子宫内膜异位症术后GnRH-a治疗与黑升麻制剂的使用

子宫内膜异位症(EMS)是临床上最常见的妇科疾病之一,术后的复发问题一直困扰着临床医师。促性腺激素释放激素激动剂(GnRH-a)的使用对于降低EMS术后的复发具有十分重要的作用,目前已成为临床上最为常用的预防EMS复发的方法。但是,GnRH-a使用后引发的围绝经期症状严重影响患者的生活质量,部分患者因此而终止治疗。激素反向添加治疗虽然很好的解决了围绝经期症状,但是激素的长期使用可能导致激素依赖性疾病的风险。作为一种植物提取物,黑升麻制剂能否较好的拮抗GnRH-a所致类围绝经期症状,而且又能避免激素反向添加治疗的风险,目前尚不明确。该文主要围绕EMS术后GnRH-a治疗的必要性及其存在的问题,黑升麻制剂的作用机制与功能,黑升麻用于缓解EMS患者术后使用GnRH-a治疗出现的类围绝经期症状的可能性及可能存在的问题进行概述。

Studies of GnRH-A Active Immunization Effects on LH and FSH Secretion and Histostructure of the Ovary and Uterus in Rabbits

The objective of the study is to investigate the effects of active immunization against gonadotropin releasing hormone agonist （GnRH-A） on secretion of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） in the pituitary, and to observe the histological structures and development about ovaries and uteri in female rabbits. 24 female rabbits （Oryctolagus cuniculus） were divided randomly into 4 groups （n=6）, namely, experimental group I （EG-I）, experimental II （EG-II）, experimental III （EG-III）, and control group （CG）. Rabbits were subcutaneously injected with 1.0 mL GnRH-A （alarelin） antigen respectively at concentrations of 100, 100 and 50 μg mL-1 respectively, in EG-I, EG-II and EG-III. Alarelin antigen was re-injected in EG-II and EG-III with the same dosage on 20 d. CG was a blank. The ovarian and uterine samples were collected aseptically at the end of the experiment of 70 d. The tissue slices were observed under light and electron microscopes. Serum concentrations of LH and FSH were measured with ELISA. The results showed that serum LH concentrations in EG-II and EG-III reached the peak levels on 50 and 40 d respectively, and LH level in EG-II exceeded other 3 groups on 50 d （P0.05）. FSH level in EG-II was higher than those in EG-I, CG （P0.01） and EG-III （P0.05） on 40 d. GnRH-A could increase the number of primary follicles, enlarge the primary follicle vertical diameter （PFV） and primary follicle transverse diameter （PFT）, and promote growth and maturation of follicles. The endometrial epithelium thickness （EET） and uterine wall thickness （UWT） in three EGs were less than that in CG （P0.05）. GnRH-A can increase the quantities of mitochondrial cristaes, cortex granules in cytoplasm, broaden and lengthen zona pellucidas and microvilli of oocytes. It also enlarged nuclei of ooxytes and mitochondria, thereby it promoted the development of oocytes. Re-injection of 100 μg alarelin antigen enhanced the secretion of LH and FSH. GnRH-A promoted the growth and maturation of ovaries and follicles, suppressed uterine development, and also influenced histostructure of ovaries and uteri in female rabbits.

Hormone naive prostate cancer： predicting and maximizing response intervals

Hormone naive advanced prostate cancer is subdivided into two disease states： biochemical recurrence and traditional M 1 （metastatic） prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy （ADT）. In biochemical recurrence/ prostate-specific antigen （PSA） recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade （peripheral androgen deprivation） to complete hormonal therapy （combined androgen blockade [CAB]） remains in debate owing to lack of randomized controlled trials （RCT）. However, there is good RCT support for use of intermittent hormonal therapy （IHT）. There is also limited research on biomarker response （PSA and testosterone decline） to predict prognosis. On the other hand, in the setting of M1 hormone naive prostate cancer, there are many more RCT＇s to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone （T） control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M 1 patient, maintaining a serum T below 20-30 ng d1-1 prolongs the response to ADT. Novel oral agents （abiraterone and enzalutamide） may soon find use in hormone naive disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.

Pituitary Suppression before Frozen Embryo Transfer Is Beneficial for Patients Suffering from Idiopathic Repeated Implantation Failure

Long-term gonadotropin-releasing hormone agonist（Gn RHa） administration before in vitro fertilization（IVF）/intracytoplasmic sperm injection（ICSI） in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term Gn RHa treatment might also be beneficial for the idiopathic repeated implantation failure（RIF） patients. In the 21 patients receiving Gn RHa and hormone replacement therapy（G-HRT） protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone（previous protocols）. Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior Gn RHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients.