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Chemical Compound Review

Leuprolide acetate     N-[1-[[1-[[1-[[1-[[1-[[1- [[5...

Synonyms: Lutrate (TN), Lupron (TN), NSC-746847, NSC746847, AC1L9B44, ...
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Disease relevance of Leuprorelin


Psychiatry related information on Leuprorelin


High impact information on Leuprorelin

  • After the first month of Lupron alone, all men received (in addition to Lupron) testosterone enanthate (200 mg intramuscular) or placebo (sesame oil as color-matched vehicle) every 2 weeks for 1 month each in a crossover design [6].
  • Lupron given every 12 h had a similar effect on fertility, but failed to protect fecundity (P less than 0.001) [7].
  • GH (Nutropin) was administered at a dose of 0.1 U/kg x day sc, until patients reached a bone age (BA) of 14 yr in girls and 16 yr in boys, and LHRH-A (Lupron depot) was administered at a dose of 300 microg/ kg every 28 days in during 3 yr [8].
  • Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner [9].
  • Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium [9].

Chemical compound and disease context of Leuprorelin

  • In a test group of 16 males, 4 males with adenocarcinoma of the prostate under treatment with lupron/flutamide tested negative [10].
  • DESIGN: Twenty-four patients suffering from severe hirsutism secondary to polycystic ovary disease (PCOD) were treated for 12 months with 3.75 mg IM LA every 28 days in association with 0.035 mg/d ethinyl E2 plus 2 mg/d CPA (Diane; Schering, Berlin, Germany) for 21 d/mo [11].
  • Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex) [12].

Biological context of Leuprorelin

  • However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures [9].
  • Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase [9].
  • In contrast, first ovulation was delayed significantly in the Lupron-GH-suppressed females (41 mo) compared to the Lupron-only females (36 mo) [13].
  • Analysis of apoptosis has shown that LA increases the percentage of apoptotic cells in PFs, EAFs, and POFs; however, Ant prevented this effect [14].
  • Treatment of follicles with epidermal growth factor (EGF) suppressed the spontaneous onset of DNA fragmentation, and a similar effect was observed in LA follicles [15].

Anatomical context of Leuprorelin

  • The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium [9].
  • LA induced meiotic maturation, but increased oocyte degeneration rate [16].
  • In addition, LA increased the number of preantral follicles (PFs) and atretic follicles, and decreased the number of early antral follicles (EAFs) and preovulatory follicles (POFs) [14].
  • Lupron therapy produces a shrinking of uterine leiomyomas by accelerating their hyaline degeneration, similar to that in postmenopausal involution [17].
  • Data have shown that Ant per se inhibited BAX translocation from cytosol to mitochondria and retained cytochrome C in the mitochondria, whereas LA induced cytochrome C release [14].

Associations of Leuprorelin with other chemical compounds

  • PURPOSE: In the initial report of the Lupron Depot Neoadjuvant Prostate Cancer Study Group patients who received 3 months of androgen deprivation had a significant decrease in the positive margin rate [18].
  • Thereafter, half the group resumed menstrual cycles (labeled Cycle), and half continued having Lupron injections in combination with transdermal estradiol (labeled Patch) and all were reevaluated a third time [19].
  • STUDY DESIGN: We performed a retrospective chart review of 120 women aged 27 to 49 years who underwent endometrial ablation after 2 months of preoperative treatment with danazol (Danocrine, 800 mg/d orally) or leuprolide (Lupron, 3.75 mg in one intramuscular injection each month) [20].
  • Irradiated rats were treated with either the GnRH agonist Lupron or the GnRH antagonist Cetrorelix, which have different mechanisms of action [21].
  • The occurrence of apoptosis following treatment with LA (10(-11), 10(-6) or 10(-5) M), alone or combined with 10(-9) M DHT, was assessed by DNA fragmentation analysis [22].

