A prospective randomized study on the measured blood loss in medical termination of early pregnancy by three different misoprostol regimens after pretreatment with mifepristone

BACKGROUND: Prolonged vaginal bleeding is a common complaint after medical abortion. The effect of a 1 week course of daily oral misoprostol after medical abortion with mifepristone and misoprostol on the amount of post-abortal blood loss was studied. METHODS: A total of 150 women (gestation 相似文献   

Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel

It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time.     

A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol

This was a randomized double-blind placebo-controlled trial to determine the effect of oral contraceptive (OC) pills taken immediately after medical abortion on the duration of bleeding and complete abortion rate. Two hundred women in the first 49 days of pregnancy were given 200 mg mifepristone orally followed by 400 microg misoprostol vaginally 48 h later. One day later, they were randomized to receive either OC pills (30 microg of ethinyl oestradiol and 0.15 mg of levonorgestrel per tablet) or placebo for 21 days. The complete abortion rates were 98% in the OC group and 99% in the placebo group. The median duration of bleeding was similar: 17 (range: 5-57) days in the OC group and 16 (range: 6-55) days in the placebo group. In the OC group there was a small but significant fall in the haemoglobin concentration by 14 days (5.3 g/dl) after administration of mifepristone. The incidence of side-effects was similar in the two groups. We conclude that the use of OC pills does not decrease the duration of bleeding after medical abortion nor does it affect the abortion rate.     

A prospective randomized,double-blinded,placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy

BACKGROUND: Vaginal misoprostol has been shown to be an effective single agent for medical abortion. This randomized, double-blinded, placebo-controlled trial compared a regimen of mifepristone and misoprostol with misoprostol alone for termination of early pregnancy. METHODS: 250 women with gestations < or = 56 days were randomized by a random number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 microg vaginal misoprostol. Administration of misoprostol was repeated every 24 h up to three doses if abortion failed to occur. Abortion success was defined as complete abortion without the use of surgical aspiration. RESULTS: Successful medical abortions occurred in 114 out of 119 subjects (95.7%) after mifepristone followed by vaginal misoprostol. In all, 110 out of 125 subjects (88.0%) successfully aborted after placebo and vaginal misoprostol. The higher success rate of complete abortion with the mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen (P < 0.05). CONCLUSIONS: A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies < or = 56 days than misoprostol alone. The 88% efficacy obtained with vaginal misoprostol alone may be clinically acceptable when mifepristone is not available.     

A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel)

BACKGROUND: The acceptability and continuation rate of oral contraceptive steroids are limited by unpredictable bleeding and the fear of long-term risks such as breast cancer. By inhibiting ovulation and by altering the receptivity of the endometrium, antagonists of progesterone, such as mifepristone, could be developed as estrogen-free novel contraceptives. METHODS: Multicentre, double-blind, randomized controlled trial comparing frequency of amenorrhoea (primary outcome), bleeding patterns, side effects and efficacy in women taking daily 5 mg mifepristone (n = 73) or 0.03 mg levonorgestrel (progestogen-only pill; POP, n = 23) for 24 weeks. RESULTS: More women were amenorrhoeic while taking mifepristone than POP (49 versus 0% P < 0.001), and fewer women bled or spotted for >5 days per month (4 versus 39% P < 0.001). Forty-eight percent of women who took mifepristone for 6 months had cystic glandular dilatation of the endometrium but none showed hyperplasia or atypia. There were no pregnancies in 356 months of exposure in women who used only mifepristone for contraception. Two pregnancies occurred in women taking mifepristone who were also using condoms for dual protection. CONCLUSIONS: Daily mifepristone (5 mg) is an effective oral contraceptive pill which has a better pattern of menstrual bleeding than an existing POP (levonorgestrel).     

