Hormones: Annotated References. compiled by doctordee | Search LMS site |

Hormone Receptors Estrogen and Cognitive Deficits Letrozole Anastrozole NOT Tamoxifen Megestrol Acetate [Megace] Lupron Depot [GnRH Agonist] Mifepristone [RU-486]
Hormone Receptors
The abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for hormone receptors and LMS 1.Mod Pathol 1999 Nov;12(11):1001-9 Comparative immunohistochemical and molecular analysis of uterine and extrauterine leiomyosarcomas. Rao UN, Finkelstein SD, Jones MW. "Eighty-percent of LM and 70% of the ULMS were estrogen receptor positive, whereas only one retroperitoneal tumor had focal weak positivity. P53 allelic imbalance was present in 29% of ULMS and 57% EULMS. Mdm2 amplification was present in three of six EULMS but not in ULMS. ... The presence of estrogen receptor staining may be helpful in identifying uterine versus nonuterine LMS. Although sample numbers are too small for definite conclusions, this study suggests that there are differences in glucose transport, expression of adhesion molecules, and estrogen receptors in ULMS and EULMS, which in part may be due to the estrogen dependency of the ULMS. P53 mutations and mdm2 amplifications appear to be more frequent in EULMS." 2. Am J Surg Pathol 1999 Sep;23(9):1082-8 Leiomyosarcoma of the pulmonary veins. Oliai BR, Tazelaar HD, Lloyd RV, Doria MI, Trastek VF. "Pulmonary vein sarcomas represent intermediate- to high-grade leiomyosarcoma. Although often lethal, complete surgical excision can lead to long-term survival. They occur predominantly in women and may express hormone receptors. Therefore, hormonal manipulation may offer promise as adjuvant therapy." Fetch PMID: 10478668 3. Am J Surg Pathol 1996 Jul;20(7):779-93 Smooth-muscle tumors of the vulva. A clinicopathological study of 25 cases and review of the literature. Nielsen GP, Rosenberg AE, Koerner FC, Young RH, Scully RE. "The clinical and pathological features of 25 smooth-muscle tumors of the vulva were analyzed."... "Thirteen of 17 tumors were positive for estrogen receptors, and 16 of 18 were positive for progesterone receptors. ... We propose ... expanded criteria to distinguish between leiomyomas and leiomyosarcomas of the vulva. Tumors that manifest three or all of the four following features should be considered sarcomas: > or = 5 cm in greatest dimension, infiltrative margins, > or = 5 mitotic figures per 10 hpf, and moderate to severe cytologic atypia. Those that have only one of these characteristics should be diagnosed as leiomyoma, and those that exhibit only two of these features should be considered benign but atypical leiomyomas." 4. Pathol Res Pract 1996 Mar;192(3):215-23 Immunohistological detection of estrogen and progesterone receptors in multiple and well differentiated leiomyomatous lung tumors in women with uterine leiomyomas (so-called benign metastasizing leiomyomas). A report on 5 cases. Jautzke G, Muller-Ruchholtz E, Thalmann U. Five "benign metastasizing uterine leiomyomata" result in development of well differentiated, leiomyomatous lung tumors that appear to be benign, usually after a period of several years. "We report on five more such cases in which we investigated the contents of estrogen and progesterone receptors in the pulmonary tumors .... All the lung tumors exhibited a high content of progesterone receptors, and in 4 out of the 5 cases a high estrogen receptor content was also found. ... it is thus recommended ... hormone receptors should be determined in well differentiated, leiomyomatous lung tumors from women. This would both provide information on the pathogenesis of these tumors and establish a basis for possible later institution of hormone treatment. It is likely that the majority of these lung tumors are in fact metastases of extremely well differentiated leiomyosarcomas of the uterus. The possibility that lung tumors of this type may constitute a small group that develop in situ as hormone-sensitive proliferations cannot, however, be fully excluded." Fetch PMID: 8739468 5. Acta Obstet Gynecol Scand 1984;63(6):505-8 Estradiol and progesterone receptors in gynecologic sarcomas. Lantta M, Karkkainen J, Wahlstrom T, Widholm O. "We report the concentrations of estradiol and progesterone receptors found in the tumor tissue of 5 patients with leiomyosarcoma, 4 of uterine and one of ventricular origin, and of 5 patients with uterine or ovarian carcinosarcoma. Steroid receptor positive and negative tumors were present in both groups of sarcoma. ....We suggest that steroid receptors should be analysed in all gynecologic sarcomas." Fetch PMID: 6507052 6. Surgery 1981 Aug;90(2):149-53 Distribution of steroid hormone receptors in human soft tissue sarcomas. Chaudhuri PK, Walker MJ, Beattie CW, Das Gupta TK. "Sixty-six human soft-tissue sarcoma specimens were assayed for incidence and distribution of steroid hormone receptors. Liposarcomas (43%) and leiomyosarcomas (60%) had a high incidence of estrogen receptor. .... The incidence of receptors for estrogen and glucocorticoid was higher in female than in male patients (62% and 38%, respectively). .... Data from this study suggest that ... receptors for steroid hormones are present in human soft tissue sarcoma and that their distribution may depend on the histogenetic origin and the sex of patients." Fetch PMID: 6266058 7. Arch Surg 1980 Mar;115(3):244-8 Estrogen receptor proteins in diverse human tumors. Stedman KE, Moore GE, Morgan RT. "Receptors were detected in many endocrine and nonendocrine tumors. ......... Some tumors also had progesterone, androgen, and/or glucocorticoid receptors. These results suggest the use of hormones and hormone antagonists for therapy of a broad range of human cancer. Clinicians of diverse expertise should be aware of, and responsive to, potential endocrinological involvement in many dissimilar disease states." Fetch PMID: 7356378
Estrogen and Cognitive Deficits
Cognitive Function and Anti-Estrogen Treatment Medical Journal Article Abstracts The abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for estrogen and cognitive function Another interesting search of Pubmed is for andropause and cognitive function 1. J Clin Endocrinol Metab 1996 Jul;81(7):2545-9 "Add-back" estrogen reverses cognitive deficits induced by a gonadotropin-releasing hormone agonist in women with leiomyomata uteri. Sherwin BB, Tulandi T. Department of Psychology, McGill University, Montreal, Quebec, Canada. "These findings are consistent with those from studies on surgically menopausal women and strongly suggest that estrogen serves to maintain verbal memory in women. These results provide support for the efficacy of add-back estrogen regimens in women treated with GnRH agonists and also imply that estrogen may be important for maintaining memory in the postmenopause." Fetch PMID: 8675575 2. Breast Cancer Res Treat 2001 Nov;64(2):165-76 Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. Paganini-Hill A, Clark LJ. Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA. annlia@juno.com "Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment." Fetch PMID: 11194452 3. J Clin Oncol 2000 Jul;18(14):2695-701 Cognitive function in breast cancer patients receiving adjuvant chemotherapy. Brezden CB, Phillips KA, Abdolell M, Bunston T, Tannock IF. Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada. "Cognitive differences were observed in breast cancer patients receiving adjuvant chemotherapy compared with healthy controls. These differences did not seem to be caused by significant differences in mood disturbance between the two groups. If confirmed, these results have substantial implications for informed consent, counseling, and psychosocial support of patients receiving adjuvant chemotherapy for breast cancer." Fetch PMID: 10894868 4. Pharmacotherapy 1999 Aug;19(8):951-6 Testosterone and andropause: the feasibility of testosterone replacement therapy in elderly men. Lund BC, Bever-Stille KA, Perry PJ. Clinical and Administrative Pharmacy Division, College of Pharmacy, University of Iowa, Iowa City 52242-1112, USA. "Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that include weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia, memory impairment, and reduced cognitive function. ... It is estimated that 20% of men aged 60-80 years have levels below the lower limit of normal. ... administration of testosterone to this population resulted in improvements in many areas. ... Preliminary data suggest that therapy may benefit elderly men with new-onset depression. ... [There is] potential for increased prostate cancer risk... Currently, insufficient evidence, primarily regarding psychologic safety and efficacy, exists to warrant general administration .... Further clinical investigations of this therapy in men with low testosterone levels and andropause symptoms are justified and necessary." Fetch PMID: 10453966 5. Cancer 1999 Feb 1;85(3):640-50 Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF. The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam. "A number of patients who have undergone adjuvant (CMF) chemotherapy for operative primary breast carcinoma have reported impaired cognitive function, sometimes even years after completion of therapy. ... Breast carcinoma patients treated with adjuvant CMF chemotherapy have a significantly higher risk of late cognitive impairment than breast carcinoma patients not treated with chemotherapy (OR 6.4). This cognitive impairment is unaffected by anxiety, depression, fatigue, and time since treatment, and not related to the self-reported complaints of cognitive dysfunction." Fetch PMID: 10091737 6. Dis Mon 1998 Sep;44(9):421-546 Wellness in women after 40 years of age: the role of sex hormones and pheromones. Cutler WB, Genovese-Stone E. Athena Institute for Women's Wellness Chester Springs, Pennsylvania, USA. "All sex hormones affect physiologic systems including the cardiovascular system, bone metabolism, cognitive function, sexual response, and sexual attractiveness." "The health and well-being of women who have already had hysterectomies, with or without ovariectomies, can be improved by a recognition of the cascade of difficulties that must addressed" Fetch PMID: 9803240 7. J Nurse Midwifery 1998 Jul-Aug;43(4):262-72 Primary and secondary prevention strategies among older postmenopausal women. Keller C, Fullerton J, Fleury J. School of Nursing, University of Texas Health Science Center at San Antonio 78284, USA. "HRT, exercise, and nutrition are reviewed in terms of their potential benefits as primary and secondary preventive therapies against coronary heart disease, osteoporosis, breast and genital cancers, and the maintenance of cognitive function among older postmenopausal women. Lifestyle alternatives involving nutrition and exercise that offer many of the same benefits as HRT are discussed. Since both pharmacologic and lifestyle interventions offer significant benefit for primary and secondary prevention of disease and disability, each should be offered ... [and] should be sustained over the long term." Fetch PMID: 9718881 8. Baillieres Clin Endocrinol Metab 1997 Jul;11(2):311-40 Menopause and post-menopause. Prelevic GM, Jacobs HS. Department of Medicine, University College London Medical School, UK. "Oestrogen therapy alleviates acute climacteric symptoms and also reduces the risk of cardiovascular disease, osteoporosis and Alzheimer's disease. ... it reduces morbidity and mortality from coronary heart disease by approximately 50%. ...Oestrogen therapy reduces the rate of post-menopausal bone loss, increases bone mineral density (BMD) and decreases fracture rate. ... The incidence of Alzheimer's disease is reduced by 50% in post-menopausal women taking oestrogen replacement. Limited clinical trials of oestrogen treatment in women with this disease have documented beneficial effects on cognitive function. The results of epidemiological studies of the effects of oestrogens on breast cancer risk are conflicting but recent evidence suggests that the risk is increased in current users after 5 years of use and among older women. In contrast, increase in the risk of venous thromboembolism is most significant within the first 12 months of therapy, strongly suggesting the importance of individual susceptibility." Fetch PMID: 9403125
Letrozole
The abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for letrozole and cancer You can also search Pubmed for letrozole and uterine cancer 1. J Clin Oncol 2001 May 15;19(10):2596-606 Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, et.al. Rigshospitalet, Copenhagen, Denmark. "Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer." Fetch PMID: 11352951 2. J Exp Clin Cancer Res 2000 Mar;19(1):17-9 Letrozole for the treatment of pretreated advanced breast cancer patients: preliminary report. Casali A, Sega FM, Casali M, Giuntini T, Cappellini GC, Terzoli E. Service of Complementary Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. Fetch PMID: 10840931 3. Crit Rev Oncol Hematol 2000 Feb;33(2):137-42 Steroidal aromatase inhibitors in elderly patients. Bajetta E, Zilembo N, Bichisao E, Pozzi P, Toffolatti L . Division of Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. Fetch PMID: 10737375 4. Endocr Relat Cancer 1999 Mar;6(1):75-92 Use of aromatase inhibitors in breast carcinoma. Santen RJ, Harvey HA. Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA. "Aromatase, a cytochrome P-450 enzyme that catalyzes the conversion of androgens to estrogens, is the major mechanism of estrogen synthesis in the post-menopausal woman. .... Inhibition of aromatase, the terminal step in estrogen biosynthesis, provides a way of treating hormone-dependent breast cancer in older patients. ... Currently available aromatase inhibitors are safe and effective in the management of hormone-dependent breast cancer in post-menopausal women failing antiestrogen therapy and should now be used before progestational agents." Fetch PMID: 10732791 5. Ann Oncol 1999 Apr;10(4):377-84 The third-generation non-steroidal aromatase inhibitors: a review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer. Hamilton A, Piccart M. Institut Jules Bordet, Brussels, Belgium. " In 1999, tamoxifen remains the first choice in the hormonal therapy of breast cancer. Following tamoxifen failure, the optimal second-line hormonal therapy remains undefined, but aminoglutethimide and megestrol acetate are no longer optimal therapy in this setting. " Fetch PMID: 10370778 6. Ann Oncol 1998 Jun;9(6):639-45 Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Letrozole International Trial Group (AR/BC3). Gershanovich M, Chaudri HA, Campos D, Lurie H, Bonaventura A, Jeffrey M, Buzzi F, Bodrogi I, Ludwig H, Reichardt P, O'Higgins N, Romieu G, Friederich P, Lassus M. N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia. Fetch PMID: 9681078 7. Oncology (Huntingt) 1998 Mar;12(3 Suppl 5):32-5 Emerging role of aromatase inhibitors in the treatment of breast cancer. Harvey HA. Section of Hematology-Oncology, Hershey Medical Center, Penn State Geissinger Health Systems, Hershey, Pennsylvania, USA. Fetch PMID: 9556789
