Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation.

BACKGROUND: There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbs used during pregnancy and lactation. This is one article in a series that systematically reviews the evidence for herbs commonly used during pregnancy and lactation. OBJECTIVES: To systematically review the literature for evidence on the use, safety and pharmacology of chastetree, focusing on issues pertaining to pregnancy and lactation. METHODS: We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS In pregnancy, there is poor evidence based on theoretical and expert opinion and in vitro studies that chastetree may have estrogenic and progesteronic activity, uterine stimulant activity, emmenagogue activity and prevent miscarriages. In lactation, theoretical and expert opinion conflict as to whether chastetree increases or decreases lactation. CONCLUSIONS: Given its relatively common use amongst women of childbearing age, it is likely that some women may consume chastetree while unknowingly pregnant. Complementary and alternative medicine, midwifery and medical practitioners should be aware of this fact when prescribing chastetree to women of childbearing age, particularly when the patient is planning a family. Key words: Chastetree, vitex agnus-castus, pregnancy, lactation, breastfeeding, systematic review.

Intratumoral hemorrhage of mammary phyllodes tumor after menstrual induction: a puzzling presentation.

BACKGROUND: Mammary phyllodes tumor is an uncommon stromal-epithelial neoplasm with a reported incidence of 0.3% to 0.5% of female breast tumors. Sudden, rapid growth of a mammary phyllodes tumor with intratumoral hemorrhage was noted in a 45-year-old woman after menstrual induction with progesterone and norethindrone acetate. This case is presented here to highlight the possibility of such an onset of phyllodes tumor in order to facilitate its prompt diagnosis. CASE PRESENTATION: A 45-year-old woman suffered from missed periods for 2 months and received progesterone for menstrual induction. After treatment, rapid enlargement of her left breast was noted. Tracing the history of the patient, we found that she had already felt an about 3 cm painless lump in her left breast 5 months before this episode. Sonography of the left breast showed a large cystic lesion with some echogenic content and about 150 mL of old blood was obtained by aspiration. Surprisingly, follow-up breast sonography 3 weeks later revealed a large irregular solid mass and a small amount of peripheral cystic content with markedly increased vascularity. Surgery was suggested. A large encapsulated mass consisting of heterogeneous yellow soft tissue and a cystic component measuring 10 x 8 cm was totally excised. Microscopically, the sections revealed branching and cystically dilated glands lined by cuboidal to columnar epithelial cells in a myxoid hypercellular fibroblastic stroma with hyperchromatic nuclei and frequent mitotic figures. The final histological diagnosis was malignant phyllodes tumor. CONCLUSION: Progesterone for menstrual induction may cause rapid growth of a phyllodes tumor with resultant internal hemorrhage. Only with the awareness of this entity can a prompt diagnosis be made and optimal treatment be given.

[Mifegyne (RU-486)]. / Mifegyne (RU-486).

The substance Mifegyne, an antigestagen, can profoundly influence progesterone-dependent situations given the relevant indications and preconditions.

RU486 (mifepristone): mechanisms of action and clinical uses.

RU486 (mifepristone) has proved to be a remarkably active antiprogesterone and antiglucocorticosteroid agent in human beings. The mechanism of action involves the intracellular receptors of the antagonized hormones (progesterone and glucocorticosteroids). At the molecular level, the most important features are high binding affinity to the receptor, interaction of the phenylaminodimethyl group in the 11 beta-position with a specific region of the receptor binding pocket, and RU486-induced transconformation differences in the ligand-binding domain. These particularities have consequences at different steps of the receptor function as compared with agonists. However, the reasoning cannot be limited to the RU486-receptor interaction, and, for instance, there is the possibility of a switch from antagonistic property to agonist activity, depending on the intervention of other signaling pathways. It would be desirable to have derivatives with only one of the two antagonistic properties (antiprogestin, antiglucocorticosteroid) in spite of similarities between steroid structures, receptors involved, and responsive machineries in target cells. Clinically, the RU486-plus-prostaglandin method is ready to be used on a large scale and is close to being as convenient and safe as any medical method of abortion may be. The early use of RU486 as a contragestive as soon as a woman fears a pregnancy she does not want will help to defuse the abortion issue. Research should now be conducted to define an efficient and convenient contraceptive method with RU486 or other antiprogestins. The usefulness of RU486 for obstetric indications, including facilitation of difficult delivery, has to be assessed rapidly. Gynecologic trials, particularly in leiomyomata, should be systemically continued. The very preliminary results obtained with tumors, including breast cancers, indicate that further studies are necessary.

