Herbal Science Research - women

Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients.

Site Editor — Fri, 02 Nov 2007 05:52:36 -0700

Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients.: Support Care Cancer. 2007 Aug;15(8):913-21 Authors: Walji R, Boon H, Guns E, Oneschuk D, Younus J

GOALS OF WORK: Black cohosh is commonly used to treat hot flashes and other symptoms associated with menopause. It is thought to have multiple mechanisms of action, including potential phytoestrogenic properties. This has caused some concern about its use by patients with hormone-sensitive cancer. This paper will present the results of a systematic review of the safety and efficacy of black cohosh (Cimicifuga racemosa [L.] Nutt.) in patients with cancer. MATERIALS AND METHODS: A critical assessment of clinical (n = 5) and preclinical (n = 21) studies of black cohosh and cancer (breast and prostate) to treat hot flashes and other related symptoms is presented. In addition, clinical studies, case reports, animal studies, and in vitro assessments of the safety of black cohosh for patients with hormonally sensitive cancers is summarized and interpreted. MAIN RESULTS: In general, the research assessing efficacy of black cohosh for the treatment of hot flashes in women with breast cancer is inconclusive. There is laboratory evidence of antiproliferative properties but no confirmation from clinical studies for a protective role in cancer prevention. Black cohosh seems to have a relatively good safety profile. Concerns about liver toxicity are inconclusive. With relevance to cancer patients, black cohosh also seems not to exhibit phytoestrogenic activity and is in fact possibly an inhibitor of tumor growth. CONCLUSIONS: The use of black cohosh appears to be safe in breast cancer patients without risk for liver disease, although further research is needed in this and other populations.

PMID: 17602247 [PubMed - indexed for MEDLINE]

The plant alkaloid sanguinarine is a potential inhibitor of follicular angiogenesis.

Site Editor — Mon, 22 Oct 2007 18:18:06 -0700

The plant alkaloid sanguinarine is a potential inhibitor of follicular angiogenesis.: J Reprod Dev. 2007 Jun;53(3):573-9 Authors: Basini G, Santini SE, Bussolati S, Grasselli F

Sanguinarine (SA), a phytobiotic from Sanguinaria Canadensis, has been demonstrated to inhibit vessel growth. Current restrictions on the use of antibiotic growth promoters have motivated addition of this alkaloid as a naturally appetizing feed additive for farm animals. However, concern may araise since angiogenesis is a fundamental event in ovarian follicle growth. Therefore, the aim of this study was to evaluate the potential negative role of SA in follicular angiogenesis. For this purpose, we studied the effect of 300 nM SA on the production of vascular endothelial growth factor (VEGF) by swine granulosa cells from follicles >5 mm and on the activation of Akt, the main effector of the VEGF signalling pathway. In addition, the potential interference of SA in vessel development was tested in an in vitro angiogenesis bioassay. SA inhibited both VEGF production and VEGF-induced Akt activation in swine granulosa cells. Moreover, it was able to block vessel growth induced by VEGF. Taken together, our results suggest that SA could be detrimental to follicular angiogenesis, and therefore supplementation of feed with this alkaloid should be carefully considered.

PMID: 17310078 [PubMed - indexed for MEDLINE]

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[...] the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.

Site Editor — Sun, 14 Oct 2007 01:17:38 -0700

A pilot and feasibility study on the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.: Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1601-9 Authors: Greenlee H, Atkinson C, Stanczyk FZ, Lampe JW

Naturopathic physicians commonly make dietary and/or dietary supplement recommendations for breast cancer prevention. This placebo-controlled, parallel-arm, pilot study tested the effects of two naturopathic interventions over five menstrual cycles on sex steroid hormones and metabolic markers in 40 healthy premenopausal women. The intervention arms were as follows: combination botanical supplement (Curcuma longa, Cynara scolymus, Rosmarinus officinalis, Schisandra chinensis, Silybum marinum, and Taraxacum officinalis; n = 15), dietary changes (3 servings/d crucifers or dark leafy greens, 30 g/d fiber, 1-2 liters/d water, and limiting caffeine and alcohol consumption to 1 serving each/wk; n = 10), and placebo (n = 15). Early-and late-follicular phase serum samples from cycles 1 and 5 were analyzed for estrogens (estrone, estrone-sulfate, total estradiol, and free estradiol), androgens (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and free testosterone), sex hormone-binding globulin, and metabolic markers (insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and leptin). Serum samples collected during the mid-luteal phase of cycles 1 and 5 were analyzed for total estradiol, free estradiol, and sex hormone-binding globulin. Urine samples collected during the late follicular phase of cycles 1 and 5 were analyzed for 2-hydroxyestrone and 16alpha-hydroxyestrone. During the early follicular phase, compared with placebo, the botanical supplement decreased dehydroepiandrosterone (-13.2%; P = 0.02), dehydroepiandrosterone-sulfate (-14.6%; P = 0.07), androstenedione (-8.6%; P = 0.05), and estrone-sulfate (-12.0%; P = 0.08). No other trends or statistically significant changes were observed. When comparing dietary changes with placebo, no statistically significant differences were observed. Overall, in this pilot study, the naturopathic interventions had no substantial effects on estrogen measures. Early-follicular phase androgens decreased with the botanical supplement.

PMID: 17684134 [PubMed - indexed for MEDLINE]

Traditional practices, beliefs and uses of medicinal plants in [...] maternal-baby health of Criollo woman in central Argentina.

