oxytocin and Dysmenorrhea

Dysmenorrhea is a prevalent gynecological disease among women at reproductive age. It is classified as the primary dysmenorrhea and the secondary dysmenorrhea according to the etiology. The primary dysmenorrhea is caused by uterine hypercontraction without any identifiable pelvic lesions, while the secondary dysmenorrhea is incurred by gynecological disorder with pelvic organic lesions. However, the underlying mechanism of dysmenorrhea is not completely clear. Animal models of dysmenorrhea, especially mouse and rat model, are helpful to explore the pathophysiological mechanism of dysmenorrhea, clarify the therapeutic effect of compounds, and guide clinical treatment. The murine model of primary dysmenorrhea is commonly induced by oxytocin or prostaglandin F

Topics: Animals; Dinoprost; Disease Models, Animal; Dysmenorrhea; Female; Humans; Mice; Oxytocin; Rats; Uterus

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

In order to study the involvement of oxytocin (OT) and vasopressin (AVP) in mechanisms of uterine activation and to clarify the therapeutic potential of antagonists to these hormones in preterm labour and primary dysmenorrhoea, studies of human uterine contractility in vivo and in vitro as well as measurements of OT and AVP V1a receptors were performed. Good correlations between OT receptor concentrations and effects on contractility were observed in both the pregnant and non-pregnant states, which indicates that OT acts specifically on its own receptor in the uterus. For AVP there was lack of such correlation which may suggest that this hormone influences both the OT and AVP V1a receptor sites. At the onset of labour both preterm and at term no marked increase in the OT receptor concentration was observed, but OT may still be involved in the initiation of labour, being produced locally in the uterus and not detectable in plasma. We observed a reduced OT receptor concentration in advanced labour and after OT infusion, which suggests that OT influences its own receptor. The AVP V1a receptor concentration and the effect of AVP on the uterus were about equal to those for OT, and the concentration of AVP V1a receptors also tended to decrease in advanced labour, observations which support an involvement also of AVP in the mechanisms of labour. In non-pregnant women AVP receptors as well as uterine effects of AVP in vitro and in vivo were about five times higher than those for OT, and the effect of AVP was increased premenstrually. This firmly supports an aetiological role of this peptide in the uterine hyperactivity of primary dysmenorrhoea. We have also shown that the analogue 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-OT, which blocks both the OT and AVP V1a receptor sites, given by intravenous infusion inhibits both preterm labour and dysmenorrhoea, and this is in agreement with our receptor and contractility findings.

Topics: Arginine Vasopressin; Dysmenorrhea; Female; Hormone Antagonists; Humans; In Vitro Techniques; Labor, Obstetric; Obstetric Labor, Premature; Oxytocin; Pregnancy; Receptors, Oxytocin; Receptors, Vasopressin; Tocolytic Agents; Uterine Contraction; Vasotocin

Topics: Amino Acid Sequence; Antidiuretic Hormone Receptor Antagonists; Clinical Trials as Topic; Dysmenorrhea; Female; Humans; Molecular Sequence Data; Obstetric Labor, Premature; Oxytocin; Peptides, Cyclic; Pregnancy; Receptors, Oxytocin; Tocolytic Agents; Uterine Contraction

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

Topics: Abortion, Induced; Cervix Uteri; Corpus Luteum; Dysmenorrhea; Female; Humans; Labor, Induced; Male; Obstetric Labor, Premature; Obstetrics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prostaglandin Antagonists; Prostaglandins; Prostaglandins, Synthetic; Uterus

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

Topics: Adrenal Cortex Hormones; Anabolic Agents; Androgens; Dysmenorrhea; Endocrinology; Endometriosis; Estrogens; Female; Fetus; Gonadotropins; Gonadotropins, Pituitary; Gynecology; Humans; Maternal-Fetal Exchange; Obstetrics; Ovulation; Oxytocin; Pituitary Gland; Pregnancy; Pregnancy Tests; Pregnanediol; Progesterone; Progestins; Steroids

To investigate the therapeutic mechanism of Jiawei Mojie Tablet (JMT) in treating primary dysmenorrhea (PD) by observing its effect on plasma oxytocin (OT) level in patients in menstrual period.. Sixty-three patients with PD enrolled in the study were randomly divided into the JMT group (n = 33) and the control Group (n = 30, treated with Yueyueshu Granule) to observe the change of OT level in the menstrual period before and after treatment.. OT level in patients with PD was obviously higher than that in healthy subjects (P < 0.01), and was positively correlated with the degree of pain (r = 0.738, P < 0.01). OT level reduced significantly after treatment (P < 0.01), the reduction was more significant in the JMT group than that in the control group (P < 0.01).. JMT could reduce the OT level in menstrual period.

Topics: Adolescent; Adult; Drugs, Chinese Herbal; Dysmenorrhea; Female; Humans; Oxytocin; Tablets

Primary dysmenorrhea is one of the most common reasons for gynecologic visits, but due to the lack of suitable animal models, the pathologic mechanisms and related drug development are limited. Herein, we establish a new mouse model which can mimic the periodic occurrence of primary dysmenorrhea to solve this problem. Non-pregnant female mice were pretreated with estradiol benzoate for 3 consecutive days. After that, mice were injected with oxytocin to simulate menstrual pain on the 4th, 8th, 12th, and 16th days (four estrus cycles). Assessment of the cumulative writhing score, uterine tissue morphology, and uterine artery blood flow and biochemical analysis were performed at each time point. Oxytocin injection induced an equally severe writhing reaction and increased PGF

Topics: Animals; Cyclooxygenase 2; Disease Models, Animal; Dysmenorrhea; Female; Humans; Mice; Oxytocin; Uterus

The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6-8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour.

Topics: Animals; Disease Models, Animal; Dysmenorrhea; Female; Ibuprofen; Inflammation; Mast Cells; Mice; Neutrophils; Oxytocin; Piper; Plant Extracts

Dysmenorrhea is one of the most common gynecological problems among menstruating females. Blood-activating and stasis-resolving herbs (BASRHs) have been employed to be the first choice for treating dysmenorrhea in China. Especially, the essential oils of some BASRHs have been confirmed to play important roles in the treatment of dysmenorrhea, but the constituents and uterine smooth muscle relaxant activity of some commonly used BASRH essential oils have not been fully assessed, and whether there are differences in the constituents and anti-dysmenorrhea effect among BASRH essential oils has not been evaluated.. This study aims to systematically investigate the chemical constituents of 10 BASRH essential oils and assess their uterine smooth muscle relaxant activity and the preliminary mechanism of the most effective essential oil.. The chemical constituents of 10 BASRH essential oils were analyzed by Gas Chromatography-Mass Spectrometer. A rat model of dysmenorrhea in vitro was established to investigate the uterine smooth muscle relaxant activity of 10 kinds of essential oils. Rat isolated uterus strips were given different dose of 10 kinds of essential oils (0.04, 0.08, 0.16 mg/mL). The contractile responses were recorded with Power Lab recording system, and contractile tension, contractile frequency, and contractile activity were evaluated. The preliminary mechanism of the essential oil of the rhizomes of Curcuma phaeocaulis Valeton (CPEO) was assessed using a rat model of dysmenorrhea in vivo and in vitro, and rats were given the CPEO (15, 30, and 60 mg/kg) by gavage. The level of Ca. The results of Gas Chromatography-Mass Spectrometer analysis showed that more than 81 components (content: 1% max appearance) were identified. The main components of the 10 BASRH essential oils were found to be monoterpenoids, sesquiterpenoids, diterpenoids, aromatics, aliphatics, and phthalides. The study of in vitro smooth muscle relaxant activity demonstrated that all the essential oils except the essential oil of the roots of Cyathula officinalis K.C.Kuan markedly decrease the contractile activity, tension, and frequency (P < 0.05 or P < 0.01). Among these oils, CPEO has the most pronounced effect. Further in vivo studies indicated that CPEO can significantly decrease the level of Ca. BASRH essential oils play an important role in inhibiting uterine smooth muscle contractions, and sesquiterpenoids and phthalides in BASRH essential oils are important active compounds for relaxing uterine smooth muscle. CPEO is a favorable candidate for developing anti-dysmenorrhea drugs.

Topics: Animals; Calcium; Calcium Signaling; Cations; China; Curcuma; Drugs, Chinese Herbal; Dysmenorrhea; Ethnopharmacology; Female; Gas Chromatography-Mass Spectrometry; In Vitro Techniques; Medicine, Chinese Traditional; Muscle Relaxation; Muscle, Smooth; Oils, Volatile; Oxytocin; Plant Roots; Rats, Sprague-Dawley; Uterine Contraction; Uterus

Akebiae Fructus, a Tujia minority folk medicine and a well-known traditional Chinese medicine for soothing the liver, regulating Qi, promoting blood circulation and relieving pain, is widely used in the treatment of primary dysmenorrhea. However, little is known about its underlying mechanism.. To explore the effect of Akebiae Fructus on primary dysmenorrhea model induced by estradiol benzoate and oxytocin, and to provide better understanding of the mechanism of Akebiae Fructus for primary dysmenorrhea treatment.. The primary dysmenorrhea mouse model was used in this study. Except for the control group and the normal administration group, the mice of other groups were subcutaneously injected with estradiol benzoate (10 mg/kg/d) for 10 consecutive days. From the 5th day of the ten-day model period, the positive control groups were given 0.075 g/kg ibuprofen and 7.5 g/kg Leonurus granule, the drug groups were given 0.2 g/kg, 0.4 g/kg, 0.8 g/kg Akebiae Fructus extract, the normal administration group was given 0.8 g/kg Akebiae Fructus extract, and the same volume saline was given in the control group. On the tenth day, oxytocin (10 U/kg) was peritoneally injected after estradiol benzoate injected 1 h. After the oxytocin injection, writhing behavior was observed for 30 min. Then the uterine tissue was collected to measure the level of PGF. Akebiae Fructus inhibited the writhing, decreased the PGF. Akebiae Fructus could effectively alleviate the symptoms of primary dysmenorrhea, regulate metabolic disorders, and control the related gene expression in primary dysmenorrhea. The study may provide clues for further study of Akebiae Fructus treatment on primary dysmenorrhea.

