Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin.

BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.

​Challenge in managing abnormal uterine bleeding in a patient on novel oral anticoagulant therapy.

This is a case report of a 48-year-old woman who presented with heavy per vaginal bleeding to the emergency department after being commenced on direct oral anticoagulants (DOACs) for venous thromboembolism. She had significant bleeding which initially required resuscitation and stabilisation. Her symptoms were ultimately managed by changing her anticoagulation agent to therapeutic low molecular weight heparin with Clexane© the agent of choice. This case study highlights the complexity of managing these patients as well as highlighting the need for ongoing research into DOACs in this area.

Rivaroxaban plus Percutaneous catheter-directed treatment for a patient with massive pulmonary embolism and colporrhagia.

Massive pulmonary embolism (PE) is defined by acute PE with sustained systemic arterial hypotension that is below 90 mm Hg for at least 15 min or requires inotropic agents (Jaff et al., 2011). For patients with absolute contraindications to thrombolysis, interventional treatment requires the removal of obstructing thrombi from the main pulmonary arteries to facilitate RV recovery and improve symptoms and survival (European Respiratory Society et al., 2014). For patients with acute PE, anticoagulation is recommended, with the objective of preventing both early death and recurrent symptomatic or fatal VTE. Rivaroxaban, an oral factor Xa inhibitor and a new oral anticoagulants, shows effective anticoagulation within hours of administration. It has a fixed-dose regimen, and requires no laboratory monitoring (EINSTEIN-PE Investigators et al., 2012). However, the efficacy and safety of rivaroxaban plus catheter-directed treatment for massive PE and bleeding is unknown. This case demonstrated that a combination of catheter-directed treatment and rivaroxaban was safe and effective in for the treatment of severe PE with vaginal bleeding.

Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series.

BACKGROUND: Observational data and results from post-hoc analyses in clinical trials suggest that direct oral factor Xa inhibitors might increase menstrual bleeding intensity in women of reproductive age, but the extent of this effect is unknown. We aimed to investigate the management and outcomes of vaginal bleeding complications during therapy with direct oral factor Xa inhibitors in a case series of women of reproductive age. METHODS: To identify individuals for inclusion in this case series, we searched two sources of prospectively collected data from women of reproductive age treated with direct oral factor Xa inhibitors: the non-interventional Dresden NOAC Registry (NCT01588119), which is based in the administrative district of Dresden (Saxony, Germany), and all locally archived data from phase 3 trials of direct oral factor Xa inhibitors done at University Hospital Carl Gustav Carus Dresden. Vaginal bleeding events were defined as any vaginal bleeding complications as reported by the patient. We collected data on type and dosage of anticoagulation; suspected or confirmed bleeding events, hospital admissions, and mortality; and pattern and management of vaginal bleeding events. For all cases of bleeding identified, we reviewed all available source data to identify examination results suggesting potential underlying anatomical causes of bleeding. FINDINGS: We identified 178 women of reproductive age who received direct oral factor Xa inhibitor therapy, of whom 57 had vaginal bleeding events, including 50 who received rivaroxaban, six who received apixaban, and one who received edoxaban. These 57 women had 72 vaginal bleeding events, including 59 cases of heavy menstrual bleeding and 13 bleeding events unrelated to the menstrual cycle. 51 (86%) of these heavy menstrual bleeding events (two major bleeding events, 17 clinically relevant non-major bleeding events, 32 minor bleeding events) were treated conservatively (eg, change of oral hormone therapy or reduction, temporary interruption, or discontinuation of direct oral factor Xa inhibitor) and the remaining eight (14%) events (three major bleeding events and five clinically relevant non-major bleeding events) required elective surgical or interventional treatment (hysterectomy, curettage, ovary excision, or excision of ovarian cysts). Of the 57 women, 13 (23%) had a second bleeding event and two (4%) had a third event. Nine patients had underlying anatomical abnormalities; compared with patients without abnormalities, these patients had more intense bleeding, more had recurrent bleeding (five [56%] of nine patients with abnormalities vs eight [17%] of 48 patients without abnormalities), and more needed surgical treatment for bleeding (eight [89%] of nine vs zero of 48). INTERPRETATION: Vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively, but patients with severe or recurrent vaginal bleeding complications should be assessed for underlying anatomical abnormalities, which might require surgical or interventional treatment. Further data are needed to provide guidance on prevention and treatment of vaginal bleeding complications in this patient population. FUNDING: None.

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration.

Blockade of tubal patency following transcervical administration of polidocanol foam: initial studies in rhesus macaques.