Site Editor — Thu, 04 Oct 2007 05:40:04 -0700

Traditional practices, beliefs and uses of medicinal plants in relation to maternal-baby health of Criollo woman in central Argentina.: Midwifery. 2007 Sep 28; Authors: Martínez GJ

OBJECTIVE: to present information on traditional practices and medicinal uses of plants for treating health diseases related to the reproductive cycle of Criollo women living in the hills of the province of Córdoba; and to interpret these uses in the context of this population's folk medicine. DESIGN: data were collected during several field trips to the study area based on the guidelines of a research project that included ethnographic and ethnobotanical aspects of the study area. SETTING: a rural community of central Argentina. PARTICIPANTS: a total of 62 peasants were interviewed on the basis of a semi-structured system. Repeated open and extensive interviews were also undertaken with seven women who had previously worked as midwives in areas of difficult access. FINDINGS: this study found that 12 different female diseases and complaints are treated using a total of 48 plant species belonging to 27 botanical families, with 71 different medicinal uses. The traditional beliefs and practices associated with maternal-baby health care in rural areas highlights the existing combination of principles reformulated from humoral medicine, the use of analogical reasoning, and ontological and functional interpretations of morbid processes. The principle of Hypocratical opposition and hot-cold categorisation are significant criteria that rule over the practices of mother and child health care during birth and puerperium. IMPLICATIONS FOR PRACTICE: consequences of traditional knowledge on the health care of peasant women are discussed, based on the analysis of traditional practices from a peasant's point of view.

PMID: 17905491 [PubMed - as supplied by publisher]

Prevention and treatment of vaginal bleeding after drug-induced abortion by Yaoliuan capsule and its effects on menses recovery.

Site Editor — Thu, 04 Oct 2007 05:20:47 -0700

Prevention and treatment of vaginal bleeding after drug-induced abortion by Yaoliuan capsule and its effects on menses recovery.: J Huazhong Univ Sci Technolog Med Sci. 2005;25(3):346-7, 367 Authors: Jin Z, Huang G

In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period < or = 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8%) of complete abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.

PMID: 16201292 [PubMed - indexed for MEDLINE]

Intake of water, herbal teas and non-breast milks during the first month of life: [...] impact on breastfeeding duration

Site Editor — Wed, 26 Sep 2007 19:09:53 -0700

Intake of water, herbal teas and non-breast milks during the first month of life: Associated factors and impact on breastfeeding duration.: Early Hum Dev. 2007 Sep 19; Authors: Giugliani ER, do Espírito Santo LC, de Oliveira LD, Aerts D

BACKGROUND:: The use of non-breast milks seems to cause more harm to the child's health than the isolated introduction of water/herbal teas. AIMS:: Study the factors associated with introduction of water/herbal teas or non-breast milks during the first month of life and determine the impact of this supplementation on breastfeeding duration. STUDY DESIGN:: Nested cross-sectional study. SUBJECTS:: 220 mother-infant pairs contacted in the maternity ward, at 7 days and at the end of 1, 2, 4, and 6 months. OUTCOME MEASURES:: Introduction of water/herbal teas or non-breast milks in the first month of life based on data collected during a home visit 30 days after delivery. RESULTS:: Introduction of water/herbal teas was associated with maternal age <20 years (prevalence ratio=1.55; 95%CI 1.14-2.09), <6 prenatal consultations (1.48; 1.09-2.01), cohabitation with maternal grandmother (1.51; 1.10-2.10), and poor latch-on at 30 days (1.87; 1.35-2.58). Introduction of non-breast milks was associated with breastfeeding of previous children for <6 months (3.18; 1.18-8.58), cesarean (1.92; 1.07-3.44), poor latch-on at 30 days (2.82; 1.55-5.11), use of pacifier at 7 days (2.75; 1.38-5.48), introduction of herbal teas in the first 7 days (2.75; 1.15-4.15) and breast engorgement at 7 days (2.19; 1.01-3.16). Introduction of non-breast milks negatively influenced breastfeeding duration (p<0.001); this was not observed with water/herbal teas (p=0.277). CONCLUSION:: Priority should be given to preventing the early introduction on non-breast milks, especially in mother-infant pairs with associated risk factors.

PMID: 17888592 [PubMed - as supplied by publisher]

[...] effects of Cimicifuga racemosa [...] on the estrogen receptor positive human breast cancer cell line MCF-7.

Site Editor — Sat, 22 Sep 2007 18:18:28 -0700

Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.: BMC Pharmacol. 2007 Sep 20; 7(1): 11 Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M

ABSTRACT: BACKGROUND: Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic Cimicifuga rhizome extract and cycloartane-type triterpenoids on the estrogen receptor positive human breast cancer cell line MCF-7. RESULTS: Both extract and purified compounds clearly inhibited cellular proliferation. Gene expression profiling with the extract allowed us to identify 431 regulated genes with high significance. The extract induced expression pattern differed from those of 17beta-estradiol or the estrogen receptor antagonist tamoxifen. We observed a significant enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, as well as an increase of mRNAs coding for gene products involved in several stress response pathways. These functional groups were highly overrepresented among all regulated genes. Also several transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Real-Time RT-PCR analysis of 13 selected genes was conducted after treatment with purified compounds - the cycloartane-type triterpene glycoside actein and triterpene aglycons - showing similar expression levels compared to the extract. CONCLUSION: No estrogenic but antiproliferative and proapoptotic gene expression was shown for black cohosh in MCF-7 cells at the transcriptional level. The effects may be results of the activation of different pathways. The cycloartane glycosides and - for the first time - their aglycons could be identified as an active principle in black cohosh.

