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Chemical Compound Review

leuprolide     N-[1-[[1-[[1-[[1-[[1-[[1- [[5...

Synonyms: Enantone (TN), CID3911, NSC-377526, AC1L1GZK, AC1Q5OPO, ...
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Disease relevance of Leuprorelin

  • RESULTS: The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo [1].
  • METHODS: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks) [2].
  • Leuprolide acetate therapy in luteinizing hormone--dependent Cushing's syndrome [3].
  • In a group of 25 premenopausal patients with progressive advanced breast cancer, daily sc administration of 1-10 mg Leuprolide [D-Leu6-Pro9GnRH ethylamide (NEt)] induced objective tumor regression in 44% with a median duration of 9 months [4].
  • The patient's nausea, vomiting, abdominal pain, and early satiety resolved after a short course of treatment with leuprolide acetate but returned after medication was discontinued [5].

Psychiatry related information on Leuprorelin

  • In response to treatment with leuprolide acetate, the threshold measured in wakefulness decreased during carbon dioxide rebreathing in the presence of low (41.05 +/- 0.77 versus 39.40 +/- 0.83 Torr; P = 0.01) and high (46.32 +/- 0.56 versus 44.78 +/- 0.83 Torr; P = 0.01) oxygen levels [6].
  • No published studies have examined women with major depression to determine whether leuprolide will exacerbate or improve depressive symptoms [7].
  • The newly developed leuprorelin acetate 3M depot, as a refinement of the established 1M depot, offers an opportunity to improve patient compliance and provides individualized and optimized, patient-orientated treatment by reducing the number of injections to four per year [8].
  • Leuprolide acetate for exhibitionism in Huntington's disease [9].
  • OBJECTIVE: To propose a protocol for minimizing medical complications associated with the use of cyproterone, medroxyprogesterone, and depot leuprolide to treat paraphilia [10].

High impact information on Leuprorelin


Chemical compound and disease context of Leuprorelin


Biological context of Leuprorelin

  • RESULTS: Mean (+/- standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% +/- 0.5% in the leuprolide group and increased by 2.5 +/- 0.5 in the bicalutamide group from baseline to 12 months (P <.001) [17].
  • We conclude that leuprolide administered to women with PCO decreases gonadal steroid production and is capable of preventing premature luteinization during hMG induction of ovulation [20].
  • Among post-menarcheal PP girls (n = 69), shorter CAG number (biallelic mean </=20) was associated with higher 17-hydroxy-progesterone levels post leuprolide (P = 0.009), indicative of ovarian hyperandrogenism, higher testosterone levels (P = 0.02), acne (P = 0.03) and hirsutism scores (P = 0.01), and more menstrual cycle irregularities (P = 0.04) [21].
  • Specific growth factors or intrafollicular hormones may contribute to this leuprolide acetate-induced difference in cell cycle kinetics [22].
  • The mean (+/-SD) numbers of oocytes retrieved were 9.8 +/- 5.4, 8.7 +/- 4.5, and 8.3 +/- 3.3; the percentages of metaphase II oocytes were 72%, 85%, and 86%; and fertilization rates were 61%, 62%, and 56% in the triptorelin, leuprorelin, and hCG group, respectively (P = NS for all three comparisons) [23].

Anatomical context of Leuprorelin

  • Preoperative leuprorelin acetate therapy increased levels of Egr-1 mRNA in normal myometrium only [24].
  • We have previously shown that the proliferative index (PI), as determined by flow cytometry of luteinized granulosa cells obtained at oocyte retrieval, is greater in ovulation induction regimens which include the GnRH analog (GnRH-a) leuprolide acetate than those using human menopausal gonadotropin (hMG) only [22].
  • Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate [25].
  • To this end, we implemented a novel clinical investigative paradigm consisting of preadministration of an LH-down-regulating dose (3.75 mg) of leuprolide acetate followed, 3-4 wk later, by controlled challenge of the testis, with pulsatile iv infusions of saline vs. recombinant human (rh) LH [26].
  • Furthermore, in a dose-dependent manner, GnRH agonist (leuprolide acetate) inhibited, but GnRH antagonist [D-pGlu1,D-Phe2,D-Trp3.6] (GnRH-Ant1) stimulated, the rate of [3H]thymidine incorporation into myometrial smooth muscle cells (P < 0.05), whereas GnRH-Ant2 (Ac-D-P-Cl-Phe1.2,D-Trp3,D-Arg6,D-Ala10) had no effect [27].

