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At least 19 recordsLinked to original sources
PubMed2004

Uterine effects of the phytoestrogen 6-(1,1-dimethylallyl)naringenin in rats.

Phytoestrogens are discussed as candidate substances to treat symptoms related to estrogen deficiency. In in vitro experiments, the naturally occurring flavonoid 6-(1,1-dimethylallyl)naringenin (6-DMAN) emerged as one of the most potent phytoestrogenic substances. 6-DMAN is not as well characterized as other flavonoids (8-prenylnaringenin) or isoflavones (genistein). We tested 6-DMAN for the first time in vivo, in a dose-dependent three-day uterotropic assay in ovariectomized Wistar rats, using 6-DMAN at three different concentrations (1.5 mg/kg; 7.5 mg/kg and 15 mg/kg BW/d). Estradiol (E2; 10 microg/kg BW/d) and the carrier castor oil were used as positive and negative controls. 6-DMAN did not have any effect on uterine wet weight, while the positive control E2 did. In contrast, 6-DMAN stimulated uterine mRNA expression of estrogen responsive genes in ovariectomized rats. Estrogen receptor alpha and beta mRNA were expressed in the uterus. They mediate the expression of genes with an estrogen responsive element in the promoter, e. g., complement C3 and the progesterone receptor. Therefore, we analyzed the expression of the above-mentioned genes in three different concentrations. 6-DMAN up-regulated progesterone receptor and particularly complement C3 mRNA expression however, less pronounced than E2. In conclusion, we demonstrated for the first time estrogenic activities of 6-DMAN in vivo. Surprisingly, although 6-DMAN regulated estrogen responsive gene expression, there was no uterine wet weight gain. These findings make 6-DMAN a very interesting candidate substance for further characterization, as it potentially represents a naturally occurring selective estrogen receptor modulator.

Animals↗
PubMed1983

Placental passage and uterine effects of fentanyl.

Using the chronic maternal-fetal sheep preparation, 27 pregnant ewes were studied to determine the effects of intravenous fentanyl on maternal and fetal physiology, with particular reference to its placental passage, and its effects on uterine blood flow and uterine tone. Three doses of fentanyl were studied--50, 75, and 100 micrograms. Maternal and fetal arterial blood was collected for determination of fentanyl levels. All blood levels, both maternal and fetal, were normalized to the 50-micrograms dose. The maternal normalized blood levels were found to fit a biexponential equation describing a two-compartment open model. The half-life of the maternal elimination phase was 42 +/- 7.0 min with an overall elimination constant (K) of 0.21 min-1. Maternal plasma fentanyl levels decreased very rapidly in the first 10 min after injection, at which time only 9% of the peak value remained. Fentanyl was detectable in fetal blood as early as 1 min and levels peaked at 5 min. Once equilibrium was established between maternal and fetal blood, the maternal levels remained 2.5 times those of the fetal level from 5 min to 60 min after drug injection. Both maternal and fetal drug levels declined in an approximately parallel fashion. No significant deleterious changes were seen in any maternal or fetal cardiovascular or acid-base parameters, and uterine blood flow and uterine tone were also unaffected (P greater than 0.05).

Acid-Base Equilibrium↗
PubMed1995

Receptor-mediated uterine effects of vasopressin and oxytocin in nonpregnant women.

