pituitrin and Dysmenorrhea

Dysmenorrhea is the leading cause of recurrent short-term school absence in adolescent girls and a common problem in women of reproductive age. Risk factors for dysmenorrhea include nulliparity, heavy menstrual flow, smoking, and depression. Empiric therapy can be initiated based on a typical history of painful menses and a negative physical examination. Nonsteroidal anti-inflammatory drugs are the initial therapy of choice in patients with presumptive primary dysmenorrhea. Oral contraceptives and depo-medroxyprogesterone acetate also may be considered. If pain relief is insufficient, prolonged-cycle oral contraceptives or intravaginal use of oral contraceptive pills can be considered. In women who do not desire hormonal contraception, there is some evidence of benefit with the use of topical heat; the Japanese herbal remedy toki-shakuyaku-san; thiamine, vitamin E, and fish oil supplements; a low-fat vegetarian diet; and acupressure. If dysmenorrhea remains uncontrolled with any of these approaches, pelvic ultrasonography should be performed and referral for laparoscopy should be considered to rule out secondary causes of dysmenorrhea. In patients with severe refractory primary dysmenorrhea, additional safe alternatives for women who want to conceive include transcutaneous electric nerve stimulation, acupuncture, nifedipine, and terbutaline. Otherwise, the use of danazol or leuprolide may be considered and, rarely, hysterectomy. The effectiveness of surgical interruption of the pelvic nerve pathways has not been established.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Complementary Therapies; Contraceptive Agents, Female; Dysmenorrhea; Endometriosis; Female; Humans; Life Style; Risk Factors; Vasopressins

Vasopressin and oxytocin are synthesised in the hypothalamus and released to the blood stream via the posterior lobe of the hypophysis. Research during later years has shown that these peptides are also produced in other parts of the brain. The secretion to plasma is stimulated by oestrogen, an effect which is counteracted by progestagen. During delivery the fetus can also produce substantial amounts of vasopressin and oxytocin. Additionally, the uterus itself may be a source of these hormones and we have recently found oxytocin mRNA in the endometrium of non-pregnant women with the highest levels around the time of ovulation. In the onset of labour preterm and at term pregnancy vasopressin and oxytocin are centrally involved and in primary dysmenorrhoea the former hormone seems to play a key role in the mechanisms of increased contractions and reduced blood flow in the uterus of the condition. In women with the latter condition the plasma concentration of vasopressin is several-fold higher than that in healthy control persons. Both in pregnant and non-pregnant women the myometrium is activated via specific vasopressin V1a and oxytocin receptors. This vasopressin receptor is different from the vasopressin V1b receptor of the anterior lobe of the hypophysis, which is important in mood changes and V2 receptor of the kidneys mediating fluid reabsorption. At the onset of labour preterm and at term the vasopressin V1a and oxytocin receptors are elevated to a moderate degree. In non-pregnant women the receptor density varies over the menstrual cycle and increase markedly at the onset of menstruation. Substances, which block the uterine vasopressin V1a and oxytocin receptors inhibit preterm labour and primary dysmenorrhoea.

Topics: Antidiuretic Hormone Receptor Antagonists; Dysmenorrhea; Female; Humans; Menstrual Cycle; Obstetric Labor, Premature; Oxytocin; Pregnancy; Receptors, Oxytocin; Receptors, Vasopressin; Uterus; Vasopressins