Anastrozole
The anastrozole [Arimidex]abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for anastrozole and cancer You can also search Pubmed for anastrozole and uterine cancer 1. Gan To Kagaku Ryoho 2001 Apr;28(4):549-60 [Development of a novel aromatase inhibitor, anastrozole (Arimidex)--its basic and clinical studies]. [Article in Japanese] Tsukagoshi S. Cancer Institute, Japanese Foundation for Cancer Research. "In US study compared anastrozole with tamoxifen, TTP with anastrozole is a significantly longer than that of tamoxifen (p = 0.005, two-sides). Anastrozole has shown to be at least as effective as tamoxifen, standard endocrine therapy for breast cancer, with good safety profiles." Fetch PMID: 11329794 2. Curr Med Res Opin 2001;16(4):276-84 The Twenty-third Annual San Antonio Breast Cancer Symposium Mokbel K. St George's Hospital, Blackshaw Road, London SW17 0QT, UK. kefahmokbel@hotmail.com "This paper reviews the recent Twenty-third Annual San Antonio Breast Cancer Symposium. ... fulvestrant (Falsodex), given as a once-monthly intramuscular injection (250 mg), was well-tolerated and at least as good as anastrozole (1 mg) in postmenopausal women with advanced breast cancer that had progressed or recurred on prior endocrine therapy. " "Another phase III randomised trial found that letrozole (2.5 mg daily) was superior to tamoxifen as a neoadjuvant therapy in postmenopausal women with ER- and/or PgR-positive breast cancer unsuitable for breast-conserving surgery." Fetch PMID: 11268712 3. Bull Cancer 2000 Dec;87 Spec No:31-39 [Aromatase inhibitors: a review of clinical trials]. [Article in French] Kerbrat P, Lefeuvre C. Departement d'oncologie medicale, Centre Eugene-Marquis, rue de la Bataille-Flandres-Dunkerque, CS 44229, 35042 Rennes Cedex, France. "new aromatase inhibitors have been synthetized; they belong to two groups: type I (formestane and exemestane) are steroidal irreversible and specific inhibitors, type II (anastrozole, letrozole and vorozole) are non steroidal reversible inhibitors, interfering with the aromatase heme. Several phase II and III trials demonstrated that these drugs are, at least, as active as aminoglutethimid or progestins in second line treatment, and are less toxic. Recently, an identical activity have been observed for anastrozole and tamoxifen in first line". Fetch PMID: 11250606 4. Anticancer Drugs 2000 Oct;11(9):701-6 Survival in patients with metastatic breast cancer: analysis of randomized studies comparing oral aromatase inhibitors versus megestrol Messori A, Cattel F, Trippoli S, Vaiani M. Laboratorio SIFO di Farmacoeconomia, Centro Informazione Farmaci, Azienda Ospedaliera Careggi, Florence, Italy. md3439@mclink.it "We conducted a meta-analysis to assess the effectiveness of aromatase inhibitors versus megestrol. ... A lifetime analysis of the pooled survival curves of aromatase inhibitors versus megestrol found a mean survival gain of 4.1 months per patient. Aromatase inhibitors confer a significant survival benefit to patients with metastatic breast cancer as compared with megestrol. Fetch PMID: 11129731 5. Oncology 2000;59 Suppl 1:19-23 Gonadotropins stimulate growth of MCF-7 human breast cancer cells by promoting intracellular conversion of adrenal androgens to estrogens. Tanaka Y, Kuwabara K, Okazaki T, Fujita T, Oizumi I, Kaiho S, Ogata E. Third Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan. Copyright 2000 S. Karger AG, Basel Resistance to estrogen ablation treatment can develop. Fetch PMID: 11096352 6. J Clin Oncol 2000 Nov 15;18(22):3758-67 Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A, von Euler M. Cancer-Cross Institute, Edmonton, Alberta, Canada. jean-marc.nabholtz@bcom "Both treatments were well tolerated. However, thromboembolic events and vaginal bleeding were reported in fewer patients who received anastrozole compared with those who received tamoxifen ... Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Furthermore, we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole. These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer." Fetch PMID: 11078488 7. Eur J Cancer 2000 Sep;36 Suppl 4:S84-5 Randomised study of anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women. Vergote I, Bonneterre J, Thurlimann B, Robertson J, Krzakowski M, Mauriac L, Koralewski L, Webster A, Steinberg M, von Euler M. Department Gynaecological Oncology, University Hospitals Leuven, Herestraat 49, B3000, Leuven, Belgium. "Anastrozole was also as effective as tamoxifen in terms of objective response-rate ... Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen. In conclusion, these findings indicate that anastrozole can be considered as first-line therapy for postmenopausal women with advanced breast cancer. " Fetch PMID: 11056332 8. Anticancer Drugs 2000 Aug;11(7):591-601 Cost-utility analysis of second-line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to megestrol acetate. Dranitsaris G, Leung P, Mather J, Oza A. Department of Pharmacy, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada. gdranit@istar.ca "Randomized trials comparing the aromatase inhibitors, anastrozole and letrozole, to megestrol acetate (MA) in postmenopausal women with advanced breast cancer demonstrated that both agents are better tolerated than MA with comparable efficacy. In addition, one trial revealed that tumor response and time to treatment failure were significantly better with letrozole. " Fetch PMID: 11036964 9. Gynecol Oncol 2000 Aug;78(2):212-6 A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB. Department of Obstetrics and Gynecology, University Hospital of Cleveland, Ohio, 44106, USA. .... "Two partial responses were noted (9%; 90% confidence interval 3 to 23%). Two additional patients had short-term stable disease. With the exception of 1 case of venous thrombosis, the toxicity profile was mild. Median durations of progression-free survival and overall survival are 1 and 6 months, respectively" "Anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer." Copyright 2000 Academic Press. Fetch PMID: 10926805 10. Recent Results Cancer Res 1998;152:227-44 The primary use of endocrine therapies. Howell A, Anderson E, Blamey R, Clarke RB, Dixon JM, Dowsett M, Johnston SR, Miller WR, Nicholson R, Robertson JF. CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK. "Primary endocrine therapy is potentially superior to primary chemotherapy in patients with ER-positive tumors. ... The fact that in ER-positive [BREAST] tumors primary endocrine therapy is associated with similar response rates to chemotherapy make it an attractive therapy for older women. ... This clinical scenario allows us to use other potentially useful assessments such as the non-invasive estimation of angiogenesis using quantitative imaging techniques of blood flow. The newer anti-estrogens and aromatase inhibitors appear ideally suited to primary therapy since they have rapid and profound inhibitory activities, few or no agonist effects, and low side effect profiles." Fetch PMID: 9928561 11. J Steroid Biochem Mol Biol 1998 Nov;67(4):293-304 The steroidal antiestrogen ICI 182,780 is an inhibitor of cellular aromatase activity. Long BJ, Tilghman SL, Yue W, Thiantanawat A, Grigoryev DN, Brodie AM. The University of Maryland School of Medicine, Baltimore 21201, USA. Two types of endocrine therapy that have been successfully applied to patients with hormone-dependent breast cancer are the non-steroidal antiestrogen tamoxifen, and inhibitors of aromatase, the enzyme that synthesizes estrogens. The major drawback