OBJECTIVE: To demonstrate the feasibility of polidocanol foam (PF) as a nonsurgical method of female permanent contraception using a nonhuman primate model. STUDY DESIGN: Four groups of adult female rhesus macaques underwent either transcervical treatment with 5% PF directly into the uterine cavity, treatment with inert (methylcellulose, MF) foam or no treatment followed by removal of the reproductive tract for histologic evaluation. Untreated animals were included in Group 1 (n=3). Group 2 animals (n=4) were treated once with MF. Group 3 (n=7) received a single, and Group 4 (n=5) received multiple monthly treatments with PF; in these 2 groups, baseline tubal patency was assessed either laparoscopically by chromopertubation (CP) or by hysterosalpingography. RESULTS: Group 1 (untreated) and Group 2 (MF) animals had normal tubal histology. In contrast, Group 3 and 4 females treated with PF showed evidence of tubal damage. In Group 4, bilateral tubal blockade was noted on CP after two (n=2) or three (n=3) treatments. Histologic analysis confirmed complete tubal occlusion (loss of epithelium, fibrosis) in three of these animals, and one showed significant tubal damage localized to the intramural segment. Nontarget (cervix, vagina, endometrium, ovary) reproductive tissues were unaffected. While similar tubal changes were observed after a single treatment (Group 3), endometrial hemorrhage was also noted as an acute change. CONCLUSION: PF is a promising candidate agent for nonsurgical permanent female contraception. The histologic features of PF occlusion are confined to the intramural portion of the tube. IMPLICATIONS: This study in rhesus macaques supports further development of transcervical administration of PF as a nonsurgical approach to permanent contraception. A nonsurgical method could reduce risks and costs associated with surgical female sterilization and increase access to permanent contraception.

Abnormal vaginal bleeding after epidural steroid injection: a paired observation cohort study.

OBJECTIVE: The use of epidural steroid injections has increased dramatically, but knowledge of potential adverse effects is lacking. An association between steroid injection and subsequent abnormal vaginal bleeding has been suspected clinically, but evidence has been limited to anecdotal reports. STUDY DESIGN: Paired observational retrospective cohort study using electronic medical records from a large integrated health care system. Participants were all nonhysterectomized women who underwent epidural steroid injections in 2011. For each steroid injection, encounters for abnormal vaginal bleeding during the 60 days preceding and 60 days after the injection were compared as paired observations. For women found to have bleeding, medical records review was performed to examine menopausal status and bleeding evaluation outcomes. RESULTS: Among 8166 epidural steroid injection procedures performed on 6926 nonhysterectomized women, 201 (2.5%) procedures were followed by at least 1 outpatient visit for abnormal vaginal bleeding. Women were 2.8 times more likely to present with abnormal vaginal bleeding during the postinjection period compared with the preinjection period (P < .0001). Of the 197 women with postinjection bleeding, 137 (70%) were premenopausal and 60 (30%) were postmenopausal. Postinjection bleeding prompted endometrial biopsy evaluation in 103 (52%) cases, with benign findings for 100% of premenopausal women (59/59) and 95% of postmenopausal women (42/44). CONCLUSION: Epidural steroid injections are associated with subsequent abnormal vaginal bleeding for both premenopausal and postmenopausal women. Women undergoing epidural steroid injection should be advised of abnormal bleeding as a potential adverse effect and providers should be aware of this association when evaluating abnormal bleeding.