Evolution of medical treatment for endometriosis: back to the roots?

Site Editor — Fri, 13 Jul 2007 18:36:22 -0700

Evolution of medical treatment for endometriosis: back to the roots?: Hum Reprod Update. 2007 Jun 16; Wieser F, Cohen M, Gaeddert A, Yu J, Burks-Wicks C, Berga SL, Taylor RN

Experimental evidence is accumulating to suggest that medicinal botanicals have anti-inflammatory and pain-alleviating properties and hold promise for treatment of endometriosis. Herein, we present a systematic review of clinical and experimental data on the use of medicinal herbs in the treatment of endometriosis. Although there is a general lack of evidence from clinical studies on the potential efficacy of medicinal herbs for the treatment of endometriosis-associated symptoms, our review highlights the anti-inflammatory and pain-alleviating mechanisms of action of herbal remedies. Medicinal herbs and their active components exhibit cytokine-suppressive, COX-2-inhibiting, antioxidant, sedative and pain-alleviating properties. Each of these mechanisms of action would be predicted to have salutary effects in endometriosis. Better understanding of the mechanisms of action, toxicity and herb-herb and herb-drug interactions permits the optimization of design and execution of complementary alternative medicine trials for endometriosis-associated pain. A potential benefit of herbal therapy is the likelihood of synergistic interactions within individual or combinations of plants. In this sense, phytotherapies may be analogous to nutraceuticals or whole food nutrition. We encourage the development of herbal analogues and establishment of special, simplified registration procedures for certain medicinal products, particularly herbal derivates with a long tradition of safe use.

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.

Site Editor — Fri, 13 Jul 2007 18:25:27 -0700

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.: Phytother Res. 2007 May;21(5):444-7 Authors: Akdoğan M, Tamer MN, Cüre E, Cüre MC, Köroğlu BK, Delibaş N

Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism.

PMID: 17310494 [PubMed - indexed for MEDLINE]

Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence.

Site Editor — Fri, 13 Jul 2007 18:22:25 -0700

Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence.: Cancer Lett. 2007 Jun 18;251(1):43-52 Authors: Ye B, Aponte M, Dai Y, Li L, Ho MC, Vitonis A, Edwards D, Huang TN, Cramer DW

There is considerable interest in herbal therapies for cancer prevention but often with little scientific evidence to support their use. In this study, we examined epidemiological data regarding effects of commonly used herbal supplements on risk for ovarian cancer and sought supporting biological evidence. 4.2% of 721 controls compared to 1.6% of 668 cases regularly used Ginkgo biloba for an estimated relative risk (and 95% confidence interval) of 0.41 (0.20,0.84) (p=0.01); and the effect was most apparent in women with non-mucinous types of ovarian cancer, RR=0.33 (0.15,0.74) (p=0.007). In vitro experiments with normal and ovarian cancer cells showed that Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in serous ovarian cancer cells, but little effect in mucinous (RMUG-L) cells. For the ginkgolides, the inhibitory effect appeared to be cell cycle blockage at G0/G1 to S phase. This combined epidemiological and biological data provide supportive evidence for further studies of the chemopreventive or therapeutic effects of Ginkgo and ginkgolides on ovarian cancer.

PMID: 17194528 [PubMed - indexed for MEDLINE]

[...] Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.

Site Editor — Sat, 23 Jun 2007 05:37:43 -0700

The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.:

The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.

Menopause. 2007 Mar-Apr;14(2):270-83

Authors: Kaszkin-Bettag M, Ventskovskiy BM, Kravchenko A, Rettenberger R, Richardson A, Heger PW, Heger M

OBJECTIVE: To investigate the efficacy of the special extract ERr 731 from the roots of Rheum rhaponticum compared with placebo on anxiety, health state, and general well-being in perimenopausal women. DESIGN: This study is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial, in which 109 perimenopausal women with climacteric complaints and anxiety received either 1 enteric coated tablet of ERr 731 (n=54) or placebo (n=55) daily for 12 weeks. The Hamilton Anxiety Scale, the Menopause Rating Scale II, the Women's Health Questionnaire, and the Psychological General Well-Being Index were used to measure anxiety, health state, and subjective psychological well-being. RESULTS: The results demonstrate that ERr 731 is highly effective in reducing anxiety in perimenopausal women compared with placebo. After 12 weeks, the Hamilton Anxiety Scale total score decreased significantly with ERr 731 (from 27.5+/-6.8 to 9.4+/-4.2 points) compared with placebo (from 25.1+/-6.0 to 21.6+/-8.6 points). ERr 731 also reduced the Hamilton Anxiety Scale factor scores for somatic and psychic anxiety. After 12 weeks, a reduction in the severity of anxiety from "moderate" or "severe" to "slight" was observed in 33 of 39 ERr 731 women completing the double-blind phase, which correlated well with the reduction in number and severity of hot flushes. This was reflected by a high rate of ERr 731 women reporting a marked improvement in health state and general well-being. CONCLUSIONS: ERr 731 is an effective medication for women with menopause-related anxiety and improves their health state and general well-being.

PMID: 17213754 [PubMed - indexed for MEDLINE]

[...] the growth stimulatory effect of soy and its isoflavones on established breast cancer

Site Editor — Sat, 23 Jun 2007 05:30:16 -0700

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?:

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?