OBJECTIVE: To study in nonpregnant women myometrial actions of vasopressin and oxytocin and the involvement in these effects of specific uterine receptors. SUBJECTS: Twenty-eight women undergoing hysterectomy for benign gynaecological disorders. INTERVENTIONS: Intrauterine pressure recordings. Intravenous bolus injections of 10 pmol/kg body weight of vasopressin and oxytocin. Repeated blood sampling for measurement of vasopressin and oxytocin concentrations in plasma. Recording of effects of vasopressin and oxytocin on isolated myometrium. Estimation of myometrial concentrations of vasopressin V1a and oxytocin receptors. Measurement of plasma oestradiol and progesterone. MAIN OUTCOME MEASURES: Vasopressin- and oxytocin-induced increases of the area under the in vivo recording curve over 10 minutes and EC50 concentrations of dose-responses in vitro. Concentrations of vasopressin V1a and oxytocin receptors. RESULTS: Vasopressin was on average four times more potent than oxytocin in vivo. The effect of vasopressin premenstrually was more pronounced than in women under oestrogen influence only (proliferative phase-hyperproliferation; P = 0.02), and tended to be more marked than in those in the luteal phase (P = 0.07). No significant variation in oxytocin response with the hormonal state was observed. EC50 concentrations of vasopressin were more than 20 times lower than those of oxytocin. The median concentration of the vasopressin V1a receptor was 208 (range 139-343) fmol/mg protein and that of the oxytocin receptor 49 (38-87) fmol/mg protein. Vasopressin receptor concentrations and in vivo effects of this peptide did not correlate, whereas for those of oxytocin a significant correlation was observed (P = 0.02). CONCLUSION: The high potency of vasopressin in nonpregnant women, particularly premenstrually, firmly supports an aetiological importance of this peptide in the uterine hyperactivity of primary dysmenorrhoea. Oxytocin seems to be less important in this condition in view of its much smaller potency and the absence of increase in effect premenstrually. Vasopressin appears to influence both the oxytocin and the vasopressin V1a receptor sites in the uterus, whereas oxytocin acts specifically on its own receptor.

Adult↗
PubMed2000

Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60.

OBJECTIVE: To assess the uterine effects of 3 years of therapy with raloxifene in healthy, postmenopausal women under age 60. METHODS: Integrated data from two identically designed, randomized, double-masked, placebo-controlled clinical trials were analyzed. Nine hundred sixty-nine healthy women with uteri (ages 45 through 60, 2 to 8 years postmenopausal) were assigned randomly to raloxifene 30, 60, or 150 mg per day, or an identical placebo for 3 years. Endometrial thickness was evaluated with transvaginal ultrasonography every 6 months for 2 years and again after 3 years. Further uterine evaluation, including endometrial sampling if necessary, was initiated for vaginal bleeding or findings of endometrial thickness greater than 5 mm. RESULTS: Endometrial thickness was unchanged by raloxifene and not significantly different from placebo at any time. One hundred seventy-two women had at least one episode of endometrial thickness greater than 5 mm or vaginal bleeding distributed equally among all groups. A total of 102 (10.5%) women underwent endometrial sampling at least once: 15 (1.5%) for vaginal bleeding, 78 (8.0%) for endometrial thickness greater than 5 mm, and nine (0.9%) for other reasons. There were no significant treatment differences in the proportion of women sampled, in the clinical findings, or in the histologic diagnoses. CONCLUSION: Raloxifene given to healthy postmenopausal women at doses from 30 to 150 mg per day does not stimulate uterine growth and does not cause vaginal bleeding, spotting, or discharge through 3 years of therapy. Thus, any bleeding during therapy should be deemed unexpected and prompt a clinical evaluation.

Endometrium↗
PubMed2000

Uterine effects of raloxifene in comparison with continuous-combined hormone replacement therapy in postmenopausal women.

OBJECTIVE: We sought to compare the uterine effects of raloxifene with those of continuous-combined hormone replacement therapy. STUDY DESIGN: This randomized, double-blind 24-month study involved 136 postmenopausal women who received raloxifene 150 mg/d or conjugated equine estrogens 0.625 mg/d with medroxyprogesterone acetate 2.5 mg/d. After baseline evaluations, endometrial biopsy specimens were obtained, and endometrial thickness was measured annually by means of transvaginal ultrasonography. Statistical analyses were performed with an intention-to-treat approach. RESULTS: In the raloxifene group at the end point of the study 94.4% of biopsy specimens showed normal benign postmenopausal endometrium and 5.6% were classified as benign stimulatory endometrium. In the continuous-combined hormone replacement therapy group at the end point of the study 78.7% of biopsy specimens showed normal benign postmenopausal endometrium, 19. 1% were classified as benign stimulatory endometrium, and 2.1% showed benign abnormal postmenopausal endometrium. Mean endometrial thickness was unchanged from baseline with raloxifene and was increased significantly by 0.5 mm at 12 months with continuous-combined hormone replacement therapy. CONCLUSION: Raloxifene 150 mg/d did not increase endometrial thickness or cause endometrial proliferation in healthy postmenopausal women.