Topics: Animals; Benzoates; Biomarkers; Dinoprost; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Dysmenorrhea; Female; Gene Expression Regulation; Inflammation; Medicine, Chinese Traditional; Metabolic Networks and Pathways; Metabolome; Mice, Inbred ICR; Oxytocin; Pain; Ranunculales; Transcriptome; Uterine Contraction; Uterus

Oxytocin-dependent mechanisms are hypothesized to contribute to painful menses, but clinical trials of oxytocin antagonists for dysmenorrhea have had divergent outcomes. In contrast, broader studies have shown that increased systemic oxytocin concentrations are associated with increased pain tolerance and improved psychosocial function. We sought to confirm whether increased serum oxytocin concentrations are associated with menstrual pain and other psychosocial factors. Women with a history of primary dysmenorrhea (n = 19), secondary dysmenorrhea (n = 12), and healthy controls (n = 15) completed pain and psychosocial questionnaires, provided a medical history, and rated their pain during the first 48 h of menses. Serum samples were collected during menses to measure oxytocin concentrations. Oxytocin was significantly lower in participants with a history of primary (704 ± 33 pg/mL; p < 0.001) or secondary (711 ± 66 pg/mL; p < 0.01) dysmenorrhea compared to healthy controls (967 ± 53 pg/mL). Menstrual pain over the past 3 months (r = -0.58; p < 0.001) and during the study visit (r = -0.45; p = 0.002) was negatively correlated with oxytocin concentrations. Pain catastrophizing (r = -0.39), pain behavior (r = -0.32), and pain interference (r = -0.31) were also negatively correlated with oxytocin levels (p's < 0.05). Oxytocin was not significantly correlated with psychosocial factors. Contrary to our hypothesis, women with a history of primary or secondary dysmenorrhea had lower oxytocin concentrations during menses when compared to healthy controls. Lower circulating oxytocin concentrations were also associated with worse menstrual pain and pain-related behavior. When considering the existing literature, low circulating oxytocin may be a sign of dysfunctional endogenous pain modulation.

Topics: Adult; Dysmenorrhea; Female; Humans; Oxytocin; Pain Measurement; Surveys and Questionnaires; Young Adult

Primary dysmenorrhea is the most common gynaecologic problem in menstruating women and is characterized by spasmodic uterine contraction and pain symptoms associated with inflammatory disturbances. Paeonol is an active phytochemical component that has shown anti-inflammatory and analgesic effects in several animal models. The aim of this study was to explore whether paeonol is effective against dysmenorrhea and to investigate the potential mechanism of cannabinoid receptor signalling.. Dysmenorrhea was established by injecting oestradiol benzoate into female mice. The effects of paeonol on writhing time and latency, uterine pathology and inflammatory mediators were explored. Isolated uterine smooth muscle was used to evaluate the direct effect of paeonol on uterine contraction.. The oral administration of paeonol reduced dysmenorrhea pain and PGE2 and TNF-α expression in the uterine tissues of mice, and paeonol was found to be distributed in lesions of the uterus. Paeonol almost completely inhibited oxytocin-, high potassium- and Ca. Paeonol partially acts through CB2R to restrain calcium influx and uterine contraction to alleviate dysmenorrhea in mice. These results suggest that paeonol has therapeutic potential for the treatment of dysmenorrhea.

Topics: Acetophenones; Animals; Calcium; Dinoprostone; Dysmenorrhea; Estradiol; Female; Mice, Inbred ICR; Molecular Docking Simulation; Myocytes, Smooth Muscle; Myometrium; Oxytocin; Receptor, Cannabinoid, CB2; Tumor Necrosis Factor-alpha; Uterine Contraction; Uterus

Primary dysmenorrhea is a common occurrence in adolescent women and is a type of chronic inflammation. Dysmenorrhea is due to an increase in oxidative stress, which increases cyclooxygenase-2 (COX-2) expression, increases the concentration of prostaglandin F2α (PGF2α), and increases the calcium concentration in uterine smooth muscle, causing excessive uterine contractions and pain. The polyphenolic compound oleocanthal (OC) in extra virgin olive oil (EVOO) has been shown to have an anti-inflammatory and antioxidant effect. This study aimed to investigate the inhibitory effect of extra virgin olive oil and its active ingredient oleocanthal (OC) on prostaglandin-induced uterine hyper-contraction, its antioxidant ability, and related mechanisms. We used force-displacement transducers to calculate uterine contraction in an ex vivo study. To analyze the analgesic effect, in an in vivo study, we used an acetic acid/oxytocin-induced mice writhing model and determined uterus contraction-related signaling protein expression. The active compound OC inhibited calcium/PGF2α-induced uterine hyper-contraction. In the acetic acid and oxytocin-induced mice writhing model, the intervention of the EVOO acetonitrile layer extraction inhibited pain by inhibiting oxidative stress and the phosphorylation of the protein kinase C (PKC)/extracellular signal-regulated kinases (ERK)/ myosin light chain (MLC) signaling pathway. These findings supported the idea that EVOO and its active ingredient, OC, can effectively decrease oxidative stress and PGF2α-induced uterine hyper-contraction, representing a further treatment for dysmenorrhea.