Mol Nutr Food Res. 2007 Jun 20;

Authors: Power KA, Thompson LU

Consumption of phytoestrogen (PE)-rich foods (i. e., soy and flaxseed (FS)) is increasing because of their suggested health benefits. However, recent studies raise concern over the safety of soy and its isoflavones, particularly genistein (GEN), for postmenopausal breast cancer (BC), due to their potential stimulatory effects on human breast tissue and on the growth of existing tumors in rodents. FS, rich in PE lignans, which is metabolized to the mammalian lignans enterolactone (ENL) and enterodiol (END), has consistently been shown to have tumor inhibitory effects in a human clinical trial as well as rodent BC models. Using the preclinical athymic mouse postmenopausal BC model, combining FS with soy protein or GEN with END and ENL, was found to negate the tumor stimulatory effects of soy protein or GEN alone. The mechanism may be related to the modulation of estrogen receptor and MAPK signaling pathways. If these studies can be confirmed in clinical trials, then consumption of combined soy and FS, or their PEs, may reduce the tumor growth stimulatory effect of soy or GEN. This may indicate that if soy is consumed with lignan-rich foods, it may continue to induce its other beneficial health effects, without inducing adverse effect on postmenopausal BC.

PMID: 17579892 [PubMed - as supplied by publisher]

[Prevention and alternative methods for prophylaxis of recurrent urinary tract infections in women]

Site Editor — Mon, 11 Jun 2007 06:43:56 -0700

[Prevention and alternative methods for prophylaxis of recurrent urinary tract infections in women]: Urologe A. 2006 Apr;45(4):443-4, 446-50 Authors: Vahlensieck W, Bauer H

General recommendations to prevent recurrent urinary tract infections (rUTI) result in about one-third of patients remaining free of recurrences. Oral and parenteral immunotherapy were effective in several controlled studies for prevention of rUTI. These therapies can be combined with acute antibiotic therapy. Vaginal prophylaxis with oestriol has proven its positive effect without serious gynaecological side effects. Also there is increasing evidence that cranberries prevent rUTI. The exact mode (juice, tablets or preserved berries), dosage and duration of this therapy remain to be defined. There are also promising therapy modalities such as changing bacterial gut flora, general immune response (acupuncture, inpatient rehabilitation) and urine acidity.

Dietary phytoestrogen intake and cognitive function in older women.

Site Editor — Wed, 30 May 2007 01:05:28 -0700

Dietary phytoestrogen intake and cognitive function in older women.: J Gerontol A Biol Sci Med Sci. 2007 May;62(5):556-62 Authors: Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, van der Schouw YT

BACKGROUND: Aging is associated with a decline in cognitive function; we explored the possible influence of dietary phytoestrogens on this decline. METHODS: We conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food-frequency questionnaire covering habitual diet in the year preceding enrolment. The endpoints were cognitive function measured in three domains: memory, processing capacity and speed, and executive function. Data were analyzed using linear regression models, after adjusting for confounders. RESULTS: No association between dietary isoflavone intake and cognitive function was found. High lignan intake was associated with a better performance in processing capacity and speed, and in executive function (p for trend over quartiles =.01 and.02, respectively). CONCLUSIONS: This finding calls for further research to elucidate the relatively underexplored role of lignans within the range of phytoestrogens.

Phytoestrogens and Coronary Microvascular Function in Women with Suspected Myocardial Ischemia: A Report from [...] (WISE) Study

Site Editor — Wed, 30 May 2007 01:03:14 -0700

Phytoestrogens and Coronary Microvascular Function in Women with Suspected Myocardial Ischemia: A Report from the Women's Ischemia Syndrome Evaluation (WISE) Study.: J Womens Health (Larchmt). 2007 May;16(4):481-8 Authors: Pepine CJ, Von Mering GO, Kerensky RA, Johnson BD, McGorray SP, Kelsey SF, Pohost G, Rogers WJ, Reis SE, Sopko G, Bairey Merz CN

Aims: Soy phytoestrogens are popular, but information on their coronary effects in patients with suspected ischemic heart disease is limited. Accordingly, we investigated the relationship between blood phytoestrogen levels and coronary reactivity in women with suspected myocardial ischemia referred for coronary angiography. Methods: Coronary flow velocity reserve (CFVR) and volumetric flow reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial-dependent responses) and acetylcholine (ACH) (endothelial-dependent response) were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE). Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were correlated with coronary reactivity measures. Results: Participants were mostly postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery disease (CAD) at angiography. Genistein blood levels were negatively correlated with nonendothelial-dependent coronary flow responses. The highest genistein tertile (>6.1 ng/mL) had a CFVR of 2.1 +/- 0.5 (mean +/- SD) and VFRADO of 1.0 +/- 0.6, and both were significantly (p= 0.0001) lower compared with the other genistein tertiles combined. Similar associations were noted for CFVR(NTG) and VFR(NTG) (p = 0.03 and p = 0.01, respectively). The highest genistein tertile was associated with lower CFVR(ACH) compared with the other tertiles (p = 0.03). In multivariable modeling, blood genistein levels were significant independent predictors of coronary flow responses to ADO. There were no significant correlations between coronary reactivity variables and daidzein or endogenous estrogen. Conclusions: In women with suspected myocardial ischemia, higher genistein blood levels are associated with impaired nonendothelial-dependent and endothelial-dependent coronary microvascular function.

Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls.

