Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-06-05T00:23:01.738Z Has data issue: false hasContentIssue false

Pharmacokinetics of gonadotropin therapy

Published online by Cambridge University Press:  03 June 2009

Tally Levy
Affiliation:
Department of Obstetrics and Gynecology, Golda Medical Center, (Hasharon Hospital), Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Israel
Zion Ben-Rafael*
Affiliation:
Department of Obstetrics and Gynecology, Golda Medical Center, (Hasharon Hospital), Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Israel
*
Department of Obstetrics and Gynecology, Golda Medical Center (Hasharon Hospital), Petah Tikva 49372, Israel.

Extract

Ovulation is the result of an integrated action of the hypothalamus, pituitary and ovaries. During the process, gonadal steroids, peptides and growth factors are produced and influence the synthesis and release of gonadotropin-releasing hormone (GnRH), follicle stimulating hormone (FSH) and luteinizing hormone (LH). These latter compounds play a crucial role in folliculogenesis and are frequently used in the management of infertility.

Type
Articles
Copyright
Copyright © Cambridge University Press 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Brown, JB. Pituitary control of ovarian function - concepts derived from gonadotropin therapy. Aust NZ J Obstet Gynaecol 1978; 18: 47–45.CrossRefGoogle Scholar
2Baird, DT. A model for follicular selection and ovulation: lessons from superovulation. J Steroid Biochem 1987; 27: 1523.CrossRefGoogle Scholar
3Ben-Rafael, Z, Strauss, JF III, Mastroianni, L Jr, Flickinger, GL. Differences in ovarian stimulation in human menopausal gonadotropin treated women may be related to follicle-stimulating hormone accumulation. Fertil Steril 1986; 46: 589–92.CrossRefGoogle ScholarPubMed
4Schoemaker, J, Van Weissenbruch, MM, Van der Meer, M. New approaches with the FSH threshold principle in polycystic ovarian syndrome. Ann NY Acad Sci 1993; 687: 296300.CrossRefGoogle ScholarPubMed
5Fritz, MA, Speroff, L. The endocrinology of the menstrual cycle: the interaction of folliculogenesis and neuroendocrine mechanisms. Fertil Steril 1982; 38: 509–29.Google ScholarPubMed
6Shoham, Z, Jacobs, HS, Insler, V. Luteinizing hormone: its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase. Fertil Steril 1993; 59: 1153–61.CrossRefGoogle ScholarPubMed
7Stanger, JD, Yovich, JL. Reduced in vitro fertilization of human oocyte from patients with raised basal luteinizing hormone levels during the follicular phase. Br J Obstet Gynaecol 1985; 92: 385–93.CrossRefGoogle ScholarPubMed
8Howles, CM, Macnamee, MC, Edwards, RG. Follicular development and early luteal function of conception and non-conceptional cycles after human in-vitro fertilization: endocrine correlates. Hum Reprod 1987; 2: 1721.CrossRefGoogle ScholarPubMed
9Homburg, R, Armar, NA, Eshel, A, Adams, J, Jacobs, HS. Influence of serum luteinizing hormone concentrations on ovulation, conception and early pregnancy loss in polycystic ovary syndrome. Br Med J 1988; 297: 1024–46.CrossRefGoogle ScholarPubMed
10Regan, L, Owen, EJ, Jacobs, HS. Hypersecretion of luteinizing hormone, infertility and miscarriage. Lancet 1990; 336: 1141–44.CrossRefGoogle ScholarPubMed
11Wide, L. Median charge and charge heterogeneity of human pituitary FSH, LH and TSH. I. Zone electrophoresis in agarose suspension. Acta Endocrinol 1985; 109: 181–89.Google ScholarPubMed
12Snyder, PJ, Bashey, HM, Gatewood, CV, Karowe, M. Characterization of human LH isohormones from fresh pituitary tissue. Mol Cell Endocrinol 1987; 54: 115–21.CrossRefGoogle ScholarPubMed
13Rathnan, P, Sazena, BB. Primary aminoacid sequence of follicle-stimulating hormone from human pituitary glands. J Biol Chem 1975; 17: 6735–42.CrossRefGoogle Scholar
14Reichert, LE Jr, Ward, DN. On the isolation and characterization of the alpha and beta subunits of human pituitary follicle-stimulating hormone. Endocrinology 1974; 94: 655–64.CrossRefGoogle ScholarPubMed
15Li, CH, Starman, B. Molecular weight of sheep pituitary interstitial cell-stimulating hormone. Nature 1964; 202: 291–92.CrossRefGoogle ScholarPubMed
16Papkoff, H, Samy, TSA. Isolation and partial characterization of the polypeptide chains of ovine interstitial cell-stimulating hormone. Biochim Biophys Acta 1967; 147: 175–77.CrossRefGoogle ScholarPubMed
17De la Llosa, P, Jutisz, M. Reversible dissociation into subunits and biological activity of ovine luteinizing hormone. Biochim Biophys Acta 1969; 181: 426–36.CrossRefGoogle ScholarPubMed
18Fiddes, JC, Goodman, HM. Isolation, cloning and sequence analysis of the cDNA for the α-subunit of human chorionic gonadotropin. Nature 1979; 281: 351–56.CrossRefGoogle ScholarPubMed
19Pierce, JG, Parsons, TF. Glycoprotein hormones: structure and function. Annu Rev Biochem 1981; 50: 465–95.CrossRefGoogle ScholarPubMed
20Gharib, SD, Wierman, ME, Shupnik, MA, Chin, WW. Molecular biology of the pituitary gonadotropins. Endocr Rev 1990; 11: 177–99.CrossRefGoogle ScholarPubMed