with tamoxifen is that it acts as a partial estrogen-agonist and this is believed to mediate, at least in part, acquired tumor resistance to the drug as well as endometrial hyperplasia and carcinoma in some patients. Fetch PMID: 9883986 12. Drugs Aging 1998 Oct;13(4):321-32 Anastrozole. A review of its use in the management of postmenopausal women with advanced breast cancer. Wiseman LR, Adkins JC. Adis International Limited, Auckland, New Zealand. demail@adis.co.nz "...Anastrozole is generally well tolerated in the majority of patients, the most common adverse events being gastrointestinal (GI) disturbances (incidence 29 to 33%). These events are generally mild or moderate and transient. Other adverse events reported with anastrozole include headache (< or = 18%), asthenia (< or = 16%), pain (< or = 15%), hot flushes and bone pain (both < or = 12%), back pain and dyspnoea (both < or = 11%) and peripheral oedema (< or = 9%). GI disturbance tended to be more common with anastrozole than megestrol, particularly at the 10 mg/day dosage; however, compared with megestrol, anastrozole is less frequently associated with weight gain..." Fetch PMID: 9805213 13. Br J Cancer 1998 Sep;78 Suppl 4:12-5 Aromatase inhibitors and their future role in post-menopausal women with early breast cancer. Lonning PE. Department of Therapeutic Oncology and Radiophysics, Haukeland University Hospital, Bergen, Norway. 'In terms of benefits over other endocrine agents, anastrozole causes significantly less weight gain than megestrol acetate; it does not have the partial agonist activity of tamoxifen, and is unlikely to lead to tumour stimulation in patients resistant to tamoxifen or to exert proliferative effects on the endometrium. The lack of oestrogen agonist activity, however, may possibly have detrimental effects on bone mineral density and blood lipid profile.' Fetch PMID: 9741783 14. Cancer Epidemiol Biomarkers Prev 1998 Jan;7(1):65-78 Aromatase inhibitors as potential cancer chemopreventives. Kelloff GJ, Lubet RA, Lieberman R, Eisenhauer K, Steele VE, Crowell JA, Hawk ET, Boone CW, Sigman CC. Chemoprevention Branch, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland 20852, USA. "one chemopreventive strategy for breast and prostate cancers is to decrease estrogen production. This can be accomplished by inhibiting aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis. .... The rationale for the use of aromatase inhibitors as chemopreventives and identification of inhibitors to serve as potential chemopreventive agents are the subjects of this review. .... The discussion focuses on those inhibitors that are clinically available or in clinical trials, including: aminoglutethimide (Cytadren), rogletimide, fadrozole hydrochloride, liarozole hydrochloride, anastrozole (Arimidex), letrozole, vorozole, formestane, exemestane, and atamestane. On the basis of results from preclinical studies, aromatase inhibitors may be promising agents for clinical trials in populations at high risk for developing estrogen-dependent cancers.Total suppression of aromatase may have adverse effects, as is evident in postmenopausal women (increased osteoporosis, cardiovascular disease, and urogenital atrophy). ...it may be possible to obtain chemopreventive effects without total suppression of aromatase and circulating estrogen levels. Suppressing local estrogen production may be an alternative strategy ...The development of drugs that target this promoter region may be possible. " Fetch PMID: 9456245 15. Cancer 1997 Feb 15;79(4):730-9 A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Arimidex Study Group. Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A.Department of Medical Oncology, M.D. Anderson Cancer Center, University of Texas Medical Center, Houston 77030, USA. Fetch PMID: 9024711 16. J Clin Oncol 1996 Jul;14(7):2000-11 Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group. Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, et.al M.D. Anderson Cancer Center, University of Texas, Houston, 77030, USA. Fetch PMID: 8683230
NOT Tamoxifen
Annotated Medical Journal Article Citations The abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for Tamoxifen and LMS You can also search Pubmed for Tamoxifen and uterine cancer And also search Pubmed for Tamoxifen and contraindications 1. Br Med Bull 2000;56(3):773-86 Novel agents to modulate oestrogen action. Dardes RC, Jordan VC. Department of Gynaecology, Federal University of Sao Paulo, Brazil (UNIFESP) "...Tamoxifen is the endocrine treatment of choice for breast cancer, but it also has beneficial effects on bone density and serum lipids in postmenopausal women. Recently, tamoxifen was shown to decrease the risk of invasive breast cancer in women at high risk. [While tamoxifen lowers the overall risk of tumors recurring in breast cancer patients, a new study suggests that if a new cancer does develop it is five times as likely to be of an aggressive type. Ed. ] However, tamoxifen has some stimulatory effects on the endometrium. [What this means is that the endometrium...the lining of the womb...is stimulated to grow by tamoxifen. So Tamoxifen is probably not a good medicine to use for uterine cancers. Ed.] Raloxifene is used to prevent osteoporosis and fractures. Raloxifene also lowers circulating cholesterol and the incidence of invasive breast cancer in postmenopausal women but does not stimulate the endometrium.[There was a recent case report about raloxifene possibly stimulating an ovarian cancer. Ed.] The SERMs have evolved from mere laboratory curiosities into drugs that hold promise for preventing several major diseases associated with ageing in women." Fetch PMID: 11255561 2. Eur J Gynaecol Oncol 1999;20(4):327-8 Uterine leiomyosarcoma in a postmenopausal woman treated with tamoxifen: case report. Sabatini R, Di Fazio F, Loizzi P. III Clinic of Obstetrics and Gynecology, University of Bari, Italy. Fetch PMID: 10475136 3. Int J Gynecol Pathol 1999 Apr;18(2):130-7 Tamoxifen and the endometrium: review of 102 cases and comparison with HRT-related and non-HRT-related endometrial pathology. Kennedy MM, Baigrie CF, Manek S. Nuffield Department of Pathology, John Radcliffe Hospital, Oxford, United Kingdom. "Tamoxifen, a synthetic anti-estrogen that paradoxically acts as a partial estrogen agonist on the endometrium, is associated with an increased frequency of proliferative endometrial lesions, including hyperplasias, neoplasms, and polyps." Fetch PMID:10202670 4. Cancer Treat Res 1998;94:195-207 Tamoxifen and the endometrium. Barakat RR. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Fetch PMID: 9587689 5. Carcinogenesis 1997 Oct;18(10):2009-14 Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen. Diwan BA, Anderson LM, Ward JM. Intramural Research Support Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. "Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women." Fetch PMID: 9364013 6. Acta Obstet Gynecol Scand 1996 Jul;75(6):593-5 Uterine leiomyosarcoma in patient receiving tamoxifen therapy. McCluggage WG, Varma M, Weir P, Bharucha H. Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland. Fetch PMID: 8693940 7. Med J Aust 1995 Aug 7;163(3):160-1 Leiomyosarcoma of the uterus in a woman taking adjuvant tamoxifen therapy. Gillett D. Publication Types: Letter Fetch PMID: 7643773 8. Int J Gynecol Pathol 1994 Jul;13(3):248-58 Malignant neoplasms of the uterine corpus in patients treated for breast carcinoma: the effects of tamoxifen. Silva EG, Tornos CS, Follen-Mitchell M. Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030. "We reviewed the clinical history and pathology material of 72 patients seen at the M. D. Anderson Cancer Center who developed malignant neoplasms of the uterine corpus after being treated for breast carcinoma with either tamoxifen or other therapeutic regimens. The purpose of this study was to investigate the type of malignant tumors seen in the uterus, their association with endometrial polyps or hyperplasia, and their possible relationship to tamoxifen treatment. This study shows that in patients treated for breast carcinoma, the uterine malignancies are characterized by several features: (a) a previously unreported high incidence of clear cell carcinoma (14 cases) and leiomyosarcoma (12 cases); (b) seven of 12 leiomyosarcomas with unusual features, such as epithelioid (5), tubular (1), and myxoid features (2); (c) a higher incidence of serous carcinoma (45% in patients treated for > or = 12 months); (d) endometrial polyps associated with carcinoma more often than endometrial hyperplasia. " Fetch PMID: 7928058