The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and participates in RU486-induced abortion. Excessive uterine bleeding is the most common side effect of RU486-induced abortion; however, its etiopathogenesis has not been fully understood. Therefore, elucidating the correlation between the Th1/Th2/Th17/Treg paradigm and the volume of uterine bleeding may offer novel therapeutic target for reducing uterine bleeding in RU486-induced abortion. Leonurus sibiricus has been used in clinics to reduce postpartum hemorrhage with low toxicity and high efficiency; however, the effective constituents and therapeutic mechanism have not been described. Stachydrine hydrochloride is the main constituent of L. sibiricus, therefore L. sibiricus is regarded as a candidate for reducing uterine bleeding in RU486-induced abortion mice by regulating the Th1/Th2/Th17/Treg paradigm. AIM OF THE STUDY: The purpose of this study was to determine the Th1/Th2/Th17/Treg paradigm in uterine bleeding of RU486-induced abortion mice and to elucidate the immunopharmacologic effects of stachydrine hydrochloride on inducing the Th1/Th2/Th17/Treg paradigm in reducing the uterine bleeding volume in RU486-induced abortion mice. MATERIALS AND METHODS: To investigate the Th1/Th2/Th17/Treg paradigm in uterine bleeding during RU486-induced abortion mice, pregnant BALB/c mice were treated with high- and low-dose RU486 (1.5mg/kg and 0.9 mg/kg, respectively), and the serum progesterone (P(4)) protein level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells in mice at the maternal-fetal interface were detected by ELISA assay, alkaline hematin photometric assay, and flow cytometry, respectively. To determine the regulatory effect of stachydrine hydrochloride on the Th1/Th2/Th17/Treg paradigm in vitro, splenocytes of non-pregnant mice were separated and treated with P(4,) RU486, and/or stachydrine hydrochloride (10(-5)M, 10(-4)M, and 10(-3)M, respectively). The proportions of Th1/Th2/Th17/Treg cells were analyzed using flow cytometry. To evaluate the effect of stachydrine hydrochloride in reducing uterine bleeding via regulation of the Th1/Th2/Th17/Treg paradigm, pregnant mice were treated with RU486 (1.5mg/kg) and/or stachydrine hydrochloride (2.5mg/kg, 5mg/kg, and 10mg/kg). The serum P(4) level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells at the mice maternal-fetal interface were detected. Moreover, the protein levels of cytokines (IL-12 and IL-6) and the cytokine soluble receptors were analyzed by ELISA assay, and the mRNA expression of transcription factors (T-bet, GATA-3, RORγt, and Foxp3) were detected by RT-PCR assay. RESULT: Th1- and Th17-biased immunity was observed in RU486-induced abortion mice. The volume of uterine bleeding during RU486-induced abortion was negatively related to the proportions of Th1 and Th17 cells, as well as the ratios of Th1:Th2 cells and Th17:Treg cells, and positively related to the proportions of Th2 and Treg cells. Stachydrine hydrochloride promoted the protein expression of IL-12 and IL-6, as well as the mRNA expression of T-bet and RORγt, while inhibiting the mRNA expression of GATA-3 and Foxp3. Therefore, the Th1/Th2/Th17/Treg paradigm in RU486-induced abortion mice shifted to Th1 and Th17 after stachydrine hydrochloride administration. The volume of uterine bleeding during RU486-induced abortion was reduced significantly after stachydrine hydrochloride administration. CONCLUSION: The Th1/Th2/Th17/Treg paradigm is closely related to the volume of uterine bleeding in RU486-induced abortion mice. The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride contributed to the reduction in uterine bleeding in RU486-induced abortion mice.

[Pregnancy and venous thromboembolism. North-American and European guidelines. American College of Chest Physicians]. / Grossesse et maladie thromboembolique veineuse. A propos des recommandations nord-américaines eteuropéennes.

Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.

Adverse effects of phytoestrogens on reproductive health: a report of three cases.

BACKGROUND: Phytoestrogens have been thought to have favorable effects on women's health and perhaps in offsetting cancers. The possible adverse effects of phytoestrogens have not been evaluated. CASES: Abnormal uterine bleeding with endometrial pathology in three women was found to be related to a high intake of soy products. The first woman had postmenopausal bleeding with uterine polyp, proliferative endometrium and a growing leiomyoma. The second woman presented with severe dysmenorrhea, abnormal uterine bleeding, endometriosis and uterine leiomyoma not responding to treatment. The third woman with severe dysmenorrhea, abnormal uterine bleeding, endometriosis and uterine leiomyomata presented with secondary infertility. All three women improved after withdrawal of soy from their diet. CONCLUSION: Additional information on phytoestrogens is necessary to ascertain their safety before they can be routinely used as supplements.

Efficacy of tibolone as "add-back therapy" in conjunction with a gonadotropin-releasing hormone analogue in the treatment of uterine fibroids.

OBJECTIVE: To assess the efficacy of tibolone add-back therapy with Goserelin treatment of uterine fibroids. DESIGN: Randomized placebo-controlled study. SETTING: Gynecology department of an inner-city teaching hospital. PATIENT(S): Seventy-five women of reproductive age with uterine fibroids. INTERVENTION(S): All women were given monthly SC implants of 3.6 mg goserelin and were randomized to take 3 months of placebo followed by 3 months of tibolone 2.5 mg daily (delayed administration), tibolone 2.5 mg daily for 6 months, or placebo for 6 months. MAIN OUTCOME MEASURE(S): Changes in bone mineral density (BMD) at the hip and spine, fibroid and uterine size, and patient symptomatology. RESULT(S): In the tibolone group, 2% loss of BMD at the spine was observed compared with 5.5% loss in the placebo group. For total hip, tibolone led to a 0.7% gain in BMD compared with a loss of 1.7% in the placebo group. Tibolone did not affect GnRH analogue-induced fibroid shrinkage. Vasomotor symptom scores in women taking tibolone were 2.2 and were significantly lower than those taking placebo or in the delayed administration groups (mean scores 2.9 and 2.7, respectively). CONCLUSION(S): Tibolone appears to be a safe and effective add-back therapy which can be given from the commencement of GnRH analogue treatment for fibroids.