Biopsy↗
PubMed1999

Selective estrogen receptor modulators: tissue selectivity and differential uterine effects.

Selective estrogen receptor modulators (SERMs) are compounds that bind to estrogen receptors and produce estrogen-like (agonist) effects in some tissues and estrogen-blocking (antagonist) effects in other tissues. One of the goals of SERM research has been to develop compounds that provide the potential benefits of estrogen in the skeleton and cardiovascular system, but avoid the negative effects of estrogen in other tissues. Estrogen therapy has been consistently associated with endometrial stimulation, including glandular proliferation, hyperplasia and cancer. In contrast, the presence or degree of endometrial stimulation observed with SERMs varies by compound. The purpose of this review is to differentiate the endometrial effects of compounds that display a SERM-like profile. Molecular mechanisms involving SERM binding to estrogen receptors, preclinical uterine effects in both tissue culture and animal models, and endometrial findings in clinical experience are discussed. There are several SERMs commercially available or in development. The favorable safety profile of raloxifene in the uterus differentiates it from the others. Future SERM development will continue to focus on finding compounds that exhibit minimal endometrial stimulation.

Animals↗
PubMed2005

Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome.

BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. METHODS: Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age- and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whilst under metformin treatment (PCOS group) and in controls, uterine, sub-endometrial and endometrial blood flow, and endometrial thickness and pattern were evaluated using serial ultrasonographic assessments. RESULTS: Before treatment, uterine, sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group. All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls. Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups. After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome, no difference in any parameter was observed. CONCLUSIONS: Metformin improves all surrogate markers of endometrial receptivity in PCOS patients, without difference between patients who had favourable or unfavourable reproductive outcome.

Adult↗
PubMed2006

Uterine effects of clomiphene citrate in women with polycystic ovary syndrome: a prospective controlled study.

BACKGROUND: Previous data on the efficacy of clomiphene citrate, the most commonly used drug for treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS), have shown a discrepancy between ovulation and pregnancy rates. In the present subanalysis (of a larger previously published randomized controlled trial), the effect of clomiphene citrate on several ultrasonographic markers of uterine receptivity in PCOS patients who ovulated under treatment was studied. METHODS: Thirty-three PCOS women who ovulated under 150 mg daily clomiphene citrate and 33 healthy controls were studied. Uterine, subendometrial and endometrial blood flows, endometrial thickness and pattern were assessed using serial ultrasonographic assessments. The data were analysed before and after grouping the clomiphene citrate-stimulated ovulatory cycles for reproductive outcome [unfavourable (ovulation alone or early pregnancy loss) or favourable outcome (clinical pregnancy and/or live birth)]. RESULTS: Both before and during treatment, uterine vascularity assessed at all sites was significantly lower in the PCOS group than in controls. Endometrial thickness and pattern were impaired in the PCOS group under clomiphene citrate treatment. A significant difference in all ultrasonographic parameters was observed between cycles ending in unfavourable versus those ended in favourable outcome. CONCLUSIONS: Clomiphene citrate administration alters several surrogate ultrasonographic parameters of uterine receptivity, and this effect could be crucial for its efficacy.

Adult↗
PubMed2002

Transvaginal sonographic monitoring of the uterine effects of raloxifene and a continuous combined replacement therapy in postmenopausal women.