Gene context of Leuprorelin

  • POF obtained from LA-treated rats showed no changes in Bcl-2 or Bax protein levels [15].
  • The increase in StAR protein expression following LA treatment was qualitatively similar to StAR mRNA expression, as determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis [23].
  • Follicular contents of StAR and P450scc proteins were measured by Western blotting following in vivo injection of eCG (control) and eCG+LA (LA) to prepubertal rats [23].
  • PATIENT(S): Women undergoing 157 consecutive IVF cycles suppressed with leuprolide acetate (LA) started in the midluteal phase and stimulated with recombinant FSH [24].
  • This could be a consequence of the significant rise in sex hormone-binding globulin (SHBG) in LA + OC and OC groups compared with LA in which there was no change in SHBG [25].

Analytical, diagnostic and therapeutic context of Leuprorelin

  • For the second approach, in vitro perfusion experiments were designed to compare the direct effects of LA (10.000 ng/ml) and hCG (50 IU) on ovarian function and to verify whether the presence of a GnRH-a in the perfusate modifies the actions of hCG [16].
  • Six adult female rhesus monkeys underwent unilateral ovariectomy and were divided into two groups that received monthly injections of either Lupron depot (LHRHa) or placebo vehicle [26].
  • INTERVENTION(S): Standard IVF-ET treatment cycle for ovarian stimulation using hMG with or without LA [27].
  • Apoptosis and cell proliferation were examined in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA), antide, and a combination of both [28].
  • The safety and efficacy of leuprolide acetate (LA) for depot suspension (Lupron depot; TAP Pharmaceuticals, North Chicago, IL), 3.75 mg versus placebo, in the treatment of pain associated with endometriosis was assessed in a randomized, double-blind, multicenter study involving 52 patients [29].