Important sources of oxytocin and vasopressin in the human, apart from the supraoptic and paraventricular nuclei of the brain, may be the fetus during labor as well as the endometrium and decidua of the uterus itself. The release of oxytocin and vasopressin to plasma is under influence of ovarian steroids. The two hormones stimulate uterine contractions in pregnant and non-pregnant women via myometrial oxytocin and vasopressin V1a receptors. At the onset of human labor preterm or at term no clear rise in the maternal plasma concentration of oxytocin and/or vasopressin has been demonstrated, but there may be an increased pulse frequency of the release of oxytocin to plasma with the advance of labor. Vasopressin is more potent than oxytocin on isolated myometrium from women undergoing Cesarean section at term. The myometrial concentration of the two receptors is about equal. At the onset of labor preterm and at term there is a tendency to an increase in the density of oxytocin and vasopressin V1a receptors, but there may be a heterogeneous expression of at least the former receptor between different myometrial cells. In advanced labor or after oxytocin treatment the receptors are markedly downregulated. The importance of oxytocin and vasopressin in mechanisms of preterm labor is confirmed by the therapeutic effect in the condition of the oxytocin and vasopressin V1a receptor blocking oxytocin analogue, atosiban. In women with primary dysmenorrhea the plasma concentration of vasopressin is elevated. The in vivo effect of vasopressin on uterine activity in non-pregnant women is about five times more pronounced than that of oxytocin, and it increases premenstrually. Correspondingly, the density of vasopressin V1a and oxytocin receptors vary to the same degree, and a premenstrual rise in the former receptor is seen. Atosiban and the non-peptide compound, SR 49059, which binds to the two receptors in a similar way as atosiban, are therapeutically effective in dysmenorrhea.

Topics: Dysmenorrhea; Female; Humans; Obstetric Labor, Premature; Oxytocin; Pregnancy; Receptors, Vasopressin; Uterus; Vasopressins

Topics: Adolescent; Adult; Analgesics; Child; Contraceptives, Oral, Hormonal; Cyclooxygenase Inhibitors; Dysmenorrhea; Female; France; Humans; Oxytocin; Parasympatholytics; Prostaglandins; Sweden; United States; Vasopressins

Mechanisms of possible pathophysiological importance in primary dysmenorrhea are discussed. Hyperactivity of the myometrium with accompanying uterine ischemia is considered to be of central importance in the causation of pain. Prostaglandins seem to be involved to a large extent in the development of the myometrial hyperactivity. Other mechanisms of possible importance such as ovarian hormones, cervical factors, vasopressin, nerves, and psychological factors can well act ultimately through prostaglandin release but an action directly on the myometrium and blood flow may also occur.

Topics: Adrenergic Fibers; Cervix Uteri; Cholinergic Fibers; Dysmenorrhea; Estradiol; Female; Humans; Menstruation; Oxytocin; Pressure; Progesterone; Prostaglandins; Regional Blood Flow; Uterine Contraction; Uterus; Vasopressins

GeGen Decoction, a well-known Chinese herbal formula, is widely used in China and other Asian countries to treat gynecological diseases, including primary dysmenorrhea. Pharmacological studies have confirmed that GeGen Decoction is able to inhibit spasmodic contractions of the uterus in vivo and in vitro.. The objective of this study is to examine the efficacy and safety of GeGen Decoction on primary dysmenorrheic patients.. This was a randomized, double-blinded, placebo-controlled trial. GeGen Decoction or placebo was administered a week before the expected start of each cycle for three consecutive menstrual periods. Between-group differences in pain intensity were detected by visual analogue scale (VAS). In addition, serum levels of arginine vasopressin (AVP) and estrogen (E) were examined by enzyme-linked immunosorbent assay. Metabolomic analysis was further used to evaluate the influence of GeGen Decoction on the metabolomics of primary dysmenorrheic patients.. A total of 71 primary dysmenorrheic women were recruited and 30 participants met the criteria were randomized into GeGen Decoction or placebo group. After three consecutive menstrual cycles' treatments, the VAS score of the GeGen Decoction group was significantly lower than that of the placebo group. Both serum levels of AVP and E decreased after GeGen Decoction administration, while the placebo seemed to have little effect on either of the index. Moreover, after GeGen Decoction treatment, seven important metabolites were identified by metabolomic analysis compared to the placebo group. No abnormalities in blood biochemical and routine physical examination pre and post GeGen Decoction intervention were observed.. GeGen Decoction can remarkably relieve the severity of menstrual pain without obvious adverse effects. Its therapeutic effect on primary dysmenorrhea might be related to the regulation of pituitary hypothalamic ovarian hormones, and interfering with the metabolic change.