21Bahl, OP, Moyle, WR. Role of carbohydrate in the action of gonadotropins. Receptors Horm Action 1978; 3: 261–89.CrossRefGoogle Scholar
22Shome, B, Parlow, AF. Human follicle-stimulating hormone: first proposal for the amino acid sequence of the hormone specific β-subunit (hFSHβ). J Clin Endocrinol Metab 1974; 39: 203205.CrossRefGoogle Scholar
23Watkins, PC, Eddy, R, Beck, AK et al. Sequence and regional assignment of the human follicle-stimulating hormone β-subunit gene to the short arm of human chromosome 11. DNA 1987; 6: 205–12.CrossRefGoogle Scholar
24Combamous, Y. Molecular basis of the specificity of binding of glycoprotein hormones to their receptors. Endocr Rev 1992; 13: 670–91.CrossRefGoogle Scholar
25Cole, LA, Perini, F, Birken, S, Ruddon, R. An oligosaccharide of the O-linked type distinguishes the free from the combined form of hCG α subunit. Biochem Biophys Res Commun 1984; 122: 1260–67.CrossRefGoogle ScholarPubMed
26Speroff, L, Glass, RH, Kase, NG. Hormone biosynthesis, metabolism and mechanism of action. In: Speroff, L, Glass, RH, Kase, NG eds. Clinical gynecologic endocrinology and infertility, fifth edition. Baltimore, MD: Williams and Wilkins, 1994: 3192.Google Scholar
27Boothby, M, Riddon, RW, Anderson, C, McWilliams, D, Boime, I. A single gonadotropin α-subunit gene in normal tissue and tumor-derived cell lines. J Biol Chem 1981; 256: 5121–27.CrossRefGoogle ScholarPubMed
28Silver, BJ, Bokar, JA, Virgin, JB, Vallen, EA, Milsted, A, Nilson, JH. Cyclic AMP regulation of the human glycoprotein hormone α-subunit gene is mediated by an 18-base-pair element. Proc Natl Acad Sci USA 1987; 84: 2198–202.CrossRefGoogle ScholarPubMed
29Deutsch, PJ, Jameson, JL, Habener, JF. Cyclic AMP responsiveness of human gonadotropin-α gene transcription is directed by a repeated 18-base pair enhancer: a-promotor receptivity to the enhancer confers cell-preferential expression. J Biol Chem 1987; 262: 12169–74.CrossRefGoogle Scholar
30Delegeane, AM, Ferland, LH, Mellon, PL. Tissue-specific enhancer of the human glycoprotein hormone α-subunit gene: dependence on cyclic AMP-inducible elements. Mol Cell Biol 1987; 7: 39944002.Google ScholarPubMed
31Jameson, JL, Hollenberg, AN. Regulation of chorionic gonadotropin gene expression. Endocr Rev 1993; 14: 203–21.Google ScholarPubMed
32Fiddes, JC, Talmadge, K. Structure, expression and evolution of the genes for the human glycoprotein hormones. Recent Prog Horm Res 1984; 40: 4378.Google ScholarPubMed
33Hussa, RO. Biosynthesis of human chorionic gonadotropin. Endocr Rev 1980; 1: 268–94.CrossRefGoogle ScholarPubMed
34Alpaugh, K, Indrapichate, K, Abel, JA, Rimerman, R, Wimalasena, J. Purification and characterization of the human ovarian LH/hCG receptor and comparison of the properties of mammalian LH/hCG receptors. Biochem Pharmacol 1990; 40: 2093–103.CrossRefGoogle ScholarPubMed
35Minegishi, T, Nakamura, K, Takakura, Y, Ibuki, Y, Igarashi, M. Cloning and sequencing of human FSH receptor cDNA. Biochem Biophys Res Commun 1991; 175: 1125–31.CrossRefGoogle ScholarPubMed
36Segaloff, DL, Ascoli, M. The lutropin/choriogonadotropin receptor … 4 years later. Endocr Rev 1993; 14: 324–47.Google ScholarPubMed
37Rodriguez, MC, Segaloff, DL. The orientation of the lutropin/choriogonadotropin receptor in rat luteal cells as revealed by site specific antibodies. Endocrinology 1990; 125: 674–81.CrossRefGoogle Scholar
38Salesse, R, Remy, JJ, Levin, JM, Jallal, B, Garnier, J. Towards understanding the glycoprotein hormone receptor. Biochimie 1991; 73: 109–20.CrossRefGoogle Scholar
39Dahl, KD, Stone, MP. FSH isoforms, radioimmunoassays, bioassays and their significance. J Androl 1992; 13: 1122.CrossRefGoogle ScholarPubMed
40Combarnous, Y, Henge, MH. Equine follicle-stimulating hormone. Purification, acid dissociation and binding to equine testicular tissue. J Biol Chem 1981; 256: 9567–72.CrossRefGoogle ScholarPubMed
41Chappel, SC, Ulloa-Aguirre, A, Coutifaris, C. Biosynthesis and secretion of follicle-stimulating hormone. Endocr Rev 1983; 4: 179211.CrossRefGoogle ScholarPubMed
42Moyle, WR, Erickson, G, Bahl, OP, Chiiotukoo, S, Gutowski, J. Action of PMSG and asialo-PMSG on rat Leydig and granulosa cells. Am J Physiol 1978; 235: E218E227.Google ScholarPubMed
43Cerpa-poljak, A, Bishop, LA, Hort, YJ et al. Isoelectric charge of recombinant human follicle-stimulating hormone isoforms determines receptor affinity and in vitro bioactivity. Endocrinology 1993; 132: 351–56.CrossRefGoogle ScholarPubMed
44Sairam, MR. Complete dissociation of gonadotropin receptor binding and signal transduction in mouse Leydig tumor cells - obligatory role of glycosylation in hormone action. Biochim J 1990; 265: 667–74.CrossRefGoogle ScholarPubMed
45Calvo, FO, Keutman, HT, Bergert, ER, Ryan, RJ. Deglycosylated human follitropin: characterization and effects on adenosine cyclic 3′5′-phosphate production in porcine granulosa cells. Biochemistry 1986; 25: 33938–43.CrossRefGoogle ScholarPubMed