Factors associated with withdrawal bleeding after administration of oral dydrogesterone or medroxyprogesterone acetate in women with secondary amenorrhea.

The effectiveness of two treatment regiments in inducing withdrawal bleeding in secondary amenorrhea was compared and correlated with the endometrial thickness and endogenous E2 and progesterone concentrations. A prospective, randomized and double-blind study was designed at the Outpatient Clinic of Reproductive Endocrinology, Central Emek Hospital, Afula, Israel. Seventy-seven premenopausal women with oligomenorrhea or amenorrhea, 48 of whom qualified for the study, underwent a 5-day course of either medroxyprogesterone acetate (MPA) 5 mg b.i.d. or dydrogesterone (DG) 10 mg b.i.d. Endogenous pretreatment values of E2 and progesterone and endometrial thickness (by transvaginal ultrasonography) were correlated with the bleeding response. Withdrawal bleeding occurred in 93% of women taking either MPA or DG. Side effects occurred similarly among the groups. Lipid concentrations were unchanged. Endogenous E2 and progesterone were limited predictive value for withdrawal bleeding. Endometrial thickness as measured by transvaginal sonography correlated significantly with the bleeding response.

Review of the embryologic development of the pituitary gland and report of a case of hypophyseal duplication detected by MRI.

We describe the clinical manifestations, associated abnormalities, MRI appearances and pathologic significance of a case of hypophyseal duplication. A 16-year-old girl presented with delayed sexual development and history of midline craniofacial anomalies. MRI revealed paired infundibula extending inferiorly to two small pituitary glands, a midline hypothalamic mass, and a midline cleft in the basisphenoid. Twelve cases of pituitary duplication have previously been described. The suggested pathogenesis is duplication of the prechordal plate and anterior end of the notochord during early embryologic development.

Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol [corrected].

The efficacy and tolerability of mifepristone in combination with misoprostol for termination of early pregnancy (up to 49 days of amenorrhea) are established. We studied the efficacy and tolerability of this combination therapy for termination of pregnancy in women up to 63 days of amenorrhea. We also examined the effect of an additional dose of misoprostol in cases of nonexpulsion within 3 hours after the first dose. The multicenter trial included 1,108 women, mean age 27.9 +/- 6.2 years. The mean duration of pregnancy was 51.7 +/- 9.2 days. On day 1, the women received an oral dose of mifepristone, 600 mg. On day 3, they received an oral dose of misoprostol, 400 micrograms, and were monitored for up to 3 hours. If they did not expel the conceptus within 3 hours, an additional dose of 200 micrograms of misoprostol was given and they were monitored for 2 more hours. From days 10 to 18, the women were followed up with clinical examination, human chorionic gonadotropin measurement, or ultrasound examination. Overall, the procedure was successful in 92.9% of women. Efficacy decreased with the duration of pregnancy, especially after 56 days of amenorrhea. Up to 42 days of amenorrhea, the success rate was 97.6%; between days 42 and 49, 94.8%; between days 50 and 56, 93.4%; between days 57 and 63, 86.8%; and after day 63, 83.3%. The most common side effects were moderate uterine cramps (80.5%) and gastrointestinal (GI) symptoms (34.9%), especially vomiting (18.3%) and diarrhea (10.5%). GI symptoms were generally mild. A second dose of misoprostol was given to 61.6% of the women. In a subgroup analysis, we assessed the efficacy of 600 mg of mifepristone plus 400 or 600 micrograms of misoprostol (one or two doses) in women with up to 49 days of amenorrhea and compared it with the efficacy in women who received mifepristone plus only 400 micrograms (one dose) of misoprostol in a previous study. The overall rate of success (termination of pregnancy) was 95.5% in the current study compared with 95.4% in the previous study. The additional dose of misoprostol did not significantly increase the overall rate of success, but did increase the rate of termination within the monitoring period (69.7% versus 64.9% (and within 72 hours after administration of mifepristone (92.7% versus 90.4%). We have confirmed that the combination of mifepristone and misoprostol was effective, safe, and well tolerated for termination of pregnancies at 49 or fewer days of amenorrhea. The efficacy decreased slightly between 49 and 56 days, and then decreased significantly between 56 and 63 days. For maximal safety and tolerability, we recommend this method only for women with 49 or fewer days of amenorrhea. A second dose of misoprostol did not improve overall efficacy, but did increase the rate of early termination.