Topics: Abdominal Pain; Aldehydes; Animals; Anti-Inflammatory Agents; Antioxidants; Calcium; Cyclooxygenase 2; Cyclopentane Monoterpenes; Dinoprost; Disease Models, Animal; Dysmenorrhea; Female; Mice; Olive Oil; Oxidative Stress; Oxytocin; Phenols; Prostaglandins; Signal Transduction; Uterine Contraction; Uterus

Dang-Gui-Shao-Yao-San () and Gui-Zhi-Fu-Ling-Tang () and among the herbal medicines commonly used to treat primary dysmenorrhea with proven record of effectiveness.. This study aims to assess the effectiveness of herbal medicines on relieving primary dysmenorrhea in a murine model and to delineate a plausible mechanism.. Herbal medicines in the form of pills (Wan) or capsules, including Gui-Zhi-Fu-Ling capsule, Gui-Zhi-Fu-Ling-Wan, Jia-Wei-Xiao-Yao-Wan, and Shao-Fu-Zhu-Yu capsule were purchased from local drug stores in Nanjing. Dang-Gui-Shao-Yao-San filled from a local hospital. The identity of the drugs was validated by HPLC profiling. Female ICR mice were used for an induced dysmenorrhea model. The severity of dysmenorrhea was evaluated and scored, the motor coordination and balance affected by induced dysmenorrhea was assessed by a Rotarod test. Uterine inflammation and edema were examined after histological and immunohistochemical staining. The effect of the drugs on COX2 activity was evaluated enzymatically.. The Chinese herbal medicines at dosages relevant to recommended uses in humans relieved painful responses, including abdominal wall contraction, pelvic twisting and/or rear limb stretching. The treatment also improved motor coordination, extending the time staying on a rotating rod from 2.64 ± 0.38 min of oxytocin-induced group to 8.59 ± 1.45 (DGSYs), 9.50 ± 1.47 (GZFLc), 8.04 ± 1.87 (GZFLw), 9.91 ± 1.62 (JWXYw), and 8.20 ± 1.35 min (SFZYc), respectively. H&E staining showed that treatment with ibuprofen or Chinese herbal medicines markedly decreased edema and inflammatory cell infiltration in uterine tissues. The treatment did not significantly affect pattern of COX2 staining. In an in vitro enzymatic assay, the Chinese herbal medicines showed strong inhibitory activity against cyclooxygenase-2. The aqueous extracts from P. lactiflora or P. suffruticosa, two of the common components in the formulae tested, also showed anti-dysmenorrhea activity in the rotarod assay.. The study demonstrates that traditionally used Chinese herbal medicines are effective against induced-dysmenorrhea. These herbal medicines relieve dysmenorrhea symptoms likely though inhibition of cyclooxygenase activity.

Topics: Animals; Drugs, Chinese Herbal; Dysmenorrhea; Female; Mice, Inbred ICR; Oxytocin; Uterus

Guizhi Fuling capsule (GFC) was an important traditional Chinese herbal medicine used for the treatment of primary dysmenorrheal (PD). The aim of this study was to evaluate the anti-dysmenorrheal effect of GFC on dysmenorrheal rats induced by oxytocin and to investigate its mechanism of action. An integrative urinary metabolomic study based on

Topics: Animals; Biomarkers; Capsules; Chromatography, High Pressure Liquid; Disease Models, Animal; Drugs, Chinese Herbal; Dysmenorrhea; Estradiol; Female; Humans; Medicine, Chinese Traditional; Metabolome; Metabolomics; Oxytocin; Proton Magnetic Resonance Spectroscopy; Rats; Rats, Wistar; Tandem Mass Spectrometry

Primary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Different doses of PHC were administrated intraperitoneally following estradiol benzoate administration. Writhing scores were assessed, and pathological changes of the uterus were observed via hematoxylin and eosin staining. Western blot and real-time PCR were used to evaluate the expression level of the M

Topics: Animals; Behavior, Animal; Calcium; Disease Models, Animal; Dysmenorrhea; Estradiol; Female; Oxytocin; Pain; Quinuclidines; Rats, Sprague-Dawley; Receptor, Muscarinic M3; Toll-Like Receptor 3; Toll-Like Receptor 4; Uterus

Compound Muniziqi granule (CMG) is usually used as a traditional Uighur medicine to treat acne, chloasma, skin inflammation, primary dysmenorrhea (PDM), and menopausal syndrome. However, there are no sufficient data to support the clinic uses of CMG in PDM.. This work aims to examine the effect of CMG as a treatment for PDM and reveal its possible therapeutic mechanism.. In vivo and in vitro mouse PDM models were utilized in this study. The mouse uterine contraction was induced by oxytocin after progynova or estradiol benzoate pretreatment. CMG, alkaloid extracts from seeds of Peganum harmala (AEP), and 10% and 95% ethanol extracts from seeds of Nigella glandulifera (EEN10 and EEN95) were given to mice in three doses by gavage. The writhing times within 30 min after oxytocin treatment were recorded to evaluate the analgesic effect, and the glutathione peroxidase (GSH-Px), malondialdehyde (MDA), 6-keto-prostaglandin F. In contrast to the control group, CMG, AEP, N10, and N95 could display analgesic activities dose dependently by reducing the writhing response of the PDM model mice. CMG, AEP, EEN10, and EEN95 could also remarkably decrease the level of PGF. CMG exhibited a significant protective effect on experimental PDM. The mechanisms are probably associated with abating lipid peroxidation and over-inflammatory reaction, and alleviating the contraction of isolated mouse uterus. The seeds of P. harmala and N. glandulifera in the CMG may play an important role in exerting protective effects on PDM. This study provides pre-clinic proof to the use of CMG in clinical practice of PDM.