46Matzuk, MM, Keene, JL, Boime, I. Site specific of the chorionic gonadotropin N-linked oligosaccharides in signal transduction. J Biol Chem 1989; 264: 2409–14.CrossRefGoogle ScholarPubMed
47Sairam, MR. Role of carbohydrates in glycoprotein hormone signal transduction. FASEB J 1989; 3: 1915–26.CrossRefGoogle ScholarPubMed
48Sairam, MR, Bhargavi, GN. A role for the glycosylation of the alpha-subunit in the transduction of biological signal in glycoprotein hormones. Science 1985; 229: 6567.CrossRefGoogle ScholarPubMed
49Chen, HC, Shimohigashi, Y, Dufau, ML, Catt, KJ. Characterization and biological properties of chemically deglycoslated human chorionic gonadotropin. Role of carbohydrate moieties in adenylate cyclase activation. J Biol Chem 1982; 257: 14446–52.CrossRefGoogle Scholar
50Sairam, MR, Manjunath, P. Hormonal antagonistic properties of chemically deglycosylated human choriogonadotropin. J Biol Chem 1983; 258: 445–59.CrossRefGoogle ScholarPubMed
51Richardson, MC, Masson, GM, Sairam, MR. Inhibitory action of chemically deglycosylated human chorionic gonadotropin on hormone-induced steroid production by dispersed cells from human corpus luteum. J Endocrinol 1984; 101: 327–32.CrossRefGoogle ScholarPubMed
52Dahl, KD, Bicsak, TA, Hsueh, AJW. Naturally occurring antihormones: secretion of FSH antagonists by women treated with GnRH analog Science 1988; 239: 7274.CrossRefGoogle ScholarPubMed
53Kawasaki, T, Ashwell, G. Chemical and physical properties of a hepatic membrane protein that specifically binds asialoglycoproteins. J Biol Chem 1976; 251: 12961302.CrossRefGoogle ScholarPubMed
54Belchetz, PE, Plant, TM, Nakai, Y, Keogh, EG, Knobil, E. Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science 1978; 202: 631–33.CrossRefGoogle Scholar
55Valk, TW, Corley, KP, Kelch, RP, Marshall, JC. Hypogonadotropic hypogonadism: hormonal response to low dose pulsatile administration of gonadotropin-releasing hormone. J Clin Endocrinol Metab 1980; 51: 730–38.CrossRefGoogle ScholarPubMed
56Hoffman, AR, Crowley, WF Jr. Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone. N Engl J Med 1982; 307: 1237–41.CrossRefGoogle Scholar
57Wildt, L, Hausler, A, Marshall, G et al. Frequency and amplitude of gonadotropin-releasing hormone stimulation and gonadotropin secretion in the rhesus monkey. Endocrinology 1981; 109: 376–85.CrossRefGoogle ScholarPubMed
58Pohl, CR, Richardson, DW, Hutchinson, JS, Germak, JA, Knobil, E. Hypophysiotropic signal frequency and the functioning of the pituitary-ovarian system in the rhesus monkey. Endocrinology 1983; 112: 2076–80.CrossRefGoogle ScholarPubMed
59Clarke, IJ, Cummins, JT, Findlay, JK, Burman, KJ, Doughton, DW. Effects on plasma luteinizing hormone and follicle-stimulating hormone of varying the frequency and amplitude of gonadotropin-releasing hormone pulses in ovariectomized ewes with hypothalamo-pituitary disconnection. Neuroendocrinology 1984; 39: 214–21.CrossRefGoogle ScholarPubMed
60Marshall, JC, Dalkin, AC, Haisenleder, DJ, Kerrigan, JR, Kirk, SE, Yasin, M. Pituitary translation of the pulsatile GnRH message. In: Filicori, M, Flamigni, C eds. Ovulation induction: basic science and clinical advances. Amsterdam: Excerpta Medica, 1994: 1119.Google Scholar
61Midgley, AR, Jaffe, RB. Regulation of human gonadotropins. Episodic fluctuations of LH during the menstrual cycle. J Clin Endocrinol Metab 1971; 33: 962–69.CrossRefGoogle ScholarPubMed
62Yen, SSC, Tsai, CC, Naftolin, F, Vandenberg, G, Ajabor, L. Pulsatile patterns of gonadotropin release in subjects with and without ovarian function. J Clin Endocrinol Metab 1972; 34: 671–5.CrossRefGoogle ScholarPubMed
63Karsch, FJ, Bittman, EL, Foster, D, Robinson, JE. Neuroendocrine basis of seasonal reproduction. Recent Prog Horm Res 1984; 40: 185211.Google ScholarPubMed
64Gharib, SD, Bowers, SM, Need, LR, Chin, WW. Regulation of rat LH subunit mRNAs by gonadal steroid hormones. J Clin Invest 1986; 77: 582–89.CrossRefGoogle ScholarPubMed
65Gharib, SD, Wierman, ME, Badger, TM, Chin, WW. Sex steroid hormone regulation of follicle-stimulating hormone subunit messenger ribonucleic acid (mRNA) levels in the rat. J Clin Invest 1987; 80: 294–99.CrossRefGoogle ScholarPubMed
66Saade, G, London, DR, Clayton, RN. The interaction of gonadotropin-releasing hormone and estradiol on luteinizing hormone and prolactin gene expression in female hypogonadal (hpg) mice. Endocrinology 1989; 124: 1744–53.CrossRefGoogle ScholarPubMed
67Mason, AJ, Hayflick, JS, Zoeller, RT et al. A Deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse. Science 1986; 234: 1366–71.CrossRefGoogle ScholarPubMed
68Wise, PM, Campo-Grossman, P, Barraclough, CA. Effects of estradiol and progesterone on plasma gonadotropins, prolactin, and LHRH in specific brain areas of ovariectomized rats. Biol Reprod 1981; 24: 820–30.CrossRefGoogle ScholarPubMed
69Clarke, IJ, Cummins, JT. Increased gonadotropin-releasing hormone pulse frequency associated with estrogen-induced luteinizing hormone surges in ovariectomized ewes. Endocrinology 1985; 116: 2376–83.CrossRefGoogle ScholarPubMed
