tolfenamic-acid and Endometriosis

Primary menorrhagia, IUD side effects and endometriotic symptoms may be a result of excessive PG release in the reproductive organs. These conditions and symptoms can be prevented or markedly alleviated by a PG synthesis inhibitor, such as tolfenamic acid. This treatment, which is used only intermittently, has been well tolerated with no serious side effects.

Topics: Cyclooxygenase Inhibitors; Endometriosis; Female; Humans; Intrauterine Devices; Menorrhagia; ortho-Aminobenzoates; Prostaglandin Antagonists; Prostaglandins; Research Design

To study the production of prostacyclin (PGI2) and thromboxane A2 (TxA2) in endometriosis in vitro, samples of endometriotic tissue taken during operation from 6 women were superfused for 4.5 hours in 95% O2/5% CO2 at 37 degrees C, and the stable metabolites of PGI2 (=6-keto-PGF1 alpha), and TxA2 (=TxB2) were measured by radioimmunoassays from the superfusates. All samples studied produced 6-keto-PGF1 alpha in the range from 0.2 to 10.5 nanograms/gram of dry tissue/minute with a mean of 3.6 ng/g/min during the whole experiment. TxB2 was also released by each sample at rates between 0.2 and 11.9 ng/g/min (mean 2.6 ng/g/min). The production of these prostanoids tended to be greater in the serosal (n = 2) than in the ovarian (n = 4) endometriosis. The addition of indomethacin of 10(-5) - 10(-3) moles/l to the superfusion medium inhibited concentration-dependently the synthesis of these prostanoids. Apart from these in vitro data implying the production of PGs in endometriosis, 18 patients with pelvic endometriosis sustained no relief for their endometriotic symptoms from the treatments with three anti-prostaglandins (acetylsalicylic acid, indomethacin, tolfenamic acid) in a double-blind, placebo-controlled trial.

Topics: 6-Ketoprostaglandin F1 alpha; Aspirin; Clinical Trials as Topic; Endometriosis; Epoprostenol; Female; Humans; In Vitro Techniques; Indomethacin; ortho-Aminobenzoates; Prostaglandin Antagonists; Prostaglandins; Thromboxane A2; Thromboxane B2; Thromboxanes

Prostaglandins (PGs) may be involved in the development of the symptoms of endometriosis. Therefore 18 patients with pelvic endometriosis were treated in placebo controlled double-blind trial with different prostaglandin biosynthesis inhibitors. These drugs were: acetylsalicylic acid (0.5 g x 3) exerting a weak PG-synthetase inhibition, indomethacin (25 mg x 3) inhibiting PG-synthetase, and as a representative of fenamates, tolfenamic acid (200 mg x 3), which both inhibits PG-synthetase and antagonizes PGs at the target level. The therapeutic effect was evaluated using a specific endometriosis score separately during menstruation and in premenstrum. Prostaglandin biosynthesis inhibitors did not alleviate premenstrual complaints better than placebo. During menstruation tolfenamic acid relieved endometriotic symptoms more effectively than placebo while indomethacin and acetylsalicylic acid did not differ from placebo. A drug which inhibit both the synthesis and action of PGs can thus be used in the alleviation of secondary dysmenorrhea due to endometriosis.. The possible role of prostaglandins (PGs) in the biochemistry of endometriosis prompted this placebo-controlled double-blind trial evaluating the effect of PG-inhibitors on symptoms of endometriosis (especially pelvic pain). The 4 drugs used were: 1) placebo, 2) acetylsalicylic acid (ASA), 3) indomethacin, and 4) tolfenamic acid. Each drug was administered orally from Day 20 of the menstrual cycle until end of menstruation for 2 consecutive cycles. During menstruation, tolfenamic acid (P.01) and ASA (P.05) lowered the endometriosis score from the pretreatment level. Tolfenamic acid was more effective than placebo (P.05), whereas ASA and indomethacin did not differ from placebo. Each treatment, including placebo, lowered the endometriosis score (P.05) during the menstrual period, but none of the PG inhibitors was more effective than placebo (P.05). According to patient's subjective judgements, tolfenamic acid alleviated symptoms more effectively than other drugs tested. Pain symptoms occurred less often during tolfenamic acid and ASA than during placebo or indomethacin (P.05). Gastrointestinal side effects were more common with indomethacin and ASA (P.05). Indomethacin treatment raised the incidence of psychic complaints over those with ASA or placebo (P.05). Side effects were fairly evenly distributed among the therapies.

Topics: Aspirin; Double-Blind Method; Dysmenorrhea; Endometriosis; Female; Humans; Indomethacin; ortho-Aminobenzoates; Pelvic Neoplasms; Placebos; Prostaglandin Antagonists