Improving cycle control in progestogen-only contraceptive pill users by intermittent treatment with a new anti-progestogen

BACKGROUND: The safety and efficacy of the anti-progestogen Org 31710 in improving cycle control in healthy women using the desogestrel progestogen-only pill was investigated in this randomized, double-blind, placebo-controlled study. METHODS: A total of 103 women using the 75 micro g desogestrel progestogen-only pill daily also received either 150 mg Org 31710 or placebo once every 28 days, starting on day 1, for a duration of 4-7 treatment cycles. RESULTS: The percentage of women with bleeding or spotting (B/S) every day in the placebo group was on average 30% during the whole treatment period and no days without reported B/S occurred. In contrast, a cyclic pattern was observed for the Org 31710 group; a peak incidence of B/S was observed on day 3 or 4 of each cycle, followed by a sharp decrease on cycle days 9-15. Compared with controls, less subjects in the Org 31710 group reported irregular, frequent or prolonged bleeding. These differences were clearly observed in the initial cycles, but were somewhat less pronounced during the later cycles of the treatment period. A relatively high incidence of B/S episodes starting in the second section of the cycle was also observed. CONCLUSION: The addition of Org 31710 once a month improved cycle control in women using daily treatment with 75 micro g desogestrel.     

A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation

BACKGROUND: A combination of mifepristone and misoprostol provides an effective method of medical abortion for early pregnancy. This is the first randomized trial comparing the use of sublingual misoprostol with vaginal misoprostol in combination with mifepristone for termination of early pregnancies up to 63 days. METHODS: A total of 224 women who requested legal termination of pregnancy up to 63 days were randomized by computer- generated list into two groups and given 200 mg of oral mifepristone followed 48 h later by either 800 micro g of sublingual (n = 112) or vaginal (n = 112) misoprostol. RESULTS: Complete abortion occurred in 98.2% (95% CI: 93-99) of women in the sublingual group and 93.8% (95% CI: 88-97) in the vaginal group. There were three ongoing pregnancies in the vaginal group but none in the sublingual group. The median duration of vaginal bleeding was 17 days. There was no serious complication. Fever, chills and gastrointestinal side-effects (nausea, vomiting and diarrhoea) were significantly more common in the sublingual group. CONCLUSIONS: The combination of mifepristone and misoprostol is effective for medical abortion up to 63 days. Both the sublingual and vaginal are effective routes of administration. Further randomized trials are required to find out the optimal dose of sublingual misoprostol that can give the highest complete abortion rate and lowest incidence of side-effects.     

Correlation of endocrine profiles with bleeding patterns during use of Nestorone contraceptive implants

The relationship between ovarian hormones and bleeding patterns during continuous progestin contraception was studied in 29 women who used Nestorone (NES) releasing implants. Oestradiol and progesterone were measured in blood samples taken twice a week for 6 consecutive weeks, during months 6, 12, 18 and 24 of implant use. Retrospectively, the association between hormonal concentrations and bleeding patterns was evaluated. Twenty-four short (相似文献   

The effect of contraceptive pills on the measured blood loss in medical termination of pregnancy by mifepristone and misoprostol: a randomized placebo controlled trial.

BACKGROUND: A prospective randomized placebo controlled trial was performed to assess the immediate use of oral contraceptive (OC) on the amount of blood loss in the post-abortion period in women undergoing medical abortion by mifepristone and misoprostol. METHODS: One hundred women were randomized by computer to receive either OC pills or placebo, immediately after medical abortion. RESULTS: There was no difference in the complete abortion rate between the two groups. The complete abortion rate was 98 and 92% in the OC and placebo groups respectively. The side-effects and duration of bleeding were also similar. The median days of vaginal bleeding were 17 (range: 3-41) and 15 (range: 5-48) in the OC and placebo groups respectively. There was a statistically significant decrease in the mean haemoglobin level on day 15 in the OC group (from 12.0 to 11.5 g/dl) whereas the mean haemoglobin level in the placebo group remained stable. The median measured blood loss was 69.9 ml in the OC group and 72.8 ml in the placebo group and there was no statistically significant difference between the two groups. CONCLUSION: We conclude that it is safe to offer women combined OC pills immediately after medical abortion as an option of contraception, as it does not affect the duration or amount of vaginal bleeding or the complete abortion rate.     