[Uterine abnormalities in non menopausal women who received tamoxifen for breast cancer adjuvant therapy]. / Anomalies utérines chez la femme non ménopausée sous tamoxifène en traitement adjuvant du cancer du sein.

OBJECTIVE: To elaborate a strategy of endometrial follow-up for premenopausal women treated with Tamoxifen as adjuvant hormonal treatment of breast cancer. PATIENTS AND METHODS: Retrospective study of 152 premenopausal patients treated with Tamoxifen in Nantes Comprehensive Cancer Center for a breast cancer from January 2003 to December 2005. Vaginal sonography was used in the follow-up of 70 of them. RESULTS: Endometrial hypertrophy was found in 26 patients. Sonohysterography and hysteroscopy allowed to find 11 polyps and three hyperplasias in the 19 women who were investigated. In our study, endometrial pathology was found in 20% of premenopausal women treated with Tamoxifen (polyps or hyperplasia). Uterine bleeding was found in half patient of this group. DISCUSSION AND CONCLUSION: Vaginal sonography monitoring could be proposed to premenopausal women treated with Tamoxifen among whom endometrial pathology is usual.

[Effect of total glycoside from Clinopodium polycephalum on uterine bleeding quantity in drug abortion model rats].

OBJECTIVE: To study the effect of total glycoside from Clinopodium polycephalum (Vaniot) C. Y. Wu et Hsuan on uterine bleeding quantity in drug abortion model rats. METHOD: Mifepristone and misoprostol were given to early-pregnancy rats orally. The change of uterine bleeding quantity was observed in uncompletive abortion model rats. RESULT: TGCP (20 mg/kg) could markedly reduce uterine bleeding quantity in drug abortion model rats. CONCLUSION: TGCP has the hemostatic effect on uterine bleeding in drug abortion model rats.

[Clinical observation on effect of xuejie jiawei decoction on vaginal hemorrhagic amount and duration in patients after drug-abortion].

OBJECTIVE: To observe the effect of Xuejie Jiawei Decoction (XJJWD) in reducing vaginal hemorrhagic amount, shortening hemorrhagic duration and lowering the curettage rate of incomplete abortion in patients after drug-abortion. METHODS: Group A was treated with XJJWD No. I from the 2nd day after abortion, one dose per day for 7 days. Group B was treated with XJJWD No. II from the 11th day after abortion, one dose per day for 5 days. The therapeutic effect of the two groups was compared with that of the untreated control group. RESULTS: In the Group A, the total score on vaginal hemorrhagic amount was markedly less than that in the control group (P < 0.01), and the vaginal hemorrhagic duration in patients with menostasis less than 45 days was shorter than that in the control group (P < 0.01). In the Group B, the total score on vaginal hemorrhagic amount in patients with menostasis less than 45 days was lower than that in the control group (P < 0.05). CONCLUSION: XJJWD could reduce the vaginal hemorrhagic amount and duration in patients after drug-abortion. It should be applied early after abortion, the less the duration of menostasis, the more effective the treatment.

Oxidative stress, vitamin E and progestin breakthrough bleeding.

Endometrial bleeding problems can be the major reason for discontinuing progestin-only contraception. In this study the endometrial angiogenic response in Norplant users was found to be lower than in women with normal menstrual cycles. These disturbances in angiogenic response may be caused by oxidant-antioxidant imbalance in the endometrium. The aims of this study were to investigate the effect of progestin only contraceptives on blood concentrations of lipid peroxide and vitamin E, and the effect of vitamin E supplementation on endometrial angiogenic response in vitro. The subjects for this study were Norplant users, depo-medroxyprogesterone acetate (DMPA) users, and controls. Circulating lipid peroxide and vitamin E concentration was measured by routine methodology. Endometrial angiogenic response was assayed using an endothelial cell migration assay. The results showed that the blood concentrations of lipid peroxide from Norplant users with bleeding problems were significantly higher than normal menstrual controls (P < 0.05) and supplementation of vitamin E (in vitro) increased the endometrial angiogenic score. Blood concentrations of lipid peroxide were significantly increased (P < 0.05), and the blood concentrations of vitamin E were significantly decreased (P < 0.05) after 3 months exposure to Norplant or DMPA. The endometrial angiogenic scores in Norplant and DMPA users were significantly lower than in controls (P < 0.02). It is concluded that in progestin-only contraceptive users, higher lipid peroxide and lower vitamin E concentration may cause endometrial cell damage and decrease the endometrial angiogenic response. It is suggested that vitamin E supplementation may counteract these unwanted side-effects.