  1. Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. Harvey, H.A., Lipton, A., Max, D.T., Pearlman, H.G., Diaz-Perches, R., de la Garza, J. J. Clin. Oncol. (1985) [Pubmed]
  2. Lupron-induced mania. Rachman, M., Garfield, D.A., Rachman, I., Cohen, R. Biol. Psychiatry (1999) [Pubmed]
  3. Does lupron dosage make a difference in outcome when treating children with precocious puberty? Foster, C.M. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  4. Endometriosis and its treatment with danazol or lupron in relation to ovarian cancer. Cottreau, C.M., Ness, R.B., Modugno, F., Allen, G.O., Goodman, M.T. Clin. Cancer Res. (2003) [Pubmed]
  5. Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study Group. Soloway, M.S., Sharifi, R., Wajsman, Z., McLeod, D., Wood, D.P., Puras-Baez, A. J. Urol. (1995) [Pubmed]
  6. The effects of pharmacologically induced hypogonadism on mood in healthy men. Schmidt, P.J., Berlin, K.L., Danaceau, M.A., Neeren, A., Haq, N.A., Roca, C.A., Rubinow, D.R. Arch. Gen. Psychiatry (2004) [Pubmed]
  7. Gonadal protection and fecundity rates in cyclophosphamide-treated rats. Montz, F.J., Wolff, A.J., Gambone, J.C. Cancer Res. (1991) [Pubmed]
  8. Near final height in pubertal growth hormone (GH)-deficient patients treated with GH alone or in combination with luteinizing hormone-releasing hormone analog: results of a prospective, randomized trial. Mericq, M.V., Eggers, M., Avila, A., Cutler, G.B., Cassorla, F. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  9. Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. Thompson, M.A., Adelson, M.D., Kaufman, L.M. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  10. Preliminary evaluation of 5 alpha-reductase type 2 in urine as a potential marker for prostate disease. Lombardo, M.E., Hudson, P.B. Steroids (1997) [Pubmed]
  11. Clinical and hormonal effects of gonadotropin-releasing hormone agonist plus an oral contraceptive in severely hirsute patients with polycystic ovary disease. Ciotta, L., Cianci, A., Giuffrida, G., Marletta, E., Aglianò, A., Palumbo, G. Fertil. Steril. (1996) [Pubmed]
  12. Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy. Solomon, M.H., McHugh, T.A., Dorr, R.P., Lee, F., Siders, D.B. Clinical and investigative medicine. Médecine clinique et experimentale. (1993) [Pubmed]
  13. Reduced growth hormone secretion prolongs puberty but does not delay the developmental increase in luteinizing hormone in the absence of gonadal negative feedback. Wilson, M.E., Chikazawa, K., Fisher, J., Mook, D., Gould, K.G. Biol. Reprod. (2004) [Pubmed]
  14. Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary. Parborell, F., Irusta, G., Vitale, A., Gonzalez, O., Pecci, A., Tesone, M. Biol. Reprod. (2005) [Pubmed]
  15. Effects of a gonadotropin-releasing hormone agonist on rat ovarian follicle apoptosis: regulation by epidermal growth factor and the expression of Bcl-2-related genes. Parborell, F., Pecci, A., Gonzalez, O., Vitale, A., Tesone, M. Biol. Reprod. (2002) [Pubmed]
  16. Effects of a gonadotropin-releasing hormone analog on rabbit ovarian function. Zanagnolo, V., Dharmarajan, A.M., Hesla, J., Wallach, E.E. Endocrinology (1996) [Pubmed]
  17. Hormonal pathology of the endometrium. Deligdisch, L. Mod. Pathol. (2000) [Pubmed]
  18. Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results. Soloway, M.S., Pareek, K., Sharifi, R., Wajsman, Z., McLeod, D., Wood, D.P., Puras-Baez, A. J. Urol. (2002) [Pubmed]
  19. Effects of short-term suppression of ovarian hormones on cardiovascular and neuroendocrine reactivity to stress in women. Matthews, K.A., Berga, S.L., Owens, J.F., Flory, J.D. Psychoneuroendocrinology (1998) [Pubmed]
  20. Prediction of endometrial ablation success according to perioperative findings. Shamonki, M.I., Ziegler, W.F., Badger, G.J., Sites, C.K. Am. J. Obstet. Gynecol. (2000) [Pubmed]
  21. GnRH agonists and antagonists stimulate recovery of fertility in irradiated LBNF1 rats. Meistrich MLWilson, G., Shuttlesworth, G., Huhtaniemi, I., Reissmann, T. J. Androl. (2001) [Pubmed]
  22. Apoptosis-related gene expression affected by a GnRH analogue without induction of programmed cell death in LNCaP cells. Angelucci, C., Iacopino, F., Lama, G., Capucci, S., Zelano, G., Boca, M., Pistilli, A., Sica, G. Anticancer Res. (2004) [Pubmed]
  23. Steroidogenic acute regulatory protein in ovarian follicles of gonadotropin-stimulated rats is regulated by a gonadotropin-releasing hormone agonist. Irusta, G., Parborell, F., Peluffo, M., Manna, P.R., Gonzalez-Calvar, S.I., Calandra, R., Stocco, D.M., Tesone, M. Biol. Reprod. (2003) [Pubmed]
  24. Follicular phase serum levels of luteinizing hormone do not influence delivery rates in in vitro fertilization cycles down-regulated with a gonadotropin-releasing hormone agonist and stimulated with recombinant follicle-stimulating hormone. Cabrera, R.A., Stadtmauer, L., Mayer, J.F., Gibbons, W.E., Oehninger, S. Fertil. Steril. (2005) [Pubmed]
  25. Combination gonadotropin-releasing hormone agonist and oral contraceptive therapy improves treatment of hirsute women with ovarian hyperandrogenism. Elkind-Hirsch, K.E., Anania, C., Mack, M., Malinak, R. Fertil. Steril. (1995) [Pubmed]
  26. Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys. Ataya, K., Rao, L.V., Lawrence, E., Kimmel, R. Biol. Reprod. (1995) [Pubmed]
  27. Prematurely condensed chromosomes and meiotic abnormalities in unfertilized human oocytes after ovarian stimulation with and without gonadotropin-releasing hormone agonist. Racowsky, C., Prather, A.L., Johnson, M.K., Olvera, S.P., Gelety, T.J. Fertil. Steril. (1997) [Pubmed]
  28. Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis. Meresman, G.F., Bilotas, M., Buquet, R.A., Barañao, R.I., Sueldo, C., Tesone, M. Fertil. Steril. (2003) [Pubmed]
  29. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group. Dlugi, A.M., Miller, J.D., Knittle, J. Fertil. Steril. (1990) [Pubmed]
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