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PubMed2004

Dendritic cells exposed to estrogen in vitro exhibit therapeutic effects in ongoing experimental allergic encephalomyelitis.

Immunomodulatory effects of estrogen have been demonstrated by clinical and experimental observations, but the mechanisms by which estrogen exhibits the effects remain to be defined. One possible mechanism by which estrogen inhibits the development of experimental allergic encephalomyelitis (EAE), a commonly used model of multiple sclerosis (MS) in humans, is over the functions of dendritic cells (DC). Here, we describe that splenic DC from Lewis rats obtained on day 12 post-immunization (p.i.) with myelin basic protein (MBP) encephalitogenic peptide 68-86+Freund's complete adjuvant (FCA), after being exposed in vitro 17beta-estradiol, exhibited therapeutic effects on acute EAE when injected subcutaneously on day 5 p.i. Blood mononuclear cells (MNC) were isolated from thus treated rats on day 12 p.i. Administration of estrogen-exposed DC prevented the expansion of CD4+ T cells and increased proportions of regulatory T cells producing IL-10 and CD4+CD28- suppressor T cells, accompanied with increased IL-10 and IFN-gamma, and reduced TNF-alpha production. Infiltrates of CD68+ macrophages within the central nervous system and MBP 68-86-induced T cell proliferation were inhibited in rats injected with estrogen-exposed DC compared to rats injected with naive DC. Estrogen up-regulated the expression of indoleamine 2,3-dioxygenase, which promotes tolerogenic properties of DC. The results suggest that in vitro exposure of DC to estrogen modulates DC functions and results in a therapeutic effect of DC.

Adjuvants, Immunologic↗
PubMed1998

HPLC-fluorescence determination of unconjugated estrogens in pharmaceuticals.

A fluorimetric liquid chromatographic method (lambda(ex) = 280 nm; lambda(em) = 312 nm) was developed for measurements of unconjugated estrogens (estradiol and estriol) in pharmaceutical dosage forms using a reversed-phase column with water acetonitrile at different composition as mobile phase. The in vitro release profiles of three different estradiol transdermal therapeutic systems were determined through a medical-grade silicone rubber subdermal implant material membrane, using a modified Franz diffusion apparatus at 37 degrees C in presence of PEG 400. The HPLC method possesses advantages of rapidity, simplicity and accuracy.

Administration, Cutaneous↗
PubMed2006

A prospective comparison of the impact of uterine artery embolization, myomectomy, and hysterectomy on ovarian function.

PURPOSE: To prospectively compare uterine artery embolization (UAE) versus myomectomy and hysterectomy with regard to ovarian function as measured by postprocedure follicle-stimulating hormone (FSH) levels and symptoms. MATERIALS AND METHODS: Fifty-five patients were prospectively enrolled in the study: 33 patients who underwent UAE, seven who underwent myomectomy, and 15 who underwent hysterectomy. Patients had serum FSH and estradiol levels measured on the third day of the menstrual cycle before their procedure and at regular follow-up visits for as long as 6 months. At these intervals, patients were also surveyed regarding menopausal symptoms. RESULTS: Although a mild transient increase in mean FSH level after UAE was noted at 3 months, there were no statistically significant differences among the three groups in mean FSH levels at 1 month, 3 months, or 6 months of follow-up. Menopausal symptoms arose in the UAE and hysterectomy groups, but there was no statistically significant difference or permanent effect in either group. CONCLUSION: There is no significant difference in impact on ovarian function after UAE, hysterectomy, or myomectomy at follow-up for a maximum of 6 months.

Adolescent↗
PubMed1990

Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats.

Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using [14C, 3H]KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer.

Animals↗
PubMed2004

[Influence of interventional radiotherapy for severe postpartum hemorrhage on postpartum menorrhea].

OBJECTIVE: To discuss the influence of interventional radiotherapy for treating severe postpartum hemorrhage on postpartum menorrhea. METHODS: From Mar. 1995 to Feb. 2002, 18 cases of severe postpartum hemorrhage treated with arterial embolization served as the interventional group. Twenty parturients without postpartum complication were recruited as control group. The continuance of lochia, recovery of menorrhea between the two groups were compared. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2)) of the non-lactating women in the two groups were assayed during the 3rd-5th days of the first menstrual cycle. RESULTS: Continuance times of lochia were (33.9 +/- 2.0) days, and (36.2 +/- 3.1) days in interventional group and control group, respectively. Recovery times of menorrhea were (75 +/- 17) days, and (95 +/- 16) days in interventional group and control group. The quantity of the postpartum menorrhea was 1.3 +/- 0.1 times of that before delivery in interventional group, 1.3 +/- 0.2 times of that in control group. The number of menstrual cycle before recovery to normal menorrhea was 2 cycles in interventional group, 1.9 cycles in control group. Postpartum menstrual cycle was (33.9 +/- 2.2) days in interventional group, (33.2 +/- 1.6) days in control group. Serum FSH, LH, E(2) of the non-lactating women during the 3rd approximately 5th days of the first menstrual cycle were (5.2 +/- 1.1) U/L, (7.5 +/- 1.6) U/L, (262 +/- 14) pmol/L in interventional group, (4.3 +/- 2.1) U/L, (6.3 +/- 1.3) U/L, (280 +/- 12) pmol/L in control group. There was no significant difference between the two groups (P > 0.05). CONCLUSIONS: No obvious influence of interventional radiotherapy for postpartum hemorrhage on postpartum menorrhea was observed.

