15-keto-13-14-dihydroprostaglandin-f2alpha and Dysmenorrhea

Non-drug therapies for women with primary dysmenorrhea are primarily based on anecdotal evidence and small-scale clinical studies. This randomized, observer-blinded, clinical trial evaluated the efficacy of spinal manipulative therapy (SMT) in the treatment of women with primary dysmenorrhea. Women were recruited from the Chicago metropolitan area and evaluated for inclusion through four screening levels. One hundred thirty eight women, ages 18-45, with primary dysmenorrhea diagnosed by participating gynecologists, were randomly assigned to either SMT or a low-force mimic (LFM) maneuver. No treatment occurred at menstrual cycle 1. Treatment for both groups took place on day 1 of cycles 2, 3 and 4, and prophylactic treatment of three visits took place during the 7 days before cycles 3 and 4. Main outcome measures were the Visual Analog Scale (VAS) and plasma concentration of the prostaglandin F2alpha metabolite, 15-keto-13,14-dihydro-prostaglandin F2alpha (KDPGF2alpha), measured 15 min before treatment and 60 min after treatment on day 1 of four consecutive menstrual cycles. The Moos' Menstrual Distress Questionnaire (MDQ) was also administered after treatment on day 1 of each cycle. At cycle 2, the post-treatment VAS scores decreased for both groups, with no statistically significant difference in pre- to post-treatment scores between the two groups (P = 0.44). The changes in pre- to post-treatment KDPGF2alpha levels were not statistically different between the SMT and LFM groups (P = 0.15). No treatment effects were detected over the three cycles for VAS, KDPGF2alpha or MDQ (P = 0.65, P = 0.61 and P = 0.78, respectively). However, there were statistically significant linear time effects for VAS (P = 0.008), MDQ (P < 0.001), and borderline significance for KDPGF2alpha (P = 0.054); these decreases were not considered clinically meaningful. The LFM maneuver used in this study was designed to act as a 'placebo-like' control treatment in comparison with SMT. Although it is possible that the trial did not continue long enough for any placebo effect of the LFM to wash out, it seems more likely that this maneuver was indistinguishable from SMT. Therefore, the postulated superior benefit of high-velocity, short-lever, low-amplitude, high-force spinal manipulation to a low-force maneuver is not supported by the results of this study. 1999 International Association for the Study of Pain.

Topics: Adolescent; Adult; Dinoprost; Dysmenorrhea; Female; Humans; Manipulation, Spinal; Middle Aged; Pain Measurement; Posture; Single-Blind Method; Surveys and Questionnaires; Treatment Outcome

The primary objectives of this study were to compare the effect of spinal manipulation vs. sham manipulation on a) circulating plasma levels of the prostaglandin F2a metabolite, 15-keto-13,14-dihydroprostaglandin (KDPGF2a), b) perceived abdominal and back pain and c) perceived menstrual distress in women with primary dysmenorrhea.. This randomized clinical pilot study investigated the outcome measures before and after either a spinal manipulation treatment (SMT) or a sham manipulation.. All subjects were treated at the National College Chiropractic clinic, a private chiropractic clinic in the suburban Chicago area.. Forty-five women with a history of primary dysmenorrhea were recruited from the local community. The volunteers ranged in age from 20-49 (mean age = 30.3 yr), and were entered into the study between April 1990 and January 1991. Twenty-four were randomly assigned to the spinal manipulation group and 21 were assigned to the sham group.. Subjects treated with spinal manipulation were placed in a side-lying position with the bottom leg straight and the top leg flexed at the knee and hip. They received a high-velocity, short lever, low-amplitude thrust to all clinically relevant vertebral levels within T10 and L5-S1 and the sacroiliac joints. In the sham manipulation, subjects were placed in a side-lying position with both hips and knees flexed. Their manipulation consisted of a similar thrust administered to the midline base of the sacrum.. Perceived abdominal and back pain were measured with a visual analog scale, and menstrual distress was measured with the Menstrual Distress Questionnaire. Both were administered 15 min before and 60 min after treatment. Blood samples were collected by venipuncture for the determination of plasma levels of KDPGF2a at the same times. The plasma was then assayed for KDPGF2a by radioimmunoassay.. Analysis of covariance and paired Student's t tests were used for the statistical evaluation. Immediately after treatment, the perception of pain and the level of menstrual distress were significantly reduced by SMT. This reduction was associated with a significant reduction in plasma levels of KDGPF2a in the SMT group. A significant and similar reduction in plasma KDPGF2a also occurred in the sham group, indicating that a placebo effect was associated with a single sham intervention.. This randomized pilot study suggests that SMT may be an effective and safe nonpharmacological alternative for relieving the pain and distress of primary dysmenorrhea. However, the large change in KDPGF2a observed in both treatment groups clearly indicates that further studies with more subjects, studied over a longer time frame, are needed to resolve the question of a placebo effect.