70Neill, JD, Patton, JM, Daily, RA, Tsou, RC, Tindall, GT. Luteinizing hormone releasing hormone (LHRH) in pituitary stalk blood of rhesus monkeys: relationship to level of LH release. Endocrinology 1977; 101: 430–34.CrossRefGoogle ScholarPubMed
71Knobil, E. The neuroendocrine control of the menstrual cycle. Recent Prog Horm Res 1981; 36: 5388.Google Scholar
72Van Vugt, DA, Lam, NY, Ferin, M. Reduced frequency of pulsatile luteinizing hormone secretion in the luteal phase of the rhesus monkey: involvement of endogenous opiates. Endocrinology 1984; 115: 1095–101.CrossRefGoogle ScholarPubMed
73Marshall, JC, Kelch, RP. Gonadotropin-releasing hormone: role of pulsatile secretion in the regulation of reproduction. N Engl J Med 1986; 315: 1459–68.Google ScholarPubMed
74Soules, MR, Steiner, RA, Clifton, DK, Cohen, NL, Aksel, S, Bremner, WJ. Progesterone modulation of pulsatile luteinizing hormone secretion in normal women. J Clin Endocrinol Metab 1984; 58: 378–83.CrossRefGoogle ScholarPubMed
75Hamernik, DL, Kim, KE, Maurer, RA, Nett, TM. Progesterone does not affect the amount of mRNA for gonadotropins in the anterior pituitary gland of ovariectomized ewes. Biol Reprod 1987; 37: 1225–32.CrossRefGoogle Scholar
76Counis, R, Corbani, M, Jutisz, M. Estradiol regulates mRNAs encoding precursors to rat lutropin (LH) and follitropin (FSH) subunits. Biochem Biophys Res Commun 1983; 114: 6572.CrossRefGoogle ScholarPubMed
77Simard, J, Labrie, C, Hubert, JF, Labrie, F. Modulation by sex steroids and [D-TRP6, des-Gyl-NH210] luteinizing hormone (LH)-releasing hormone ethylamide of α subunit and LHβ messenger ribonucleic acid levels in the rat anterior pituitary gland. Mol Endocrinol 1988; 2: 775–84.CrossRefGoogle Scholar
78Wang, QF, Famworth, PG, Findlay, JK, Burger, HG. Inhibitory effect of pure 31-kilodalton bovine inhibin on gonadotropin-releasing hormone (GnRH)-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells. Endocrinology 1989; 124: 363–68.CrossRefGoogle ScholarPubMed
79Culler, MD, Negro-Vilar, A. Endogenous inhibin suppresses only basal follicle-stimulating hormone secretion but suppresses all parameters of pulsatile luteinizing hormone secretion in the diestrous female rate. Endocrinology 1989; 124: 2944–53.CrossRefGoogle Scholar
80Campen, CA, Vale, W. Interaction between purified ovine inhibin and steroid on the release of gonadotropins from cultured pituitary cells. Endocrinology 1988; 123: 1320–28.CrossRefGoogle Scholar
81Wide, L, Bakos, O. More basic forms of both human follicle-stimulating hormone and luteinizing hormone in serum at midcycle compared with the follicular or luteal phase. J Clin Endocrinol Metab 1993; 76: 885–89.Google ScholarPubMed
82Stanton, PG, Robertson, DM, Burgon, PG, Schmauk-White, B, Hearn, MTW. Isolation and physicochemical characterization of human follicle-stimulating isoforms. Endocrinology 1992; 130: 2820–32.CrossRefGoogle ScholarPubMed
83Chappel, SC, Bethea, CL, Spies, HG. Existence of multiple forms of follicle-stimulating hormone within the anterior pituitaries of cyanomolgue monkeys. Endocrinology 1984; 115: 452–61.CrossRefGoogle ScholarPubMed
84Padmanabhan, V, Lang, LL, Sonstein, J, Kelch, RP, Beitinis, IZ. Modulation of serum follicle-Stimulating hormone bioactivity and isoform distribution by estrogenic stroids in normal women and in gonadal dysgenesis. J Clin Endocrinol Metab 1988; 67: 465–73.CrossRefGoogle Scholar
85Ulla-Aguirre, A, Espinoza, R, Damian-Matsumura, P, Chappel, SC. Immunological and biological potencies of different molecular species of gonadotropin. Hum Reprod 1988; 3: 491501.CrossRefGoogle Scholar
86Ulloa-Aguirre, A, Chappel, SC. Multiple species of follicle-stimulating hormone exist within the anterior pituitary gland of male golden hamsters. J Endocrinol 1982; 95: 257–62.CrossRefGoogle ScholarPubMed
87Chappel, SC, Ulloa-Aguirre, A, Ramaley, JA. Sexual maturation in female rats: time course of the appearance of multiple species of anterior pituitary FSH. Biol Reprod 1982; 29: 196207.Google Scholar
88Galle, P, Ulloa-Aguirre, A, Chappel, SC. Effects of estradiol phenobarbitone and LHRH upon isoelectric focusing profile of pituitary follicle-stimulating hormone in ovariectomized hamster. J Endocrinol 1983; 99: 3140.CrossRefGoogle Scholar
89Wide, L. Male and female forms of human follicle-stimulating hormone in serum. J Clin Endocrinol Metab 1982; 55: 682–88.CrossRefGoogle ScholarPubMed
90Stokman, PGW, De Leeuw, R, Van Der Wijngaard, HAGW, Kloosterboer, HJ, Vemer, HM, Sanders, ALM. Human chorionic gonadotropin in commercial human menopausal gonadotropin preparations. Fertil Steril 1993; 60: 175–78.CrossRefGoogle ScholarPubMed
91Duijkers, UM, Beerens, MC, Coelingh-Bennink, HJT, Huisman, JAM, Rombout, F, Vemer, HM. Pharmacokinetics of two human menopausal gonadotropin preparations after single intravenous administration during pituitary suppression. Hum Reprod 1995; 10: 1367–72.CrossRefGoogle ScholarPubMed