Effects of mifepristone on proliferation and apoptosis of human endometrium in new users of medroxyprogesterone acetate

BACKGROUND: Mifepristone has been demonstrated to decrease breakthrough bleeding (BTB) in users of progestin-only contraceptives. METHODS: Endometrial biopsies were collected from 50 normal cycling women who were new users of depot medroxyprogesterone acetate (DMPA) randomized to receive either mifepristone or placebo before, during and after treatment. Proliferation, apoptosis and sex steroid receptors were evaluated by either immunohistochemistry or TUNEL assay. RESULTS: Administration of mifepristone to DMPA-exposed endometrium for 1 week significantly increased endometrial expression of Ki-67 (MKI67), estrogen receptor (ER)alpha and progesterone receptors A and B (PRAB) and decreased the number of TUNEL-positive and caspase-3 (CASP3)-active cells in the endometrial stroma. However, after 10 weeks of mifepristone treatment, no significant difference in proliferation, apoptosis and the expression of ERalpha or PRAB could be detected between the endometrium treated with DMPA alone and endometrium treated with mifepristone and DMPA. CONCLUSIONS: Administration of mifepristone to DMPA users significantly increases endometrial proliferation and decreases endometrial stromal apoptosis in the short term. Prolonged exposure to mifepristone does not counteract the inhibitory effects of progestin therapy on endometrial proliferation. Estrogen and progesterone receptors may play an important role in these effects.     

Effects of doxycycline in patients with acute cough and purulent sputum: a double blind placebo controlled trial.

BACKGROUND: Acute cough with purulent sputum is a common complaint presented to general practitioners. AIM: A randomized, double blind, placebo controlled clinical trial was undertaken to determine the efficacy of doxycycline in persons aged 18 years and over presenting to 22 general practices in the Netherlands with acute cough and purulent sputum. METHOD: Patients were excluded if they were pregnant, had an allergy or intolerance to tetracyclines, had severe dyspnoea and fine crackles on auscultation, purulent rhinitis together with maxillary tenderness, chronic airways disease, or had taken antibiotics in the previous two weeks. Patients entered in to the study were given oral doxycycline for 10 days, 200 mg on the first day, followed by 100 mg on the next nine days, or placebo. RESULTS: Duration of frequent daytime cough after entry was a mean of 1.5 days shorter in the group of 71 patients receiving doxycycline than in the group of 69 patients on placebo (4.7 days versus 6.2 days, respectively). In patients aged 55 years and over the mean duration of frequent day-time cough after entry was 4.1 days shorter in the group taking doxycycline than in the placebo group. Patients with a very frequent cough and who also felt ill at entry regained their normal daily activities 2.1 days earlier when using doxycycline than the control group. CONCLUSION: Doxycycline has small beneficial effects in patients with acute cough and purulent sputum. These beneficial effects are more prominent, and probably clinically relevant, in patients aged 55 years and over and in patients who cough very frequently and who also feel ill.     

The kinetics of serum hCG and progesterone in response to oral and vaginal administration of misoprostol during medical termination of early pregnancy

BACKGROUND: Misoprostol is widely used in combination with mifepristone for medical termination of pregnancy. We studied the endocrine parameters of trophoblast function during medical termination of early pregnancy using mifepristone in combination with oral or vaginal misoprostol. The effect of prolonged misoprostol administration was also examined. METHODS: Thirty-four women, requesting termination of pregnancy and with 相似文献   

The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium

Contraceptive use often leads to disrupted endometrial bleeding patterns in women. In this study, two different contraceptive regimes (Mircette, a monophasic oral contraceptive and Implanon, a long-acting gestagen) were used and their effects on the immunoreactivity of vascular endothelial growth factor (VEGF), oestrogen receptor (ER), progesterone receptor (PR) and endothelial cell number were determined. During the untreated normal cycle, there was a significant increase (P = 0.005) in glandular VEGF immunoreactivity and a significant decrease (P < 0.05) in PR immunoreactivity in the mid- and late secretory phases compared with the proliferative phase. There was a significant positive correlation (gamma = 0.38, P = 0.046) between stromal VEGF immunoreactivity and endothelial cell number. This correlation was also apparent during treatment with Implanon, but not with Mircette. Disrupted bleeding patterns were associated with Implanon and, to a lesser extent, with Mircette. Both contraceptives significantly reduced glandular VEGF immunoreactivity. Implanon significantly increased (P = 0.016) glandular PR staining, but Mircette significantly reduced (P = 0.027) stromal PR staining when compared with secretory before-treatment biopsies. There were no changes in endothelial cell number or glandular or stromal ER during the normal cycle, or with use of either contraceptive. There was no association between the parameters measured with bleeding patterns and histological category.     

Inhibition of ovulation by low-dose mifepristone (RU 486).

Mifepristone (RU 486) is a potent antigestagen and antiglucocorticoid which when given at a dose of 25-600 mg disrupts folliculogenesis, inhibits ovulation and induces menses in healthy women. This study reports the effects of much lower doses of mifepristone than used previously, given for the duration of a complete menstrual cycle. Healthy female volunteers (n = 11) with regular menstrual cycles were given mifepristone at a daily dose of 5 mg (n = 6) or 2 mg (n = 5) for 30 days, beginning immediately after an ovulatory placebo cycle. Mifepristone prevented menstruation for the duration of the treatment period, with recurrence of menses 15-29 days after replacement of mifepristone with placebo. Daily mifepristone given in either 5 mg or 2 mg doses inhibited ovulation, as indicated by the lack of a rise in urinary pregnanediol excretion. The excretion of oestrone glucuronide in urine rose during treatment, suggesting ovarian follicular development. Inhibition of ovulation appeared to result from a failure of the positive feedback effect of oestradiol on the hypothalamo-pituitary axis, as no surges of luteinizing hormone were seen despite pre-ovulatory levels of oestrone glucuronide being measured during exposure to mifepristone. The cycle immediately following treatment was shorter than the pre-treatment cycle, with lower peak levels of pregnanediol glucuronide, suggesting an inadequate luteal phase. Recovery from the effects of mifepristone treatment was more rapid after 2 mg than after 5 mg and one subject conceived in the immediate post-treatment phase, indicating adequate ovulation and luteinization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of difference among progestins on the anti-atherogenic effect of ethinyl estradiol: a rabbit study

BACKGROUND: Progestins in combination with estrogen are believed to have different effects on the cardiovascular system. The aim of this study was to investigate the influence of different oral contraceptive formulations on the development of experimental atherosclerosis and vascular reactivity. METHODS: A total of 160 sexually mature rabbits were ovariectomized and randomly assigned to equally large groups: (i) a cholesterol-rich diet (320 mg/day), either given alone (placebo), or together with (ii) ethinyl estradiol (EE 70 micro g/day, oral), (iii) desogestrel (DSG 525 micro g/day, oral), (iv) gestodene (GSD 262.5 micro g/day, oral), (v) levonorgestrel (LNG 525 micro g/day, oral), (vi) EE + DSG, (vii) EE + LNG, or (viii) EE + GSD. After 31 weeks of treatment, aortic accumulation of cholesterol and vascular vasoreactivity (in vitro) were determined. RESULTS: Progestins alone did not reduce the accumulation of cholesterol. EE alone or in combination with a progestin reduced the accumulation of cholesterol relative to placebo (P < 0.0001). Isolated vessels from EE-treated animals relaxed significantly more to physiological concentrations of acetylcholine than did placebo (P < 0.001), whereas vessels treated with EE plus a progestin showed an intermediate response. CONCLUSION: The progestins investigated can be combined with EE without attenuating the anti-atherogenic effect of EE.     