Adult↗
PubMed2004

Ovarian function after uterine artery embolization and hysterectomy.

STUDY OBJECTIVE: To evaluate the effect of uterine artery embolization (UAE) and hysterectomy on ovarian function. DESIGN: Prospective case control study (Canadian Task Force classification II-2). SETTING: University teaching hospital. PATIENTS: Eighty-four healthy premenopausal women with symptomatic uterine myoma(s) undergoing UAE or hysterectomy. INTERVENTION: Patients had blood drawn to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and underwent transvaginal ultrasound to measure volume of the myoma(s) and uterus on cycle day 3 before the procedures. These measurements were repeated 3 and 6 months after treatment. MEASUREMENTS AND MAIN RESULTS: The main outcome was the differences in serum FSH, LH, E2, and ultrasound findings before and after UAE or hysterectomy. Of the 68 patients who underwent UAE and 16 who underwent hysterectomy, 48 and 13 respectively, completed 6-month follow-up. The mean age of the patients in the UAE group was 44.9 +/- 3.8 years and 43.7 +/- 5.6 years in the hysterectomy group. There was no significant difference in serum FSH before (8.9 +/- 0.7 IU/L) and 6 months after UAE (9.9 +/- 1.0 lU/L), and between the baseline (10.4 +/- 1.8 lU/L) and 6 months posthysterectomy (7.8 +/- 1.8 lU/L). The uterine volume 6 months after UAE (361 +/- 50 mL) was significantly smaller than before UAE(538 +/- 38mL; p =.005, 95% CI 44-241). Compared with baseline (154 +/- 20 mL), the dominant myoma volume was smaller at 6 months after UAE (97 +/- 16 mL; p <.05, 95% CI 1.57-62). CONCLUSION: Uterine artery embolization is associated with a significant reduction in myoma and uterine volume. Ovarian function at 6 months, as indicated by day 3 FSH levels, is not affected by UAE or hysterectomy.

Adult↗
PubMed2004

Uterine artery embolization for fibroids does not have adverse effects on ovarian reserve in regularly cycling women younger than 40 years.

OBJECTIVE: To evaluate the impact of uterine artery embolization (UAE) for fibroids on ovarian reserve in women younger than 40 years. DESIGN: Prospective study. SETTING: University-based reproductive endocrinology unit. PATIENT(S): Twenty regularly cycling women aged 33-39 years undergoing UAE for fibroids. All had cycle day 3 FSH levels <10 mIU/mL. INTERVENTION(S): Measurements of serum FSH and E2 levels and of the total ovarian volume and antral follicle number by transvaginal ultrasonography on day 3 of the menstrual cycle preceding UAE and on day 3 of the cycles occurring in months 3, 6, and 12 after UAE. MAIN OUTCOME MEASURE(S): Preprocedural and postprocedural hormone levels, ovarian volumes, and antral follicle numbers. RESULT(S): There were no significant changes from baseline in the mean day 3 FSH and E2 levels, ovarian volume measurements, and antral follicle numbers measured at 3, 6, and 12 months after UAE. CONCLUSION(S): Although this study might be not sensitive enough to conclude that UAE for fibroids does not interfere with a woman's ovarian status, these data indicate that in this series of reproductive-aged women UAE did not have short- or mid-term effects on ovarian reserve as assessed by hormonal and sonographic parameters.

Adult↗
PubMed1998

Effectiveness of Cyclofem in the treatment of depot medroxyprogesterone acetate induced amenorrhea.

A total of 100 women who were using depot medroxyprogesterone acetate (DMPA) for contraception and who had experienced at least 6 months of drug induced amenorrhea, were randomized to either switching their method of contraception to Cyclofem, or continuing with DMPA. At the end of 6 months, 82% of the Cyclofem users had experienced some vaginal bleeding, compared with 10% of DMPA users. Time to resumption of vaginal bleeding was related to the duration of DMPA use to the duration of DMPA induced amenorrhea, and to the body mass index of the user. Over the 6 months of follow-up, 94% of Cyclofem users complained of some side effects, compared with 22% of DMPA users. The most frequently cited problems among Cyclofem users included breast tenderness, abdominal pain, and dysmenorrhea; yet a third of these women opted to stay on Cyclofem at the end of the study. It is concluded that switching to Cyclofem is a new option for DMPA users who are concerned about amenorrhea. Although using Cyclofem in this setting will not meet the needs of all such women, its effectiveness in inducing vaginal bleeding justifies a trial in those who have no contraindication to estrogen treatment.

