市场牛奶和传统牛奶对乳腺癌发生影响的研究

目的:评价市场牛奶和传统牛奶对二甲基苯并蒽(DMBA)诱导的大鼠乳腺肿瘤发生的影响。方法:120只雌性大鼠采用致癌剂DMBA诱发乳腺癌后,将大鼠分为市场牛奶组(C)、内蒙古黄牛奶组(T)和自来水组(W),比较3组大鼠的乳腺肿瘤发生率、发生时间和数量。结果:C组大鼠乳腺首发肿瘤出现最早(DMBA干预后的第5周),T和W组分别比C组晚1和2周;C组大鼠肿瘤发生的潜伏期〔(9.1±3.8)周〕短于T组〔(11.7±4.0)周〕;C、T和W组肿瘤发生率分别为80.0%(32/40)、80.0%(32/40)和52.5%(21/40);C组肿瘤发生的数量(142个)高于T组(92个)和W组(65个)。结论:目前,我国市场上销售的牛奶对DMBA诱导的大鼠乳腺肿瘤的发生具有促进作用,牛奶中的雌孕激素,特别是雌激素在促癌实验中发挥了关键作用。     

Clinical and pathological responses of progestin therapy for non-atypical endometrial hyperplasia: a prospective study

AIMS: To evaluate the clinical and pathological responses and factors predicting non-responders to various progestins currently prescribed for the treatment of non-atypical endometrial hyperplasia. METHODS: A prospective observational study was conducted in the Gynecologic Endocrinology Unit, Faculty of Medicine, Siriraj Hospital, Thailand, from 1998 to 2003. A 6-month course of progestin therapy was offered to all patients. The clinical response was evaluated from the vaginal bleeding pattern during the first 4 months of treatment. The pathological response was evaluated from the histopathology of the endometrium after completion of the 6-month therapy. RESULTS: Of 250 registered patients, the number of cases qualified for the evaluation of the clinical and pathological response were 198 and 134 cases, respectively, revealing the overall clinical and pathological response rates of 93.4% and 92.5%, respectively. Among 13 clinical non-responders, 84.6% might have associated pelvic pathology. Among 10 pathological non-responders, three had surgical treatment, and progressive disease was found in one case. Significant factors predicting clinical non-responders included a history of prior bleeding (odds ratio [OR] = 8.79, 95% confidence interval [CI] = 1.63, 47.53), the presence of associated pelvic pathology (OR = 25.52, 95% CI = 3.21, 203.01), and treatment using progestins other than medroxyprogesterone acetate. Factors predicting pathological non-responders were not statistically significant. CONCLUSIONS: The current regimens of progestin therapy for non-atypical endometrial hyperplasia have high response rates. Patients who fail to have a clinical response should be evaluated for associated pelvic pathology. Follow-up endometrial biopsy should be offered to the patients, because 7.5% have persistent or progressive lesions, necessitating aggressive treatment.     

The differential effects of oestrogens and progestins on vascular tone.

The purpose of this paper is to present reported findings of the effects of ovarian steroids on vascular tone. The medical literature was reviewed for relevant contributions. Oestrogen replacement therapy in postmenopausal women is associated with a reduction in mortality from coronary artery disease. Many different cellular actions have been described which help explain the cardioprotective effects of oestrogens, and among these are effects on vascular tone. Oestrogens induce vasodilation through mechanisms involving the arterial endothelium and through endothelial-independent actions. Progestins have varying effects on arterial tone, including induction of vascular smooth muscle relaxation as well as induction of smooth muscle constriction. The effects of oestrogens and progestins on vascular tone are clinically meaningful. Pathophysiological arterial conditions, including angina pectoris and migraine headaches, have been associated with oestradiol deficiency and improvement has been associated with oestradiol replacement. Women with coronary artery disease show improved arterial vasodilator responses after oestradiol treatment which can be reduced by the addition of progestin treatment. Androgens are also vasoactive. Study of the effects of ovarian hormones on vascular tone has become an important area for basic and clinical research.     

Menopausal hormone therapy and breast cancer risk: Impact of different treatments. The European Prospective Investigation into Cancer and Nutrition

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country‐specific self‐administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow‐up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country‐specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person‐years of follow‐up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23–1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40–2.24; p = 0.02 for combined vs. estrogen‐only). Continuous combined regimens conferred a 43% (95% CI: 19–72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen‐only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.     

伍用雌孕激素对雷公藤致雌鼠生殖系统损害的保护作用

目的观察雷公藤多苷伍用雌孕激素对雌鼠生殖系统的影响。方法将具有正常动情周期的雌性大鼠随机分为3组,以生理盐水组为对照,观察雷公藤多苷(TWP)组及TWP伍用激素替代治疗(TWP HRT)组大鼠子宫卵巢的重量、动情周期、血清雌激素(E2)、卵泡刺激素(FSH)、黄体生成素(LH)水平及卵巢子宫的病理变化。结果与对照组相比,TWP组大多动情周期延长或紊乱,E2降低(P<0.05),FSH及LH水平升高(P<0.05),卵巢及子宫重量明显下降(P<0.05),卵巢各级卵泡减少,子宫内膜变薄,腺体减少;TWP HRT组无明显改变。结论在TWP治疗的同时伍用HRT可减少TWP对雌鼠生殖系统的损伤,保护卵巢功能。     

Pharmacologic treatment of the ovarian endometrioma

Introduction: Treatment of ovarian endometriomas is commonly achieved through laparoscopic surgery and this can be effective in eliminating the disease, although a majority of recent trials documented an adverse effect of surgery on ovarian reserve markers. With the advancement in imaging techniques, ovarian endometriomas are increasingly diagnosed at an earlier stage when the endometrioma may be smaller, less fibrotic and more responsive to medical treatment, making an evaluation of medical options critically important.

