Epidural Hematoma Associated with Red Clover Use After Epidural Injection: A Case Report.

An epidural hematoma is a rare but devastating complication after interventional pain procedures. The etiology is multifactorial, including anatomical variations, inherited coagulation disorders, and consumption of anticoagulants or antiplatelet substances. Specifically, in regard to platelet aggregation, the consumption of herbal medicine is often forgotten as a potential cause for coagulation profile disorders, potentially leading to an epidural hematoma. We present the case of a patient who developed an epidural hematoma after a cervical epidural block, most likely associated with daily "red clover" consumption.

In vivo prediction of CYP-mediated metabolic interaction potential of formononetin and biochanin A using in vitro human and rat CYP450 inhibition data.

Formononetin (FMN) and Biochanin A (BCA) are the principal isoflavones present in commercially available extracts of red clover that are widely been consumed for various health benefits. We investigated the in vitro effects of FMN and BCA on catalytic activity of human/rat cytochrome P450 enzymes to assess the drug interaction potential of red clover. IC50 and Ki values of FMN and BCA for CYPs were determined in human/rat liver microsomes. FMN and BCA showed concentration-dependent inhibition of CYP1A2 activity with IC50 values of 13.42 and 24.98µM in human liver microsomes and 38.57 and 11.86µM in rat liver microsomes, respectively. The mode of inhibition of human CYP1A2 by FMN was found to be competitive with apparent Ki value of 10.13±1.96µM. FMN also inhibited human CYP2D6. BCA exerted moderately inhibitory effects on human CYP2C9. The predicted in vivo inhibition for CYP1A2 was insignificant (R value <1.1) at hepatic level while at intestinal level, it was significant (R value >11). The inhibitory effects on other CYPs were found to be minimal. Red clover may be considered safe to be consumed along with co-prescribed medications; however, precaution must be taken while co-administering it with CYP1A2 substrates.

Effects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause women.

OBJECTIVE: To evaluate the effects of treatment with Trifolium pratense on climacteric symptoms and sexual satisfaction in postmenopausal women. METHODS: This is a prospective, randomized, double-blind, placebo-controlled study. Initially, 120 women aged 45-65 years with menopausal symptoms, more than 12-month amenorrhea and no treatment in the past six months were selected. The participants were then divided into two groups: TG ­ receiving 40 mg Trifolium pratense, 1 capsule/day; PG ­ receiving placebo capsules containing lactose (control), 1 capsule/day. The duration of treatment was 12 months. The patients underwent clinical and laboratory evaluation before treatment and at four, eight and 12 months of treatment. The Kupperman Menopausal Index and the Golombok Rust Inventory of Sexual Satisfaction (GRISS) were used. At the end of the study, each group comprised 50 patients. RESULTS: According to the Kupperman Menopausal Index, there was significant improvement in menopausal symptoms after four months of treatment, especially in relation to hot flashes, when compared to baseline data in both groups. However, no significant differences were observed between groups. There was no improvement in sexual satisfaction after treatment. CONCLUSION: A 12-month treatment with a daily dose of 40 mg Trifolium pratense did not yield a significant improvement in menopausal symptoms and sexual satisfaction.

Efeitos do Trifolium pratense nos sintomas climatéricos e sexuais na pós-menopausa / Effects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause

OBJETIVO: Avaliar os efeitos do tratamento com Trifolium pratense nos sintomas climatéricos e na satisfação sexual de mulheres na pós-menopausa. MÉTODOS: Este estudo foi prospectivo, randomizado, duplo-cego e controlado com placebo. Foram selecionadas 120 mulheres na faixa etária de 45 anos a 65 anos com sintomas climatéricos, amenorreia superior a um ano e sem tratamento nos últimos seis meses. Após a seleção, foram divididas em dois grupos: GT -receberam Trifolium pratense na dose de 40 mg, 1 capsula/dia; GP -receberam placebo (controle), contendo lactose, 1 cápsula/dia. A duração do tratamento foi de 12 meses. As pacientes foram avaliadas clinica e laboratorialmente antes do tratamento e com quatro, oito e 12 meses de tratamento. Foi empregado também o Índice Menopausal de Kupperman (IMK) e o Inventário de Satisfação Sexual Golombok Rust. No final do estudo, cada grupo tinha 50 pacientes. RESULTADOS: Houve melhora significante dos sintomas menopausais após quatro meses de tratamento pelo IMK, principalmente em relação aos fogachos, comparando os dados antes do tratamento nos dois grupos, porém, não houve diferença significante entre os grupos. Não houve melhora na sexualidade antes e após o tratamento. CONCLUSÃO: O tratamento por 12 meses com Trifolium pratense, na dose de 40mg/dia, não promoveu melhora significante dos sintomas menopausais e na satisfação sexual.