Termination of early pregnancy with ZK 98, 734: pharmacokinetic behaviour and clinical effect

The antiprogestin RU 486 (mifepristone) is highly effectivein inducing early abortion in women only if the compound iscombined with a prostaglandin analogue. A new related antiprogestin,ZK 98, 734, has been reported in animal studies to be much morepotent as an abortifacient than mifepristone, concomitant withless antiglucocorticoid activity. The aim of the present two-centrestudy was to explore the abortifacient efficacy and plasma concentrationsof ZK 98, 734 in women seeking abortion. A total of 96 pregnantwomen with amenorrhoea of <49 days were treated with oraldoses of 12.5, 25, 50 or 100 mg ZK 98, 734 twice daily for 4days. The overall rate of complete abortion and continuing livepregnancies was 68 and 20% respectively, i.e. results comparablewith treatment with mifepristone alone. No dose-response relationshipwas noted. In patients with complete abortion, signs of lutealsysfunction in terms of oestradiol and progesterone productionwere evident on the fourth treatment day, in contrast to patientswith failures. Increased amounts of cortisol and prolactin werefound during treatment both in successfully treated patientsand failures, whereas aldosterone values remained unaffected.The effect on cortisol may indicate some antiglucocorticoidactivity in the human. The concentrations of ZK 98, 734 in peripheralblood after 25, 50 and 100 mg twice daily for 4 days were similar.The values were slightly above 0.5µmol/l on the secondday of treatment. Maximal concentrations of 0.7 µmol/lwere seen on treatment day 4. Plasma concentrations of ZK 98,734 did not differ in cases of complete abortion and failures.In conclusion, the abortifacient efficacy in relation to doseof the new antigestaged ZK 98, 734 does not essentially differfrom that of mifepristone treatment alone.     

Continuous intrauterine compared with cyclic oral progestin administration in perimenopausal HRT

OBJECTIVES: Two hormone replacement therapy (HRT) regimens of combined oral estradiol with either continuous intrauterine or cyclic oral progestin were compared for 2 years. METHODS: 200 perimenopausal women randomly received an intrauterine system with continuous levonorgestrel release (20 microg/24 h) combined with oral estradiol (2 mg daily), or a cyclic oral regimen of norethisterone acetate (1 mg on day 13-22) and estradiol (days 1-21; 2 mg, days 22-28; 1 mg). Efficacy on endometrial protection, vaginal bleeding patterns, blood loss and practical use were compared during 26 cycles. RESULTS: Endometrial protection was adequate in both regimens. The cyclic regimen induced a more regular bleeding pattern. The continuous local administration induced a reduction in bleeding (P=0.001) with an initial period of prolonged and frequent bleeding. 38% became amenorrhoeic. Women found both regimens acceptable. CONCLUSIONS: Continuous intrauterine Levonorgestrel administration by using an intrauterine system can well be recommended for use in combination with oestrogen replacement therapy in perimenopausal women.     

Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo

BACKGROUND: Intranasal corticosteroids used with antibiotics are known to improve rhinosinusitis symptoms compared with antibiotic therapy alone. However, the efficacy of intranasal corticosteroid monotherapy for acute, uncomplicated rhinosinusitis is not established. OBJECTIVES: To evaluate efficacy and safety of mometasone furoate nasal spray (MFNS) versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis. METHODS: In this double-blind, double-dummy trial, subjects (> or =12 years; N = 981) were randomized to MFNS 200 microg once daily or twice daily for 15 days, amoxicillin 500 mg 3 times daily for 10 days, or respective placebo. Follow-up was 14 days. The primary efficacy endpoint was mean am/pm major symptom score over the treatment phase. Secondary efficacy endpoints included total symptom score. Safety assessments included disease recurrence during follow-up and adverse event monitoring. RESULTS: Mometasone furoate nasal spray 200 microg twice daily was significantly superior to placebo (P < .001) and amoxicillin (P = .002) at improving major symptom score. Starting on day 2, MFNS 200 microg twice daily improved total symptom score throughout treatment versus amoxicillin (P = .012) and placebo (P < .001). Global response to treatment was significantly greater with MFNS 200 microg twice daily versus amoxicillin (P = .013) and placebo (P = .001). Although significantly superior to placebo, MFNS 200 microg once daily was not superior to amoxicillin for the primary or secondary efficacy endpoints. All treatments were well tolerated with a similar incidence of adverse events. CONCLUSION: In patients with acute, uncomplicated rhinosinusitis, MFNS 200 microg twice daily produced significant symptom improvements versus amoxicillin and placebo, without predisposing the patient to disease recurrence or bacterial infection.     