Areas covered: The review focuses on currently utilized pharmacologic therapies for endometrioma (oral contraceptives, the levonorgestrel-releasing IUS, the hormone-releasing subdermal implant, Implanon); experimental and future treatments are also mentioned (GnRH antagonists, progesterone receptor modulators, antioestrogens, newer subdermal implants and intracystic administration of pharmacologic agents). Finally, the usefulness of post-operative adjuvant medical treatments is discussed

Expert opinion: Today, reliable, non-invasive diagnostic procedures of an ovarian endometrioma are available and should be utilized to identify its presence and type of pathology. In a young patient, classic medical therapies such as oral contraceptives and synthetic progestins should be tried first to alleviate symptoms. Only when these regimens fail, should a minimally invasive surgery be envisaged. Following endoscopic surgery, adjuvant medical treatment may reduce recurrence of both symptoms and the lesion.     

孕激素对在位内膜构建子宫内膜异位症裸鼠的影响

目的：比较雌激素（E组）与雌孕激素（E＋P组）两种体外培养条件对在位内膜构建裸鼠子宫内膜异位症（EMs）模型的影响。方法：将EMs患者的在位内膜碎片加入到含10％小牛血清的去酚红DMEM／Ham’s F-12培养液中，同时E组加入雌激素（10nmol／L），E＋P组加入孕激素（100nmol／L）及雌激素（10nmol／L）分别培养24h后接种于裸鼠腹腔。结果：E＋P组种植成功率高于E组，与E组比较病灶数目有增多趋势（Z=2．21，P=0．05），病灶直径减小（Z=2．24，P〈0．05）。免疫组化显示E＋P组培养后在位内膜腺体的表达无显著性改变，但PR、Ki-67表达有减弱趋势；成模的裸鼠异位灶腺体中Ki-67的表达也降低（Z=2．27，P〈0．05），PR有降低趋势。异位灶间质中微血管密度显著减低（Z=2．73，P〈0．05）。雌孕激素培养后获得的异位灶间质细胞增生，异位灶与周围组织接合更为紧密。结论：加入孕激素的体外培养条件不影响在位内膜成模，但血管生成、细胞增殖并未加强。     

Estrogen and progestin effects in human breast carcinogenesis

Summary The influences of estrogen and progestin on human mammary neoplasia are reviewed with a view to identifying what is known about their effects. Estrogens promote growth of established cancer and pharmacological levels of progestins induce remission.In vivo, highest proliferation of histologically normal mammary epithelium occurs in the progestogenic phase of the menstrual cycle or under the progestogenic influence of oral contraceptives. Little additional hard data exist to indicate whether progestins promote or inhibit human mammary carcinogenesis. Effects on proliferation, steroid receptor content and development are discussed together with interpretation of epidemiological data on risk factors that have hormonal components. Progestins may not be the benign or beneficial agents previously supposed, and there are virtually no data to suggest that they are antiestrogenic. It is hypothesized that carcinogenesis may be accompanied by increased sensitivity to estrogen, which provides a growth advantage to the tumor by maximizing use of the low estrogen concentrations encountered in the postmenopausal state.     

Megestrol acetate: Phase II study of a single daily administration in advanced breast cancer

Summary A new formulation of megestrol acetate, a semisynthetic oral progestin used in the hormonal treatment of breast cancer, allows the administration of 160 mg of the drug in a single daily dose. Sixty-nine postmenopausal patients with advanced breast cancer have been treated with this regimen: five patients received megestrol acetate as first-line treatment of their metastatic disease, while all the others had been previously treated with one or more regimens of chemotherapy and/or hormone therapy. The median duration of the treatment for evaluable patients was 3 months (range 1–13+). Among 65 evaluable patients 2 complete responses and 12 partial responses (objective response rate 21.5%; 95% confidence limits 12.31%–33.49%) were observed. Median duration of response was 7 months (range 2–12+). Responses were observed both in visceral and in non-visceral sites of disease. Twenty-nine patients obtained a stabilization of disease (44.7%), and twenty-two progressed (33.8%). Median duration of stabilization was 4 months (range 3–13+). Median survival for all patients from the start of megestrol acetate was 9 months (range 1–22+). The most common side effect of therapy was weight gain, occurring in 36% of patients. Megestrol acetate on a single-daily-dose schedule can be considered as an interesting hormonal treatment for advanced breast cancer, especially in the clinical instance of patients who, after having obtained a remission or stabilization of disease with tamoxifen, need further palliative treatment.     

Steroid hormones and the brain: Cellular mechanisms underlying neural and behavioral plasticity

(1) Steroid hormone action on brain is discussed as an example of environmentally-directed neural plasticity. (2) Current research is summarized for three systems in studying this topic: (a) glucocorticoids and the hippocampus; (b) estrogens and progestins and the hypothalamus; (c) androgens and the syrinx in songbirds.