Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review.
Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH) or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH) and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a combined stimulation with FSH and LH seems to be the best treatment choice. In the first half of the stimulation cycle the FSH dosage should exceed that of LH by 2:1, with an inverse ratio for the second half.
Krause
Bernd Th
BT
Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany. bthkrause@web.de
Ohlinger
Ralf
R
Haase
Annette
A
J Clin Endocrinol Metab. 1992 Apr;74(4):842-9
1548349
Clin Endocrinol (Oxf). 2008 Sep;69(3):471-8
18485121
J Clin Endocrinol Metab. 1998 May;83(5):1507-14
9589647
J Clin Endocrinol Metab. 1980 Jul;51(1):173-5
6247361
J Clin Endocrinol Metab. 1968 Mar;28(3):355-8
5642687
Neuroendocrinology. 1994 Mar;59(3):297-308
8159279
Hum Reprod. 2006 Oct;21(10):2593-600
16785262
J Clin Endocrinol Metab. 2002 May;87(5):2194-200
11994363
Breast Cancer Res Treat. 1986;7(3):129-45
3096402
Endocr Rev. 1984 Winter;5(1):76-127
6142819
J Clin Endocrinol Metab. 1993 Jul;77(1):125-9
8325934
Hum Reprod. 2005 Feb;20(2):359-67
15567880
Mol Cell Endocrinol. 2000 Mar 30;161(1-2):25-30
10773387
Hum Reprod. 1994 Feb;9(2):188-91
8027271
Endocrinology. 1986 Nov;119(5):2025-32
3095100
Endocrinology. 1981 Apr;108(4):1379-85
6258904
J Clin Endocrinol Metab. 1996 Feb;81(2):437-42
8636244
Am J Obstet Gynecol. 1990 Nov;163(5 Pt 2):1732-6
2122729
Mol Cell Endocrinol. 2001 Oct 25;183(1-2):29-32
11604221
Fertil Steril. 1996 Apr;65(4):711-7
8654626
Neuroendocrinology. 1991 Oct;54(4):321-6
1758574
Hum Reprod. 2001 Aug;16(8):1636-43
11473955
J Clin Endocrinol Metab. 1992 Jun;74(6):1471-3
1592896
Hum Reprod. 1999 Sep;14(9):2230-5
10469685
Hum Reprod. 2002 Jan;17(1):88-91
11756367
Fertil Steril. 1991 Dec;56(6):1048-53
1743320
J Clin Endocrinol Metab. 1986 Jun;62(6):1136-44
3084534
J Clin Endocrinol Metab. 1997 Nov;82(11):3748-51
9360535
Fertil Steril. 2001 Feb;75(2):324-31
11172834
Mol Cell Biol. 2007 Mar;27(5):1914-24
17194751
Mol Genet Metab. 1999 Oct;68(2):191-9
10527669
Clin Endocrinol (Oxf). 2007 Oct;67(4):563-9
17692110
Hum Reprod. 2001 Mar;16(3):492-4
11228217
Hum Reprod. 1988 May;3(4):491-501
3134393
Fertil Steril. 1993 Apr;59(4):738-42
8458489
Hum Reprod. 2001 Jun;16(6):1058-64
11387269
Hum Reprod. 2005 Mar;20(3):629-35
15618252
Endocr Rev. 2006 Apr;27(2):170-207
16434510
Cochrane Database Syst Rev. 2003;(1):CD003973
12535497
Endocr Rev. 1990 Feb;11(1):177-99
2108012
J Clin Endocrinol Metab. 2004 Jul;89(7):3189-98
15240592
J Reprod Fertil. 1999 Nov;117(2):355-67
10690204
Endocr Rev. 1997 Feb;18(1):71-106
9034787
Hum Reprod Update. 2006 Jan-Feb;12(1):3-12
16123054
Hum Reprod. 1995 Jul;10(7):1678-83