Topics: Analgesics; Animals; Dysmenorrhea; Female; Mice; Nigella; Oxytocin; Peganum; Phytotherapy; Plant Extracts; Seeds; Uterine Contraction; Uterus

The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea (PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction (GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F2 alpha (PGF2α) and Ca(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF2α and Ca(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.

Topics: Animals; Blood Flow Velocity; Drugs, Chinese Herbal; Dysmenorrhea; Female; Humans; Mice; Mice, Inbred ICR; Oxytocin; Uterine Contraction; Uterus

Guizhi Fuling formula, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, is composed of Cinnamomum cassia (L.) J.Presl (Cassia bark), Poria cocos (Schw.) Wolf (Poria), Paeonia suffruticosa andrews (Moutan Cortex), Paeonia lactiflora Pall (Herbaceous peony), and Amygdalus persica L.(Persicae Semen). It has clinical efficacy of activating blood circulation to dissipate blood stasis and is commonly used for the treatment of primary dysmenorrhea. However, its therapeutic mechanism has not been clearly elucidated. The aim of this study is to reveal molecular mechanisms of action using in vivo and in vitro experimental models.. The ICR mouse uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment. Mice were given GZFLC (0.54, 1.08g/kg) by gavage. The levels of NO, PGF2α and Ca(2+) in uterine tissue were determined according to instructions. Cyclooxygenase-2 (COX-2) and oxytocin receptor (OTR) proteins in uterine tissue were assessed by Western Blot. Mouse isolated uterus strips were mounted in tissue organ baths containing Locke's solution. The contractile responses were recorded with Power Lab recording system. The effect of GZFLC on spontaneous uterine contraction, and uterine contraction induced by oxytocin, PGF2α was observed. Myometrial cells were exposed to oxytocin (5U/L) to induce calcium release, and the effect of GZFLC and its components (PL, PGG, CA) on intracellular Ca(2+) was analyzed with fluorometry imaging.. In vivo study demonstrated that GZFLC significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 55%. It also decreased the levels of NO, PGF2α and Ca(2+) in oxytocin-induced mice uterine tissue. Moreover, Western blot analysis showed that COX-2 and OTR expressions in uterine tissue of dysmenorrhea mice were significantly reduced. GZFLC inhibited spontaneous uterus contractions in a dose-dependent manner, and the IC50 value was 0.99mg/ml. The IC50 values of GZFLC on PGF2α, oxytocin-induced contractions were 1.45mg/ml, 3.53mg/ml, respectively. Further in vitro studies indicated that GZFLC and its components (PL, PGG, CA) could restrain intracellular calcium levels in favour of uteri relaxation.. Both in vivo and in vitro results indicated that GZFLC possessed a significant spasmolytic effect on uterine tetanic contraction. The present study provides in vivo and in vitro experimental evidence to support the use of GZFLC for the clinical treatment of primary dysmenorrheal (PD).

Topics: Animals; Calcium; Cyclooxygenase 2; Dinoprost; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Dysmenorrhea; Estradiol; Female; In Vitro Techniques; Mice, Inbred ICR; Nitric Oxide; Oxytocics; Oxytocin; Parasympatholytics; Receptors, Oxytocin; Tocolytic Agents; Uterine Contraction; Uterus

Primary dysmenorrhea (PDM), a common, clinically heterogeneous endocrine disorder affecting young women, is associated with endocrinopathy and metabolic abnormalities. The Xiang-Fu-Si-Wu Decoction (XFSWD) is a traditional Chinese medicine preparation used to treat PDM.. In the current study, a plasma metabonomics method based on the ultra-high-performance liquid chromatography-quantitative time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS) system was employed to examine the mechanism of XFSWD action in PDM.. Estradiol benzoate (0.01 g/kg/d) and oxytocin (5 mL/kg) were used to create the dysmenorrhea rat model. Based on the chromatographic data of plasma samples at different time-points following oral administration of XFSWD mixed in water (37.8 g crude herbs/kg) on day 7, partial least square (PLS) and discriminate analysis (DA) were applied to visualize group differentiation and marker selection.. Systemic changes occurring in PDM reflect alterations in not only uterus function but also whole-body metabolism. The XFSWD was effective as a therapeutic agent for PDM by reflect metabolic pathway. Prostaglandins and lysophospholipids were identified as two marker types for oxytocin-induced dysmenorrhea syndrome, including LysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0), PGJ₂, 11-deoxy-11-methylene-PGD₂, 15-deoxy-δ-12,14-PGJ₂, LysoPC(20:3), etc. Specifically, the concentrations of prostaglandins compounds (PGJ₂, 11-deoxy-11-methylene-PGD₂, 15-deoxy-δ-12,14-PGJ₂) were increased while those of lysophospholipid compounds [lysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0)] were decreased to a significant extent (p < 0.05) in dysmenorrheal rats. Upon treatment with the XFSWD at 12 h, the concentrations of lysophospholipids showed no significant differences (P > 0.05) between the model and normal groups. The lysophospholipid levels were restored. Lysophospholipids were the key factors in phospholipid metabolism. Thus, disruption of phospholipids metabolism appears critical for the development of dysmenorrhea. The XFSWD exerted its effects by interfering with the sphingolipid metabolic pathway.. The metabonomics method presents a promising tool to treat PDM in animal models, and may be applicable for clinical treatment of the human disease in the future.