Associations of Leuprorelin with other chemical compounds


Gene context of Leuprorelin


Analytical, diagnostic and therapeutic context of Leuprorelin


  1. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. Schmidt, P.J., Nieman, L.K., Danaceau, M.A., Adams, L.F., Rubinow, D.R. N. Engl. J. Med. (1998) [Pubmed]
  2. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. Smith, M.R., McGovern, F.J., Zietman, A.L., Fallon, M.A., Hayden, D.L., Schoenfeld, D.A., Kantoff, P.W., Finkelstein, J.S. N. Engl. J. Med. (2001) [Pubmed]
  3. Leuprolide acetate therapy in luteinizing hormone--dependent Cushing's syndrome. Lacroix, A., Hamet, P., Boutin, J.M. N. Engl. J. Med. (1999) [Pubmed]
  4. Treatment of breast cancer with gonadotropin-releasing hormone. Manni, A., Santen, R., Harvey, H., Lipton, A., Max, D. Endocr. Rev. (1986) [Pubmed]
  5. Evolution of acute cytomegalovirus gastritis to chronic gastrointestinal dysmotility in a nonimmunocompromised adult. Nowak, T.V., Goddard, M., Batteiger, B., Cummings, O.W. Gastroenterology (1999) [Pubmed]
  6. Treatment with leuprolide acetate decreases the threshold of the ventilatory response to carbon dioxide in healthy males. Mateika, J.H., Omran, Q., Rowley, J.A., Zhou, X.S., Diamond, M.P., Badr, M.S. J. Physiol. (Lond.) (2004) [Pubmed]
  7. The hypothalamic-pituitary-gonadal axis in mood disorders. Young, E.A., Korszun, A. Endocrinol. Metab. Clin. North Am. (2002) [Pubmed]
  8. Randomized open labelled comparative study of the efficacy, safety and tolerability of leuprorelin acetate 1M and 3M depot in patients with advanced prostatic cancer. Wechsel, H.W., Zerbib, M., Pagano, F., Coptcoat, M.J. Eur. Urol. (1996) [Pubmed]
  9. Leuprolide acetate for exhibitionism in Huntington's disease. Rich, S.S., Ovsiew, F. Mov. Disord. (1994) [Pubmed]
  10. Protocols for the use of cyproterone, medroxyprogesterone, and leuprolide in the treatment of paraphilia. Reilly, D.R., Delva, N.J., Hudson, R.W. Canadian journal of psychiatry. Revue canadienne de psychiatrie. (2000) [Pubmed]
  11. Changes in mammographic densities induced by a hormonal contraceptive designed to reduce breast cancer risk. Spicer, D.V., Ursin, G., Parisky, Y.R., Pearce, J.G., Shoupe, D., Pike, A., Pike, M.C. J. Natl. Cancer Inst. (1994) [Pubmed]
  12. Pregnancy after age 50: application of oocyte donation to women after natural menopause. Sauer, M.V., Paulson, R.J., Lobo, R.A. Lancet (1993) [Pubmed]
  13. Pseudotumor cerebri associated with leuprorelin acetate. Arber, N., Shirin, H., Fadila, R., Melamed, E., Pinkhas, J., Sidi, Y. Lancet (1990) [Pubmed]
  14. 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]
  15. Transdermal delivery of peptides by iontophoresis. Hirvonen, J., Kalia, Y.N., Guy, R.H. Nat. Biotechnol. (1996) [Pubmed]
  16. Predictors of improved outcome for patients with localized prostate cancer treated with neoadjuvant androgen ablation therapy and three-dimensional conformal radiotherapy. Zelefsky, M.J., Lyass, O., Fuks, Z., Wolfe, T., Burman, C., Ling, C.C., Leibel, S.A. J. Clin. Oncol. (1998) [Pubmed]
  17. Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. Smith, M.R., Goode, M., Zietman, A.L., McGovern, F.J., Lee, H., Finkelstein, J.S. J. Clin. Oncol. (2004) [Pubmed]
  18. Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer. Dawson, N.A., Figg, W.D., Cooper, M.R., Sartor, O., Bergan, R.C., Senderowicz, A.M., Steinberg, S.M., Tompkins, A., Weinberger, B., Sausville, E.A., Reed, E., Myers, C.E. J. Clin. Oncol. (1997) [Pubmed]
  19. Polycystic ovaries in Hirsute women with normal menses. Carmina, E., Lobo, R.A. Am. J. Med. (2001) [Pubmed]