92Keene, JL, Matzuk, MM, Otani, T et al. Expression of biologically active human follitropin in Chinese hamster ovary cells. J Biol Chem 1989; 246: 4769–75.CrossRefGoogle Scholar
93Yen, SSC, Llerena, LA, Pearson, OH, Littell, AS. Disappearance rates of endogenous follicle-stimulating hormone in serum following surgical hypophysectomy in man. J Clin Endocrinol Metab 1970; 30: 325–29.CrossRefGoogle ScholarPubMed
94Amin, HK, Hunter, WM. Human pituitary follicle-stimulating hormone: distribution, plasma clearance and urinary excretion as determined by radioimmunoassay. J Endocrinol 1970; 48: 307–17.CrossRefGoogle ScholarPubMed
95Diczfalusy, E, Harlin, J. Clinical-pharmacological studies on human menopausal gonadotropin. Hum Reprod 1988; 3: 2127.CrossRefGoogle Scholar
96Urban, RJ, Padmanabhan, V, Beitinis, I, Veldhuis, JD. Metabolic clearance of human follicle-stimulating hormone assessed by radioimmunoassay, immunoradiometric assay, and in vitro Sertoli cell bioassay. J Clin Endocrinol Metab 1991; 73: 818–23.CrossRefGoogle ScholarPubMed
97Jockenhövel, F, Fingscheidt, U, Khan, SA, Behre, HM, Nieschlag, E. Bio and immuno-activity of FSH in serum after intramuscular injection of highly purified urinary human FSH in normal men. Clin Endocrinol 1990; 33: 573–84.CrossRefGoogle ScholarPubMed
98Mizunuma, H, Takagi, T, Honjyo, S, Ibuki, Y, Igarashi, M. Clinical pharmacodynamics of urinary follicle-stimulating hormone and its application for pharmacokinetics simulation program. Fertil Steril 1990; 53: 440–45.CrossRefGoogle ScholarPubMed
99Dobbs, KE, Dumesic, DA, Dumesic, JA, Shapiro, SS. Differences in serum follicle-stimulating hormone uptake after intramuscular and subcutaneous human menopausal gonadotropin injection. Fertil Steril 1994; 62: 978–83.CrossRefGoogle ScholarPubMed
100Handelsman, DJ, Turner, L, Boylan, LM, Conway, AJ. Pharmacokinetics of human follicle-stimulating hormone in gonadotropin-deficient men. J Clin Endocrinol Metab 1995; 80: 1657–63.Google ScholarPubMed
101le Cotonnec, J-Y, Porchet, HC, Beltrami, V, Howles, C. Comparative pharmacokinetics of two urinary human follicle stimulating hormone preparations in healthy female and male volunteers. Hum Reprod 1993; 8: 1604–11.CrossRefGoogle ScholarPubMed
102Mannaerts, B, De Leeuw, R, Geelen, J et al. Comparative in vitro and in vivo studies on the biological characteristics of recombinant human follicle-stimulating hormone. Endocrinology 1991; 129: 2623–30.CrossRefGoogle ScholarPubMed
103le Cotonnec, J-Y, Porchet, HC, Beltrami, V, Khan, A, Toon, S, Rowland, M. Clinical pharmacology of recombinant human follicle-stimulating hormone (FSH). I. Comparative pharmacokinetics with urinary human FSH. Fertil Steril 1994; 61: 669–78.CrossRefGoogle ScholarPubMed
104le Cotonnec, J-Y, Porchet, HC, Beltrami, V, Khan, A, Toon, S, Rowland, M. Clinical pharmacology of recombinant human follicle-stimulating hormone II.Single doses and steady state pharmacokinetics. Fertil Steril 1994; 61: 679–86.CrossRefGoogle Scholar
105Mannaerts, B, Shoham, Z, Schoot, D et al. Single-dose pharmacokinetics and pharmacodynamics of recombinant human follicle-stimulating hormone (Org 32489) in gonadotropin-deficient volunteers. Fertil Steril 1993; 59: 108–14.CrossRefGoogle ScholarPubMed
106Zuidema, S, Pieters, FA, Duchateau, GS. Release and absorption rate aspects of intramuscular injected Pharmaceuticals. Int J Pharm 1988; 47: 112.CrossRefGoogle Scholar
107Matikainen, T, De Leeuw, R, Mannaerts, B, Huhtaniemi, I. Circulating bioactive and immunoreactive recombinant human follicle-stimulating hormone (Org 32489) after administration of gonadotropin deficient subjects. Fertil Steril 1994; 61: 6269.CrossRefGoogle ScholarPubMed
108Shoham, Z, Mannaerts, B, Insler, V, Coelingh-Bennink, H. Induction of follicular growth using recombinant human follicle-stimulating hormone in two volunteer women with hypogonadotropic hypogonadism. Fertil Steril 1993; 59: 738–42.CrossRefGoogle ScholarPubMed
109Porchet, HC, le Cotonnec, J-Y, Loumaye, E. Clinical pharmacology of recombinant human follicle-stimulating hormone. III. Pharmacokinetics-pharmacodynamic modeling after repeat subcutaneous administration. Fertil Steril 1994; 61: 687–95.CrossRefGoogle Scholar
110Schoot, D, Coelingh-Bennink, H, Mannaerts, B, Lamberts, S, Bouchard, P, Fauser, B. Human recombinant follicle-stimulating hormone induces growth of preovulatory follicles without concomitant increase in androgen and estrogen biosynthesis in a woman with isolated gonadotropin deficiency. J Clin Endocrinol Metab 1992; 74: 1471–73.Google Scholar
111Yen, SSC, Llerna, O, Little, B, Pearson, OH. Disappearance rates of endogenous luteinizing hormone and chorionic gonadotropin in man. J Clin Endocrinol 1968; 28: 1763–67.CrossRefGoogle ScholarPubMed
112Kjeld, JM, Harsoulis, P, Kuku, SF, Marshall, JC, Kaufman, B, Fauser, TR. Infusion of hFHS and hLH in normal men. Acta Endocrinol 1976; 81: 225–33.Google Scholar