Topics: Abdominal Pain; Adult; Back Pain; Chiropractic; Dinoprost; Dysmenorrhea; Female; Humans; Manipulation, Orthopedic; Middle Aged; Pilot Projects; Spine

Oral contraceptives reduce menstrual pain but the interaction with vasopressin and prostaglandin F2 alpha, two uterine stimulants related to the condition, is unknown. Ten women with a history of moderate to severe dysmenorrhoea were studied. Repeated blood samples were taken during a first menstrual cycle without treatment, during the first 21 days of a second cycle when they received an oral contraceptive (150 micrograms levonorgestrel and 30 micrograms ethynyloestradiol) and on the first or second day of the bleeding following hormonal withdrawal. Measurements were made of plasma concentrations of arginine vasopressin, 15-keto-13,14-dihydroprostaglandin F2 alpha, oestradiol-17 beta, progesterone, ethynyloestradiol, levonorgestrel, FSH, LH and prolactin, and serum osmolality was measured. Seven of the women rated their discomfort as moderate to severe on the first two menstruations, but as none or light at the withdrawal bleeding; with the rating scale for degree of pain that was used, this decrease in pain was significant (P less than 0.001). The plasma concentration of vasopressin in these seven women showed significant variation, with the highest concentrations being obtained at the beginning of the two painful menstruations (3.76 +/- 0.76 and 1.75 +/- 0.30 (S.E.M.) pmol/l) and at ovulation in the control cycle (1.91 +/- 0.58 pmol/l). During treatment the concentrations were consistently low, except on the first day of withdrawal bleeding (2.33 +/- 0.35 pmol/l). The concentrations of the prostaglandin F2 alpha metabolite showed less variation, but again the values at withdrawal bleeding (271 +/- 39 pmol/l) were not different from those obtained over the painful menstruations (255 +/- 24 and 217 +/- 25 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS). To learn more about the beneficial effect of combined oral contraceptives (OCs) on symptoms in primary dysmenorrhea, plasma levels of vasopressin and a prostaglandin F2-alpha metabolite in dysmenorrheic women were investigated before and during treatment with a gestagen-dominated OC. The 10 subjects were administered an OC containing 150 mcg of levonorgestrel and 30 mcg of ethinyl estradiol for 21 days. The 7 women with dysmenorrheic symptoms at the time of blood sampling during the 1st menstruation graded their pain as averaging 2.1 (moderate to severe) + or - 0.3; during the 2nd menstruation, the average value was 2.9 (severe) + or - 0.1, indicating a significant increase in pain at the start of the withdrawal bleeding. Vasopressin concentrations in samples obtained on days 1-3 of the control cycle were significantly higher than those on days 6-8, 20-22, and 24-26 of the control cycle and days 1-2 of the next menstruation. Thus, the highest concentrations were obtained at the beginning of the 2 painful menstruations and at ovulation in the control cycle. During treatment, vasopressin concentrations were consistently low, except on the 1st day of withdrawal bleeding. The concentrations of the prostaglandin F2-alpha metabolite showed less variation, again, values at withdrawal bleeding were not different from those obtained during painful menstruation. Plasma concentrations of ovarian and adenohypophysial hormones, as well as osmolality, were normal throughout. Thus, the present study provided no evidence that there is a reduced release of vasopressin and/or prostaglandin F2-alpha capable of accounting for the beneficial effect of OCs on dysmenorrhea. It is possible, however, that a difference in ovarian hormone concentrations is more pronounced in uterine tissue than in plasma.

Topics: Adolescent; Adult; Arginine Vasopressin; Contraceptives, Oral, Combined; Dinoprost; Dysmenorrhea; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Norgestrel; Prostaglandins F

Topics: Adult; Dinoprost; Dysmenorrhea; Endometriosis; Female; Humans; Infertility, Female; Prostaglandins F

The diurnal uterine activity in four normal women in the secretory phase of their menstrual cycles and one woman suffering from dysmenorrhea were studied in relation to concomitant hormone levels in blood (progesterone, hGH, prolactin, cortisol, vasopressin, and 15-keto-13,14-dihydro-PGF2 alpha). In the four normal women uterine activity decreased after midnight, unrelated to circulating levels of 15-keto-13,14-dihydro-PGF2 alpha. But during a dysmenorrheic episode the uterine hypercontractility pattern correlated well with levels of the PGF2 alpha-metabolite, indicating a role of endogenous-produced PGF2 alpha in this condition. The results demonstrate a diurnal rhythm, possibly related to the wake-sleep cycle. No simple associations were seen between vasopressin, cortisol, prolactin, hGH, the PGF2 alpha-metabolite, and uterine activity.