Site Editor — Fri, 11 May 2007 16:18:53 -0700

Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls.: Environ Health Perspect. 2007 Jan;115(1):116-21 Authors: Wolff MS, Teitelbaum SL, Windham G, Pinney SM, Britton JA, Chelimo C, Godbold J, Biro F, Kushi LH, Pfeiffer CM, Calafat AM

BACKGROUND: Hormonally active environmental agents have been measured among U.S. children using exposure biomarkers in urine. However, little is known about their variation by race, age, sex, and geography, and no data exist for newly developed biomarkers. OBJECTIVE: Our goal was to characterize relevant, prevalent exposures for a study of female pubertal development. METHODS: In a pilot study among 90 girls from New York City, New York, Cincinnati, Ohio, and northern California, we measured 25 urinary analytes representing 22 separate agents from three chemical families: phytoestrogens, phthalates, and phenols. Exposures occur chiefly from the diet and from household or personal care products. RESULTS: Participants represented four racial/ethnic groups (Asian, black, Hispanic, white), with mean age of 7.77 years. Most analytes were detectable in > 94% of samples. The highest median concentrations for individual analytes in each family were for enterolactone (298 microg/L), monoethylphthalate (MEP; 83.2 microg/L), and benzophenone-3 (BP3; 14.7 microg/L). Few or no data have been reported previously for four metabolites: mono(2-ethyl-5-carboxypentyl) phthalate, tridosan, bisphenol A (BPA), and BP3; these were detected in 67-100% of samples with medians of 1.8-53.2 microg/L. After multivariate adjustment, two analytes, enterolactone and BPA, were higher among girls with body mass index < 85th reference percentile than those at or above the 85th percentile. Three phthalate metabolites differed by race/ethnicity [MEP, mono(2-ethylhexyl) phthalate, and mono-3-carboxypropylphthalate]. CONCLUSIONS: A wide spectrum of hormonally active exposure biomarkers were detectable and variable among young girls, with high maximal concentrations (> 1,000 microg/L) found for several analytes. They varied by characteristics that may be relevant to development.

Gene expression analysis of the mechanisms whereby black cohosh inhibits human breast cancer cell growth.

Site Editor — Fri, 11 May 2007 15:55:23 -0700

Gene expression analysis of the mechanisms whereby black cohosh inhibits human breast cancer cell growth.: Anticancer Res. 2007 Mar-Apr;27(2):697-712 Authors: Einbond LS, Su T, Wu HA, Friedman R, Wang X, Jiang B, Hagan T, Kennelly EJ, Kronenberg F, Weinstein IB

BACKGROUND: Previous studies indicate that specific extracts and the pure triterpene glycoside actein obtained from black cohosh inhibit growth of human breast cancer cells. Our aim is to identify alterations in gene expression induced by treatment with a methanolic extract (MeOH) of black cohosh. MATERIALS AND METHODS: We treated MDA-MB-453 human breast cancer cells with the MeOH extract at 40 microg/ml and collected RNA at 6 and 24 h; we confirmed the microarray results with real-time RT-PCR for 18 genes. RESULTS: At 6 h after treatment there was significant increase in expression of ER stress (GRP78), apoptotic (GDF15), lipid biosynthetic (INSIG1 and HSD17B7) and Phase 1 (CYP1A1) genes and, at 24 h, decrease in expression of cell cycle (HELLS and PLK4) genes. CONCLUSION: Since the MeOH extract activated genes that enhance apoptosis and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer.

[...] studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Iscador).

Site Editor — Wed, 21 Feb 2007 18:21:15 -0800

Randomised and non-randomised prospective controlled cohort studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Iscador): a re-analysis.: Eur J Med Res. 2006 Nov 30;11(11):485-95 Authors: Grossarth-Maticek R, Ziegler R

OBJECTIVE: Expanded presentation and re-analysis of previously published data of randomized and non-randomized studies on mistletoe therapy with breast cancer patients [3, 4]. The main question is: Does a re-analysis confirm the previously reported effects of prolonging the survival of patients with breast cancer under long-term application of a complementary/anthroposophic therapy with the European mistletoe preparation Iscador? DATA SOURCES: (1) Randomised matched-pairs study: Breast cancer patients with only lymphatic metastases (17 pairs) that had never used mistletoe therapy were matched for several prognostic factors. By paired random allocation, one patient of a pair received a suggestion of mistletoe therapy to be applied by the attending physician. (2) Non-randomised matched-pairs studies: Patients that had already received mistletoe (Iscador) therapy were matched to control patients from the same pool using the same prognostic criteria. Three groups were recruited by this procedure: breast cancer with local recurrences and no metastases (42 pairs), breast cancer with only lymphatic metastases (55 pairs), and breast cancer with distant metastases (83 pairs). ANALYSIS: Cox proportional hazard models and sensitivity analyses based on subsets of the original data sets according to strict or lose application of the matching criteria. RESULTS: The results of this re-analysis are consistent with the earlier results, even when comparing different methods and subsets. In the randomised study, the effect of long-term Iscador therapy on overall survival is significantly in favour of the Iscador therapy: Estimate of the median difference and 95 % confidence interval in years 2.5 (0.83, 4.50). The results for the non-randomised studies were also in favour of the Iscador therapy: Breast cancer with local recurrences and no metastases: estimate of hazard ratio and 95 % confidence interval 0.52 (0.23, 1.17); breast cancer with lymphatic metastases: 0.27 (0.15, 0.50); breast cancer with distant metastases: 0.53 (0.32, 0.88). As a short-term effect of this therapy, psychosomatic self-regulation noticeably increases within 3 months in the Iscador group in comparison to the control group in the randomised study: estimate of the median difference 0.90 (0, 1.75). CONCLUSION: The re-analysis demonstrates that the effects shown in the previously published data are consistent despite using different analytic methods and different subsets. Overall, the survival of patients receiving mistletoe treatment with Iscador is longer in these studies. In the short term, psychosomatic self-regulation, as a measure of autonomous coping with the disease, rises more under Iscador therapy than under conventional therapy alone.