113Porchet, HC, le Cotonnec, J-Y, Neuteboom, B, Canalli, S, Zanolo, G. Pharmacokinetics of recombinant human luteinizing hormone after intravenous, intramuscular and subcutaneous administration in monkeys and comparison with intravenous administration of pituitary human luteinizing hormone. J Clin Endocrinol Metab 1995; 80: 667–73.Google ScholarPubMed
114Porchet, HC, Munafo, A, Beltrami, V, le Cotonnec, J-Y. Clinical pharmacology of rhLH (Lhaditm). Hum Reprod 1994, 9S4: 23.Google Scholar
115Wide, L, Johannisson, E, Tillinger, K-G, Diczfalusy, E. Metabolic clearance of human chorionic gonadotropin administered to non pregnant women. Acta Endocrinol 1968; 59: 579–94.Google ScholarPubMed
116Rizkallah, T, Gurpide, E, Vande, Wiele RL. Metabolism of HCG in man. J Clin Endocrinol 1969; 29: 92100.CrossRefGoogle ScholarPubMed
117Saal, W, Glowania, H-J, Hengst, W, Happ, J. Pharmacodynamics and pharmacokinetics after subcutaneous and intramuscular injection of human chorionic gonadotropin. Fertil Steril 1991; 56: 225–29.CrossRefGoogle ScholarPubMed
118Martikainen, H, Huhtaniemi, I, Vihko, R. Response of peripheral serum sex steroids and some of their precursors to a single injection of hCG in adult men. Clin Endocrinol (Oxf) 1980; 13: 157–66.CrossRefGoogle ScholarPubMed
119Saez, JM, Forest, MG. Kinetics of human chorionic gonadotropin-induced steroidogenic response of the human testis. I. Plasma testosterone: implications for human chorionic gonadotropin stimulation test. J Clin Endocrinol Metab 1979; 49: 278–83.CrossRefGoogle ScholarPubMed
120Ryan, KJ, Petro, F, Kaiser, J. Steroid formation by isolated and recombinant ovarian granulosa and theca cells. J Clin Endocrinol Metab 1968; 28: 355–58.CrossRefGoogle Scholar
121Erickson, GF, Magofffin, DA, Dyer, CA, Hofeditz, C. The ovarian androgen producing cells: a review of structure/function relationships. Endocr Rev 1985; 6: 371–99.CrossRefGoogle Scholar
122McNatty, KP, Markis, A, DeGrazia, C, Osathanondh, R, Ryan, KJ. Steroidogenesis by recombinant follicular cells from the human ovary in vitro. J Clin Endocrinol Metab 1980; 51: 1286–92.CrossRefGoogle ScholarPubMed
123Gougeon, A. Dynamics of follicular growth in the human: a model from preliminary results. Hum Reprod 1986; 1: 8187.CrossRefGoogle Scholar
124Baird, DT, Baker, TF, McNatty, KP, Neal, P. Relationship between the secretion of the corpus luteum and the length of the follicular phase of the ovarian cycle. J Reprod Fertil 1975; 45: 611–19.CrossRefGoogle ScholarPubMed
125Zeleznik, AJ, Kubik, CJ. Ovarian responses in Macaques to pulsatile infusion of follicle-stimulating hormone (FSH) and luteinizing hormone: increased sensitivity of the maturing follicle to FSH. Endocrinology 1986; 119: 2025–32.CrossRefGoogle ScholarPubMed
126Van Weissenbruch, MM. Gonadotropins for induction of ovulation, immunological, pharmacological and clinical studies [Dissertation]. Amsterdam: Free University, 1990.Google Scholar
127Van Santbrink, EJP, Hop, WC, Van Dessel, TJHM, de Jong, FH, Fauser, BCJM. Decremental follicle-stimulating hormone and dominant follicle development during the normal menstrual cycle. Fertil Steril 1995; 64: 3743.CrossRefGoogle ScholarPubMed
128Benadiva, CA, Ben-Rafael, Z, Strauss, JF III, Mastroianni, L Jr, Flickinger, GL. Ovarian response of individuals to different doses of human menopausal gonadotropin. Fertil Steril 1988; 49: 9971001.CrossRefGoogle ScholarPubMed
129Ben-Rafael, Z, Lipitz, S, Bider, D, Mashiach, S. Ovarian hyporesponsiveness in combined gonadotropin-releasing hormone agonist and menotropin therapy is associated with low serum follicle-stimulating hormone levels. Fertil Steril 1991; 55: 272–75.CrossRefGoogle ScholarPubMed
130Benadiva, CA, Ben-Rafael, Z, Blasco, L, Tureck, R, Mastroianni, L Jr, Flickinger, GL. Ovarian response to human menopausal gonadotropin following suppression with oral contraceptives. Fertil Steril 1988; 50: 516–18.CrossRefGoogle ScholarPubMed
131Riklein, TA, Mishell, DR. Gonadotropin, prolactin and steroid hormone levels after discontinuation of oral contraceptives. Am J Obstet Gynecol 1977; 127: 585–89.Google Scholar
132Couzinet, B, Lestrat, N, Brailly, S, Forest, M, Schaison, G. Stimulation of ovarian follicular maturation with pure follicle-stimulating hormone in women with gonadotropin deficiency. J Clin Endocrinol Metab 1988; 66: 552–56.CrossRefGoogle ScholarPubMed
133Shoham, Z, Balen, A, Patel, A, Jacobs, HS. Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients. Fertil Steril 1991; 56: 1048–53.CrossRefGoogle ScholarPubMed
134Sherizly, I, Galiani, D, Dekel, N. Regulation of oocyte maturation. Communication in the rat cumulus-oocyte complex. Hum Reprod 1988; 3: 761–66.CrossRefGoogle ScholarPubMed
135Dekel, N, Lawrence, TS, Gilula, NB, Beers, WH. Modulation of cell-to-cell communication in the cumulus-oocyte complex and the regulation of oocyte maturation by LH. Dev Biol 1981; 86: 356–62.CrossRefGoogle ScholarPubMed
