Estetrol review: Profile and potential clinical applications

Climacteric

Volumn 11, Issue SUPPL. 1, 2008, Pages 47-58

  Coelingh Bennink, H J T ^a   Holinka, C F ^b   Diczfalusy, E ^c  

^a Pantarhei Bioscience   (Netherlands)

^b PharmConsult   (United States)

^c KAROLINSKA INSTITUTE   (Sweden)

Author keywords

E4; Estetrol; Review

Indexed keywords

ADRENERGIC RECEPTOR; ANDROSTANOLONE; DIMETHYLBENZ[A]ANTHRACENE; ESTETROL; ESTRADIOL; ESTRIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; ESTRONE; ETHINYLESTRADIOL; FOLLITROPIN; LUTEINIZING HORMONE; MORPHINE; NALOXONE; ORAL CONTRACEPTIVE AGENT; OSTEOCALCIN; PROGESTERONE RECEPTOR; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TAMOXIFEN; TESTOSTERONE;

AUTOIMMUNE DISEASE; BONE; BONE DENSITY; BREAST CANCER; CARDIOVASCULAR DISEASE; CELL STRAIN MCF 7; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG CLASSIFICATION; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG SELECTIVITY; DYSPAREUNIA; ENDOMETRIUM; ESTROGEN ACTIVITY; ESTROGEN DEFICIENCY; ESTROGEN THERAPY; FETUS LIVER; FOLLITROPIN BLOOD LEVEL; GYNECOLOGIC DISEASE; HORMONAL CONTRACEPTION; HORMONE RECEPTOR INTERACTION; HORMONE SUBSTITUTION; HORMONE SYNTHESIS; HOT FLUSH; HUMAN; ISOTOPE LABELING; KERATINIZATION; LIBIDO DISORDER; LIQUID CHROMATOGRAPHY; LIVER METABOLISM; LUTEINIZING HORMONE BLOOD LEVEL; MASS SPECTROMETRY; MATERNAL PLASMA; MIGRAINE; MORPHINE ADDICTION; NONHUMAN; ORAL CONTRACEPTION; OSTEOPOROSIS; OVARIECTOMY; OVULATION INHIBITION; POSTMENOPAUSE; POSTMENOPAUSE OSTEOPOROSIS; PREGNANCY; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN BINDING; RECEPTOR BINDING; REVIEW; SINGLE DRUG DOSE; TREATMENT INDICATION; UTERUS WEIGHT; VAGINA ATROPHY; VAGINA EPITHELIUM; WRINKLE;

ESTETROL; ESTROGEN RECEPTOR MODULATORS; ESTROGEN REPLACEMENT THERAPY; FEMALE; HOT FLASHES; HUMANS; MENOPAUSE; RECEPTORS, ESTROGEN; RISK ASSESSMENT; SAFETY; WOMEN'S HEALTH;

EID: 48249091684     PISSN: 13697137     EISSN: 14730804     Source Type: Journal    
DOI: 10.1080/13697130802073425     Document Type: Review

References (47)