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.

Site Editor — Wed, 21 Feb 2007 18:03:54 -0800

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.: Phytother Res. 2007 Feb 20; Authors: Akdoğan M, Tamer MN, Cüre E, Cüre MC, Köroğlu BK, Delibaş N

Apigenin suppresses cancer cell growth through ERbeta.

Site Editor — Wed, 31 Jan 2007 19:21:50 -0800

Apigenin suppresses cancer cell growth through ERbeta.: Neoplasia. 2006 Nov;8(11):896-904 Authors: Mak P, Leung YK, Tang WY, Harwood C, Ho SM

Two flavonoids, genistein and apigenin, have been implicated as chemopreventive agents against prostate and breast cancers. However, the mechanisms behind their respective cancer-protective effects may vary significantly. The goal of this study was to determine whether the antiproliferative action of these flavonoids on prostate (DU-145) and breast (MDA-MB-231) cancer cells expressing only estrogen receptor (ER) beta is mediated by this ER subtype. It was found that both genistein and apigenin, although not 17beta-estradiol, exhibited antiproliferative effects and proapoptotic activities through caspase-3 activation in these two cell lines. In yeast transcription assays, both flavonoids displayed high specificity toward ERbeta transactivation, particularly at lower concentrations. However, in mammalian assay, apigenin was found to be more ERbeta-selective than genistein, which has equal potency in inducing transactivation through ERalpha and ERbeta. Small interfering RNA-mediated downregulation of ERbeta abrogated the antiproliferative effect of apigenin in both cancer cells but did not reverse that of genistein. Our data unveil, for the first time, that the anticancer action of apigenin is mediated, in part, by ERbeta. The differential use of ERalpha and ERbeta signaling for transaction between genistein and apigenin demonstrates the complexity of phytoestrogen action in the context of their anticancer properties.

Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador).

Site Editor — Wed, 31 Jan 2007 19:17:06 -0800

Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador).: Forsch Komplementarmed. 2006 Oct;13(5):285-92 Authors: Grossarth-Maticek R, Ziegler R

BACKGROUND: Mistletoe preparations such as Iscador (Weleda, Schwäbisch Gmünd, Germany) are commonly used in complementary and alternative / anthroposophic medicine for many cancer indications, particularly for solid cancers. Efficacy of this complementary therapy is still controversial. OBJECTIVE: Does long-term therapy with Iscador show any effect on survival, tumor progression and psychosomatic self-regulation of patients with breast cancer? PATIENTS AND METHODS: Prospective recruitment and long-term follow-up of two controlled cohort studies: (1) Randomized matched-pair study (38 pairs): breast cancer patients without any recurrences or metastases and no mistletoe therapy were matched for prognostic factors. By pairwise random allocation, one of the patients was suggested mistletoe therapy to be applied by the attending physician. (2) Non-randomized matched-pair study (84 pairs): breast cancer patients without recurrences or metastases that already received mistletoe therapy were matched to control patients without Iscador therapy. RESULTS: For overall survival, the nonrandomized study shows significant effects in favor of Iscador therapy: hazard ratio HR estimate and 95% confidence interval CI: 0.43 (0.27-0.68). The effect of long-term Iscador therapy on tumor progression as measured by the time to local recurrences, lymphatic or distant metastases in breast cancer patients without any such events at first diagnosis, is in most cases significant in favor of the Iscador group, in the randomized as well as in the non-randomized study. Psychosomatic self-regulation in the Iscador group improves significantly within 12 months compared with the control group in the randomized as well as in the non-randomized study: estimate of the median difference and 95% CI: 0.35 (0.05-0.60), respectively 0.20 (0-0.35). CONCLUSION: Iscador shows a clinically relevant effect on breast tumor progression as measured by overall survival as well as by the time to recurrences, lymphatic or distant metastases. In the short term, psychosomatic self-regulation increases more markedly under complementary Iscador therapy than under conventional therapy alone.

Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status.

Site Editor — Sat, 20 Jan 2007 16:28:29 -0800

Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status.: Breast Cancer Res Treat. 2006 Oct;99(3):309-11 Authors: McCann SE, Kulkarni S, Trevisan M, Vito D, Nie J, Edge SB, Muti P, Freudenheim JL

We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.

The use of herbs and dietary supplements in gynecology: an evidence-based review.

Site Editor — Fri, 19 Jan 2007 18:43:30 -0800

The use of herbs and dietary supplements in gynecology: an evidence-based review.: J Midwifery Womens Health. 2006 Nov-Dec;51(6):402-9 Authors: Dennehy CE

Consumers frequently use herbs and dietary supplements to treat chronic conditions that are poorly responsive to prescription drugs or when prescription drugs carry a high side effect burden. Women may use herbs and supplements for chronic gynecologic conditions, such as menopause, premenstrual syndrome, dysmenorrhea, cyclic mastalgia, and infertility. This review is an evidence-based evaluation of herbs and supplements for these conditions. Therapies that carry a higher level of support from randomized controlled trial evidence include black cohosh for menopause; vitamins B(1) and E for dysmenorrhea; calcium, vitamin B(6), and chasteberry for premenstrual syndrome; and chasteberry for cyclic mastalgia. There were too few trials involving herbs and supplements in infertility to warrant a solid recommendation, but chasteberry, antioxidants, and Fertility Blend have some preliminary support. Midwives may want to consider these alternatives in addition to more traditional treatment options when meeting with patients.