Adult↗
PubMed2001

Laparoscopic bipolar coagulation of uterine vessels: a new method for treating symptomatic fibroids.

OBJECTIVE: To evaluate the effects of laparoscopic bipolar coagulation of uterine vessels in treating symptomatic fibroids. DESIGN: Prospective clinical study. SETTING: University-affiliated tertiary referral center. PATIENT(S): Eighty-seven women with symptomatic fibroids warranting surgical treatment and wanting to retain their uteri. INTERVENTION(S): Laparoscopic bipolar coagulation of uterine arteries and anastomotic sites of uterine arteries with ovarian arteries. MAIN OUTCOME MEASURE(S): Percentage reduction in the dominant fibroid size and clinical response evaluation. RESULT(S): Eighty-five (97.7%) of 87 patients underwent technically successful laparoscopic coagulation of uterine vessels without intraoperative complications. The mean follow-up time was 10.2 months. Symptomatic improvement was reported in 76 (89.4%) of 85 patients, including 18 (21.2%) with complete resolution of symptoms. Significant reductions in the dominant fibroid size (average, 76%) and the uterine volume (average, 46%) were sonographically demonstrated. Two patients conceived 4 and 9 months, respectively, after treatment. Three (3.5%) premenopausal women became postmenopausal postoperatively. CONCLUSION(S): Laparoscopic bipolar coagulation of uterine vessels appears to be a promising new method for treating fibroid-related menorrhagia and pelvic pain.

Adult↗
PubMed1977

Effects of aging on the hypothalamic-hypophyseal-gonadal axis in female rats.

The failure of reproductive function in aged rats could be due to deficiencies at the level of the ovary, pituitary, hypothalamus, or higher brain centers. The classic explanation that the ovary is depleted of follicles does not receive adequate support on the basis of histologic studies of aged ovaries. Basal serum gonadotropin levels change with increasing age in female rats. Serum follicle-stimulating hormone (FSH) levels rise while serum luteinizing hormone (LH) levels fall. Likewise, the characteristic response to castration is markedly altered in aged female rats with a reduced secretion of FSH and a minimal elevation of LH. However, the pituitaires of these animals are still caapable of responding to exogenous LH-releasing hormone with a delayed LH response whose magnitude simulates that seen in younger female animals. With increasing age there is decreased pituitary and/or hypothalamic sensitivity to the feedback action of estradiol. These data are consistent with the postulation that there is an altered hypothalamic-hypophyseal function in aged rats.

Aging↗
PubMed1996

The effect of transdermal oestradiol on bleeding pattern, hormonal profiles and sex steroid receptor distribution in the endometrium of Norplant users.

The most common side-effect and reason for discontinuation with Norplant use is bleeding disturbance. The aim of this study was to investigate whether the 6 week application of a patch which released 100 micrograms/day oestradiol would reduce the number of abnormal bleeding days or eliminate the problem. Another objective was to find out the correlation between the bleeding pattern and endometrial concentrations of oestrogen receptor (ER) and progesterone receptor (PR). Of 98 Norplant users, 34 patients had normal bleeding patterns and 64 patients had abnormal bleeding patterns. An oestradiol patch or a placebo patch were randomly used to treat 33 and 31 women with abnormal bleeding respectively. There was a clinical improvement in the oestradiol group compared with the placebo group, although this was not statistically significant. There were no correlations between PR and ER concentration and the serum oestradiol, progesterone, levonorgestrel and sex hormone-binding globulin concentrations. Significantly increased mean immunostaining scores of stromal PR were observed in those Norplant users whose endometrium had an atrophic histological appearance. The serum oestradiol concentration did not show a significant change after treatment with the oestradiol patch compared with the placebo patch.

Administration, Cutaneous↗
PubMed1977

Potent inhibitory effect of a new antiestrogen (RU 16117) on the growth of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.

At the daily dose of 24 mug for a period of 4 weeks, RU 16117 (11alpha-methoxyethinyl estradiol), a new antiestrogen, led to 65% reduction of the number of already established dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Not only the tumor number but also the tumor size was reduced by RU 16117 in a manner similar to that seen after ovariectomy. The absence of an inhibitory effect of doses of 0.1 to 12.5 mug 17beta-estradiol (E2) per day, a dose-range which covers the low estrogenic activity of the RU 16117 doses used, suggested that the inhibitory effect of RU 16117 was not due to its estrogenic activity. Decreased levels of receptors for E2, progesterone, and prolactin were found in the tumors remaining after ovariectomy; treatment with the dose of RU 16117 sufficient to inhibit tumor growth (24 mug) had a similar inhibitory effect on the levels of E2 and prolactin receptors. These data suggested that a reduction of hormone receptor levels in the tumor tissue could be a mechanism by which RU 16117 acts as a potent inhibitor of the growth of DMBA-induced mammary carcinoma.

9,10-Dimethyl-1,2-benzanthracene↗