The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study
Open accessAbstract
OBJECTIVE: Estetrol (E4) is an estrogen produced exclusively by the human fetal liver during pregnancy. In this study the pharmacodynamic effects of escalating doses of E4 in postmenopausal women were investigated. METHODS: This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women. Participants were randomized to receive either 2 mg E4 or 2 mg estradiol-valerate (E2 V) for 28 days. Subsequent dose-escalation groups were (non-randomized): 10, 20 and 40 mg E4. Blood samples were collected regularly for measuring endocrine and hemostasis variables, lipids and lipoproteins, fasting glucose and bone turnover markers. RESULTS: Estetrol treatment resulted in a decrease of follicle-stimulating hormone and luteinizing hormone and an increase of sex-hormone binding globulin. Changes in hemostasis variables were small. A lowering effect on low-density lipoprotein cholesterol was accompanied with an increase in high-density lipoprotein cholesterol and no or minimal changes in triglycerides. The considerable decrease in osteocalcin levels in the three highest E4 dose groups and the small decrease in C-telopeptide levels were comparable to the E2 V control group and suggest a preventive effect on bone loss. All changes observed were dose-dependent. CONCLUSIONS: In this study, estetrol treatment showed dose-dependent estrogenic effects on endocrine parameters, bone turnover markers, and lipids and lipoproteins. The effect on triglycerides was small as were the effects on hemostatic variables. These results support the further investigation of estetrol as a candidate for hormone therapy. Quantitatively, the effects of 10 mg estetrol were similar to the study comparator 2 mg estradiol valerate.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The lower estrogenic effect of E4/DRSP was also reflected by the low impact of E4/DRSP on hemostatic activation [ 15 , 16 , 21 ].”
From Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone (2021) · cites this paper as [16]
In the citing paper
“EE/DRSP increased HDL-C slightly and EE/LNG decreased HDL-C, which is in line with previous studies [ 14 , 16 ].”
From Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone (2021) · cites this paper as [16]
Citations
Cites
Valery (1995) · doi:10.1001/jama.1995.03520270033028 · Cited by 2,320
Chapman, M. J., Ginsberg, H. N., Amarenco, P., Andreotti, F., Borén, J., Catapano, A. L., Descamps, O. S., Fisher, E., Kovanen, P. T., Kuivenhoven, J. A., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr112 · Cited by 1,227
Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis
Garnero, P., Sornay‐Rendu, E., Chapuy, M. C., & Delmas, P. D. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110307 · Cited by 1,000
2016 IMS Recommendations on women’s midlife health and menopause hormone therapy
Baber, R., Panay, N., & Fenton, A. J. (2016) · Climacteric · doi:10.3109/13697137.2015.1129166 · Cited by 968
Metabolic risk factors for coronary heart disease in women: Perspective from the Framingham Study
Kannel, W. B. (1987) · American Heart Journal · doi:10.1016/0002-8703(87)90511-4 · Cited by 459
Rosen, H. N., Moses, A. C., Garber, J. R., Iloputaife, I., Ross, D. S., Lee, S. L., & Greenspan, S. L. (2000) · Calcified Tissue International · doi:10.1007/pl00005830 · Cited by 288
Bagger, Y. Z., Tankó, L. B., Alexandersen, P., Hansen, H. B., Møllgaard, A., Ravn, P., Qvist, P., Kanis, J. А., & Christiansen, C. (2004) · Bone · doi:10.1016/j.bone.2003.12.021 · Cited by 189
Postmenopausal Hormone Replacement Therapy Increases Coagulation Activity and Fibrinolysis
Teede, H. J., McGrath, B. P., Smolich, J. J., Malan, E., Kotsopoulos, D., Liang, Y., & Peverill, R. E. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.5.1404 · Cited by 132
Haemostasis Factors in Angina Pectoris; Relation to Gender, Age and Acute-phase Reaction
Haverkate, F., Thompson, S. G., & Duckert, F. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1653821 · Cited by 127