[Effectiveness and safety of the treatment of menopausal syndrome with Cimicifuga racemosa dry extract]

Site Editor — Wed, 17 Jan 2007 06:30:11 -0800

[Effectiveness and safety of the treatment of menopausal syndrome with Cimicifuga racemosa dry extract]: Ginekol Pol. 2006 Sep;77(9):678-83 Authors: Radowicki S, Skórzewska K, Rudnicka E, Szlendak-Sauer K, Wierzba W

OBJECTIVES: Phytoestrogens could be an alternative method of the treatment of menopausal syndrome in women with contraindications to hormonal replacement therapy. Design: The aim of the study was to evaluate efficacy and safety of the therapy with Cimicifuga racemosa dry extract. MATERIAL AND METHODS: Twenty women aged mean 52.4 +/- 4.9 years with climacteric syndrome were treated with Cimicifuga racemosa dry extract in a dose of 40 mg a day during 6 months. Kupperman's Index, biochemical parameters and hormonal profile were estimated before and after 3 and 6 months of the therapy. RESULTS: Mean values of Kuppermen's Index were decreased from 30.2 +/- 5.7 points before the therapy to 8.5 +/- 6.3 points after 3 months and to 2.6 +/- 2.1 points after 6 months of the therapy (p < 0.05). No statistical differences in biochemical parameters' concentrations and hormonal profile were observed. CONCLUSIONS: Cimicifuga racemosa dry extract was an effective and safe therapy of climacteric women with contraindications to hormonal replacement therapy.

Trial of Essiac to Ascertain Its Effect in Women with Breast Cancer (TEA-BC).

Site Editor — Sat, 13 Jan 2007 21:36:04 -0800

Trial of Essiac to Ascertain Its Effect in Women with Breast Cancer (TEA-BC).: J Altern Complement Med. 2006 Dec; 12(10): 971-80. Authors: Zick SM, Sen A, Feng Y, Green J, Olatunde S, Boon H

Background: Breast cancer is a major cause of morbidity, mortality, and medical expenditures among women in Canada. Essiac (Resperintrade mark Canada Limited, Waterloo, Ontario, Canada), a blend of at least four herbs (burdock root [Arctium lappa], Indian rhubarb [Rheum palmatum], sheep sorrel [Rumex acetosella], and the inner bark of slippery elm [Ulmus fulva or U. rubra]), has become one of the more popular herbal remedies for breast-cancer treatment, secondary prevention, improving quality of life, and controlling negative side-effects of conventional breast-cancer treatment. Objectives: Our primary objective was to determine the difference in health-related quality of life (HR-QOL), as assessed by the Functional Assessment of Cancer Therapy Breast Cancer Version, between women who are new Essiac users (since breast cancer diagnosis) and those who have never used Essiac. Secondary endpoints included differences in depression, anxiety, fatigue, rate of adverse events, and prevalence of complications or benefits associated with Essiac during standard breast-cancer treatment. Additionally, we described the pattern of use of Essiac in this cohort of women. Methods: We performed a retrospective cohort study in 510 women, randomly chosen from the Ontario Cancer Tumour Registry, with a diagnosis of primary breast cancer in 2003. Results: With the exception changes in a Physical well-being subscale and a relationship with doctor subscale, Essiac did not have a significant effect on HR-QOL or mood states. Even for Physical well-being and relationship with doctor, Essiac seemed to have a negative effect, with Essiac users doing worse than the non-Essiac users. This might be attributed to the fact that the group of users comprised younger women with more advanced stages of breast cancer, and both of these subgroups of patients have been shown to be at a significantly increased risk for negative mood states and/or a decreased sense of well-being. The women were taking low doses (total daily dose 43.6 +/- 30.8 mL) of Essiac that corresponded to the label directions found on most Essiac products. Friends were the most common source of information, and most women were taking Essiac to boost their immune systems or increase their chances of survival. Only 2 women reported minor adverse events, whereas numerous women reported beneficial effects of Essiac. Conclusions: Essiac does not appear to improve HR-QOL or mood states. Future studies are needed to determine whether other clinical outcomes, such as cancer reoccurrence, are affected by Essiac.

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.

Site Editor — Sat, 06 Jan 2007 19:01:39 -0800

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.: Int J Cancer. 2007 Jan 4; Authors: Rebbeck TR, Troxel AB, Norman S, Bunin GR, Demichele A, Baumgarten M, Berlin M, Schinnar R, Strom BL

Hormone-related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population-based case-control study in 3 counties of the Philadelphia metropolitan area consisting of 949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p = 0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p = 0.003), ginseng (12.5% vs. 7.9%, p < 0.001) and red clover (4.7% vs. 0.6%, p < 0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22-0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer. (c) 2006 Wiley-Liss, Inc.

Proliferative activity of Echinacea angustifolia root extracts on cancer cells: interference with doxorubicin cytotoxicity.