OBJECTIVE: To evaluate effects of treatment with Trifolium pratense on climacteric symptoms and sexual satisfaction in postmenopausal women. METHODS: This study was prospective, randomized, double-blind and placebo-controlled. We selected 120 women, aged between 45 and 65 years with climacteric symptoms, with absence of menstruation (amenorrhea) for more then one year and without any treatment in the last six months. After selection, women were divided into two groups: GT received 40 mg of Trifolium pratense (one capsule per day); GP received placebo (control, one capsule of lactose per day). Treatment lasted 12 months and women were evaluated before and after four, eight and twelve months of treatment by clinical (Kupperman Menopausal Index -KMI and the Golombok Rust Inventory of Sexual Satisfaction) and laboratory exams. At study end, each group had 50 patients. RESULTS: There was a significant decrease of symptoms after four months of treatment according to the KMI, mainly of hot flashes in relation to baseline data for both groups, but not between both groups. Evaluation of sexual satisfaction did not disclose any difference in both groups before and after treatment. CONCLUSION: The 40mg/day Trifolium pratense treatment may not ameliorate menopausal symptoms or improve sexual satisfaction.

Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of black cohosh and red clover compared with placebo for the relief of menopausal vasomotor symptoms. METHODS: This study was a randomized, four-arm, double-blind clinical trial of standardized black cohosh, red clover, placebo, and 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA; n = 89). Primary outcome measures were reduction in vasomotor symptoms (hot flashes and night sweats) by black cohosh and red clover compared with placebo; secondary outcomes included safety evaluation, reduction of somatic symptoms, relief of sexual dysfunction, and overall improvement in quality of life. RESULTS: Reductions in number of vasomotor symptoms after a 12-month intervention were as follows: black cohosh (34%), red clover (57%), placebo (63%), and CEE/MPA (94%), with only CEE/MPA differing significantly from placebo. Black cohosh and red clover did not significantly reduce the frequency of vasomotor symptoms as compared with placebo. Secondary measures indicated that both botanicals were safe as administered. In general, there were no improvements in other menopausal symptoms. CONCLUSIONS: Compared with placebo, black cohosh and red clover did not reduce the number of vasomotor symptoms. Safety monitoring indicated that chemically and biologically standardized extracts of black cohosh and red clover were safe during daily administration for 12 months.

Effects of botanicals and combined hormone therapy on cognition in postmenopausal women.

OBJECTIVE: The aim of this study was to characterize the effects of red clover, black cohosh, and combined hormone therapy on cognitive function in comparison to placebo in women with moderate to severe vasomotor symptoms. METHODS: In a phase II randomized, double-blind, placebo-controlled study, 66 midlife women (of 89 from a parent study; mean age, 53 y) with 35 or more weekly hot flashes were randomized to receive red clover (120 mg), black cohosh (128 mg), 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA), or placebo. Participants completed measures of verbal memory (primary outcome) and other cognitive measures (secondary outcomes) before and during the 12th treatment month. A subset of 19 women completed objective, physiological measures of hot flashes using ambulatory skin conductance monitors. RESULTS: Neither of the botanical treatments had an impact on any cognitive measure. Compared with placebo, CEE/MPA led to a greater decline in verbal learning (one of five verbal memory measures). This effect just missed statistical significance (P = 0.057) in unadjusted analyses but reached significance (P = 0.02) after adjusting for vasomotor symptoms. Neither of the botanical treatment groups showed a change in verbal memory that differed from the placebo group (Ps > 0.28), even after controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led to a decrease in immediate digit recall and an improvement in letter fluency. Only CEE/MPA significantly reduced objective hot flashes. CONCLUSIONS: Results indicate that a red clover (phytoestrogen) supplement or black cohosh has no effects on cognitive function. CEE/MPA reduces objective hot flashes but worsens some aspects of verbal memory.

Multifocal and recurrent subarachnoid hemorrhage due to an herbal supplement containing natural coumarins.

INTRODUCTION: Over-the-counter herbal and alternative medicines are classified as dietary supplements and, unlike drugs, are not rigorously regulated by the United States Food and Drug Administration. Their potential adverse effects are often poorly characterized. METHOD: Red clover, dong quai, and Siberian ginseng are herbal compounds used for treatment of perimenopausal symptoms such as hot flashes. These compounds are known to contain coumarins, and thus carry the potential for hemorrhagic complications; however, no cases of intracranial hemorrhage have been reported. DISCUSSION: We report a 53-year-old woman with spontaneous subarachnoid hemorrhage due to the use of an herbal supplement containing red clover, dong quai, and Siberian ginseng.

Clinical studies of red clover (Trifolium pratense) dietary supplements in menopause: a literature review.

Red clover (Trifolium pratense L., Fabaceae) botanical dietary supplements have received much attention recently for their potential use in the treatment of menopause symptoms, maintenance/improvement of bone and cardiovascular health, and reported benign effects on the breast and endometrium. Literature searches of four computerized databases were run to identify clinical studies of red clover botanical dietary supplements. The manufacturer of the red clover products used in the majority of the studies was contacted for unpublished information and/or clarification regarding the chemical content of their products. Red clover studies were reviewed that pertained to women's health or menopause. Clinical evidence is presently lacking to support the efficacy of semipurified red clover isoflavone extracts for alleviation of climacteric vasomotor symptoms or reduction of low-density lipoprotein levels in the blood. Furthermore, the safety of use of red clover isoflavone supplements in patients with breast or endometrial cancer has not been established. Limited evidence suggests possible efficacy in maintenance of bone health and improvement of arterial compliance, a risk factor for atherosclerosis. This literature review covers red clover botanical dietary supplement clinical studies having a possible impact on the health care of mature and menopausal women, and provides historical perspective regarding the traditional uses of red clover.