Topics: Animals; Biomarkers; Discriminant Analysis; Disease Models, Animal; Drugs, Chinese Herbal; Dysmenorrhea; Estradiol; Female; Least-Squares Analysis; Lysophospholipids; Metabolic Networks and Pathways; Metabolome; Oxytocin; Prostaglandins; Syndrome

Xiang-Fu-Si-Wu Decoction (XFSWD) has been widely used to treat primary dysmenorrhea in clinical practice for hundreds of years and shown great efficacy. One fraction of XFSWD, which was an elution product by macroporous adsorption resin from aqueous extract solution with 60% ethanol (XFSWE), showed great analgesic effect. The present study was conducted to investigate the possible pharmacokinetic and tissue distribution profiles of four major bioactive constituents (berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine) after oral administration of XFSWE in dysmenorrheal symptom rats, and to compare the difference between normal and dysmenorrheal symptom rats.. Estradiol benzoate and oxytocin were used to produce dysmenorrheal symptom rat model. The experimental period was seven days. At the final day of experimental period, both normal and dysmenorrheal symptom rats were orally administrated with XFSWE, and then the blood and tissues samples were collected at different time points. Berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine in blood and tissue samples were determined by LC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration-time data using non-compartmental methods. The differences of pharmacokinetic parameters among groups were tested by one-way analysis of variance (ANOVA).. There were statistically significant differences (P<0.05) in Cmax, Tmax, AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞) and CL/F between normal and dysmenorrheal symptom rats that orally administered with same dosage of XFSWE. In tissue distribution study, the results showed that the overall trend was C(Spleen)>C(Liver)>C(Kidney)>C(Uterus)>C(Heart)>C(Lung)>C(Ovary)>C(Brain)>C(Thymus), C(M-60 min)>C(M-120 min)>C(M-30 min)>C(C-60 min)>C(C-120 min)>C(C-30 min). The contents of protopine in liver, spleen and uterus were more than that in other tissues of dysmenorrheal symptom rats. Compared to normal rats, partial contents of the compounds in dysmenorrheal symptom rats׳ tissues at different time points had significant difference (P<0.05).. This study was the first report about pharmacokinetic and tissue distribution investigation in dysmenorrheal symptom animals. The results indicated that berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine have higher uptake and slower elimination in the rats with dysmenorrheal syndrome, which suggests that the rate and extent of drug metabolism were altered in dysmenorrheal syndrome rats. And the results also demonstrated that berberine, protopine and tetrahydropalmatine in normal and dysmenorrheal symptom rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in dysmenorrheal symptom animals.

Topics: Administration, Oral; Animals; Disease Models, Animal; Drugs, Chinese Herbal; Dysmenorrhea; Estradiol; Female; Oxytocin; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Tissue Distribution

The Chinese herbs of myrrh and frankincense are often combined for treating some inflammatory pain diseases with synergistic therapeutic effects. In this study, we investigated the effects of individual herbal extracts and combined extract on anti-inflammatory and analgesic activities in vivo and analyzed the potential bioactive components from the combination extract by ultra-performance liquid chromatography coupled with mass spectrum (UPLC-MS/MS).. The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin and carrageenan. In addition, we determined the levels of PGE(2) and nitrite in the edema paw. The analgesic activity was examined against oxytocin-induced dysmenorrhea in mice. The effects of the administration of dolantin or indomethacin were also studied for references. The components in combination extract (CWE) were analyzed by UPLC-MS/MS.. The results showed that myrrh water extract (MWE) and the combined extract (CWE) at the 3.9 g/kg, and 5.2 g/kg showed inhibition of formalin-induced paw edema with inhibition rate of 30.44%, and 23.50%, respectively. The PGE(2) production was inhibited significantly by all samples (P<0.01 or P<0.05). CWE showed stronger suppression on carrageenan-induced mice paw edema at 2 and 3h after administration of drugs. The inhibitory effect of CWE on nitrite production was between that of MWE and water extract of frankincense (FWE) at 5.2 g/kg. The dysmenorrhea mice test showed MWE could remarkably reduce the writhing times (P<0.05) and prolong the latency period, while FWE showed no obvious effects on the writhing times. CWE significantly reduced the writhing times and prolong the latency period (P<0.01).. These results demonstrated MWE, FWE, and CWE exhibited significant anti-inflammatory and analgesic activities. The findings suggest that CWE may be therapeutically more useful for mitigating inflammatory pain than individual herbal extract. In addition, 12 potential active compounds were identified from CWE. These data may support the fact the traditional application of this combined extract in treating various diseases associated with inflammatory pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Boswellia; Carrageenan; Chromatography, Liquid; Commiphora; Dinoprostone; Disease Models, Animal; Drug Combinations; Dysmenorrhea; Edema; Female; Formaldehyde; Indomethacin; Meperidine; Mice; Mice, Inbred ICR; Molecular Structure; Motor Activity; Nitrites; Oxytocin; Pain Measurement; Pain Threshold; Plant Extracts; Plants, Medicinal; Reaction Time; Tandem Mass Spectrometry; Time Factors