Megestrol Acetate [Megace]
Some Annotated Medical Journal Citations The abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for megestrol acetate and LMS You can also search Pubmed for megestrol acetate and sarcoma As well as megestrol acetate and uterine cancer 1. Gynecol Oncol 1998 Dec;71(3):458-60 Low-grade endometrial stromal sarcoma preoperative treatment with Depo-Lupron and Megace. Scribner DR Jr, Walker JL. Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, 73190, USA. Two doses of depot Lupron 7.5mg, and Megace 160mg/day, were given to control bleeding and shrink the low grade, inoperable ESS tumor mass in a 46 year old woman. This neoadjuvant therapy allowed for shrinkage of tumor mass, and surgical resection with a TAH with BSO. Additional research is necessary to define the exact role of chemo, radiation, and hormal therapy. Copyright 1998 Academic Press. Fetch PMID: 9887250 2. Surg Today 1996;26(2):138-41 The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: report of a case. Uchida T, Nakakawaji K, Sakamoto J, Kojima H, Murakami H, Kato J, Yasue M Department of Surgery, Aichi Prefectural Hospital, Kakemachi, Okazaki, Japan. "A 51-year-old woman was admitted to our hospital for further investigation of chest X-ray films which showed multiple shadows that had been growing slowly over 2 years. ... The resected specimens were pathologically diagnosed as metastasizing leimyosarcoma which was positive for the progesterone and estrogen receptors. Thus, 1 month postoperatively, a course of medroxyprogesterone (MPA), 600 mg daily, was commenced. The residual lesions in her chest started to diminish, shortly afterward. She has remained well on this MPA regimen for 45 months. The prognosis of patients with metastasizing leiomyosarcoma is poor because of its low sensitivity to chemotherapy; however, some types of leiomyosarcoma are hormone-sensitive. It is therefore important to examine the hormone receptors of excised tumors from patients suspected of having metastasizing leiomyoma or leimyosarcoma." Fetch PMID: 8919287 3. Fertil Steril 1995 Jul;64(1):191-2 Fibroid growth in response to high-dose progestogen. Harrison-Woolrych M, Robinson R. Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, United Kingdom. "To challenge the conventional belief that leiomyomata are estrogen-dependent tumors by presentation of a case report suggesting high-dose progestogen therapy is associated with a dramatic increase in size of a fibroid uterus. ...One white woman treated with tamoxifen and high-dose megestrol acetate for breast carcinoma... While taking tamoxifen and high-dose megestrol acetate, the patient suffered a dramatic increase in size of her fibroid uterus, which reversed when the progestogen was withdrawn. " [NB both megestrol acetate and tamoxifen have been associated with a tumor flare phenomenon.] Fetch PMID: 7789558 4. Clin Endocrinol (Oxf) 1995 Jan;42(1):91-3 Megestrol-induced Cushing's syndrome. Steer KA, Kurtz AB, Honour JW. Bloomsbury Department of Chemical Pathology, Middlesex Hospital, London, UK. . Fetch PMID: 7889638 5. Eur J Gynaecol Oncol 1993;14(1):44-5 Response of "benign" metastasizing leiomyoma to progestin withdrawal. Case report. Cohen JD, Robins HI. Division of Hematology/Oncology Denver Veterans Administration Medical Center. "We report a rare case of a benign metastasizing leiomyoma in which progestin therapy permitted or promoted pulmonary metastases, but progestin withdrawal induced a marked tumor regression. The significance of these observations is discussed relative to the estrogen and progesterone receptor positivity of this patient's tumor." Fetch PMID: 8472731 6. Gynecol Oncol 1989 Nov;35(2):275-8 Low-grade endometrial stromal sarcoma recurring over three decades. Styron SL, Burke TW, Linville WK. Department of Obstetrics and Gynecology, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200. "Endometrial stromal sarcoma (ESS) is an uncommon uterine malignancy with a variety of histologic characteristics and clinical courses. We describe a patient who recently underwent her third resection of a locally recurring low-grade ESS 29 years after original diagnosis. Tissue from her recurrent tumor contained high levels of estrogen and progesterone receptors and had a diploid DNA content. In addition to multiple resections, she has previously been treated with vincristine chemotherapy and is now receiving megestrol acetate therapy. Mitotic activity is the most important prognostic feature distinguishing high- and low-grade ESS. The mainstay of therapy for both high- and low-grade tumors is surgical excision. A beneficial adjuvant role for cytotoxic chemotherapy or radiotherapy is yet to be clearly established for low-grade ESS; however, recent reports suggest that progestational agents may produce significant responses in recurrent or persistent disease patients whose tumors produce steroid hormone receptors. Indolent tumors may require years of close observation and multiple treatment approaches to maintain a patient in a functional capacity." Fetch PMID: 2807024 7. Gan To Kagaku Ryoho 1987 Oct;14(10):2837-44 [Hormone dependency and progestogen therapy in the treatment of endometrial cancer]. [Article in Japanese] Okada H, Nakata Y, Fujimoto J, Fujita H. Dept. of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine. "The anti-tumor activities of steroid compounds on endometrical cancer (Ishikawa cell line) were examined in vitro by human tumor clonogenic assay (HT CA). Clinically effective progestational compounds including medroxyprogesterone acetate (MAP), and 17 alpha hydroxy-progesterone caproate were effective. Norethindrone (ENT), which is also a potent progestational compound, and RU486, which is known to be a progesterone antagonist were ineffective in this in vitro system, neither having any influence on the effect of MAP. These results indicated that the anti-tumor activity of MAP did not proceed via the so-called progesterone receptor system. Morphological changes induced by MAP in undifferentiated endometrial cancer, the effectiveness of tamoxifen, hormonochemotherapy, and the use of MAP for adjuvant therapy and prophylaxis were also discussed." Fetch PMID: 2959204 8. Gynecol Oncol 1987 Jan;26(1):87-97 Endometrial stromal sarcoma: a clinicopathologic study of 11 cases with determination of estrogen and progestin receptor levels in three tumors. Katz L, Merino MJ, Sakamoto H, Schwartz PE. "All four of the patients who were treated with hormonal therapy [megestrol acetate] are alive, free