Double-blind randomized trial of mifepristone in combination with vaginal gemeprost or misoprostol for induction of abortion up to 63 days gestation

BACKGROUND: Gemeprost and misoprostol are two of the most widely used prostaglandins in combination with mifepristone for medical abortion in early pregnancy. However, the efficacy and side-effects of those two drugs given vaginally have not been assessed in a randomized trial. METHODS: Randomized double-blind controlled trial involving 999 women undergoing an abortion at gestational age < or =63 days who received either 0.5 mg gemeprost (group I, n = 499) or 800 microg misoprostol (group II, n = 500) vaginally approximately 48 h after taking 200 mg mifepristone by mouth. The rate of complete abortion and the side-effects were compared between the groups. RESULTS: A total of 89 cases was excluded from full analysis of outcome because either they aborted after mifepristone alone (n = 2), had an ectopic pregnancy (n = 1), or because the outcome was uncertain as they failed to attend their follow-up appointment (n = 86). The rate of complete abortion was very high (>95%) in both groups but significantly higher after treatment with misoprostol than with gemeprost [436/453 (98.7%) versus 451/457 (96.2%), P = 0.019, difference 2.5%, confidence interval 0.4-4.7%] and there were fewer ongoing pregnancies (n = 1 versus n = 8, P < 0.018). Surgical intervention rose significantly with gestation in women who received gemeprost (P < 0.03) but not with misoprostol. The incidence of side-effects such as diarrhoea (13.7 versus 16.4%) and vomiting (27.8 versus 29.7%) was similar in women who received misoprostol or gemeprost respectively, as was the duration and amount of bleeding. CONCLUSIONS: (i) Both regimens using a reduced dose of mifepristone are highly effective methods of inducing abortion in early pregnancy; (ii) vaginal misoprostol is the preferred prostaglandin because it is it is associated with fewer failures than low-dose gemeprost, particularly at gestation > or =49 days.     

Mifepristone-induced amenorrhoea is associated with an increase in microvessel density and glucocorticoid receptor and a decrease in stromal vascular endothelial growth factor

BACKGROUND: We have previously shown that the progesterone antagonist mifepristone is a contraceptive when given in a dose of 2 or 5 mg per day. The majority of women experience amenorrhoea rather than the irregular break through bleeding usually occurring with other estrogen-free contraceptive pills, such as progestogen-only pill (POP). We investigated the effects of low-dose mifepristone on endometrial parameters which may be associated with changes in endometrial function, such as microvasculature, vascular endothelial growth factor (VEGF) and glucocorticoid receptor (GR) content. METHODS AND RESULTS: Endometrial biopsies were collected from 16 women before (late proliferative phase) and 60 and 120 days after taking 2 or 5 mg mifepristone daily for 120 days. Seven of the eight women who received 2 mg mifepristone and all eight women who received 5 mg were amenorrhoeic during the study. Mean estradiol (E(2)) concentrations remained in the mid-proliferative range, and the majority (9/16) of women showed proliferative endometrial histology at 60 and 120 days following treatment. There was a significant increase in the density of the endometrial stroma (P < 0.05) and microvessels (P < 0.01) following 120 days of treatment. Immunocytochemistry showed that GR, hitherto localized specifically in endometrial stroma, was up-regulated in the nuclei of glands (P < 0.05) and surface (luminal) epithelium (P < 0.01) by 60 days and maintained at 120 days. There was a significant reduction in stromal VEGF protein expression by day 120 of treatment (P < or = 0.01). CONCLUSION: The high incidence of amenorrhoea in women taking mifepristone may be related to changes in the regulation of vascular function.