OBJECTIVE: To study the effect of 17beta-estradiol+norethisterone acetate and raloxifene on the endometrium and uterine volume in postmenopausal women. METHODS: Patients were randomly assigned to 17beta-estradiol 2 mg+norethisterone acetate 1mg (E2+NETA) daily (n=90) or raloxifene HCl 60 mg (Evista) daily (n=43). Transvaginal sonography was done at baseline and at 6, 12 and 18 months, and at 6 and 12 months in-patients treated with E2+NETA and EVISTA respectively. Patients were asked to record bleeding-spotting episodes. Whenever required patients were referred for hysteroscopy+/-biopsy of the endometrium. RESULTS: Patients under E2+NETA had a higher bleeding-spotting incidence (48.6%) compared with EVISTA (7.7%). Endometrial thickness increased significantly under E2+NETA as compared with baseline; however, at end point thickness reverted to baseline values. Evista had a non-stimulatory effect on the endometrium. Changes in uterine volume were not statistically significant. CONCLUSIONS: Both treatment regimens provided comparable uterine safety. However, raloxifene exhibited a more favorable safety profile on the uterus as expressed in the bleeding-spotting incidence and the effect on endometrial thickness and uterine volume. Transvaginal sonography appears to be a dependable method for monitoring the effect of treatment on the uterus.

Administration, Oral↗
PubMed2000

Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects.

Recent analysis of mice deficient in both oxytocin (OT) and cyclooxygenase-1 has shown that OT exerts significant effects on both the ovarian corpus luteum and the uterine myometrium during pregnancy. To better define the roles of OT during pregnancy, we evaluated OT action and OT receptor regulation in wild-type and OT-deficient knockout (KO) mice. Continuous infusion of OT revealed that OT can either delay labor at low doses or initiate preterm labor at high doses. The infusion rates of OT necessary for these effects were reduced in OT KO mice. The dose of OT that delayed labor also delayed the normal decrease in plasma progesterone late in gestation, implicating a primary effect on the corpus luteum. Consistent with this hypothesis, luteal OT receptor expression exceeded that of the myometrium until luteolysis occurred. We propose that the downregulation of OT receptors in the corpus luteum and induction of OT receptors in the myometrium serve to shift the predominant consequence of OT action during murine pregnancy from labor inhibition to labor promotion.

Animals↗
PubMed1980

Uterine effects of N-alpha-triglycyl-(8-lysine)-vasopressin and 8-lysine-vasopressin in the first trimester of pregnancy.

Myometrial effects of a vasopressin hormonogen (N-alpha-triglycyl-(8-lysine)-vasopressin, TGLVP) and of 8-lysine-vasopressin (LVP) were studied in early pregnancy. Intrauterine pressure was recorded in 28 women, who were to have a therapeutic abortion at 8-12 weeks of gestation, and intravenous injection of TGLVP (0.5 and 1 mg) or LVP (0.1, 0.2 and 0.4 IU) were given, or control recordings without drug injection were obtained. TGLVP generally caused a biphasic increase in uterine activity with a rise in uterine tone as the most conspicuous initial effect followed by an increase in amplitude and duration of contractions. In the higher dose group the uterine activity remained significantly higher than in the controls during the rest of the recording period of 4-7 h. The magnitude of effect with the two doses of TGLVP did not differ significantly. The initial myometrial response to LVP resembled that to TGLVP but the effects disappeared within 10-45 min. In the controls the uterine activity did not change. It is suggested that vasopressin analogues could have a therapeutic value in the induction of abortion, but further basic studies are required to define this.

Adult↗
PubMed2005

Potentiation of uterine effects of prostaglandin F2{alpha} by adenosine 5'-triphosphate.