A Comparative Study of Lipid Profile and Oestradiol in Pre- and Post-Menopausal Women
Kilim, S. R. (2013) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2013/6162.3234 · Cited by 127
Estetrol: a unique steroid in human pregnancy
Holinka, C. F., Diczfalusy, E., & Coelingh Bennink, H. J. T. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.03.027 · Cited by 123 · cited 3×
“The fetal liver is the exclusive site responsible for the 15a- and 16a-hydroxylation and therefore E4 is only present during pregnancy.(2) These small structural differences as compared to the other estrogens, including E2,”
BackgroundEstetrol review: profile and potential clinical applications
Bennink, H. J. T. C., Holinka, C. F., & Diczfalusy, E. R. (2008) · Climacteric · doi:10.1080/13697130802073425 · Cited by 121
Statins for primary prevention of cardiovascular disease
Majeed, A. (2014) · BMJ · doi:10.1136/bmj.g3491 · Cited by 103
Høibraaten, E., Mowinckel, M., de Ronde, H., Bertina, R. M., & Sandset, P. M. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.03111.x · Cited by 92
Apter, D., Zimmerman, Y., Beekman, L., Mawet, M., Maillard, C., Foidart, J.-M., & Coelingh Bennink, H. J. T. (2016) · Contraception · doi:10.1016/j.contraception.2016.04.015 · Cited by 77
Self-citationLipoprotein metabolism in postmenopausal and oophorectomized women
Wakatsuki, A., & Sagara, Y. (1995) · Obstetrics and Gynecology · doi:10.1016/0029-7844(94)00452-j · Cited by 76
In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism
de Visser, M., Foidart, J., & Bennink, H. J. T. C. (2008) · Climacteric · doi:10.1080/13697130802050340 · Cited by 76
Self-citationMETABOLISM OF 17-BETA-OESTRADIOL-4-14-C IN EARLY INFANCY.
Hagen, A. A., BARR, M., & Diczfalusy, E. (1965) · PubMed · Cited by 73
Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation
Gérard, C., Blacher, S., Communal, L., Courtin, A., Tskitishvili, E., Mestdagt, M., Munaut, C., Noël, A., Gompel, A., Péqueux, C., et al. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0549 · Cited by 70
Self-citationOral bioavailability and bone-sparing effects of estetrol in an osteoporosis model
Bennink, H. J. T. C., Heegaard, A., de Visser, M., Holinka, C. F., & Christiansen, C. (2008) · Climacteric · doi:10.1080/13697130701798692 · Cited by 69
Self-citationDuijkers, I. J. M., Heger-Mahn, D., Drouin, D., et al. (2015) · The European Journal of Contraception & Reproductive Health Care · doi:10.3109/13625187.2015.1044082 · Cited by 67
Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells
Hammond, G. L., Hogeveen, K. N., Visser, M., & Coelingh Bennink, H. J. T. (2008) · Climacteric · doi:10.1080/13697130701851814 · Cited by 65
Self-citationDuijkers, I. J. M., Klipping, C., Zimmerman, Y., Appels, N., Jost, M., Maillard, C., Mawet, M., Foidart, J.-M., & Coelingh Bennink, H. J. T. (2015) · The European Journal of Contraception & Reproductive Health Care · doi:10.3109/13625187.2015.1074675 · Cited by 61
Self-citationFirst human exposure to exogenous single-dose oral estetrol in early postmenopausal women
de Visser, M., Holinka, C. F., & Bennink, H. J. T. C. (2008) · Climacteric · doi:10.1080/13697130802056511 · Cited by 61
Self-citationOvulation inhibition by estetrol in an in vivo model
Bennink, H. J. T. C., Skouby, S. O., Bouchard, P., & Holinka, C. F. (2008) · Contraception · doi:10.1016/j.contraception.2007.11.014 · Cited by 60
Bennink, H. J. T. C., Verhoeven, C., Zimmerman, Y., de Visser, M., Foidart, J., & Gemzell‐Danielsson, K. (2016) · Maturitas · doi:10.1016/j.maturitas.2016.06.017 · Cited by 57
Self-citationPreventive effect of oral estetrol in a menopausal hot flush model
Holinka, C. F., Brincat, M., & Bennink, H. J. T. C. (2008) · Climacteric · doi:10.1080/13697130701822807 · Cited by 50
Gérard, C., Mestdagt, M., Tskitishvili, E., Communal, L., Gompel, A., Silva, E. A., Arnal, J., Lenfant, F., Noël, A., Foidart, J., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4184 · Cited by 49