Site Editor — Sat, 06 Jan 2007 00:22:54 -0800

Proliferative activity of Echinacea angustifolia root extracts on cancer cells: interference with doxorubicin cytotoxicity.: Chem Biodivers. 2006 Jun; 3(6): 695-703 Authors: Huntimer ED, Halaweish FT, Chase CC

Doxorubicin is an anticancer drug that causes apoptosis in cells, but cardiotoxicity limits the cumulative dose that can remain in the blood. Echinacea extracts have been prescribed to supplement cancer chemotherapy. In a recent study, it was reported that Echinacea purpurea extracts protected noncancerous cells from apoptosis. Our study aimed to determine interference with doxorubicin chemotherapy, and if fractions and compounds from Echinacea angustifolia roots protected the cells. Cervical and breast cancer cells were treated with the Echinacea samples and doxorubicin. At 0.05 and 0.5 microM doxorubicin concentration, cynarine increased HeLa cell growth by 48-125% and 29-101%, respectively (p<0.01). At 0.05 microM doxorubicin concentration, chicoric acid increased cell growth by 23-100% (p<0.01). When MCF-7 cells were treated with Echinacea and doxorubicin, the ethyl acetate fraction increased cell growth by 20-25%, and chicoric acid increased cell growth by 10-15%. Cynarine showed proliferative activity on HeLa cells, but showed antiproliferative activity on MCF-7 cells. Results indicate that phenolic compounds are responsible for proliferative activity. Studies with individual compounds show that chicoric acid and cynarine interfered with cells treated with 0.5 microM doxorubicin. The results of this study show that Echinacea herbal medicines affect cell proliferation despite cancer treatment, and that herbal medicines require further study with respect to anticancer drugs.

Herbal medicine: women's views, knowledge and interaction with doctors: a qualitative study.

Site Editor — Thu, 04 Jan 2007 18:13:28 -0800

Herbal medicine: women's views, knowledge and interaction with doctors: a qualitative study.: BMC Complement Altern Med. 2006;6:40 Authors: Vickers KA, Jolly KB, Greenfield SM

BACKGROUND: There is growing concern that serious interactions are occurring between prescribed/over the counter and herbal medicines and that there is a lack of disclosure of herbal use by patients to doctors. This study explores women's perspectives about the safety of herbal remedies, herb-drug interactions and communication with doctors about herbal medicines. METHODS: Qualitative, cross-sectional study, with purposive sampling which took place in Cheshire, UK. Eighteen in depth semi-structured interviews were conducted with female herbal medicine users aged 18 years and above. RESULTS: The large majority did not inform their GPs of their use of herbal medicines. This was due to lack of physician enquiry, perception of importance and fear of a negative response. Several women were not aware that herbal remedies could interact with prescribed or over the counter medicines. Of the women who had experienced adverse effects none had reported them, believing them of low importance. CONCLUSION: The women had little knowledge about herb-drug interactions and rarely disclosed use of herbal medicines to their doctor. Doctors' communication and openness regarding herbal medicines needs to improve and there should be increased access to accurate information on herbal medicines in the public and health care domain.

Plasma Phytoestrogens and Subsequent Breast Cancer Risk.

Site Editor — Thu, 04 Jan 2007 18:06:21 -0800

Plasma Phytoestrogens and Subsequent Breast Cancer Risk.: J Clin Oncol. 2007 Jan 2; Authors: Verheus M, van Gils CH, Keinan-Boker L, Grace PB, Bingham SA, Peeters PH

PURPOSE: Phytoestrogens are plant compounds that are structurally and functionally similar to mammalian estrogens. By competing for estrogen receptors, phytoestrogens possibly inhibit binding of the more potent endogenous estrogens and decrease their potential effects on breast cancer risk. We investigated the association between plasma phytoestrogen levels and breast cancer risk in a prospective manner. PATIENTS AND METHODS: We performed a nested case-control study within the Prospect cohort, one of the two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition. A total of 383 women (87 pre- or perimenopausal women [mean age, 52 years] and 296 postmenopausal women [mean age, 59 years]) who developed breast cancer were selected as case subjects and were matched to 383 controls, on date of blood sampling. Plasma levels of isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and lignans (enterodiol and enterolactone) were measured. The isotope dilution liquid chromatography/tandem mass-spectrometry method incorporating triply (13)C-labeled standards was used for all analyses. Breast cancer odds ratios were calculated for tertiles of phytoestrogen plasma levels using conditional logistic regression analysis. RESULTS: For genistein, the risk estimate for the highest versus the lowest tertile was 0.68 (95% CI, 0.47 to 0.98). Similar protective effects, although not statistically significant, were seen for the other isoflavones. Lignan levels did not appear to be related to breast cancer risk. Results were the same in pre- or perimenopausal women, and in postmenopausal women. CONCLUSION: High genistein circulation levels are associated with reduced breast cancer risk in the Dutch population. No effects of lignans on breast cancer risk were observed.

Treating threatened abortion with Chinese herbs: a case report.

Site Editor — Thu, 04 Jan 2007 17:47:04 -0800

Treating threatened abortion with Chinese herbs: a case report.: Phytother Res. 2006 Oct;20(10):915-6 Authors: Qu F, Zhou J

In the report a patient who suffered from threatened abortion was successfully cured with Chinese herbs. After treatment, vaginal bleeding stopped and the aching sensation in the loins and prolapsing sensation in the abdomen disappeared. The gestational ring changed from a crescent moon shape to a normal shape.