OBJECTIVE: To investigate the interaction of exogenous adenosine 5'-triphosphate (ATP), a P2 receptor agonist, with prostaglandin F(2alpha) (PGF(2alpha)) on pregnant women in labor as well as on isolated human pregnant uterus preparations. METHODS: For an in vitro study, myometrial samples were obtained from 27 women undergoing elective cesarean delivery at term. Concentration-response relationships for ATP (10(-8) -3 x 10(-4) mol/L), PGF(2alpha) (10(-9) -10(-5) mol/L), and their combination were obtained by using routine pharmacological organ bath technique. An in vivo study was performed with 34 pregnant women with dysfunctional abnormalities of the active stage of labor who were randomly allocated into 2 study groups. The women in the control group (18 patients) received intravenous prostaglandin F(2alpha) at an initial rate of 7.5 mug/min, whereas the women in the ATP group (16 patients) received prostaglandin F(2alpha) concomitantly with ATP (0.45 nmol/min, intravenously). RESULTS: Adenosine 5'-triphosphate at concentrations of 10(-6) -3 x 10(-4) mol/L and PGF(2alpha) at concentrations of 10(-8) -10(-5) mol/L caused concentration-dependent contractions of isolated smooth muscle preparations of the human pregnant uterus. At concentrations of 10(-6) mol/L and below, ATP had no effects on mechanical activity of the isolated uterus, but at concentrations of 10(-7) mol/L and 10(-6) mol/L, it significantly potentiated the contractile responses of the uterus induced by PGF(2alpha) (P < .05, 2-way analysis of variance). Patients receiving intravenous infusion of ATP as a supplement to PGF(2alpha) treatment, compared with those without ATP, had a significantly shorter interval from the start of the treatment to full cervical dilatation (3.31 +/- 1.49 hours and 4.67 +/- 1.11 hours in ATP and control groups, respectively; P = .014, Wilcoxon Mann-Whitney test). The total dose of prostaglandin received was significantly lower in the ATP group than that of controls (1,489.8 +/- 699.9 mug and 3,394.2 +/- 1,951.9 mug, respectively; P = .003, Wilcoxon Mann-Whitney test). No side effects of ATP treatment were observed during or after infusion. CONCLUSION: Adenosine 5'-triphosphate potentiates effects of PGF(2alpha) on pregnant human uterus in vitro and in vivo and thus could be a useful supplemental drug to increase uterine contractility at labor.

Adenosine Triphosphate↗
PubMed2005

Uterine effect of cervical buffeting: role of the cervicouterine reflex in coitus.

OBJECTIVE: To investigate the hypothesis that cervical buffeting during coitus effects reflex relaxation and dilatation of the corpus uteri (CorU) smooth muscle; that mechanism acts to suck the ejected semen into the CorU. STUDY DESIGN: The CorU response to electrical and mechanical stimulation of the CU was recorded in 22 healthy women (mean age, 38.2 +/- 7.6 SD years). Cervical electrical stimulation was effected by an electromyographic needle electrode and mechanical stimulation by pencil electrode. The test was repeated after individual anesthetization of the CU and CorU and after normal saline injection. RESULTS: Slow waves, superimposed or followed by action potentials, were recorded at rest from the CorU electrode. Electrical or mechanical stimulation of the CU effected a significant reduction of the electric wave parameters and pressure in the CorU; this response was reproducible. Separate stimulation of the anesthetized CU or CorU did not evoke the response, while saline infiltration did. CONCLUSION: CU stimulation resulted in diminished CorU electrical activity and pressure; that presumably indicates uterine wall relaxation. Repeated CU buffeting apparently leads to an intermittent uterine pressure decline, with resulting semen siphonage from the vagina to the uterus. Diminished CorU electrical activity and pressure on cervical stimulation or buffeting might be mediated through the cervicouterine inhibitory reflex. This reflex seems to be evoked by penile thrusting during coitus and may prove of diagnostic significance in sexual disorders.

Action Potentials↗
PubMedDate not supplied

Uterine effects of tamoxifen: a prospective study.