136Schultz, RM, Montgomery, RR, Belanoff, JR. Regulation of mouse oocyte meiotic maturation: implication of a decrease in oocyte cAMP and protein dephosphorylation in commitment to resume meiosis. Dev Biol 1983; 97: 264–73.CrossRefGoogle ScholarPubMed
137Vivarelli, E, Conti, M, de Felici, M, Siracusa, G. Meiotic resumption and intracellular cAMP levels in mouse oocytes treated with compounds which act on cAMP metabolism. Cell Differ 1983; 12: 271–76.CrossRefGoogle ScholarPubMed
138Aberdam, E, Hanski, E, Dekel, N. Maintenance of meiotic arrest in isolated rat oocytes by the invasive adenylate cyclase of Bordetella pertussis. Biol Reprod 1987; 36: 530–35.CrossRefGoogle ScholarPubMed
139Yoshimura, Y, Santulli, R, Atlas, SJ, Fuji, S, Wallach, EE. The effects of proteolytic enzymes on in vitro ovulation in the rabbit. Am J Obstet Gynecol 1987; 157: 468–75.CrossRefGoogle ScholarPubMed
140Coelingh-Bennink, HJT, Bouchard, P, Devroey, P, Fauser, BCJM, Harlin, J, Shoham, Z. Potential clinical applications of recombinant FSH. In: Filicori, M, Flamigni, C eds. Ovulation induction, basic science and clinical advances. Amsterdam: Excerpta Medica, 1994: 219–25.Google Scholar
141Thompson, CR, Hansen, LM. Pergonal (menotropins): a summary of clinical experience in the induction of ovulation and pregnancy. Fertil Steril 1970; 21: 844–53.CrossRefGoogle ScholarPubMed
142Rabau, E, David, A, Serr, DM, Mashiach, S, Lunenfeld, B. Human menopausal gonadotropin for anovulation and sterility. Am J Obstet Gynecol 1967; 98: 9298.CrossRefGoogle ScholarPubMed
143Taymor, ML, Sturgis, SH, Goldstein, DP, Lieberman, B. Induction of ovulation with human postmenopausal gonadotropin. Fertil Steril 1967; 18: 181–90.CrossRefGoogle ScholarPubMed
144Fauser, BCJM. Step-down follicle-stimulating hormone regimens in polycystic ovary syndrome. In: Filicori, M, Flamigni, C eds. Ovulation induction, basic science and clinical advances. Amsterdam: Excerpta Medica, 1994: 153–62.Google Scholar
145Schenker, JB, Weinstein, D. Ovarian hyperstimulation syndrome: a current survey. Fertil Steril 1978; 30: 255–62.Google ScholarPubMed
146Tonetta, SA, DiZerega, GS. Intragonadal regulation of follicular maturation. Endocr Rev 1989; 10: 205–29.CrossRefGoogle ScholarPubMed
147Homburg, R, Pariente, C, Lunenfeld, B, Jacobs, HS. The role of insulin-like growth factor I (IGF-I) and IGF binding protein I (IGFBP-I) in the pathogenesis of polycystic ovary syndrome. Hum Reprod 1992; 7: 1379–83.CrossRefGoogle Scholar
148Kamrava, MM, Seibel, MM, Berger, MK, Thompson, I, Taymor, ML. Reversal of persistent anovulation in polycystic ovarian disease by administration of chronic low dose follicle-stimulating hormone. Fertil Steril 1982; 37: 520–23.CrossRefGoogle ScholarPubMed
149Polson, DW, Mason, HD, Kiddy, DS, Winston, RML, Margara, R, Franks, S. Low dose follicle-stimulating hormone in the treatment of polycystic ovary syndrome: a comparison of pulsatile subcutaneous with daily intramuscular therapy. Br J Obstet Gynaecol 1989; 96: 746–48.Google ScholarPubMed
150Sagle, MA, Hamilton-Fairley, D, Kiddy, DS, Franks, S. A comparative randomized study of low dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome. Fertil Steril 1991; 55: 5660.CrossRefGoogle ScholarPubMed
151Franks, S, Polson, DW, Sagle, M, Hamilton-Fairley, D, White, DM. Low-dose gonadotropin regimens for induction of ovulation. In: Filicori, M, Flamigni, C eds. Ovulation induction, basic science and clinical advances. Amsterdam: Excerpta Medica, 1994: 145–51.Google Scholar
152Buvat, JB, Buvat-Herbaut, M, Marcolin, G, Dehaene, JL, Verbecq, P, Renouard, O. Purified follicle-stimulating hormone in polycystic ovary syndrome: slow administration is safer and more effective. Fertil Steril 1989; 52: 553–59.CrossRefGoogle ScholarPubMed
153Shoham, Z, Patel, A, Jacobs, HS. Polycystic ovarian syndrome: safety and effectiveness of stepwise and low dose administration of purified follicle-stimulating hormone. Fertil Steril 1991; 55: 1051–56.CrossRefGoogle ScholarPubMed
154Homburg, R, Levy, T, Ben-Rafael, Z. A comparative prospective study of conventional regimen with chronic low-dose administration of follicle-stimulating hormone for anovulation associated with polycystic ovary syndrome. Fertil Steril 1995; 63: 729–33.CrossRefGoogle ScholarPubMed
155Herman, A, Ron-El, R, Golan, A, Soffer, Y, Bukovsky, I, Capsi, E. Overstimulated cycles under low-dose gonadotropins in patients with polycystic ovary syndrome: characterization and management. Hum Reprod 1993; 8: 3034.CrossRefGoogle ScholarPubMed
156Mizunuma, H, Takagi, T, Yamada, K, Ibuki, Y, Igarashi, M. Ovulation induction by step-down administration of purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome. Fertil Steril 1991; 55: 1195–97.CrossRefGoogle ScholarPubMed
157Blankstein, J, Shalev, J, Saadon, T et al. Ovarian hyperstimulation syndrome: prediction by number and size of preovulatory ovarian follicles. Fertil Steril 1987; 47: 597602.CrossRefGoogle ScholarPubMed