Topics: Adolescent; Adult; Biomarkers; China; Double-Blind Method; Drugs, Chinese Herbal; Dysmenorrhea; Estrogens; Female; Humans; Metabolomics; Neurophysins; Pain Measurement; Protein Precursors; Severity of Illness Index; Time Factors; Treatment Outcome; Vasopressins; Young Adult

A model to study the effect of vasopressin V1a antagonist in dysmenorrhea.. A double-blind, randomized, placebo-controlled, cross-over trial was performed. Eight patients with primary dysmenorrhea and eight tuballigated, healthy subjects participated on days 1-2 of two consecutive menstruations. At each menstruation a bolus injection of 10 pmol/kg of vasopressin was administered before and during infusion of either 300 microg/min of atosiban or placebo. Intrauterine pressure was measured as area under the curve throughout the experiments. Ischemia markers in plasma and pain recorded by a visual analog scale were measured before and after each vasopressin injection as well as before and after the start of either atosiban or placebo infusion.. Vasopressin injections elevated area under the curve in both healthy volunteers and dysmenorrhea subjects. The vasopressin-induced rise in area under the curve was lower during atosiban administration than during infusion of placebo in both groups. None of the ischemia markers differed between or within groups at vasopressin injections or atosiban/placebo infusions. In subjects with dysmenorrhea the increase in pain following the administration of vasopressin was significantly lower during atosiban than during placebo infusion. Healthy volunteers experienced only slight discomfort after the vasopressin injections.. Atosiban reduces vasopressin-induced intrauterine pressure in both healthy volunteers and dysmenorrheics, and reported pain in subjects with dysmenorrhea. The ischemia markers are not a useful biomarker index in women with dysmenorrhea. The dysmenorrhea pain evoked by vasopressin correlated poorly with area under the curve, which may suggest that the effect is mediated by more than one V1a-like receptor. We conclude that this model with recordings in healthy women is useful in the evaluation of drug candidates for primary dysmenorrhea.

Topics: Adult; Antidiuretic Hormone Receptor Antagonists; Area Under Curve; Biomarkers; Cross-Over Studies; Double-Blind Method; Dysmenorrhea; Female; Hormone Antagonists; Humans; Ischemia; Pain Measurement; Prospective Studies; Receptors, Vasopressin; Treatment Outcome; Uterine Contraction; Vasopressins; Vasotocin

The myometrial hyperactivity and reduced uterine blood flow of primary dysmenorrhea is to a large extent caused by increased vasopressin secretion. A new therapeutic approach for this condition is to develop antagonists of uterine vasopressin V1a receptors. We studied a test model of vasopressin-induced dysmenorrhea in healthy, sterilized women and compared responses against those in dysmenorrheic subjects.. Eight women with primary dysmenorrhea and eight sterilized, healthy women participated in recordings of intrauterine pressure and experienced pain on days 1-2 of two menstruations. We tried to identify biochemical markers in plasma of uterine ischemia. Furthermore, the effects of repeated bolus injections of 10 pmol/kg b w of vasopressin or placebo on these parameters were assessed.. The vasopressin injections caused statistically significant increases in the area under the intrauterine pressure curve (AUC) in both healthy volunteers and patients with dysmenorrhea, the overall responses being greater in healthy volunteers. The experienced pain measured by visual analog scale in individual dysmenorrheic subjects tended to show higher maximal post-dose scores for the vasopressin injections than for placebo. Maximum visual analog scale scores and maximum AUCs in individual subjects tended to be related. Mean creatine kinase MB levels were higher in women with dysmenorrhea than in healthy subjects both before and after vasopressin administration, the converse being observed for C-reactive protein levels.. The present model appears to be useful for evaluating new drugs for the treatment of primary dysmenorrhea.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Dysmenorrhea; Female; Humans; Infertility, Female; Pain Measurement; Placebos; Pressure; Uterus; Vasopressins

We compared menstrual pain, uterine contractility and blood circulation, and plasma concentrations of vasopressin and prostaglandin F(2alpha) metabolite in women with versus without primary dysmenorrhea, and determined the effects of a vasopressin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (Atosiban), on these parameters. Our results do not support the contention that vasopressin is involved in the etiology of dysmenorrhea, plasma concentrations of vasopressin being similar in dysmenorrheic women and controls, and the vasopressin antagonist Atosiban having no effect on menstrual pain, intrauterine pressure or uterine artery pulsatility index in dysmenorrheic women.