The purpose of the study was to evaluate tamoxifen-associated changes in the vagina and uterus in postmenopausal breast cancer patients. Between June 1994 and December 1998, 45 patients enrolled in a prospective study before commencing tamoxifen therapy. Patients with endometrial thickness >5 mm or neoplasia were excluded. Transvaginal ultrasonography, vaginal maturation indexes (VMI), and endometrial biopsy were performed at baseline and repeated at 6 months (n= 42), 1 year (n= 39), 2 years (n= 32), 3 years (n= 26), 4 years (n= 19), and 5 years (n= 15). For the 39 patients followed for 1 year, VMI (% parabasal/intermediate/superficial) was 21/71/8 at baseline compared with 1/90/9 at 1 year (P value = 0.0008/0.001/0.78). At baseline, mean endometrial thickness and uterine volume were 2.6 mm and 64 cm(3), respectively, compared with 5.8 mm and 84 cm(3) at 1 year (P= 0.0002, 0.002). At baseline, 80% of patients had atrophic endometrium and 9% proliferative endometrium compared with 61% and 26% at 1 year, respectively (P= 0.04). No cases of endometrial hyperplasia or adenocarcinoma were detected. Findings observed at 6 months persisted through 5 years of follow-up. Tamoxifen exerts a weak estrogenic effect on the vagina and uterus in highly prescreened postmenopausal women without preexisting endometrial pathology.

Adult↗
PubMed2004

Breast and uterine effects of soy isoflavones and conjugated equine estrogens in postmenopausal female monkeys.

In this study we evaluated the long-term effects of soy isoflavones on intermediate markers of cancer risk in the normal postmenopausal monkey breast and uterus. Ovariectomized female cynomolgus monkeys were randomized to receive one of three diets for 36 months: 1) isoflavone-depleted soy protein isolate (SPI-) (n = 57); 2) soy protein isolate with the equivalent of 129 mg/d isoflavones (SPI+) (n = 60); or 3) isoflavone-depleted soy protein isolate with conjugated equine estrogens at a dose scaled to approximate 0.625 mg/d in women (n = 62). End points included breast and uterine proliferation markers, sex steroid receptor expression, and serum estrogens. Epithelial proliferation and progesterone receptor expression in the breast and uterus were significantly higher in the conjugated equine estrogen group, compared with SPI+ and SPI- groups, whereas no significant differences were detected between the SPI+ and SPI- groups. SPI+ treatment resulted in significantly lower serum concentrations of estrone (P < 0.01) and estradiol (P < 0.05) vs. SPI-. Within the SPI+ group, serum isoflavone concentrations were inversely correlated with serum estrone and mammary glandular area. These findings suggest that high dietary levels of soy isoflavones do not stimulate breast or uterine proliferation in postmenopausal monkeys and may contribute to an estrogen profile associated with reduced breast cancer risk.

Animals↗
PubMedDate not supplied

Controversy about uterine effects and safety of SERMs: the saga continues.

From the perspective of endometrial safety, there has been great controversy about what special management, if any, tamoxifen-treated patients should undergo. Periodic blind endometrial sampling or transvaginal ultrasound has been advocated by some. Because of the problems associated with either of these techniques alone, we recommended an approach that used transvaginal ultrasound and then proceeded to sonohysterography when the endometrial echo on transvaginal ultrasound was not reliably thin and distinct. The American College of Obstetricians and Gynecologists (ACOG), in its committee opinion, stated that patients receiving tamoxifen therapy should only have an annual pelvic exam with pap smear if they remain asymptomatic. Newer data suggest, however, that there are high- and low-risk groups that can be identified by pretreatment screening. Before tamoxifen therapy, 17% of patients have polyps. These patients have 17 times the incidence of atypical hyperplasia than those whose uterus was negative before tamoxifen therapy. Such findings call into question the validity of the only study of raloxifene where uterine safety was the primary endpoint. In that study, any woman with baseline endometrial findings other than pristinely negative (i.e., low risk) was excluded. However, other raloxifene studies without pretreatment screening show relative risk (RR) = 0.8 (95% CI = 0.2, 2.7) for endometrial carcinoma. This compares with the women over 50 years of age in the Breast Cancer Prevention Trial (National Surgical Adjuvant Breast and Bowel Project P-1) with tamoxifen when the RR = 4.01 (95% CI= 1.70, 10.90). The existence of potentially high- and low-risk groups should be taken into account in any future clinical trials looking at the endometrial safety of selective estrogen receptor modulators (SERMs).

Endometrial Neoplasms↗