1. Hagen AA, Barr M, Diczfalusy E. Metabolism of 17β-oestradiol-4-14C in early infancy. Acta Endocrinol 1965;49:207-20
2. Gurpide E, Schwers J, Welch MT, Vande Wiele RL, Lieberman S. Fetal and maternal metabolism of estradiol during pregnancy. J Clin Endocrinol Metab 1966;26:1355-65
3. Zucconi G, Lisboa BP, Simonitsch E, Roth L, Hagen AA, Diczfalusy E. Isolation of 15α-hydroxyl-oestriol from pregnancy urine and from the urine of newborn infants. Acta Endocrinol 1967;56:413-23
4. Schwers J, Eriksson G, Wiqvist N, Diczfalusy E. 15α-hydroxylation: a new pathway of estrogen metabolism in the human fetus and newborn. Biochim Biophys Acta 1965;100:313-16
5. Schwers J, Govaerts-Videtsky M, Wiqvist N, Diczfalusy E. Metabolism of oestrone sulphate by the previable human foetus. Acta Endocrinol 1965;50:597-610
6. Mancuso S, Benagiano G, Dell'Acqua S, Shapiro M, Wiqvist N, Diczfalusy E. Studies on the metabolism of C-19 steroids in the human foeto-placental unit. Acta Endocrinol 1968;57:208-27
7. Fishman J. Fate of 15α-hydroxyestriol-3H in adult man. J Clin Endocrinol 1970;31:436-8
8. Fishman J, Schut H, Solomon S. Metabolism, production and excretion rates of 15α-hydroxyestriol in late pregnancy. J Clin Endocrinol Metab 1972;35:339-44
9. Jirku H, Kadner S, Levitz M. Pattern of estetrol conjugation in the human. Steroids 1972;19:519-34
10. Nagatomi K, Osawa Y, Kirdani RY, Sandberg AA. Studies on phenolic steroids in human subjects. XVII. The kidney and fate of 15a-hydroxyestrogens. J Clin Endocrinol Metab 1973;37:887-900
11. Schut HAJ, Bowman JM and Solomon S. Precursor role of 15α-hydroxyestradiol and 15α-hydroxyandrostenedione in formation of estetrol. Can J Biochem 1978;56:101-6
12. Heikkilä J, Adlercreutz H. A method for the determination of urinary 15α-hydroxyestriol and estriol. J Steroid Biochem 1970;1:243-53
13. Heikkilä J. Excretion of 15α-hydroxyestriol and estriol in maternal urine during normal pregnancy. J Steroid Biochem 1971;2:83-93
14. Holinka CF, Diczfalusy E, Coelingh Bennink HJT. Estetrol: a unique steroid in human pregnancy. J Steroid Biochem Molec Biol 2008; in press
15. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJT. Maternal and fetal estetrol levels during pregnancy. Climacteric 2008;11(Suppl 1):69-72
16. Den K, Matsumoto H, Fujii KT, Furuya K, Yoshida T, Takagi S. A radioimmunoassay of plasma unconjugated and conjugated estetrol. Steroids 1977;30:521-9
17. Tulchinsky D, Frigoletto FD, Ryan KJ, Fishman J. Plasma estetrol as an index of fetal well-being. J Clin Endocrinol Metab 1975;40:560-7
18. Kundu N, Wachs M, Iverson GB, Petersen LP. Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies. Obstet Gynecol 1981;58:276-81
19. Sciarra JJ, Tagatz GE, Notation AD, Depp R. Estriol and estetrol in amniotic fluid. Am J Obstet Gynecol 1974;118:626-42
20. YoungLai EV, Solomon S. Formation of estra-1,3,5(10)-triene-3,15α, 16α,17β-tetrol (estetrol) and estra-1,3,5(10)-triene-3,15α, 17β-triol from neutral precursors. J Clin Endocrinol 1968;28:1611-17
21. Adlercreutz H, Luukkainen T. Identification and determination of oestrogens in various biological materials in pregnancy. Ann Clin Res 1970;2:365-80
22. Fishman J, Guzik H. Radioimmunoassay of 15α-hydroxyestriol in pregnancy plasma. J Clin Endocrinol Metab 1972;35:892-6
23. Heikkilä J, Luukkainen T. Urinary excretion of estriol and 15α-hydroxyestriol in complicated pregnancies. Am J Obstet Gynecol 1971;110:509-21
24. Tulchinsky D, Frigoletto FD, Ryan KJ, Fishman J. Plasma estetrol as an index of fetal well-being. J Clin Endocrinol Metab 1975;40:560-7
25. Notation AD, Tagatz GE. Unconjugated estriol and 15α-hydroxyestriol in complicated pregnancies. Am J Obstet Gynecol 1977;128:747-56
26. Kundu N, Grant M. Radioimmunoassay of 15α-hydroxyestriol (estetrol) in pregnancy serum. Steroids 1976;27:785-96
27. Kundu N, Wachs M, Iverson GB, Petersen LP. Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies. Obstet Gynecol 1981;58:276-81
28. Tseng L, Gurpide E. Competition of estetrol and ethynylestradiol with estradiol for nuclear binding in human endometrium. J Steroid Biochem 1976;7:817-22
29. Martucci C, Fishman J. Uterine estrogen receptor binding of catecholestrogens and of estetrol (1,3,5(10)-estratriene-3,15α,16α, 17β-tetrol). Steroids 1976;27:325-33
30. Jozan S, Kreitmann B, Bayard F. Different effects of oestradiol, oestriol, oestetrol and of oestrone on human breast cancer cells (MCF-7) in long term culture. Acta Endocrinol 1981;98:73-80
31. Holinka CF, Gurpide E. In vivo effects of estetrol on the immature rat uterus. Biol Reprod 1979;20:242-6
32. Holinka CF, Bressler RS, Zehr DR, Gurpide E. Comparison of effects of estetrol and tamoxifen with those of estriol and estradiol on the immature rat uterus. Biol Reprod 1980;22:913-26
33. Holinka CF, Diczfalusy E, Coelingh Bennink HJT. Estetrol: a unique steroid in human pregnancy. Climacteric 2008;11(Suppl 1):1
34. (a summary from J Steroid Biochem Molec Biol 2008; in press)
35. Warmerdam EGJC, Visser M, Coelingh Bennink HJT, Groen M. A new route of synthesis of estetrol. Climacteric 2008;11(Suppl 1):59-63
36. Patent application on E4 synthesis; publication number WO/2004/041839
37. Visser M, Foidart J-M, Coelingh Bennink HJT. In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism. Climacteric 2008;11(Suppl 1):64-8
38. Coelingh Bennink HJT, Heegaard AM, Visser M, Holinka CF, Christiansen C. Oral bioavail-ability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric 2008;11(Suppl 1):2-14
39. Visser M, Holinka CF, Coelingh Bennink HJT. First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric 2008;11(Suppl 1):31-40
40. Hammond GL, Hogeveen KN, Visser M, Coelingh Bennink HJT. Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells. Climacteric 2008;11(Suppl 1):41-6
41. Guidelines for the Preclinical and Clinical Evaluation of Agents Used in the Prevention or Treatment of Postmenopausal Osteoporosis. Division of Metabolic and Endocrine Drug Products. Washington, DC: US Food and Drug Administration, 1994
42. Holinka CF, Brincat M, Coelingh Bennink HJT. Preventive effect of oral estetrol in a menopausal hot flush model. Climacteric 2008;11(Suppl 1):15-21
43. Heegaard AM, Holinka CF, Kenemans P, Coelingh Bennink HJT. Estrogenic uterovaginal effects of oral estetrol in the modified Allen-Doisy test. Climacteric 2008;11(Suppl 1):22-8
44. Coelingh Bennink HJT, Singer C, Simoncini T, Genazzani AR, Holinka CF, Kubista E. Estetrol, a pregnancy-specific human steroid, prevents and suppresses mammary tumor growth in a rat model. Climacteric 2008;11(Suppl 1):29
45. Coelingh Bennink HJT, Skouby S, Bouchard P, Holinka CF. Ovulation inhibition by estetrol in an in vivo model. Contraception 2008;77:186-90
46. Coelingh Bennink HJT, Skouby S, Bouchard P, Holinka CF. Ovulation inhibition by estetrol in an in vivo model. Climacteric 2008;11(Suppl 1):30
47. (a summary from Contraception 2008;77:186-90)