of disease, or with stable tumor from 2 to 6 years after diagnosis. The presence of estrogen receptors (ER) and progestin receptors (PR) was demonstrated in the tumor in some of the cases; this may explain the sensitivity of this neoplasm to hormonal therapy." Fetch PMID: 3792939 9. Semin Oncol 1985 Mar;12(1 Suppl 1):23-7 Progestin therapy in lesions of the endometrium. Wentz WB. "This paper details several studies of the effect of a single progestin, megestrol acetate, in patients with persistent endometrial hyperplasia and recurrent or persistent endometrial adenocarcinoma. Results of these studies indicate that megestrol acetate inhibits recurrence of adenomatous and atypical hyperplasia as well as adenocarcinoma in situ. These diseases when left untreated often progress to invasive adenocarcinoma. Additional studies presented here show that megestrol acetate is effective in the treatment of endometrial adenocarcinoma in inoperable patients and increases survival in patients with recurrent endometrial cancer." Fetch PMID: 3975648 10. Am J Obstet Gynecol 1983 Jun 1;146(3):316-22 Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia. Gal D, Edman CD, Vellios F, Forney JP. "Fifty-two postmenopausal women who were poor surgical risks and had histologically proved adenomatous hyperplasia, atypical hyperplasia, or adenocarcinoma in situ of the endometrium were treated with megestrol acetate, 40 mg per day, continuously for 9 to 104 months (mean, 42 months). More than 90% of these women had complete remissions of the hyperplasia. Three women with carcinoma in situ were followed up for 57, 65, and 104 months, without recurrence of the disease. Four women required hysterectomy; none had invasive adenocarcinoma. No adverse side effects of the drug were observed. Thus, we conclude that the continuous use of megestrol acetate is an effective, safe, alternative form of therapy for endometrial hyperplasia in postmenopausal women. " Fetch PMID: 6859142
Lupron Depot [GnRH Agonist]
Some Annotated Medical Journal Citations The abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for Lupron and LMS You can also search Pubmed for Lupron, leiomyoma, LMS As well as Lupron and uterine cancer 1. Obstet Gynecol 1998 Oct;92(4 Pt 2):664-6 Aborted leiomyosarcoma after treatment with leuprolide acetate. Mesia AF, Williams FS, Yan Z, Mittal K. Department of Pathology, Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA. "Leuprolide acetate has been used to decrease uterine size and shrink leiomyomata. In carefully selected patients, its treatment benefits are well recognized. However, if leuprolide acetate is inadvertently given to a patient with an unsuspected leiomyosarcoma, complications may occur... A patient presumed to have leiomyomata was treated with monthly injections of leuprolide acetate... In the third month of treatment, unusual manifestations, including increased bleeding, aborting mass, urinary retention, and severe pain, occurred suggesting a possible malignancy and requiring immediate operation... The use of leuprolide acetate can delay the diagnosis and treatment of leiomyosarcoma and thus may increase the risk of morbidity and affect the treatment outcome of patients with leiomyosarcoma. The histologic changes ascribed to leuprolide acetate treatment in leiomyomata also were seen in this leiomyosarcoma." Fetch PMID: 9764655 2. Gynecol Oncol 1993 May;49(2):266-7 Gonadotropin releasing hormone (GnRH) agonist therapy for reduction of leiomyoma volume. Murphy NJ, Wallace DL. Department of Obstetrics and Gynecology, St. Luke's Hospital, Kansas City, Missouri 64111. "A patient with menorrhagia, dysmenorrhea, and an enlarged uterus was treated with a GnRH agonist for leiomyoma volume reduction. A laser-assisted myomectomy yielded five tumors that did not appear to be well demarcated and had a combined weight of only 30 g. Postoperative pathologic evaluation revealed leiomyosarcoma with 22 mitoses per 10 high-power fields. The 8-month delay in therapy was associated with Stage IV, grade 3 disease at diagnosis. In rare cases GnRH agonist therapy may palliate symptoms and delay definitive surgical therapy of leiomyosarcoma, resulting in more advanced disease at diagnosis." Fetch PMID: 8504999 3. Obstet Gynecol 1990 Mar;75(3 Pt 2):529-32 Unsuspected leiomyosarcoma: treatment with a gonadotropin-releasing hormone analogue. Meyer WR, Mayer AR, Diamond MP, Carcangiu ML, Schwartz PE, DeCherney AH. Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut. "We present a case of a 46-year-old woman evaluated for abnormal uterine bleeding and an enlarged uterus, with normal endometrial sampling. Three months of leuprolide acetate injections resulted in a nonenlarging uterus and resolution of iron deficiency anemia and menorrhagia. Intraoperative examination suggested leiomyosarcoma, which was confirmed by postoperative permanent histologic sections. Residual uterine sarcomatous disease was confirmed on reexploration. Similar cases will continue to raise arguments against conservative hormonal intervention in the perimenopausal woman with an enlarged uterus. As the gynecologist gains familiarity with the use of gonadotropin-releasing hormone analogue therapy in the treatment of myomatous uteri, the criteria for hysterectomy will become less rigid and the potential for delay in the diagnosis and treatment of sarcomatous disease will become more common. Physicians must be cognizant of this potential complication of conservative therapy of leiomyomata uteri." Fetch PMID: 2106109 Lupron Depot and Breast & Ovarian Cancer Annotated References Search Pubmed for Lupron Depot and Breast Cancer http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=PubMed&term=lupron%20cancer%20breast Search Pubmed for Lupron Depot and Ovarian Cancer http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=PubMed&term=lupron%20cancer%20ovary 4. Zentralbl Gynakol 1998;120(6):284-92 [Primary endocrine therapy as pre- and perimenopausal metastatic breast carcinoma with leuprorelin acetate depot. German Leuprorelin Study Group]. [Article in German] Untch M. "Leuprorelinacetate-depot is a safe and effective palliative drug for pre- and perimenopausal metastatic breast cancer patients. Like other GnRH-agonists which have been evaluated for this indication, leuprorelinacetate-depot can be used as first-line endocrine treatment in these patients". Fetch PMID: 9659699 5. Eur J Gynaecol Oncol 1996;17(4):286-8 Leuprolide acetate as a salvage-therapy in relapsed epithelial ovarian cancer. Marinaccio M, D'Addario V, Serrati A, Pinto V, Cagnazzo G. I Department of Obstetrics and Gynecology, University of Bari Medical School, Italy. ""Treatment is well-tolerated and no toxicity has been noted. These data stress the significant activity of Leuprolide acetate as a salvage therapy in patients with relapsed advanced epithelial ovarian cancer after previous platinum-based chemotherapies." Fetch PMID: 8856307 6. J Clin Endocrinol Metab 1993 Jun;76(6):1439-45 A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin "add-back" regimens for women with leiomyomata uteri. Friedman AJ, Daly M, Juneau-Norcross M, Rein MS, Fine C, Gleason R, Leboff M. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. Fetch PMID: 8501148 Lupron Depot AND Endometrial Cancer 7. Arch Gynecol Obstet 2000 Feb;263(3):148-9 Uterine adenocarcinoma after GnRH agonist treatment. Dessole S, Ruiu GA, Cherchi PL, Ambrosini G. We report endometrial adenocarcinoma in two patients shortly after suspending GnRH-agonist treatment for menometrorrhagia and uterine fibromata. Fetch PMID: 10763848 8. Gynecol Oncol 1998 Dec;71(3):458-60 Low-grade endometrial stromal sarcoma preoperative treatment with Depo-Lupron and Megace. Scribner DR Jr, Walker JL. Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, 73190, USA. Two doses of depot Lupron 7.5mg, and Megace 160mg/day, were given to control bleeding and shrink the low grade, inoperable ESS tumor mass in a 46 year old woman. This neoadjuvant therapy allowed for shrinkage of tumor mass, and surgical resection with a TAH with BSO. Additional research is necessary to define the exact role of chemo, radiation, and hormal therapy. [abstract rewritten because of copyright. Ed.]. Copyright 1998 Academic Press. Fetch PMID: 9887250 9. Gynecol Oncol 1998 Dec;71(3):396-403 Differential inhibitory effects on human endometrial carcinoma cell growth of luteinizing hormone-releasing hormone analogues. Borri P, Coronnello M, Noci I, Pesciullesi A, Peri A, et. al. Istituto di Clinica Ginecologica ed Ostetrica, Universita degli Studi di Firenze, Viale Morgagni 85, Florence, 50134, Italy. Copyright 1998 Academic Press. Fetch PMID: 9887238 10. Depress Anxiety 1998;7(4):171-7 Depressive symptoms associated with gonadotropin-releasing hormone agonists. Warnock JK, Bundren JC, Morris DW. Department of Psychiatry, University of Oklahoma Health Sciences Center-Tulsa, Oklahoma 74129, USA. Fetch PMID: 9706454 11. J Reprod Med 1996 Jun;41(6):415-21 GnRH agonists before surgery for uterine leiomyomas. A review. Crosignani PG, Vercellini P, Meschia M, Oldani S, Bramante T. L. Mangiagalli Obstetrics and Gynecologic Clinic, University of Milan, Italy. Fetch PMID: 8799917
Mifepristone [RU-486]
Some Annotated Medical Journal Citations for Mifepristone [RU 486], an Anti-Progestogen Agent. The abstracts below have been edited. The full abstract of the Medical Journal articles are available on Pubmed. To obtain them, search Pubmed for RU486 and Leiomyosarcoma You can also search Pubmed for RU486 and VEGF 1. Environ Health Perspect 2000 Oct;108 Suppl 5:785-90 Regulation of vascular endothelial growth factor expression by estrogens and progestins. Hyder SM, Huang JC, Nawaz Z, Boettger-Tong H, Makela S, Chiappetta C, Stancel GM. Department of Integrative Biology and Pharmacology, University of Texas-Houston Medical School, Houston, Texas 77225, USA. "Estrogens increase the expression of vascular endothelial growth factor (VEGF) mRNA in the rodent uterus. This regulatory effect is rapid, beginning within 1 hr after hormone treatment, dose dependent, and blocked by the pure antiestrogen ICI 182,780. The induction of the transcript is blocked by inhibitors of RNA but not of protein synthesis, and we have recently identified estrogen response elements in the VEGF gene. Collectively, these findings indicate that estrogens regulate uterine VEGF expression at the transcriptional level via the classical nuclear estrogen receptor pathway. Estrogen induction of VEGF occurs in the stromal layer of the rodent uterus, and estradiol induces expression of VEGF transcript levels in cultured human uterine stromal cells. Progestins also induce VEGF expression in the rodent uterus, although the effect is less marked and slower in onset than estrogenic effects. The effect of progestins is blocked by the antiprogestin mifepristone (RU-486), suggesting that it is also mediated by a classical nuclear receptor pathway. In addition, progestins regulate expression of VEGF mRNA and protein in cultured human T47-D breast cancer cells. The development of uterine leiomyomas is associated with exposure to ovarian sex steroids, abnormal uterine bleeding is commonly seen in patients with leiomyomas, and fibroids require an increased vascular supply for their growth. These observations suggest that VEGF and other angiogenic factors may represent potential targets for the treatment and prevention of uterine fibroids " Fetch PMID: 11035983 2. Presse Med 1999 Dec 4;28(38):2123-31 [Anti-progesterones] [Article in French] Sitruk-Ware R. Service d'Endocrinologie, Hopital Saint-Antoine, Paris. "THERAPEUTIC APPLICATIONS: Antiprogestins are a promising class of therapeutic agents in the field of reproductive health. Mifepristone (exRU486) remains the leading compound of this class and is the only one presently used in clinical practice. Beyond the main action of antiprogestins on human pregnancy, these compounds may prove useful in the treatment of uterine leiomyomas and endometriosis, and for contraception. IN CANCEROLOGY: Rare tumors such as meningiomas or leiomyoarcomas expressing progesterone receptors may [perhaps, ed.] be successfully treated with these antihormones. MAIN INDICATIONS: The main characteristics of the different antiprogestins discovered so far are addressed and the key results from the large clinical studies conducted with mifepristone are described here for indications where the product is approved for clinical use: medical termination of pregnancy during the first trimester, cervical dilatation prior to surgical termination of pregnancy, preparation for prostaglandin action in the therapeutic termination of pregnancy beyond the first trimester, labor induction in case of foetal death in utero." Fetch PMID: 10613204 3.J Soc Gynecol Investig 1998 Nov-Dec;5(6):334-8 Inhibition of endometrial cancer cell lines by mifepristone (RU 486). Schneider CC, Gibb RK, Taylor DD, Wan T, Gercel-Taylor C. Department of Obstetrics and Gynecology, University of Louisville School of Medicine, Kentucky 40202, USA. Fetch PMID: 9824816 4. Zhonghua Fu Chan Ke Za Zhi 1998 Aug;33(8):490-2 [A clinical control study on the treatment of uterine leiomyoma with gonadotrophin releasing hormone agonist or mifepristone]. [Article in Chinese] Zeng C, Gu M, Huang H. 4th Municipal Hospital, Wuhan. "To compare the results and side effects in treating uterine leiomyoma with gonadotrophin releasing hormone agonist (GnRH-a) or mifepristone. ... 75 patients with uterine leiomyoma who had clinical symptoms ... were divided into two groups. The GnRH-a group (30 patients) was treated by injection of GnRH-a 150 micrograms/day subcutaneously for three months, and the mifepristone group (45 patients) was treated by mifepristone 12.5 mg/day po for three months. ... The clinical symptoms improved obviously in both groups. The volume of leiomyoma reduced 20.0% or more in 90.0% (27/30) of the patients in GnRH-a group, while it was 91.1% (41/45) in mifepristone group. However, the recurrent rates were 40.0% and 17.8% in the 2 groups. ... It suggested that mifepristone is a more practical and hopeful drug in treating uterine leiomyoma." Fetch PMID: 10806751 5. Cancer Res 1998 Feb 1;58(3):392-5 Progestin regulation of vascular endothelial growth factor in human breast cancer cells. Hyder SM, Murthy L, Stancel GM. Department of Integrative Biology, Pharmacology and Physiology, University of Texas Health Sciences Center-Houston, "Vascular endothelial growth factor (VEGF) is a potent angiogenic factor associated with the degree of vascularity, progression, and metastasis of breast cancer, and cases of this disease with increased vascular density have a poor prognosis. We show that in T47-D human breast cancer cells, progesterone induces a dose-dependent increase of 3-4-fold in media VEGF levels, with a maximum response occurring at a concentration of 10 nM. This effect is blocked by the antiprogestin RU 486. ..." Fetch PMID: 9458078 6.Fertil Steril 1997 Dec;68(6):967-76 Mifepristone (RU486): a review. Mahajan DK, London SN. Department of Obstetrics and Gynecology, Louisiana State