Topics: Adult; Blood Flow Velocity; Cross-Over Studies; Dinoprost; Double-Blind Method; Dysmenorrhea; Female; Hormone Antagonists; Humans; Uterine Contraction; Uterus; Vasopressins; Vasotocin

The pathogenesis of primary dysmenorrhea is still poorly understood. The objective of the present investigation was to study differences in plasma concentrations of reproductive hormones in women with primary dysmenorrhea vs. healthy controls. In a prospective, parallel-group study we determined the plasma concentrations of oxytocin, vasopressin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17beta-estradiol (17beta-E2), progesterone and prostaglandin F 2alpha metabolite (15-keto-13,14-dihydro-PGF 2alpha) over one menstrual cycle in eight women with primary dysmenorrhea and eight healthy volunteers. In dysmenorrheic women the plasma concentration of oxytocin was significantly higher at menstruation (p = 0.0084) and that of vasopressin significantly lower at ovulation (p = 0.0281) compared with healthy women. They had also higher FSH levels in the early follicular phase (p = 0.0087) and at menstruation (p = 0.0066) and the 17beta-E2 concentration was higher in the late follicular phase (p = 0.0449). No differences were seen for LH, progesterone and PGF 2alpha metabolite. The differences of oxytocin, vasopressin, FSH and 17beta-E2 concentrations found in plasma suggest an involvement of these hormones in mechanisms of primary dysmenorrhea. These mechanisms seem to be mainly regulated through the hypothalamus and pituitary. The influence of oxytocin on the non-pregnant uterus seems to be more important than earlier believed.

Topics: Adult; Algorithms; Case-Control Studies; Dinoprost; Dysmenorrhea; Female; Gonadal Steroid Hormones; Gonadotropins; Health; Humans; Menstrual Cycle; Ovary; Oxytocin; Vasopressins; Young Adult

To investigate gene expressions for neurohypophyseal and ovarian hormones as well as their receptors in the endometrium of women with primary dysmenorrhoea and healthy subjects at ovulation.. A group of eight women with moderate to severe dysmenorrhoea and eight healthy subjects were compared in parallel between 18 and 35 years of age, regularly menstruating, non-overweight and nulliparous. The study was performed at The Department of Obstetrics and Gynecology, University Hospital of Lund, Sweden. Endometrial biopsies were taken around the time of ovulation, which was determined by repeated ultrasound examinations. Receptor and gene expressions for oxytocin and vasopressin in the tissue were measured.. The gene expression for oxytocin receptor was significantly lower in dysmenorrhoic than in healthy women, in median 1.21 and 3.44 oxytocin-receptor/actin, respectively (p=0.048). The expressions for oxytocin peptide, vasopressin V1a receptor, oestrogen receptor alpha, beta and progesterone receptor did not differ between the two groups. Expression of vasopressin peptide was not detectable.. A lower oxytocin receptor gene expression at mid-cycle could be involved in the aetiology of primary dysmenorrhoea. However, the importance of a paracrine effect of oxytocin and its receptor at ovulation warrants further investigation.

Topics: Adult; Biopsy; Case-Control Studies; Dysmenorrhea; Endometrium; Female; Humans; Menstrual Cycle; Ovulation; Oxytocin; Prospective Studies; Receptors, Estrogen; Receptors, Oxytocin; Receptors, Progesterone; Receptors, Vasopressin; RNA, Messenger; Vasopressins

Topics: Dysmenorrhea; Female; Humans; Labor, Obstetric; Obstetric Labor, Premature; Oxytocin; Pregnancy; Uterus; Vasopressins

Topics: Dysmenorrhea; Female; Humans; Leukotrienes; Prostaglandins; Vasopressins

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

Topics: Dysmenorrhea; Female; Humans; Vasopressins