Self-citationGiretti, M. S., Guevara, M. M. M., Cecchi, E., et al. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00080 · Cited by 45
Biochemical Markers of Bone Metabolism
Schönaü, E., & Rauch, F. (2003) · Elsevier eBooks · doi:10.1016/b978-012286551-0/50016-6 · Cited by 41
Post, M. S., Rosing, J., van der Mooren, M. J., Zweegman, S., van Baal, W. M., Kenemans, P., & Stehouwer, C. D. A. (2002) · British Journal of Haematology · doi:10.1046/j.1365-2141.2002.03957.x · Cited by 40
Stevenson, J. C., Panay, N., & Pexman-Fieth, C. (2013) · Maturitas · doi:10.1016/j.maturitas.2013.05.018 · Cited by 37
Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model
de Visser, M., Kloosterboer, H. J., & Bennink, H. J. T. C. (2012) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2012-0015 · Cited by 30
Self-citationSerum cholesterol efflux potential is an independent predictor of coronary artery atherosclerosis
Mikkola, T. S. (2003) · Atherosclerosis · doi:10.1016/s0021-9150(03)00247-8 · Cited by 30
Estrogenic uterovaginal effects of oral estetrol in the modified Allen–Doisy test
Heegaard, A., Holinka, C. F., Kenemans, P., & Bennink, H. J. T. C. (2008) · Climacteric · doi:10.1080/13697130701842490 · Cited by 30
Roehm, E. (2015) · Obstetrics and Gynecology International · doi:10.1155/2015/713295 · Cited by 22
Bittner, V. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)01149-9 · Cited by 18
Pattern of estetrol conjugation in the human
Jirku, H., KADNER, S. S., & Levitz, M. (1972) · Steroids · doi:10.1016/s0039-128x(72)80019-9 · Cited by 15
Fate of 15α-Hydroxyestriol-3H in Adult Man
Fishman, J. (1970) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-31-4-436 · Cited by 14
[Biochemical markers of bone metabolism].
Miki, T., & Nakatsuka, K. (1998) · PubMed · Cited by 6
Cited by
Sorted by citations
Iorga, A., Cunningham, C. M., Moazeni, S., Ruffenach, G., Umar, S., & Eghbali, M. (2017) · Biology of Sex Differences · doi:10.1186/s13293-017-0152-8 · Cited by 914
Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone
Klipping, C., Duijkers, I., Mawet, M., Maillard, C., Bastidas, A., Jost, M., & Foidart, J.-M. (2021) · Contraception · doi:10.1016/j.contraception.2021.01.001 · Cited by 108
Self-citationGaspard, U., Taziaux, M., Mawet, M., Jost, M., Gordenne, V., Coelingh Bennink, H. J. T., Lobo, R. A., Utian, W. H., & Foidart, J.-M. (2020) · Menopause · doi:10.1097/gme.0000000000001561 · Cited by 52
Self-citation
Metadata
- Authors
- Coelingh Bennink, H. J. T., Verhoeven, C., Zimmerman, Y., Visser, M., Foidart, J.-M., & Gemzell-Danielsson, K.
- Affiliations
- Pantarhei Bioscience BV, Zeist, The Netherlands
- Pantarhei Bioscience (Netherlands) (NL)
- University of Liège (BE)
- Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
- Venue
- Menopause
- Published
- 2017-06
- Volume
- 24
- Issue
- 6
- Pages
- 677-685
- ISSN
- 1072-3714 (ISSN-L)
- 1530-0374
- OpenAlex
- W2588950891
- Cited by
- 45
- References
- 40
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 3
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Menopause The Journal of The North American Menopause Society (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Nursing › Nutrition and Dietetics › Phytoestrogen effects and research
- Keywords
- estetrol, postmenopausal women, hormone therapy, estradiol valerate, follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, lipoproteins, LDL cholesterol, HDL cholesterol, triglycerides, bone turnover markers, osteocalcin, C-terminal telopeptide, bone loss prevention, dose-dependent effects, hemostasis
- MeSH terms
- Aged, Cholesterol, Dose-Response Relationship, Drug, Estetrol, Estradiol, Female, Follicle Stimulating Hormone, Humans, Luteinizing Hormone, Cholesterol, HDL, Cholesterol, LDL, Middle Aged, Peptides, Sex Hormone-Binding Globulin, Osteoporosis, Postmenopausal, Osteocalcin, Postmenopause, Collagen Type I
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