158School, DC, Pache, TD, Hop, WC, De Jong, FH, Fauser, BCJM. Growth pattern of ovarian follicles during induction of ovulation with decreasing doses of human menopausal gonadotropin following presumed selection in polycystic ovary syndrome. Fertil Steril 1992; 57: 1117–20.Google Scholar
159Fauser, BC, Schoot, DC, Van Dessel, T. Serum hormone levels during gonadotropin induction of ovulation in a decremental dose regimen in PCOS [Abstract]. 75th Annual Meeting of the Endocrine Society, Las Vegas. Bethesda, MD: Endocrine Society Press, 1993: 75 [Abstract 100].Google Scholar
160Van Santbrink, EJP, Donderwinkel, PFJ, Van Dessel, TJHM, Fauser, BCJM. Gonadotropin induction of ovulation using a step-down dose regimen: single-centre clinical experience in 82 patients. Hum Reprod 1995; 10: 1048–53.CrossRefGoogle ScholarPubMed
161Steinkampf, MP, Banks, KS. Step-down versus conventional FSH treatment in patients with WHO group II amenorrhea: results of a US multicenter clinical trial [Abstract]. American Fertility Society Annual Meeting, Montreal, Canada. Birmingham, AL, American Fertility Society, 1993: S21S22 (Abstract 0–044).Google Scholar
162Ben-Rafael, Z, Levy, T, Schoemaker, J. Pharmacokinetics of follicle-stimulating hormone: clinical significance. Fertil Steril 1995; 63: 689700.Google ScholarPubMed
163Shoham, Z, Schachter, M, Loumaye, E, Weissman, A, MacNamee, M, Insler, V. The luteinizing hormone surge – the final stage in ovulation induction: modern aspects of ovulation triggering. Fertil Steril 1995; 64: 237–51.Google ScholarPubMed
164Messinis, IE, Templeton, A. In vivo bioactivity of gonadotropin surge attenuating factor (GnSAF). Clin Endocrinol (Oxf) 1990; 32: 213–18.CrossRefGoogle Scholar
165Gidley-baird, AA, O'Neill, C, Sinosich, MJ, Porter, RN, Pike, IL, Saunders, DM. Failure of implantation in human in vitro fertilization and embryo transfer patients: the effect of altered progesterone/estrogen ratios in human and in mice. Fertil Steril 1986; 45: 6974.CrossRefGoogle Scholar
166Forman, R, Fries, N, Testart, J, Belaisch-Allart, J, Hazout, A, Frydman, R. Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation. Fertil Steril 1988; 49: 118–22.CrossRefGoogle ScholarPubMed
167Yding, Anderson C, Westergaard, IG, Figenschau, Y, Bertheussen, K, Forsdahl, F. Endocrine composition of follicular fluid comparing human chorionic gonadotropin to a gonadotropin-releasing hormone agonist for ovulation induction. Hum Reprod 1993; 8: 840–43.Google Scholar
168Imoeddemhe, DAG, Sigue, AB, Pacpaco, ELA, Olazo, AB. Stimulation of endogenous surge of luteinizing hormone with gonadotropin-releasing hormone analog after ovarian stimulation for in vitro fertilization. Fertil Steril 1991; 55: 328–32.CrossRefGoogle Scholar
169Kenigsberg, D, Littman, BA, Williams, RF, Hodgen, GD. Medical hypophysectomy. II. Variability of ovarian response to gonadotropin therapy. Fertil Steril 1984; 42: 116–26.CrossRefGoogle ScholarPubMed
170Zelinski-Wooten, MB, Hutchinson, JS, Hess, DL, Wolf, DP, Stouffer, RL. Follicle stimulating hormone alone supports follicle growth and oocyte development in gonadotropin-releasing hormone antagonist-treated monkeys. Hum Reprod 1995; 10: 1658–66.CrossRefGoogle ScholarPubMed
171Punnonen, R, Ashorn, R, Vilja, P, Heinonen, PK, Kujansuu, E, Tuohimaa, P. Spontaneous luteinizing hormone surge and cleavage of in vitro fertilized embryos. Fertil Steril 1988; 49: 479–82.CrossRefGoogle ScholarPubMed
172Homburg, R, Eshel, A, Kilborn, J, Adams, J, Jacobs, HS. Combined luteinising hormone releasing hormone analogue and exogenous gonadotropins for the treatment of infertility associated with polycystic ovaries. Hum Reprod 1990; 5: 3235.CrossRefGoogle ScholarPubMed
173Homburg, R, Berkowitz, D, Levy, T, Feldberg, D, Ashkenazi, J, Ben-Rafael, Z. In vitro fertilization and embryo transfer for the treatment of infertility associated with polycystic ovary syndrome. Fertil Steril 1993; 60: 858–63.CrossRefGoogle ScholarPubMed
174Loumaye, E, Porchet, HC, Beltrami, V et al. Ovulation induction with recombinant follicle-stimulating hormone and luteinizing hormone. In: Filicori, M, Flamigni, C eds. Ovulation induction, basic science and clinical advances. Amsterdam: Excerpta Medica, 1994: 227–36.Google Scholar
175Anderson, RE, Cragun, JM, Chang, RJ, Stanczyk, FZ, Lobo, RA. A pharmacodynamic comparison of human urinary follicle-stimulating hormone and human menopausal gonadotropin in normal women and polycystic ovary syndrome. Fertil Steril 1989; 52: 216–20.CrossRefGoogle ScholarPubMed
176Van Weissenbruch, MM, Schoemaker, HC, Drexhage, HA, Schoemaker, J. Pharmaco-dynamics of human menopausal gonadotropin (HMG) and follicle-stimulating hormone (FSH). The importance of the FSH concentration in initiating follicular growth in polycystic ovary-like disease. Hum Reprod 1993; 8: 813–21.CrossRefGoogle ScholarPubMed
177Daya, S, Gunby, J, Hughes, EG, Collins, JA, Sagle, MA. Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization cycles: a meta-analysis. Fertil Steril 1995; 64: 347–54.CrossRefGoogle ScholarPubMed