8582960
Endocr Rev. 2000 Apr;21(2):200-14
10782364
Nature. 1984 Jan 5-11;307(5946):37-40
6690982
Hum Reprod. 1991 Oct;6(9):1206-12
1752920
Hum Reprod. 1994 Aug;9(8):1563-70
7989523
Fertil Steril. 2000 Feb;73(2):338-43
10685540
Clin Obstet Gynecol. 1984 Dec;27(4):927-40
6098403
Curr Med Res Opin. 2003;19(2):83-8
12740151
J Clin Endocrinol Metab. 1985 Nov;61(5):851-8
3900122
J Clin Endocrinol Metab. 1992 Mar;74(3):600-7
1740493
J Clin Endocrinol Metab. 2000 Sep;85(9):3239-44
10999815
Horm Res. 1992;37 Suppl 1:5-11
1330862
Mol Hum Reprod. 2008 Feb;14(2):75-83
18204068
Aust N Z J Obstet Gynaecol. 1997 Feb;37(1):92-4
9075556
Hum Reprod. 1996 Oct;11(10):2076-7
8943503
Annu Rev Biochem. 1981;50:465-95
6267989
Mol Cell Endocrinol. 2001 Jun 20;179(1-2):39-46
11420129
J Clin Endocrinol Metab. 1995 Feb;80(2):667-73
7852534
J Clin Endocrinol Metab. 1996 Apr;81(4):1401-5
8636341
Hum Reprod. 1994 Jul;9(7):1237-42
7962424
Neuroendocrinology. 1993;57(2):289-98
7685504
Fertil Steril. 1997 May;67(5):889-99
9130895
Hum Reprod. 2000 May;15(5):1003-8
10783342
Endocrinology. 1974 Sep;95(3):818-25
4368756
Obstet Gynecol. 1987 May;69(5):800-6
3106871
Hum Reprod. 1990 May;5(4):357-76
2193939
Hum Reprod. 2008 Mar;23(3):499-503
18182396
J Clin Endocrinol Metab. 1989 Mar;68(3):693-7
2493041
Am J Obstet Gynecol. 1971 Nov 1;111(5):708-10
5113890
Hum Reprod. 1993 Nov;8 Suppl 2:112-6
8276943
J Clin Endocrinol Metab. 1988 Mar;66(3):552-6
3127417
Brain Res. 1989 Jul 17;492(1-2):305-13
2665903
J Clin Endocrinol Metab. 2002 Mar;87(3):1156-61
11889180
J Clin Endocrinol Metab. 1988 Sep;67(3):465-73
3137241
Fertil Steril. 1995 Aug;64(2):347-54
7615113
Hum Reprod. 1993 Jun;8(6):829-33
8345070
J Steroid Biochem. 1989 Oct;33(4B):663-8
2513450
Am J Obstet Gynecol. 1976 Sep 1;126(1):91-4
961752
Hum Reprod. 1988 May;3(4):473-7
3134391
Hum Reprod. 2001 Feb;16(2):319-25
11157827
Endocrinology. 1975 Aug;97(2):366-72
1157757
J Clin Endocrinol Metab. 1999 Jan;84(1):228-32
9920089
J Clin Endocrinol Metab. 1999 Aug;84(8):2659-63
10443656
Hum Reprod. 2001 Dec;16(12):2525-32
11726569
Physiol Rev. 1980 Jan;60(1):51-89
6243782
Hum Reprod. 2003 Feb;18(2):314-22
12571167
J Clin Endocrinol Metab. 2001 Apr;86(4):1437-41
11297565
Hum Reprod. 1998 Aug;13(8):2064-7
9756269
Lancet. 1990 Nov 10;336(8724):1141-4
1978024
J Clin Endocrinol Metab. 2001 Jan;86(1):337-43
11232021
Fertil Steril. 2002 Jun;77(6):1170-7
12057724
Mol Hum Reprod. 2004 May;10(5):299-311
15026540
J Clin Endocrinol Metab. 1988 Feb;66(2):361-6
3123512
J Clin Endocrinol Metab. 1993 Jul;77(1):241-8
8325947
Horm Behav. 1994 Dec;28(4):417-23
7537244
Fertil Steril. 1999 Dec;72(6):1118-20
10593393
Am J Obstet Gynecol. 1988 Jul;159(1):210-5
3134814
Fertil Steril. 1995 Jul;64(1):37-43
7789578