University School of Medicine, Shreveport 71130, USA. "Mifepristone effectively blocks P receptors in the placenta, resulting in the termination of pregnancy. In addition, it has been used in the treatment of leiomyomata, endometriosis, advanced breast cancer, and meningioma. It is a powerful tool to study the molecular action of P and in the future may be used as an estrogen-free contraceptive." Fetch PMID: 9418681 7. Hum Reprod Update 1995 Jan;1(1):19-34 Clinical uses of antiprogestogens. Van Look PF, von Hertzen H. Special Programme, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland. "Antiprogestogens, which block the action of progesterone at the cellular level through binding to the progesterone receptor, are proving to be one of the most significant developments in endocrinology in recent years. ... Most of the clinical research to date has focused on the use of mifepristone given in combination with prostaglandin for termination of early pregnancy.... In fertility regulation, the sequential combination regimen of mifepristone plus prostaglandin as used for inducing abortion has proved to be effective also for menses induction and can be expected to be an efficacious once-a-month contraceptive. Mifepristone alone, without adjuvant prostaglandin, has yielded promising results as an anti-implantation agent and in emergency contraception. Other potential uses include once-a-week contraception, ovulation inhibition (in a sequential regimen with a progestogen), and as a daily mini-pill. Mifepristone, and other antiprogestogens for which biological data have been reported also bind to the cellular receptors for glucocorticoid hormones and, consequently, possess antiglucocorticoid in addition to their antiprogestational activity. Because of this antiglucocorticoid effect, mifepristone has been employed successfully in the palliative treatment of hypercortisolism due to Cushing's syndrome, and its use has been proposed for treating certain forms of depression and of glaucoma, and in wound healing. However, for scientific and practical reasons, it would be preferable if molecules were developed that have only the antiprogestational or the antiglucocorticoid activity rather than both." Fetch PMID: 9080204 8. Am J Obstet Gynecol 1994 Jun;170(6):1623-7; discussion 1627-8 The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: a prospective, randomized study. Reinsch RC, Murphy AA, Morales AJ, Yen SS. Department of Obstetrics and Gynecology, Kaiser Permanente, University of California, San Diego 92103. " We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months. There was no significant decrease between groups. ...: Both RU 486 (25 mg daily) and leuprolide acetate (3.75 mg monthly) are effective in decreasing blood flow to the uterus (increasing resistive index) and decreasing uterine volume at 3 months. A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery." Fetch PMID: 8203418 9. Curr Opin Obstet Gynecol 1994 Jun;6(3):269-78 RU486: pharmacology and potential use in the treatment of endometriosis and leiomyomata uteri. Murphy AA, Castellano PZ. Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia. "RU486 has been shown to relieve pelvic pain associated with endometriosis and to decrease American Fertility Society endometriosis scores. Uterine leiomyomata show a significant reduction in size after administration of RU486 for 3 months. Although much research remains to be carried out, RU486 appears promising as alternative therapies for these diseases." Fetch PMID: 8038415 10. Presse Med. 1999 Dec 4;28(38):2123-31. [Anti-progesterones] [Article in French] Sitruk-Ware R. Service d'Endocrinologie, Hopital Saint-Antoine, Paris. "Antiprogestins are a promising class of therapeutic agents in the field of reproductive health. Mifepristone (exRU486) remains the leading compound of this class and is the only one presently used in clinical practice. Beyond the main action of antiprogestins on human pregnancy, these compounds may prove useful in the treatment of uterine leiomyomas and endometriosis, and for contraception." "IN CANCEROLOGY: Rare tumors such as meningiomas or leiomyosarcomas expressing progesterone receptors may be successfully treated with these antihormones. "MAIN INDICATIONS: The main characteristics of the different antiprogestins discovered so far are addressed and the key results from the large clinical studies conducted with mifepristone are described here for indications where the product is approved for clinical use: medical termination of pregnancy during the first trimester, cervical dilatation prior to surgical termination of pregnancy, preparation for prostaglandin action in the therapeutic termination of pregnancy beyond the first trimester, labor induction in case of foetal death in utero." Fetch PMID: 10613204 11. Diskussionsforum Med Ethik. 1992;(6-7):XXXVIII-XLIII. [Mifepristone (RU 486)] [Article in German] Bonelli RM. "The antiprogestin RU 486 converts the early pregnant uterus by increasing the sensitivity of the myometrium to prostaglandin (PG). These effects of antiprogestin have resulted in the development of nonsurgical procedures to abort embryos based on a combination of RU 486 and different PG-analogues administered vaginally or intramuscularly. RU 486 also has a softening effect on the cervix which may be used as pretreatment in second and third trimester abortions. The effects, mode of action, dangers, and the many other postulated clinical implications (like breast cancer, meningioma, ectopic pregnancy, fetal death in utero, induction of labour, initiation and promotion of lactation, endometrial or ovarian cancers, leukemia, Cushing's syndrome, uterine adenomyosis, acute uremia, leiomyosarcoma, hypertension, etc.) are discussed." Fetch PMID: 1514299 12. Int J Cancer. 1989 Dec 15;44(6):1034-40. The influence of glucocorticoids on the growth of a human leiomyosarcoma cell line SK-LMS-1. Madsen WE, Gupta TK, Walker MJ. Department of Surgery, University of Illinois College of Medicine, Cook County Hospital, Chicago. "A cell line derived from a human leiomyosarcoma, SK-LMS-I, has cystolic ... glucocorticoid receptor, by Scatchard analysis of tumors grown in male athymic mice. Tumor growth of SK-LMS-I cells in male athymic mice is inhibited by daily s.c. injection of DEX 5 micrograms, DEX 25 micrograms, DEX 5 micrograms with 5 mu RU-486 and 5 micrograms RU-486. In sharp contrast, in vitro, glucocorticoid markedly stimulates the growth (as determined by cell number) of SK-LMS-I cells, principally at higher cell densities (days 10-21 of growth carried on over a 21- to 23-day period), the greatest stimulation being seen with DEX 10(-6) to 10(-8) M, and no stimulation being seen with DEX 10(-9) and 10(-10) M. In vitro, glucocorticoids with higher affinity for the GR stimulate growth, steroids with lower affinity inhibit growth. No alterations in cell-cycle distribution (percent G0/G1, S, or G2/m) could be found by flow cytometric analysis of glucocorticoid-stimulated asynchronously growing cultures. Single, isolated, untreated SK-LMS-I cells form colonies in soft agar with an efficiency of 1.78 +/- 0.10%. Pre-treatment of cells with DEX 10(-7) M increases this to 3.24 +/- 0.17%, while cells pre-treated with both DEX 10(-7) M RU-486 10(7) M form colonies with the same efficiency as untreated cells. Glucocorticoids have inhibitory effects on in vivo growth and stimulatory effects on in vitro growth of a GR-positive human leiomyosarcoma cell line. Fetch PMID: 2606572

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