Xiang-fu-si-wu decoction has been widely used to treat blood stasis syndromes in gynecology diseases, such as primary dysmenorrhea in clinical practice for hundreds of years and show great efficacy. The efficient components and mechanism of action on uterus contraction were seldom reported.. The present study was conducted to evaluate the inhibitory effects of active fractions and its main bioactive components of xiang-fu-si-wu decoction on uterine contraction.. Model of non-pregnant mice uterine contraction induced by oxytocin was used to evaluate activity. Levels of Ca(2+) and nitric oxide (NO) in primary dysmenorrheal model mice uterus were also been detected. Components in active fraction were identified and quantified by HPLC-DAD.. It was found the active fraction of xiang-fu-si-wu decoction may become potential Ca(2+) channel blocking agents. Alkaloids like berberine were main active components in bioactive fraction of xiang-fu-si-wu decoction for dysmenorrhea on uterus contraction.

Topics: Alkaloids; Animals; China; Disease Models, Animal; Drugs, Chinese Herbal; Dysmenorrhea; Ethnopharmacology; Female; Humans; In Vitro Techniques; Medicine, Chinese Traditional; Mice; Mice, Inbred ICR; Oxytocin; Phytotherapy; Plants, Medicinal; Uterine Contraction

To observe effects of Shujing Ketong soft capsules (SJKTSC) on activities of the uterine of the rat in vitro and in vivo.. The isolated rat uterine were mounted in the improved Genell solution with a final content of 0. 96, 1.92, 3.84 microg x g(-1) of SJKTSC at 37 degrees C; and 9. 6, 19. 2, 38.4 mg x kg(-1) of SJKTSC and 2 g x kg(-1) of Tongjingbao granules were given to the rat through the duodenum respectively. Their effects on frequency, amplitude and activity of contraction of rat uterus in vitro and in vivo were investigated.. SJKTSC could significantly inhibit the frequency, amplitude and activity of contraction of the normal rat uterus in vitro and decrease the oxytocin-induced increase of contraction of the rat uterus in vitro; lowered the frequency, amplitude and activity of the oxytocin-induced contraction of the rat uterus in vivo and inhibit the oxytocin-induced the strengthening of contraction of the rat uterus in vivo.. Shujing Ketong soft capsules maybe used for treatment of dysmenorrhea induced by spasm of uterine smooth muscle.

Topics: Animals; Capsules; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Dysmenorrhea; Female; In Vitro Techniques; Muscle, Smooth; Oxytocin; Rats; Rats, Wistar; Time Factors; Uterine Contraction; Uterus

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

In the present study, the effects of ligustilide (LIG) on uterine contraction in vitro were investigated. In isolated rat uterine, LIG (2-8 microg/ml) inhibited the spontaneous periodic contraction in a concentration-dependent manner (EC(50)=4.4 microg/ml, 95% confidence interval 2.7-6.1 microg/ml), and attenuated prostaglandin F2alpha (PGF(2)alpha)- or acetylcholine chloride (Ach)-induced uterine contractions. At 8 microg/ml, LIG nearly completely blocked the PGF(2)alpha-induced contractions (95.3%). In the case of Ach-induced contraction, about 73.9% was inhibited by LIG at this dosage. It was also observed that LIG affected significantly oxytocin-induced increase in the contraction of uterine horns that were incubated not only in the Locke solution but also in a Ca(2+)-free solution. In addition, LIG caused concentration-dependent inhibition of uterine contraction induced by K(+) (56.3 Mm) depolarization, reaching the significant level at 2 microg/ml (EC(50)=3.3 microg/ml, 95% confidence interval 2.5-4.1 microg/ml). The findings clearly show that LIG has multiple effects on the uterine smooth muscles, suggesting that LIG possesses a non-specific antispasmodic function. The data also imply strongly that LIG is one of active ingredients of Danggui and has the potential to be developed into an effective drug for the prevention and treatment of primary dysmenorrhoea.

Topics: 4-Butyrolactone; Acetylcholine; Angelica; Animals; Calcium; Dinoprost; Dose-Response Relationship, Drug; Dysmenorrhea; Female; Oxytocics; Oxytocin; Phytotherapy; Potassium; Rats; Uterine Contraction; Uterus

Increasing the ectopic uterine motility is the major reason for primary dysmenorrhea. This motility is the basis for several symptoms including for pain is the main complaints of patients with primary dysmenorrhea. There are several mechanisms, which initiate dysmenorrhea. Therefore, different compounds can be employed to control its symptoms. In long-term therapy, combination of oestrogens and progestins may be useful. In short-term therapy, dysmenorrhea sometimes non-steroidal anti-inflammatory drugs (NSAIDs) are used. Most of NSAIDs in long-term therapy show severe adverse effects. In an attempt to find agents with less adverse effect the fennel essential oil (FEO) was chosen for this investigation. In this article, effects of FEO on the uterine contraction and estimation of LD(50) in rat were described. For assessment of pharmacological effects on the isolated rat uterus, oxytocin (0.1, 1 and 10 mu/ml) and prostaglandin E(2) (PGE(2)) (5x10(-5) M) were employed to induce muscle contraction. Administration of different doses of FEO reduced the intensity of oxytocin and PGE(2) induced contractions significantly (25 and 50 microg/ml for oxytocin and 10 and 20 microg/ml PGE(2), respectively). FEO also reduced the frequency of contractions induced by PGE(2) but not with oxytocin. LD(50) of FEO was obtained in the female rats by using moving average method. The estimated LD(50) was 1326 mg/kg. No obvious damage was observed in the vital organs of the dead animals.

Topics: Animals; Bronchi; Dysmenorrhea; Endocardium; Female; Ferula; In Vitro Techniques; Kidney Cortex; Lethal Dose 50; Liver; Oils, Volatile; Oxytocin; Phytotherapy; Plant Oils; Plants, Medicinal; Plants, Toxic; Rats; Rats, Sprague-Dawley; Rats, Wistar; Stomach; Uterine Contraction; Uterus

Lyprinol exhibits anti-inflammatory activity distinct from that of most NSAIDs, controlling chronic but not acute inflammation. Unlike Cox-1 inhibitors (aspirin, meclofenamic acid) it is not gastro-toxic. Predosing rats with Lyprinol can modify both (i) the spontaneous and (ii) the oxytocin-induced contractions of the uterus. In humans there is anecdotal evidence that Lyprinol can relieve dysmenorrhea. This report explores the concept that the uterotrophic actions of Lyprinol are conditioned by: the intrinsic profile of estrogenic hormones and progestagens and, certain extrinsic stimuli. Evidence from in vitro studies indicates that Lyprinol is not a smooth muscle relaxant and that its uterotrophic mechanism is not that of a cyclo-oxygenase inhibitor, but may mimic that of a leukotriene receptor antagonist.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Bivalvia; Cyclooxygenase Inhibitors; Disease Models, Animal; Drug Evaluation, Preclinical; Dysmenorrhea; Estrus; Female; Gastric Mucosa; Gonadal Steroid Hormones; Hormone Antagonists; Indomethacin; Leukotriene Antagonists; Lipids; Models, Biological; Muscle Relaxation; Myometrium; New Zealand; Ovariectomy; Oxytocin; Rats; Rats, Wistar

Topics: Antidiuretic Hormone Receptor Antagonists; Dysmenorrhea; Endometrium; Female; Gene Expression Regulation; Hormone Antagonists; Humans; Indoles; Lypressin; Myometrium; Oxytocin; Pyrrolidines; Receptors, Vasopressin; Regional Blood Flow; Uterus

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

A synthetic analogue, deamino-ethyl-oxytocin, which competitively inhibits vasopressin action on uterine activity both in vitro and in animal experiments was developed. The uterine effect of this analogue was studied during the recording of intrauterine pressure in 16 gynecologically healthy women. Increased uterine activity and dysmenorrhea-like pain was induced by infusing lysine vasopressin in a dose of 0.08 microgram/min. Deamino-ethyl-oxytocin inhibited vasopressin action, the threshold dose being approximately 200 micrograms given as a single intravenous injection for about 20 minutes. When given intranasally the drug was also shown to be effective in inhibiting vasopressin-induced uterine activity and symptoms. These results suggest that deamino-ethyl-oxytocin could be of therapeutic value in primary dysmenorrhea, a condition associated with increased vasopressin secretion.

Topics: Adult; Arginine Vasopressin; Dysmenorrhea; Female; Humans; Lypressin; Oxytocin; Pressure; Uterine Contraction; Uterus

Topics: Adult; Apgar Score; Coitus; Dysmenorrhea; Female; Humans; Labor, Induced; Labor, Obstetric; London; Obstetrical Forceps; Orgasm; Oxytocin; Parity; Postpartum Period; Pregnancy

Topics: Adolescent; Adult; Biological Assay; Dysmenorrhea; Female; Humans; Muscle Contraction; Oxytocin; Uterus

Topics: Abortion, Habitual; Abortion, Threatened; Adolescent; Contraceptive Agents; Contraceptives, Oral; Dysmenorrhea; Endometriosis; Estrogens; Female; Gonadotropins; Gynecology; Humans; Infertility; Infertility, Female; Lactation; Menopause; Obstetrics; Oxytocin; Pregnancy; Pregnancy in Diabetics; Progestins; Uterine Hemorrhage; Vaginitis