Stovall Dale W, Pinkerton Joann V
The University of Virginia Health System, Department of Obstetrics and Gynecology, Divisions of Reproductive Endocrinology and Midlife Health, Box 801104, Charlottesville, VA 22903, USA.
Curr Opin Investig Drugs. 2009 Apr;10(4):365-71.
During peri- and postmenopausal stages, the majority of women experience moderate-to-severe vasomotor symptoms, such as hot flashes and night sweats, that interfere with sleep and reduce quality of life. Estrogen alone or in combination with a progestagen has been the standard therapy for such vasomotor symptoms; however, this therapeutic regimen is associated with severe side effects, such as breast cancer or cardiovascular events. To provide a better treatment option for menopausal women, Bionovo Inc is developing the estrogen receptor (ER)beta-selective agonist MF-101. Selective ER agonists can stimulate either ERalpha or ERbeta and induce tissue-specific estrogen-like effects, thus providing a safer alternative to conventional hormone therapy. MF-101 is derived from 22 herbs that are traditionally used in Chinese medicine for the treatment of menopausal symptoms. MF-101 did not promote the growth of breast cancer cells or stimulate uterine growth in preclinical studies and, in a phase II trial, was demonstrated to be safe and more effective in reducing the frequency and severity of hot flashes in postmenopausal women compared with placebo. To confirm the safety and efficacy of MF-101, larger phase III trials were planned for 2009. Although MF-101 appears to be a promising therapeutic, the herbal composition of the drug may be a disadvantage, because of the increased risk of causing allergic reactions in the general population. Studies with the MF-101-isolated active compounds liquiritigen and chalcone demonstrated selectivity for ERbeta, with no induction of proliferative events. If these isolates were demonstrated to be as effective and safe in clinical trials as preliminary data suggest regarding MF-101, these compounds could change the way clinicians treat menopause-associated symptoms.
在围绝经期和绝经后期，大多数女性会经历中度至重度的血管舒缩症状，如潮热和盗汗，这些症状会干扰睡眠并降低生活质量。单独使用雌激素或与孕激素联合使用一直是治疗此类血管舒缩症状的标准疗法；然而，这种治疗方案会带来严重的副作用，如乳腺癌或心血管事件。为了为绝经后女性提供更好的治疗选择，Bionovo公司正在研发雌激素受体（ER）β选择性激动剂MF-101。选择性ER激动剂可以刺激ERα或ERβ，并诱导组织特异性的雌激素样作用，从而为传统激素疗法提供一种更安全的替代方案。MF-101源自22种传统上用于中医治疗绝经症状的草药。在临床前研究中，MF-101不会促进乳腺癌细胞的生长或刺激子宫生长，并且在一项II期试验中，与安慰剂相比，它被证明在减轻绝经后女性潮热的频率和严重程度方面更安全、更有效。为了确认MF-101的安全性和有效性，计划在2009年进行更大规模的III期试验。尽管MF-101似乎是一种有前景的治疗药物，但由于该药物的草药成分可能会增加普通人群发生过敏反应的风险，这可能是一个劣势。对MF-101分离出的活性化合物甘草素和查尔酮的研究表明，它们对ERβ具有选择性，不会诱导增殖事件。如果这些分离物在临床试验中被证明与关于MF-101的初步数据所表明的一样有效和安全，那么这些化合物可能会改变临床医生治疗绝经相关症状的方式。