Benefits of vitamin E supplementation to Norplant users--in vitro and in vivo studies.

Norplant subcutaneous implantation is a contraceptive method used in Indonesia. Endometrial bleeding is one major reason to discontinue the use of Norplant. Angiogenic response in the endometrium of Norplant users was found to be lower than in women with normal menstrual cycle. This disturbance in the angiogenic process may be caused by an imbalance of pro- and antioxidant processes in the endometrium of Norplant users. The aim of this study is to investigate the effect of vitamin E on the endometrial angiogenic activity and to assess the efficacy of vitamin E supplementation in treating endometrial bleeding in Norplant users. Subjects for this study were selected from Norplant users with an exposure of at least 3 months, with endometrial bleeding and recruited on the basis of fully informed consent. TBA reaction was used to measure degradation products of lipid peroxidation. The endometrial angiogenic response was assayed according to Folkman et al. (Folkman et al., 1989. Nature 239, 58-61). Samples from endometrial biopsies were incubated in vitro with vitamin E or placebo before angiogenic measurement. For in vivo supplementation, vitamin E 200 mg/day, or placebo for 10 days/month were given to the subjects with double blind randomisation. The results showed that the blood levels of TBA-reactive substances were significantly higher in Norplant users than in controls. In the endometrium from Norplant users with bleeding problems, in vitro supplementation of vitamin E resulted in a significantly higher angiogenic score than placebo. Although a highly significant reduction of bleeding days in both groups, vitamin E and placebo, was seen during the 2 months of the study, the number of bleeding days was significantly lower in women treated with vitamin E than with placebo.

[Clinical and experimental studies on qumotang for bleeding after medical abortion in 214 cases].

OBJECTIVE: To relieve the side-effect of heavy vaginal bleeding after medical abortion. METHODS: Two hundred and fourteen clinical cases were enrolled, 111 of them were treated with Qumotang (QMT) and 103 cases were the control group. RESULTS: The average bleeding durations is 8.7 +/- 6.4 days and 13.6 +/- 7.1 days respectively. The percentages of the cases with bleeding amount less than normal menstruation in QMT group and the control were 18.44% and 30.63% respectively, the difference was significant (P < 0.05). CONCLUSIONS: QMT increased the intrauterine pressure and contraction frequency of rabbit uterus in vivo and it is the effective herbal recipe for bleeding after medical abortion. QMT presented its efficacy of removing blood stasis and stopping bleeding, increasing the contraction of uterine muscles and vessels.

Purified neem (Azadirachta indica) seed extracts (Praneem) abrogate pregnancy in primates.

The use of neem (Azadirachta indica) seed extracts (Praneem) given orally for abrogation of pregnancy in subhuman primates is described. Oral administration of Praneem was initiated after confirmation of pregnancy using Leydig cell bioassay estimating rising levels of chorionic gonadotropin (CG) in the blood from day 25 onwards of the cycle and continued for six days. Termination of pregnancy was observed with the appearance of blood in the vaginal smears and decline in CG and progesterone. Pregnancy continued in the control animals treated with peanut oil at the same dose. The effect was observed in both baboons and bonnet monkeys. The treatment was well tolerated; blood chemistry and liver function tests had normal values. The animals regained their normal cyclicity in the cycles subsequent to Praneem treatment.

High dose methotrexate infusion with leucovorin rescue for treatment of ectopic pregnancy.

The purpose of this article is to evaluate the effectiveness, side effects, and complications of high dose methotrexate infusion with leucovorin rescue in select patients with ectopic pregnancy. Between January 1991 and November 1994, 28 patients with ectopic pregnancies were prospectively treated with methotrexate (100 mg/m2 intravenous bolus followed by a 200 mg/m2 infusion over six hours) with leucovorin rescue. Twenty-seven of 28 patients (96%) were successfully treated. Only one patient (4%) required a second course of methotrexate to reach a normal hCG titer. One patient failed methotrexate infusion 45 days after treatment at a hCG titer of 12 mIU/mL. No Gynecologic Oncology Group grade 3 or 4 clinical, biochemical or hematologic toxicities occurred. Uterine bleeding and abdominal pain, not requiring transfusion or hospitalization, occurred in 71% and 56% of patients. The authors conclude that high dose methotrexate infusion with leucovorin rescue is a highly effective, well tolerated, nonsurgical treatment for select patients with ectopic pregnancy.