78 %) had been unable to work during the first day of menstruation, the rate of working days lost was reduced to 4 % with ketoprofen and 9 with indomethacin. Mild side-effects occurred during 12 ketoprofen and 14 indomethacin therapies. Ketoprofen thus seems to be as effective and tolerable as indomethacin in the treatment of primary dysmenorrhea.     

Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy

A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationship between prostaglandin F and dysmenorrhea is suggested by these studies     

Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy.

A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationsship between prostaglandin F and dysmenorrhea is suggested by these studied.     

Prostaglandins,the kidney,and hypertension.

Prostaglandins are part of the family of oxygenated metabolites of arachidonic acid known collectively as eicosanoids. While they are formed, act, and are inactivated locally and rarely circulate in plasma, they can affect blood flow in some tissues and so might contribute to the control of peripheral vascular resistance. Few studies have shown any derangement of total body prostaglandin synthesis or metabolism in hypertension, but increased renal synthesis of one prostanoid, thromboxane A2, has been noted in spontaneously hypertensive rats and some hypertensive humans. This potent vasoconstrictor may account for the increased renal vascular resistance and suppressed plasma renin activity seen in many patients with hypertension. Increased renal vascular resistance could increase the blood pressure directly as a component of total peripheral resistance or indirectly by increasing glomerular filtration fraction and tubular sodium reabsorption. Specific thromboxane synthesis inhibitors not only decrease renal thromboxane production but also increase renal vasodilator prostaglandin synthesis when prostaglandin synthesis is stimulated. This redirection of renal prostaglandin synthesis toward prostacyclin might be of benefit in correcting a fundamental renal defect in patients with hypertension.     

Prostaglandins, cyclic nucleotides and cell function

Based upon the ability of the E-prostaglandins to stimulate cyclic AMP formation in a dose-related manner and the correlation between this property and their affinity for a membraneous receptor, the action of these prostaglandins was proposed to be expressed largely via cyclic AMP. The failure of the F-prostaglandins to demonstrate significant activity in these two parameters led to the suggestion that they must act at another receptor via a different mediator. The recent isolation of a receptor unique to PGF_2α and the demonstrated ability of this prostaglandin to increase tissue cyclic GMP levels are consistent with this concept that the E-prostaglandins and PGF_2α play distinctly different roles in cell regulation.     

Prostaglandins and Glaucoma

Human aqueous humour was found to contain a substance which contracted the rat stomach strip. The mean activity was significantly higher in specimens from open angle glaucoma cases than in specimens from patients with cataract. The pharmacological and chromatographic properties of the active material were studied in aqueous humour obtained from cadavers; activity seemed to be due to prostaglandin E₁. These results suggest that prostaglandin E₁ may play some part in the aetiology of open angle glaucoma.