  20. The effect of leuprolide acetate on ovulation induction with human menopausal gonadotropins in polycystic ovary syndrome. Dodson, W.C., Hughes, C.L., Whitesides, D.B., Haney, A.F. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  21. Androgen receptor gene CAG repeat polymorphism in the development of ovarian hyperandrogenism. Ibáñez, L., Ong, K.K., Mongan, N., Jääskeläinen, J., Marcos, M.V., Hughes, I.A., De Zegher, F., Dunger, D.B. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  22. Gonadotropin-releasing hormone agonist-induced differences in granulosa cell cycle kinetics are associated with alterations in follicular fluid müllerian-inhibiting substance and androgen content. Seifer, D.B., MacLaughlin, D.T., Penzias, A.S., Behrman, H.R., Asmundson, L., Donahoe, P.K., Haning, R.V., Flynn, S.D. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  23. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. Fauser, B.C., de Jong, D., Olivennes, F., Wramsby, H., Tay, C., Itskovitz-Eldor, J., van Hooren, H.G. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  24. Decreased expression of early growth response-1 and its role in uterine leiomyoma growth. Shozu, M., Murakami, K., Segawa, T., Kasai, T., Ishikawa, H., Shinohara, K., Okada, M., Inoue, M. Cancer Res. (2004) [Pubmed]
  25. Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate. Shozu, M., Sumitani, H., Segawa, T., Yang, H.J., Murakami, K., Inoue, M. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  26. Pulsatile iv infusion of recombinant human LH in leuprolide-suppressed men unmasks impoverished Leydig-cell secretory responsiveness to midphysiological LH drive in the aging male. Mulligan, T., Iranmanesh, A., Veldhuis, J.D. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  27. Gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in human myometrium and leiomyomata and the direct action of GnRH analogs on myometrial smooth muscle cells and interaction with ovarian steroids in vitro. Chegini, N., Rong, H., Dou, Q., Kipersztok, S., Williams, R.S. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  28. Inhibition of testosterone production with ketoconazole alone and in combination with a gonadotropin releasing hormone analogue in the rat. English, H.F., Santner, S.J., Levine, H.B., Santen, R.J. Cancer Res. (1986) [Pubmed]
  29. Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: a pathogenic marker. Banno, H., Adachi, H., Katsuno, M., Suzuki, K., Atsuta, N., Watanabe, H., Tanaka, F., Doyu, M., Sobue, G. Ann. Neurol. (2006) [Pubmed]
  30. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Somers, E.C., Marder, W., Christman, G.M., Ognenovski, V., McCune, W.J. Arthritis Rheum. (2005) [Pubmed]
  31. Source localization of androgen excess in adolescent girls. Ibáñez, L., Potau, N., Zampolli, M., Prat, N., Gussinyé, M., Saenger, P., Vicens-Calvet, E., Carrascosa, A. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  32. Effects of gonadal steroid suppression on skeletal sensitivity to parathyroid hormone in men. Leder, B.Z., Smith, M.R., Fallon, M.A., Lee, M.L., Finkelstein, J.S. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  33. Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin-releasing hormone agonist therapy. Dou, Q., Zhao, Y., Tarnuzzer, R.W., Rong, H., Williams, R.S., Schultz, G.S., Chegini, N. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  34. Leuprorelin acetate affects ERK1/2 activity in prostate cancer cells. Iacopino, F., Lama, G., Angelucci, C., Sica, G. Int. J. Oncol. (2006) [Pubmed]
  35. Expression of estrogen receptor alpha and beta mRNAs in prostate cancers treated with leuprorelin acetate. Maruyama, S., Fujimoto, N., Asano, K., Ito, A., Usui, T. Eur. Urol. (2000) [Pubmed]
  36. GnRH agonist inhibits human telomerase reverse transcriptase mRNA expression in endometrial cancer cells. Nagai, N., Oshita, T., Mukai, K., Shiroyama, Y., Shigemasa, K., Ohama, K. Int. J. Mol. Med. (2002) [Pubmed]
  37. 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]
  38. Regression of rat mammary tumors by a potent luteinizing hormone-releasing hormone analogue (leuprolide) administered vaginally. Okada, H., Sakura, Y., Kawaji, H., Yashiki, T., Mima, H. Cancer Res. (1983) [Pubmed]
  39. The ovarian contribution to peripherally derived serum C19 conjugates. Matteri, R.K., Stanczyk, F.Z., Cassidenti, D.L., Paulson, R.J., Lobo, R.A. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  40. Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty. Tanaka, T., Niimi, H., Matsuo, N., Fujieda, K., Tachibana, K., Ohyama, K., Satoh, M., Kugu, K. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
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