Topics: Circadian Rhythm; Dinoprost; Dysmenorrhea; Female; Humans; Hydrocortisone; Menstruation; Prolactin; Prostaglandins F; Sleep; Uterine Contraction; Vasopressins; Wakefulness

Both vasopressin and PGF2 alpha are effective uterine stimulants in the non-pregnant human uterus, especially around the onset of menstruation. In order to clarify the relationship of these hormones to menstrual pain, plasma concentrations of vasopressin and two prostaglandin metabolites (15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites) were measured in serial blood samples taken premenstrually and during menstruation. Five women with premenstrual pain gave 7-9 blood samples at intervals of 30 minutes on the day preceding the onset of menstruation. From 5 women with severe primary dysmenorrhea a corresponding series of blood samples were taken during the first day of menstruation. Two groups of 5 women with no symptoms served as controls, either premenstrually or during menstruation. In the women with premenstrual pain the vasopressin concentrations were significantly higher than in the corresponding control group. Even higher and markedly fluctuating vasopressin levels were found in the women with dysmenorrhea who, in general, had more intense pain than the women with premenstrual symptoms. In the group with dysmenorrhea there was also a significant rise in plasma concentration of the PG metabolites. No such increase was seen in the group with premenstrual pain. It is concluded that the pathophysiology of premenstrual pain could imply increased vasopressin secretion. The more severe pain in primary dysmenorrhea seems to be the result of a combined effect of vasopressin and PGF2 alpha.

Topics: Adolescent; Adult; Dinoprost; Dysmenorrhea; Estradiol; Female; Humans; Osmolar Concentration; Pain; Premenstrual Syndrome; Progesterone; Prostaglandins F; Vasopressins

PGE2, PGF2 alpha, and 13,14-dihydro-15-keto-PGF2 alpha were determined in two-day intervals by means of radio-immuno-assay from plasma of the arm veins of eight women with primary dysmenorrhoea. No evidence could be produced to any rise in plasma concentration of primary prostaglandins and of the main metabolite of PGF2 alpha in the course of one full menstrual cycle. These findings are likely to show that in cases of dysmenorrhoea determination of prostaglandins in peripheral venous blood is unsuitable for verification of high endogenous formation from the endometrium.

Topics: Biotransformation; Dinoprost; Dinoprostone; Dysmenorrhea; Estradiol; Female; Humans; Prostaglandins; Prostaglandins E; Prostaglandins F; Radioimmunoassay

In a double-blind, crossover study of 32 women with primary dysmenorrhea, the analgesic efficacy of naproxen sodium was compared to that of aspirin and placebo. The treatment started 1 to 5 days before the onset of menses and continued for 3 to 5 days. At the same time, a radioimmunoassay established concentrations of 13,14-dihydro-15-keto-prostaglandin F2-alpha, a prostaglandin F2-alpha metabolite (PGF-M) in blood samples obtained from before the treatment and on the first day of menses. In affording pain relief, naproxen sodium was superior to aspirin (p = 0.02) and placebo (p = 0.002); however, aspirin was not superior to placebo (p = 0.05). During naproxen sodium treatment, the patients' daily activities were less impaired than during both the aspirin and the placebo treatment courses. During naproxen sodium treatment, the mean blood PGF-M levels decreased by 73.5%, from a mean of 50.5 to 13.4 pg/ml; during aspirin treatment they decreased by 31.2%, from a mean of 44.2 to 30.4 pg/ml; during placebo treatment, an increase of 13.6% was observed, from a mean of 46.3 to 52.6 pg/ml. The PGF-M decrease during the naproxen sodium treatment was significantly more prominent than that during both aspirin and placebo treatments (p = 0.0001). Changes caused by aspirin treatment were significantly different from those occurring during the placebo treatment (p = 0.001). The study confirms that at the doses utilized in this study the analgesic properties of naproxen sodium are superior to those of the more conventional prostaglandin synthetase inhibitor, aspirin, and that pain relief is related to the inhibition of prostaglandin synthesis.

Topics: Activities of Daily Living; Adolescent; Adult; Aspirin; Dinoprost; Double-Blind Method; Drug Evaluation; Dysmenorrhea; Female; Humans; Naproxen; Placebos; Prostaglandins F